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Biomedical subjects

D Gold

Publications and source records attributed to D Gold.

At least 19 recordsLinked to original sources

Adhesion of Trichomonas vaginalis to plastic surfaces: requirement for energy and serum constituents.

The ability of Trichomonas vaginalis to adhere to plastic surfaces in the presence of various agents and under different growth conditions was examined in wells of microtitre plates containing unsupplemented TYI medium or the same, with various supplements. Following incubation, the wells were thoroughly washed and adhesion was determined by microscopic counting of the adherent organisms. There was no detectable adhesion in the absence of both serum and carbohydrate. Optimal adhesion (about 10-20% of the total number of parasites) was obtained throughout the growth curve in culture media supplemented with either serum or serum Cohn fractions IV-I (rich in alpha-globulin) or IV-4 (rich in alpha + beta-globulin) and 25 mM glucose, maltose or fructose, but not in plates pre-coated with the Cohn fractions. Cohn fraction II + III (rich in beta + gamma-globulin) moderately enhanced adhesion while Cohn fractions II (rich in gamma-globulin) or V (albumin), fibronectin, Tamm-Horsfall glycoproteins and polylysine were without effect. Non-metabolizable sugars (methyl derivatives of glucose, mannose or fucose) did not support growth, but, surprisingly, enhanced adhesion. At 4 degrees C, the trichomonads were not able to adhere and pre-adherent organisms detached from the plastic surface. Optimal adhesion was obtained at a pH range of 6.5-7.5 but was already detectable at pH 5.5. Cytochalasin E markedly suppressed adhesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

On the interaction between macrophages and developmental stages of Schistosoma mansoni: effect of muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) treatment on mice survival and the generation of schistosomulicidal macrophages.

Schistosomiasis is a chronic disease afflicting hundreds of millions of people throughout the world against which there is as yet no effective vaccine. In the present study we tested the effect of the immunomodulator muramyl tripeptide phosphatidyl ethanolamine (MTP-PE) on the survival of Schistosoma mansoni-infected mice and on the induction in them of schistosomulicidal macrophages. Mice exposed to 80 cercariae each and then treated with MTP-PE showed prolonged survival following either single or repeat infection. The treatment with MTP-PE, when initiated 70 days post the schistosome infection, diminished significantly the mortality of infected mice over an observed period of 110 days. In terms of treatment efficacy there was no evident difference between the intravenous and intraperitoneal mode of administration of the drug. MTP-PE treatment significantly reduced granuloma size and markedly diminished liver damaged as judged by the lower levels of alkaline phosphatase in the serum. Such treatment exerted no significant effect on the spleen or liver weight in infected mice nor on the worm burden resulting from either a single or double infection. In infected and non-treated mice, schistosomulicidal macrophages appeared after 8-10 weeks of infection. In infected mice treated with MTP-PE there was an accelerated appearance of such macrophages and these exhibited a greater cidal effect on the schistosomula. These immunostimulatory and life-prolonging effects of MTP-PE on S. mansoni-infected mice might indicate an effect of this reagent on cells involved in the granulomatous process.

Acetylmuramyl-Alanyl-Isoglutamine

On the possible schistosomulicidal effect of macrophage-derived lysozyme.

Lysozyme secretion from macrophages of Schistosoma mansoni-infected mice was time dependent, rising significantly from the 8th week post-infection, the macrophages thereafter exhibiting very high levels (greater than 90%) of schistosomulicidal activity. Despite the ability of lysozyme to kill schistosomula in vitro, the concentrations required for such killing were several hundred-fold to several thousand-fold higher than those detected in the supernatants from infected-mice macrophages cultured with or without schistosomula. An in vitro lysozyme inhibitor, N,N,N-triacetyl chitobiose, did not abrogate the cytotoxic ability of macrophages from schistosome-infected mice, but an inhibitor of arginine-dependent cytotoxicity, NG-monomethyl arginine, markedly inhibited schistosomulicidal activity. Evidently, concentrations of ambient lysozyme from macrophage cultures are too low to affect schistosomula in culture, while the main schistosomulicidal pathway in vitro seems to be arginine dependent.

Animals

Chronic fatigue in adolescents.

