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Biomedical subjects

R Wallace

Publications and source records attributed to R Wallace.

At least 127 records · Page 7Linked to original sources

Lens capsule abnormalities in Alport's syndrome.

The ultrastructure of the glomerular basement membrane in Alport's syndrome is well known and characteristic of this disease, but the anterior lenticonus that frequently occurs in this syndrome has not been similarly studied. An anterior lens capsule from a 30-year-old patient with lenticonus who had Alport's syndrome was obtained at capsulectomy and found to be one third the normal thickness centrally and to be more fibrillar than usual. There were large numbers of partial capsular dehiscences containing fibrillar material and vacuoles. Cellular debris and more recent ruptures of lens epithelial cell membranes underlaid the breaks. The anterior capsule is clearly fragile in this disease, forming the basis for the progressive lenticonus and anterior polar cataract. These abnormalities correlate well with a defect in the type IV collagen molecule, as has been recently reported in Alport's syndrome.

Adult↗

Turnover of rat liver ornithine transcarbamylase.

The relative half-life of ornithine transcarbamylase from rat liver has been determined using the double isotope technique and affinity chromatography. The calculated half-life (6-9 days) is similar to that of mitochondria and of the other mitochondrial enzyme of the urea cycle, carbamoyl-phosphate synthase. Therefore, both mitochondrial urea cycle enzymes are most probably degraded mainly via the lysosomal (autophagic) pathway of mitochondrial protein degradation.

Animals↗

Growth of Vibrio costicola and other moderate halophiles in a chemically defined minimal medium.

A simple chemically defined minimal medium consisting of sodium glutamate, glucose, vitamins, and salts was devised to support growth of the moderate halophile, Vibrio costicola, over as wide a range of NaCl concentrations as the complex medium, proteose peptone + tryptone. The lag period at higher NaCl concentrations was longer in the chemically defined minimal medium than in proteose peptone + tryptone. Chemically defined minimal medium also supported the growth of an unidentified moderate halophile, HX, and of Vibrio alginolyticus and Vibrio cholerae. The Mg2+ concentration required for good growth changed with the growth temperature for both V. costicola and HX.

Culture Media↗

Update on external cephalic version performed at term.

External cephalic version under tocolysis at term was investigated during a prospective study at the Los Angeles County/University of Southern California Medical Center from October 1, 1979 to March 16, 1983. Two hundred twelve patients were considered for attempted version. Forty-one patients were excluded, and 23 patients as previously reported were randomized to the control group. The procedure was successful in 73% (108 of 148). Of the 102 successful versions observed until delivery (six lost to follow-up), 93% (95 of 102) presented in labor with a vertex presentation; seven fetuses reverted to abnormal lies. The cesarean section rate in the success group with a vertex presentation was 24% (23 of 95).

Breech Presentation↗

Estrogen use and breast cancer. Interaction with body mass.

With few exceptions, most epidemiologic studies do not show an excess relative risk of breast cancer associated with menopausal estrogen therapy. Other studies show a relationship of breast cancer to obesity, which is characterized by increased endogenous estrogen production. This study explored the possibility of an interaction between ponderosity and exogenous estrogen use in a case-control study of 113 postmenopausal breast cancer patients and pair-matched hospital control subjects. In this series, neither menopausal estrogen use nor relative weight were significantly associated with breast cancer risk. However, among estrogen users, the relative risk of breast cancer was strikingly influenced by the ponderosity of the subjects; the relative risk was 0.41 for women whose relative weight was less than the median, compared with 1.29 for those whose relative weight exceeded the median. The mean age was also examined at diagnosis in order to explore the potential of exogenous estrogen as a tumor promotor. The mean age at breast cancer diagnosis in estrogen users, 58.1 years, was significantly lower than in nonusers, 63 years. A significant linear relationship was found between age at diagnosis and body weight among estrogen users. Estrogen-treated women in the lowest tertile of body weight had the diagnosis of breast cancer made seven years earlier than those in the highest tertile of weight. There was no significant difference in the distribution of clinical stages at diagnosis between estrogen users and nonusers. These data suggest that relative body weight is an important modifier of the effect of exogenous estrogens on breast cancer biology.

Age Factors↗

Effect of estrogen/progestin potency on lipid/lipoprotein cholesterol.

