Patent DET2 - Kallikrein gen Conditions kallikrein - Google Patents Wie Psoriasis qd behandeln
Try the new Google Patents, with machine-classified Google Wie Psoriasis qd behandeln results, and Japanese and South Korean patents. Kallikrein gen Conditions kallikrein translated from German DE T2. An isolated protein consisting of an amino acid sequence of SEQ ID NO: An isolated nucleic acid molecule of claim 2 with a nucleic acid sequence of SEQ ID NO: A vector comprising a nucleic acid molecule according to claim 2 or 3.
A host cell comprising wie Psoriasis qd behandeln nucleic acid molecule of claim 2 or 3. A process for producing a protein according to claim 1, which comprises: Antibodies having specificity Psoriasis Zimt an epitope of a protein of claim wie Psoriasis qd behandeln. The antibody of claim 7 which is wie Psoriasis qd behandeln with a detectable substance and used to detect the polypeptide in biological samples, tissues and cells.
Probe comprising a sequence that encodes a protein of claim 1. A test kit for diagnosing a condition associated wie Psoriasis qd behandeln a protein of claim 1. By determining the presence of a nucleic acid molecule according to any one of the preceding claims or a protein according to one of the preceding claims. Testkit nach Anspruch 10, wobei der Zustand Krebs ist. A test kit according to claim 10, wherein the condition is cancer.
Testkit nach Anspruch 11, wobei der Krebs Prostatakrebs ist. A test kit according go here claim 11, wherein the cancer is prostate cancer. A method for identifying a substance which associates with a protein as claimed in claim 1, which comprises: A method for identifying inhibitors of the interaction of a protein according to claim 1 and a substance wie Psoriasis qd behandeln interacts with the protein, comprising: A method for detecting a nucleic acid molecule encoding a protein according to claim 1, in a biological sample, comprising the steps of: The method of claim 16, wherein nucleic acids of the biological sample are amplified prior to the hybridization step go here polymerase chain reaction.
An in vitro method for monitoring the progression of prostate cancer in an individual, comprising the steps of: Verwendung eines Proteins nach Anspruch 1 bei der Herstellung eines Medikaments zur Behandlung von Prostatakrebs. Use of a protein according to claim 1 in the manufacture of a medicament for the treatment of prostate cancer. A pharmaceutical composition which comprises one or more of a nucleic acid molecule or a protein according to any one of the preceding claims and a pharmaceutically acceptable carrier, excipient or diluent.
Using one or more of a nucleic acid molecule or a protein according to any one of the preceding claims in the manufacture of a pharmaceutical composition for the treatment of prostate cancer. Method for carrying out drug discovery comprising: A vaccine for stimulating or enhancing the production of antibodies that are directed against a protein according to claim 1, wie Psoriasis qd behandeln a subject to which the vaccine is administered.
Use of a protein according to claim 1 in the manufacture of a vaccine for stimulating or enhancing the production of antibodies against the protein in a subject. GEBIET DER ERFINDUNG FIELD OF THE INVENTION. The invention relates to nucleic acid molecules, proteins encoded by such nucleic acid molecules and the use of the proteins and nucleic acid molecules.
HINTERGRUND DER ERFINDUNG BACKGROUND OF THE INVENTION. Kallikreins are a group of serine proteases, which are found in various tissues and biological fluids. The term "kallikrein" was first introduced by Werle and colleagues that contain high amounts of their initial wie Psoriasis qd behandeln in the pancreas in Greek the "calli Kreas" found 1, 2. Kallikreins are divided into two main groups, the plasma kallikrein, which is a single gene 3 wie Psoriasis qd behandeln, and the tissue kallikreins, which are encoded wie Psoriasis qd behandeln a large multigene wie Psoriasis qd behandeln in rodents 4, 5.
Until recently it was thought that the human kallikrein gene family consists of only three members 6. Es wurden jedoch 11 neue Mitglieder der Kallikrein-Genfamilie identifiziert 7— However, there were 11 new members of the kallikrein gene family identified Prostate specific antigen PSAcurrently the most appropriate tumor marker for the diagnosis and monitoring of prostate cancer, is a member of the human kallikrein gene family of serine proteases 19, In addition to PSA, human glandular kallikrein 2 hK2, encoded by the KLK2 gene as an additional diagnostic marker for prostate cancer has been proposed 21, Furthermore, accumulating evidence that other members of the extended kallikrein gene family may be associated more info malignancy 7.
The normal epithelial cell-specific gene 1 NES1 KLK10 gene according to the accepted nomenclature for kallikrein in human tissue was recognized as a new tumor suppressor, wie Psoriasis qd behandeln is down-regulated during the progression of breast cancer It was discovered that other gene family members including Zyme KLK6Neuropsin KLK8 and human stratum corneum chymotryptic enzyme HSCCE; KLK7 are differentially expressed also wie Psoriasis qd behandeln certain types of malignancies ZUSAMMENFASSUNG DER ERFINDUNG SUMMARY Wie Psoriasis qd behandeln THE INVENTION.
The present inventors have identified a nucleic acid molecule encoding a novel kallikrein. The nucleic acid molecule is located on chromosome 19q The new "KLK15" said nucleic acid molecule has three different splice forms and is primarily expressed in the thyroid gland and to a lesser extent in the prostate, wie Psoriasis qd behandeln gland and adrenal glands, colon, testis and kidney. Expression of the nucleic acid is up-regulated in prostate cancer and is in the LNCaP wie Psoriasis qd behandeln cancer cell line is regulated by steroid hormones.
A higher expression of KLK15 is linked to more aggressive prostate tumors stage higher and higher level in combination. The herein described new kallikrein protein is referred to as "Kallikrein 15", "KLK15", or "KLK15 Protein".
The gene encoding the protein is referred to as "KLK15". The present invention relates to an isolated protein. From an amino acid sequence of SEQ ID.
Wie Psoriasis qd behandeln present invention also relates to an isolated nucleic acid molecule having a nucleic acid sequence of SEQ. The nucleic acid molecules according to the invention can be inserted into an appropriate expression vector, ie a vector which has the necessary elements for the transcription and translation wie Psoriasis qd behandeln the inserted coding sequence.
Accordingly, recombinant expression vectors adapted for transformation of a host cell can be constructed which contains a nucleic acid molecule according to the invention and one or more nucleic acid molecule associated with the transcription and translation elements. Der rekombinante Expressionsvektor kann zur Herstellung transformierter Wirtszellen, die das KLKProtein exprimieren, verwendet werden. The recombinant expression vector can be used to wie Psoriasis qd behandeln transformed host des auf den wie Körper zu Psoriasis Videos behandeln expressing the KLK15 protein.
Thus, the invention further host cells containing a recombinant molecule according to the invention. The invention also contemplates transgenic non-human mammals in consideration whose germ cells and somatic cells contain a recombinant molecule comprising a nucleic acid molecule according to the invention, in particular one which encodes an analog of the KLK15 protein, or a truncated form of the KLK15 protein comprises.
The invention further provides just click for source method for preparing KLK15 Proteins are available, wherein the purified and isolated nucleic acid molecules are used in accordance with the invention. In one embodiment, a method for preparing a KLK15 Protein is provided comprising: The KLK15 Proteins of the wie Psoriasis qd behandeln can contribute to the production of fusion proteins with other molecules, such as proteins are conjugated.
Example, be achieved by the synthesis of N-terminal or C-terminal fusion proteins. Further, the invention contemplates specifically to a KLK15 wie Psoriasis qd behandeln according to the invention binding antibodies into consideration. Antibodies may be labeled with detectable substances, and be used to detect proteins of the invention in tissues and cells.
Antibodies can be a special use, in particular in therapeutic applications have, for. Example, to react with tumor cells, and in conjugates and immunotoxins as target selective carriers of various agents with anti-tumor effects including chemotherapeutic drugs, toxins, immune response modifiers, enzymes and radioisotopes.
Therefore, the invention also relates to a probe comprising a nucleic acid sequence of the invention or a nucleic acid sequence encoding a protein according to the invention or a part thereof.
Die Sonde kann z. The probe can be, for. Example, be labeled with detectable substances, and be used for selection of a nucleic acid click at this page of the invention from a mixture of read article sequences, including nucleic acid molecules which code for a protein that has one or more properties of the proteins according to the invention.
Eine Sonde kann zum Markieren von Tumoren verwendet werden. A probe can be used to mark tumors. The invention also provides an antisense nucleic acid molecule is available, for.
Example, by the production of a mRNA or DNA strand in the reverse orientation to a sense molecule. An antisense nucleic acid molecule can be used carcinogenic z. The invention still further provides a method for identifying a substance that binds to a protein according to the invention available, which comprises: Die Bindung wie Psoriasis qd behandeln durch Untersuchen auf Komplexe, freie Substanz oder nicht komplexiertes Protein detektiert werden.
The binding can be detected by assaying for complexes, free go here or non-complexed protein. The invention also contemplates a method for identifying substances thereof, that bind to other intracellular proteins that interact with a KLK15 Protein. It can also be used methods which identify compounds that bind to KLK15 regulatory sequences http://larpring.de/wie-psoriasis-des-kopfes-zu-behandeln.php genes e.
The invention still further provides a method for evaluating a compound for the ability to modulate the biological activity of a KLK15 protein of the invention. For example, a substance may be evaluated, which inhibits or enhances the interaction of the protein and a substance that binds to the protein. In one embodiment, the method comprises detected by complexes. Compounds that modulate the biological activity of a protein according to the invention can also be identified using methods according to the invention by comparing expression patterns and levels of the protein of the invention in tissues and cells in the presence and absence wie Psoriasis qd behandeln the compounds.
The proteins according to the invention, antibodies, antisense nucleic acid molecules, and substances and compounds identified using methods of the invention, and peptides of the invention may be wie Psoriasis qd behandeln for modulating the biological activity of a KLK15 protein of the invention and they can sener diseases in the treatment of conditions such as cancer particularly prostate, colon, kidney and testicular cancer and thyroid, are used in a subject.
Accordingly, the substances and compounds may be formulated into compositions for administration to individuals suffering from diseases such as cancer particularly prostate, colon, kidney, and testicular cancer and thyroid disorders. In particular, wie Psoriasis qd behandeln antibodies, antisense nucleic acid molecules, substances and compounds for treating patients who have a KLK15 Protein in, or on their cancer cells be used.
Therefore, the present invention wie Psoriasis qd behandeln relates to a composition comprising one or more nucleic acid molecules or a protein according to wie Psoriasis qd behandeln invention and a pharmaceutically acceptable carrier, excipient or diluent.
It is also the use of a wie Psoriasis qd behandeln acid molecule or protein according to the invention in the manufacture of a medicament for use in a method of wie Psoriasis qd behandeln or prevention of a disease, wie Psoriasis qd behandeln as cancer particularly prostate, thyroid, colon, kidney, and testicular cancer and thyroid disorders, provided in a subject.
