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Biomedical subjects

S M Friedman

Publications and source records attributed to S M Friedman.

At least 127 records · Page 7Linked to original sources
PubMed1983

Functionally restricted, allospecific, human helper T cell lines that amplify either B cell or cytolytic T cell responses.

Using a panel of partially cloned, OKT4+, DRw-1-specific, alloproliferative human T cell lines, we have identified two functionally restricted and reciprocating types of helper T cells. One provides major histocompatibility complex-restricted help for plaque-forming cell responses by DRw 1+ allogeneic B cells; the other preferentially amplifies the generation of allospecific cytotoxic T lymphocytes (CTL) from CTL precursors that have been suboptimally triggered by alloantigen.

Antibodies, Monoclonal↗
PubMed1983

Monovalent and divalent ions in vascular tissue.

Steep transmembrane concentration gradients in vascular smooth muscle for all ions are maintained by energy-requiring pumps. The Na+ gradient appears to dominate the distribution of the other ions primarily because it controls cell hydration and energizes the transport of sugars, amino acids, and Ca++, Mg++, and H+. The Na+ gradient is a closely regulated constant (about ten to one) and is not perturbed except by changes in the limited permeability of the vascular smooth muscle membrane to Na+ or in the activity of its transport enzyme, the Na+-K+ATPase. Increased permeability to Na+ has been seen in vascular smooth muscle and in erythrocytes in salt-dependent forms of experimental hypertension, as well as in essential hypertension. A compensatory increase in Na+ transport (extrusion) has been seen. This increase in transport can be produced by a moderate increase in aldosterone acting alone or by a lesser increase acting synergistically with vasopressin.

Animals↗
PubMed1983

National case-control study of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men: Part 1. Epidemiologic results.

To identify risk factors for the occurrence of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men, we conducted a case-control study in New York City, San Francisco, Los Angeles, and Atlanta. Fifty patients (cases) (39 with Kaposi's sarcoma, 8 with pneumocystis pneumonia, and 3 with both) and 120 matched homosexual male controls (from sexually transmitted disease clinics and private medical practices) participated in the study. The variable most strongly associated with illness was a larger number of male sex partners per year (median, 61 for patients; 27 and 25 for clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, have had syphilis and non-B hepatitis, have been treated for enteric parasites, and have used various illicit substances. Certain aspects of a lifestyle shared by a subgroup of the male homosexual population are associated with an increased risk of Kaposi's sarcoma and pneumocystis pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Antigen-specific and polyclonal immunoglobulin production induced by a cloned tetanus toxoid-specific T cell line.

This report describes the isolation and the phenotypic and functional characterization of a cloned, IL 2 dependent, TT-specific human helper T cell line (TCL), designated 1A1. 1A1 was derived by limiting dilution culture of a bulk IL 2-dependent TCL that was found to contain both TT and trinitrophenyl (TNP) altered self-reactive T cells. Specifically, 1A1 represents the outgrowth of one well of a microwell cloning plate initially seeded at 1 TCL/well, from which less than 4% (3/96) wells grew. Phenotypic analysis, utilizing a battery of monoclonal antibodies, demonstrates that all 1A1 cells are T cells belonging to a stable and discrete T cell subset: T3+, T4+, T17+, T8-. In proliferative assay, 1A1 responds specifically to TT but not to other soluble antigens against which the donor is sensitized, a panel of allogeneic stimulators, nor to TNP-modified-self. Moreover, 1A1 is HLA-DRw-restricted, proliferating only to TT in association with DRw3+ antigen-presenting cells. Of greater interest is the observation that 1A1 is an antigen-specific helper T cell line. Thus, by utilizing ELISA systems to quantitate class-specific immunoglobulin and antigen-specific antibody, it was determined that co-culture of autologous B cells, 1A1 cells, and a low concentration (1 to 10 ng/ml) of TT results in an IgG response that is predominantly, if not exclusively, antigen-specific antibody. In contrast, the presence of high concentrations of TT (4 micrograms/ml) triggers a polyclonal immunoglobulin response comprised of IgM with a small IgG component that is essentially devoid of anti-TT antibody. These results demonstrate that depending on the mechanism of activation, a cloned antigen-specific helper T cell line can mediate antigen-specific or polyclonal help for autologous B cells.

Antibodies, Bacterial↗
PubMed1983

[Relation between erythrocyte free protoporphyrins and usual iron intake in a group of University of Buenos Aires students].

