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Biomedical subjects

M W Smith

Publications and source records attributed to M W Smith.

At least 235 records · Page 13Linked to original sources
PubMed1983

Unlicensed foreign medical graduates in California. Social and demographic characteristics and progress toward licensure.

Foreign-born physicians graduated from foreign medical schools who were unlicensed in California are described by nationality, age, sex, location, visa status, employment, English fluency, and specialty. Over 1,210 unlicensed foreign medical graduates (FMGs) were located in California and 736 were interviewed, approximately 40% of the estimated 3,000 FMGs residing in the state. Most of the FMGs who passed the ECFMG and FLEX were young, had specialty training, had studied for the examination, had participated in review courses, and were unemployed. GMENAC projections for the number of FMGs entering the residency pool to the year 1990 may be far too low, because many unlicensed FMGs are already in the country. Two thirds of the FMGs studied came to the United States after immigration of FMGs was restricted in 1977. Many were refugees or were from countries in political upheaval. Policy issues raised are the role of FMGs in improving care to the underserved, medical standards, humanitarian issues related to the resettlement of refugees and immigrants, and the projected oversupply of physicians.

Adult↗
PubMed1983

Cellular adaptation of amino acid transport following intestinal resection in the rat.

1. The ability of rat ileal enterocytes to take up alanine and lysine before and after proximal resection of the small intestine has been assessed using both autoradiographic and dual-isotope methods of analysis. 2. The length of individual villi was approximately doubled after resection. Alanine uptake measured in the presence or absence of Na, represented per cm2 mucosal surface area, decreased following intestinal resection. 3. Alanine and lysine uptake were confined to villus tip enterocytes in both control and ileal remnants. The net effect of intestinal resection was to increase amino acid uptake calculated per individual villus or per unit length of intestine. 4. Adaptational changes occurring as a result of resection included a shortening of the time needed for enterocytes to reach the stage where they first began to absorb amino acids and a doubling of the rate at which absorption increased during the later stages of enterocyte differentiation. 5. It is suggested that the physiological response to intestinal resection can best be appreciated by studying events taking place within individual enterocytes. The way in which adaptational changes become organized within the mucosa remains to be elucidated.

Adaptation, Physiological↗
PubMed1983

Tissue distribution of exogenous amino acids during transport across the vascularly perfused anuran small intestine.

Microdensitometric analysis of autoradiographs has been used to measure the distribution and intracellular concentration of L-leucine and L-lysine during transport across the vascularly perfused small intestine of Rana pipiens. L-leucine was not accumulated in the mucosal epithelium to a concentration higher than that in the lumen under steady-state conditions, whereas L-lysine was concentrated on average three- to four-fold. 2. At the end of 30 min loading, the majority of both amino acids were found in the mucosal epithelium and the villous core, although significant amounts were also present in the muscle. Lysine showed a gradient of accumulation within the mucosal epithelium along the length of the villous folds, the highest concentrations being achieved in the cells near the tip. Leucine showed no such gradient under steady-state conditions. 3. Superfusion of the mucosal surface of the tissue with leucine for only 3 min did reveal a gradient for uptake into the mucosal epithelium, although it was still not as steep as that seen for lysine. 4. The presence of leucine in the vascular bed while lysine was perfused through the lumen significantly lowered the concentration of lysine in the mucosal epithelium and villous core and eliminated the concentration gradient in the mucosal epithelium seen along the villous fold. 5. When leucine was perfused on its own through the vascular bed, the uptake into the muscle was greatly increased compared to when the amino acid was presented from the lumen. At the same time, the uptake into the mucosal epithelium was reduced by 45%. 6. Analysis of the tissue content of leucine after loading for 30 min from the lumen and then washing out the amino acid for 15 min showed that the mucosal epithelium, villous core and muscle had contributed 74%, 17% and 9% respectively to the total amino acid lost from the tissue. 7. These results are discussed with regard to the significance of the exit mechanisms for these amino acids and the validity of previous compartmental analyses made under similar conditions.

Animals↗
PubMed1983

Modification by diet and environmental temperature of enterocyte function in piglet intestine.