Nine female and 6 male adolescents (mean age 14.5 +/- 1.7 [SD] years) were evaluated for chronic fatigue associated with at least three additional symptoms present for 18.4 +/- 8.4 months. Eleven subjects experienced the onset of symptoms with an acute illness (seven Monospot-positive). Medical history, physical examination, and laboratory testing yielded little helpful information. Serologic testing for Coxsackie B viruses 1 through 6, cytomegalovirus, Epstein-Barr virus, human herpesvirus 6, and Toxoplasma gondii in subjects and healthy controls provided little evidence for an infectious cause of persistent fatigue. Children's Depression Inventory scores and psychiatric interviews with the Schedule for Affective Disorders and Schizophrenia-Children's Version (K-SADS) identified five subjects with major depression. On the K-SADS, the 10 fatigued subjects without major depression endorsed many secondary symptoms of depression but were less likely than depressed psychiatric clinic patients to endorse primary symptoms such as depressed mood, guilt, and suicidality. At telephone follow-up 13 to 32 months after intake, 4 subjects were completely well, 4 markedly improved, and 7 unimproved or worse. Further research is necessary to determine whether chronic fatigue in adolescents is prodromal depression, a discrete psychosomatic condition, or an infectious or immunologic disorder that mimics depression.

Adolescent

Chronic fatigue. A prospective clinical and virologic study.

To evaluate the clinical and virologic course of patients with chronic fatigue who had elevated Epstein-Barr virus (EBV) titers, we prospectively followed up 26 patients with serial cultures for EBV in blood and saliva and serial EBV serologic and clinical and psychiatric evaluations, and we compared these results with those for healthy controls. The frequency of isolating EBV in blood or demonstrating EBV infection by in situ hybridization in blood lymphocytes or in saliva was similar in patients and controls. The prevalence and titers of antibody to human herpesvirus type 6 were also similar in the two populations. Patients with chronic fatigue did demonstrate higher in vitro natural killer activity and lower in vitro interleukin 2 production than controls, and patients had a high frequency of DSM-III depressive illness. Over 50% of patients with chronic fatigue improved over the course of follow-up. Improvement was not associated with any discernible change in titers of EBV proteins. No evidence of ongoing EBV infection with either transforming or nontransforming strains was demonstrated in this population of patients with chronic fatigue. Clinically, most patients gradually improve over time.

Adult

The effect of immunosuppressive and immunostimulatory treatment on experimental amoebiasis.

Immunosuppressive treatments consisting of ionizing irradiation or drugs were employed in inbred and outbred mice and in golden hamsters. Following treatment, mice were challenged intracaecally or intrahepatically with virulent, axenically-grown Entamoeba histolytica. Hamsters were challenged by intraperitoneal injection of the amoebae. Many of the experimental animals died of the combined effects of treatment and challenge. Mice remained essentially refractory to infection with E. histolytica regardless of the immunosuppressive means employed. Liver infection rates in treated and control hamsters were largely similar to one another, i.e. immunosuppressive treatment had no effect on resistance to infection. Our inability to alter the susceptibility of mice and hamsters to amoebic infection by suppressing components of the immune system does not enable us to draw any clearcut conclusions as to the effect of immunosuppression on human amoebiasis. Of the various immunostimulatory materials employed in hamsters, including polysaccharides, BCG and muramyl peptides, only glucan displayed protective capacity against infection with E. histolytica, making it an effective protective agent in an extracellular parasitic infection in addition to its published effectiveness in intracellular protozoal infections. Peritoneal cells extracted from hamsters injected intraperitoneally with E. histolytica seemed capable of reducing the infectivity of virulent amoebae after coincubation in vitro, as shown by reduced infection rates in challenged hamsters. Apparently polymorphonuclear cells, which constituted the vast majority of the extracted cells 24 hours after the stimulatory injection, can, under certain conditions, diminish the infectivity of E. histolytica.

Animals

Predictors of asthma and persistent wheeze in a national sample of children in the United States. Association with social class, perinatal events, and race.

This study analyzes data from the Second National Health and Nutritional Examination Survey to determine whether black children are more likely to have asthma or wheeze, even after adjusting for environmental and socioeconomic exposures. For children 6 months to 11 yr of age, the unadjusted prevalence for asthma was 3.0% among white children and 7.2% among blacks; prevalence of frequent wheeze was 6.2% among whites and 9.3% among blacks. In a logistic regression model including race, age, and sex, the relative odds (RO) of asthma for black children as compared to white children were 2.5 (95% confidence interval [Cl], 1.9 to 3.4). Other predictors of asthma in a stepwise logistic regression included age, sex (boys versus girls, RO = 1.4), younger maternal age (2 standard deviation [SD] drop in age, RO = 1.4), residence in the central city (RO = 1.6), and family income (RO for the lowest versus highest tertile, RO = 1.7). After adjusting for these risk factors, age and sex, black children still had a 1.7 RO (95% Cl, 1.2 to 2.1) of having asthma. Frequent wheeze was associated with race (black versus white, RO = 1.6), sex (boys versus girls, RO = 1.3), birth weight (2 SD deficit in birth weight, RO = 1.4), and triceps skinfold thickness (increase in odds of asthma for 2 SD increase in skinfold, RO = 1.6). The significant effect of maternal age and birth weight after adjusting for other confounding variables suggests that the in utero environment may be an important determinant of asthma.(ABSTRACT TRUNCATED AT 250 WORDS)