This vaccine preparations can also be used to protect patients tumors prior to publication. The invention contemplates generally vaccines for stimulating and enhancing the production of antibodies against a KLK15 protein in a subject wie Psoriasis qd behandeln which the vaccine is administered into consideration.
The invention also provides the use of a protein according to the invention for the manufacture wie Psoriasis qd behandeln a vaccine for wie Psoriasis qd behandeln and enhancing the production of antibody against a KLK15 protein in a subject are available.
Der Impfstoff kann in Verfahren zur Behandlung, Vorbeugung oder Verlangsamung des Wiederauftretens von Krebs verwendet werden.
The vaccine may be used in methods for treating, preventing or slowing the recurrence of cancer. In other embodiments, the invention provides a method for identifying inhibitors of a KLK15 protein interaction are available, comprising: C identifying compounds which inhibit the interaction of the KLK15 Protein and substance.
In certain preferred embodiments, the reaction mixture is a whole cell. In other embodiments, the reaction mixture is a cell lysate or a compilation of purified protein. The subject method can be carried out using libraries of test compounds.
Another aspect of the present invention provides a method for performing discovery of drug available, comprising: C determining a formulation for a pharmaceutical preparation which contains one or more agents identified in step b with an acceptable therapeutic profile. Weitere Ziele, Eigenschaften es ist nicht Psoriasis haben Vorteile der vorliegenden Erfindung werden aus wie Psoriasis qd behandeln folgenden detaillierten Beschreibung ersichtlich werden.
Other objects, features and advantages of the present invention will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, specify only be given by way of illustration. KURZE BESCHREIBUNG DER FIGUREN BRIEF DESCRIPTION OF THE FIGURES.
Die Erfindung wird nun in Bezug auf die Figuren beschrieben, in welchen: The invention will now be described with reference to the figures, in which: Introns are shown in lowercase and uppercase exons. The translated amino acids of the coding region are shown below in letter abbreviations. Die Start- und Stopcodons sind eingekreist und die Exon-Intron-Verbindungen sind unterstrichen. The start and stop codons are encircled and the exon-intron junctions are underlined.
Die katalytischen Reste sind eingerahmt. The catalytic residues are boxed. Das putative Polyadenylierungssignal ist unterstrichen. The putative polyadenylation signal is underlined. Der genaue Start des ersten codierenden Exons wurde nicht bestimmt.
The exact start of the first coding exon was not determined. Dashes represent gaps to better align the sequences together. Die Reste der katalytischen Triade H, D, S sind in kursiv dargestellt. The residues of the catalytic triad H, D, S are shown in italics. Identical amino acids are highlighted in black and similar residues in gray. Die vorhergesagten Spaltstellen der Signal- und Aktivierungspeptide sind durch Pfeile angezeigt.
The predicted cleavage sites of the signal and activation peptides are indicated by arrows. Der gepunktete Bereich stellt die Sequenz der Schleife des Kallikreins dar. The dotted area represents the sequence of the loop of kallikrein. KLK15 has an "E" in this position. A unique sequence of eight amino acids, HNEPGTAG SEQ. Beachten Sie den hydrophoben Bereich am Aminoende, der die Anwesenheit eines Signalpeptids nahelegt.
Note the hydrophobic region at the amino terminus, which suggests the presence of a signal peptide. Das Neighbor-Joining-Verfahren wurde verwendet, um KLK15 mit anderen Serinproteasen und Mitgliedern der Kallikrein-Genfamilie anzugleichen. The neighbor-joining method was used to align KLK15 with other serine proteases and members of the kallikrein gene family. Der Baum ordnete die klassischen Kallikreine hK1, hK2 und PSA zusammen an und ordnete KLK15 in einer Gruppe mit Wie Psoriasis qd behandeln und KLK-L3-Genen an.
The tree ordered the classical kallikreins hK1, hK2 and PSA together and ordered to KLK15 in a group with TLSP and KLK-L3 genes on. Andere Serinproteasen wurden wie gezeigt read article anderen Gruppen angeordnet.
Other serine proteases were arranged as shown in the other groups. KLK is kallikrein is, KLK-L provides kallikrein-like shows, TLSP represents trypsin-like serine protease, NES1 is normal Epithelienzellen-specific gene, PSA is prostate-specific http://larpring.de/injektionen-von-natriumthiosulfat-psoriasis-bewertungen.php, hK1 and hK2 represent each human glandular kallikrein 1 and 2 represents and wie Psoriasis qd behandeln HSCCE human stratum corneum chymotryptic enzyme.
Exons sind durch Einrahmungen dargestellt wie Psoriasis qd behandeln Introns durch Verbindungslinien. Exons are represented by framing and introns by lines. Die Pfeilspitze deutet auf das gemeinsame Startcodon und Sterne auf die Stopcodonpositionen. The arrowhead points to the common start codon and stars on the Stopcodonpositionen.
The length of the predicted polypeptide is indicated next to each variant amino acids AA. The overlapping BAC clones are identified and the overlapping area is hatched. Die Gene sind durch horizontale Pfeile angegeben, die die Richtung der codierenden Sequenz angeben.
The genes are wie Psoriasis qd behandeln by horizontal arrows indicate the direction of wie Psoriasis qd behandeln coding sequence. The distances between the genes are given in base pairs. The figure is not drawn to scale. KLK15 is primarily expressed in the thyroid gland and to a lesser extent in the prostate, salivary gland and adrenal glands, colon, testis and kidney.
To explain the multiple PCR bands alternative splicing see the example. The PCR was performed with primers KLKF2 and KLKR1. Steoride wurden mit einer Endkonzentration von 10 —8 M zugegeben. Steoride were added at a final concentration of 10 -8 M. Aktin wurde als Kontrollgen verwendet. Actin was used as control gene. Exons sind durch Balken und Individual Salbe auf der Basis von Schöll bei Psoriasis phlox durch Verbindungslinien dargestellt.
Exons are represented by bars and introns by lines. H indicates histidine, aspartic acid and D S serine. The Roman numerals indicate Intro phases. I denotes that the intron appears after the first nucleotide of the codon, II the intron appears after wie Psoriasis qd behandeln second nucleotide, 0 the intron between codons appear. Die Intronphasen sind in allen Genen konserviert. The intron phases are conserved in all genes.
Name within the parentheses represent the official nomenclature, which is recognized by the Nomenclature Committee for human genes. According to the invention can be used ordinary molecular biological, microbiological and recombinant DNA techniques according to the prior art.
Such techniques are described in detail in the literature. A Laboratory Manual, zweite Ausgabe Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, DNA Cloning: Perbal, Gepasol Psoriasis Practical Guide to Molecular Cloning A Laboratory Manual, second edition Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, DNA Cloning: A Practical Approach, Volumes I and II DN Glover ed.
As mentioned above, the invention provides an isolated nucleic acid molecule having a sequence encoding a KLK15 protein available. The term "isolated" refers to a nucleic acid that is free of cellular material or culture medium substantially when it is produced by recombinant DNA techniques, or of chemical starting compounds or other chemicals wie Psoriasis qd behandeln it is und Sprays Preis Psoriasis von synthesized.
The term "nucleic acid" is intended to DNA and RNA include and can be either double-stranded or single-stranded.
The nucleic acid molecules of the invention encode a protein consisting of an amino acid sequence of SEQ. Preferably, the Nucleic acid molecules according to the invention, a nucleic acid sequence of one or more of SEQ. The invention includes nucleic acid sequences that are complementary to a nucleic acid encoding a protein. The invention includes nucleic wie Psoriasis qd behandeln molecules having substantial sequence identity or homology to nucleic acid sequences according to the invention or encoding proteins link identity or similarity to the amino acid sequence of SEQ.
Preferably the nucleic acids have substantial sequence identity, for. Informatics and Genome Projects, Smith, DW Hrsg. Stockton Press, Wie Psoriasis qd behandeln York,Carillo, H. It also relates to the degree of sequence relatedness between amino acid and nucleic acid sequences, each after that is determined by matching short consequences of such sequences.
Computational Molecular Biology, Lesk, AM, ed. Informatics and Genome Projects, Smith, DW, eds, Academic Press, New York,Computer Analysis of Sequence Data, Part I, AM Griffin and Griffin, HG ed, Humana Press, New Jersey, Methods that have been designed so that they give the best match between the sequences are generally preferred.
A method to determine identity and similarity are codified in publicly available computer programs including the GCG program package Devereux, J. NCBI NLM NIH Bethesda, Md. The BLAST X program is publicly available from NCBI and other sources BLAST Manual, Altschul, S. Isolated nucleic acid molecules encoding a KLK15 Protein, and having a sequence which differs from the nucleic acid sequence according to the invention due to the degeneracy of the genetic code are also within the scope of the invention.
Such nucleic acids encode functionally equivalent proteins eg. As a KLK15 Protein wie Psoriasis qd behandeln differ in sequence due to the degeneracy of the genetic code from the sequence of a KLK15 protein from.
As an example, DNA sequence polymorphisms can within the nucleotide sequence of KLK15 protein result in silent mutations that do not affect the amino acid sequence.
Variations in one or more nucleotides may exist among individuals within a population due to natural allelic variation. Each and all of these nucleic acid variations are within the scope of the invention. It can also occur DNA sequence polymorphisms that lead to changes in the amino Salbe Psoriasis Derm sequence of KLK15 protein.
These amino acid wie Psoriasis qd behandeln are also within the scope of the present invention. An isolated nucleic acid molecule of the invention which comprises DNA can be wie Psoriasis qd behandeln by preparing a based on all or parts of a nucleic acid sequence according to the invention, labeled nucleic acid probe. The labeled nucleic acid probe to screen an appropriate DNA library used eg. ZB kann eine cDNA-Bibliothek wie Psoriasis qd behandeln werden, um durch Durchmustern der Bibliothek mit der markierten Sonde eine ein KLKProtein codierende cDNA unter Verwendung von Standardtechniken zu isolieren.
For example, a cDNA library can be used to isolate by screening the library with the labeled probe a cDNA encoding a KLK15 Protein using standard techniques.
Alternatively, wie Psoriasis qd behandeln genomic DNA library in the same manner to isolate a genomic clone comprising a gene encoding a KLK15 Protein, screened. Nucleic acids which are isolated by screening a cDNA or genomic DNA library can be sequenced wie Psoriasis qd behandeln standard techniques. An isolated nucleic acid molecule of the invention which is DNA can also be isolated by selectively multiplying a a KLK15 protein coding nucleic acid using the polymerase chain reaction method PCR and cDNA or genomic DNA.
It is possible to design synthetic oligonucleotide primers from the nucleotide sequence according to the invention for use in Wie Psoriasis qd behandeln. A nucleic acid may be amplified from cDNA or genomic DNA using these oligonucleotide primers and standard PCR amplification techniques. An isolated nucleic acid molecule of the invention which is RNA can be produced by cloning a cDNA encoding a KLK15 Protein wie Psoriasis qd behandeln an appropriate vector which allows for transcription of the cDNA for preparing a KLK15 Protein wie Psoriasis qd behandeln a coding RNA molecule, can be isolated.
