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Biomedical subjects

J M Diamond

Publications and source records attributed to J M Diamond.

At least 19 recordsLinked to original sources
PubMed1992

Upregulation of nutrient transport in fetal rabbit intestine by transamniotic substrate administration.

Delivery of nutrients to the developing fetal gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. To examine the effect of intrauterine nutrient administration on the uptake capacity of the intestine, 16 maternal rabbits underwent bilateral ovarian-end transamniotic catheter placement on gestational Day 24. Study fetuses received a galactose solution; the contralateral controls received mannitol, a physiologically inert carbohydrate. Infusions were continued until Day 30 when an everted sleeve technique was used to measure radiolabeled uptake of both galactose and glucose in the proximal, middle, and distal small intestine. Mucosal scrapes were obtained, weighed, and the percentage of weight was calculated. Results were analyzed by ANOVA and Student's t test with P less than 0.05 being considered significant. There were 2 maternal deaths with 11 fetal pairs surviving (79%). There was increased uptake of galactose in the study fetuses compared to controls reaching significance in the middle and distal segments. Similarly, glucose uptake was significantly increased in the proximal and distal segments. Mucosal weight was increased in all regions, reaching significance in the proximal segment. Total intestinal uptake of galactose and glucose was significantly increased in the study fetuses compared to controls. Intraamniotic galactose infusion caused not only upregulation of its own mucosal transport but also that of glucose, along the entire fetal small intestine, achieving statistical significance particularly in distal segments. Fetal implications for transamniotic feeding are under investigation.

Amnion↗
PubMed1991

Uptake and distribution of continuously infused intraamniotic nutrients in fetal rabbits.

Nutrient delivery via the fetal gastrointestinal tract may be a potential prenatal treatment for intrauterine growth retardation. Uptake from continuous intraamniotic infusions with nutrient incorporation into developing fetal tissues has not previously been shown. To study this, ovarian-end fetuses of 18 time-mated rabbit does underwent amniotic cavity catheterization and either esophageal ligation (EL) or sham operation (SH) on gestational day 23 (term, 33 days). Saline plus 14C D-glucose and 3H proline were infused into the amniotic fluid for 4 days. Nutrients absorbed by the EL fetus represent only those taken up into the maternal circulation and subsequently redelivered hematogenously to the fetus. Radioactivity of fetal blood and organs was determined using a liquid scintillation counter. All infused does and 10 of 18 infused fetuses (56%) survived the entire study period. In SH fetuses, uptake of 14C per mg of tissue was highest in the lung and significantly greater in the stomach, jejunum, ileum, and lung than in fetal blood (P less than .05). Uptake of 3H per mg of tissue was also highest in the lung and significantly greater than fetal blood in the stomach, small intestine, lung, and liver (P less than .05). Each organ's 14C and 3H uptake was greater in SH than in EL fetuses (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1991

Dietary regulation of intestinal brush-border sugar and amino acid transport in carnivores.

The ability of omnivores and herbivores to regulate reversibly their intestinal brush-border nutrient transporters is functionally related to the unpredictably variable composition of their natural diets. To determine whether carnivores are able similarly to regulate the activities of their intestinal nutrient transporters, we fed to three species of vertebrates that are carnivorous as adults (cats, mink, and leopard frogs) diets with either at least 50% digestible carbohydrate or with negligible carbohydrate levels. Rates of transport for the sugars glucose and fructose and the amino acids (AAs) aspartate, leucine, lysine, and proline were measured throughout the intestine (only proline and glucose in the frogs) by an in vitro everted-sleeve method. Although all three species consume much carbohydrate during early development, only the mink was able to regulate sugar transporter activity in response to changes in levels of dietary carbohydrate. In contrast, the sugar transporters of the cat were unresponsive to varying carbohydrate levels, and long-term feeding of a high-carbohydrate diet caused down-regulation of sugar transport in frogs. Of the three species, only the mink is a member of a family that includes omnivorous species, whereas all members of the families to which the cat and frog belong are carnivorous as adults. All three species were able to regulate rates of AA transport, though the patterns and magnitude of the responses differed between species as well as between AAs, suggesting independent regulation of some AA transporters.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

Adaptive changes in ileal mucosal nutrient transport following colectomy and endorectal ileal pull-through with ileal reservoir.

