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Biomedical subjects

R Lester

Publications and source records attributed to R Lester.

At least 73 records · Page 4Linked to original sources

Gonadal function in chronic alcoholic men.

Alcoholism affects nine million individuals in the United States according to United States Government estimates. As many as 80% of hard-core alcoholic men show evidences of feminization including impotence, testicular atrophy, sterility, gynecomastia and changes in bodily hair. The causes of feminization of male alcoholics have remained obscure until recently. Largely as a result of advances in the techniques of measurement of sex hormones, it has become possible to begin to examine the pathogenesis of feminization. The results of initial studies suggest that alcoholics become feminized through the secondary effects of alcohol-induced liver disease, and also through primary effects of alcohol on the endocrine system. It can be shown that liver disease permits the peripheral escape of steroid precursors and their conversion to estrogenic substances. These substances are then inadequately cleared by the liver. In addition, however, alcohol alters testicular steroidogenesis and testosteronogenesis. Hypothalamic-pituitary function also is diminished in chronic alcoholics, and this change contributes to the syndrome of feminization.

Alcoholism

Alcohol: its effect on the kidney.

The effect of ethanol feeding on renal function, gross and microscopic morphology and constituent analysis was determined and compared to similar studies in isocalorically fed animals ingesting the same diet except that dextrimaltose was isocalorically substituted for ethanol. Alcohol-fed animals have significantly reduced renal function (p less than 0.01) and interstitial edema compared to their isocaloric controls. When renal mass and renal constituent analysis were normalized for body weight, alcohol-fed animals were found to have renal hypertrophy characterized by significantly increased absolute amounts of protein (p less than 0.01), fat (p less than 0.01) and water (p less than 0.01). All of these constituents increased in proportion to their percentage of total renal mass in control animals. In contrast, DNA content per kidney was similar for alcohol and isocalorically fed animals.

Animals

Alcohol: its effect on the kidney.

The effect of ethanol feeding on renal function, gross and microscopic morphology, and constituent content was determined in alcohol-fed rats and compared to similar studies in isocalorically fed animals ingesting the same diet except that dextrimaltose was isocalorically substituted for ethanol. Alcohol-fed animals have significantly reduced renal function and interstitial edema compared to their isocaloric controls. When renal mass and renal constituent analysis were normalized for body weight, alcohol-fed animals were found to have renal hypertrophy characterized by significantly increased absolute amounts of protein (p less than 0.01), fat (p less than 0.01), and water (p less than 0.01). All of these constituents increased in proportion to their percentage of total renal mass in control animals. In contrast, DNA content per kidney was similar for alcohol and isocalorically fed animals.

Alanine Transaminase

Fetal bile salt metabolism. The intestinal absorption of bile salt.

The intestinal absorption of sodium taurocholate was studied in the near-term fetal and neonatal dog. Absorption rates were measured in vivo in isolated loops of fetal jejunum and ileum. Absorption was also measured in vitro in everted sacs and rings of fetal and neonatal jejunum and ileum. The maximal rates of taurocholate absorption observed after instillation of 1 micronmol taurocholate into closed segments of fetal jejunum and ileum with intact blood supply were not significantly different (P less than 0.2), and equalled 0.282+/-0.026 (mean+/-SEM) and 0.347+/-0.051 micronmol/h per 10-cm segment length jejunum and ileum, respectively. Similarly, the rates of absorption from open segments of jejunum and ileum perfused with 0.4 and 1.0 mM taurocholate were nearly identical (0.232+/-0.040 and 0.255+/-0.039, respectively at 0.4 mM, and 0.470+/-0.065 and 0.431+/-0.013, respectively at 1.0 mm) (P greater than 0.2). At perfusate concentrations of 4.0 mM, moreoever, jejunal absorption exceeded ileal absorption (1.490+/-0.140 and 0.922+/-0.200, respectively (P less than 0.05). As expected, concentration of taurocholate by the mucosa was readily demonstrated in adult ileal, but not in adult jejunal everted rings. In contrast, there were no significant differences in mucosal uptake of taurocholate by fetal jejunal and ileal rings. Fetal ileal mucosal concentrations were not significantly above those in the incubation medium after 1-h exposure of the mucosa to 0.003, 0.03, and 0.3 mM taurocholate. Uptake was proportional to incubation medium concentration over the full range of values. This was also true of tissues from 1-wk-old neonates. However, by 2 wk of age, ileal mucosal concentration of taurocholate was evident and adult levels were attained by 5 wk of age. It is concluded that taurocholate is absorbed by the fetal gut and that ileal absorption is no more efficient than jejunal absorption. Although active glucose transport was demonstrable in both jejunum and ileum, it was not possible to demonstrate an ileal mechanism for active transport of taurocholate in the fetus. Active ileal transport was not demonstrable in the newborn until at least 2 wk after birth.

Age Factors

A syndrome of immunoglobulin A deficiency, diabetes mellitus, malabsorption, a common HLA haplotype. Immunologic and genetic studies of forty-three family members.

Three persons in a kindred of 43 had variable expression of a syndrome consisting of immunoglobulin A deficiency, diabetes mellitus, malabsorption, and a common HLA haplotype. Findings from the proband included life-threatening malabsorption; idiopathic intestinal mucosal atrophy with infalmmation; IgA deficiency and antibodies to multiple endocrine organs; insulin-dependent diabetes mellitus; and the major histocomptability antigens HLA-A2, B8, and DW3. In addition to the described syndrome other conditions present in the family include Graves' disease, vitiligo, hypocomplementemia, rheumatic fever, multiple sclerosis, and a high frequency of antibodies to endocrine tissue. Since Graves' disease, diabetes mellitus, and idiopathic Addison's disease have all been described in association with HLS-B8 and DW3, we believe that the occurrence of these diseases in this family suggests that a single immune response gene or gene complex is linked with HLA-B8 and DW3.