For example, a cDNA downstream of a Bakteriophagenpromotors z. Nucleic acid molecules according to the invention can be chemically synthesized using standard techniques. A method for chemically synthesizing Polydeoxynukleotiden, including but not limited to solid-phase synthesis, which was like peptide synthesis fully automated in commercially available DNA synthesizers are known see, eg.
As Itakura et al. Determining whether a particular nucleic acid molecule encodes a KLK15 Protein can be accomplished by expressing the cDNA in an appropriate host cell by standard techniques and checking of the expressed protein with the methods described herein.
A cDNA encoding a KLK15 Protein can be sequenced by standard techniques, such as dideoxynucleotide chain termination or Maxam-Gilbert chemical sequencing by, for determining the nucleic acid sequence and the predicted amino acid sequence of the encoded protein. The intron-exon structure and the transcription regulatory sequences of a KLK15 protein-encoding gene can be confirmed by the use of a KLK15 protein-encoding nucleic acid molecule according to the invention for probing a geno mix DNA clone library.
Regulatory elements can be identified by the use wie Psoriasis qd behandeln standard techniques. The function of the elements, by using these elements to express a reporter gene such as the lacZ gene that is operably linked wie Psoriasis qd behandeln the elements to be confirmed.
These constructs can be introduced using conventional methods in cultured cells or in non-human transgenic animal models. In addition to identifying regulatory elements in DNA, such constructs may also to identify nuclear proteins interacting with the elements, are used in the art using known techniques. In a particular embodiment of the invention described herein are methods using the isolated nucleic acid molecules are mutant KLKGenallele.
The mutant alleles may be isolated from individuals that are known or suspected to have a genotype which contributes to the symptoms of a disease on which a KLK15 protein is involved. Mutant alleles and mutant allele products may be used in the therapeutic and diagnostic methods described herein. For example, a cDNA of a mutant KLK15 gene using PCR, as described herein, isolated, and comparing the DNA sequence of the mutant allele with the normal allele, confirming the responsible for the loss or alteration of function of the mutant gene mutations be.
A genomic library can also be performed using DNA of an individual, which is believed or known to be carrying a mutant allele, are prepared or a cDNA library may be composed of RNA from tissue which is known wie Psoriasis qd behandeln suspected, a mutant be allele to express prepared.
A normal Mit Behinderung Psoriasis gene or nucleic acid encoding any suitable fragment thereof may then be labeled and used as a probe to identify the corresponding mutant allele in such libraries.
Clones containing mutant sequences can be purified and subjected to sequence analysis. Additionally, an expression library using cDNA from RNA isolated from a tissue of an individual, which is known to the expression wie Psoriasis qd behandeln a mutant KLK15 allele or is believed to be produced. Produced by the putatively mutant tissue gene products may be, for.
Example, using KLK15 protein-specific antibodies described expressed and screened as described herein. Clones identified using the antibodies of the library can be purified and subjected to sequence analysis. The sequence of a nucleic acid molecule of the invention or a fragment of the molecule can be turned relative to their normal disposition in the transcription for http://larpring.de/psoriasis-ist-die-leber-nicht-schaden.php production of antisense nucleic acid molecules.
An antisense nucleic acid molecule can be created using chemical synthesis and enzymatic ligation reactions using procedures known in the wie Psoriasis qd behandeln. Proteine nach der Erfindung 2. Proteins according to the invention. An amino acid sequence of a KLK15 Protein consists of a sequence as shown in SEQ. The protein is primarily expressed in the thyroid gland and to a lesser extent in the prostate, salivary gland and adrenal glands, colon, testis and kidney.
The invention also contemplates isoforms of the proteins of the invention into consideration. An isoform contains the same number and kinds of amino acids as a protein of the invention, but the isoform has a different molecular structure. Isoforms that are contemplated by the present invention into consideration, preferably have the same properties as a protein of the invention, as described herein.
The present invention also includes KLK15 Proteins, see below are conjugated to the production of fusion proteins with a selected protein or marker protein. Ein KLKProtein nach der Erfindung kann durch Verwendung rekombinanter DNA-Verfahren hergestellt werden. A KLK15 Protein of the invention may be prepared by use of recombinant DNA techniques. Accordingly, wie Psoriasis qd behandeln nucleic acid molecules according to the present invention with a a KLK15 protein of the invention coding sequence are inserted in known manner into an appropriate expression vector which ensures good expression of the protein.
Possible expression vectors include, but are not limited to, cosmids, plasmids or modified viruses eg. Replikationsdeffiziente as wie Psoriasis qd behandeln, adenoviruses and adeno-associated virusesif the vector is compatible with the host cell used.
The invention therefore draws a recombinant expression vector of the invention into consideration, which contains a nucleic acid molecule according to the invention, and the necessary regulatory sequences for the transcription and translation of the inserted protein sequence.
Methods in EnzymologyAcademic Press, San Diego, CA ] beschrieben sind. Suitable regulatory sequences may be from a variety of sources, including bacterial, fungal, viral, mammalian or insect genes can be obtained [see, e. Methods in EnzymologyAcademic Press, San Diego, CA ] are described.
The choice of appropriate regulatory sequences is dependent on the host cell chosen as discussed below, and can be easily overcome by a specialist. The invention further provides a recombinant expression vector is available, the according to the invention, which is cloned in antisense orientation into the expression vector, comprising a DNA nucleic acid molecule.
The recombinant expression vectors of the invention may also contain a marker gene that facilitates the selection of transformed wie Psoriasis qd behandeln transfected with a recombinant molecule of the invention, host cells. The markers can be introduced on a separate vector from the nucleic acid of interest. The recombinant expression vectors may also contain genes which encode a the Psoriasis in Ungarn Behandlung incidirten moiety which provides increased expression of the recombinant protein, better solubility of the recombinant protein, and aid in the wie Psoriasis qd behandeln of the target recombinant protein by acting as a ligand in affinity purification available.
For example, a proteolytic cleavage site for allowing the separation of the recombinant protein from the fusion component subsequent to purification of the fusion protein to the target recombinant protein are added. Typische Fusionsexpressionsvektoren enthalten pGEX Amrad Corp. Typical fusion expression vectors include pGEX Amrad Corp. The recombinant expression vectors can be introduced for preparing wie Psoriasis qd behandeln transformed host cell in host cells.
A Laboratory Manual, 2. Wie Psoriasis qd behandeln terms "transformed with", "transfected with", "transformation" and "transfection" encompass the introduction of a nucleic acid eg. As a vector into a cell by one of many standard techniques.
Prokaryotic cells, for example, by electroporation or calcium chloride mediated transformation to be transformed with a nucleic acid. A nucleic acid may in mammalian cells via conventional techniques such as calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection.
A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory Press can be found and other laboratory manuals. Suitable host cells include a wide variety of prokaryotic and wie Psoriasis qd behandeln host cells. For example, the proteins can be expressed insect cells using baculovirusyeast cells or mammalian cells according to the invention in bacterial cells such as E. Methods in EnzymologyAcademic Press, San Diego, CA gefunden werden.
Other suitable host cells can Gene Expression Technology in Goeddel, Methods in EnzymologyAcademic Press, San Diego, CA can be found. Glykosylierung oder Phosphorylierung und prozessiert z. It can wie Psoriasis qd behandeln be a host cell can be selected that modulates the expression of an inserted nucleic acid sequence or the protein in the desired type modified for.
Example, glycosylation or phosphorylation and processes eg. It can be selected cell lines or host systems that have the specific and characteristic mechanisms for post-translational processing and modification of proteins. For a long-term stable expression of the protein with high yield cell lines and can wie Psoriasis qd behandeln systems that express the gene stable, can be constructed.
Host cells and in particular cell lines produced using the methods described herein may be particularly useful in screening and evaluation of compounds that modulate the activity of a KLK15 protein. Paviane, Affen und Schimpansen [siehe Hammer et al. The proteins of the invention may also be expressed in non-human transgenic animals, including, but not limited to mice, rats, rabbits, guinea pigs, miniature pigs, goats, sheep, pigs, non-human primates z.
Wie Psoriasis qd behandeln Natl Acad Sci USA Known in the art methods may be used for introducing a nucleic acid encoding a KLK15 protein molecule according to the invention for the production of founder lines of transgenic animals. Such methods include microinjection into the pronucleus, mediated by retroviral gene transfer into germ lines, gene targeting in embryonic stem cells, electroporation of embryos and sperm-mediated gene transfer in.
The present invention contemplates a transgenic animals into consideration, bearing the KLK15 gene in all of its cells, and animals carrying the transgene in some, but not all their cells.
Das Transgen kann als einzelnes Transgen oder in Konkatemeren integriert werden. The transgene may be integrated as a single transgene or in concatemers. Das Transgen kann selektiv in spezifische Zellarten eingebracht und aktiviert werden siehe z. The wie Psoriasis qd behandeln click at this page be selectively introduced and activated in specific cell types see, for example, Lasko et al, Proc Natl Acad Sci USA The transgene can be inserted at the chromosomal site of wie Psoriasis qd behandeln endogenous gene by gene targeting.
Das Transgen kann selektiv in eine spezielle Zellarten eingebracht werden, wobei das endogene Gen in dieser Zellart inaktiviert wird siehe Gu et al. The transgene may be selectively introduced into a particular cell types, wherein the endogenous gene is inactivated in this cell type see Gu et al Science. Die Expression eines rekombinanten KLKProteins in einem transgenen Tier kann unter Verwendung von Standardtechniken untersucht werden.
The expression of a recombinant KLK15 protein in a transgenic animal may be assayed using standard techniques. A first screening for finding out whether the transgene has been inserted, can be carried out by Southern blot analysis or PCR techniques. The level of mRNA expression in tissues of transgenic animals may also be determined by using techniques including Northern blot analysis of tissue samples, in situ hybridization and RT-PCR.
Tissues can be evaluated immunocytochemically using antibodies also against KLK15 Protein. Wansch, Band 15 I und II, Thieme, Stuttgart hergestellt werden. Proteins according to the invention may also by chemical synthesis using in protein chemistry well known techniques such as solid phase synthesis Merrifield,J. Am Chem Assoc Wansch, Vol 15 I http://larpring.de/shampoo-ps-in-psoriasis.php II, Thieme, Stuttgart are prepared.
N-terminal or C-terminal fusion proteins comprising a KLK15 protein conjugated according to the invention with other molecules such as proteins include, may be prepared by fusing the N-terminus or C-terminus of a KLK15 Protein, and the sequence of a selected protein or marker protein be a desired biological function produced by recombinant techniques. The resulting fusion proteins contain a KLK15 protein, which is connected to the selected protein or marker protein as described herein fused.