In order to analyze the interrelationships between free erythrocyte protoporphyrins and the usual iron intake in adult students, biochemical, and hematological values, and dietary daily intake, obtained using the recall method during seven days, were studied. Hematocrit (Hto.), hemoglobin (Hb) and free erythrocyte protoporphyrins (FEP) were determined in a group of 145 female university students, healthy according to the standard parameters of the Buenos Aires University Health Department. Mean iron intake was 23.0 +/- 1.5 mg per day, about 44% being provided by animal sources; 74.5% of the population was within the recommended daily intake according to FAO/WHO; only 0.7% of the population did not cover protein requirements while 35% did not cover energy needs. Hto. and Hb were below normal levels in 7.8% of the population when compared with standards according to ICNND. To obtain information about normal values to FEP, expressed as microgram/100 ml red cells (FEP% r.c.) and FEP/Hb ratio, the group of students with adequate intake of energy and proteins who had normal values for Hb and Hto. was selected. This group, including 94 women, had a mean FEP% r.c. of 15.71 +/- 7.26 and a mean FEP/Hb ratio of 0.44 +/- 0.21. There was observed an inverse correlation between FEP% r.c. and FEP/Hb with total iron intake (r = 0.80 and r = 0.78, respectively) and between FEP% r.c. and Hb concentration (r = 0.81). These results confirm the usefulness of the free erythrocyte protoporphyrins determination as a good index of iron stores and usual intake of this population.

Adult↗
PubMed1982

An epidemiologic evaluation of leprosy in New York City.

Leprosy is a transmissible disease that is propagated from human to human. At the US Public Health Service hospital, New York City, the number of new leprosy cases per year during the 1970s was about three times greater than in the previous decade. This review of our 100 most recent leprosy patients shows that 60% were of the lepromatous and borderline lepromatous type. Ninety-nine of the patients were foreign born, originating in more than 26 countries. This emphasizes that, at this time, the leprosy problem in New York City is almost exclusively a reflection of immigration patterns. The majority of the patients were asymptomatic at the time of entering the United States. The average latent period from entering the United States until onset of symptoms was 4.8 years, with a range of 0 to 38 years. These figures emphasize the need for physicians to be aware that leprosy can occur as long as five to 40 years after emigration from endemic areas. For all types of leprosy, the average lag from the onset of symptoms to the time of diagnosis was 29.0 months (range, 0 to 245 months). Our experience indicates that a program of urban leprosy treatment using available drugs and supportive care is feasible.

Diagnosis, Differential↗
PubMed1982

Ion-selective electrode studies of cell Na components in vascular smooth muscle of WKY and SHR.

Vascular smooth muscle cells of the rat tail artery were enriched with Na by overnight incubation at 10 degrees C in K-free physiological salt solution (K-free PSS). The cells were then returned to normal PSS in a series of steps so as to define the effect of varying temperature between 3 and 37 degrees C, the effect of ouabain, the effect of readmitting K+ in the continuing presence of ouabain, and, finally, the effect of removing ouabain in the continuing presence of K+. The effects were measured with flow-through Na+ and K+ glass-cannula electrodes as changes in a superfusate moving slowly past the artery. Where possible, confirmatory evidence was obtained by conventional incubations followed by chemical analysis of the tissues. About 10 mmol Na+/kg dry wt is transferred out of the cells when temperature is raised from 3 to 37 degrees C. Exposure of the tissue to ouabain while the tissue is still in the K-free state produces a further loss of about 8 mmol Na+/kg dry wt and 4 mmol k+/kg dry wt. Readmittance of K+ in the continuing presence of ouabain induces a further loss of about 25 mmol Na+/kg dry wt in exchange for an uptake of about 13 mmol K+ measured electrometrically or about 20 mmol K measured chemically. Finally, the removal of ouabain is followed by an extrusion of about 155 mmol Na+/kg dry wt in exchange for an uptake of 133 mmol K%. The ouabain-insensitive exchange of Na+ and K+ is enhanced in spontaneously hypertensive rats as compared with normotensive rats.

Animals↗
PubMed1982

Allospecific human T cell lines and clones which mediate HLA-DR restricted helper activity.

