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Biomedical subjects

L Schlesinger

Publications and source records attributed to L Schlesinger.

At least 19 recordsLinked to original sources

Interleukin 1 and tumor necrosis factor in obese alcoholics compared with normal-weight patients.

We performed a liver biopsy and measured plasma concentrations of interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha), and spontaneous and lipopolysaccharide-stimulated in vitro monocyte production of IL-1 beta and TNF-alpha in 19 obese and 17 age-matched, normal-weight alcoholics admitted for treatment of their alcoholism. Nine healthy normal-weight alcoholics had cirrhosis in their liver biopsy (Fisher's exact test: P=0.031). A histologic score (derived from the sum of fat, necrosis, fibrosis, and inflammation in the biopsy) correlated with body mass index and the percentage body fat, calculated by using the sum of four skinfold-thickness measures. Plasma concentrations and spontaneous in vitro monocyte production of IL-1 beta and TNF-alpha were below detection limits. No significant differences were observed between normal-weight and obese alcoholics with or without cirrhosis and normal control subjects in lipopolysaccharide-stimulated monocyte production of IL-1 beta (6.5 +/- 0.8, 10.1 +/- 2.7, 7.9 +/- 1.6, and 5.28 +/- 4.24 micrograms/L, respectively) or TNF-alpha (2.8 +/- 0.4, 3.7 +/- 1.0, 3.0 +/- 0.44, and 1.97 +/- 1.01 micrograms/L, respectively). However, a positive correlation was found between IL-1 beta production and body mass index (r=0.333, P=0.047), percentage body fat (r=0.412, p=0.013), abdominal circumference (r=0.416, P=0.012), and total histologic score (r=0.331, P=0.049). A multiple-regression model accepted abdominal circumference as the only independent predictor of IL-1 beta production. TNF-alpha did not correlate with any of the above-mentioned indexes. We conclude that obese alcoholics have a higher frequency of histologic liver damage and that IL- 1 beta production by stimulated monocytes is related to abdominal fat accumulation.

Adult

Immune depression induced by protein calorie malnutrition can be suppressed by lesioning central noradrenaline systems.

Depressed immune function is well documented in protein calorie malnutrition (PCM). Also, central noradrenergic hyperactivity has recently been reported in malnourished animals. Increase in central noradrenaline activity could be responsible for cell-mediated immune depression. The present study is designed to address this hypothesis by testing whether neurotoxic lesion of central noradrenergic systems by 6-hydroxydopamine (6-OHDA) could improve lymphoproliferative response to mitogens and interleukin (IL)-1 production in PCM rats. A significant enhancement of lymphoproliferative response to concanavalin A (ConA) and in IL-1 production was observed in spleen mononuclear cells of PCM rats injected intracerebroventricularly with 120 micrograms of 6-OHDA, as compared with solvent injected and untreated PCM animals. A significant decrease in brain noradrenaline levels was produced in the drug-injected animals. These results suggest that central noradrenergic hyperactivity is one of the mechanisms involved in the immunodepression produced by malnutrition.

Animals

Depressed immune response in malnourished rats correlates with increased thymic noradrenaline level.

Depressed immune response is well documented in protein-calorie malnutrition (PCM). Also, central and peripheral noradrenaline (NA) activities have been reported to be increased in malnourished animals. Since increases in central and peripheral NA may inhibit immune function, it is possible that malnutrition-induced immunodepression could be mediated by noradrenergic hyperactivity. To address this hypothesis the effect of malnutrition on cell-mediated immune response, as well as on NA levels of the median eminence, spleen and thymus was studied in PCM rats. Decreased lymphoproliferative response and IL-1 production by mononuclear macrophages was observed in PCM. Besides, increased NA concentration was detected in thymuses of PCM rats, while unchanged levels of this neurotransmitter were observed in median eminence and spleen. These data suggest a positive correlation between malnutrition-induced immunodepression and sympathetic noradrenergic activity in thymus, an organ implicated in immune cell differentiation during early development.

Animals

Zinc supplementation impairs monocyte function.

Zinc has been shown to be involved in many functions of the immune system. This study was conducted to examine the effect of zinc supplementation on phagocytic, fungicidal and metabolic activity of blood monocytes of marasmic infants during nutritional rehabilitation. A controlled, double-blind design was used in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same, unfortified formula. Evaluation of phagocytic-fungicidal capacity, growth, zinc, copper and iron status was performed in both groups on admission and after 60 and 105 days of nutritional rehabilitation. Although energy, copper and iron intakes were similar in the two groups, a decrease in the number of infants able to phagocytose one or more Candida buds was observed after 60 days of zinc supplementation compared to admission (p < 0.03). No change in phagocytic ability was detected between admission and 60 days in the control group. The number of infants with depressed fungicidal activity increased significantly after 105 days of nutritional rehabilitation in the zinc-fortified group as compared to controls (p < 0.04). The number and duration of impetigo episodes was significantly greater in the group fed the zinc-fortified formula. These results suggest that zinc supplements at the RDA level may impair monocyte function.

