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Biomedical subjects

I L Bernstein

Publications and source records attributed to I L Bernstein.

At least 199 records · Page 11Linked to original sources

Learned food aversions: heterogeneity of animal models of tumor-induced anorexia.

Learned food aversions have been implicated in the anorexia which develops in rats with transplantable PW-739 tumors. There appear to be striking differences in growth characteristics and physiological effects of different experimental tumors. The present studies examined the issue of heterogeneity of tumor models, while assessing the generality of the finding that learned food aversions arise in anorexic, tumor-bearing animals. This was done by comparing effects on food intake and diet preferences of two transplantable tumors, the Leydig cell tumor, LTW(m), and the Walker-256 carcinosarcoma. We found that animals with Leydig tumors, like those with PW-739 tumors, developed strong aversions to the specific diet they had eaten after tumor implant. In contrast, animals with Walker-256 tumors did not develop diet aversions. These results support the idea that learned food aversions contribute to anorexia in animals with Leydig but not Walker tumors. They further suggest that learned food aversions in tumor-bearing animals are not a response to illness, in general, but rather that the unconditioned stimulus responsible for these aversions is quite specific, and may ultimately prove identifiable.

Animals↗

Chronic lithium chloride infusions: conditioned suppression of food intake and preference.

A modified learned food aversion paradigm simulated the prolonged food and illness exposure likely to characterize nutrient deficiencies or tumor growth. In this paradigm, a continuously available food was associated with a slow, continuous infusion of LiCl provided by osmotic minipump. Significant aversions were acquired when the available diet was novel but not when it was familiar. Effects of drug infusions on daily food intake were found to parallel those on aversion formation. Marked, persistent suppression of food intake was seen in drug-treated animals consuming a novel diet, but only transient declines were seen in those with a familiar diet. By separating the direct from the conditioned effects on food intake of chronic drug infusions, these studies provided strong evidence that learned food aversions can lead to anorexia.

Animals↗

Vagotomy produces learned food aversions in the rat.

Subdiaphragmatic vagotomy produces hypophagia and weight loss in normal rats and can reverse the hyperphagia and obesity of rats with ventromedial hypothalamic lesions. Vagotomy surgery can also produce symptoms of nausea and discomfort. Since such symptoms are highly effective as unconditioned stimuli in food aversion conditioning, the present studies examined whether some of the depression in food intake observed in rats with vagotomy could be due to the development of aversions to the foods eaten after their surgery. In the first study, significant aversions developed to the specific novel diet consumed after vagotomy, results indicating that the symptoms associated with vagotomy can serve as effective unconditioned stimuli in the acquisition of learned food aversions. The second study compared vagotomized animals consuming familiar laboratory chow with those consuming a novel diet. In contrast to the novel diets, learned aversions did not develop to the familiar chow, and hypophagia was less persistent and severe. It is concluded that learned food aversions can contribute to the appetite and weight loss exhibited by vagotomized animals. Consideration of the conditions under which these aversions arise after vagotomy surgery may allow for the design of studies so as to minimize the aversions and thereby separate these nonspecific effects from direct regulatory deficits produced by vagotomy.

Animals↗

The guinea pig model of diisocyanate sensitization. I. Immunologic studies.

Two strains of guinea pigs were parenterally immunized with well-characterized diisocyanate-protein conjugates. Hapten-specific IgE antibodies were detected in the sera of English short-hair strain guinea pigs immunized with either toluene diisocyanate-human serum albumin (TDI-HSA) or hexamethylene diisocyanate-HSA (HDI-HSA) when these sera were analyzed by the 168 hr passive cutaneous anaphylaxis (PCA) technique followed by intravenous challenges with conjugates of respective ligands coupled to an unrelated carrier protein, transferrin. IgG1 antibodies and precipitating antibodies were demonstrated in Hartley strain guinea pigs immunized with TDI/HDI-HSA conjugates. The hapten specificity of these antibodies was proved by PCA inhibition experiments and antibody absorption experiments. In the precipitating antibody system, this was further confirmed by immunoelectrophoretic analysis. Cross-reactivity between HDI and TDI was not observed in the PCA experiments. However, apparent cross-reactivity in the double gel diffusion experiments was due to new antigenic determinants formed by isocyanates after conjugation with proteins. It was therefore apparent that immune responses of guinea pigs immunized with protein conjugates of bifunctional isocyanates were heterogeneous and involved multiple specificities for hapten, carrier protein, and new antigenic determinants. It was postulated that the complex nature of the immune response generated by diisocyanate compounds in the guinea pig may also serve as a more appropriate model of isocyanate-induced human sensitivity reactions, which are known to involve diverse immunologic and nonimmunologic mechanisms.

