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Biomedical subjects

S M Friedman

Publications and source records attributed to S M Friedman.

At least 145 records · Page 8Linked to original sources

High molecular weight antigens present on human T cells.

A series of eight high molecular weight (140,000-220,000) glycoproteins on human peripheral T cells were recognized by radioimmunoprecipitation with a rabbit antiserum. The pattern of antigens present on each of eight human T cell lines studied was unique, and no line displayed the range of antigens present on peripheral T cells. The pattern of bands on peripheral T cells changed after allogeneic or lectin stimulation. Adsorption/elution experiments with antiserum showed that some of these proteins were antigenically related, and at least three different groups of proteins were present. Two of these groups could be partially distinguished by their ability to bind to ricin or lentil lectin and by their reactivity with two additional rabbit antisera. On some cell lines, it was found that proteins bound by lentil lectin but not ricin were precursors of higher molecular weight material recognized by ricin. Taken together, the data suggest that these proteins may be the products of a multigenic or multiallelic system, probably equivalent to the murine Ly 5 antigens.

Antigens, Surface↗

MLC-derived human helper factor(s) that promote B cell differentiation: induction, functional characterization, and role of Ia antigens.

Utilizing a PFC assay to quantitate the polyclonal activation of human peripheral blood B lymphocytes, we have investigated the induction and functional activity of MLC-derived human helper factor(s). Our data demonstrate that highly purified responder T cells, but not B or null cells, are required for the elaboration of MLC helper factor(s) that trigger the in vitro differentiation of B lymphocytes into PFC. Helper factor can trigger B cell maturation in the absence of helper T cells, since complement- (C) mediated lysis of the small (less than 5%) fraction of T cells present in anti-F(ab)2 immunoabsorbent column purified B cell population eliminates the PWM induced, but not the helper factor-induced PFC response. Responder T cells required for helper factor production do not bear surface membrane Ia, since alpha p23,30 + C treatment of this population does not affect helper factor generation. In contrast, alpha p23,30 + C treatment of the allogeneic stimulator cell population eliminates helper factor production. Taken together, these results demonstrate that interaction between Ia-bearing stimulator cells and Ia- responder T cells is required for the production of MLC-derived helper factor. In additional experiments, we determined that alpha p23,30, in the absence of C, totally abrogates the PFC response triggered by MLC helper factors. This result suggests an important role for Ia antigens in the functional activity of preformed helper factor molecules.

Antibodies↗

Hapten-specific human T cell lines. I. Functional analysis with respect to cytotoxic and helper activity.

Human PBL cells, sensitized in vitro to TNP or FITC-modified autologous stimulators, have been successfully grown in long-term culture by using TCGF derived from PHA-activated tonsil cells. Long-term cultures consist almost exclusively of T lymphocytes as defined by the formation of spontaneous rosettes with sheep erythrocytes and C-mediated lysis with heteroantibodies to human T cells (R alpha T H). The majority, but not all of these T cells, bear surface Ia antigens as detected by C-mediated lysis in the presence of alpha p23,30. Functionally, these cultures maintain high levels of hapten-specific cytolytic activity during many weeks of culture. In addition, a number of these T cell lines exhibit hapten specific proliferation when co-cultured with x-irradiated hapten modified autologous cells. During this proliferative response, helper factor(s) are released that trigger B cell differentiation into AFC. Data are presented that demonstrate that helper factor(s) production by T cell line cells is preferentially triggered by autologous, but nt allogeneic stimulator cells, bearing the relevant hapten.

Animals↗

Functional analysis of human T cell subsets defined by monoclonal antibodies. I. Collaborative T-T interactions in the immunoregulation of B cell differentiation.

T-B and T-T interactions involved in the regulation of PWM-triggered human B cell differentiation were studied in vitro. Functionally distinct human T cell subsets were isolated by C-mediated lysis by using the monoclonal antibodies OKT4 and OKT8. Graded numbers of either untreated or irradiated T cell subsets were added to autologous B cells, and total antibody synthesis was measured after 5 to 6 days of culture by using a highly sensitive reverse hemolytic plaque assay. The data indicate that a) the helper activity that is exclusively contained within the OKT4+ population is radiosensitive. Only at high T/B ratios can this radiosensitivity be overcome; b) the OKT8+ population contains radiosensitive cells important in suppressing B cell differentiation, and c) the suppression induced with OKT8+ cells requires the presence of radiosensitive OKT4+ cells. Thus, OKT8+ cells added to cultures containing B cells and irradiated OKT4+ cells do not suppress the PFC response. Addition of unirradiated OKT4+ cells to these cultures permits reexpression of suppression by OKT8+ cells. It is concluded that two radiosensitive cells, one within the OKT4+ population and the other within the OKT8+ population, collaborate to induce suppression. Possible mechanisms for this suppressive interaction including induction of suppressor precursor cells within the OKT4+ population or inhibition of OKT4+ helper cells by OKT8+ cells are discussed.

