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Biomedical subjects

M Stern

Publications and source records attributed to M Stern.

374 records · Page 21Linked to original sources
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Food proteins and maturation of small intestinal microvillus membranes (MVM). I. Binding characteristics of cow's milk proteins and concanavalin A to MVM from newborn and adult rats.

To study maturational changes of food protein and lectin binding to rat small intestinal microvillus membranes (MVM), MVM were prepared from newborn and adult animals by a modified CaCl2 precipitation technique. Radiolabeled cow's milk proteins [alpha-lactalbumin, alpha-casein, beta-lactoglobulin, bovine serum albumin (BSA)] and the lectin concanavalin A (Con A) were used for incubations. Binding assays were done using miniature ultracentrifugation for separation of unbound material. Binding of Con A to MVM from newborn and adult rats was strong, specific, and saturable. Binding of Con A was inhibited by cold Con A and by the sugar ligand polymer mannan. Adult MVM bound more Con A than newborn preparations. Unlike Con A, binding of cow's milk proteins by MVM was weak, nonspecific, and noninhibitable. Newborn MVM bound more cow's milk proteins than adult controls. This was true for all the proteins tested (p less than 0.001). Binding rose with decreased molecular weight of cow's milk proteins, but molecular weight was not the only determining factor for binding. Trypsin treatment of MVM caused a marked increase of BSA binding in adult but not in newborn preparations. This finding indicated the importance of protein components of MVM for cow's milk protein binding. Maturational changes in protein-lipid interactions and membrane fluidity possibly influence nonspecific cow's milk protein binding to MVM. Differences in binding between newborns and adults were not directly related to maturational shifts in membrane glycosylation that are indicated by differential Con A binding. Increased cow's milk protein binding in newborn individuals might increase the potential risk to develop an adverse reaction to food proteins.

Animals↗
PubMedDate not supplied

Food proteins and maturation of small intestinal microvillus membranes (MVM). II. Binding of gliadin hydrolysate fractions and of the gliadin peptide B3142.

To investigate in vitro interactions between gliadin peptide fractions that have been shown to be toxic to celiac small intestinal mucosa in humans and small intestinal microvillus membranes (MVM) from rats during postnatal maturation, MVM were prepared from newborn, 18-day-old preweanling, and adult rats. Partially hydrolyzed gliadin peptide fractions B1-B4, and the pure gliadin peptide B3142 were radioiodinated and used for binding assays. Miniature ultracentrifugation was used for separation of unbound material. Binding of gliadin fractions to MVM was weak and nonspecific in terms of lacking saturation and inhibition. There was no inhibition of binding by mannan. Enzyme pretreatment of MVM (trypsin, neuraminidase, phospholipase C) did not result in any significant change of binding. Compared with peptides prepared from bovine serum albumin as a control, there was no significant difference in binding of gliadin peptide fractions to MVM. Thus, a lectin-like effect of gliadin peptides toward MVM, or the existence of a specific intestinal surface receptor for gliadin peptides appeared improbable. There were, however, consistent maturational changes in MVM binding in that newborn MVM bound more B1-B4 and B3142 compared with adult controls (p less than 0.001). Nonspecific binding of gliadin fractions to MVM might be related to the initiation of nonspecific in vitro effects of gliadin, particularly toward the immature small intestine. The MVM binding model in the rat clearly does not provide a system for studying celiac disease pathogenesis, but it might help clarify basic processes in the interaction between food-derived substances and elements of the gastrointestinal mucosal barrier.

Animals↗
PubMedDate not supplied

Handling of gliadin peptides B1-B4 and of cow's milk proteins by rat jejunum gut sacs.

The rat everted gut sac was used as a model of intestinal protein and peptide handling to study small intestinal binding and uptake of different gliadin peptide fractions (B1, B2, B3, B4) in comparison with bovine serum albumin (BSA), alpha-lactalbumin (alpha-LA), and a BSA peptide fraction (BSA-P). Not only binding curves, but also uptake curves of BSA, alpha-LA, and BSA-P were run in parallel between 1 and 30 min. Binding and uptake obviously depended on molecular weight. BSA-P binding was found to be highest of all. Binding of BSA was significantly lower. After 20 and 30 min, significantly more alpha-LA and BSA-P were taken up than was BSA. There was no difference in handling of the gliadin peptide fractions tested by the gut mucosal surface. Binding of B1-B4 was significantly higher than binding of BSA and was significantly lower than binding of BSA-P. No difference was found between binding of B1-B4 and alpha-LA. There was a consistently higher uptake of all gliadin peptide fractions, independent of molecular weight. Slopes for uptake curves of B1-B4 were steeper than those of BSA, alpha-LA, and BSA-P. Crossing of uptake over binding curves was consistently observed with gliadin fractions, but never with cow's milk proteins/peptides. Differences in uptake between gliadin peptide fractions and cow's milk proteins/peptides might be based on a specific interaction between gliadin peptides and the gut surface.

Animals↗
PubMedDate not supplied

Lung in acquired immune deficiency syndrome: infectious and immunological status assessed by bronchoalveolar lavage.