Animals↗

Occupational asthma induced by inhalation and ingestion of garlic.

Repeated exposure to garlic dust induced severe asthma in an atopic patient. Subsequently, the patient also developed marked adverse responses after ingestion of garlic. Immunologic investigations carried out in an asymptomatic period revealed significant skin reactivity and bronchospasm after challenge with both garlic dust and extract. The results of a controlled oral challenge test to garlic dust were also positive. The patient's serum contained unusually high quantities of garlic-specific IgE. Cross allergenicity between garlic and other members of the Liliaceae family were documented by the RAST inhibition technique.

Adult↗

The prevalence of house dust mites, Dermatophagoides spp, and associated environmental conditions in homes in Ohio.

Abundance of the house dust mites, Dermatophagoides farinae and D. pteronyssinus, in various sites in the homes of dust-sensitive patients was sequentially monitored at approximately 3 wk intervals for 2 yr, and mite density was correlated with indoor physical and climatic factors. Significantly higher mite levels occurred on the most heavily used fabric-upholstered furniture and carpeted floor areas of the living/family room and bedrooms. Mattresses were not found to be the major foci for mites. No significant positive correlation was noted between mite abundance and frequency or thoroughness of cleaning, amount of dust, and age of furnishings or dwelling. Significantly higher mite levels occurred on carpeted floors than on noncarpeted floors. Successive vacuuming did not significantly reduce mite abundance. Mite density exhibited a seasonal fluctuation, with highest density occurring in the humid summer months and the lowest density during the dryer, late heating season. Live mites were more abundant than dead mites during the period when total abundance was high. In homes inhabited by both species, D. farinae was the dominant species, except in one home that had a significantly higher relative humidity.

Animals↗

Efficacy and safety of triamcinolone acetonide aerosol in chronic asthma. Results of a multicenter, short-term controlled and long-term open study.

Triamcinolone acetonide aerosol (TAA) and a placebo aerosol were compared in a six-week, double-blind multicenter study. Ninety-six steroid-independent asthmatic patients were randomized into two parallel groups. Each patient was evaluated weekly. After four weeks of treatment, those patients treated with TAA showed highly significant (P less than 0.001) improvement from baseline in pulmonary function tests (FEV1, FVC, and FEF25-75%) and in asthmatic symptoms, whereas no significant improvement was observed in those patients who received placebo aerosol. In the TAA-treated patients, 78 percent were rated wtih an excellent or good response, compared with 24 percent in the placebo patients. During the subsequent one-week washout period, mean pulmonary function test values of the TAA-treated group were significantly reduced (P less than 0.0001). Eighty-eight patients continued into the one-year, open-label phase of the study. Highly significant (P less than 0.001) improvement from baseline was observed in pulmonary function tests and in asthmatic symptoms at each bimonthly evaluation during the 12-month segment. Mean plasma-cortisol level changes were not statistically significant. At the end of the long-term study, the performance of TAA was subjectively rated by the investigators (excellent or good in 92 percent of the patients) and by the patients (excellent or good in 89 percent). Mild-to-moderate adverse reactions (sore throat, hoarseness) were reported by six patients during the six-week phase and by ten patients during the 12-month phase. Thus, TAA was a safe and effective treatment in this series of bronchial asthma patients.

Adolescent↗

Studies on Alternaria allergens. III. Effect of Alternaria tenuis on the humoral response to three T cell-dependent antigens in rats.

The effects of an extract of the saprophytic mold, Alternaria tenuis (AT-CE) on the humoral response to a ragweed allergen extract (DWSR), ovalbumin and sheep red blood cells (SRBC) was investigated in female Wistar rats. Animals pretreated with 100 micrograms or 2 mg AT-CE showed enhancement (p less than 0.05) in the reaginic response (IgE antibody) to DWSR at 25 and 18 days postimmunization. On the other hand, animals posttreated with AT-CE showed substantial reduction in anti-DWSR IgE antibody response. Contrasting results were obtained when ovalbumin was used as an immunizing antigen. There was a remarkable enhancement in the reaginic response to ovalbumin in rats pre- or posttreated with 10 micrograms of AT-CE. Pretreatment with AT-CE did not affect the hemagglutination titers to ovalbumin, while posttreatment with 100 micrograms or 1 mg AT-CE increased the hemagglutination titers of IgM antibody. There was a significant reduction in hemagglutinin, and hemolysin titers to SRBC in animals pretreated with all concentrations of AT-CE; at day 21, suppression was noted in animals pre- or posttreated with all concentrations of AT-CE. On the other hand, greatly increased hemagglutination titers were found in animals posttreated with 100 micrograms or 1 mg AT-CE. Hence, enhancement and suppression can both occur depending on the dose and time of administration of AT-CE together with the nature of the immunizing antigen.