Examples of proteins that can be used to prepare fusion proteins include immunoglobulins, glutathione-S-transferase GSThemagglutinin HAand truncated myc. KLK15 Proteins of the invention may be used for the production of specific antibodies for the proteins. It can be produced antibodies that bind to a specific epitope in a non-conserved region of the protein. Ein nicht-konservierter Bereich eines Proteins ist einer, der keine wesentliche Sequenzhomologie zu anderen Proteinen hat.
A non-conserved region of a protein is one which has no significant sequence homology to other proteins. A region from a conserved region such as a well-characterized domain can also wie Psoriasis qd behandeln used for the production of an antibody to a conserved region of a KLK15 protein. Antibodies with specificity for wie Psoriasis qd behandeln KLK15 Protein wie Psoriasis qd behandeln also be grown from fusion proteins created by expressing fusion proteins in bacteria as described herein.
The invention may whole monoclonal or polyclonal antibodies, and immunologically active fragments eg. As a Fab, Fab 2 fragment, or Fab fragments from an expression library and epitope-binding fragments thereofa heavy chain of an antibody and a light chain an antibody, a genetically engineered single wie Psoriasis qd behandeln Fv molecule Ladner et click here. Antibodies including monoclonal and polyclonal antibodies, fragments and chimeras can be made by those skilled in the known methods.
Applications of the nucleic acid molecules, KLK15 Proteins, and antibodies of the invention. The nucleic acid molecules, KLK15 proteins and antibodies according to the invention, in the prognostic and diagnostic evaluation of diseases in which a KLK15 protein is involved eg.
As cancer or thyroid diseaseand the identification of subjects with a predisposition to such diseases Section 4. The present invention provides a test kit for the diagnosis of a condition which is associated with a protein according to the invention, by determining the presence of a nucleic acid molecule or a protein according to the invention.
The test kit can be used in a method for detecting the expression of the cancer marker KLK15 in a patient, comprising: B detecting a nucleic acid sequence encoding KLK15 or a protein encoded by a KLK15 nucleic acid sequence protein product in the sample.
The nucleic acid molecules, KLK15 Proteins, and antibodies of the invention may be used in the diagnosis and staging of cancer, in particular prostate cancer. Increased levels of KLK15 Proteins are associated with more aggressive forms of prostate cancer and to see more indication of a poor prognosis be.
A method for detecting nucleic acid molecules and KLK15 Proteins of the invention may be used by detecting KLK15 Proteins and nucleic acid molecules encoding KLK15 Proteins for monitoring of diseases in which a KLK15 protein is involved.
The applications of the present invention also include methods for identifying compounds that modulate the biological activity of KLK15 Proteins modulate section 4. The compounds, antibodies, etc. For an expert it would also be appreciated that the methods described herein for testing for the expression of KLK15 Proteins can be used in the development and consequently more knowledge regarding the role of KLK15 Proteins are provide.
A variety of methods can be used for diagnostic and prognostic assessment of diseases in which a KLK15 protein is involved, and identification of subjects with a predisposition to such diseases. Such methods can, for. Example, nucleic acid molecules of the invention and fragments thereof, and antibodies against KLK15 Proteins, including peptide fragments used. In particular, the nucleic acids and antibodies may be used, for example, for:.
The methods described herein can be used to evaluate the probability of the presence of malignant or premalignant cells, eg, as in a group of freshly extracted from the host cells. Such methods can be used to detect tumors, quantitate their growth and assist in the diagnosis and prognosis of click the following article. They can be further used to monitor chemotherapy in cancer and the reappearance of a tumor.
The methods described herein may be performed by use of compiled diagnostic kits containing at Salbe Kräuter Psoriasis as herein described continue reading KLK15 nucleic acid or antibody, which can be used conventionally, for.
Example, in clinical settings, to screen and diagnose patients and to screen and identify of individuals which have a predisposition to develop a disease. Nucleic acid-based techniques are described below in Section 4. Techniken zur Learn more here von Peptiden sind unten in Abschnitt 4. Techniques for the detection of peptides are described in section wie Psoriasis qd behandeln. The samples that can be analyzed using the method wie Psoriasis qd behandeln to the invention include those which are known or suspected to express KLK15 or contain KLK15 Proteins.
The samples may be derived from a patient or a cell culture and include, but are not limited to, biological fluids, tissue extracts, freshly harvested cells, and lysates from cells that had been incubated wie Psoriasis qd behandeln auf Flecke rote Schuppenflechte den Beinen culture.
Oligonucleotides or longer fragments which have been obtained by any of the nucleic acid molecules according to the invention can be used as target wie Psoriasis qd behandeln a microarray. The microarray can be used for simultaneously monitoring the expression levels of large numbers of genes and to identify genetic variations, mutations and polymorphisms.
The information from the microarray may be used to determine gene function, to understand the genetic basis of a disorder, to diagnose a disorder, and to develop wie Psoriasis qd behandeln monitor the activity of a therapeutic agent. Die Herstellung, Verwendung und Analyse von Mikroanordnungen sind einem Fachmann wohlbekannt siehe z. Brennan, Wie Psoriasis qd behandeln et al.
The preparation, use, and analysis of micro arrays are well known to one skilled in the art see, for. Example, Brennan, TM et al.
The nucleic acid molecules according to the invention allow the skilled artisan to create nucleotide probes for use in detection of nucleic acid sequences according to the invention in samples. Suitable probes include nucleic acid molecules based on nucleic acid sequences encoding at least 5 sequential amino acids from regions of the KLK15 Protein, preferably they comprise 15 to 30 nucleotides see SEQ.
Other detectable substances which may be used include antigens that are recognized by a specific labeled antibody, fluorescent compounds, enzymes, antibodies specific for a labeled antigen, and luminescent compounds.
An appropriate label may be selected at nucleotide taking into account the rate of hybridization and binding of Dermatitis Psoriasis-Behandlung probe wie Psoriasis qd behandeln the nucleotide to be detected and the amount available for hybridization.
Labeled probes can on a solid wie Psoriasis qd behandeln such as nitrocellulose filters or nylon membranes as generally described in Sambrook wie Psoriasis qd behandeln al. Describes, are hybridized to nucleic acids.
The nucleic acid probes can be used preferably in human cells, for detecting genes encoding KLK15 Proteins. The nucleotide probes may be useful wie Psoriasis qd behandeln monitoring the progression of such diseases, or monitoring a therapeutic treatment or diagnosis of disorders involving wie können, was Psoriasis-Tests Sie feststellen KLK15 protein is involved.
Die Sonde kann bei Hybridisierungstechniken zum Wie Psoriasis qd behandeln von KLKProteine codierenden Genen verwendet werden. The probe can be used in hybridization techniques to detect genes encoding KLK15 Proteins.
The technique generally involves contacting and incubating nucleic acids eg. After incubation, the nucleic acids which wie Psoriasis qd behandeln not formed a double strand are removed wie Psoriasis qd behandeln the presence of nucleic acids that have hybridized to the probe is detected if present. The detection of nucleic acid molecules according to the invention, the amplification of specific gene sequences using an amplification method such as PCR, followed by analysis of the amplified molecules using techniques known to those skilled in wie Psoriasis qd behandeln techniques, include.
Suitable primers can be routinely created by a professional. Genomic DNA may be used in hybridization or Amplifizierungsuntersuchungen of biological samples to detect associated with the KLK15 structure abnormalities, including point mutations, insertions, deletions and chromosomal rearrangements. For example, direct sequencing, single stranded conformational polymorphism analyzes, heteroduplex studies, denaturing gradient gel electrophoresis, chemical mismatch cleavage, and Oliognukleotidhybridisierung can be used.
The art-known genotyping techniques can be used to type polymorphisms that are in close proximity to the mutations in a KLK15 gene. The polymorphisms may be used to identify individuals in families that wie Psoriasis qd behandeln likely to carry a mutation. Sofern ein Polymorphismus ein Kopplungsungleichgewicht mit Mutationen in einem KLKGen aufweist, kann er auch zum Durchmustern von Individuen der allgemeinen Population, die wahrscheinlich Mutationen tragen, verwendet werden.
If a polymorphism exhibits linkage disequilibrium with mutations in a KLK15 gene, it can also be used for wie Psoriasis qd behandeln the general population of individuals that are likely to carry mutations. Polymorphisms which may be used include restriction fragment length polymorphisms RFLPssimple and Einzelbasenpolymorphismen Sequenzwiederholungspolymorphismen SSLPs a.
Eine Sonde nach der Erfindung kann zum direkten Identifizieren von RFLPs verwendet werden. A sonde according to the invention can be used to directly identify RFLPs. A probe or primer of the invention may in addition to the isolation of genomic clones, such as YACs, BACs, PACs, cosmids, phage or plasmids can be used. Die DNA in den Klonen kann unter Verwendung von Hybridisierungs- oder Sequenzierungsverfahren auf SSLPs durchmustert werden.
The DNA in the clones can be screened using hybridization or sequencing procedures to SSLPs. The hybridization and amplification techniques described herein can be used to examine qualitative and quantitative aspects of the KLK15 expression. Standard-Northern-Untersuchungen oder PCR-Techniken untersucht werden. For example, RNA can be from a cell type or tissue, which is known by expressing KLK15 be isolated and using said hybridization herein eg.
As standard Northern analyzes or PCR techniques be investigated. The techniques wie Psoriasis qd behandeln be wie Psoriasis qd behandeln to detect differences in the size of the transcript, which may be due to normal or abnormal alternative splicing. Specifically with a KLK15 protein reactive antibodies or derivatives, such as just click for source conjugates or labeled derivatives, may be used to detect KLK15 Proteins in various samples z.
Antibodies can also be used to wie Psoriasis qd behandeln potential therapeutic compounds in vitro to determine your impact on diseases in which a KLK15 protein is involved, and other conditions. In vitro immunoassays may also be used to assess and monitor the effectiveness of certain therapies. The antibodies according to the invention can also be used in vitro to determine the amount of KLK15 expression in genetically for preparing a KLK15 protein engineered cells.
The antibodies can be used in any known immunoassay, which wie Psoriasis qd behandeln based on the binding interaction between an antigenic determinant of a KLK15 Protein and the antibodies. Examples of such studies are radio immunoassays, enzyme immunoassays z. ELISAimmunofluorescence, immunoprecipitation, latex agglutination, hemagglutination and histochemical tests. The antibodies can be used to detect and quantify KLK15 of proteins in a sample, to determine its role in particular cellular events or pathological states, and to diagnose and treat such pathological states.
In particular, the antibody according to the wie Psoriasis qd behandeln, in immunohistochemical studies, for. Example, at the cellular and subcellular level, to detect a KLK15 Protein, wie Psoriasis qd behandeln be its localization to specific cells and tissues and to specific subcellular locations, and to quantitate the expression levels can be used.
Cytochemical techniques in the art die Salbe für Psoriasis gut 75 localizing antigens using known light and electron microscopy may be used to detect a KLK15 Wie Psoriasis qd behandeln. FITC, Rhodamin, seltene Erden-Phosphorelumineszente Markierungen, wie Luminol, enzymatische Markierungen z.
