Search PubMed⌕ Search

Biomedical subjects

S M Friedman

Publications and source records attributed to S M Friedman.

At least 91 records · Page 5Linked to original sources
PubMed1991

Cystoid macular edema secondary to juxtafoveolar telangiectasis in Coats' disease.

A 28-year-old man with unilateral Coats' disease and cystoid macular edema secondary to juxtafoveolar telangiectasis underwent successful juxtafoveolar argon green laser photocoagulation therapy with resolution of the edema and improvement in metamorphopsia and visual acuity. Despite this success, the effect of laser therapy in these patients remains uncertain. It should be considered only after detailed discussion with the patient about the possibility of posttreatment paracentral scotomata and the alternative of a reasonable period of observation for possible spontaneous resolution of the edema.

Adult↗
PubMed1990

Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.

Experimentally induced murine graft-vs.-host disease may be characterized by hypergammaglobulinemia, autoantibody formation, and immune complex-mediated organ system damage that mimics SLE. These autoimmune phenomena are mediated by abnormal Th-B cell cooperation, across MHC disparities, in which donor-derived allospecific Th cells recognize and interact with MHC class II antigens on the surface of recipient B cells. Microbial toxins, termed superantigens, which bind to MHC class II molecules and activate selected T cells based on TCR variable gene usage, may induce a similar form of Th-B cell interaction. In the present study, we generated and characterized human Th cell lines reactive with the Mycoplasma arthritidis superantigen (MAM). The essential observation is that resting human B cells bind MAM and present it to superantigen-reactive autologous or allogeneic Th cells, resulting in both Th cell activation and a consequent polyclonal Ig response by the superantigen-bearing B cells.

Antigens↗
PubMed1990

Retinochoroidal degeneration associated with progressive iris necrosis.

A 34-year-old man in good general health became bilaterally totally blind by an unusual retinochoroidal degenerative disease 3 years after the initial onset of visual symptoms. The advanced stages of the retinochoroidal disease were associated with bilateral progressive iris necrosis and severe ocular pain. The constellation of findings and course of this disease represent a clinical entity that has not been previously described in the literature.

Adult↗
PubMed1990

The relation of blood sodium concentration to blood pressure in the rat.

Rises or falls in blood sodium concentration ([Na]) within a physiological range of +/- 15 mmol/l, sustained for 5 h, were produced in the rat by intraperitoneal dialysis with physiological salt solutions containing variable amounts of Na. In general, systolic and diastolic blood pressure rose and fell in direct relation to the alteration in [Na]. Solutions of equivalent osmolarity produced changes in blood pressure that were the inverse of those induced by Na. These effects could not be explained in terms of changes in blood or extracellular fluid volume, and indicated the need for an exploration of the partition of Na and water across the vascular smooth muscle cell.

Animals↗
PubMed1990

The relation of cell volume, cell sodium and the transmembrane sodium gradient to blood pressure.

Blood sodium concentration [Na] was changed over a limited range of about +/- 15 mmol/l by intraperitoneal dialysis with physiological salt solutions containing variable amounts of Na. The transmembrane distribution of Na, K and water in vivo was measured in rapidly excised tail arteries. Cell Na varied linearly by about 0.3 mmol/kg dry weight for a 1 mmol/l change in extracellular sodium concentration [( Na]o). Expressed as the concentration in cell water [( Na]i), the change was about 0.4 mmol/l for a 1 mmol/l change in [Na]o. The Na gradient varied inversely with [Na]i. Systolic and diastolic blood pressures were directly related to [Na]i and inversely related to the Na gradient. We conclude that this relationship is part of a causal chain regulating blood pressure. The effect of a change in Na partition was blunted by the concurrent change in osmolarity which affects vascular smooth muscle tension by a different mechanism acting in the opposite way. We suggest that this latter mechanism is based on the special geometry of the cell, which elongates when water is withdrawn and shortens when water is imbibed.

Animals↗
PubMed1989

Interleukin 1 production during accessory cell-dependent mitogenesis of T lymphocytes.

