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Biomedical subjects

D A Cohen

Publications and source records attributed to D A Cohen.

At least 91 records · Page 5Linked to original sources

Legionella-like organisms.

The family Legionellaceae contains the new genus and species Legionella pneumophila; organisms that resemble L pneumophila but differ in one or more phenotypes are called legionella-like organisms and constitute a growing list of new species now numbering over two dozen, and the characterization of additional species of legionellae continues to expand. Similar to L pneumophila, some of these new species have additional serogroups within the species. These new species have varying degrees of clinical and epidemiological importance. We will review historical, laboratory, and clinical aspects of Legionella species other than L pneumophila and L micdadei.

Humans↗

Serum interleukin-1 (IL-1) activity in alcoholic hepatitis.

Interleukin-1 (IL-1) is a monokine which has been demonstrated to produce a variety of seemingly diverse metabolic events including fever, neutrophilia, anorexia, altered mineral metabolism, muscle catabolism, and fibroblast proliferation. Because many of the clinical features of alcoholic hepatitis are metabolic abnormalities that have been shown to be caused by IL-1, we questioned whether patients with alcoholic hepatitis had elevated serum levels of IL-1. Six patients with alcoholic hepatitis had serum IL-1 activity measured by the thymocyte costimulator assay after serum inhibitors were removed. Their values were compared to those of 6 age and sex-matched healthy controls. Patients with alcoholic hepatitis had markedly elevated serum IL-1 activity, with the integrated value of all fractions having serum IL-1 activity being 9.8 times that of controls. IL-1 activity in serum from alcoholic hepatitis patients also was blocked by antibody to IL-1. We conclude that patients with alcoholic hepatitis have increased serum IL-1 activity which may play a role in certain of the metabolic complications of alcoholic hepatitis.

Adult↗

HLA-Dr-unrestricted accessory cell function in human neutrophils.

Human polymorphonuclear leukocytes (PMN) were purified from purified protein derivative (PPD)-immune individuals and assayed for their ability to act as antigen-presenting cells for PPD to autologous purified lymphocytes or as accessory cells in a PHA mitogenic response with autologous lymphocytes. PMNs were very efficient accessory cells in that the PHA mitogenic response was augmented fourfold by the addition of PMNs to the culture. In contrast, PMNs did not appear to present antigen. Accessory cell function by PMNs was HLA unrestricted in that allogeneic PMNs were equally effective accessory cells. Furthermore, the accessory cell function of PMNs appeared to require cell-cell contact, since culture supernatants from PMNs failed to replace intact PMNs in the mitogenic response.

Antigen-Presenting Cells↗

The use of interleukin 1+ and interleukin 1- cell lines to dissociate signals involved in the induction of cytolytic T cells.

The availability of paired homogeneous Ia+ tumour cell lines (P388AD, interleukin (IL)-1+, and P388NA, IL-1-), which differ in inducibility for IL-1, provided a unique opportunity to assess directly the role of Ia and IL-1 in the induction of cytolytic T cells (CTL) to trinitrophenol (TNP)-modified self. TNP-P388AD but not TNP-P388NA consistently induced H-2-restricted, hapten-specific CTL. However, in the presence of an exogenous source of IL-1, TNP-P388NA was able to induce CTL of the magnitude seen with TNP-P388AD. Both Ia expression and IL-1 secretion were necessary in that when TNP-modified purified T cells were utilized as stimulators, CTL activity was not demonstrated even if IL-1 was added, but was only seen when unmodified, P388AD, or spleen cells were added to the cultures.

Animals↗

Zinc metabolism in alcoholic liver disease.

