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Biomedical subjects

R E Kleinman

Publications and source records attributed to R E Kleinman.

At least 19 recordsLinked to original sources
PubMed1992

Rejection of murine congenic bile ducts: a model for immune-mediated bile duct disease.

Immune-mediated injury of prenatal and postnatal extrahepatic bile duct epithelium has been poorly characterized. In a transplantation model of bile duct allografts, segments of the common bile duct from fetal day 18, postnatal day 7 and day 21, and adult (greater than 6-weeks) mice were grafted under the renal capsule of adult congenic mice. The progression of rejection injury in these bile duct allografts was then followed by histological evaluation at 1-week intervals. After 3 weeks there was a significant difference in the number of fetal congenic bile duct grafts that had maintained their luminal architecture compared with the more mature adult congenic grafts that had fibrosclerosed. The onset and progression of the rejection injury in the adult congenic bile duct grafts was associated with an induction of class I and class II histocompatibility antigen expression in the adult bile duct epithelium; the severity of this injury could be attenuated by treatment of the recipient mice with cyclosporin A. Thus, the fibrosclerosing lesion of extrahepatic ducts observed in this model of rejection injury is similar to the histopathology of neonatal biliary atresia or primary sclerosing cholangitis, and susceptibility to this injury is dependent on the age of the donor tissue. The immune nature of the injury and the ontogeny of expression of histocompatibility antigen in bile duct tissue indicate that the above factors may be important to the pathogenesis of these extrahepatic bile duct diseases. This experimental model may be used to test for novel factors that may modulate immune responses directed against extrahepatic bile duct epithelium.

Animals↗
PubMed1992

Cow milk allergy in infancy and hypoallergenic formulas.

Substitute feedings have been used to treat infants with cow milk protein allergy for most of this century. For the past 50 years, several infant formulas based on animal proteins, both intact and chemically modified, or on vegetable protein have been labeled "hypoallergenic." Because of the risk of anaphylaxis and other serious adverse reactions, formulas that are claimed to be hypoallergenic should be subjected to rigorous preclinical and clinical testing. At a minimum, such formulas should not provoke any allergic signs or symptoms in 90% of infants with documented cow milk protein allergy when tested in double-blind, placebo-controlled trials. A standardized definition of "hypoallergenic" will allow clinicians and parents to understand the true risks to a cow milk-allergic infant fed such hypoallergenic formulas.

Animals↗
PubMed1992

Efficacy of domperidone in infants and children with gastroesophageal reflux.

This study sought to define the therapeutic efficacy of domperidone in infants and children with gastroesophageal reflux. A double-blind, placebo-controlled trial was performed in seventeen children (ages 5 months to 11.3 years) with moderate to severe gastroesophageal reflux who had not responded to standard nonpharmacological therapy. Subjective and objective measures (weight gain, esophageal pH probe study, radionuclide gastric emptying scan) of gastroesophageal reflux were evaluated. Therapy with domperidone for 4 weeks was effective only in reducing the total number of reflux episodes in the two-hour postprandial period (p less than 0.01); however, it did not result in symptomatic improvement or significant improvement in other measures of gastroesophageal reflux or gastric emptying. After therapy for 8 weeks symptomatic improvement was reported in some patients who had denied improvement after 4 weeks of therapy, suggesting that more than 4 weeks of therapy may be required for some patients to obtain a clinical response. Mild self-limited diarrhea was reported by six patients (four domperidone, two placebo). We conclude that domperidone is tolerated by most infants and children with gastroesophageal reflux; however, 4 weeks of therapy was only minimally effective in producing objective improvement of gastroesophageal reflux and did not result in symptomatic improvement. Further studies of longer duration are needed to resolve the question raised by this study: that domperidone may be beneficial for patients with gastroesophageal reflux when given for more than four weeks.

Child↗
PubMed1991

Anergy in immature B lymphocytes. Differential responses to receptor-mediated stimulation and T helper cells.