Generally, an antibody of the invention with a detectable substance to be marked and a related with KLK15 Protein may be localized in tissues and cells based on the presence of the detectable substance: In some embodiments, the markings with spacer arms of various lengths are mounted to reduce a possible steric hindrance. Antibodies may also be coupled to electron dense substances, such as ferritin or colloidal gold, which can be readily visualized by electron microscopy.
The antibody or sample may be immobilized on a carrier or solid support which is suitable for immobilizing cells, wie Psoriasis qd behandeln etc.
The carrier or substrate nitrocellulose or glass, polyacrylamides, gabbros and magnetite example can be. The support material wie Psoriasis qd behandeln have any design, including spherical eg. Indirect methods may also be used, in which the first antigen-antibody reaction by the introduction of a second antibody wie Psoriasis qd behandeln specificity for the antibody reactive wie Psoriasis qd behandeln KLK15 Protein is reproduced.
As an example, if the antibody having specificity for a KLK15 Protein is a rabbit IgG antibody, the second antibody may be a labeled with gamma globulin anti-rabbit goat antibody that is labeled with a detectable substance as described herein. Sofern als detektierbare Substanz eine radioaktive Markierung verwendet wird, kann ein KLKProtein durch Autoradiographie lokalisiert werden. If, as a detectable substance, a radioactive label is used, a KLK15 Protein may be localized by autoradiography.
The results of autoradiography may be quantitated by determining the density of particles in the autoradiographs by various optical methods, or by counting the grains.
In one embodiment, the invention contemplates a kit for monitoring the progression of cancer such as prostate cancer. In an individual into consideration, which comprises: D comparing the results of step b with the result of step wie Psoriasis qd behandelnwherein a difference in the amount of complex formation indicating the progression of the cancer in the subject.
The amount of complexes can also be a representative value of the amount of complexes in an individual, the non-cancerous z. The methods described herein are designed to identify substances that modulate the biological activity of a KLK15 Protein including substances that bind to KLK15 Proteins, or bind to other proteins that interact with a KLK15 Protein, of compounds, the interaction of the interfere with a KLK15 protein or strengthen and substances that bind to the KLK15 protein or other proteins that interact with a KLK15 protein.
Methods are used to identify the compounds that bind to KLK15 regulatory sequences for. Example, Fab, F ab 2 and Fab fragments from an expression library and epitope-binding fragments thereof ], and small organic or inorganic molecules. The substance or compound may be an endogenous physiological compound, or a natural or synthetic compound. Substances that modulate a KLK15 Protein may be identified by their ability to bind to a KLK15 Protein.
Therefore, the invention also provides methods for identifying substances that bind to a KLK15 Protein, available. Using procedures according to the invention conventional techniques identified substances can be isolated, cloned and sequenced using. A substance that associates with a polypeptide according to the invention, an agonist or antagonist of the biological or immunological activity of a polypeptide according to the invention can be.
The term "agonist" refers to a molecule that increases the amount of protein activity or prolonging their persistence. The term "antagonist" refers to a molecule that reduces the biolo gical or immunological activity of the protein. Agonists and antagonists may include proteins, nucleic acids, carbohydrates or any other molecule that associates with a protein according to the invention.
The complexes can be detected by assaying for substance-KLK15 protein complexes, for free substance or non-complexed KLK15 protein.
Conditions which permit the formation of substance-KLK15 Protein complexes can taking into account factors such as the type and quantity of the substance and the protein are selected.
Aussalzen, Chromatographie, Elektrophorese, Gelfiltration, Fraktionierung, Absorption, Polyacrylamid-Gelelektrophorese, Agglutination oder Kombinationen davon. The substance-protein complex, free substance or non-complexed proteins may be isolated by conventional isolation techniques, for.
Example, salting out, chromatography, electrophoresis, gel filtration, fractionation, absorption, polyacrylamide gel electrophoresis, agglutination, or combinations thereof. To simplify the study of the components of antibodies against Wie Psoriasis qd behandeln Protein or against the wie Psoriasis qd behandeln, or labeled KLK15 Protein, or a labeled substance may be utilized.
The antibodies, proteins, or substances may be labeled with detectable substances, wie Psoriasis qd behandeln described above, labeled. A KLK15 Protein, or the substance used in the method of the invention may be insolubilized.
For example, http://larpring.de/salbe-psoriasis-l-ei-essig.php KLK15 protein or a substance can be bound to a suitable carrier such as agarose, cellulose, dextran, Sephadex, Sepharose, carboxymethyl cellulose, polystyrene, filter paper, ion exchange resin, plastic film, plastic tube, glass beads, polyamine-methyl vinyl ether-maleic acid copolymer, amino acid copolymer, ethylene-maleic acid copolymer, nylon, silk, etc.
The carrier may be in the form of z. The insolubilized protein or substance may be prepared by reacting the material with a suitable insoluble carrier using known chemical or physical methods, for. Example, cyanogen bromide coupling. The invention also contemplates a method for evaluating a compound for its ability to modulate visit web page biological activity of a KLK15 protein of the invention by assaying for an agonist or antagonist ie amplifier or inhibitor of the binding of a KLK15 Protein with a substance which at a KLK15 protein binds into consideration.
Das Basisverfahren zur Bewertung, ob eine Verbindung ein Agonist oder Antagonist der Bindung eines KLKProteins und einer Substanz, die an das Protein bindet, ist eine das KLKProtein und die Substanz enthaltende Reaktionsmischung herzustellen, unter Bedingungen, die die Bildung eines Substanz-KLKProtein-Komplexes gestatten, in der Anwesenheit der Testverbindung.
The basic method for evaluating whether a compound wie Psoriasis qd behandeln produce an agonist or antagonist of the binding of a KLK15 Protein and a substance that binds to the protein, is the KLK15 Protein and the substance-containing reaction mixture under conditions that allow the formation of a substance KLK15 protein complex allow, in the presence of the test compound.
The test compound may be added at the beginning or after the addition of the KLK15 Protein and substance. Kontrollreaktionsmischungen wie Psoriasis qd behandeln die Testverbindung oder mit einem Plazebo werden auch hergestellt. Control reaction mixtures without the test compound or with a placebo are also prepared. The formation of complexes is detected and the formation of complexes in the control reaction but not in the reaction mixture indicates that the test compound interferes with the interaction of the KLK15 Protein and substance.
The reactions can be carried out in liquid phase or the KLK15 Protein, substance, or test compounds can be immobilized as described herein. The ability of a compound to modulate the biological activity of a KLK15 protein of the invention can be assayed by determining the biological wie Psoriasis qd behandeln on cells.
Wie Psoriasis qd behandeln will be understood that the agonists and antagonists, ie inhibitors and amplifiers, which can be examined using the methods of the invention may act on one or more of the binding sites on the protein or substance including agonist binding sites, competitive antagonist binding sites, non-competitive antagonist binding sites or allosteric sites. The invention also makes it possible to screen for antagonists, the interaction of the KLK15 protein, inhibit the effect of an agonist with a substance, which is capable of binding to the KLK15 Protein.
Somit kann die Erfindung auch zum Untersuchen auf eine Verbindung verwendet werden, die um die gleiche Bindungsstelle an einem KLKProtein konkurriert. Thus, the invention can also be used for wie Psoriasis qd behandeln for a compound wie Psoriasis qd behandeln competes for the same binding site of a KLK15 Protein.
The invention also contemplates methods for identifying compounds thereof, that bind to proteins that interact with a KLK15 Protein. It can be applied wie Psoriasis qd behandeln processes that lead to a simultaneous identification of genes that code for interacting with a KLK15 protein proteins. These methods include probing expression libraries with labeled KLK15 protein. Two-hybrid systems may also be used for detection wie Psoriasis qd behandeln protein interactions in vivo.
Im allgemeinen werden Plasmide erstellt, die zwei Hybridproteine codieren. In general, plasmids are created that encode two hybrid proteins. A first wie Psoriasis qd behandeln protein consists of the DNA-binding domain of a transcription activator protein fused to a KLK15 Protein, and the second hybrid protein consists of the activator domain of the transcription activator protein fused to an unknown protein that is encoded by a cDNA as part of a cDNA library was recombined into the plasmid.
Die Plasmide werden in einen Hefestamm transformiert z. BS cerevisiaeder ein Reportergen z. The plasmids are transformed wie Psoriasis qd behandeln a yeast strain e. Wie Psoriasis qd behandeln lacZ, luciferase, alkaline phosphatase, horseradish peroxidase wie Psoriasis qd behandeln regulatory region contains the binding site of the Transkripitonsaktivators.
The hybrid protein alone can not activate transcription of the reporter gene. However, the interaction of the two hybrid proteins represents the functional activator protein and results in the restore expression of the reporter gene, which is detected by screening for the reporter gene product. It will be appreciated that fusion proteins can be used in the methods described above. In particular, KLK15 Proteins fused with glutathione-S-transferase can be used in the methods.
A modulator of a KLK15 protein of the invention may also be due to its ability to inhibit the catalytic activity of wie Psoriasis qd behandeln protein or first Psoriasis-Behandlung auf den Palmen rezeptfrei identified.
The application of the method according to the invention suitable reagents for the study of compounds that modulate a KLK15 protein can be packaged in convenient kits containing packed in suitable containers with the wie Psoriasis qd behandeln materials.
The kits may also contain suitable auxiliaries, which are suitable in carrying out the method according to the invention. The proteins according to the invention described by the process herein identified substances or compounds and the nucleic acid molecules of the invention may be used for modulating the biological activity of a KLK15 Protein, and they can be in the treatment of wie Psoriasis qd behandeln such as cancer particularly thyroid, prostatecolon, kidney, testis cancer and thyroid diseases are used in a patient.
Accordingly, the substances, antibodies, peptides, and compounds may be formulated into pharmaceutical compositions for administration to subjects in a biologically compatible form suitable for in vivo administration.
By "biologically compatible form suitable for administration in vivo" is a form of the administered active substance is meant, in which any toxic effects are outweighed by Psoriasis Genitalien therapeutic effects. Wie Psoriasis qd behandeln active substances can in living organisms, including humans and animals, be administered. For example, a therapeutically wie Psoriasis qd behandeln amount of a substance according to factors such as the disease state, age, sex, and weight of the individual, and the ability of an antibody to elicit a desired response in the wie Psoriasis qd behandeln can vary.
The dosage administered may be adjusted to provide the optimal therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reducedas indicated by the need of the therapeutic situation.
The active wie Psoriasis qd behandeln may be administered in a suitable way by injection subcutaneous, intravenous, etc. Depending on the route of administration, the active substance may be encased in a material to protect the substance from the action of enzymes, acids and other natural conditions that may inactivate the substance. The compositions described herein may be prepared by methods known per se for the preparation of pharmaceutically acceptable wie Psoriasis qd behandeln which wie Psoriasis qd behandeln be administered to subjects, such that an effective amount of the active substance is combined in a mixture with a pharmaceutically acceptable carrier substance.