Asthma

Delayed-type hypersensitivity to Entamoeba histolytica in mice and hamsters: a comparison.

Delayed-type hypersensitivity (DTH) to live or fixed Entamoeba histolytica was induced and compared in mice and hamsters. Peak reactions were obtained 24 h post-challenge. In mice, challenge with 10(5) amoebae produced maximal, specific footpad swelling; in hamsters, 5 x 10(4) were required. Elicitation of DTH in mice was strongest 1 week after induction and remained comparatively high for 8 weeks. In hamsters, elicitability declined after 1-2 weeks. Cyclophosphamide increased footpad reactions in mice and hamsters when given 1 day prior to induction but not prior to challenge. Reactions were usually somewhat (but not significantly) stronger in mice than in hamsters, which was also evident from adoptive transfer experiments. Thus, differences in cell-mediated immunity as expressed by DTH in mice and hamsters do not explain the differential susceptibility of these animals to infection with this parasite. In hamsters, multiple footpad injections of live or fixed amoebae lowered the percentage of subsequent liver infections after i.p. injection of virulent amoebae.

Amebiasis

[Glossectomies].

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Adolescent

Compliance and problem-solving competence in girls and boys.

The problem-solving abilities of 4- and 5-year old children (N = 208) were assessed to test the hypothesis that high levels of compliance are negatively related to problem solving. Problem-solving competence was examined with a task-specific measure and a standardized measure of general problem-solving performance. Low compliant children performed better on both measures. The role of compliance in the cognitive development of girls and boys is discussed.

Achievement

Comparison of monoclonal antibodies for rapid detection of cytomegalovirus in spin-amplified plate cultures.

Cytomegalovirus (CMV) was detected in 56 of 275 specimens (20%); 50 of 56 (89%) were detected by conventional culture, and 37 (66%) were detected by rapid assay at 72 h with a commercial monoclonal antibody and a pooled monoclonal antibody. Although the two antibodies were equally sensitive at 72 h, the pooled antibody gave a brighter, more easily detected signal. Other viruses were isolated from 9 specimens (3.3%) by conventional culture. Use of rapid assays alone fails to detect slow-growing CMV and non-CMV viral pathogens.

Antibodies, Monoclonal

The relationship between longitudinal change in pulmonary function and nonspecific airway responsiveness in children and young adults.

The relationship between airway hyperresponsiveness and longitudinal change in lung function was assessed in a population-based sample of 184 children and young adults observed over a maximum span of 12 yr. Pulmonary function was assessed annually with spirometry, and health and household information was obtained with standardized questionnaires. Nonspecific airway responsiveness to eucapneic hyperventilation with subfreezing air was measured on at least two occasions between the sixth and twelfth annual surveys. At any given survey, a significant bronchoconstrictor response was defined as [( prechallenge FEV1-postchallenge FEV1]/pre-FEV1) greater than or equal to 0.13, a value that identified 10% of the population. Subjects were classified as "never", "always", or "inconsistent" responders according to the consistency of responsiveness determined in different surveys. Subjects were classified further as "labile" if their maximal survey-to-survey difference in delta FEV1/FEV1 was greater than or equal to 0.18, and as "nonlabile" otherwise. A Markov-type autoregressive model that adjusts for previous pulmonary function level, sex, growth variables, and smoking exposures was used to model growth of FEV1, FEF25-75, and FVC. Overall, 135 (73%) of subjects never responded to the cold air challenge, six (3%) always responded, and 43 (24%) responded on one but not all occasions. Levels and rates of increase in level of FEF25-75 were significantly lower in the inconsistent and always responders. In contrast, levels of FVC were greatest and increased most in the always responders. In labile subjects, both FEF25-75 and FEV1 growth rates were reduced. These effects persisted when asthmatics were excluded from the analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Analysis of a major target of the human immune response to cytomegalovirus using monoclonal antibodies.

