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Biomedical subjects

M W Smith

Publications and source records attributed to M W Smith.

At least 217 records · Page 12Linked to original sources

Thyroid hormone effects on lactase expression by rat enterocytes.

Thyroxine (T4) and triiodothyronine (T3) injected into adult rats causes first an increase and then a decrease in lactase activity measured subsequently in intestinal homogenates of rat jejunum. These changes are not associated with any alteration in intestinal structure or enterocyte migration rate. Quantitative cytochemistry shows T4 stimulation and inhibition of lactase activity to take place in upper villus and crypt cells respectively (O- and C-enterocytes). T3 injected into thyroidectomized rats produces identical stimulatory effects on lactase development to T4 injected into control animals. Radioactive T3 is distributed in all cell types following intraperitoneal injection into thyroidectomized rats. Highest amounts of recovered T3 are found in C- rather than O- enterocytes. Quantitative autoradiography shows intracellular T3 to be located in nuclear and cytoplasmic compartments following intraperitoneal injection. Simultaneous injection of non-radioactive hormone displaces 50-75% of radioactive T3. These results are discussed in relation to what is already known concerning the ability of thyroid hormones to affect intestinal development. The future need to study the physiological effects of T3 at the cellular level in the intestine is also emphasized.

Animals↗

Binding of triiodothyronine by fully differentiated rat enterocytes.

The cellular binding characteristics of triiodothyronine (T3) have been measured in a preparation of isolated fully differentiated enterocytes prepared from thyroidectomized rats. Specific binding of [125I]T3, defined as that portion displaced by the presence of 20 microM-non-radioactive hormone, was shown to become maximal after 100 min incubation with cells at a temperature of 15 degrees C. The cellular release of lactic dehydrogenase measured under these conditions was found to be 18%. Thin layer chromatography of radioactive compounds recovered from enterocytes and from incubation medium showed less than 2% radioactivity to be as free iodide. The amount of [125I]T3 specifically bound to enterocytes showed a curvilinear dependence on the concentration of T3 present in the incubation medium. Scatchard plot analysis of this data revealed the presence of both high (KD 1.2 +/- 1.1 X 10(-9) M) and low (KD 1.9 +/- 0.8 X 10(-7) M) affinity binding sites in these cells. Previous injection of non-radioactive T3 into thyroidectomized rats, at a time chosen to ensure negligible levels of circulating T3 at the time of the experiment, caused a 3-fold reduction in the maximal binding capacity of the low-affinity site (83 compared with 28 pmol/mg protein). Neither the affinity nor the number of high-affinity binding sites for T3 were significantly affected by this treatment. These results are compared with those obtained using other types of cell responsive to T3. The possible physiological importance of these findings is discussed.

Animals↗

Identification of intestinal cells responsive to calcitriol (1,25-dihydroxycholecalciferol).

The location of intestinal cells taken from the base of the crypt to the tip of the villus responsive to calcitriol (1,25-dihydroxycholecalciferol) and the distribution of [3H]calcitriol within the intestinal epithelium has been determined in vitamin D-deficient rats. The calcitriol responses examined were CaBP (Ca2+-binding protein) levels as measured by immunodiffusion and alkaline phosphatase levels as determined cytochemically. Calcitriol had no effect on villus structure or on enterocyte kinetics. This made it possible to compare levels of CaBP and alkaline phosphatase activity in enterocytes at different ages in rats at known times after hormone injection. Cells from both the crypt and villus synthesized CaBP in response to calcitriol. Alkaline phosphatase activity was not detectable in crypt cells, although a pool of precursor was produced in these cells in response to calcitriol. Enzyme activity was increased in all villus cells in response to calcitriol, but the quantitative description of this effect was very different from that found for calcitriol effects on CaBP synthesis. Calcitriol injected into vitamin D-deficient rats was detected, within 2h, in all cells of the crypt and villus. Most of the binding was to sites having a high affinity for the injected hormone.

Alkaline Phosphatase↗

Selective expression of brush border hydrolases by mouse Peyer's patch and jejunal villus enterocytes.