We have compared the responses of purified neonatal and adult B lymphocytes to stimulation by anti-Ig antibodies, which are functional analogues of Ag, and by Th cells. Neonatal B cells are markedly deficient in proliferative responses to anti-Ig antibodies + IL-4 or to anti-Ig conjugated to dextran, both of which induce strong proliferation of adult B cells in the absence of T lymphocytes. Anti-Ig antibodies actually inhibit the functional responses of neonatal B cells, even to polyclonal stimuli such as LPS. However, Th cells induce both proliferation and Ig secretion by neonatal B cells in the presence of Ag that bind to B cell Ig and are subsequently presented by the B cells. Thus, in neonatal B lymphocytes, cross-linking of membrane Ig in the absence of Th cells has a net inhibitory effect, and this inhibition is overcome by T cell help. These results also suggest that unresponsiveness or tolerance to thymus-independent Ag is induced in the B cells themselves, but tolerance to thymus-dependent proteins resides primarily in the T cell compartment.

Aging↗
PubMed1991

Milk protein enteropathy after acute infectious gastroenteritis: experimental and clinical observations.

Animal models of allergic gastroenteropathy have defined both morphologic and physiologic changes that accompany the immune-mediated reaction to a dietary protein. In such models a broadening of the allergic response to other dietary proteins present in the gastrointestinal tract may occur during the localized anaphylactic reaction. The characteristic histologic intestinal findings of food protein-induced enteropathy may develop in selected infants with protracted diarrhea after infectious enteritis. Mechanisms underlying the induction of this response remain to be explained, but they may in part be similar to the broadening of the hypersensitivity response seen in experimental models of allergic enteropathy.

Acute Disease↗
PubMed1990

Divalent hapten-induced intestinal anaphylaxis in the mouse enhances macromolecular uptake from the stomach.

The capacity of the stomach to participate in anaphylaxis induced by the hapten N,N'-di-2,4,dinitrophenyllysine (di-DNP-lysine) was examined in BDF1 female mice immunized with dinitrophenylated Ascaris suum extract. Immunized animals underwent laparotomy and nontraumatic pyloric occlusion using a microvascular clamp. Following wound closure, animals were gavage-fed ovalbumin together with di-DNP-lysine. Other mice were subjected to systemic anaphylaxis by intravenous injection of di-DNP-lysine administered 1 min after gavage feeding of ovalbumin. The intravenous and intragastric administration of di-DNP-lysine led to a sixfold or greater increase in serum immunoreactive ovalbumin. Examination of 1-micron sections of gastric tissue from DNP-Asc-immunized and unimmunized mice showed an intact mucosal and submucosal architecture. A 75% increase in the number of mast cells below the muscularis mucosa was seen in immunized compared with unimmunized BDF1 mice. Gastric tissue sections from immunized mice challenged orally or intravenously with di-DNP-lysine showed compaction of erythrocytes in blood vessels, degranulation of mast cells, degenerative changes in the gastric epithelium, expulsion of mucus from gastric glands, and edema in the lamina propria. The present model may be useful for further defining the consequences of anaphylaxis on the development of immune responses to dietary antigens.

Anaphylaxis↗
PubMed1989

Nutritional support for pediatric patients with inflammatory bowel disease.

Pediatric patients with ulcerative colitis and Crohn's disease often suffer from malnutrition and growth failure. This is particularly true in pubertal children. Chronic insufficient nutrient intake is most often the cause of growth failure. Both parenteral nutrition and defined enteral formulas are available to rehabilitate patients with malnutrition and growth failure. Assessment of nutritional status and growth and the use of parenteral nutrition and defined enteral formulas to reverse malnutrition, growth failure, and inflammation in pediatric patients with inflammatory bowel disease are discussed.

Adolescent↗
PubMed1989

Divalent hapten-induced intestinal anaphylaxis in the mouse: uptake and characterization of a bystander protein.

