Biomedical subjects

L Berberian

Publications and source records attributed to L Berberian.

6 recordsLinked to original sources

PubMed1994

Effects of HIV infection on VH3 (D12 idiotope) B cells in vivo.

The abnormalities of B lymphocytes in human immunodeficiency virus (HIV) infection usually have been attributed to secondary consequences of disturbed immunoregulation. However, recent work has revealed avid binding of HIV gp120 to a conserved immunoglobulin motif unique to the VH3 gene family and the selective gp120-induced activation of VH3 B cells in vitro. This cross-sectional clinical study tests whether HIV infection is associated with a selective response of VH3 B cells in vivo. Levels of blood B cells and serum immunoglobulins (Ig) expressing the D12 idiotope of the VH3 gene family were measured in subjects of the Multicenter AIDS Cohort Study grouped according to clinical stages of HIV infection. A 3-fold elevation in D12 B cells was observed in HIV seropositive versus seronegative groups. This was selective for the D12 population, since total B cell numbers were identical in the two groups. The levels of D12 B cells and CD4 T cells were significantly correlated, and D12 B cells were markedly reduced in the AIDS group (4- and 10-fold, compared to the seronegative and seropositive groups). Analogous differences were also seen in the levels of serum anti-gp120 D12 Ig. This change in VH3 B cells among groups of HIV-infected individuals provides further evidence identifying gp120 as a VH3 B cell superantigen.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Immunoglobulin VH3 gene products: natural ligands for HIV gp120.

Infection with human immunodeficiency virus-type 1 (HIV-1) depletes T cells expressing CD4 and B cells expressing immunoglobulin (Ig) VH3 gene products. A subpopulation of normal B cells from non-HIV-infected individuals was shown to bind to HIV gp120 by means of membrane Ig; most of these B cells expressed VH3 family Ig. Serum VH3 IgM from uninfected individuals also avidly bound gp120. Finally, gp120 selectively induced Ig secretion by VH3 B cells, indicating that the binding of gp120 functionally activated these cells. These results indicate that naturally occurring VH3 Ig is a second ligand for gp120 and a candidate superantigen for VH3 B cells.

Adolescent↗

PubMed1992

Restricted use of fetal VH3 immunoglobulin genes by unselected B cells in the adult. Predominance of 56p1-like VH genes in common variable immunodeficiency.

The large VH3 family of human immunoglobulin genes is commonly used throughout B cell ontogeny. However, B cells of the fetus and certain autoantibody-producing clones are restricted to a recurrent subset of VH3 genes, and VH3 B cells are deficient in certain immunodeficiency diseases. In this study, we have sequenced a set of rearranged VH3 genes generated by genomic polymerase chain reaction (PCR) from normal adults and those with common variable immunodeficiency (CVI). In both groups, all cones were readily identifiable with the fetal VH3 subset, and were further distinguished by limited DH motifs and exclusive use of JH4. In CVI, the residual population of VH3 B cells were notable for predominant use of 56p1-like VH genes. All clones displayed sequence divergence (including somatic mutation) with evidence of strong selection against complementarity-determining region (CDR) coding change. A survey of other V gene families indicates that human V gene diversity may be restricted in general by germline mechanisms. These findings suggest that the expressed antibody repertoire in the human adult may be much smaller than anticipated, and selected by processes in part distinct from the paradigm of maximal antigen-binding diversity.

Antibody Diversity↗

PubMed1991

A VH clonal deficit in human immunodeficiency virus-positive individuals reflects a B-cell maturational arrest.

A major feature of human immunodeficiency virus (HIV) infection is disordered B-cell function, which paradoxically includes both pathologic overactivity (elevated serum antibodies, lymphadenopathy, and increased risk for lymphoma) and underactivity (impaired antibody immunity, particularly to bacterial polysaccharide antigens). B-cell immune dysfunction contributes significantly to HIV-related morbidity and also represents an obstacle to eventual definitive treatment by anti-HIV immunization. Our laboratory has recently identified in normal B-cell populations certain VH gene subfamilies with a developmentally regulated pattern of utilization. In particular, B cells bearing rearranged VH3L were rare in the germinal center but uniformly abundant in the blood and lymphoid mantle zone. We used this index gene subfamily as a clonal criterion for the pattern of B-cell development in lymphocytes of HIV-positive individuals. In a series of 19 HIV-positive subjects, a striking deficit of VH3L B cells was observed; in contrast, none of the 16 normal subjects showed this abnormality. Other VH subfamilies (VH1N, VH4/6, and VH5N) were unaffected in the HIV-positive patients. This VH3L clonal deficit and other recent phenotype and histopathologic findings suggest that the general B-cell dysfunction in HIV is due to a discreet maturational arrest at the germinal center stage.

B-Lymphocytes↗

PubMed1989

Does nitroglycerin induce heparin resistance?

We studied the possibility that intravenous nitroglycerin may produce heparin resistance both in vitro and prospectively in a group of 10 patients following coronary angioplasty. Nitroglycerin in physiologic to pharmacologic concentrations (41-250 micrograms/ml) did not produce heparin resistance in vitro as measured by activated partial thromboplastin time and thrombin time. The maximum reduction in activated partial thromboplastin time was 7%. In patient studies, the activated partial thromboplastin time at baseline on heparin alone (93 + 22 s) was not significantly different (p = 0.61) from activated partial thromboplastin measured upon addition of nitroglycerin (94 +/- 27 s) or 30 min following cessation of the nitroglycerin infusion while continuing the same dose of heparin (91 +/- 24 s). We conclude that intravenous nitroglycerin does not induce heparin resistance in vitro or in patients during short-term administration.

Angioplasty, Balloon↗

PubMed1986

Elevated serum D dimer: a degradation product of cross-linked fibrin (XDP) after intravenous streptokinase during acute myocardial infarction.

D dimer, a degradation product of cross-linked fibrin, is generated by lysis of fibrin but not by lysis of fibrinogen and can be reliably detected by specific monoclonal antibody techniques. The generation of D dimer after intravenous streptokinase in acute myocardial infarction was studied with the use of a semiquantitative latex agglutination immunoassay. This assay utilizes the monoclonal antibody DD-3B6/22, raised by conventional hybridoma technology, against a highly purified preparation of human D dimer and is adjusted to give a positive agglutination at a D dimer serum concentration of greater than 200 ng/ml (upper limit of normal). Twenty-one patients with acute transmural myocardial infarction of less than 3 hours' duration were studied. Fifteen patients received 0.75 to 1.5 million U intravenous streptokinase and 6 patients were treated conventionally without thrombolytic therapy. An elevated serum level of D dimer was detected before treatment in only 1 of 15 patients receiving intravenous streptokinase and within 2 hours of treatment in the remaining 14 patients who received streptokinase. In contrast, an elevated serum D dimer level was not detected during the first 24 hours in any of the six conventionally treated patients, including two patients who manifested the clinical syndrome of spontaneous reperfusion. The data suggest that in patients with acute myocardial infarction, an elevated serum level of D dimer, a cross-linked fibrin degradation product occurs early after administration of a large dose of streptokinase, but is infrequent during the first 24 hours in conventionally treated patients with acute infarction. Measurement of D dimer may be potentially useful for monitoring thrombolysis in patients with acute myocardial infarction.

Aged↗