We studied 374 women taking oral contraceptives, 284 women taking estrogen preparations after menopause, and 1086 women taking no hormones, to determine the relation of plasma lipids and lipoprotein cholesterol concentrations to various types of estrogen/progestin formulations. Premenopausal women, using oral contraceptives containing a relatively low dose of estrogen combined with a medium or high dose of progestin (Norlestrin, Ovral, or Demulen) had a 24 per cent higher median concentration of low-density-lipoprotein cholesterol than did those not using hormones (P less than 0.05). Women using oral contraceptives that are high in estrogen and low in progestin (Enovid or Oracon) had significantly higher concentrations of high-density-lipoprotein cholesterol than did nonusers; those using Ovral, a low-estrogen and high-progestin formulation, had significantly lower levels of high-density-lipoprotein cholesterol. In postmenopausal women the use of estrogen was associated with concentrations of low-density-lipoprotein cholesterol that were 11 to 19 per cent below the levels in postmenopausal women who did not use hormones. The effects of estrogen-progestin balance on low-density and high-density lipoproteins may underlie the increased incidence of stroke and myocardial infarction in women of childbearing age who take oral contraceptives.

Adult↗

Glucocorticoid induction of tryptophan oxygenase. Attenuation by intragastrically administered carbohydrates and metabolites.

In vivo tryptophan 2,3-dioxygenase (TPO) activity in male rats was estimated from the rate of production of 14CO2 after intragastric administration of [14C-2]tryptophan. The synthetic glucocorticoids hydrocortisone-21-sodium succinate or Triamcinolone acetonide were injected to elevate hepatic TPO activity on an acute (1-6 hr) or chronic (24 hr) basis. Glucose, fructose, or glycerol was intragastrically intubated in doses ranging from 4 to 16 mmoles to assess their abilities to attenuate acute or chronic increases of TPO activity by these glucocorticoids. Hydrocortisone-21-sodium succinate at doses of 0, 25, and 50 mg/kg produced dose-dependent elevations of TPO. A 50 mg/kg dose produced a 3-fold elevation of enzyme activity when measured in vitro as product produced by liver homogenates and a 2-fold elevation when assessed from expired radioactive carbon dioxide from radiolabeled tryptophan in vivo. Enzyme activity measured by 14CO2 production reached peak values in 2-3 hr and returned to baseline in 5 hr. Glucose, fructose or glycerol completely prevented the rise in conversion of [14C-2]tryptophan produced by hydrocortisone hemisuccinate when administered at doses of 12 or 16 mmoles 0.5 hr before the steroid. Lower doses had less effect. The potencies of the compounds in inhibiting acute increases in TPO activity produced by hydrocortisone hemisuccinate were in the order glycerol greater than fructose greater than glucose. Chronic Triamcinolone treatment elevated in vivo TPO activity by 2.5-fold and in vitro TPO activity by 5-fold. The chronic elevation of in vivo TPO by Triamcinolone could be arrested within 1 hr by an intragastric fructose load. The present finding, that acute or chronic glucocorticoid-induced increases in in vivo TPO activity were rapidly blocked by intragastric carbohydrate loads, is consistent with the view that dietary carbohydrates modulate hepatic TPO activity via feedback repression and not by a cessation of TPO enzyme synthesis.

Animals↗

The New York City fire epidemic as a toxic phenomenon.

Reductions in the fire service in New York City from 1972 to 1976 appear to have caused a disproportionate increase in fire-fighter work load through several unexpected mechanisms of fire contagion. In turn, the work load increase has itself had a disproportionate physiologic impact: A classic dose-response relation has been observed between a composite measure of per capita structural fire work load and the percentage of the fire-fighting work force retiring under conditions of disability. After 1974, the increase in work load seems to have caused entry to the 'linear' portion of the dose-response curve. Implications of this synergism are explored for both New York City and other American urban areas now suffering 'fiscal crises' or planning fire service reductions.

Disability Evaluation↗

Turnover of adenosine triphosphatase from rat liver mitochondria. Effect of high-protein and low-protein diets.