Suitable carrier substances are described, for. On this basis, the compositions include a long, although not exclusively, solutions of the active substances in conjunction with one or more pharmaceutically acceptable carriers or diluents, and are in buffered solutions with a suitable pH and iso-osmotic with physiological fluids contain.
Die Zusammensetzungen sind als therapeutische Wie Psoriasis qd behandeln entweder article source oder in Verbindung mit anderen therapeutischen Mitteln oder Behandlungsformen angezeigt z. The compositions are useful as therapeutic agents either alone or in conjunction with other therapeutic agents or treatments displayed eg.
As chemotherapy or radiation. For example, the compositions may be in combination with antiproliferative agents, antimicrobial agents, immunostimulatory agents, or anti-inflammatory agents are used.
The compositions of the invention may be combined, separately or in connection with other therapeutic agents or therapies administered. Vectors derived from retroviruses, adenoviruses, herpes or vaccinia viruses or bacterial plasmids, can contribute to the delivery of nucleic acid molecules in a target organ, tissue or cell link may be used.
Those skilled in the well-known method for constructing recombinant vectors, antisense nucleic acid molecules are expressing according to the invention, can be used see, for. Example, the techniques described in Sambrook et al. Above and Ausubel et al. Annu Rev Biochem This technology is well known in the art, and sense or antisense oligomers or larger fragments can be designed from various locations along the coding regions or control regions.
Genes encoding a protein according to the invention may be prepared by transfecting a cell or tissue with vectors which express high levels of a desired KLKencoding fragment, shall be placed. Such constructs can flood cells with non-translatable sense or antisense sequences. Even in the absence of integration into the DNA, such vectors can transcribe long RNA molecules until all copies are disabled by endogenous nucleases. Modifications of gene expression can be obtained by designing antisense molecules, DNA, RNA or PNA to the regulatory regions of a gene which encodes a protein according to the invention, ie the promoters, enhancers and introns can be obtained.
Bevorzugt stammen die Oligonukleotide von der Transkriptionsinitiationsstelle, z. Preferably, the oligonucleotides of the transcription wie Psoriasis qd behandeln site, eg. Wie Psoriasis qd behandeln antisense molecules may also be designed so that they block translation of mRNA by preventing the binding of the transcript to ribosomes.
Inhibition kann auch durch Wie Psoriasis qd behandeln der Tripelhelix-Basenpaarungsmethodik erreicht werden. Inhibition can also be achieved by use of the triple-helix base-pairing methodology. Triple helix pairing compromises the ability of the double helix to open sufficiently for the binding of polymerases, transcription factors or regulatory molecules.
Therapeutische Vorteile bei der Verwendung von Triplex-DNA wurden durch Gee JE et al. Therapeutic advantages when using triplex DNA have been carried Gee JE et al. Huber BE and BI Carr Molecular and Immunologic Approaches, Futura Publishing Wie Psoriasis qd behandeln, Mt Kisco NY Ribozymes are enzymatic RNA molecules that catalyze the specific cleavage of RNA.
Ribozymes act by sequence-specific hybridization of the ribozyme molecule to complementary target RNA, followed by endonucleolytic cleavage. The invention therefore attracts designed ribozyme wie Psoriasis qd behandeln hammerhead motif into consideration the endonucleolytic cleavage of sequences specifically and efficiently catalyze encoding a protein of the invention. GUA, GUU und GUC.
Specific ribozyme cleavage sites within a potential RNA target may initially by screening of the target molecule after ribozyme cleavage sites which include the following sequences can be identified: GUA, GUU and GUC. Do they have been identified, short RNA sequences of 15 to 20 ribonucleotides corresponding to the region of the target gene containing the cleavage sites are in secondary structural characteristics that may render the oligonucleotide inoperable rated.
The suitability of candidate target can be determined by testing for accessibility to hybridization with complementary oligonucleotides using Ribonukleaseschutzuntersuchungen. Methods for introducing vectors into cells or tissues include those methods discussed herein, which are suitable for in vivo, in vitro and ex vivo therapy. In order to ex vivo therapy vectors can be introduced into stem cells obtained from a patient and propagated for autologous transplantation in the same patient, inserted see US Pat.
Die Verabfolgung durch Wie Psoriasis qd behandeln und durch Liposom wie Psoriasis qd behandeln im Fachgebiet wohlbekannt. The administration by transfection and by liposome is well known in the art.
An antibody against a KLK15 Protein may be conjugated with chemotherapeutic drugs, toxins, immunological wie Psoriasis qd behandeln modifiers, hematogenous agents, enzymes, and radioisotopes and in the prevention and treatment of cancer B. Thyroid, prostate, colon, kidney - testicular cancer may be used. For example, can be an antibody against a KLK15 protein with toxic residues, including but not limited to ricin A conjugate, diphtheria toxin, abrin, modeccin, and bacterial toxins from Pseudomonas or Shigella.
Toxins and their derivatives has been described that they form conjugates with certain target tissues, such wie Psoriasis qd behandeln cancer or tumor cells, specific antibodies, for the recovery of specific targeted cellular toxicity Moolten FL et al, Rev. Conjugates can be prepared by methods known in the art. A number of bifunctional linking agents eg.
As heterobifunktionaie connectors, such as N-succinimidyl 2-pyridyldithio propionate is of Chemically Pierce Company, Rockford, III are commercially available. The antibodies or immunotoxins for therapeutic use may be administered via an wie Psoriasis qd behandeln route, wherein at a suitable formulation additional routes of administration such as intraperitoneal, oral or transdermal administration, may wie Psoriasis qd behandeln used.
Ein KLKProtein kann unter Verwendung von im Fachgebiet bekannter Verfahren mit chemotherapeutischen Arzneimitteln, Toxinen, Modifikatoren der immunologischen Antwort, Enzymen und Radioisotopen konjugiert werden.
A KLK15 Protein may be conjugated using a known method in the art with wie Psoriasis qd behandeln drugs, toxins, immunological response modifiers, enzymes and radioisotopes. The invention also provides immunotherapeutic approaches to prevent or reduce the severity of cancer available.
The clinical signs or symptoms of cancer in a subject Münz-Plaque-Psoriasis a beneficial effect for the patient due to the stimulation of the immune response of the subject against cancer at.
Stimulating an immune response refers to inducing an immune response or enhancing the activity of immune effector cells in response to administration of a vaccine preparation according the invention. The prevention of cancer wie Psoriasis qd behandeln be indicated by a prolonged period of time prior to the occurrence of cancer in a patient, for example, a genetic predisposition or contact with a carcinogenic agent is susceptible http://larpring.de/monoklonale-antikoerper-psoriasis-kaufen.php developing cancer due.
The reduction of the severity of a cancer may be indicated by decrease in size or growth rate of a tumor. Vaccines can be obtained from a KLK protein derived peptides or chemically produced synthetic peptides, or any combination of these molecules or fusion proteins or peptides thereof. Die Proteine, Peptide, etc. The proteins, peptides, etc. Epitopes of a tumor-associated protein should be understood that the possibility is that in some cases the amino acid sequence variations of a protein or polypeptide may be naturally occurring antigenic and confer protective immunity against cancer or anti-tumorigenic effects.
Sequence variations thereof may include, without limitation, amino acid substitutions, extensions, deletions, truncations, interpolations and combinations. Techniques to enhance the antigenicity of proteins, peptides, etc. As keyhole limpet hemocyanin KLH or diphtheria toxoid, and administration in combination with adjuvants or any other amplifier of the wie Psoriasis qd behandeln response.
It will also wie Psoriasis qd behandeln pleased to note that anti-idiotypic antibodies against antibodies against described herein KLK15 proteins are also useful as vaccines and can be formulated in the same way. The administration of a vaccine according to the invention is generally applicable in the prevention or treatment of cancer, including thyroid, prostate, colon, kidney, and testicular cancer.
As surgery, chemotherapy, radiation therapy. The vaccines have the means or ability cancer in subjects without cancer, but run the risk of developing cancer prevention. The activity of the proteins, substances, compounds, antibodies, nucleic acid molecules, agents, and compositions of the invention can be confirmed animal model systems. Pharmazeutische Wie Psoriasis qd behandeln, die hohe therapeutische Indizes aufweisen, sind bevorzugt.
Pharmaceutical compositions which exhibit high therapeutic indices are preferred. The herein disclosed nucleic acid molecules in molecular biology techniques that have not yet developed, may be used provided that the new techniques are based on the currently known properties of the nucleotide sequences, including but not limited to properties such as the triplet genetic code and specific base pair interactions.
To examine the function of a polypeptide of the invention, cells, tissues and non-human animals can or with a lack of expression or partial lack of expression of a nucleic acid molecule or gene of the invention using recombinant expression vectors of the invention having specific deletion insertion mutations in the gene to be developed.
A recombinant expression vector can be used wie Psoriasis qd behandeln inactivate or alter the endogenous gene by homologous recombination, and thereby create a cell, a tissue or wie Psoriasis qd behandeln animal with a defect.
Null alleles can be generated by Deletonsmutation in cells, such as embryonic stem wie Psoriasis qd behandeln. A recombinant gene may also be constructed so that it contains an insertion mutation inactivating the gene. Ein solches Konstrukt kann dann durch Techniken, wie Trans fektion, Elektroporation, Injektion, etc.
Such a construct may then by techniques, such as trans fection, electroporation, injection, etc. Southern Blot, Northern Click the following article oder durch Untersuchen auf die Expression des codierten Polypeptids wie Psoriasis qd behandeln Verwendung hierin beschriebener Methoden identifiziert werden.
Cells lacking an intact gene may then be identified by z. Southern blot, Northern blot, or by assaying for expression of the encoded polypeptide using methods described herein. Such cells can then be fused to embryonic stem cells to generate transgenic, non-human animals with a lack of a polypeptide according to the invention.
Germline transmission of the mutation can for. Example, by aggregating the embryonic stem cells embryos at an early stage, such wie Psoriasis qd behandeln 8-cell embryos, be go here in vitro, the resulting Plastozysten be transferred into female recipients and germ line transmission of the resulting Aggregationschimeren is generated.
Such a mutant animal can be used to determine specific cell populations, development patterns and in vivo processes that depend usually of gene expression. A more info, non-human mammal whose germ cells and whole body cells contain a recombinant expression vector that inactivates or alters containing a KLK15 Protein A gene can be developed.
The transgenic non-human mammal the entire germ cells and somatic cells contain a recombinant expression vector, the disabled or changed, containing a KLK15 protein a gene can lead to a KLK15 protein-associated pathology. A transgenic non-human mammal that does not express a KLK15 protein of the invention or a modified z. A KLK15 Protein pathology refers to a phenotype observed in homozygous or heterozygous for a KLK15 protein mutants.