Candida albicans

Comorbidity of fibromyalgia with medical and psychiatric disorders.

PURPOSE: Patients with fibromyalgia have been reported to display high rates of several concomitant medical and psychiatric disorders, including migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. To test further these and other possible associations, we assessed the personal and family histories of a broad range of medical and psychiatric disorders in patients with fibromyalgia. PATIENTS AND METHODS: Subjects were 33 women (mean age 42.1 years) who each met American College of Rheumatology criteria for fibromyalgia and presented to a rheumatologist at a tertiary referral center. They received the Structured Clinical Interview for DSM-III-R (SCID); a supplemental interview, in SCID format, for other medical and psychiatric disorders, including migraine, irritable bowel syndrome, and chronic fatigue syndrome; and an interview for family history of medical and psychiatric disorders. RESULTS: Patients with fibromyalgia displayed high lifetime rates of migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder. They also exhibited high rates of familial major mood disorder. CONCLUSIONS: The finding that migraine, irritable bowel syndrome, chronic fatigue syndrome, major depression, and panic disorder are frequently comorbid with fibromyalgia is consistent with the hypothesis that these various disorders may share a common physiologic abnormality.

Adult

Effect of a zinc-fortified formula on immunocompetence and growth of malnourished infants.

This study attempted to define the possible contribution of zinc nutrition to immunocompetence and growth in severely malnourished infants. The effect of zinc supplementation was evaluated in marasmic infants during nutritional rehabilitation by using a controlled double-blind design in which 19 infants fed a zinc-fortified formula were compared with 20 infants fed the same non-supplemented formula. Evaluation of immunocompetence, growth, and zinc, copper, and iron status was performed on admission and at 30, 60, and 105 d of nutritional rehabilitation. Although energy intake was similar in both groups, the zinc-supplemented infants had significantly higher linear growth gain, and their immune function improved as demonstrated by conversion of their delayed hypersensitivity skin reactions, enhanced lymphoproliferative response to PHA, and increased salivary IgA concentrations. Thus, the use of a zinc-fortified formula during nutritional rehabilitation can prevent the development of zinc deficiency and improve growth and immune function.

Copper

Resurgence of tuberculosis.

Since 1985 there has been an 18% increase in the number of cases of tuberculosis nationally. Even more alarming is the increasing incidence of multidrug-resistant tuberculosis which presents a serious public health problem, particularly for HIV-infected patients.

Anti-Bacterial Agents

Immunogenicity of Salmonella typhi Ty21a vaccine for young children.

An attenuated Salmonella typhi Ty21a vaccine was administered to 18 infants and toddlers (less than or equal to 24 months old) to determine its safety and immunogenicity. The vaccination (10(9) CFU per dose, three doses) was well tolerated. However, after the vaccination there was no evidence of a humoral or cellular immune response to S. typhi. The vaccine used was known to be immunogenic for older children and adults. The results support the view that the immunogenicity of Ty21a is age dependent.

Administration, Oral

Functional capacity of colostral leukocytes from women delivering prematurely.

The phagocytic, bactericidal, and metabolic activity of colostral leukocytes from mothers delivering preterm infants was compared with that of colostral leukocytes from mothers of term infants. In addition, the proliferative capacity of colostral lymphocytes was compared. Preterm adherent colostral leukocytes had a significantly higher phagocytic index than term colostral adherent leukocytes. Mean +/- SEM values were 5.4 +/- 0.5 versus 2.7 +/- 0.2, respectively (p less than 0.001). Bactericidal capacity against Escherichia coli and nitroblue tetrazolium reduction of preterm and term colostral leukocytes were comparable. Lymphocyte proliferative response was equivalent in preterm and term milk. We conclude that colostral leukocytes from preterm mothers are at least as functional in their antimicrobial activity and possibly phagocytose even better than the colostral cells of mothers of term infants.

Adult

Immunity to Salmonella typhi: considerations relevant to measurement of cellular immunity in typhoid-endemic regions.

