Search PubMed⌕ Search

Biomedical subjects

J N Udall

Publications and source records attributed to J N Udall.

At least 55 records · Page 3Linked to original sources
PubMed1989

Trypsin uptake and trypsin-inhibitor complexes. Differences between suckling and adult rats.

Previous studies have suggested that both newborn animals and humans absorb intact proteases from the intestine in greater amounts than do adults. Absorbed proteases are rapidly complexed in plasma by several inhibitors which inactivate free proteases. In order to confirm increased intestinal uptake in newborns, we evaluated the plasma trypsin activity in both 2-week-old and adult rats following a trypsin feed. In addition, we studied the interaction between absorbed trypsin and rat trypsin inhibitors (alpha-macroglobulin, alpha 1-inhibitor 3, and alpha 1-protease inhibitor) by determining the concentration of alpha-macroglobulin complexes both in vivo and in vitro following trypsin feeding and by evaluating the amount of trypsin activity complexed with the different inhibitors. In vivo experiments demonstrated that trypsin uptake was significantly increased in newborns compared to adult rats and that 50-70% of plasma trypsin activity was associated with alpha 1-inhibitor 3. Increased uptake was not accompanied by increased alpha-macroglobulin complexes. In vitro trypsin incubation did not lead to increased alpha-macroglobulin complexes until the other inhibitors were removed. These findings suggest that newborns have increased trypsin uptake, and the trypsin initially binds to alpha 1-inhibitor 3 before being transferred to alpha-macroglobulin for clearance. Further studies are needed in order to understand the interaction between intestinal uptake and plasma inhibition of absorbed proteases.

Aging↗
PubMed1987

Elevated levels of alpha 2-macroglobulin-protease complexes in infants.

Proteases form stable complexes with alpha 2-macroglobulin (alpha 2-MG) in human plasma. We previously showed that the intestine of newborn rabbits takes up greater amounts of proteases than the intestine of weaned animals, and we suggested that the same phenomenon might occur in the human newborn. To test this possibility, alpha 2-MG complexes were sought in plasma from 3-day-old human infants and adults. In addition, the level of alpha 2-MG was measured. The concentration of alpha 2-MG complexes and of alpha 2-MG was significantly increased in the plasma of infants compared to adults. We suggest that the elevated levels of alpha 2-MG complexes in infants may reflect the enhanced uptake of proteases from the intestine. In addition, there may also be decreased clearance of complexes by the mononuclear phagocytic system in infants. The elevated levels of alpha 2-MG in the infant may reflect a response to the need for neutralizing proteases absorbed from the intestine.

Adult↗
PubMed1986

Behavioral effects of sucrose on preschool children.

Despite speculation that sucrose consumption affects behavior, little empirical information is available. Accordingly, this study investigated the effect of sucrose consumption on the behavior of eight preschool children. Children were tested individually using a double-blind, crossover design. On separate mornings each child received 6 ounces of juice, sweetened on one morning with sucrose and on the other with an artificial sweetener. Children were observed for 90 minutes following the drinks, alternating between 15-minute sessions of work on structured tasks and 15-minute sessions of free play. Following the sucrose drink the children showed a decrement in performance in the structured testing situation, and they demonstrated more "inappropriate" behavior during free play. These differences in behavior were most pronounced approximately 45 to 60 minutes after the drinks. Thus, the study provides objective evidence in young children of a rather subtle, yet significant, time-dependent behavior effect of sucrose ingestion.

Attention↗
PubMed1985

Liver disease in alpha 1-antitrypsin deficiency. A retrospective analysis of the influence of early breast- vs bottle-feeding.

We identified children with alpha 1-antitrypsin deficiency from the medical records of the Massachusetts General Hospital and Children's Hospital, Boston, and investigated their early feeding history. Between 1969 and 1983, forty children with the deficiency were seen at one or both hospitals. Clinical information was obtained from hospital records and from questionnaires mailed to the parents. Complete morbidity, mortality, and early feeding data were obtained for 32 of the children who were born at 38 to 42 weeks' gestation and whose weights were appropriate for gestational age. We compared the presence of severe liver disease and the death rate of those who had been exclusively breast-fed for one month with those who had been bottle-fed. Severe liver disease was present in eight (40%) of bottle-fed and one (8%) of breast-fed infants. Twenty-four of the 32 infants were still alive at the termination of the study; 12 had been breast-fed and 12 bottle-fed during their first month of life. All eight deceased infants had been bottle-fed. The mortality rate in the bottle-fed group was significantly greater than that of the breast-fed group. Our study suggests that breast-feeding may offer some protection against severe liver disease and early death in infants with alpha 1-antitrypsin deficiency.

Birth Weight↗
PubMed1985

Development of gastrointestinal mucosal barrier. VII. In utero maturation of microvillus surface by cortisone.