We have studied the control and significance of IL-1 production in human leukocyte cultures during accessory cell-dependent, T lymphocyte mitogenesis using sensitive bioassays and immunolabeling techniques. In primary antigen-dependent systems like the MLR, IL-1 production was not detected in accessory cells (monocytes, dendritic cells) or T cells, suggesting that it is not an early product in these responses. However, monocytes could be induced to make IL-1 after interacting with sensitized antigen-specific T cells. Both alloreactive T cell clones or freshly prepared lymphoblasts induced IL-1 provided the monocytes carried the HLA-DR antigens to which the T cells were initially sensitized. Even in these circumstances, dendritic cells and B cells failed to make IL-1. The mechanism whereby activated T cells induce IL-1 in monocytes was explored. Supernatants from cocultures of monocytes and T cells or several recombinant cytokines induced little or no IL-1. A more potent antigen independent pathway of IL-1 induction was identified. IL-1 could be induced in third-party HLA-DR nonspecific monocytes in cocultures of alloreactive T cell clones or blasts and HLA-DR-specific dendritic cells. The induction was factor independent since dendritic cells and T blasts placed in a chamber separate from third-party monocytes by a semipermeable membrane did not induce monocyte IL-1. These results suggest that a cell contact mechanism rather than an IL-1-inducing factor leads to IL-1 production. The role of IL-1 in T cell proliferation was tested with a polyclonal anti-IL-1 antibody. The antibody failed to block the proliferation of primary T cells, or alloreactive T cell clones and blasts stimulated with HLA-specific monocytes or dendritic cells, even though IL-1 in the medium was neutralized.

Antigen-Presenting Cells↗
PubMed1989

Human peripheral blood T helper cell-induced B cell activation results in B cell surface expression of the CD23 (BLAST-2) antigen.

We have developed an in vitro system to assess the early stages of B cell activation induced by peripheral blood T helper cells. Peripheral blood mononuclear cells are cultured for 16 hr with anti-CD3 monoclonal antibody (mAb), T lymphocytes are then removed by sheep red blood cell rosette depletion, and expression of the B cell surface activation antigen CD23 (BLAST-2) is assessed by indirect immunofluorescence. Anti-CD3 mAb, but not a control anti-CD5 mAb, stimulates the expression of CD23 on 20-50% of peripheral blood B cells cultured with autologous T cells. T cell subset depletion studies show that the CD4+ T cell subset is responsible for anti-CD3-mediated induction of CD23 on autologous B cells. Anti-CD3-induced, T helper cell-dependent CD23 expression is not MHC-restricted, as allogeneic combinations of T and non-T cells, cultured in the presence of anti-CD3 antibody, also result in the expression of B cell CD23. Individuals whose monocyte Fc receptors bind murine IgG1 mAb poorly fail to trigger T cell proliferation in response to murine IgG1 anti-CD3 mAb and also fail to express B cell CD23 following culture of PBMC with IgG1 anti-CD3 mAb, while the usual expression of CD23 is seen after culture with IgG2a anti-CD3 mAb. The mechanism of anti-CD3-induced B cell activation was addressed in experiments using a two-chamber culture system. While little IL-4 activity was detected in anti-CD3-stimulated culture supernatants, optimal induction of CD23 was observed when T and B cells were cultured together in a single chamber. This suggests that under physiologic conditions, in which quantities of lymphokine may be limiting, close physical contact between the anti-CD3-activated Th cell and B cell may be required for CD23 expression. The anti-CD3-induced BLAST-2 assay will facilitate the analysis of Th cell-mediated B cell activation in any individual and should permit us to separately evaluate the roles of Th cells and B cells in the impaired immunoregulation characteristic of autoimmune disorders.

Antibodies, Monoclonal↗
PubMed1989

T helper cell-induced CD23 (BLAST-2) expression: an activation marker for the high density fraction of human B cells.