Antibodies↗

Red cell sodium and potassium in hemorrhagic shock measured by lithium substitution analysis.

A new method of measuring intracellular Na and K using Li substitution analysis was applied to a study of red cell Na changes in hemorrhagic shock. Using a rat hemorrhagic shock model, significant changes in red cell Na were found after 2 hours. Red cell Na in shocked animals was significantly higher than in control animals (p less than 0.025). A small decrease in red cell K occurred. There was no intracellular shift of Li. In addition, a fall in plasma Na and a rise in plasma K occurred with progressive shock. In a 2-hour period following retransfusion there was no significant change in cell Na or K, but the plasma Na and K returned toward preshock levels. These results confirm a prolonged and significant impairment of red cell membrane function in shock and suggest that impaired Na-K pump function may be responsible for the changes.

Animals↗

Association between hepatobiliary cancer and typhoid carrier state.

A case-control study of deceased typhoid carriers registered by the New York City Health Department between 1922 and 1975 was carried out to test for an association between the typhoid-carrier state and death due to hepatobiliary cancer. 471 carriers were matched with 942 controls for sex, age at death, year of death, borough in which the carrier died, and where they were born. The results show that chronic typhoid carriers die of hepatobiliary cancer six times more often than the matched controls and that this difference is significant (P less than 0.001) by simple chi2 test and by the Mantel-Haenszel method of chi2 for matched triples. Possible mechanisms for this association are discussed.

Adult↗

Sodium in blood vessels. A brief review.

Extracellular Na can be accurately partitioned into free and bound components; the latter component is directly related to the hydration and stiffness of the vascular wall. Cell Na can be similarly partitioned: [Na+]i is about 10mM and the transmembrane gradient about 15:1 in a physiological medium. The transmembrane gradient remains constant over a wide range of change in [Na+]0. Although active Na transport is largely responsible for developing the transmembrane ion distribution pattern, the membrane potential depends mainly on movements of K+ and C1-. No certain direct role can be assigned to Na+ in short-term vasoconstriction, but an indirect role through the regulation of catecholamine release and uptake is now established. There is evidence that the entry of Na+ into cells plays a fundamental role in the protein-synthesizing activity of the vascular smooth muscle cell and is thereby involved in the longer term determination of peripheral vascular resistance.

Animals↗

The induction of TNP-altered, self-reactive human cytotoxic T cells by soluble factors: the role of Ia antigens.

This report demonstrates that human peripheral blood T lymphocytes, triggered by allogeneic cells or soluble antigens, elaborate helper factor(s) that promotes the in vitro differentiation of TNP altered-self reactive human CTL. Helper factor(s) alone is not sufficient for the generation of these killer cells, but requires the presence of TNP-derivatized autologous stimulators during sensitization. Additional experiments were performed with antisera to a human Ia-like antigen, p23, 30. These studies indicate that human Ia-like antigens play an important role in both the induction of helper factor(s) and in the functional activity of preformed helper factor(s) molecules.

Cytotoxicity, Immunologic↗

The rat-tail artery maintained in culture: an experimental model.

The rat-tail artery was maintained in vitro for 2 weeks to investigate its suitability as an experimental model. The criteria were that (a) it should retain the overall histological organization with normal ultrastructural appearance of the smooth-muscle cells; (b) stored neurotransmitter which could be activated by experimental treatment should be absent; and (c) smooth-muscle ion transport mechanisms should fall within normal range. Vessels were maintained in Falcon tissue-culture dishes in Dulbecco's modified Eagle's medium. Either 2% or no serum supplement was found to be more suitable than 10% serum due to the high rate of cell proliferation induced by the latter. Light and electron microscopy of cross sections of the vessels indicated that the overall normal vessel architecture was retained, and the ultrastructural features predicted normal function. There were no discernible differences dependent on the length (up to 8- to 10-cm lengths) of the cultured vessel. Preliminary experiments with fluorescent microscopy showed that stored neurotransmitter in the nerves of the vessel wall was no longer present after 48 hr. Ultrastructural examination revealed that storage vesicles in vitro lost their dense cores, representing noradrenalin, between 41 and 48 hr in culture. Normal ion transport mechanisms were retained in the smooth-muscle cells of the arteries in vitro for up to 2 weeks when tested with ion-specific electrodes. Morphological and physiological evidence support the suitability of the rat-tail artery as a model for experimental testing of vascular tissues.

Animals↗

Evidence for enhanced Na transport in hypertension induced by DOCA in the rat.

Uninephrectomized rats were treated with DOCA-saline for 3 weeks. Active Na transport activity was assessed in the rat tail artery in three separate ways. In the first method, Na-K exchange was expressed in terms of steady-state values in normal and ouabain-blocked arteries. In the second method, the relation of free cell Na to [Na]0 was measured after equilibration in media in which [Na]0 varied from about 25 to 140 mM. In the third method, the relation of cell K to [k]0 was measured with glass electrodes during the reestablishment of normality following prolonged K depletion. All methods yielded evidence of enhanced net active transport activity in the incubated artery (zero intraluminal pressure) in steady state.

