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R E Kleinman

Publications and source records attributed to R E Kleinman.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1986

Transfer of protein antigens into milk after intravenous injection into lactating mice.

We investigated the transfer of bovine serum 125I-albumin (125I-BSA), bovine 125I-gamma-globulin (125I-BGG), 125I-ovalbumin (125I-OVA), and 125I-beta-lactoglobulin (125I-BLG) from the blood into the milk of lactating mice. Equal amounts (by weight) of the radiolabeled proteins were injected intravenously into mice 1 wk postpartum. Total radioactivity, trichloroacetic acid-precipitable radioactivity, and specifically immunoprecipitable radioactivity were measured in serum, mammary gland homogenate, and milk. Clearance of immunoreactive OVA (iOVA) and iBLG from the circulation was more rapid than iBSA and iBGG. The radioactivity in mammary tissue associated with BSA and BGG was greater than 70% immunoprecipitable throughout the 4-h test interval; 125I-OVA and 125I-BLG were less than 12% precipitable 1 and 4 h after injection. In milk obtained at 4 h, there was an approximately 10-fold greater accumulation of iBSA or iBGG than of iOVA or iBLG. These experiments demonstrate that protein antigens differ in their ability to transfer from maternal circulation into milk. The transfer into milk appeared to be in proportion to persistence of the antigens in the maternal circulation.

Animals↗
PubMed1986

Influence of circulating maternal antibody on the transfer of dietary antigen to neonatal mice via milk.

125I-BSA injected intravenously into lactating mice persisted in the circulation for 4 h, entered the mammary gland, and was transferred to the neonate via the milk. When injected with anti-BSA antibodies, it was rapidly cleared from the circulation. Although animals receiving anti-BSA antibodies transferred more radioactivity to the neonate via the milk, the radioactivity was not TCA-precipitable or bound to staphylococcal protein A, nor was it immunoreactive. These findings suggest that circulating maternal antibody can limit the transfer of specific protein antigen from mother to newborn.

Animals↗
PubMed1985

Intestinal resection in the neonatal rat: stimulus for precocious intestinal maturation.

To investigate whether intestinal resection accelerates mucosal maturation in suckling rats, macromolecular absorption, sucrase and lactase activity, RNA/DNA ratios, and intestinal morphology were determined 5 days after partial small intestinal resection or intestinal transection in 15-day-old rats. Villous height and crypt depth, lactase and sucrase activity, and RNA/DNA ratios were significantly increased in remaining intestine in animals that underwent surgery. These animals, together with normal control animals, were also gavaged with 100 mg bovine serum albumin, and serum levels were determined after 2.5 h. Mean serum levels of bovine serum albumin were 0.135 +/- 0.034 micrograms/ml/cm of residual intestine after transsection, 0.257 +/- 0.078 micrograms/ml/cm after resection, and 0.404 +/- 0.030 micrograms/ml/cm in controls. These studies demonstrate that intestinal resection during the suckling period of the infant rat results in several morphologic and physiologic changes that resemble precocious maturation of the small intestine.

Animals↗
PubMed1985

Food proteins and gut mucosal barrier. III. The influence of lactation and prolactin on the in vitro binding and uptake of bovine serum albumin and ovalbumin in the rat jejunum.

The everted gut sac technique was used to study adaptive changes in small intestinal handling and uptake of radiolabeled bovine serum albumin and ovalbumin during lactation in rats. Binding and uptake of both proteins by the gut sacs of lactating animals were significantly less, compared to controls (p less than 0.001, after 30 min of incubation). This change was reversible after lactation ceased. The differences could not be explained by oral immunization since there were no specific antibodies found in sera, mucosal extracts, or breast milk; prior exposure to the protein did not alter the observed differences. No differences in mucosal breakdown of bovine serum albumin could be demonstrated by precipitation with trichloroacetic acid (10%); an increase in breakdown of ovalbumin in the lactating animals was shown under the same conditions. The injection of prolactin produced differences in bovine serum albumin binding and uptake similar to the ones observed in the lactating group (p less than 0.01, after 30 min of incubation, compared to solvent-injected controls). Since food protein antigen binding, breakdown and uptake are functions of the local intestinal host defense, these findings suggest that there are adaptive changes of the gut mucosal barrier during lactation which decrease the transfer of dietary antigens from mother to infant. The adaptation of the maternal intestinal host defense was shown to be influenced by prolactin.

Animals↗
PubMed1984

Antigen processing and uptake from the intestinal tract.

We have attempted, in this discussion, to summarize the processes and evidence for absorption of antigenic macromolecules in both animals and humans, comparing the infant to the adult. The mature gut retains the capacity to absorb macromolecules by an energy-dependent pinocytotic mechanism similar to that described for the transport of immunoglobulins and other enteric antigens in certain mammalian species in the neonatal state. The vast majority of adults show no ill effects as a result of this physiologic phenomenon. However, when increased (pathologic) quantities of antigenic macro-molecules gain access to the body because of a derangement in the intraluminal digestive process, or because of a defect in the mucosal barrier, both of which are present in the immature intestine, macromolecular absorption may be altered and result in either local intestinal or systemic disorders.

Animals↗
PubMed1983

Passive transplacental immunization: influence on the detection of enteric antigen in the systemic circulation.

