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Biomedical subjects

R Gold

Publications and source records attributed to R Gold.

At least 127 records · Page 7Linked to original sources

Results from the 1995 National College Health Risk Behavior Survey.

Results from the 1995 National College Health Risk Behavior Survey, which monitored health risk behaviors among US college and university undergraduates, suggest that many students' behaviors increase their likelihood of adverse health outcomes. During the 30 days preceding the survey, 34% of the participants had consumed five or more alcoholic drinks on at least one occasion, and 27% had drunk alcohol and driven a car. Thirty-one percent had smoked cigarettes regularly during their lifetimes, 49% had ever used marijuana, 30% had used a condom during their last sexual intercourse, 21% were overweight, and 38% had participated in vigorous physical activity on 3 or more of the 7 days preceding the survey. These data were analyzed by gender, age group, race and ethnicity, and institution type. They can be used by those responsible for the health and education of college students to reduce risks associated with the leading causes of mortality and morbidity.

Adolescent↗

Side effects of high-dose intravenous immunoglobulins.

Intravenous immunoglobulins (IVIgs) are used increasingly as therapy for neuroimmunologic and other autoimmune diseases. With broader use, the number of reported side effects also is growing. Here we review the literature on adverse reactions reported after administration of i.v.Igs. Despite a few recent reports about a high frequency of complications of IVIgs, by and large they can be considered as safe. Mild and self-limited side effects may occur, but severe complications are rare and often associated with other risk factors for these complications. A careful screening for preexisting illnesses and monitoring of some laboratory parameters can minimize the risks of IVIg therapy.

Dose-Response Relationship, Drug↗

Secretion of nitrite by Schwann cells and its effect on T-cell activation in vitro.

To assess a potential immunoregulatory role of Schwann cells in the peripheral nervous system we examined whether they are able to secrete nitric oxide metabolites. Schwann cells treated with IFN-gamma and TNF-alpha upregulated iNOS-specific mRNA within 12 hr and released nitrite in a time- and dose-dependent manner, reaching a plateau of secretion after 3 days. Nitrite secretion was inhibited by NMMA, suggesting that Schwann cells are endowed with a cytokine-inducible NO synthase. TGF-beta and IL-1 failed to modulate nitrite release. When assessing their role as APC, we note that Schwann cells activated CD4+ antigen-specific T-cell lines, but in contrast to professional thymic APC this ability declined markedly after Day 1. Theoretically diminished T-cell proliferation and finally death might be achieved by secretion of nitric oxide metabolites by Schwann cells. Inhibition of NO production by NMMA did not restore T-cell proliferation after Day 2 or prevent apoptosis of T-cells. However, in a coculture model Schwann cells exerted a strong suppressive effect on T-cell activation by thymic APC, which was almost completely abrogated by addition of NMMA. We suggest that Schwann cells may exert potent immunoregulatory functions beyond their role as APC. They may terminate immunoinflammatory reactions in the peripheral nervous system by releasing NO.

Animals↗

In situ demonstration of T cell activation and elimination in the peripheral nervous system during experimental autoimmune neuritis in the Lewis rat.

The mechanisms of activation and termination of autoimmune responses are poorly understood. We have studied the sites and mode of activation and elimination of T cells in actively induced experimental autoimmune neuritis (EAN) and in adoptively transferred by P2-specific T cells (AT-EAN). The bromodeoxyuridine (BrdU) technique was employed to detect in situ proliferating cells in spleen and sciatic nerve. We assessed the nuclear morphology of infiltrating T cells using morphological criteria of apoptotic cell death. Apoptosis of lymphoid cells was also investigated using molecular labeling techniques. In AT-EAN, the number of BrdU positive cells in splenic germinal centers peaked at day 2 after cell transfer [554 +/- 267] (mean +/- SEM per mm2, controls 98 +/- 35), 1 day before disease onset, and declined thereafter. BrdU incorporation in spleens from animals with active EAN peaked at day 11, around disease onset, but reached lower total values (165 +/- 29 per mm2). In neither model did we observe a significant proportion of BrdU-positive T cells in the peripheral nervous system. However, T cells exhibiting morphological signs of apoptosis were detected in the sciatic nerve immediately after disease onset. The number of these cells was highest on day 7 in AT-EAN (6.6 +/- 3.2 per mm2) and on day 17 in active EAN (11.2 +/- 2.2 per mm2) corresponding to the maximum of T cell infiltration in both animal models. T cell activation occurs systematically and not just in the autoimmune lesion. Infiltrating T cells are eliminated by apoptosis in situ, terminating the inflammatory process. Further insight into these mechanisms may help to develop new therapeutic strategies for autoimmune disorders of the peripheral nervous system.

