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Biomedical subjects

C Haibach

Publications and source records attributed to C Haibach.

5 recordsLinked to original sources
PubMed1998

The number of kringle IV repeats 3-10 is invariable in the human apo(a) gene.

The human apolipoprotein(a) (apo(a)) gene is a member of a family of related genes including plasminogen, apo(a)rg-B and apo(a)rg-C, which are clustered on chromosome 6q 2,7. Apo(a) contains ten different types of plasminogen-like kringle IV repeats (K-IV 1-10) one of which (K-IV 2) varies in number resulting in a remarkable size polymorphism of the protein. Sequence analysis of human apo(a) alleles and indirect evidence have suggested that K-IV 1 and K-IV 3-10 are each present once in individual alleles and that the 3' apo(a) region encompassing kringles IV 3-10, kringle V and the protease domain is invariable. To directly test this, we have constructed a restriction map of the apo(a) gene region from genomic DNA and from a yeast artificial chromosome (YAC) (K-IV 13) which contains the entire apo(a) gene. The presence of a 63 kb ClaI fragment encompassing kringles IV 3-10, kringle V and the protease domain and a 46 kb SwaI fragment, spanning kringles IV 5-10, kringle V and the protease domain was demonstrated by PFGE/Southern blotting in 30 unrelated subjects, who represented a range of apo(a) size alleles containing from 11 to 49 kringles. Our analysis demonstrates that the number of kringles IV 3-10 is invariable in the human apo(a) gene, suggesting that the 3'domain of Apo(a) is functionally important.

Apolipoproteins↗
PubMed1995

A functional factor X deficiency.

A functional factor X deficiency is described which caused pronounced reduction in the in vitro activation of the extrinsic system while marginally affecting the in vitro activation of the intrinsic pathway. All studies were normal with the exception of a prolonged PT, an elevated factor X antigen, and low factor X activity. Western blot analysis revealed the presence of two factor X species. The abnormal molecule was of higher molecular weight. Interestingly, there was no bleeding associated with this deficiency. The biochemical basis of this defect is currently under investigation.

Adult↗
PubMed1995

Sequence polymorphism in kringle IV 37 in linkage disequilibrium with the apolipoprotein (a) size polymorphism.

Apolipoprotein(a) [apo(a)] contains a variable number of identical (K-IV A/B) or nearly identical (K-IV 1, K-IV 30-37) kringle repeats that are homologous to K-IV from plasminogen. The sizes of 414 apo(a) alleles were determined by pulsed-field gel electrophoresis (PFGE) of KpnI-digested DNA. Furthermore, sequence variation in the apo(a) K-IV 30-37 domain was analysed. Reverse transcription/polymerase chain reaction (RT-PCR) cloning of human liver poly A+ RNA followed by sequencing revealed a single nucleotide exchange in the ultimate K-IV (K-IV 37) of apo(a) (codon 4168); this results in an ATG (Met) to ACG (Thr) substitution. A PCR-based restriction assay of genomic DNA demonstrated that this substitution represents a common polymorphism. In 231 unrelated Tyroleans, the frequencies for the K-IV 37 Thr and K-IV 37 Met alleles were 0.66 and 0.34, respectively. The phase between the K-IV 37 Met/Thr and the KpnI size polymorphism was determined for 224 alleles. A significant linkage disequilibrium was detected between the sequence and size polymorphisms of apo(a). K-IV 37 Met was significantly associated with KpnI allele no. 18 (DAB = 0.0267 +/- 0.0101; chi 2 = 10.09, df = 1). The Met/Thr polymorphism was further used to test whether deletions or duplications of K-IV 37 occur frequently in the apo(a) gene. Some 40 apo(a) alleles, 22 of which were from subjects that appeared to be double heterozygotes for K-IV repeat number and the Met/Thr variation were separated by PFGE and analysed for the 4168 Met/Thr polymorphism. The Met and Thr sequences were always present on different size alleles and no evidence for a duplication or deletion of K-IV 37 was obtained. This suggests that the copy number of K-IV 37 is invariable, in contrast to the highly variable K-IV A/B domain of the gene. The 4168 Met/Thr polymorphism had no effect on Lp(a) concentration, neither did it influence the lysine-binding property of the Lp(a) particle.

Adult↗
PubMed1995

Detection of a 67-kD glycoprotein in human tumor cell lines by a monoclonal antibody established against a recombinant human endogenous retrovirus-K envelope-gene-encoded protein.

Endogenous retroviruses in humans are discussed as putative etiologic agents in tumorigenesis. Molecular mimicry of cellular epitopes by retroviruses may be of importance for the genesis of autoimmune diseases. A group of human endogenous retroviruses, HERV-K, which is related to the mouse mammary tumour virus, has been characterised previously and open reading frames have been found covering their gag, pol, prt and env genes. Transcription of HERV-K genomes at the mRNA level as well as antibodies in human sera directed against HERV-K env have been detected recently. We have generated a monoclonal antibody (mAb), anti-HERV1, against a recombinant HERV-K Env protein. This mAb is capable of immunoprecipitating a 67-kD glycoprotein from the human breast carcinoma cell line T47D, the amount of which is strongly enhanced after stimulation with estradiol followed by progesterone. The same band could be precipitated from other carcinoma cell lines (Hep2, MCF7 and HeLa), but not from the human B-lymphoblastoid cell line Raji and from cultured human fibroblasts. Incubation of this antigen in the presence of endoglycosidase F indicates the presence of N-linked carbohydrate moieties of at least 7-9 kD.

Animals↗