Bronchoalveolar lavage (BAL) has been performed in 63 patients with acquired immune deficiency syndrome (AIDS) and 20 patients with chronic generalized lymphadenopathy (CGL) for the diagnosis of lung opportunistic infections and analysis of immune effector cells of the lower respiratory tract. In patients with AIDS, Pneumocystis carinii was found in 63%. Cytomegalovirus (CMV) pneumonia was assessed by viral cultures of BAL fluid and microscopic examination: CMV was found in 62% and 39% respectively. Mycobacteria were encountered in 22% of cases. Altogether BAL yielded at least one opportunistic agent in 94% of patients who presented with clinical and/or radiographic pulmonary involvement, and in 80% of patients who presented with fever only. Conversely BAL was negative in all patients with CGL, except one positive CMV culture. Analysis of BAL cells revealed an increased cellularity in AIDS and CGL patients with normal numbers of alveolar macrophages. Alveolar lymphocytes were surprisingly increased in most patients with AIDS (mean 26.1 +/- 21.9%; range 1-76%) and CGL (mean 26.6 +/- 22.6%; range 3-76%) with criteria of activation contrasting with the blood lymphopenia. Evaluation of lung lymphocyte phenotypes revealed a marked decrease in T4 cell percentages, specially in AIDS, whereas the large majority of alveolar lymphocytes expressed the T8 phenotype. We conclude that BAL is a very reliable means for diagnosis of opportunistic lung infections and give interesting prospects to study local immunity in patients with AIDS and CGL.

Acquired Immunodeficiency Syndrome↗
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[Fatal case of metformin-induced lactic acidosis after urography in a diabetic patient (author's transl)].

The authors report a new case of lactic-acidosis in a diabetic patient receiving metformin. This patient, after urography developed an acute renal failure and a fatal lactic acidosis. Risks of urography in diabetic patients and guidelines for use of metformin are recalled; careful assessment of risk versus benefit for every proposed urography in diabetic patients never use metformin if creatinin is over 140 micromoles/liter, if an urography must be undergone, metformin must be stopped 3 days before urography and resumed only 3 days after it, if renal function allows it.

Acidosis↗
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Survey of incidence of and physicians' attitudes toward sexual assault.

In a recent pilot project, the number of women treated by private physicians for sexual assault was surveyed, and information was obtained regarding the physicin's knowledge of, and attitudes toward, issues related to sexual assault. The high incidence rates for treatment of rape by private physicians that have been speculated in the literature were not confirmed by the survey results. Sixty-seven percent of the 458 physicians responding to the survey reported seeing no rape victims during the study year. Since, however, the proportion of physicians seeing rape victims may show regional variations, this result should not be applied too generally. Ten factual questions about rape were sent to more than 1,000 physicians and given to 258 undergraduate psychology students of both sexes. Both the responding physicians and the students answered approximately 60 percent of the questions correctly (that is, selected the answers that best reflect current understanding about sexual assault). The respondents' attitudes toward sexual assault were inferred from the direction of their responses. Physicians were seen to share attitudes similar to those of the male students, but not of the female students. The female students tended to overestimate the incidence of rape, the physical trauma associated with it, and the timing of its psychological after effects.

Attitude↗
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Nebulized cyclosporine for prevention of acute pulmonary allograft rejection in the rat: pharmacokinetic and histologic study.

BACKGROUND: With regard to limiting the systemic effects of cyclosporine A and obtaining better control of acute pulmonary allograft rejection, local immunosuppressive therapy with aerosolized cyclosporine A seems of interest. Given the in situ immunologic mechanisms of acute rejection, as well as the anatomic structure of the lung, this therapy is feasible as previously described by others. The aim of our study is to determine the pharmacokinetic parameters of nebulized cyclosporine A and the best modalities of administration. METHODS: In a pharmacokinetic study, the cyclosporine A was given either by intramuscular injection (10 mg/kg) or by aerosol at 10 and 25 mg/kg doses; 70 rats were killed at 25 and 50 minutes and 2, 4, 6, 8, 12, 24, or 48 hours after cyclosporine A administration. Cyclosporine A levels were measured in whole blood and in the lung. The areas under the concentration time curves were determined. Twenty-four lung transplantations were then performed. The rats were killed on postoperative day 9. Acute rejection was scored on a scale of 0 to 4, and cyclosporine A trough levels were measured in the lung and in the blood. RESULTS: With a jet nebulizer, the mass median aerodynamic diameter was 2.5 microns, with a standard geometric deviation of 2.3. In blood, the area under the concentration curve was greater for intramuscular (80.6 ng.hr/ml) than for aerosol administrations at 10 (15.1 ng.hr/ml) and 25 mg/kg (41.0 ng.hr/ml) doses. In the lungs, the area under the concentration curve was greater for the aerosol route at 25 mg/kg doses (588 ng.hr/mg) than for the low-dose (200 ng.hr/mg) or intramuscular administration (200 ng.hr/mg). The lung targeting index of cyclosporine A (ratio area under the concentration curve-lungs/area under the concentration curve-blood) was greater for both aerosol administrations than for the intramuscular route. In the study of the prevention of acute rejection, rats without immunosuppression (n = 6), rats receiving daily doses of cyclosporine A intramuscularly (10 mg/kg), and rats with aerosolized cyclosporine A daily (10 and 25 mg/kg/day) showed mean grades of acute rejection of, respectively, 4, 2.03 +/- 0.27, 2.33 +/- 0.52, and 2.17 +/- 0.46. The deposition of nebulized cyclosporine A was lower in transplanted than in native lung. CONCLUSIONS: Nebulized cyclosporine A allows better pulmonary concentration than intramuscular administration, and results in lower systemic levels. Prevention of acute rejection is as good with aerosolized cyclosporine A as with intramuscular cyclosporine A. This first pharmacokinetic study of nebulized cyclosporine A could lead to clinical applications.

Administration, Inhalation↗
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Cystic fibrosis: basic chemical and cellular mechanisms.

Cystic fibrosis (CF) primarily affects epithelial-lined organs, the most important being the lungs. Much of the known pathogenesis of the disease has been elucidated by the identification of the gene mutated in CF which encodes the cystic fibrosis transmembrane conductance regulator, a chloride channel in the apical membrane of epithelial cells of the respiratory and intestinal tracts.

Chloride Channels↗