Animals↗

Lipocortin-1 (annexin-1) suppresses activation of autoimmune T cell lines in the Lewis rat.

Increased levels of lipocortins occur in the nervous system in multiple sclerosis, in experimental autoimmune encephalomyelitis and experimental neuritis at the height of disease and decrease thereafter, suggesting their potential involvement in recovery from disease. We therefore investigated whether lipocortins may suppress activation of autoimmune T cells. Antigen-specific and growth factor-mediated proliferation of T cell lines reactive with myelin basic protein (MBP) was measured in the presence of recombinant lipocortin-1, -2, and -5, and natural bovine lipocortin-1 using various concentrations and incubation periods. We also employed an N-terminal lipocortin-1 peptide spanning aa 1-26, a proteolytic fragment of lipocortin-1 where the respective N-terminal region was clipped off, tested blocking with a neutralizing antibody, and investigated the effect of alkaline phosphatase treatment. Both human recombinant and bovine lipocortin-1 had a marked suppressive effect on T cell activation by MBP and the respective immunogenic peptide. When added at 3 micrograms/ml we observed up to 90% inhibition of T cell proliferation between day 2 and 3, but not at earlier time points of activation. The inhibitory effect of human lipocortin-1 was blocked after addition of a neutralizing antibody directed against lipocortin-1. Lipocortin-2 and -5, and the N-terminal peptide of lipocortin-1 were ineffective, whereas the fragment spanning residues 27-345 of lipocortin-1 retained full activity. Treatment of bovine lipocortin-1 with alkaline phosphatase did not alter immunosuppressive properties.

Amino Acid Sequence↗

Healthcare reform: a survey of college health services.

As federal legislators moved closer to enacting significant healthcare reform during fall 1994, it was apparent to the college health community that campus health programs could be significantly affected. Uncertainty over the impending legislation led college health directors to consider two important questions: What is the federal government going to do? and What could college health directors do to position their organizations more effectively to respond to pending reform? The former question was debated on a daily basis throughout the United States with no resolution in sight. The latter question was the ultimate focus of this survey research involving 56 of 79 schools (71% response rate from institutions in 38 states). Half of the schools had enrollments between 15,001-25,000 students; 86% used prepaid fees as their primary financing mechanism. Survey results identified college health directors' preferences for 27 different organizational strategies in response to possible healthcare reform initiatives.

Health Care Reform↗

Antigen presentation by astrocytes primes rat T lymphocytes for apoptotic cell death. A model for T-cell apoptosis in vivo.

In this study we have characterized apoptotic cell death of autoreactive T cells resulting from their interaction with astrocytes and the modulatory effect of steroid hormones. Time kinetics of T-cell activation by interferon (IFN)-gamma-treated astrocytes from neonatal Lewis rats and by professional antigen presenting cells (APCs) from bulk suspensions of thymus or spleen were performed. [3H]Thymidine incorporation of neuritogenic P2- and encephalitogenic myelin basic protein (MBP)-specific T-cell lines declined after 48 h in culture with astrocytes. A similar suppressive effect was observed when T cells were cocultured with thymic APCs and astrocytes. This effect disappeared when astrocytes were separated by a transwell system. After 72 h of culture with astrocytes a mean of 17.5 +/- 12.4% T cells exhibited morphological signs of apoptosis. Apoptosis was identified by light microscopy, and confirmed by electron microscopy, by in situ tailing reaction and by agarose gel electrophoresis. Glucocorticosteroids and oestrogen specifically enhanced T-cell apoptosis within 8 h (69.8 +/- 23.1% and 69 +/- 17.1%, respectively) when added after 72 h to the astrocyte system, but not at earlier time points of T-cell activation or when thymic APCs were used. Glucocorticoid-mediated T-cell apoptosis was inhibited by the steroid-receptor antagonist RU 486. Pregnenolone, lipocortin-1, indomethacin and transforming growth factor-beta did not induce apoptosis in this system. The steroid effect was not associated with CD28, IL-2 receptor, or transferrin-receptor expression, which were equally upregulated on T cells activated by astrocytes or thymic APC as shown by fluorescence activated cell sorting (FACS) analysis. We conclude that astrocytes as CNS-specific APC may render T cells susceptible for induction of apoptotic cell death. Some steroid hormones can markedly enhance this process in vitro and may augment an additional effect of a systemic corticosteroid response in vivo during recovery from autoimmune encephalomyelitis.