Alternaria↗

Diverse profiles of immunoreactivity in toluene diisocyanate (TDI) asthma.

Possible immunoreactivity to chemically well-characterized mono- and diisocyanate protein conjugates was reevaluated in 15 workers with TDI asthma and 17 normal (nonexposed) volunteers. Lymphocytes of nine sensitive workers were incubated with TDI human serum albumin (HSA) conjugates. Leucocyte inhibitory factor (LIF) was produced. Leucocyte inhibitory factor was also induced by hexamethylene diisocyanate (HDI) protein conjugates in four of these workers who had no prior history of exposure to HDI. Disappearance of TDI- and HDI-induced LIF was noted in several sensitive workers who were removed from further TDI exposure. Three LIF-positive workers also demonstrated positive intracutaneous reactivity to TDI-HSA. One workers had a markedly positive RAST (25.5% binding) to a monofunctional (p-tolyl isocyanate) protein reagent. These studies suggest that isocyanates have the potential for eliciting heterogeneous immune responses in certain subpopulations of exposed workers. Continued contact with isocyanates may be necessary for maintenance of specific immunity. Possible cross reactivity between TDI and HDI may be determined by new antigenic sites created by isocyanate protein interactions.

Adult↗

Localized and systemic hypersensitivity reactions to human seminal fluid.

Reaginic humoral antibodies to human seminal plasma were present in two women with systemic reactions. In one patient, IgE antibodies were demonstrated by direct skin tests, leukocyte histamine release, passive transfer to a nonallergic human recipient, the radioallergosorbent test, inhibition of the radioallergosorbent test and neutralization of passive transfer antibodies. A similar mechanism was established in the other case by direct skin tests and antigen-induced leukocyte histamine release. Sephadex G-100 fraction 2, derived from human seminal plasma, showed greater reaginic activity than other chromatographic fractions. Two other patients with histories of localized reactions did not develop humoral antibodies but did evince cell-mediated immunity to seminal fluid antigens. One patient with localized reactions also had significant titers of IgM and IgG sperm agglutinating antibodies to seminal plasma. Both reaginic and cell-mediated sensitization to human sperm extract were also observed in this series of patients. Histocompatibility leukocyte antigen (HLA) typing of all patients and their sexual partners showed a marked degree of shared histocompatibility focus antigens in members of each of two couples.

Female↗

Studies on alternaria allergens. II. Presence of two related antigens with contrasting allergenic properties in Alternaria tenius extracts.

Earlier, it was reported that most of the allergenic activity of Alternaria tenuis seemed to reside in the last Sephadex G-100 fraction (G3, molecular weight approximately 20,000). These conclusions were based on results obtained by the in vitro techniques of radioallergosorbent tests (RAST) and RAST inhibition. In the present studies, the allergenic activity of A. tenuis fractions was measured in vivo. It was found that fraction G3 was neither capable of inducing reaginic (IgE) antibodies in rats nor eliciting a skin reaction in rats sensitized with reagins against A. tenuis non-dialyzable fraction (MW greater than 12,000). On the other hand, subfractions G2D3 and G2D4 obtained from the middle fraction of G-100 (G2, MW approximately 30,000-40,000) followed by ion-exchange chromatography on DEAE-cellulose, showed the greatest allergenic activity in vivo, giving high titered reaginic antibodies in rats. When compared by RAST inhibition, the activities of fractions G2D3 and G2D4 were slightly lower than that of G3. Fraction G3 was immunogenic in rabbits. In immunodiffusion tests, G2D3, G2D4 and G3 appeared to be identical and they were cross-inhibiting in RAST inhibition tests. It was concluded that the sizes and multivalent properties of G2 and G3 antigens exerted a strong influence on their allergenic activities in rats (IgE antibody production) but this factor was of little importance for their antigenic activity in rabbits (precipitin antibody production) and their behaviour in the in vitro tests.

Alternaria↗