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Biomedical subjects

A Bukovsky

Publications and source records attributed to A Bukovsky.

27 records · Page 2Linked to original sources
PubMed1994

Functional association of cyclophilin A with HIV-1 virions.

Cyclophilins are a family of proteins that bind the immunosuppressant cyclosporin A, possess peptidyl-prolyl cis-trans isomerase activity, and assist in the folding of proteins. Human cyclophilins A and B are host cell proteins that bind specifically to the HIV-1 Gag polyprotein p55gag in vitro. Here we report that viral particles formed by p55gag, in contrast to particles formed by the Gag polyproteins of other retroviruses, contain significant amounts of cyclophilin A. Sequences in the capsid domain of p55gag are both required and sufficient for the virion-association of cyclophilin A. The association of cyclophilin A with HIV-1 virions was inhibited in a dose-dependent manner by cyclosporin A as well as by SDZ NIM811 ([Melle-4]cyclosporin), a non-immunosuppressive analogue of cyclosporin A. Drug-induced reductions in virion-associated cyclophilin A levels were accompanied by reductions in virion infectivity, indicating that the association is functionally relevant. Moreover, SDZ NIM811 inhibited the replication of HIV-1 but was inactive against SIVMAC, a primate immunodeficiency virus closely related to HIV-1, which does not incorporate cyclophilin A.

Amino Acid Isomerases↗
PubMed1994

Functional domains of the capsid protein of human immunodeficiency virus type 1.

A series of deletions was introduced into the CA domain of the human immunodeficiency virus type 1 Gag polyprotein to examine its role in virus particle and core formation. The mutations resulted in two phenotypes, indicating the existence of two functionally distinct regions within the CA domain. Deletions within a conserved stretch of 20 amino acids referred to as the major homology region (MHR) and deletions C terminal to this region blocked virus replication and significantly reduced the ability to form viral particles. Deletions N terminal to the MHR also prevented virus replication, but the mutants retained the ability to assemble and release viral particles with the same efficiency as the wild-type virus. The mutant particles contained circular rather than cone-shaped cores, and while they were of a density similar to that of wild-type particles, they were more heterogeneous in size. These results indicate that CA domain sequences N terminal to the MHR are essential for the morphogenesis of the mature cone-shaped core.

Base Sequence↗
PubMed1992

Tissue factor in normal and transplanted human kidneys.

Tissue factor (TF) plays a central role in the initiation of blood coagulation that frequently is enhanced in renal allografts. The identification and localization of TF was studied immunocytochemically in biopsies from normal and transplanted human kidneys and classified according to its distribution. The clinical status of each allograft was then correlated with the TF classifications. From these correlations, four distributional types of TF were identified. In normal kidneys, TF was localized to glomerular epithelium and basement membranes. Glomerular TF expression did not colocalize with mesangial or endothelial HLA-DR reactivity as determined by double antibody techniques. Tissue factor in donor kidneys also was identified in the renal capsule and in the adventitia of large arteries. These structures were not reactive in long-term transplanted grafts. Some cadaver kidneys prepared for transplantation had depleted glomerular TF, and exhibited TF reactivity within stromal tissues. Long-term allografts with progressive loss of renal function and kidneys with advanced rejection exhibited diminished TF reactivity of glomerular epithelium and basement membranes. This was frequently associated with fibrin deposition within the glomeruli and in the intertubular microcirculation. These findings indicate that the evaluation of TF in transplanted kidneys is related to the prognosis of graft survival.

Adult↗
PubMed1992

Novel immunohistochemical markers of human renal allograft dysfunction--antithrombin III, Thy-1, urokinase, and alpha-smooth muscle actin.

We have studied the expression of alpha-smooth muscle actin (alpha sm-1) by mesangial cells, and the expression of Thy-1 glycoprotein, antithrombin III (ATIII), and urokinase by tubular epithelial cells in normal kidneys and dysfunctional renal allografts. Kidney biopsies were studied immunocytochemically for changes in each of these markers and the findings were classified into two groups and compared with creatinine plasma levels at the time the biopsies were taken. In dysfunctional grafts, mesangial alpha sm-1 and tubular epithelial Thy-1 reactivities were greatly diminished, and urokinase and ATIII were missing from proximal renal tubular epithelial cells. Urokinase, which was absent from normal renal glomeruli, appeared in glomeruli of some dysfunctional allografts. The possible usefulness of these markers in patient evaluations was supported by our finding that the distribution of vinculin, fibronectin, myosin, actin B4, desmin, glomerular HLA-DR, and the tubular expression of CD15 remained unchanged. These data prompt us to suggest that the immunocytochemical localization and evaluation of alpha sm-1, Thy-1, ATIII, and urokinase in kidney allografts may be useful adjuncts in the assessment of function in renal allografts.

Actins↗
PubMed1991

Antigens of immunoglobulin G-Fc receptor III in human male reproductive tract accessory glands.

We have documented the presence of soluble antigens of immunoglobulin (Ig)G-Fc receptor type III (FcRIII) in human seminal plasma that retain an affinity for the Fc fragment of IgG. The origin of these FcRIII antigens within the male reproductive tract was not known. By using polyclonal and monoclonal antibodies directed against different epitopes on FcRIII molecules, we demonstrated FcRIII reactivity in human prostate and seminal vesicle epithelial cells as well as in their glandular secretions. The FcRIII monoclonal antibody reactivity was removed by absorption with either seminal plasma or polymorphonuclear leukocytes that express FcRIII. Absorption of FcRIII monoclonal antibody with polymorphonuclear leukocytes also removed the reactivity with seminal plasma and vice versa. These data show for the first time that male accessory glands are a source of soluble FcRIII antigens.

Adult↗
PubMed1979

Ovarian function and the immune system.

A hypothesis is presented on the interaction between the immune system and ovary in the regulation of the reproductive system and in the origin of some of its disorders. It has been suggested that the beginning, duration and age dependent failure of ovarian ovulatory function depends among other things on the adequate relationship between the immune system and approriate ovarian target structures. The cyclicity of ovarian function is considered to be primarily dependent on the induction of a specific cyclic immune response to the ovary. Similarly, the selection of a species-specific number of ovulating follicles during sexual maturity is thought to be ensured by immune mechanisms. This hypothesis, on the role of the immune system in regulation of ovulatory ovarian function respects the physiological effect of gonadotropins and steroids on the ovarian structures. The interaction between the ovary and the hypothalamus-pituitary system appears to be modulated by the relationship between the ovary and the immune system.

Aging↗
PubMed1978

Role of the immune system in regulation of ovarian function-hypothesis.

A hypothesis is presented on the interaction between the immune system and ovary in the regulation of the reproductive system and in the origin of some of its disorders. The cyclicity of ovarian function is considered to be primarily dependent on the induction of a specific cyclic immune response to the ovary. Similarly, the selection of a species-specific number of ovulating follicles during sexual maturity is thought to be ensured by immune mechanisms.

Animals↗