We examined the mucosal barrier function during anaphylaxis induced by the hapten N,N'-di-2,4,dinitrophenyl-lysine (di-DNP-lysine) in BDF1 female mice immunized with dinitrophenylated Ascaris suum extract. Immunized mice were gavaged with 10 mg or 50 mg of ovalbumin (OVA) with or without N,N'-di-2,4,-DNP-lysine (di-DNP-lysine). Animals that received di-DNP-lysine underwent anaphylaxis and were observed to have significantly greater serum concentrations of immunoreactive OVA (iOVA) than control mice. The severity of anaphylaxis, which varied with the dose of di-DNP-lysine administered, influenced the uptake of OVA; greater amounts of iOVA were detected in serum of mice undergoing more severe anaphylaxis. On gel permeation of serum from both groups of mice, immunoreactive OVA was found to have a molecular size similar to native OVA. Di-DNP-lysine is a synthetic hapten that reliably induced anaphylaxis in sensitized animals challenged by gavage. Anaphylaxis resulted in the uptake into the circulation of greater quantities of an unrelated protein antigen present in the intestinal lumen. The protein antigen that was taken up into the circulation appeared to be intact and thus may have an influence on the development of the immune response, or lack thereof, to this bystander antigen.

Anaphylaxis↗
PubMed1989

Intestinal adaptation during lactation in the mouse. I. Enhanced intestinal uptake of dietary protein antigen.

Small quantities of dietary protein antigens cross the intestinal epithelium of the lactating mouse, enter the circulation, are transferred across the mammary gland into the milk and reach the suckling neonate. In this study, we sought to determine whether intestinal uptake of ovalbumin (OVA) was enhanced in lactating compared to control mice. OVA was administered by gavage under ether anaesthesia. Blood was obtained at 15, 30, 60 and 120 min and immunoreactive OVA (iOVA) measured by enzyme immunoassay. At 30 and 60 min, a three- to four-fold higher concentration of iOVA was detected in lactating compared to control mice. Because this increase in concentration of iOVA might be explained by changes in plasma volume, rate of clearance of OVA from the circulation or altered uptake from the intestine, plasma volume was measured by isotope dilution after i.v. injection of 125I-bovine serum albumin (BSA) and clearance was assessed by measuring elimination of OVA from the circulation after i.v. injection of OVA. In comparison to controls, plasma volume of Day 7-10 lactating mice was increased two-fold and no difference in clearance rate was noted. Because the increase in concentration of iOVA in lactating mice is several-fold greater than in controls, we suggest that increased intestinal uptake of the protein occurs during lactation.

Animals↗
PubMed1988

Attenuation of rat conjunctival response by repeated hapten applications.

Attenuation of the rat conjunctival response by repeated topical challenge with dinitrophenyl (DNP) hapten was demonstrated in our study. Adult rats were immunized by intraperitoneal injections of dinitrophenylated Ascaris suum extract (DNP-Asc) and alum. Serum levels of anti-DNP homocytotropic antibody were determined by passive cutaneous anaphylaxis in rats prepared with antibody 48 hours earlier. In other animals, topical challenge was performed by applying N,N'-di-2,4-DNP-L-lysine (di-DNP-lysine) in phosphate-buffered saline (PBS) to one eye; PBS alone was applied to the fellow eye. The degree of conjunctival reaction was assessed clinically, and ocular tissues were processed for histological evaluation. The intensity of the conjunctival reaction and extent of mast cell degranulation were significantly greater after one challenge with di-DNP-lysine than after multiple challenges. In the multiple-challenge group, the contralateral eye remained responsive to a single challenge with di-DNP-lysine. These results may have implications for therapeutic interventions in ocular anaphylaxis.

Anaphylaxis↗
PubMed1987

TPN cholestasis in premature infants: the role of parenteral nutrition solutions.

In conclusion, cholestatic liver disease is a frequent complication in low birthweight infants who receive parenteral nutrition. The etiology of this disorder is probably multifactorial. Although the composition of parenteral nutrition solutions may play a role in the development of cholestasis, at this time, there are limited data to suggest how to change parenteral solutions to alter the course of this disease. Further work is necessary to elucidate therapies to prevent and treat this disorder.

Amino Acids↗