We previously reported that the coculture of cloned, allospecific human T helper (Th) cells with allogenic B cells bearing the relevant major histocompatibility complex class II antigen induces expression of the B cell activation antigen CD23 (BLAST-2) on a fraction of the B cells. To determine if Th cell-induced CD23 expression defines a distinct subset of human B cells, allospecific Th cells were cultured with B cell fractions isolated on discontinuous Percoll gradients. Our results show that the majority of high density resting B cells, those bearing surface IgD and little of the 4F2 activation antigen, express high intensity CD23 after culture with relevant allospecific Th cells. Essentially all of the low density, presumably in vivo-activated, B cell subpopulation and a fraction of the high density B cell pool remain CD23 negative after repeated culture with relevant allospecific Th cells. We utilized the CD23 induction assay to investigate a potential synergistic effect in B cell activation mediated by Th cell signaling and antigen analog-induced cross-linking of B cell surface Ig receptors. These studies show that phorbols known to result in PKC activation, one of the biochemical consequences of sIg-mediated B cell signaling, enhance both the intensity of CD23 expression and the percentage of cells expressing CD23 after allospecific Th cell or IL-4 interaction with high density, but not low density B cells. Finally, we show that while Th-induced B cell activation, as measured by CD23 expression, is a property of high density B cells, induction of Th cell proliferation is a property of the low density B cell population. These results suggest that the antigen-specific interaction between Th cells and resting B cells may serve to activate the B cell in preference to the T cell.

Antigens, Differentiation, B-Lymphocyte↗
PubMed1989

Polyamines of sulfur-dependent archaebacteria and their role in protein synthesis.

Several strains of the sulfur-dependent archaebacterium, Sulfolobus, were analyzed for their polyamine content. Caldine (norspermidine), spermidine, and thermine were found to be major components in all of the cells tested. The most abundant polyamine in all cultures examined was spermidine. The Langworthy strain had the highest spermine content, whereas S. acidocaldarius strain no. 7 was devoid of this polyamine. Cultures of strain no. 7 grown at 70 degrees C were rich in spermidine and caldine (triamines) and the thermine: spermidine ratio was much lower than that of cultures grown at 78 degrees C. Equal amounts of thermine and spermidine were present in strain DSM 1616. Preincubation of Langworthy strain extracts at 10 degrees C did not overcome the requirement for polyamines in protein synthesis. Putrescine exerted a concentration-dependent inhibition of the spermine-induced stimulation of protein synthesis at 70 degrees C. Increasing concentrations (6 and 9 mM) of spermine and thermine progressively inhibited poly(U)-dependent phenylalanine incorporation at 45 degrees C to about the same extent, whereas the same concentrations of these polyamines had little effect on the reaction at 70 degrees C. Although 3 mM spermine had only a slight stimulatory effect on the attachment of phenylalanine to tRNA at 65 degrees C, this polyamine had a pronounced effect on the formation of 70S ribosomes in a standard buffer containing 10 mM Mg2+. Increasing the Mg2+ concentration to 30 mM in the absence of spermine was even more effective in causing the reassociation of subunits to form 70S particles.

Amino Acids↗
PubMed1989

Human immunodeficiency virus infection of helper T cell clones. Early proliferative defects despite intact antigen-specific recognition and interleukin 4 secretion.

HIV selectively inhibited the proliferative response of clonal CD4+ T lymphocytes to alloantigen while other alloantigen-dependent responses were unperturbed. Specifically, impaired blastogenesis could be dissociated from alloantigen-specific induction of the B cell activation molecule CD23, IL-4 release, and inositol lipid hydrolysis. In addition, membrane expression of pertinent T cell receptor molecules, including CD2, CD3, and T cell antigen receptor (Ti), remained intact. Using two MHC class II-specific human CD4+ helper T cell clones, the proliferative defect was shown to be an early consequence of HIV infection, occurring within 4 d of viral inoculation and preceding increases in mature virion production. It was generalizable to three distinct methods of T cell activation, all independent of antigen-presenting cells: anti-CD3 mediated cross-linking of the CD3/Ti complex; anti-CD2 and phorbol 12-myristic 13-acetate (PMA); and anti-CD28 plus PMA. These abnormalities were not mitigated by addition of exogenous IL-2, even though expression of the IL-2 receptor (CD25) was unaltered. These studies define a selective blockade in T cell function early after HIV exposure that could serve as a model for certain in vivo manifestations of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Biochemical basis of synergy between antigen and T-helper (Th) cell-mediated activation of resting human B cells.