Developmental profiles describing the expression of lactase, alpha-glucosidase, and alkaline phosphatase activities have been determined quantitatively in mouse jejunal enterocytes during migration over villi and Peyer's patch lymphoid tissue. The predicted maximal lactase and alpha-glucosidase activities expressed by enterocytes migrating over Peyer's patch follicles were about one-quarter and one-half of values found in control villi. Alkaline phosphatase activity was, on the other hand, one third greater in Peyer's patch compared with villus enterocytes. Expression of lactase and alpha-glucosidase activities was initially less in enterocytes migrating along interfollicular compared with control villi. Subsequent increase in hydrolase activities occurred during the later stages of enterocyte migration over interfollicular villi. Lactase activity in athymic mice Peyer's patch enterocytes was identical to that recorded for control mice. The corresponding value for villus lactase was, however, only half that found in control tissue. Factors produced locally in lymphoid follicles are probably responsible for selective effects on enterocyte differentiation.

Alkaline Phosphatase↗

Maxillary nerve involvement in bacterial endocarditis.

A case of right maxillary nerve paresthesia during an active phase of bacterial endocarditis probably due to embolic occlusion of the nerve's vascular supply is reported. The authors suggest that infective endocarditis be considered as a rare but potential cause of unexplained trigeminal nerve branch lesions, and that such lesions be sought in cases of established endocarditis.

Embolism↗

A comprehensive description of brush border membrane development applying to enterocytes taken from a wide variety of mammalian species.

Pieces of small intestine taken from rabbit, rat, mouse, guinea-pig, hamster and pig have been used to determine microvillus length in enterocytes located at different points along the crypt-villus axis. Thymidine labelling has also been used to convert measurements of enterocyte position into age of enterocyte. Microvillus lengths showed lower and upper plateaux (a and a + c respectively) with fairly rapid transition from one to the other defined by an exponential coefficient b. The mid-point of elongation (m) usually occurred within 60 micron of the crypt-villus junction. Correlations were found to exist between a and m and between a, m and the depth of the intestinal crypt. Values of b and bc/4, the maximal rate of microvillus elongation, were also found to be correlated with the size of the crypt. None of these parameters were related in any way to the villus height or enterocyte turnover time. The possibility that some factor associated with the physical size of the crypt might be exerting positional and temporal control over the subsequent structural differentiation of enterocytes is discussed.

Animals↗

Positional dependence of enterocyte membrane potential in hamster and rabbit enterocytes.

A technique is described allowing microelectrode impalement of enterocytes located at known positions along intestinal villi from rabbits and hamsters. Using this technique a 5 mV hyperpolarization in membrane potential is shown to occur as enterocytes migrate over the basal third of intestinal villi. The villus structure of the hamster ileum is similar to the rabbit, but the enterocyte lifespan in these two tissues differs considerably (enterocyte migration rates of 17.6 and 6.3 microns hr-1 for hamster and rabbit respectively). A correlation was found between the position an enterocyte occupied on the crypt-villus axis and the developmental state of the membrane potential. No such correlation existed when making comparisons on a time basis. These results are discussed both in terms of what is now known concerning different aspects of enterocyte development and in relation to what type of control mechanism might be generally responsible for initiating differentiation in this tissue.

Animals↗

Protein synthesis and secretion by hamster, rat and mouse jejunum.

The synthesis and secretion of [35S]methionine-labelled proteins by hamster, rat and mouse jejunum has been measured in vitro after 60 min incubation in culture medium. Twenty-three major bands of radioactively labelled proteins were detected by PAGE analysis of enterocyte extracts. Three of these proteins having mol. wts of 28,000, 43,000 and 60,000 appeared to be synthesised preferentially by older enterocytes. A small number of radioactively labelled proteins also appeared in culture medium at the end of incubation. Three of these proteins, accounting for most of the recovered radioactivity, had mol. wts of 28,000, 43,000 and 60,000. Secretion of these proteins was inhibited by monensin. Further experiments showed these secreted proteins to be acidic and possibly glycoprotein in nature. Their rapid turnover, selective secretion and changing abundance in enterocytes of different ages all suggest that they may have important functions to perform in the intestine.