Alterations in zinc metabolism or zinc deficiency frequently occur in patients with alcoholic liver disease. Potential manifestations of zinc deficiency include skin lesions, hypogonadism, impaired night vision, impaired immune function, anorexia, altered protein metabolism, diarrhea, and depressed mental function. Because of the variety of ways in which zinc deficiency may present in alcoholic liver disease, clinicians must maintain a high index of suspicion for this nutrient deficiency when caring for these patients. Not only may zinc deficiency occur with alcoholic liver disease, but there also may be altered zinc metabolism. Recent data from alcoholic hepatitis patients demonstrate increased serum levels of the monokine interleukin 1, which is known to cause hypozincemia and an internal redistribution of zinc. This monokine has a host of metabolic functions other than its effect on mineral metabolism that have relevance for alcoholic liver disease such as fever production, neutrophilia, and muscle catabolism. We suggest that the patient with alcoholic liver disease frequently has problems with either zinc deficiency or altered zinc metabolism and the potential implications of this are discussed.

Acrodermatitis↗

Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals.

The development of functional Fc receptors (FcR) during induced differentiation with the tumor promoter, phorbol myristate acetate (PMA), was studied in the murine tumor cell line, P388. PMA induced the appearance of FcR on the membranes of P388 cells as indicated by the binding of IgG-coated sheep red blood cells (IgG-SRBC). Concentrations of PMA as low as 1 ng/ml were sufficient to induce the expression of FcR as well as to inhibit cellular division and to induce adherence in the P388 tumor cell line; however, optimal FcR induction occurred at PMA concentrations of 10-100 ng/ml. Immunofluorescent analysis with heat-aggregated myeloma proteins indicated that PMA induced FcR which were capable of binding IgG2a and IgG2b immunoglobulins, but not IgG1. Adherence to a substratum was determined to be a second required signal for expression of FcR, since PMA induction of P388 tumor cells in teflon dishes failed to fully develop FcR and adherence of P388 cells to poly-L-lysine-coated culture dishes in the absence of PMA was insufficient for FcR expression. FcR which appeared after PMA induction were non-functional in the sense that membrane-bound IgG-SRBC were not ingested to any significant extent by the tumor cells. However, if FcR induction occurred in the presence conA-induced rat spleen cell culture supernatants, phagocytosis of membrane-bound erythrocytes occurred. These findings suggest that for the expression of FcR which are capable of particle internalization, at least three identifiable membrane-transmitted signals are required during differentiation.

Animals↗

Comparison of metrizamide computed tomography and magnetic resonance imaging in the evaluation of lesions at the cervicomedullary junction.

We compared intrathecal metrizamide-enhanced CT (metrizamide-CT) and magnetic resonance imaging (MRI) in the evaluation of 17 patients with clinical suspicion of lesions at the cervicomedullary junction. MRI was superior in imaging the position of the cerebellar tonsils and the size and extent of mass lesions. MRI and metrizamide-CT were equal in detecting syringomyelia. CT with and without IV contrast enhancement was necessary to detect calcium or defects in the blood-brain barrier within neoplasms.

Adolescent↗

Sodium periodate-induced T cell mitogenesis: an analysis of the requirement for Ia and IL 1.

T lymphocytes oxidized with the mitogen sodium periodate undergo a proliferative response when cultured in the presence of Ia+ accessory cells. However, the exact role(s) the accessory cells play in such a response has not been clearly defined. We have evaluated the role of Ia and the requirement for interleukin 1 (IL 1) in periodate mitogenicity by using the Ia+ cloned tumor cell lines P388AD (Ia+, IL 1 inducible) and P388NA (Ia+, IL 1 noninducible) as accessory cells. P388AD but not P388NA was able to supply accessory cell function to periodate-treated T cells, suggesting that Ia expression alone was not sufficient to reconstitute a response. Monoclonal anti-I-Ad and anti-I-Ed antibody blocked the accessory cell function of P388AD. In addition, monoclonal antibody GK 1.5, directed against the T cell determinant L3T4a, blocked the P388AD/periodate-treated T cell interaction, confirming that this interaction was restricted by class II molecules. Although Ia expression was required, the response was not major histocompatibility complex (MHC) restricted, because allogeneic as well as syngeneic macrophages were capable of supplying accessory cell function to periodate-treated T cells. Exogenous IL 1 alone was able to trigger periodate-treated T cells, suggesting that Ia was required for the induction of IL 1 synthesis by the accessory cells. Furthermore, purified IL 2, devoid of IL 1 activity, was able to fully reconstitute the proliferative response of accessory cell-depleted oxidized T cells to a level equal to that of whole spleen accessory cells or P388AD. These data suggest that periodate-treated T cells can proliferate with IL 1 alone and that Ia+ accessory cells in periodate-mediated T cell mitogenicity may function in the release of IL 1 and the induction of IL 2 synthesis by the T cells.

