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Biomedical subjects

S R Mitchell

Publications and source records attributed to S R Mitchell.

36 records · Page 2Linked to original sources
PubMed1990

Increased risk of neisserial infections in systemic lupus erythematosus.

Survival in systemic lupus erythamatosus (SLE) continues to improve because of better ancillary care, earlier diagnosis, and earlier treatment. However, infection remains a leading cause of morbidity and mortality in this disease. Although corticosteroids and immunosuppresives increase the risk of opportunistic infection, the SLE patient is still most at risk from common bacterial pathogens. As the prototypic immune-complex disease, patients with active SLE have low circulating complement as well as a reticuloendothelial system (RES) saturated with immune complexes. It seems intuitive that SLE patients should be most at risk for organisms dependent for their removal on the RES or complement for opsonization or bacteriolysis. The current series presents four patients with SLE and disseminated neisseria infection and brings to 14 the number of patients in the literature with disseminated neisserial infection. They are typically young, female, with renal disease, and either congenital or acquired hypocomplementemia, and may present with all features of a lupus flare. Surprisingly, they are not all on corticosteroids or immunosuppressives and have some features that are unusual for non-SLE patients with these infections. There seems to be an over-representation of Nisseria meningitidis (despite potential reporting bias), and there ironically may be better tolerance with fewer fulminant complications in patients who have complement deficiencies. The best approach for the physician treating SLE is to immunize all SLE patients with available bacterial vaccines to N meningitidis and Streptococcus pneumonia, have a low threshold of suspicion for the diagnosis of disseminated neisserial or other encapsulated bacterial infection in the SLE patient who is sick, and to treat empirically with third generation cephalosporins after appropriate cultures.

Adolescent↗
PubMed1990

Modulation of suppression of mitogen-induced T cell-dependent B cell responses by natural killer cells.

We examined the ability of human natural killer (NK) cells to modualte pokeweed mitogen (PWM)-induced polyclonal antibody production. Highly purified NK cells inhibited plaque-forming cell (PFC) responses and this suppression could be substantially increased by preincubation of NK cells with the known enhancers of NK cell lytic activity, interferon (IFN)-alpha, IFN-gamma, and interleukin-2. Additionally, costimulation of NK cells with two anti-CD2 antibodies (9-1 and 9.6), which recognize different epitopes on the CD2 molecule, also augmented the inhibitory effect. When subpopulations of NK cells were assayed for suppressor cell activity, this activity was primarily mediated by NK cells bearing Leu-7 but not Leu-2 (CD8) antigens. Thus, alteration of NK cell lytic activity may have significant effects on the immunoregulatory functions of these cells, which may have important implications for the in vivo manipulation of cytotoxic responses.

Antibodies, Monoclonal↗
PubMed1990

Hand preference and performance on unimanual and bimanual tasks in capuchin monkeys (Cebus apella).

Patterns of manual preference and the extent to which preference provided a benefit in performance (movement time) were evaluated in 7 young adult capuchin monkeys (Cebus apella). Directions of preference were inconsistent within individual animals across home-cage activities, unimanual, and bimanual experimental tasks. Preferences were more strongly expressed in the experimental tasks than in the home cage. A left bias in the population for prehension, predicted by recent theories, was not evident in any setting. Movement time was moderately negatively correlated with degree of preference within experimental tasks. The benefit to performance conferred by lateral preference was not dependent on whether the right or left hand was preferred. Lateralization of prehension appears to be a flexible process in these monkeys, which can result in quickly realized benefits in some conditions.

Animals↗
PubMed1989

Natural killer cells can enhance the proliferative responses of B lymphocytes.

In addition to lytic activity against malignant and virally transformed target cells, recent evidence has suggested that natural killer (NK) cells can modulate immune activities such as the suppression of B cell responses through noncytotoxic means. Using human B cells and highly purified autologous NK cells, we have demonstrated that NK cells can substantially augment the proliferative responses of B cells stimulated with the surface immunoglobulin crosslinking agents anti-IgM or Staphylococcus aureus Cowan strain I (SAC). This "enhancer" activity of NK cells was quite potent and was observed at an NK:B cell ratio as low as 0.05. Peak blastogenic responses of B cells cocultured with NK cells in the presence of B cell activators were observed at 2-3 days, similar to the responses of B cells in the absence of NK cells. Using the inhibitor of DNA synthesis mitomycin C, we determined that B cells and not NK cells were proliferating in cocultures of these lymphocytes stimulated with SAC. Activated B cells neither prevented the lysis of the isotope-labeled NK-sensitive target cell line K562 nor formed conjugates with NK cells, suggesting that cell contact was not a prerequisite for the effect. These studies have further expanded the functional repertoire of NK cells to include enhancer as well as suppressor and lytic activities.