To study ileal mucosal function when used in an ileal reservoir or ileostomy, eight dogs underwent colectomy and endorectal ileal pull-through with creation of a lateral ileal reservoir. Ileal mucosal biopsy specimens were obtained at the initial operation, from the ileostomy and dormant ileal reservoir at the time of ileostomy closure, and from the reservoir 3 months later. Rates of uptake for four different substrates were determined by radioactive absorption techniques. Absorption of carbohydrates, amino acids, and bile acids was markedly decreased and of short-chain fatty acid mildly reduced in ileal reservoir mucosa compared with normal ileum, largely owing to a decrease in reservoir absorptive surface area from flattened villi. Reservoir uptake of the substrates evaluated within 3 months after operation was similar to that for normal colonic mucosa. Uptake of all measured substrates from ileostomy mucosa approximated that of normal ileum. The use of short ileal reservoirs and the avoidance of stasis may favor reduced bacterial growth and increased nutrient absorption.

Adaptation, Physiological↗
PubMed1990

The future of DNA-DNA hybridization studies.

This article draws on many vertebrate examples to assess the future of DNA-DNA hybridization studies. I first discuss whether applications of the method have reached the point of diminishing returns, or rather the start of a great leap forward, in our evolutionary understanding. Vertebrate groups whose relationships are especially likely to be illuminated include parrots, pigeons, bats, pinnipeds, mammalian carnivores, frogs, and rodents. There are at least two reasons why classifications based on DNA-DNA hybridization may prove to differ from classifications based on particular character, whether these be noncoding DNA sequences or protein sequences or anatomical characters. Because evolutionary relationships can now be deduced independently of anatomical characters, this should permit a renaissance in comparative anatomical studies of adaptation. The origin of major functional shifts from changes in a small fraction of the genome is illustrated by polar bears, sea otters, warblers, vultures, and especially by humans.

Animals↗
PubMed1990

Fetal rabbit intestinal absorption: implications for transamniotic fetal feeding.

Delivery of nutrients to the fetus via the developing gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. Previous studies have demonstrated significant increases in fetal length and weight following continuous intraamniotic nutrient infusions in animals. The ideal composition of intraamniotic feedings has yet to be determined. Thirteen time-mated rabbit does underwent ceserean section between gestational days 27 and 33 to deliver 54 fetuses. The everted intestinal sleeve technique was used to measure radiolabeled carbohydrate and amino acid uptake rates from 1-cm segments of midjejunum. Uptake of galactose was more than double that of glucose and fructose. Active uptake of glucose, fructose, and galactose increased by 3.3-fold, 6.2-fold, and 2.1-fold, respectively, during the final 7 days of gestation when expressed as uptake per mg intestine. In contrast, uptake of the amino acids leucine, lysine, and proline decreased by 41%, 34%, and 17%, respectively, during the final 5 days of gestation. The demonstrated changes in intestinal absorption and nutrient delivery in the rabbit model, during the last days of gestation, suggest that certain substrates are absorbed more rapidly than others. Galactose may be the preferred intraamniotic carbohydrate for fetal growth.

Amino Acids↗
PubMed1990

Changes in mucosal nutrient transport in small and large ileal reservoirs after endorectal ileal pullthrough.

It has been hypothesized that, following colectomy and endorectal ileal pullthrough with ileal reservoir (PTR), reservoir tissue might lose some of its normal nutrient transport capacity and assume properties of the colon. Whether reservoir size influences the expected alterations in normal mucosal absorption and thus contributes to changes in intraluminal ecology has not previously been investigated. To study this, the everted intestinal sleeve technique was used to measure uptake of four nutrients in two groups of dogs who underwent PTR: five with a small (5 cm) lateral reservoir and five with a large (18 cm) reservoir. Mucosal samples were taken from normal ileum and colon and from reservoirs 3 months postoperation. Active uptake of carbohydrates (glucose), amino acids (proline), and bile acids (taurocholate) and passive uptake of short chain fatty acids (propionate) were markedly decreased in mucosa of both reservoir sizes compared to normal ileum (P less than 0.05, t test) and more closely approximated that of normal colon. Uptake of glucose, proline, and taurocholate in large reservoirs was significantly less than that in small reservoirs (P less than 0.05). We conclude that (1) ileal reservoir mucosa has a significantly reduced capacity for nutrient uptake, (2) ileal mucosa in small reservoirs shows higher nutrient uptake rates than mucosa in large reservoirs, and (3) short, well-emptying reservoirs appear best suited to optimizing the intraluminal environment and thus enhance reservoir function when performing PTR.

