ZIB

Hits per page

hits 1 - 2 | 2 hits

Sorting

Electronic Resource

Disease-causing mutations in the human genome (2000)

Antonarakis, Stylianos E. ; Krawczak, Michael ; Cooper, David N.

Springer

European journal of pediatrics 159 (2000), S. S173

add to mindlist on the mindlist

Details

ISSN: 1432-1076

Keywords: Key words Databases ; Deletions ; Gene mutations ; Insertions ; Substitutions

Source: Springer Online Journal Archives 1860-2000

Topics: Medicine

Notes: Abstract A considerable number of gene mutations has now been reported in a total of more than 1000 different human genes. Data on these mutations and their associated phenotypes have been collated and are available online through two major databases: Online Mendelian Inheritance in Man in Baltimore and the Human Gene Mutation Database in Cardiff. Since the non-randomness of mutation is determined largely by the local DNA sequence environment, the study of mutation may not only yield information on underlying mechanisms but also lead to the optimization of mutation search strategies. Conclusion There is a high frequency of CG to TG or CA mutations in the human genome due to deamination of 5′methyl-cytosine. The second most common type of mutations in human disorders is short deletions or insertions of less than 20 nucleotides.

Type of Medium: Electronic Resource

URL: http://dx.doi.org/10.1007/PL00014395

Permalink

Library	Location	Call Number	Volume/Issue/Year	Availability

Others were also interested in ...

Paper (German National Licenses)

Fulltext

Electronic Resource

Prothrombin cleavage by human vascular smooth muscle cells: A potential alternative pathway to the coagulation cascade (1995)

Benzakour, Omar ; Kanthou, Chryso ; Lupu, Florea ; [et al.]

New York, N.Y. : Wiley-Blackwell

Journal of Cellular Biochemistry 59 (1995), S. 514-528

add to mindlist on the mindlist

Details

ISSN: 0730-2312

Keywords: prothrombin ; prethrombin 2 ; fragment 1.2 ; α-thrombin ; prothrombin activation ; serine proteinase ; human vascular smooth muscle cells ; mitogenic activity ; enzymatic activity ; Life and Medical Sciences ; Cell & Developmental Biology

Source: Wiley InterScience Backfile Collection 1832-2000

Topics: Biology , Chemistry and Pharmacology , Medicine

Notes: Thrombin is a potent mitogen for human vascular smooth muscle cells (HVSMC) and its enzymatic activity is required for this function. The present study demonstrates that prothrombin is also mitogenic for HVSMC due to the generation of enzymatically active thrombin which occurs upon incubation of prothrombin with the cells. Analysis by SDS-PAGE, immunoblotting, and amino acid sequencing revealed that prothrombin incubated with HVSMC undergoes limited proteolysis. Prethrombin 1 was formed through cleavage at R155-S156. Cleavage at R271-T272 generated fragment 1.2 and prethrombin 2 whilst cleavage at R284-T285 yielded truncated prothrombin 2 (prethrombin 2′). However, cleavage at R320-I321 which, during prothrombin activation produces two-chain α-thrombin, was not detectable. Studies on HVSMC-conditioned medium revealed that a similar pattern of prothrombin cleavage occurred by a cell-secreted factor(s). Amidolytic activity analysis indicated that 1-3% catalytically active thrombin-like activity was generated upon incubation of prothrombin with HVSMC-conditioned medium. By treating conditioned medium with various classes of proteinase inhibitors or hirudin, it was determined that prothrombin is cleaved by a cell-derived serine proteinase-like factor(s) at R271-S272 and by α-thrombin at R155-S156 and R284-T285. Antibodies neutralising the activity of either urokinase, tissue plasminogen activator, or factor Xa failed to alter the prothrombin cleaving activity of conditioned medium. This activity which may catalyse an alternative pathway for the generation of thrombin, was eluted from a gel filtration column as a single peak with apparent molecular mass of 30-40 kDa. © 1995 Wiley-Liss, Inc.

Additional Material: 5 Ill.