Intestinal morphology, enterocyte life span and alanine transport have been studied in the small intestine of piglets fed different amounts of food at high and low environmental temperatures. Villus height and crypt depth were both greater in pigs maintained on a high energy intake. Environmental temperature produced negligible effects on intestinal structure. Enterocyte life span increased from 45 h in pigs kept at 35 degrees C to about 70 h in animals living at 10 degrees C. A low energy intake prolonged enterocyte life span at an environmental temperature of 10 degrees C. The Na-dependent fraction of alanine uptake, judged by analysis of autoradiographs and by measurement of alanine-dependent short-circuit current, was greater in intestines taken from pigs maintained on a restricted diet. This effect, which appeared to be due to changes in the number of carriers (Jm) rather than the apparent affinity of the carrier for the amino acid (Km) was most noticeable using intestines taken from pigs kept at 10 degrees C. The Na-independent fraction of alanine uptake remained unchanged either by alterations in diet or in the environmental temperature at which pigs were kept. Restricting the diet of pigs at low environmental temperature leads to a relative increase in the capacity of the intestine to absorb alanine through an Na-dependent process. This increase appears to be caused by an extension of enterocyte life span rather than by any change in the time of onset or rate of expression of carrier function in a single enterocyte.

Alanine↗
PubMed1983

Effect of diet upon enterocyte differentiation in the rat jejunum.

Positional and temporal correlates for the development of microvillus membranes and for two of the hydrolytic enzymes they contain have been determined and compared with the ability of enterocytes to transport valine during migration from crypt base to villus tip in jejunal tissue taken from rats maintained on diets containing different amounts of protein. Microvillus elongation and the appearance of both aminopeptidase N (APN) and isomaltase (IM) activities reached maximal rates of expression in enterocytes located 16 +/- 5 micron from the crypt-villus junction. This close positional correlation was not found for the later development of the valine transport function. Feeding rats isoenergetic diets containing 20% instead of 5% protein caused significant increases in both villus height and crypt depth without changing the positional correlations described above. The maximal rates for microvillus elongation and APN and IM appearance were greater and occurred earlier in enterocytes taken from rats fed a high-protein diet. The time of onset and capacity to transport valine were found to be closely correlated for rats maintained on high- and low-protein diets. The ratio of APN to IM activity in fully differentiated enterocytes was either 0.7 or 1.2 depending on whether rats had been fed a low- or high-protein diet. The maximal length of microvillus membranes in fully differentiated enterocytes from rats on a low-protein diet was 1.4 times that found in rats maintained on a high-protein diet. Possible ways in which the microvillus membrane structure of enterocytes, enzyme activity and the ability to transport amino acids might be controlled are discussed. Relative estimates are also made of the probable effects that changes in diet will have on the capacity of the intestine to digest and absorb nutrients.

Aminopeptidases↗
PubMed1983

Proteins induced by anaerobiosis in Escherichia coli.

The contribution of protein induction and repression to the adaptation of cells to changes in oxygen supply is only poorly understood. We assessed this contribution by measuring the levels of 170 individual polypeptides produced by Escherichia coli K-12 in cells growing aerobically or anaerobically with and without nitrate. Eighteen reached their highest levels during anaerobic growth. These 18 polypeptides include at least 4 glycolytic enzymes and pyruvate formate-lyase (beta-subunit). Most of these proteins were found at significant levels during aerobic growth and appeared to undergo metabolic regulation by stimuli other than anaerobiosis. Anaerobic induction ratios ranged from 1.8- to 11-fold, and nitrate antagonized the anaerobic induction of all of the proteins except one. The time course of synthesis of the proteins after shifts in oxygen supply revealed at least three distinct temporal patterns. These results are discussed in light of known physiological alterations associated with changes in oxygen availability.

Anaerobiosis↗
PubMed1983

Proteins induced by aerobiosis in Escherichia coli.