Animals↗

Antigen presentation in the rat. II. An Ia+ radiosensitive T cell can present antigen to primed Ia- T cells.

We demonstrated previously the presence of an Ia+ (OX-6+) antigen-presenting cell within the rat T cell fraction that is capable of presenting antigen to antigen-primed OX-6-T cells. This antigen-presenting cell (T-APC) reacted with the monoclonal antibodies W3/25 and W3/13, which is known to react mainly with rat T cells. Further characterization of the T-APC indicated that the cell also reacted with the monoclonal antibody OX-19, which is highly specific for rat T cells. Moreover, the antigen-presenting function of the T-APC was sensitive to treatment with mitomycin C or gamma-irradiation (2000 rad). Under similar conditions, antigen presentation by partially purified dendritic cells or macrophages was totally resistant to these treatments. The antigen-presenting activity of gamma-irradiated T-APC was not reconstituted by the addition of the lymphokines IL 1, IL 2, or Con A supernatants. Although unirradiated T-APC were able to stimulate an MLR response, this function was also sensitive to gamma-irradiation, whereas the MLR-stimulating ability of macrophages and dendritic cells was resistant to gamma-irradiation. These data indicate that Ia+ T cells from the rat are capable of presenting antigen to antigen-primed T lymphocytes and that, in contrast to antigen presentation by macrophages and dendritic cells, the function of T-APC is gamma-radiation sensitive.

Animals↗

Abortive ectromelia virus infection in peritoneal macrophages activated by Corynebacterium parvum.

We have previously demonstrated that peritoneal macrophages (M phi S) from C3H mice were resistant to in vitro infection by ectromelia virus, following activation by intraperitoneal injection of the immunomodulator Corynebacterium parvum. In contrast, resident and mineral oil-elicited M phi S were fully susceptible to virus infection. This report analyzes the infectious cycle of ectromelia virus in C parvum-activated and mineral oil-elicited M phi S and demonstrates that an abortive infection occurred in the activated M phi S that blocked the infectious cycle prior to the release of DNA from the infecting virions. The kinetics of adsorption of radiolabeled virus were similar in both susceptible and resistant M phi cultures; however, viral-induced incorporation of uridine and thymidine occurred only in the mineral oil-elicited and not the C parvum-activated M phi S. In addition, the late protein hemagglutinin was only detected in infected cultures of susceptible mineral oil-elicited M phi S. An electron micrographic analysis of the infectious cycle indicated that the adsorption of virus to the plasma membrane, uptake into lysosomes, and the primary undercoating and release of viral cores into the M phi cytoplasm were identical in both M phi types. In contrast, secondary uncoating (release of genomic DNA from the viral cores into the cytoplasm) was never detected in infected C parvum M phi S. These data are consistent with our previous findings and with the hypothesis that activation of M phi S by C parvum induces an interferon-mediated resistance to ectromelia virus infection.

Animals↗

Antigen presentation in the rat: role of a nonadherent, nonphagocytic, W3/13, OX-6 positive T cell in the presentation of antigen to primed T lymphocytes.