Animals↗
PubMed1990

Ontogenetic development of nutrient transporters in bullfrog intestine.

The ratio of intestinal glucose (Glc) to amino acid (AA) transporter activity rises with age in animals of species in which the ratio of dietary carbohydrate to protein also rises. Does this shift function to match transporter activity to current dietary substrate levels or to the high AA requirements of young growing animals? We compared intestinal brush-border uptake of Glc and the AA proline (Pro) in adult and tadpole bullfrogs, since with age this species changes from an herbivore to a carnivore and hence its dietary carbohydrate-to-protein ratio decreases rather than increases. Like typical adult herbivores, tadpoles have a long, highly coiled, narrow-bore, thin-walled intestine with a long, heavy colon, whereas adult bullfrogs have a short, wide-bore, thick-walled intestine typical of carnivores. The ratio of Glc to Pro uptake capacity is essentially the same in adults as in larval tadpoles and is typical of carnivores but unprecedently low for herbivores. This suggests that both functions proposed for developmental shifts of Glc and AA transport in other species are significant and that their effects cancel each other in bullfrogs. Transporter kinetic constants vary predictably with developmental stage. Intestinal daily uptake capacity is comparable to actual daily intake for Glc in adults and for Pro in both tadpoles and adults but is much lower than intake for Glc in tadpoles, probably because most carbohydrate ingested by tadpoles is in the form of high molecular weight polymers that are not utilized.

Aging↗
PubMed1990

Ontogenetic development of transporter regulation in bullfrog intestine.

Intestinal nutrient transporter activity is adapted to dietary substrate levels on three time scales: reversibly, within an adult individual, to rapid dietary changes; developmentally, to normal ontogenetic changes in diet; and evolutionarily, among carnivores, omnivores, and herbivores, to a species' natural diet. Does the capacity for rapid reversible adaptation itself vary adaptively during development? Substrate-dependent regulation would make functional sense in herbivorous/omnivorous tadpoles in which dietary substrate levels fluctuate unpredictably, but would serve no purpose in strictly carnivorous adult bullfrogs in which dietary protein is always high and carbohydrate is low. Hence, we fed premetamorphosis bullfrog tadpoles either boiled lettuce (high in carbohydrate, low in protein) or ground beef (high in protein, low in carbohydrate). Gut weight relative to body weight was higher in lettuce-fed tadpoles. Glucose uptake was greater and proline uptake slightly less in lettuce-fed than in beef-fed tadpoles. The resultant ratio of glucose uptake capacity to proline uptake capacity was nearly twice as high in lettuce-fed as in beef-fed tadpoles, corresponding to a much higher ratio of dietary carbohydrate to protein. Adult frogs have been shown to lack such regulation. Therefore, the regulatory capacity seen in tadpoles must become lost during amphibian metamorphosis.

Aging↗
PubMed1990

Ontogenetic development of monosaccharide and amino acid transporters in rabbit intestine.

We measured brush-border uptakes of seven sugars and amino acids by rabbit intestine as a function of age from the day of birth to adulthood. Gut dimensions, especially those of the colon and cecum, increase more rapidly with body weight than would be true if rabbits maintained identical proportions as they grew. However, nominal small intestinal area increases in approximately direct proportion to the animal's basal metabolic rate. For all solutes except fructose, uptake per milligram of intestinal tissue is maximal at or near birth and declines to a level 2.5-5 times lower in the adult. Because of small intestinal growth, though, the total uptake capacity of the whole length of the small intestine increases in approximately direct proportion to metabolic rate. Fructose uptake per milligram is unique in increasing steeply at the time of weaning, correlated with the post-weaning first appearance of fructose in the natural diet. Age-related changes in uptake ratios among aldohexoses or amino acids suggest developmental sequences of related transporters. Correlated with the very high protein content of rabbit milk, the proline-to-glucose uptake ratio is higher in suckling rabbits than in other sucking mammals. Remarkably, the ratio for adult rabbits is higher than in other monogastric herbivores and is instead similar to values for carnivores. In explanation, although the transport capacity of the small intestine appears to account for proline absorption in rabbits of all ages and for sugar absorption in suckling rabbits, the hindgut may be a major site of carbohydrate digestion in adult rabbits.

Aging↗