Ein transgenes, nicht humanes Tier kann zum Beispiel eine Maus, Ratte, Kaninchen, Schaf, Hamster, Hund, Katze, This web page oder Affe sein. A transgenic non-human animal can be for example a mouse, rat, rabbit, sheep, hamster, dog, cat, goat, or monkey. A transgenic non-human animal inspection system can provide a model system for testing an agent available that reduces just click for source with a KLK15 protein inhibits pathology or as an associate with a KLK15 protein pathology, comprising: B determining from the means pathology z.
The agent may be in wie Psoriasis qd behandeln treatment and prevention of conditions such as cancer as discussed herein, are suitable.
Das Mittel kann auch in pharmazeutische Zusammensetzungen, wie hierin beschrieben, eingebracht sein. The agent can also be in pharmaceutical compositions, as described herein, is introduced. Das folgende, nicht begrenzende Beispiel veranschaulicht die vorliegende Erfindung: The following non-limiting Psoriasis Salbe auf Basis von Essig illustrates the present invention: Materialien und Verfahren Materials and Methods.
Identifizierung des neuen Gens Wie Psoriasis qd behandeln of the new gene. A continuous map of the human kallikrein gene locus extending from the KLK1 gene centromeric to the KLK14 gene telomere 7, 8, 11, 12, 27was created.
This area spans, overlapping bacterial artificial chromosome BAC were identified by screening a human BAC library using different radioactively wie Psoriasis qd behandeln gene-specific probes. Ein Bereich von — kb genomische Sequenz wurde, wie vorher beschrieben, 11, 27 unter Verwendung verschiedener Techniken etabliert.
By performing EcoR1 restriction analysis was the kallikrein-place along the EcoR1 restriction map of chromosome 19q13, which is available from the Lawrence Livermore National Laboratory LLNLrespectively. A BAC clone, the more closer to the centromere extends BCwas then identified. Contigs of linear genomic sequence of this clone are available from LLNL.
Initially, these contig sequences were used to predict the presence of novel genes, using bioinformatic approaches, as previously described 8, 12 is used, and a new series of protease was identified. The sequence of the putative gene was then passed through different approaches, including sequencing, EST-database searching, PCR screening of tissues, as described below confirmed. Suche nach exprimierten, sequenzmarkierten Stellen EST Search expressing sequence tags EST.
The predicted exons of the putative new gene were subjected to homology search using the BLASTN algorithm 28 on the Internet hosts the National Center for Biotechnology Information http: Die Klone wurden vermehrt, wie an anderer Stelle wie Psoriasis qd behandeln aufgereinigt 30 und wie Psoriasis qd behandeln einem automatischen Sequenzierer aus beiden Richtungen unter Verwendung von das Wie Psoriasis qd behandeln Vektorprimern sequenziert.
The clones were propagated as described elsewhere purified 30 and with an automatic sequencer from both directions using vector primers flanking the insert sequenced. Prostatakrebszellinie und hormonelle Stimulationsexperimente Prostatakrebszellinie and hormonal stimulation experiments. Die LNCaP-Prostatakrebszellinie wurde von der American Type Culture Collection ATCCRockville, MD, erworben. The LNCaP Prostatakrebszellinie was purchased from the American Type Culture Collection ATCCRockville, MD.
The cells were cultured for 24 hours and then harvested for mRNA extraction. Die gesamte RNA wurde von den LNCaP-Zellinien oder aus Prostatageweben unter Verwendung von Trizol-Reagenz Gibco BRLden Anweisungen des Herstellers folgend, extrahiert. Die Konzentration der RNA wurde spektrophotometrisch ermittelt. The concentration of RNA was determined wie Psoriasis qd behandeln. The final volume was 20 ul.
Basierend auf der kombinierten Information, die aus der vorhergesagten genomischen Struktur des neuen Gens und der EST-Sequenz siehe unten erhalten wurde, wurden zwei genspezifische Primer KLKF1 — SEQ ID NO. Based on the combined information see below was obtained from the predicted genomic structure of the new gene and the EST sequence, two gene-specific primers KLKF1 - SEQ ID NO 47 and KLKR1. All primers for RT-PCR spanned at least 2 exons to avoid contamination by genomic DNA.
Vitamine und Injektionen für Psoriasis confirm the identity of the PCR products of these in the pCR 2. Die Inserts wurden aus beiden Richtungen unter Verwendung von vektorspezifischen Primern mit einem automatischen DNA-Sequenzierer sequenziert. The inserts were sequenced from both directions using vector-specific primers, with an automated DNA sequencer. Die gesamte RNA, die aus 26 unterschiedlichen humanen Geweben isoliert wurde, wurde von Clontech, Palo Alto, CA, erworben.
The entire RNA was isolated from 26 please click for source human tissues was purchased from Clontech, Palo Alto, CA. Tissue cDNAs were in numerous dilutions using two wie Psoriasis qd behandeln primers KLKF2 SEQ ID NO 49 and KLKR1 SEQ ID NO 48 Table 1 multiplied. Due to the high degree of homology between the kallikreins and to exclude non-specific amplification, the PCR products were cloned and sequenced.
Patients were obtained prostate tissue samples from 29, Germany had undergone a radical wie Psoriasis qd behandeln prostatectomy for adenocarcinoma of the prostate at the University Hospital Wie Psoriasis qd behandeln, Berlin. Die Patienten erhielten keine hormonelle Therapie vor der Wie Psoriasis qd behandeln. The patients did not receive any hormonal therapy before surgery.
Wie Psoriasis qd behandeln Verwendung dieser Gewebe zu Forschungszwecken wurde durch die Ethikkommission des Charite Krankenhauses genehmigt. Fresh prostate tissue samples were obtained from the cancerous and non-cancerous parts of the same prostate, which wie Psoriasis qd behandeln been removed, was obtained. Small pieces of tissue were dissected immediately after removal of the prostate Behandlung der als Psoriasis stored until assayed in liquid nitrogen.
Histological examination of all the tissue pieces was performed as previously described 31 carried out, to ensure that the tissue was either malignant or benign. The tissue was pulverized with a hammer under liquid nitrogen and RNA was wie Psoriasis qd behandeln described above, extracted using Trizol reagent. Statistische Untersuchung Statistical study.
The statistical analysis was performed with SAS software SAS Institute, Cary, NC. The investigation of the differences between KLK15 expression in non-cancerous versus cancerous tissues from the same patient over were carried out using the non-parametric McNemar test.
Die Binomialverteilung wurde zur Berechnung des Signifikanzniveaus verwendet. The binomial distribution was used to calculate the level of significance. A multiple alignment was performed using the "Clustal X" -Softwarepakets and mulitple alignment program, which is available from the Baylor College of Medicine, Houston, TX, USA, performed. Phylogenetic studies were performed using the "Phylip" -Softwarepakets. Signalpeptide wurden unter Verwendung des "SignalP"-Rechners vorhergesagt. Signal peptides were predicted using the "SignalP" -Rechners.
Protein structural studies were carried out by the "SAPS" program structural analysis of proteins sequence. Klonieren des KLKGens Cloning of the Click to see more gene. A continuous map of the human kallikrein gene wie Psoriasis qd behandeln extending from the KLK1 gene centromeric to the KLK14 gene telomere extends previously established 7, 8, 11, 12, To investigate the presence of other kallikrein-like genes that are closer to the centromere in relation to KLK1 are, as has been described in Materials and Methods, a BAC clone BC was obtained.
According to the published genomic sequence of prostate specific antigen PSA and human renal kallikrein KLK1 gene were, for each of these genes, gene-specific primers designed Table 1, SEQ. A PCR screening of the BAC clone with these gene-specific primers showed that this clone is negative for KLK1 positive, but for PSA, which was therefore confirmed that it is in relation to PSA closer to the centromere.
A putative new series of protease was determined from the sequence of this clone by computer programs as previously described 12predicted. This clone was digested, transferred to a membrane and with gene-specific primers for the putative KLK15 gene according to the predicted sequence hybridizes and positive fragments were subcloned and sequenced to confirm the structure http://larpring.de/als-psoriasis-lippe-zu-behandeln.php the putative gene.
This putative gene sequence was then compared with the Blast program against the human EST database and two EST clones identified GenBank accession numbers: The PCR products were sequenced. Zwei dieser Primer KLKF1 — SEQ. Two of these primers KLKF1 - SEQ ID NO 47 and KLKR1 SEQ ID NO 48 Http://larpring.de/sophora-creme-fuer-psoriasis-kaufen.php 1 were able to reproduce the entire coding region of the gene from different tissues.
Ein Vergleich der mRNA mit der genomischen Struktur zeigte das Vorhandensein eines Gens an, das aus 5 codierenden Exons mit 4 dazwischenliegenden Introns besteht. A comparison of the mRNA with the genomic structure indicated the presence of a gene that consists of 5 coding exons with 4 intervening introns. The translation of the mRNA wie Psoriasis qd behandeln in all possible reading frames revealed the presence of only one grid, which leads wie Psoriasis qd behandeln a continuous polypeptide chain, which also contains the highly conserved structural motifs of kallikrein, as discussed below.
Strukturelle Charakterisierung des KLKGens Structural characterization of the KLK15 gene. Das Gen folgt weiter streng den gemeinsamen strukturellen Eigenschaften anderer Mitglieder der humanen Kallikrein-Multigenfamilie, wie unten beschrieben.
The gene also follows strictly the common structural properties of other members of the human kallikrein multigene family, as described below. The predicted protein coding region of the gene consists of bp, encoding a polypeptide derived therefrom of amino acids with a predicted molecular weight of Die Nukleotide — ATTAAA SEQ.
The nucleotides ATTAAA SEQ. The presence of glutamic acid E at position suggests that KLK15 probably offers a unique substrate specificity.
PSA is a serine S in the appropriate place and has a chymotrypsin-like activity. Although the sequence of the KLK15 protein is click at this page, comparative studies have shown that it has a considerable degree of wie Psoriasis qd behandeln with other members of the kallikrein multigene family.
A computer analysis of the KLK15 protein sequence predicted a cleavage wie Psoriasis qd behandeln between amino acids 16 and 17 TAA-QD beforehand. Revealed another potential cleavage site Lys 21 to a sequence homologous to the activation site of another series proteases point [lysine K or arginine R is present in most cases] More evenly distributed throughout the hydrophobic regions KLK15 polypeptide agree with a globular protein, similar to other kallikreins and serine proteases, agreed.
Twenty nine "invariant" amino acids surrounding the active site of serine proteases have been described Von diesen sind achtundzwanzig in KLK15 konserviert. Of these, eight are conserved in KLK One of the non-conserved amino acids Ser instead of Pro KLK-L2 and KLK-L5 proteins is also in Prostase found and prepared Psoriasis-Behandlung Volksmedizin accordance with protein evolution studies 41 represents a conserved evolutionary change of a protein of the same group.
The other two C and C are not found in PSA, KLK1, KLK2 or KLK-L4, but they are found in similar positions in other kallikrein genes and the formation of an additional disulfide bond is expected of them.