Antibodies, Anti-Idiotypic↗
PubMed1989

Suppression of B cell responses by natural killer cells is mediated through direct effects on T cells.

We examined the ability of human natural killer (NK) cells to modulate T cell-dependent mitogen-induced B cell responses. Highly purified NK cells inhibited the polyclonal antibody responses of autologous pokeweed mitogen (PWM)-stimulated unfractionated mononuclear cells in a reverse hemolytic plaque-forming cell (PFC) assay. Investigation of the possible mechanism(s) of the suppressor activity of NK cells revealed that lysis of mitogen-stimulated cells was unlikely. Chromium-51 release cytotoxicity assays of PWM-stimulated mononuclear cells did not demonstrate lysis by NK cells. Additionally, the monoclonal antibody 13.3, which abrogates NK cell cytolysis, did not reverse NK cell-dependent suppression of PFC formation. The putative lytic molecule elaborated by NK cells, NK cytotoxic factor, did not suppress B cell responses, further supporting a nonlytic inhibitory mechanism. That NK cell-derived lymphokines such as IFN-alpha, IFN-gamma, or IL-2 were uninvolved in the down-regulation of B cells was corroborated by the failure of antibodies to these mediators to reverse the suppression. NK cells did not suppress PFC formation when T cells were replaced by supernatants from PWM-stimulated T cells; additionally, NK cells had no effect on the generation of these necessary T cell factors. However, the coculture of T cells with NK cells resulted in the induction of suppressor activity within the T cell population suggesting that this was the mechanism of NK cell-mediated suppression of B cell responses.

Antibody Formation↗
PubMed1989

Disseminated neisserial infection in pregnancy: the empress may have a change of clothing.

A case of disseminated neisserial disease during pregnancy with good perinatal outcome is presented along with two examples of disseminated N. meningitidis from endocervical site. Upon close review, it is clear that the biological similarities of both N. gonorrhoeae and N. meningitidis may outweigh their differences. The two organisms may behave in clinically indistinguishable fashion and probably justify a more cautious approach to the clinical syndromes we have considered the inviolate domain of the gonococcus. The management of disseminated neisserial disease in pregnancy should include prompt empiric parenteral therapy while aggressive diagnostic confirmation of the organism is pursued. In addition, neonatal conjunctivitis caused by a Gram-negative diplococci should be treated parenterally until clinical response and identity of the organism is confirmed.

Adult↗
PubMed1987

Monitoring waste in an intravenous admixture program.

A method for collecting and analyzing data on i.v. admixture waste is described, and examples of the use of these data to reduce waste are presented. In 1984, a pharmacy department serving 580 hospital beds projected annual expense for waste of i.v. products to be nearly $30,000. Five major changes were implemented to reduce waste. Modification of expiration dating policies for cefoxitin and tobramycin substantially reduced waste. After an operating room pharmacy satellite was opened, decreased waste of dobutamine, dopamine, nitroglycerin, and nitroprusside was estimated to save $1000 per year. Changing times of batch processing of i.v. admixtures resulted in cost savings that were not significantly different for three-month periods before and after the change. The method of identifying small-volume injections (SVIs) to be manufactured was improved, and SVIs of expensive drugs were prepared every 12, instead of 24, hours; these changes resulted in reduction of one technician full-time equivalent but little change in the percentage or cost of SVIs wasted. Decentralized pharmacists were asked to order certain items on an as-needed basis; this did not affect costs or waste. From 1984 to 1985, total costs associated with waste decreased an estimated $11,000, or 27.5%. This department's attempt to change i.v. admixture procedures based on timely data has resulted in substantial reductions in the cost of waste.

Cost Control↗