Addison Disease

Giant multinucleated hepatocytes in an adult with chronic active hepatitis.

A case of an adult with chronic active hepatitis associated with giant multinucleated liver cells is presented. The giant liver cells in this case are widespread and the picture resembles neonatal hepatitis. The morphology, pathogenesis, and epidemiology of giant hepatocytes found in human neonates and adults and in experimental animals is discussed. Because the proliferative phase of giant hepatic cells is transient, this reaction may be more common than generally believed.

Adult

Bile acid conjugation in fetal hepatic organ cultures.

A new technique has been developed in which mammalian fetal liver can be maintained in organ culture for prolonged periods with intact structure and function. Near-term rat fetal liver explants were incubated in vitro for periods of up to 3 wk with preservation of normal cellular morphology and intercellular (organ) relationships. [14C]cholate was incorporated into tissue and medium conjugates at a constant rate during 21 days in vitro. During a 24-h incubation with radioactively labeled cholic acid, bile acid conjugates accumulated in tissues to a maximum value by 6 h and maintained this value through 24 h. During the same 24-h incubation with [14C]cholate, conjugates were secreted into the medium at a constant rate. Addition of 8 X 10(-4) M taurine to the medium during a 4-day incubation produced a threefold enhancement in the rate of conjugate formation in tissues and medium. Enhanced conjugation in the presence of additional taurine was due almost entirely to increased taurocholate formation and no significant difference was observed in the amount of glycocholate formed. Exposure of explants to 3.6 X 10(-4) M cycloheximide for prolonged periods resulted in inhibition of conjugate formation, but when this concentration of cycloheximide was maintained for only 24 h a significantly (P less than 0.001) increased rate of conjugate formation was observed. The results indicate that metabolic processes in the organ-culture system are in a state of dynamic equilibrium and that morphologic integrity and specific hepatocytic function are maintained after 21 days in vitro. Preferential taurocholate formation was demonstrated in rat fetal liver, and the data suggest that glycine and taurine interact with separate enzymatic systems in bile acid conjugation. The possible mechanisms that mediate the effect of cycloheximide are discussed.

Animals

Alcoholism: its effect on hypothalamic pituitary gonadal function.

Both as the result of liver disease and of alcoholism per se, chronic alcoholics develop infertility, sterility, gonadal atrophy, hypoandrogenization, and feminization. The hypothalamic-pituitary abnormalities associated with alcoholism include hyperprolactenemia-increased estrogen-stimulated neurophysin levels, suppressed secretion of plasma gonadotropins, and loss of gonadotropin reserve. Several of the possible mechanisms potentially responsible for the development of these endocrine abnormalities have been discussed. The rational for suspecting that alcohol might interfere with either vitamin A metabolism of alter the redox state of the testes, thus affecting germ cell proliferation and steroidogenesis, has been presented. A possible mechanism for the sexual changes observed in chronic alcoholic men has been proposed. Much work remains to be done in this area before a complete understanding of the pathogenesis of these phenomena is obtained. The omission of any consideration of the effects of alcohol on sexual function in women is an admission of gross ignorance greatly in need of rectification. The necessity for couching a description of even the natural history of the syndrome in alcoholic men in conditional terms is a reflection of the limited state of the art. Nevertheless, it behooves the gastroenterologist, who is frequently called upon to be the primary physician for alcoholic men, to keep abreast of the nongastrointestinal medical consequences of alcohol addiction so that they can be recognized early and incorporated into long range medical planning designed to care for the chronic alcoholic patient.

Alcoholism

Crustacean intestinal detergent promotes sterol solubilization.

Although crustacean tissue cholesterol content is high, Crustacea, like other arthropods; are incapable of cholesterol synthesis, and presumably are dependent for maintaining tissue cholesterol stores on the intestinal absorption of ingested sterol. A detergent, N-(N-dodecanoylsarcosyl)taurine, representative of a set of detergents synthesized by the crustacean hepatopancreas and secreted into the intestine, is capable of efficient cholesterol solubilization, and thus of promoting sterol absorption.

Animals

Plasma estrone, prolactin, neurophysin, and sex steroid-binding globulin in chronic alcoholic men.

The feminization frequently observed in men with alcoholic liver disease has not been satisfactorily explained by existing reports. We have measured plasma estrone, prolactin, estrogen-stimulated neuorphysin, and sex steroid-binding globulin concentrations in 50 men with chronic alcoholism and varying degrees of alcoholic liver disease in an effort to further elucidate possible hormonal mechanisms responsible for the observed feminization. Plasma concentrations of each of these parameters were at least two-fold elevated (p smaller than or equal to 0.01) when compared to values obtained for the same steroid or protein in plasma obtained from normal men. The plasma concentrations of estrone and prolactin in men studied with synecomastia were significantly greater (p smaller than or equal to 0.01 and p smaller than or equal to 0.05, respectively) than were the concentrations of these two hormones in those without this physical sign. Similarly, those men with spider angiomata had significantly greater (p smaller than or equal to 0.01) plasma estrone levels than did the men without this cutaneous vascular abnormality. These significant hormone elevations may contribute to the pathogenesis of feminization so frequently observed in chronic alcoholic men.

Adult