Analysis of Variance↗

H2O2 and nitric oxide-mediated oxidative stress induce apoptosis in rat skeletal muscle myoblasts.

In many degenerative and metabolic muscle diseases cells die without a marked inflammatory response. A potential mechanism how this could be accomplished is apoptotic cell death. Since there are no data available about apoptosis in cells of myogenic origin, we examined rat skeletal myoblasts for their potential to undergo apoptosis when exposed to reactive oxygen intermediates and nitric oxide. We observed morphologic changes typical for apoptotic cell death, and DNA fragmentation was confirmed by gel electrophoresis and molecular labeling assays. With these methods we could show that both reactive oxygen intermediates and nitric oxide can induce apoptosis in myoblasts in a dose-dependent manner. These results are discussed with regard to possible implications on the pathophysiology of various muscle diseases.

Animals↗

MHC class I-mediated cytotoxicity does not induce apoptosis in muscle fibers nor in inflammatory T cells: studies in patients with polymyositis, dermatomyositis, and inclusion body myositis.

Apoptosis plays a crucial role in natural recovery from T cell-mediated autoimmune disorders of the nervous system. Whether apoptosis also occurs in human inflammatory myopathies is unclear. In this study we examined muscle biopsy specimens from untreated patients with polymyositis (n = 12), dermatomyositis (n = 12), and inclusion body myositis (n = 12) for the presence of apoptosis using morphological criteria and DNA fragmentation by in situ tailing. In all these disorders, only rare T cells exhibited signs of apoptosis by nuclear morphology and in situ labeling techniques. Although Fas-expression was upregulated in a few inflammatory cells, increased apoptosis of the surrounding T cells was not observed. Further, nuclei of degenerating muscle fibers did not show morphological signs of apoptosis and were not labeled by the tailing reaction. We conclude that in the inflammatory myopathies, T cell inflammation is not cleared by apoptosis and affected muscle fibers do not die by apoptosis. The observations are consistent with the non-self-limited nature of these disorders and suggest that, in contrast to the nervous system, the local microenvironment in muscle does not deliver pro-apoptotic stimuli.

Adult↗

Cytomegalovirus infections in Toronto child-care centers: a prospective study of viral excretion in children and seroconversion among day-care providers.

OBJECTIVES: To prospectively determine the rate of cytomegalovirus shedding in children and the rate of seroconversion to cytomegalovirus in providers at 38 infant-toddler day care centers in Toronto, Canada. METHODS: Urine was collected for shell vial assay in 471 children between the ages of 3 and 42 months. Providers (n = 206) were tested for the presence of cytomegalovirus antibody by latex agglutination. Of the 68 providers who were seronegative, 56 were retested approximately 1 year later. RESULTS: Viruria was documented in 79 (17%) children and antibody in 67% of providers. Seropositivity was significantly related to country of birth outside Canada, presence of children at home < 5 years of age and increased household size. Seroconversion was documented in 12.5% (n = 7). Of these providers 71% worked at centers where workers never wore gloves for diaper changing vs. 33% of those who did not seroconvert (P = 0.06), and all were younger than 30 years vs. 59% of those who did not seroconvert (P = 0.04). In centers with viruria the association of seroconversion with lack of glove use was enhanced (P = 0.04). Seroconversion was marginally more likely in providers working with infants only than with infants and toddlers or with toddlers alone. Logistic regression confirmed that seroprevalence was more likely in providers who were born outside Canada, had children younger than age 5 years in the household and with an increased number of people in the household. Seroconversion was more likely if the provider worked at centers not using gloves for diaper changes, worked with infants only rather than with toddlers and infants and was < 30 years old, with each factor contributing independently to the model. CONCLUSIONS: Cytomegalovirus infection is common in children and providers in Toronto day-care centers.