We have utilized CD23 expression as a marker for B cell activation in order to investigate the biochemical basis for synergy between antigen and T helper (Th) cells in the activation of resting human B cells. Our results confirm that while ligation of surface immunoglobulin (sIg) receptors by antigen analogues (e.g., F(ab')2 goat anti-human IgM) does not lead to CD23 expression, this stimulus markedly enhances CD23 expression induced during antigen specific Th-B cell interaction or by rIL-4. Utilizing a panel of monoclonal anti-human IgM antibodies, we observed a positive correlation between the capacity of a particular antibody to synergize with rIL-4 in CD23 expression and with B cell growth factor in B cell proliferation; suggesting that synergy in CD23 expression reflects the transduction of a functionally important signal via the sIg receptor. We next assayed analogues of the "second messenger" molecules, released during inositol lipid hydrolysis, for their capacity to amplify CD23 expression. These studies showed that protein kinase C (PKC) activating phorbol esters and the synthetic diacylgylcerol analogue, DiC8, synergize with either Th cells or rIL-4 in CD23 expression, while under no experimental condition does increasing B cell [Ca2+]i with ionomycin enhance CD23 expression. Taken together, these data suggest that activation of B cell PKC is the crucial biochemical event that primes antigen-activated B cells to respond more vigorously to interaction with Th cells and/or their soluble products.

Antibodies, Monoclonal↗
PubMed1988

T cell antigen receptors in autoimmunity.

Three mAb to variable region determinants of the alpha/beta-chain TCR were used to detect discrete populations of peripheral blood T cells. T cells sharing a TCR determinant defined by such an antibody presumably use the same or similar TCR V or J genes for their alpha- or beta-chains. Thus analysis with these mAb provides a tool to investigate TCR gene usage and expression. Since autoantigen specific T cells may play an important role in initiating autoimmune diseases, TCR were analyzed in different autoimmune diseases and control groups including rheumatoid arthritis, Graves disease, idiopathic thrombocytopenic purpura, psoriasis, SLE, insulin-dependent diabetes mellitus, and in nonautoimmune control diseases and normals. Purified T cells were stained by indirect immunofluorescence with three mAb to TCR variable regions: mAb S511 stains 1.8 +/- 0.9% (mean +/- 2 SD), mAb C37 stains 3.4 +/- 1.5% and mAb OT145 stains from 0 to 6% of T cells from normal donors. Several individuals were identified with expanded subsets of positive T cells. One patient with adult ITP followed during a 12-mo period consistently had elevated percentages of T cells staining with the mAb OT145 (15.9 to 24.5%). These cells were found to be exclusively CD8+. By Southern blotting DNA prepared from these OT145+, CD8+ cells, but not DNA from the patient's OT145- T cells, revealed a clonal rearrangement using a beta-chain C region probe. Thus this patient had a monoclonal expansion of CD8+, OT145+ cells. Hyperexpression of a TCR variable region, as defined by the available mAb, could not be associated with any of the diseases studied. Examination of T cells at the site of autoimmunity, such as T cells from rheumatoid arthritis synovial fluid, revealed normal percentages of cells staining with these mAb. Immunoperoxidase staining of psoriatic lesional skin showed no striking enrichment of T cells bearing one or the other TCR type.

Aged↗
PubMed1988

Direct human T helper cell-induced B cell activation is not mediated by inositol lipid hydrolysis.

The Ag-specific interaction between cloned allospecific human Th cells and class II MHC determinants on the surface of allogeneic B cells induces a significant fraction of resting B cells to express a B cell specific activation Ag BLAST-2 (CD23). On the other hand, cross-linking of B cell surface Ig R by Ag analogues does not lead to BLAST-2 expression. By utilizing the BLAST-2 induction assay as a positive control for efficient Th-B cell interaction, we have investigated the biochemical basis of human B cell activation mediated by Ag and Th cells. Our data demonstrate that ligands for sIg R, including F(ab')2 goat anti-human IgM and Staphylococcus aureus protein A, stimulate the metabolism of B cell membrane inositol lipids as assessed by: 1) increased [3H]inositol phosphates formation in myo-[3H]inositol-labeled B cells; 2) selective incorporation of [32P]orthophosphate into phosphatidic acid and phosphatidylinositol, but not into phosphatidylethanolamine or phosphatidylcholine; and 3) rapid increase in B cell cytoplasmic ionized Ca2+ concentration ([Ca2+]i). In contrast, direct Th-B cell interaction leads to high intensity BLAST-2 expression on the B cell surface but this response is not mediated by changes in inositol lipid metabolism or [Ca2+]i. Further, Th-B cell interaction does not affect the changes in B cell inositol lipid metabolism or [Ca2+]i triggered by sIg cross-linking. Taken together, our results suggest that Ag and Th cells induce different functional B cell responses by activating distinct second messenger systems within the B cell.