Two murine monoclonal antibodies (C6D1 and D2B1) were found to react with a set of cytomegalovirus (CMV)-infected cell polypeptides, which comprise a major target of the human immune response to CMV. C6D1 reacted with proteins of 50 kilodaltons (KD) and 40KD molecular weight; D2B1 reacted with these two proteins plus a third of 35KD. Western blot analysis demonstrated that these protein targets also react with serum antibody from patients with acute or latent CMV infection. Immunofluorescence staining of CMV-infected diploid fibroblast cells by C6D1 and D2B1 showed that the protein targets are found in the nucleus throughout the course of viral infection. The proteins were shown to be late proteins dependent on viral DNA synthesis for their expression. Not all wild-type CMV strains tested expressed proteins that react with C6D1 and D2B1. Using an immunofluorescence stain of diploid fibroblasts infected with CMV strains from infected patients, we found that 70 of 76 (92%) wild-type strains reacted with C6D1 and 23 of 24 (96%) with D2B1. One strain was not reactive with either C6D1 or D2B1. Western blot analysis of 11 wild-type strains revealed that two isolates either lack the C6D1 and D2B1 protein targets or have forms of these proteins that migrate at different molecular weights.

Animals

Measurement and correlates of verbosity in elderly people.

Two studies were conducted to develop measures of verbosity in elderly people and to determine the social and psychological correlates of verbose speech. In the first study, 346 elderly people were classified into three categories of verbosity on the basis of their verbal behavior during an interview and questionnaire session. Personality variables, stress in daily living, and age differentiated extremely verbose individuals from others. In the second study, frequency and extent of off-target speech were rated quantitatively for the verbal behavior of 203 older men, with a second rater independently making the same ratings for 98 of the men. Classification into the three categories of verbosity was made for 179 of the men. Interrater reliability was established at .76 and .70 for the two measures of verbosity. There was significant agreement between the qualitative classification and the quantitative rating assessments of verbosity. In addition to the previously found associations between verbosity and personality and social variables, higher nonverbal intellectual performance scores obtained in the early adult years combined with poorer current nonverbal scores predicted verbosity in late life.

Age Factors

Immunoblot analysis of the humoral immune response in primary cytomegalovirus infection.

Cytomegalovirus is a common infection in immunologically normal adults. It may cause an asymptomatic infection or may manifest symptomatically as heterophilic-negative mononucleosis. Studies of CMV infection in immunocompromised patients indicate that humoral immune response plays a role in modulating disease severity; however, the effect of antibodies to CMV in modifying disease expression and transmission in immunologically normal individuals has not been well characterized. Using immunoblot technology, we have demonstrated that immune serum from normal adults contains antibodies to at least 15 CMV-associated proteins and that there is strain-to-strain variation in the expression of these immunogens. The kinetics of the immune response were evaluated by using serial sera collected from normal adults after primary CMV infection; analysis of immunoblots of these sera identified one group of antibodies to CMV proteins that arise early and are stable over time, a second group that appear late after infection, and a third group that are variable among patients and over time.

Adult

Chronic-dose acyclovir to suppress frequently recurring genital herpes simplex virus infection: effect on antibody response to herpes simplex virus type 2 proteins.

To determine the effect of prolonged suppressive acyclovir therapy on the antibody response to herpes simplex virus type 2 (HSV-2) proteins, we studied sequential sera from 33 patients with frequently recurring (six or more recurrences per year) genital herpes. Twenty-two patients received 400 mg of oral acyclovir and 11 received placebo, twice daily for one year. Sera collected at enrollment, after six months and 12 months of therapy, and during the first recurrence after cessation of therapy were evaluated by western blot for levels of antibodies to HSV-2, gB, gG, gC/gE, VP16, and gD. Mean levels declined by 27%-39% after one year of acyclovir. The magnitude of the decrease in antibody levels was not correlated with disease severity either during or after therapy. Patients with high relative antibody levels to gB after therapy had more-severe first recurrences after therapy than did patients with antibody levels to gB less than or equal to the median. Antibody levels were not restored after the first untreated recurrence.

Acyclovir

Survival after acute endosulfan intoxication.

The clinical course following endosulfan ingestion in a suicidal attempt is described. The clinical picture comprised three stages: the acute cardiac and convulsive stage followed by subacute pulmonary and convulsive stage and finally the slow recovery stage. This is the first known survivor of endosulfan ingestion.

Adult