Adolescent↗

Phosphorus magnetic resonance spectroscopy in the evaluation of mitochondrial myopathies: results of a 6-month therapy study with coenzyme Q.

31P magnetic resonance spectroscopy (MRS) was used to study an open therapeutic trial of coenzyme Q10 (CoQ) in mitochondrial encephalomyopathies. Eight patients were treated with 150 mg CoQ per day for 6 months. 31P MRS spectra of calf muscle were recorded at rest, during exercise and in the immediate postexercise recovery period. Although there was an improvement of the mean ratio of phosphocreatine (PCr) to inorganic phosphate during the post-exercise recovery period after 3 months of treatment, this finding was mainly due to a single therapy responder and did not reflect a beneficial effect on the whole group. Improved repletion of PCr persisted after 6 months of therapy. Our study identified a single responder to this therapy, whose response could not be predicted on the basis of clinical, biochemical or molecular data. These findings suggest that therapeutic trials of CoQ should be performed under close metabolic monitoring in order both to identify responders for subsequent long-term treatment and to evaluate possible mechanisms of this supportive therapy.

Administration, Oral↗

[Acute organic psychosis after malaria tropica].

Neuropsychiatric complications in the course of plasmodium falciparum infection are usually summarized as cerebral malaria. Heterogeneous clinical symptoms, different courses and inconstant parasitemia, however, suggest different pathogenic mechanisms. We report a case of an acute symptomatic psychosis occurring two weeks after successful therapy of a primary manifestation of plasmodium falciparum infection. The diagnosis of meningoencephalitis was based on lymphocytic pleocytosis of cerebrospinal fluid and hyperintense lesions in cranial magnetic resonance imaging. Due to the lack of plasmodium falciparum parasitemia and of serological evidence of viral infection a final diagnosis was not possible. Considering the pertinent literature, an immune-mediated complication of plasmodium falciparum infection (acute disseminated encephalomyelitis, ADEM) appears to be more probable than a direct viral or plasmodium CNS infection. We propose to reverse the term cerebral malaria for the cases with direct pathogenic influence of plasmodium falciparum, and to distinguish it from cases with possible immune-mediated pathogenesis.

Adult↗

Response to measles, mumps and rubella vaccine in paediatric bone marrow transplant recipients.

Bone marrow transplant (BMT) recipients are routinely reimmmunized with the childhood vaccine series after transplantation excluding the live attenuated vaccines. In this study, the clinical and serologic responses to measles, mumps and rubella (MMR) vaccine in children after BMT was assessed. Twenty-two BMT recipients were vaccinated with MMR II (MSD). All were at least 2 years post-BMT and without GVHD. Their underlying conditions were leukemia (11), aplastic or Fanconi's anemia (7), thalassemia (3) and metabolic disease (1). All were allogeneic transplants with matched related donors. The mean age at transplantation was 6.9 years. There were no reported adverse effects of the vaccination. Antibody status for MMR was determined using commercial assays (IFA and ELISA) on paired specimens. The mean interval between transplantation and vaccination was 48 months. Pre-vaccination, no BMT recipient was sero-positive for all three, but 23% were positive for measles, 31% for mumps and 14% for rubella. Post-vaccination, 68% of BMT recipients were sero-positive for all three, with 77% for measles, 87% for mumps and 91% for rubella. Therefore, MMR vaccination at 2 years or later after BMT in paediatric recipients without GVHD was safe and significantly increased the proportion sero-positive for MMR.

Anemia, Aplastic↗

Autoimmunity in the peripheral nervous system.

The PNS is an immunocompetent organ. The participating cellular and humoral elements in the local immune circuitry have been identified. The model disorder EAN is extensively being used to examine the induction, amplification and effector phase of autoimmune responses to peripheral nerve antigens (Figure 9). Potential autoantigens contained in the myelin sheath and on the axolemma have been characterized. Recent years have seen a rapid growth of information concerning the pathogenesis of the Guillain-Barré syndrome, which has turned out to be a heterogeneous disorder, both in clinical characteristics, course and prognosis, and in the underlying pathology. It can be anticipated that using the better understanding of principal mechanisms of autoimmunity in the PNS will aid in the development of more specific and efficacious treatments.

Antibody Formation↗