Antigens↗
PubMed1988

Amplification of altered self-reactive cytolytic T lymphocyte responses by cloned, allospecific human Th cells.

The effect of a cloned allospecific human Th cell, termed 86, on the in vitro generation of altered self-reactive cytolytic T lymphocytes (CTL) was investigated. Utilizing the induction of hapten altered self-reactive CTL as a model for virus or tumor-specific cell-mediated immunity, we determined that the presence of small numbers of clone 86 cells markedly amplified the generation of hapten altered self-reactive CTL. The killer cells induced belong to the CD4-, CD8+ subset, are specific for the hapten-modified autologous stimulator cells present in culture, and are MHC class I restricted. The CTL induced under these culture conditions are readily expanded in the presence of IL-2 with maintenance of efficient and specific altered self-killing. Of interest, clone 86 cells preferentially enhance the growth of CD8+ T cells and selectively amplify altered self-cytolysis but not NK cell activity. Although in vitro clone 86 cells mediate help for CTL generation via the production of lymphokines (IL-4 but little IL-2), one can envision immunotherapeutic strategies for human disease that involve the adoptive transfer of Th cells functionally analogous to clone 86.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1988

Hepatitis B screening in a New York City obstetrics service.

A cross-sectional chart review study was performed of hepatitis B virus (HBV) surface antigen screening of 532 women admitted to a New York City hospital obstetrics service from 1984 to 1985. Comparison of serologic results to risk factors for hepatitis B revealed that women born outside the United States and those with a positive test for or history of a sexually transmitted disease were more likely to be infected with HBV. Obstetric clinics with large immigrant populations should consider screening all patients for HBV.

Adolescent↗
PubMed1988

The relation of cellular sodium to the onset of hypertension induced by DOCA-saline in the rat.

Groups of 15 rats were injected subcutaneously with a microcrystalline suspension of DOCA and given 1% saline as drinking water for periods ranging from 2 to 16 days. The in vivo transmembrane distribution of Na and K in relation to blood pressure was assessed in terms of plasma [Na] and [K] measured with ion-specific electrodes; smooth muscle cell Na, K and water were measured in the rapidly excised tail artery. A small increase in blood pressure was observed in week 1 of treatment and was followed by an abrupt increase to higher levels at about day 10. Plasma [Na] was elevated and [K] lowered throughout in a new steady state with a reciprocal change of about 1 mmol/l. There were minor changes in intracellular [K] in rapidly excised fresh tail artery samples so that the transmembrane K gradient (EK) was at all times increased by greater than 10 mV, indicating enhanced Na-K transport. In general, intracellular [Na] was directly and Na gradient inversely related to blood pressure (P less than 0.01).

Animals↗
PubMed1987

Increased sodium permeability and transport as primary events in the hypertensive response to deoxycorticosterone acetate (DOCA) in the rat.

We report here that 18-24 h after subcutaneous administration of DOCA to the rat, plasma [Na] was significantly increased and [K] reduced without change in cell Na concentration, [Na]i, or cell K concentration, [K]i, as measured in rapidly excised tail arteries. The large increase in the transmembrane K gradient, operationally [K]i/[K]o, was associated with a significant decline of about 7 mV in the transmembrane membrane potential (Em) measured in small mesenteric arteries in situ, and a small but significant rise in blood pressure. We conclude that the permeability of the membrane to Na relative to K was increased at this time but enhanced transport of both ions was sufficient to maintain near-normal cell concentrations. These were primary events in relation to the hypertension induced by DOCA, as the rise in plasma [Na] and fall in [K] were already apparent at 6 h.

Animals↗