Female New Zealand white rabbits were immunized with bovine serum albumin (BSA). Litters which had never suckled, from immunized and nonimmunized rabbits, were tested at 4 h, 24 h, and 48 h after birth. After obtaining an initial blood sample, all infant rabbits were gavaged with 100 mg of BSA plus tracer amounts of [125I]-BSA. Infant rabbits born to immunized mothers had circulating antibody before feeding and pups from nonimmunized mothers had no detectable antibody to BSA. The fed animals were sacrificed at 3-4 h after gavage. Serum obtained from cardiac and portal blood was examined for protein bound radioactivity and for the presence of immunoreactive BSA (iBSA) by electroimmunodiffusion. All infant rabbits had radioactivity in their blood. Approximately 50% of the radioactivity in the serum of infant rabbits from nonimmunized does was protein bound and all of these animals had iBSA in portal or cardiac serum samples. Of the 33 infant rabbits from immunized does, only four had protein bound radioactivity in their serum. This radioactivity appeared to be associated with circulating immune complexes of [125I]-BSA-rabbit-anti-BSA antibodies. None of the 33 infant rabbits had iBSA detectable by electroimmunodiffusion.

Animals↗
PubMed1983

The role of developmental immune mechanisms in intestinal allergy.

Maternal transplacental antibody, circulating antibody and secretory antibody may influence neonatal processing of enteric antigen which in turn may influence the development of both a systemic and mucosal immune response later in life. Immune responses of different isotypes to enteric antigens appear to require the passage of antigen through the specialized cells overlying by lymphoid aggregates. As this schema demonstrates (Figure 7), transplacental antibody present in the infant's intestinal mucosa may complex with antigen and cause it to be recognized in a different way. Post-partum, maternal serum antibody may affect the passage of foreign antigens into the breast milk, and finally those antigens that are present in the milk may also form immune complexes upon arriving in the milk and again affect the processing of antigen in the infant's intestine.

Animals↗
PubMed1981

Enteric alimentation in specialized gastrointestinal problems: an alternative to total parenteral nutrition.

This review has focused on the enteric nutritional management of infants with abnormalities of volume tolerance, digestion, and/or absorption. The necessity of individually assessing the patient's needs vis-à-vis the alternatives cannot be overemphasized. In some patients, enteral feedings are precluded and IV alimentation is the only alternative. For a discussion of IV nutrition options we refer the physician to an excellent review. We also wish to emphasize that in a review of this nature we cannot discuss the relative virtues of closely related formulas. We therefore encourage the physician to obtain product handbooks from the manufacturers.

Animals↗
PubMedDate not supplied

Hepatobiliary clearance of IgA immune complexes formed in the circulation.

The formation and clearance of circulating IgA immune complexes from blood to bile was investigated in this study. The i.v. injection of either MOPC-315, an IgA M-component with antidinitrophenyl (DNP) specificity, or TEPC-15, an IgA M-component of a different specificity, was followed by i.v. injection of 125I-DNP10-bovine serum albumin (BSA) as the antigen. The formation and clearance of IgA immune complexes in the circulation of MOPC-315-treated, but not TEPC-15-treated animals was demonstrated by immunoprecipitation with polyacrylamide beads coated with rabbit anti-mouse IgA. IgA-125I-DNP10-BSA complexes were identified in the bile from MOPC-315-treated, but not TEPC-15-treated animals utilizing this same immunoprecipitation technique. These observations suggest that the liver or bile ducts transport IgA immune complexes from blood into bile. The clearance of 125I-DNP10-BSA from the circulation was documented by coprecipitation with rabbit anti-BSA and BSA. The clearance of this circulating antigen was slower in the MOPC-315-treated than in the TEPC-15-treated animals suggesting that under the conditions of the present experiment, circulating antigen is cleared more slowly after IgA immune complex formation.

Animals↗
PubMedDate not supplied

The liver: an integral part of the enteric mucosal immune system.

The inclusion of the liver and biliary tract as an integral part of the enteric mucosal immune defense has come about in the past 5 years as a result of experimental studies in laboratory animals. The importance of secretory IgA and IgA immune complexes in the generation of an immune response and their participation in the immune exclusion of potentially pathogenic molecules and organisms are areas of active investigation. The transport of IgA and IgA immune complexes by the liver from serum to bile may provide another means of immune-mediated host defense against enteric pathogens.

Animals↗
PubMedDate not supplied

The effect of bile duct obstruction on the clearance of circulating IgA immune complexes.

The clearance of circulating IgA immune complexes following acute bile duct obstruction was investigated in this study. IgA immune complexes were formed in vitro from MOPC-315, an IgA M-component with anti-dinitrophenyl (DNP) specificity, and 125I-DNP10 bovine serum albumin (BSA). Eighteen hours after laparotomy during which the common bile duct was either identified only or identified and ligated, the IgA immune complexes were injected intravenously. Groups of bile duct-ligated and bile duct-patent rats were also injected intravenously with IgG anti-DNP-125I-DNP10BSA immune complexes and 125I-bovine liver beta-glucuronidase to assess the hepatic clearance of materials not dependent on an intact biliary system. Clearance of IgA immune complexes was delayed after bile duct ligation. Although the clearance of IgA immune complexes was delayed, only 10% of these complexes remained in the circulation at 3 hr. The clearance of IgG immune complexes and beta-glucuronidase was not affected by ligation. These experiments demonstrate the physiologic importance of a patent bile duct in the normal clearance of IgA immune complexes in the rat. The observation that clearance is delayed, but not completely inhibited by bile duct ligation suggests that alternate mechanisms exist for removing IgA immune complexes from the circulation.

Animals↗