Age Factors↗

Basic emergency medical care of patients with acute myocardial infarction: initial prehospital characteristics and in-hospital complications.

This prospective study documents the natural history of the prehospital phase of 110 patients with acute myocardial infarction transported by a basic emergency medical system during a 22 month period. Ambulances in a mixed urban-rural county were staffed by basic emergency medical technicians certified in basic life support and the administration of intravenous fluids. Systolic blood pressure, pulse rate and cardiac rhythm were noted for all patients at the time of ambulance arrival and intermittently during transport. Analyses of patient data were performed to determine the relation between the occurrence of subsequent in-hospital urgent complications and death and 1) patient delay time, 2) initial pulse rate, 3) initial systolic blood pressure, and 4) initial cardiac rhythm. Twenty-three (21%) of the 110 patients died and 66 (60%) experienced at least one in-hospital urgent complication. When initial rhythm, pulse rate and blood pressure were considered, patients with hypotension had a higher mortality rate than did those who were either normotensive or hypertensive. The 10 patients with initial sinus bradycardia but no hypotension constituted a subgroup with zero mortality. These results identify high and low risk patient subgroups that may benefit from either providing or withholding interventions directed toward hemodynamic stabilization during the prehospital phase of acute myocardial infarction.

Adult↗

Developmental changes in intra-enterocyte cation activities in hamster terminal ileum.

Intracellular Na+ and K+ activities have been determined under visual control in enterocytes located at known positions along hamster ileal villi in vitro. The intracellular K+ activity found in enterocytes migrating over the basal third of villi was significantly less than that found in older enterocytes (83 and 113 mM respectively). The intracellular Na+ activity remained unaffected by the state of enterocyte development (32 mM throughout). Extracellular K+ and Na+ activities measured close to the luminal surface of the intestine were always similar to those measured in the bulk of the bathing medium. There was, however, a small difference in K+ activity detected between the bulk solution and solution near the luminal surface of enterocytes (3 . 4 and 3 . 6-3 . 7 mM respectively). Na+ activity in the villus core was also similar to that of the bathing medium. The brush border membrane content of sucrase-isomaltase, determined cytochemically, was found to increase rapidly as enterocytes migrated over the basal third of the villus and to plateau at a point roughly equivalent to that where intracellular K+ activities became maximal. The numerous ways by which enterocytes might control their intracellular K+ concentrations during development are emphasized. Attention is nevertheless drawn to the close correspondence seen between different aspects of brush border membrane development and the ability of enterocytes to maintain high internal concentrations of K+.

Animals↗

Dissipation of amino acid concentration gradients within rabbit ileal enterocytes.

The distribution of alanine, lysine and methionine within the cytoplasm of functionally mature enterocytes in rabbit ileum was measured by autoradiography after a short period of contact with tritiated substrate. Pronounced intracellular concentration gradients were noted for alanine and lysine, the concentration of these amino acids in the apical part of the enterocyte being 2- to 3-times that found near the base of the cell. No such concentration gradient was seen for methionine. Subsequent superfusion of the mucosal surface of the tissue with substrate-free medium caused intracellular concentration gradients for alanine and lysine to disappear. There was also a decrease in the enterocyte content of all three amino acids unassociated with backflux into the intestinal lumen. The ease with which intracellular concentration gradients for alanine and lysine can be manipulated is used as an argument against the possibility that their creation results from selective attachment to cytoplasmic structures in the apical part of the enterocyte.

Alanine↗

Ureteral reaction to suture material.

Dog ureters were anastomosed end to end using either chromic catgut, polyglycolic acid (PGA), polyglactin-910, or polypropylene sutures. Analysis of luminal diameters, fibrosis, scar vascularity, and inflammatory reaction four and seven months later indicated that in ureters of the uninfected dog the best results were obtained with polyglycolic acid. Ureters anastomosed with catgut gave results that were slightly less acceptable.

Animals↗