The nature of accessory cells in rat lymph nodes which can present antigen to primed T cells was investigated. Removal of adherent, phagocytic cells from antigen-primed lymph node cells by passage over glass-bead and nylon wool columns followed by treatment with carbonyl iron did not abrogate the antigen-specific proliferative response to keyhole limpet hemocyanin (KLH) or to the synthetic polypeptide L-glutamic acid-L-alanine-L-tyrosine (GAT). This T cell-enriched population was free of contaminating macrophages as determined by latex bead ingestion and morphological criteria during a 4-day culture period. Treatment of the T cell preparation with rabbit anti-rat IgG and complement or rosetting with IgG-coated sheep erythrocytes to remove any remaining B cells or macrophages did not significantly affect the proliferative response to antigen. Analysis of the T cell preparation by panning techniques with monoclonal antibodies to T cell surface markers suggested that both the responding T cell and the antigen-presenting cell were positive for the rat T cell marker, W3/13. The KLH-primed LN T cell-enriched fraction contained two distinct cell populations that were separable on the basis of their reactivity to OX-6 antibody. Two populations, an OX-6+ and an OX-6-, interacted synergistically in a KLH-dependent in vitro proliferative response. The cells within the T cell-enriched fraction that were positive for the OX-6 marker functioned primarily as the APCs, while the OX-6- cell fraction contained cells that proliferated to antigen when OX-6+ cells from either the T cell fraction or the adherent fraction were present. The implications of these findings are discussed.

Animals↗

T-lymphocyte heterogeneity in the rat: separation of distinct rat T-lymphocyte populations which respond in syngeneic and allogeneic mixed lymphocyte reactions.

These experiments were designed to determine if separate subpopulations of T cells were involved in the syngeneic and allogeneic mixed lymphocyte reaction. Rat lymph node T cells were separated into W3/25+ and W3/25- subpopulations by panning with the monoclonal antibody W3/25 and tested for their ability to proliferate in both syngeneic (SMLR) and allogeneic (MLR) mixed lymphocyte responses, as well as to develop cytotoxicity against allogeneic, syngeneic, and trinitrophenol (TNP)-modified syngeneic targets. The W3/25+ T cells reacted strongly in the SMLR and the MLR whereas the W3/25- fraction proliferated only in response to allogeneic stimulation and with a kinetic pattern distinct from W3/25+. Furthermore, addition of W3/25 monoclonal antibody directly to the cultures was shown only to inhibit the proliferation of the W3/25+ T-cell fraction. The W3/25- subpopulation contained cytotoxic T cells (CTLs) against both allogeneic determinants and TNP-modified self. However the requirements for the activation of allospecific CTLs were distinct from those for CTLs for TNP-self in that W3/25- allospecific CTLs required no detectable help from W3/25+ T cells but generation of the CTL response against TNP-self required the presence of W3/25+ helper T cells (Th). These data suggest that in the rat, there exist subsets of T cells recognized by their cell surface phenotype that distinguish between self and nonself determinants and the requirements for activation are different for each of these populations.

Animals↗

Clinical pharmacists prescribing drug therapy in a geriatric setting: outcome of a trial.

Clinical pharmacists, under the supervision of a family practitioner physician, assumed responsibility for drug management of geriatric patients in a Los Angeles skilled nursing facility. In a quasi-experimental, pretest-post-test control group design, outcome criteria were measured. Compared with the control group which received traditional patient care, the prescribing clinical pharmacists' group had a significantly lower number of deaths (P = 0.05), a significantly higher number of patients being discharged to lower levels of care (P = 0.03), and a significantly lower average number of drugs per patient (P = 0.04). The lower number of patients hospitalized approached significance (P = 0.06) in the prescribing clinical pharmacists' group. The practice of having clinical pharmacists prescribe drug therapy and render general care, under the supervision of a physician, has the potential for saving the health care system approximately $70,000 per year per 100 skilled nursing facility beds.

Aged↗

The lateral periodontal cyst. A report of 37 cases.

The lateral periodontal cyst is a developmental cyst of odontogenic origin which is located along the lateral aspect of a tooth root. Thirty-seven previously unreported lateral periodontal cysts ( LPCs ) are presented. Clinical, roentgenographic and histologic features of the LPC are reviewed. Further, the importance of distinguishing the developmental LPC from laterally positioned inflammatory cysts of pulpal or periodontal disease origin and laterally occurring odontogenic keratocysts is stressed.

Adult↗