The role of protein induction and repression in the adaptation of Escherichia coli to changes in the supply of oxygen and other electron acceptors is only poorly understood. We have studied the changes in cellular protein composition associated with this adaptation by measuring the levels of 170 individual polypeptides produced during aerobic or anaerobic growth of E. coli, with and without nitrate. Nineteen polypeptides had levels highest during aerobic growth. These proteins include the enzymes of the pyruvate dehydrogenase complex, several tricarboxylic acid cycle enzymes, superoxide dismutase, and tetrahydropteroyltriglutamate transmethylase. The other aerobiosis-induced proteins have not been identified. These polypeptides are major cellular proteins during aerobic growth and display several different patterns of regulation in response to medium composition. Induction ratios for oxygen ranged from 2.2 to 11.2, with one exceptional member, superoxide dismutase, increasing 71-fold with aeration. Most of the proteins were also induced by nitrate during anaerobic growth. The time course of induction after shifts in oxygen supply revealed similarities in response among proteins of related function or metabolic regulation class. These results are discussed in relation to previously reported information on the identified aerobiosis-induced proteins.

Aerobiosis↗
PubMed1983

2-Oxoacid dehydrogenase complexes of Escherichia coli: cellular amounts and patterns of synthesis.

The oxidative decarboxylations of pyruvate and 2-oxoglutarate in Escherichia coli are carried out by two large, multienzyme complexes: pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase. The enzyme complexes each contain three subunits: two are unique to the individual complexes, the third is shared between them. Resolution of the polypeptide subunits on two-dimensional gels allowed quantitative analysis of their cellular levels and patterns of synthesis in growing cells. Cells growing in glucose-salts medium were found to contain roughly 85 to 136 pyruvate dehydrogenase complexes and 73 2-oxoglutarate complexes. Lipoamide dehydrogenase, the subunit shared by the two complexes, was found to be in significant excess of its stoichiometric demand in the two enzyme complexes under most growth conditions. The subunits unique to each of the complexes were coordinately regulated over a wide variety of growth conditions and a broad range of expression. The two complexes responded to different, but partially overlapping, regulatory signals. Most importantly, the shared subunit was actively regulated to accommodate its demand in both enzymes. These results are discussed with regard to possible mechanisms of regulation of the enzyme complexes in general and of the shared subunit specifically.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
PubMed1982

Membrane potentials of differentiating enterocytes.

A positional analysis of enterocyte membrane potential has been carried out using in vitro preparations of rabbit distal ileum. Young enterocytes were found to possess a microvillar membrane potential significantly less than that seen in older enterocytes. The length of enterocyte microvilli was also found to be significantly less in younger enterocytes. It is suggested that developmental changes in membrane potential, occurring during the early stages of enterocyte differentiation, probably reflect a changed permeability to ions associated with the establishment of a fully developed microvillar membrane. Other explanations for the observed findings are also considered.

Age Factors↗
PubMed1982

Distribution of transported amino acid within rabbit ileal mucosa.

1. Pieces of rabbit distal ileum, incubated for short periods of time in solutions containing tritiated amino acids, have been processed for autoradiography and the profiles of amino acid concentration across the villi determined by microdensitometry. 2. The concentration profiles of a series of amino acids could be described in terms of two descending exponentials, one extending from the brush border to the basal membrane of the enterocyte and the other from the base of the epithelial layer to the centre of the villus. 3. Exponential coefficients describing the steepness of these gradients were highest for basic amino acids. Coefficients for short-chain amino acids were greater than for long-chain neutral amino acids. None of these values changed for times of incubation varying from 5 to 180 sec. 4. Enterocytes accumulated amino acids in the apical cytoplasm, against a concentration gradient, within the first few seconds of incubation. This step-up in concentration decreased as the external concentration was increased, in a manner dependent on the amino acid used. 5. It is suggested that amino acid concentration gradients within enterocytes arise by diffusion and that the amino acid specificity of this process originates from an ability of the more lipophilic amino acids to permeate structures acting as barriers to the more hydrophilic molecules.

Amino Acids↗
PubMed1982

Amino acid efflux from rabbit ileal enterocytes.