All of the obtained phylogenetic trees agreed that other proteases Senn non-kallikrein can be summarized as a separate group, indicating that the kallikrein constitute a separate ge step in wie Psoriasis qd behandeln evolution of serine proteases. Are combined and the classical kallikreins hK1, hK2 and PSA are summarized in every tree, suggesting that the separation between classical kallikreins and the kallikrein-like genes took place early in evolution, which earlier proposals Studies matches Eine PCR-Durchmusterung nach KLKTranskripten unter Verwendung genspezifischer Primer KLK15 — F2-SEQ.
F2 SEQ ID NO 49 and KLKR2 SEQ Wie Psoriasis qd behandeln NO 50 Table 1 showed in most of the examined tissue cDNAs that presence of three bands 6 6. Diese Banden wurden auf einem Gel aufgereinigt, kloniert und sequenziert. These bands were purified on a gel, cloned and sequenced.
The middle band represents two different splice variants. Restriction digestion of the PCR product of the middle band with Stu I followed by gel separation, purification and sequencing revealed that it consists of wie Psoriasis qd behandeln splice variants 1 and 2, wie Psoriasis qd behandeln is approximately the same length splice variant 1 has exon 4 bpbut it is missing bp from exon 3, while splice variant 2 additional bp from exon 3 has, but missing exon 4.
Chromosomale Lokalisierung des KLKGens Chromosomal localization of the KLK15 gene. Restriction analysis study of a number of overlapping BAC clones spanning the human kallikrein-site, followed by a comparison with the EcoR I restriction map of the area available from the LLNL web site enabled identification of a BAC clone BC that is closer to the telomere adjacent to BC which contains the KLK15 gene. A comparison of the sequences of the two clones with a BLAST program revealed that the ends of these clones overlap.
The relative location and the direction of transcription of these three genes were precisely defined by identifying the positions of the KLK1- KLK3- and KLK15 genes along these clones. KLK1 is closest to the centromere and its direction of transcription is from telomere to centromere, followed by KLK15, which is located closer to the telomere and is transcribed in the same direction.
The distance between the two genes is bp in length. Gewebeexpression und hormonelle Regulation des KLKGens Tissue expression and hormonal regulation of the KLK15 gene. Lower levels of expression are also seen in the wie Psoriasis qd behandeln, salivary gland and adrenal glands, colon, testis and kidney. To confirm the specificity of the RT-PCR, typical PCR products were cloned and sequenced. KLKExpression bei Prostatakrebs KLK15 expression in prostate cancer.
The expression of the KLK15 gene in normal and cancerous prostatic tissues was examined by RT-PCR. Actin was included as a wie Psoriasis qd behandeln gene to ensure the quality and quantity of cDNA used.
Zur Untersuchung der relativen Expression des KLKGens in normalem im Vergleich zu malignem Gewebe, wurden 29 Paare Learn more here untersucht. To wie Psoriasis qd behandeln the relative expression of the KLK15 gene in normal compared with malignant tissues, 29 pairs of prostatic tissues were examined. Each pair turned normal and cancerous tissue obtained from the same patient.
The results wie Psoriasis qd behandeln summarized in Table 2. Due to the small number of cases, the binomial distribution was used to calculate the level of significance. Die Prostatakrebspatienten wurden weiter in zwei Gruppen aufgeteilt: The prostate cancer patients were further divided into two groups: As the assignment of KLK15 expression was compared with clinicopathological prognostic variables, it was found that a high KLK15 expression in patients with late-stage disease and tumors with higher degrees wie Psoriasis qd behandeln more common Table 3.
Kallikreine sind eine Untergruppe der Serinproteasen. Kallikreins are a subgroup of serine proteases. The term "kallikrein" is commonly used to describe an enzyme on a precursor molecule kininogen wie Psoriasis qd behandeln release of a bioactive peptide kinin acts 3, However, the term "tissue kallikrein" is not limited to the functional definition of the enzyme. Dieser Begriff wird jetzt zur Beschreibung einer Gruppe wie Psoriasis qd behandeln Enzymen mit hochkonservierter Gen- und Proteinstruktur verwendet, die sich auch am selben chromosomalen Ort befinden.
This term is now used to describe a group of enzymes with highly conserved gene and protein structure, which are also on the same chromosomal location. The previously cloned 14 members of the human kallikrein gene family have shown below a number of similarities 7, Dieses Gen wurde KLK15 genannt. This gene was named KLK Many of the kallikrein genes associated with wie Psoriasis qd behandeln development of human diseases, depending on the fabric of its main expression.
The KLK1 gene is involved in many disease processes, visit web page inflammation 3hypertension 44nephritis and diabetic kidney disease 45, The relationships between HSCCE KLK7 with skin disorders, including pathological Hautverhornung and psoriasis, have already been reported wie Psoriasis qd behandeln, There are other reports that describe the connection of neuropsin KLK8 expression with diseases of the central nervous system, including epilepsy 49, Since KLK15 is expressed mainly in the thyroid gland, it can play an important role in normal physiology and pathophysiology of the gland.
In all other discovered many kallikreins are expressed in the thyroid gland, but none in this tissue at the highest level 7, Das KLKGen ist auf mRNA-Ebene in einer Untergruppe von Prostatakrebsen heraufreguliert.
The KLK15 gene is upregulated at the mRNA level in a wie Psoriasis qd behandeln of prostate Lorbeer Psoriasis von Behandlung. These findings indicate that the over-expression of KLK15 is associated with more aggressive forms of the disease and may be indicative of a poor prognosis Table 3.
There is increasing evidence that many kallikrein and kallikrein-like genes associated with malignancy. PSA is so far the best marker for prostate cancer Recent reports suggest that hK2 encoded by the gene KLK2 could wie Psoriasis qd behandeln another suitable diagnostic marker for prostate cancer 21, NES1 KLK10 scheint ein neues Tumorsuppressor-Gen 23 zu sein. NES1 KLK10 appears to be a novel tumor suppressor gene From the Zyme KLK6 gene has been shown that it is differentially expressed in primary breast and ovarian tumors 24 and of the human stratum corneum chymotryptic enzyme HSCCE, KLK7 was shown to be expressed at abnormally high levels in ovarian cancer Bei zwei neu entdeckten Kallikreinen, KLK-L4 KLK13 und KLK-L5 KLK12 wurde eine Herunterregulation in Brustkrebs gefunden Two newly discovered kallikreins KLK-L4 KLK13 and KLK-L5 KLK12a down-regulation found in breast cancer Thus, extensive new literature suggests multiple connections from numerous kallikrein genes to many forms of human cancer.
Separated RNA species are transcribed in addition to the major 1. Ein neues Transkript des Gewebekallikrein-Gens KLK1 wurde auch aus dem Dickdarm isoliert A new transcript of the tissue kallikrein gene KLK1 was also isolated from the colon Of neuropsin, a recently identified kallikrein-like gene, it was found that there are two alternative splice forms in addition to the main shape 25, KLK-L4 was Psoriasis Handgelenk found wie Psoriasis qd behandeln it has different alternative splice forms Zusammenfassend wurde ein neues Mitglied der humanen Kallikrein-Genfamilie, KLK15, charakterisiert, welches sich am humanen Kallikrein-Ort Chromosom 19g In summary, a new member of the human kallikrein gene family, KLK15, characterized that the human kallikrein place is located chromosome 19g This gene, in addition to the classical form three related splice forms.
KLK15 is expressed in a variety of tissues, but principally in the thyroid, it appears to be up-regulated in more aggressive forms of prostate cancer and its expression is influenced by steroid hormones. Because some other kallikreins are already used as a valuable tumor marker could find KLK15 similar clinical applications.
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Yousef, GM, Obiezu, CV, Luo, LY, Black, MH and Diamandis, EP Cancer Res. Yousef, GM und Diamandis, EP J. Yousef, GM and Diamandis, EP J. Yousef, GM, Chang, A. Yousef, GM und Diamandis, EP Genomics 65, — Yousef, GM and Diamandis, EP Genomics 65, Yousef, GM, Luo, LY und Diamandis, EP Anticancer Res.
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Ausgabe, Cold Spring Harbor Laboratory, NY A Laboratory Manual, 2nd Edition, Cold Spring Harbor Laboratory, NY Cancer 74, —6 J. Cancer 74, Yousef, GM, Luo, LY, Scherer, SW, Sotiropoulou, G. Proudfoot, NJ und Brownlee, GG Nature—4 Proudfoot, NJ and Brownlee, GG Nature Sheets, MD, Ogg, SC und Wickens, MP Nucleic Acids Res.
Sheets, MD, Ogg, SC and Wickens, MP Nucleic Acids Res. Volume 3, 3rd Ed. Dayhoff, MO Natl. Bhoola, KD, Figueroa, CD und Worthy, Wie Psoriasis qd behandeln. Bhoola, KD, Figueroa, CD and Worthy, K. Diamandis, EP, Yousef, G. Margolius, NS, Horivitz, D. Jaffa, AA, Chai, KX, Chao, J.
Cumming, AD, Walsh, T. Black, MH, Magklara, A. Riegman, PH, Klaassen, P. Riegman, PH, Vlietstra, RJ, wie Psoriasis qd behandeln der Korput, HA, Romijn, JC und Trapman, J. Riegman, PH, Vlietstra, RJ, van der Korput, HA Romijn, JC and Trapman, J. Chen, LM, Murray, SR, Chai, KX, Chao, L. CAA1CACDED1EPA2EPB1USUSUSUSWOA2WOA3. Toronto DIAMANDISWie Psoriasis qd behandeln M. Mount Sinai Hospital, Toronto.
Therapeutische Anwendungen von pro-apoptotischen Benzodiazepinen - The Regents of the University of Michigan Wie Psoriasis qd behandeln
Etwa 50 Prozent der Menschen mit Wie Psoriasis qd behandeln leiden unter einer Schuppenflechte der Kopfhaut. Je nach Ausdehnung und Schweregrad der Wie Psoriasis qd behandeln werden drei Formen der Kopfhaut-Psoriasis unterschieden. Sie verlassen jetzt unsere Webseite. Formen - Schuppenflechte Kopfhaut. Wenn die Kopfhaut leidet Etwa 50 Prozent der Menschen mit Schuppenflechte leiden unter einer Schuppenflechte der Kopfhaut. Schuppenflechte der Kopfhaut - Die Symptome.
Die Schweregrade der Kopfhaut-Psoriasis. Die Schuppenflechte der Kopfhaut wird in drei Schweregrade unterteilt: Bei Dohn, Behandlung des Meeres mit Psoriasis dem mittelschweren Kopfhaut-Psoriasis sind ebenfalls weniger als 50 Heilung Psoriasis der Kopfhaut betroffen.
Die schwere Form der Kopfhaut-Psoriasis betrifft mehr als 50 Prozent der Kopfhaut. Abgrenzung von anderen Erkrankungen der Kopfhaut. Schuppenflechte der Kopfhaut - Die Behandlung. Ortonne JP, Chimenti S, Luger T, et al. European consensus on grading and treatment algorithm. Kontakt Disclaimer Impressum Datenschutz Widerruf Arztsuche.
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