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Biomedical subjects

N K Hall

Publications and source records attributed to N K Hall.

At least 19 recordsLinked to original sources

Hospitalization and mortality rates for nursing home-acquired pneumonia.

BACKGROUND: The effect of hospitalization on nursing home patients with pneumonia is not known. We hoped to learn more about the effect of hospitalization on outcome by comparing patients with pneumonia from 2 nursing homes. METHODS: Using a retrospective chart review, we compared a total of 129 patients with pneumonia from 2 community nursing homes in upstate New York over a 2-year study period. The main intervention measures were treatment in the hospital or treatment in the nursing home. The main outcome measures were resolution or mortality at 6 weeks. RESULTS: Nursing home B had a hospital admission rate for pneumonia (38.8%) that was double that of nursing home A (19.4%). The patient populations were judged to be similar, and the overall mortality outcome for both (weighted average = 24.8%) was essentially identical. CONCLUSIONS: Doubling the hospital admission rate in 1 of 2 similar groups of nursing home patients with pneumonia was not associated with an improved mortality outcome at 6 weeks.

Activities of Daily Living↗

The University of Oklahoma College of Medicine Rural Health Educational Program.

Training of physicians to meet the health care needs of rural residents has long been a priority of the University of Oklahoma College of Medicine. With establishment of the much imitated Rural Preceptorship Program in 1948, the college launched an ongoing series of efforts all directed toward increasing the number of graduates choosing to practice in rural locations. In addition to the required senior Preceptorship Program, a series of educational programs is available in each year of medical school, actually beginning prior to freshman enrollment. As a result, the college now offers a comprehensive series of educational experiences involving not only four years of medical school, but graduate training in the primary care specialties as well. This report summarizes the various activities of the college that now make up the rural emphasis program, all of which are designed to help ensure an adequate supply of physicians for rural Oklahoma.

Curriculum↗

Changes in demographics at the University of Oklahoma College of Medicine.

Efforts in recruitment and retention of students by the University of Oklahoma College of Medicine have resulted in an increased size of applicant pool to the college over the past three years. Curriculum changes and programmatic innovations have provided new opportunities for students and incentives to remain in the State of Oklahoma. Continuing and expanding recruitment efforts can be enhanced by the active participation and support of the physicians of the state.

Education, Medical↗

Characterization of a suppressor factor that regulates phagocytosis by macrophages in murine cryptococcosis.

A T-suppressor factor which inhibits the phagocytic activity of a macrophage subset has been further characterized. This suppressor factor was first described for a murine model of cryptococcosis but was later found to be common to models of immunologic unresponsiveness. The suppressor factor was produced when suppressor cells were cultured in the presence of specific cryptococcal antigen. It could not be extracted from spleen cells and was not induced by antigen in cultures of lymph node cells. The suppressor factor was filtered through Amicon filters of 100-kilodalton (kDa) exclusion limit but was retained by filters excluding molecules of less than 50 kDa. By Sephadex G-100 chromatography, the factor eluted just ahead of bovine serum albumin (68 kDa). The activity of the suppressor factor could not be inhibited by anticryptococcal antibody, but it was inhibited by anti-I-J alloantiserum of the same genotype as the lymphocyte which produced the factor. Absorption with an encapsulated strain of Cryptococcus neoformans removed the suppressor factor from culture supernatants, while absorption with a nonencapsulated mutant or an unrelated yeast cell had not effect. On the basis of these observations, it was apparent that the suppressor factor was idiotypic in nature and that I-J and/or the I-J-interactive molecule played a role in the function of the suppressor factor. The requirement for antigenic stimulation for the production of suppressor factor in vitro distinguished it from the T-suppressor factor 3 described by others which regulates delayed-type hypersensitivity in cryptococcosis.

Absorption↗

Induction of a macrophage-suppressive lymphokine by soluble cryptococcal antigens and its association with models of immunologic tolerance.

Soluble extracts of Cryptococcus neoformans were examined for their ability to induce a macrophage-regulatory T-suppressor cell known to appear in the spleens of mice infected with cryptococci. Suppressor cells were induced by injection of extracts of encapsulated or thinly encapsulated strains of cryptococci. Dose-response analysis showed that as little as 25 micrograms of soluble capsular polysaccharide antigen could induce significant suppressor cell activity, with maximum suppression occurring at a dose of 100 micrograms. The suppressor cells appeared within 1 week of injection of antigen and persisted for at least 2 months. Suppressor cells were induced in animals given tolerogenic doses of levan, human gamma globulin, and soluble capsular polysaccharide antigen. When these same antigens were administered in immunogenic form, no suppressor cell activity was detected. Therefore, the suppressive mechanism was common to models of immunologic tolerance and was not unique to cryptococcal disease or cryptococcal capsular polysaccharide antigen. The phagocytosis-inhibiting lymphokine produced by the suppressor cell population completely inhibited the phagocytic activity of only a portion of peritoneal exudate cells. Other macrophages in the population were not totally inhibited but exhibited a reduction in the number of yeast cells engulfed.