In order to analyze the immunoregulatory activity of allospecific human T cells, we have combined the techniques of limiting dilution culture and IL-2 dependent T cell growth to generate cloned alloreactive T cell lines (TCL). These TCL have been expanded in continuous culture for greater than 8 mo with retention of stable phenotypic and functional characteristics. For example, phenotypic analysis of alloproliferative TCL, utilizing a panel of monoclonal antibodies, demonstrate that these cultures are comprised of T cells belonging exclusively to the T3+ T4+ T8- "helper" or "inducer" T cell subset. Coculture of cloned alloproliferative TCL cells with a panel of allogeneic stimulators reveals that these clones are specifically reactive against the HLA-DRw1 determinant. Of greater interest, coculture of selected alloproliferative TCL cells with DRw1+ but not DRw1- B cells results in a vigorous polyclonal response as measured by the reverse hemolytic plaque assay. Although major histocompatibility complex restriction of this T-B interaction operates at the inductive level, help is at least partially unrestricted at the effector level as alloantigen-activated TCL cells provide demonstrable, although not maximal, help for DRw1- B cells.

Clone Cells↗
PubMed1982

Characterization of the alloactivated E+Ia+ cell capable of stimulating in mixed lymphocyte culture.

Human peripheral blood E+ lymphocytes were alloactivated by E- cells and then purified by repeat E+ selection. As described by others, alloactivated cells (E+d6) but not unactivated E+ cells were capable of stimulating both allogeneic and autologous mixed lymphocyte cultures (MLC). To further characterize the subset of cells responsible for this function, we used a variety of monoclonal antibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacintibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacintibodies to human T cells and monocytes. Treatment of E+d6 cells with anti-Ia OKI1) plus complement (C) abrogated their stimulating capacity. In contrast, treatment with the anti-T cell antibodies OKT3, OKT11A, OKT4, OKT8 plus C or anti-macrophage antibody (OKM1) plus C failed to eliminate their MLC stimulatory capacity. Because OKT3 recognizes the majority of T cells and OKT11A recognizes virtually all E+ cells, we reasoned that a contaminating non-T cell containing the MLC-stimulating capacity may be present within the alloactivated E+ population. To further address this question, E+d6 cells were positively and negatively selected using a rosetting technique with anti-Ig-coated red cells. The positively selected OKT3, OKT11A, OKT4, or OKT8 E+d6 cells retained minimal ability to stimulate MLC, whereas the corresponding negatively selected populations were highly enriched in this function. Phenotypic analysis of the isolated populations failed to demonstrate greater than 1% surface membrane Ig(SmIg) positive cells. Taken together, these results suggest that the MLC stimulatory capacity of alloactivated E+ cells is contained within an Ia+, OKM1-, SmIg- non-T cell subset.

Antibodies, Monoclonal↗
PubMed1982

OT-CLL: a human T cell chronic lymphocytic leukemia that produces IL 2 in high titer.

This report identifies and describes a human T cell chronic lymphocytic leukemia, OT-CLL, which can be triggered by selected mitogens (either PHA or Con A) to produce IL 2 in high titer. Optimal IL 2 production requires culturing OT-CLL cells at 2 to 5 X 10(6)/ml for 24 hr in the presence of 1 to 2% PHA-M. Under these conditions, the titer of IL 2 generated is greater than 20-fold that obtained from conventional sources, e.g., from mitogen-activated tonsillar lymphocytes. Two lines of experimental evidence suggest that the tumor cell product(s) is IL 2. First, in functional assays, suprenatants derived from cultures of PHA-activated OT-CLL cells trigger the proliferation and long-term growth of IL 2-dependent human TCL cells. Second, a partial biochemical purification of the active moiety(ies) derived from OT-CLL demonstrates marked similarity to conventional human IL 2. Thus, the biologically active material(s) precipitates in 50 to 70% saturated (NH4)2 SO4 solutions; elutes from DEAE-Sepharose in the presence of 0.04-0.08 M NaCl; and has an apparent m.w. of approximately 14,000, as determined by Sephadex G-100 gel filtration. In addition, analysis of OT-CLL cells by indirect immunofluorescence, utilizing a panel of monoclonal antibodies, confirms not only that these tumor cells are of T cell lineage but that they display surface antigens that define the normal human peripheral T cell subset subserving helper or inducer function: OKT3+, OKT4+ , OKT8-.

Cell Count↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. IV. Induction of suppressor cells within the OKT4+ population.