When studying mucosal barrier function of developing animals, we noted that intestinal microvillus membranes (MVM) of newborn animals differ in their fluidity and binding characteristics to lectins compared with adult MVM. To further investigate these differences and determine whether maturation of the microvillus surface could be accelerated in utero, pregnant rats were given intraperitoneal cortisone beginning on the 17th day of gestation. Control and cortisone-treated animals were allowed to deliver normally, and the small intestines from newborns were used to isolate MVM. Microvillus membrane surface characteristics were evaluated by employing an 125I-labeled fucose-specific lectin, Ulex europeus (UEA). Changes in MVM proteins were monitored by disaccharidase activities and sodium dodecyl sulfate-polyacrylamide electrophoresis. MVM fluidity was accessed using a 5-doxyl stearic acid label and electron-spin-resonance spectroscopy. Results from these studies indicate that the birth weights of newborn rats exposed to cortisone in utero were significantly reduced; sucrase activity was prematurely induced and specific activities of lactase and maltase were enhanced in the intestines of the cortisone-treated newborns as contrasted with control animals. Furthermore, binding of 125I-UEA to MVM was greatly increased in treated animals. MVM fluidity decreased (P less than 0.001) compared with control animals and resembled the structural characteristics of more mature MVM. These results suggest that cortisone exposure in utero accelerate maturation of the microvillus surface of enterocytes.

Animals↗
PubMed1985

The effect of short-term starvation on mucosal barrier function in the newborn rabbit.

The compromised human newborn frequently presents with overwhelming feeding problems which lead to inadequate intake. These problems may affect the development of the small intestine, especially mucosal barrier function, leading to increased infections and susceptibility to allergens. To study this, an animal model was established using neonatal rabbits deprived of nutrients from birth until 72 h. Mucosal barrier function was compared in deprived and control (naturally fed 72-h-old animals) rabbits by measuring immunoreactive bovine serum albumin in serum 4 h after intragastric infusion of crystalline bovine serum albumin (200 mg/100 g body weight). Trypsin activity was measured in rinse fluid obtained from the small intestine. Representative sections of jejunum from control and experimental animals were formalin fixed and stained with hematoxylin and eosin for morphologic comparison. Following the bovine serum albumin feeding, a significantly increased serum immunoreactive bovine serum albumin and significantly decreased trypsin-like activity of the small intestinal rinse fluid was noted in starved animals compared to controls. In addition, the enterocytes of malnourished animals were more cuboidal and contained fewer and smaller supranuclear granules on microscopic examination than the enterocytes of controls. This study suggests that short-term starvation in newborns affects mucosal barrier function. Acute starvation may place newborns at increased risk for infections and allergic disease.

Acute Disease↗
PubMed1984

The tolerance and nutritional value of two microfungal foods in human subjects.

The tolerance of human subjects to two microfungal food products was studied in separate double-blind cross-over studies. As an addition to the subject's usual diets, cookies with and without 20 g of a product from Fusarium graminearium were fed to a group of 100 individuals daily. In a second study, cupcakes with and without 10 g of Paecilomyces variotii were given daily to 50 individuals. Mild rashes possibly related to one of the microfungal food products occurred in two individuals fed P variotii. Except for a decrease in serum cholesterol during the F graminearium study, no significant changes were noted in 17 serum constituents. During nutritive value studies, digestibility, biological value, and net protein utilization were calculated for the two microfungal proteins and for milk. The values for milk were 95, 85, and 80%, respectively. The values for F graminearium were 78, 84, and 65%, respectively. For P variotii corresponding figures were 81, 67, and 54%. On the basis of these results both microfungal foods may be deemed safe for human consumption at the levels tested.

Adolescent↗
PubMed1984

Intestinal uptake of trypsin in newborn and weaned rabbits.

Earlier studies have shown that the uptake of intact proteins from the intestinal lumen into the systemic circulation is increased in neonates. The present experiments tested the uptake of trypsin in newborn compared with 4-wk-old weaned rabbits. Trypsin (200 mg/100 g body wt) was administered by gavage to newborn and 4-wk-old rabbits. Four hours later, the tryptic activity and immunoreactive trypsin (i-trypsin) content of serum from newborn rabbits exceeded that of the older animals. After Sephadex G-200 gel filtration of serum from animals gavaged with trypsin, tryptic activity was detected in the excluded volume (presumably reflecting trypsin bound to alpha 2-macroglobulin), and i-trypsin was detected in the included volume (presumably reflecting trypsin bound to alpha 1-antitrypsin). In vitro experiments demonstrated that large amounts of trypsin were required to overwhelm the antiprotease present in normal rabbit serum. We suggest that complete or partial deficiencies of serum protease inhibitors may permit proteases taken up from the intestinal lumen of the neonate to circulate, reach the liver, and induce tissue injury at this site.

Animals↗
PubMed1984

Development of the gastrointestinal mucosal barrier. IV. The effect of inhibition of proteolysis on the uptake of macromolecules by the intestine of the newborn rabbit before and after weaning.