Animals↗

Monoclonal antibodies cross-reactive with group A streptococci and normal and psoriatic human skin.

Infection with group A streptococci has been implicated as a factor capable of exacerbating psoriasis. In order to explore the possibility of cross-reactivity between streptococcal antigens and human skin in this phenomenon, skin from psoriatic patients and control subjects was reacted with 3 monoclonal antibodies against group A streptococci and antibody binding was estimated by the indirect immunofluorescence technique. Monoclonal antibody 54.2.8 stained the nuclei and cytoplasm of cells within the epidermis and epidermal appendages, as well as cells scattered throughout the dermis. In contrast, monoclonal antibodies 49.8.2 and 36.2.2 labeled the cytoplasm of epidermal cells and epidermal appendages but did not react with nuclei. No difference in the staining patterns of control skin and uninvolved skin from patients with psoriasis was observed. However, skin from psoriatic lesions contained large amounts of cross-reactive skin component(s). Sera from patients with guttate psoriasis did not react differently with normal or psoriatic skin when compared with normal sera. Western immunoblots of skin extracts demonstrated that monoclonal antibody 54.2.8 reacted with a family of proteins in the molecular weight range of 60-70K. The results indicate that component(s) in human skin share cross-reactive epitopes with group A streptococci. Immunologic cross-reactions between group A streptococci and human skin may play an important role in the exacerbation of certain skin disorders following streptococcal infections.

Adolescent↗

A study of anti-group A streptococcal monoclonal antibodies cross-reactive with myosin.

Anti-group A streptococcal monoclonal antibodies were obtained from BALB c/BYJ mice immunized with purified membranes from M type 5 Streptococcus pyogenes. Two of the anti-streptococcal monoclonal antibodies were previously shown to cross-react with muscle myosin. In this study the monoclonal antibodies were reacted with tissue sections of normal human heart and skeletal muscle. Antibody binding was estimated by indirect immunofluorescence and immunoperoxidase techniques. Both of the monoclonal antibodies (36.2.2 and 54.2.8) investigated in this report reacted with heart and/or skeletal muscle sections. When evaluated by immunofluorescence, monoclonal antibody 54.2.8 demarcated the periphery of cardiac striated muscle cells and reacted to a lesser degree with subsarcolemmal components. Monoclonal antibody 36.2.2 failed to react with heart sections, but both of the monoclonal antibodies reacted strongly with skeletal muscle sections. Results similar to those observed with indirect immunofluorescence were obtained with the immunoperoxidase technique. By Western immunoblotting and competitive inhibition assays, monoclonal antibodies 36.2.2 and 54.2.8 both were found to react with the heavy chain of skeletal muscle myosin. However, only 54.2.8 reacted with the heavy chain of cardiac myosin. The specificity of the monoclonal antibodies for subfragments of skeletal muscle myosin indicated that monoclonal antibody 36.2.2 was specific for light meromyosin fragments, whereas 54.2.8 reacted with both heavy and light meromyosin. The data demonstrated that two monoclonal antibodies against streptococci were specific for skeletal muscle and/or cardiac myosin and for subfragments of the myosin molecule. The reactions of the monoclonal antibodies with human tissue sections were consistent with the immunochemical reactions of the monoclonal antibodies with both denatured and native myosin.

Animals↗

Non-specific immunosuppression by Cryptococcus neoformans infection.

Cryptococcus neoformans-infected animals were found to be immunosuppressed when tested by a variety of assays for immune competence. Primary humoral immune responses and delayed-type hypersensitivity reactions to sheep erythrocytes were suppressed in animals which had been infected for two weeks. Lymphocyte proliferation (LP) assays to sRBC stroma were also significantly diminished at two weeks of infection. Spleen cells of infected mice suppressed the LP response of sRBC immunized, normal mice in vitro. At least a part of the suppression could be attributed to a nylon wool non-adherent cell. Suppressor cells continued to be present in spleen cell suspensions following treatment with anti-T cell serum or anti-immunoglobulin and complement. When infected spleen cells were separated by adherence to plastic, both the adherent and non-adherent fractions exhibited suppressive activity. Incubation of infected spleen cells in tissue culture for 48 hr resulted in the elaboration of soluble immunosuppressive factors into the tissue culture medium. These data indicated that immune suppression in cryptococcosis can occur as a result of infection with Cryptococcus neoformans, and that at least one mechanism involved is the induction of adherent and non-adherent suppressor cells in the spleens of infected mice.