In this report, we explored the functional heterogeneity within the OKT4+ subset of human T cells. Evidence was obtained that although in vitro pokeweed mitogen-activated OKT4+ cells can function as radioresistant helper cells, these activated OKT4+ cells could also exert potent feedback suppression. Despite the induction of suppressor cells after pokeweed mitogen activation, the OKT4+ population maintains its original OKT3+, OKT4+, nd OKT8- surface phenotype. The suppressor cells contained within the activated OKT4+ population were found to be radiosensitive. Importantly, the suppression mediated by activated OKT4+ cells required the presence of radiosensitive cells contained within the resting OKT4+ population. Taken together, these results suggest that the OKT4+ subset of human T cells contains cells that can be activated to differentiate into suppressor cells independent of OKT8+ cells.

Antibodies↗
PubMed1981

Dissection of distinct human immunoregulatory T-cell subsets by a monoclonal antibody recognizing a cell surface antigen with wide tissue distribution.

A monoclonal antibody, PVR-11, was obtained after hybridization of X63Ag8.653 murine myeloma cells with spleen cells from a mouse immunized with human lymphocytes. It recognizes a 175,000- to 185,000-dalton surface antigen present on approximately 80% of normal human peripheral T lymphocytes, 50% of non-T non-B cells, and less than 10% of B cells as determined by complement-dependent microcytotoxicity. It is also present on various leukemia T cells, on some but not all T lymphoblastoid cell lines, and on a small fraction of some B lymphoblastoid cell lines. Some B-cell chronic lymphocytic leukemia cells also express the PVR-11 antigen. Functional analysis of normal human T lymphocytes demonstrated that the PVR-11-depleted T-cell subset contains the precursors of both cytotoxic and suppressor cells but lacks helper cells. On the other hand, cytotoxic effector T cells express the PVR-11 antigen. These results demonstrate that antigenic determinants with relatively wide tissue distribution can dissect functionally distinct human immunoregulatory T-cell subsets.

Antibodies↗
PubMed1981

Pseudobacteremia attributed to contamination of povidone-iodine with Pseudomonas cepacia.

Pseudomonas cepacia was recovered from the blood cultures of 52 patients in four hospitals in New York over 6 months from April through October 1980. Epidemiologic investigation in one hospital indicated that the positive results of blood culture represented pseudobacteremias and implicated a 10% povidone-iodine solution used as an antiseptic and disinfectant (Pharmadine; Sherwood Pharmaceutical Company, Mahwah, New Jersey) as the source of contamination. Physicians who drew blood cultures positive for P. cepacia were more likely to have left povidone-iodine on the skin before venipuncture (p = 0.026) and were more likely to have applied povidone-iodine to the blood culture bottle tops and to have left it there while inoculating the blood culture media (p = 0.007) than those who drew cultures negative for P. cepacia. Direct inoculation of Pharmadine into brain-heart infusion broth yielded P. cepacia; however, 2 weeks after the first cultures, the same Pharmadine bottles were culture negative. The iodine concentrations of the contaminated Pharmadine solutions were similar to those of 10% povidone-iodine solutions distributed by other manufacturers.

Blood Specimen Collection↗
PubMed1981

Functional analysis of human T cell subsets defined by monoclonal antibodies. II. Collaborative T-T interactions in the generation of TNP-altered-self-reactive cytotoxic T lymphocytes.

In previous reports we have demonstrated that human T cells, responding to soluble and alloantigens, release helper factor(s) that amplify primary in vitro hapten-altered-self-reactive CTL responses. In the present studies, we have employed complement-fixing monoclonal antibodies (OKT4 and OKT8) that recognize functionally distinct human T cell subsets to investigate the role of T-T interaction in the generation of these killer cells. In all experiments, purified OKT4+ responder T cells were deficient in cytotoxic activity, whereas responder populations containing OKT8+ T cells generated substantial cytotoxicity; demonstrating that TNP-altered-self-reactive CTL precursors are contained within the OKT8+ T cell subset. Further, optimal cytotoxic responses were obtained from responder populations containing both OKT4+ and OKT8+ T cells, suggesting that cooperative interaction between these subsets may result in an amplification of killer cell activity. This interpretation was supported by the following observations: (1) the amplifying effect of soluble antigen required the presence of both OKT4+ and OKT8+ responders; (2) during MLC, OKT4+ but not OKT8+ responder T cells generate helper factor(s) that amplify TNP-altered-self-reactive CTL responses; (3) helper factor(s) bypass the requirement for direct OKT4-OKT8 T cell interaction, triggering a CTL response that is proportional to the percentage of OKT8+ T cells present within the responder population. In additional studies, we determined that the TNP-altered-self-reactive effector CTL maintain the OKT3+, OKT4-, OKT8+ surface phenotype displayed by the CTL precursor.

Antibodies↗