Animals↗

Cell-mediated lympholysis of trinitrophenyl-derivatized autologous human cells: in vitro triggering by nonspecific signals.

This report describes the primary in vitro generation of human CTL that lyse TNP-derivatized autologous cells. Although in the majority of these studies, a direct cytotoxic response to the TNP-modified autologous stimulators was not achieved, in all experiments the addition of either allogeneic cells or soluble antigen triggered the generation of killer cells which destroy TNP-modified, but not unaltered, autologous targets. Fractionation of responder lymphocyte populations demonstrated that the cytotoxic activity was mediated by T cells. Killer cell specificity was tested by assaying for cytotoxicity to a variety of targets, and by blocking the cytolysis of TNP-altered autologous targets with various populations of nonradiolabeled cells. Results indicated that these CTL were cytotoxic for TNP-modified autologous cells but not unaltered autologous or TNP-modified allogeneic targets. The capacity of soluble antigen and alloantigens to facilitate the in vitro generation of altered-self reactive human CTL is not an isolated phenomenon. This "helper" effect has now been observed for the cytotoxic response to chemically modified autologous cells and MHC identical human leukemic blasts. It is possible that in vivo, similar responses to nonspecific antigenic stimuli may play a role in the maintenance of immune surveillance.

Antigens↗

Intracellular sodium and potassium changes in vascular smooth muslce during hemorrhagic shock.

The vascular smooth muscle cell sodium and potassium changes occurring in hemorrhagic shock were studied in rats subjected to hemorrhagic shock at 30 millimeters of mercury for a two hour period. A new ion exchange method, based upon the substitution of lithium for extracellular sodium was used to measure the intracellular sodium and potassium. A significant rise in cell sodium and fall in cell potassium levels occurred. These changes suggest that vascular smooth muscle cell membrane function is impaired in hemorrhagic shock. The normal homeostatic vascular responses to hemorrhage may be significantly affected by these changes.

Animals↗

Inhibition of proliferative and plaque-forming cell responses by human bone-marrow-derived lymphocytes from peripheral blood by antisera to the p23, 30 antigen.

A recently described technique for the polyclonal induction of plaque-forming cells from human bone-marrow derived (B) lymphocytes of peripheral blood has been used to assess the role of a human Ia-like antigen (p23,30) in differentiation of human B cells. In particular, the effects of antisera to p23,30 on the plaque-forming cells and proliferative responses of human B cells stimulated by pokeweed mitogen or soluble products of activated human thymus-derived lymphocytes (T cells) have been examined. Antisera to p23,30 eliminated the development of plaque-forming cells induced by both T cell products and pokeweed mitogen. While these antisera also abrogated B cell proliferation induced by T cell supernatants, the proliferative response generated by pokeweed mitogen was only partially reduced. It was also determined that while the p23,30 antigen continues to be expressed on fully differentiated plaque-forming cells, antisera to this determinant exert inhibitory effects on B cell differentiation only when present during the early stages of B cell cultures. These results lend further support to the analogy between p23,30 and murine Ia antigens. Moreover, they demonstrate a major role for this antigen in the early events involved in human B cell differentiation into antibody-forming cells.

Antigen-Antibody Reactions↗

The effects of external sodium substitution on cell sodium and potassium in vascular smooth muscle.

1. The entry of Li into the vascular smooth muscle cells of the rat tail artery follows first-order kinetics with a rate constant of approximately 1.3 hr(-1) at 10 mM-[Li](o). The rate constant decreases gradually to ca. 0.5 hr(-1) when the [Li](o)/[Na](o) ratio is increased.2. Replacement of Na with Li over the range of [Li](o) from 1 to 115 mM, accomplished at constant ionic strength and osmolarity of the bathing solution, produces changes in cell Na and K without apparent change in cell water. At equilibrium, cell Li increases in linear proportion to [Li](o), at a ratio of 2:1 throughout the range. The increase in cell Li is associated with inverse falls in both cell K and Na such that the ratio of cell K to cell Na remains constant at ca. 10:1 throughout.3. The changes in the ionic contents, induced by equilibration of the tissue with a Na-free, Li-substituted solution, are reversible.4. Replacement of Na with sucrose over the range of 40-115 mM results, at equilibrium, in a linear fall in cell Na without conspicuous change in cell K. A constant portion of the cell Na, ca. 10 m-mole/kg dry wt., does not participate in this exchange.5. At equilibrium, reductions in [Na](o) are reflected in corresponding reductions in apparent [Na](i) such that the [Na](o)/[Na](i) ratio remains constant.

Animals↗