The half-life of mitochondrial adenosine triphosphatase and the relative rate constants of protein degradation for several fractions of rat liver have been measured by the double-isotope technique. It has been shown that the apparent turnover rates of some mitochondrial enzymes, far apart in size, such as carbamoyl phosphate synthetase, glutamate dehydrogenase and malate dehydrogenase, are not related to molecular weight or to size of subunits. In view of the possibility that mitochondrial proteins are degraded by different mechanisms, it was of interest to determine the half-life of a protein tightly bound to the inner membrane such as adenosine triphosphatase. The rate constants of degradation for rats fed a basal diet and injected at three-day intervals with isotopic leucine were: homogenate, kd = 0.195 days-1; mitochondria, kd = 0.135 days-1; cytosol, kd = 0.140 days-1; microsomes, kd = 0.28 days-1; ATPase, kd = 0.275 days-1. The rate constants of the cellular fractions of liver of rats fed a high protein diet did not change or showed a small increase, compared with those of animals fed the basal diet, while those from rats on the protein-free diet showed a decrease. The rate constant for adenosine triphosphatase showed an increase with high-protein and a decrease with protein-free diet. A procedure for the purification of ATPase from a single liver of a rat is described.

Adenosine Triphosphatases↗

Relationship of body weight to menarcheal and menopausal age: implications for breast cancer risk.

Early menarche and late menopause are risk factors for the development of breast cancer. An adequate hormonal mechanism for those observations has not been described. Because obesity has also been associated with increased breast cancer risk, we examined the relationship among height, weight, adiposity, and menstrual cycle characteristics in women who prospectively recorded menstrual cycle intervals and reproductive events as part of the Menstrual and Reproductive History Research Program. Within this study cohort, adult height, weight, and a derived index of adiposity were related to both earlier age at menarche and later age at menopause. The association of early age at menarche with adiposity persisted from age 18 yr through middle age and into the menopausal years. There was no relationship between body mass and age at first pregnancy, another breast cancer risk factor. Women who were heavier at 18 yr of age and thereafter gained 5 lb or more had significantly greater mean menstrual cycle length and variability during the 7-yr period after menarche than the other members of the cohort. There was no obvious relationship between weight indices and menstrual cycle pattern during mature reproductive life or during the 7 yr before menopause. Our data suggest that menarcheal and menopausal age may have a common relationship to nutritional status and to constitutional features that predate the onset of menarche and persist into later life.

Adipose Tissue↗

Intracellular degradation of mitochondrial enzymes.

Quantitation of the pool of short-lived mitochondrial proteins in cultured cells by a new method shows it to be very low, i.e. approximately 1.35%. Degradation of three long-lived mitochondrial enzymes of rat liver which make up approximately 25-30% of the mitochondrial protein necessitates the cooperation of mitochondrial and lysosomal components. The degradation of carbamyl phosphate synthetase (t1/2, 7.7 d) and of ATPase (t1/2, 2-3 d) requires both a protein component from the inner mitochondrial membrane and lysosomes while degradation of glutamate dehydrogenase (GDH) (t1/2, approximately 1 d) necessitates a mitoplast factor, identified as NADP, which facilitates the inactivation by lysosomes. Chemotropic modification (carbamylation) of GDH also changes stability to rat liver proteases. All three enzymes are synthesized as pro-enzymes. Their processing and possibly control of degradation by maturases as well as the relation of both processes to molecular plasticity is presented.

Adenosine Triphosphatases↗

Nutrition and age at first birth in breast-cancer risk.

Urban/rural breast-cancer incidence ratios in the state of Iowa for 1950 and 1969-71 were contrasted with corresponding urban and rural distributions of age-at-first-birth and population nutrition, variable measured approximately 15 years before each morbidity survey and putatively related to breast-cancer incidence. Over the study interval, the decline in the urban/rural breast-cancer incidence ratio correlated better with changing nutritional patterns than with changing age-at-first-birth.

Adult↗

Turnover and degradation of mitochondria and their proteins.

Very little is known about intracellular protein degradation. We have concentrated on mitochondrial proteins for simplicity. Even this is a complex problem and several mechanisms may be involved. The half-lives of mitochondrial proteins vary widely. Using immunological, autoradiographic (ferritin and iodine) and biochemical techniques we are delineating the extent of intra-mitochondrial protein degradation, lysosomal participation in that degradation, and signals controlling the overall process. As a high yielding dividend of our autoradiographic and immunological experiments it seems possible to clarify such important questions as whether there is a selective inactivation and turnover of mitochondria and their proteins. Calculations of autophagy and vacuoles, the concentration of mitochondrial proteins within lysosomes, as well as key aspects of the initiation and regulation of protein turnover and its elasto-plastic control are presented.

Animals↗