1. A method is described for converting tissue concentrations of amino acid, determined autoradiographically using sections of rabbit distal ileum, into measurements of total uptake. 2. Using this method the quantity of amino acid recovered from the villus core following short-term incubation with tritiated amino acid was shown to be directly related to the intra-enterocyte concentration of amino acid determined at a site immediately adjacent to the basal membrane. No evidence was obtained for saturation of efflux across the basal membrane of the enterocyte. 3. Amino acid efflux from the mucosa to the villus core, calculated for a constant intra-enterocyte concentration of substrate, was found to be greater for methionine and leucine than for alanine, serine, lysine or arginine. 4. The distribution of amino acids within the core of the villus following efflux from the enterocyte could not be explained by diffusion alone. 5. It is suggested that quantitative autoradiography can be used as an alternative method to study mechanisms responsible for amino acid movement across the basal membranes of enterocytes. Advantages and limitations of the technique are discussed.

Amino Acids↗
PubMed1982

Functional differentiation of enterocytes in the follicle-associated epithelium of rat Peyer's patch.

The ability of the follicle-associated epithelium (FAE) of rat Peyer's patch to accumulate valine has been measured using a new technique of autoradiographic analysis. Maximum uptake of valine was achieved by enterocytes present in the dome region of the FAE. Valine uptake was not seen in enterocytes present on the lower slopes of the FAE or in follicle-associated crypts. The ability of the FAE to absorb valine was generally much less than that seen in enterocytes present on adjacent villi. The main reason for this discrepancy lay in the apparent inability of the FAE to develop a second phase of amino acid transport similar to that seen in villus enterocytes. It is suggested that this failure results from some unexplained interaction taking place between the FAE and its underlying lymphoid tissue.

Animals↗
PubMed1981

The case control or retrospective study in retrospect.

The epidemiologic case control design is described background information on its resurgence in popularity despite historical criticisms by its detractors. Weaknesses charged to the design by Feinstein and others such as its potential for recall bias in the use of retrospective data. Neyman's case selection bias, and the diagnostic suspicion bias are analyzed and shown to affect both the cohort incidence design and the clinical trial design as well as the case control.

Humans↗
PubMed1981

Autoradiographic analysis of alanine uptake by newborn pig intestine.

All villus enterocytes in the newborn pig intestine take up alanine by a process which is largely Na-dependent. Uptake in the adult rabbit intestine is confined to enterocytes near the tips of villi. Previous conclusions about how transport changes during development are reviewed on the basis of these findings.

Alanine↗
PubMed1981

Electrophysiology of pig distal colon measured during early post-natal development.

1. Brush border membrane (Vm) and transepithelial (Vms) potential differences, transepithelial resistance (Rep) and the brush border membrane/basolateral membrane resistance ratio (Rm/Rs) have been measured in distal colons taken from new-born and 4-day-old pigs. 2. Vm remained independent of the age of the animal. Substituting choline or Tris for Na+ hyperpolarized Vm; substituting SO4(2-) for Cl- or increasing the concentration of K+ depolarized Vm in colons taken from new-born pigs. K+ depolarization was not seen using colons taken from 4-day-old animals. 3. The effect of Na+ or Cl- replacement on Vms and Rm/Rs was in agreement with the hypothesis that the brush border membrane of the distal colon possessed a conductance for both these ions. The brush border membrane of the new-born, but not the 4-day-old pig colon possessed an additional conductance for K+. 4. These electrical measurements were repeated using 4-day-old pig distal colons in the presence of amiloride, to enable values for the electromotive force across the brush border membrane (Em) and the basolateral membrane (Es) to be calculated. The Em of the 4-day-old pig colon was found to be about 23 mV negative with respect to the mucosal solution. Cl- conductance appears to predominate in colons taken from these very young animals. 5. Separate experiments showed net transport of Na+ and measured short-circuit current to be partly dependent upon the presence of Cl. Na+ transport measured in the absence of Cl- was approximately equal to that calculated from the measurement of short-circuit current. 6. It is suggested that the brush border membrane of the neonatal pig colon is conductive to both Na+ and Cl-, that the transport of these ions are partly coupled in some way and that this alone is sufficient to explain the discrepancies noted previously when measuring Na+ flux and short-circuit current in Cl- -containing medium. The possible physiological importance of this transient transport function is discussed.

Animals↗