Animals↗

Functional testing and chemical composition of cryptococcal extracts.

Three antigens were compared for their ability to detect immune responses in C57Bl/6 mice sensitized to Cryptococcus neoformans. Elicitation of responses in vitro was greatest with a urea extract antigen, followed in efficiency by an alkali extract and a soluble capsular polysaccharide preparation. The reactivity paralleled the protein content of the preparation.

Animals↗

Modification of macrophage phagocytosis in murine cryptococcosis.

Normal C57BL/6J peritoneal cells exhibited a decreased phagocytosis when cultured with a cell wall antigen of Cryptococcus sp. and lymphocytes from mice infected with C. neoformans. Direct cell-to-cell interaction was not required in that supernatant fluids from cultures of lymphocytes from infected animals could be incubated with normal macrophage monolayers to give comparable suppression. The induction of the suppressor factor required specific cryptococcal antigen; however, suppression at the macrophage level was nonspecific in that the phagocytosis of C. neoformans and Saccharomyces cerevisiae were both decreased. Suppression appeared with lymphocyte supernatants taken from mice infected for 14 days and thereafter. The factor was heat stable, trypsin sensitive, and allospecific.

Animals↗

Suppression of responses to cryptococcal antigen in murine cryptococcosis.

Subpopulations of spleen cells responsible for responsiveness and unresponsiveness to cryptococcal antigen in vitro were identified. Lymphocytes which responded in lymphocyte transformation (LT) assays were nylon wool nonadherent and theta antigen positive. These lymphocytes required the presence of an accessory cell which could be supplied by normal peritoneal exudate cells. Spleen cells taken from mice which had been infected for 3 to 15 days were tested to determine their ability to respond to cryptococcal antigen in LT assays. A minimal response was detected at the ninth day of infection. The response of infected spleen cells was attributed to a nonadherent lymphocyte. Nonadherent spleen cells of infected animals had enhanced responses after removal of adherent cells and addition of normal peritoneal exudate cells. Suppressor cells were detected in the spleens of infected mice by the 12th day of infection and thereafter. A nonadherent suppressor cell was identified, but indirect evidence suggested that an adherent cell could also be present in infected spleens.

Animals↗

Immunosuppression by avirulent, pseudohyphal forms of Cryptococcus neoformans.

Our previous reports have shown that animals inoculated for 8 weeks with 1 X 10(5) pseudohyphal, avirulent C. neoformans exhibited prolonged survival upon challenge with virulent cryptococci. This paper described a transient phase of immunosuppression which occurs during the initial weeks of the immunization protocol. Animals injected with pseudohyphal organisms had depressed responses to T and B-cell mitogens. In addition, they had lowered responses to immunization with sheep erythrocytes. Both humoral and cell mediated responses were affected.

Animals↗

Immunization of mice with an avirulent pseudohyphal form of Cryptococcus neoformans.

Mice were immunized with a viable, avirulent strain of Cryptococcus neoformans. Lymphocyte blastogenic assays showed a 10-fold increase in reactivity of sensitized spleen cells, and histopathologic examination revealed marked splenic hyperplasia. Thirty-two days after intravenous inoculation with a virulent strain of C. neoformans, none of the control animals survived whereas 60 percent of the immunized mice were alive with no clinical evidence of disease. This animal model shows that protective immunity can be established, and once developed, provide a better model for the study of important aspects of immunity in fungal disease.

Animals↗

Kinetics of lymphocyte transformation in mice immunized with viable avirulent forms of Cryptococcus neoformans.

A murine model was developed to study the cell-mediated immune response of mice immunized with one of two live, avirulent forms of Cryptococcus neoformans: a nonencapsulated mutant and a thinly encapsulated pseudohyphal variant. A lymphocyte transformation assay was used to evaluate the cellular response of control and sensitized spleen cells after in vitro incubation with three merthiolate-killed whole-cell antigens of C. neoformans. An antigen-to-spleen cell ratio of 10:1 and 5 days of incubation of antigen-spleen cell mixtures were established as optimal conditions for maximum lymphocyte transformation. Maximum responses occurred from 2 to 3 weeks after the last of eight weekly intraperitoneal inoculations of C. neoformans. This assay provided an accurate, reproducible method of studying cell-mediated immunity to C. neoformans, and applications to the study of cryptococcal pathogenesis are proposed.

Animals↗