Experiments were performed in Baltimore, Maryland and in Santiago, Chile, to determine the level of Salmonella typhi antigen-driven in vitro lymphocyte replication response which signifies specific acquired immunity to this bacterium and to determine the best method of data analysis and form of data presentation. Lymphocyte replication was measured as incorporation of 3H-thymidine into desoxyribonucleic acid. Data (ct/min/culture) were analyzed in raw form and following log transformation, by non-parametric and parametric statistical procedures. A preference was developed for log-transformed data and discriminant analysis. Discriminant analysis of log-transformed data revealed 3H-thymidine incorporation rates greater than 3,433 for particulate S. typhi, Ty2 antigen stimulated cultures signified acquired immunity at a sensitivity and specificity of 82.7; for soluble S. typhi O polysaccharide antigen-stimulated cultures, ct/min/culture values of greater than 1,237 signified immunity (sensitivity and specificity 70.5%).

Adolescent

Anemia of a mild viral infection: the measles vaccine as a model.

To define the hematologic changes during a mild viral infection, 93 infants were immunized with live attenuated measles virus and studied prospectively at 0, 4, 9, 14, 21, and 30 days. Hemoglobin concentration decreased significantly by days 9 and 14. The decrease was greater than 1.0 g/dL in 8.6% and greater than 0.6 in 24.3% of the infants. Of the nonanemic infants, 22% became anemic. Serum iron and percentage saturation of transferrin decreased, whereas serum ferritin increased significantly. Mean cell volume, iron-binding capacity, protoporphyrin, and haptoglobin did not show changes. Reticulocyte index and erythropoietin increased significantly at 30 days. Leukocyte counts, Zetacrit, and C-reactive protein did not help to predict the hemoglobin decrease. These results suggest that a mild viral infection in infants induces a significant decrease in hemoglobin that may persist for 14 to 30 days and may be difficult to distinguish from iron deficiency.

Anemia

Functional and biochemical studies of multinucleated giant cells derived from the culture of human monocytes.

We compared phagocytic and metabolic activities of multinucleated giant cells (MGC) and macrophages derived from human monocytes after 9-14 d in culture. Phagocytosis of sheep erythrocytes (E) coated with IgG, of E coated with IgM and complement, and of Candida albicans was comparable in MGC and macrophages. The same percentage of ingested fungi was killed by MGC (24 +/- 4%) and macrophages (21 +/- 5%). Approximately 70% of MGC and macrophages exhibited superoxide-dependent reduction of nitroblue tetrazolium during stimulation. Ia antigen was present on approximately 75% of both cell types. Analysis of cell populations separated by nuclear fluorescence indicated that beta-glucosaminidase, acid phosphatase, and beta-glucuronidase activity per cell was higher in MGC, but specific activity of these enzymes was greater in macrophages. These results suggest that MGC have the capacity to function like macrophages in host defense against infection.

Adult

T-cell dysfunction in minimal-change nephrotic syndrome of childhood.

Cell-mediated immunity was studied in 25 children with minimal-change nephrotic syndrome in different stages of their disease. This was assessed by delayed cutaneous hypersensitivity reactions, number of T lymphocytes, and blastogenic response to phytohemagglutinin and PPD. Patients with active nephrosis could not become sensitized to dinitrochlorobenzene and had decreased response to common recall antigens. T-cell number ranged within normal values in all nephrotic patients. During active disease, lymphocyte transformation was markedly reduced, but improved considerably when cells were cultured in normal plasma. During remission, patients showed normal proliferative response. Reactivity of normal lymphocytes to both stimulants was inhibited by nephrotic plasma. Our results suggest the existence of a serum factor that affects T-cell function.

Adolescent

Leukocyte migration inhibition factor production in marasmic infants.

Production of leukocyte migration inhibition factor was measured in vitro with purified protein derivative and phytohemagglutinin in 14 marasmic infants 6 to 18 months of age. Twenty-seven well-nourished infants served as controls. All the children had received BCG vaccine in the neonatal period. Tuberculin reaction was positive in four of 14 of the marasmic infants and 13 of 27 of the controls. When leukocyte migration inhibition factor was induced with purified protein derivative, the four tuberculin positive malnourished subjects had a mean migration inhibition index of 55.7% which was significantly higher than the mean migration inhibition index of 38.2% in the tuberculin positive controls. In the tuberculin negative subjects the mean migration inhibition index was 24.7 and 16.6% in the marasmic and control groups, respectively. The difference was not statistically significant. Phytohemagglutinin-induced migration inhibition was comparable in malnourished and control infants. There was no correlation between leukocyte migration inhibition factor production and biochemical indices of iron nutrition, erythrocyte or serum folate, vitamin A, carotene, or serum zinc levels in either group. It is suggested the capacity of lymphocytes to produce leukocyte migration inhibition factor is unchanged in marasmus.

Blood Proteins