Prior to weaning, young rabbits take up increased amounts of macromolecules across the intestine and into the circulation. The increased macromolecular uptake may be due in part to decreased intestinal proteolysis in these animals. To assess the effect of intestinal proteolysis on macromolecular uptake, we initially tested the basal level of intestinal trypsin-like activity in newborn and 4-week-old weaned animals. The newborn rabbits had significantly less trypsin-like activity in their small intestinal rinse fluid compared to the 4-week-old animals. Subsequently, we tested the effect of the protease inhibitor, aprotinin, on small intestinal rinse fluid trypsin-like activity and the intestinal uptake of bovine serum albumin (BSA). Newborn and 2-week-old rabbits were force-fed with aprotinin or phosphate-buffered saline (PBS) followed after several hours by BSA. Animals pretreated with aprotinin had significantly decreased levels of small intestinal rinse fluid trypsin-like activity and increased concentrations of immunoreactive BSA (iBSA) in plasma compared to PBS-pretreated control animals. 4-week-old weaned rabbits force-fed with equivalent amounts (on the basis of body weight) of aprotinin and BSA had significantly decreased trypsin-like activity in small intestinal rinse fluid compared to control animals. However, plasma iBSA was not significantly different from that of PBS-pretreated controls. These findings suggest that the inhibition of intestinal proteolytic activity is associated with increased macromolecular uptake in young rabbits prior to weaning. At weaning, suppression of proteolytic activity was not associated with increased macromolecular uptake detectable with the same assay procedures used successfully in the newborn animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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↗
PubMed1982

Transport of proteases across neonatal intestine and development of liver disease in infants with alpha-1 antitrypsin deficiency.

The transport of macromolecules from the intestinal lumen into the systemic circulation is considerably greater in neonatal than in adult animals. Transport of both immunoglobin and non-immunoglobulin proteins is enhanced. It is postulated that luminal enzymes are also transported into the systemic circulation of the neonate and reach the liver. In the absence of protease inhibitors, such as occurs in alpha 1-antitrypsin (alpha 1-AT) deficiency, these intestinal enzymes may cause inflammation and, eventually, fibrosis of the liver. If this hypothesis is valid, treatment with trypsin inhibitors and elemental diets until the excessive macromolecular transport across the intestine ceases may help to prevent the liver disease associated with (alpha 1-AT) deficiency.

Biological Transport↗
PubMed1981

Development of gastrointestinal mucosal barrier. I. The effect of age on intestinal permeability to macromolecules.

Indirect evidence has suggested that increased quantities of antigen may penetrate the intestinal mucosa and enter the systemic circulation during the newborn period compared to adult life. However, no direct measurement of macromolecular transport has been reported as a function of perinatal age. To study this process, we administered 100 mg of tritiated bovine serum albumin ([3H]BSA) by gavage to rabbits at birth, one wk, 2 wk, 6 wk, and one year of age and measured plasma radioactivity 4 hr after gavage. Plasma concentration of trichloroacetic acid insoluble radioactivity and immunoreactive bovine serum albumin radioactivity decreased significantly after one wk of age. When adult animals were gavaged with the same amount of [3H]BSA per body weight as the one-wk-old animals, they failed to transport as much of the antigen as the younger animals. This study, therefore, provides objective evidence that the intestinal mucosal barrier of newborns may be incompletely developed at birth and allow increased intestinal transport of antigens into the circulation.

Age Factors↗
PubMed1981

Development of gastrointestinal mucosal barrier. II. The effect of natural versus artificial feeding on intestinal permeability to macromolecules.

We have recently reported that the intestinal transport of intact macromolecules into the circulation decreases with age presumably due to maturation of mucosal barrier factors. To extend this observation and determine the effect of natural versus artificial feeding on maturation of intestinal mucosal "barrier function" we conducted experiments which assessed both macromolecular transport and epithelial cell morphology. To study barrier function, we gavage fed a physiologic quantity (100 mg) of bovine serum albumin (BSA) to weight-matched breast- and bottle-fed infant rabbits at 1 and 2 wk of age and quantitated intestinal macromolecular transport by measuring circulating plasma concentrations of the intact antigen 4 hr later. a significant decrease (P less than 0.02) in immunoreactive bovine serum albumin (I-BSA) concentration was noted in breast-fed (6.12 +/- 0.77 micrograms I-BSA per ml plasma) compared with bottle-fed (9.19 +/- 0.93 micrograms I-BSA per ml plasma) animals at one wk. However, at 2 wk, no difference could be demonstrated between the two groups. Furthermore, small intestinal morphology evaluated by light and electron microscopy was similar in both groups each age. To determine if the lower plasma I-BSA noted at one wk in naturally fed animals was related to the presence of anti-BSA antibodies in breast milk and/or in plasma of the pups, breast milk and plasma from the breast-fed animals was evaluated by counterimmunoelectrophoresis and hemagglutination. No anti-BSA antibodies were detected. Moreover, plasma from breast- and artificially fed rabbits not gavage fed BSA contained no I-BSA. These data suggest that intestinal transport of antigens in the immediate neonatal period is decreased earlier in breast- as compared to bottle-fed animals. Therefore, we suggest that breast milk may exert a protective function to control the transport of potentially antigenic molecules into the systemic circulation of newborn animals by either facilitating the early maturation of intestinal barrier function or by providing passive barrier factors until the newborn's natural barrier can develop.

Animal Feed↗