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Biomedical subjects

M D Morris

Publications and source records attributed to M D Morris.

At least 109 records · Page 6Linked to original sources
PubMed1983

Human low density lipoprotein structure: correlations with serum lipoprotein concentrations.

Human low density lipoproteins (LDL) were isolated and purified from individuals having widely differing serum lipid concentrations. Very low density lipoproteins (VLDL) and high density lipoproteins (HDL) were also isolated and quantitated. HDL2 and HDL3 were separated by flotation velocity in the analytical ultracentrifuge and their relative weight percent determined. The mean density of LDL from 41 individuals was determined by flotation velocity at two different solvent densities. The mean density of LDL was directly proportional to the triglyceride (r = 0.65) and VLDL (r = 0.50) concentrations and inversely proportional to the HDL (r = -0.55) and HDL2 (r = -0.74) concentrations (all significant at P less than 0.001). The mean molecular weight of LDL from 42 individuals was determined by flotation equilibrium centrifugation. The mean molecular weight of LDL was directly proportional to the HDL (r = 0.49) and HDL2 (r = 0.48) concentrations and inversely proportional to the serum triglyceride (r = -0.60) and VLDL (r = -0.48) concentrations (all significant at P less than 0.005 except triglyceride--P less than 0.001). The molecular weight of LDL was inversely proportional to its density, and thus inversely proportional to its protein/lipid ratio which was confirmed by composition measurements. The density and molecular weight of LDL had no relationship to the concentration of LDL (r = 0.04 and 0.03).

Adult↗
PubMed1983

Effects of cholesterol feeding on primate serum lipoproteins. III. The change in high density lipoprotein components.

Sooty mangabey (Cercocebus atys) monkeys had a lower serum HDL cholesterol concentration than any other Old World monkey species reported. In addition, they had a higher serum Lp(a) concentration than other species. The mangabeys were fed a cholesterol-fat diet for 5 weeks. HDL2 and HDL3 amounts were determined from the two peaks apparent upon analytical ultracentrifugation. In the first 1-3 weeks, 13 of the 14 mangabeys increased 30% (mean) in total HDL, this increase occurring only in the HDL2 fraction. After 5 weeks, HDL and HDL2 decreased markedly. During the cholesterol feeding, HDL3 continually decreased in flotation rate, indicating it was either smaller and/or denser. HDL2 and HDL3 separated well on molecular sieving agarose columns during the diet period, whereas a single symmetrical elution peak was found for chow-fed HDL. Thus on a cholesterol-fat diet, HDL2 and HDL3 increased in difference in molecular size.

Aging↗
PubMed1983

The measurement and interpretation of proportionate mortality.

The standardized proportionate mortality ratio (SPMR) is shown to be a summary measure which is a weighted average of age-specific proportionate mortality ratios which uses an internally derived set of standard weights. As with any summary measure, the SPMR is only meaningful when the stratum-specific values can be judged to represent a common value. When stratum-specific values are not homogeneous, the use of the stratum-specific values themselves is more appropriate than the use of a summary measure. A test for homogeneity of the age-specific proportionate mortality ratios is presented. The test also provides an estimate of the common value and its variance, when that single parameter can be presumed to exist. A procedure of external standardization is presented which uses weights derived from the standard population.

Adult↗
PubMed1982

Lysosome lipid storage disorder in NCTR-BALB/c mice. III. Isolation and analysis of storage inclusions from liver.

Livers of NCTR-BALB/c mice, affected by excessive accumulation of cholesterol and phospholipid, were fractionated by sucrose density gradient centrifugation. Lysosomes of very low density (rho = 1.05 - 1.08) were found, which by electron microscopy appeared identical to the storage inclusions seen in fixed tissues. These lysosomes could be purified about 10-fold over the original homogenate, and represented 4% of the total protein and 30-40% of the liver acid hydrolase content. The preparations were nearly free of mitochondrial, endoplasmic reticulum, and plasma membrane contamination. The lysosomes were laden with cholesterol and phospholipid. Cholesterol (greater than 97% unesterified) accounted for half of the total lipid, and sphingomyelin accounted for another 20%. Phosphatidylcholine and phosphatidylethanolamine were also present in substantial quantities. All of the excess cholesterol and sphingomyelin of liver could be attributed to the low density lysosomes. Lysosomal acid sphingomyelinase activity, measured with a synthetic substrate, was found to be 10-60% of BALB/c mouse control levels in liver, spleen, and cerebellum, while two other lysosomal enzymes, N-acetyl-beta-glucosaminidase and beta-glucuronidase, were increased 2-8-fold in the same tissues. These data and the morphologic observations of the preceding paper establish that the disorder affecting NCTR-BALB/c mice is a lysosome storage disease. We propose several possible mechanisms to explain the cholesterol and phospholipid overloading of lysosomes. The specific gene defect remains to be established.

Animals↗
PubMed1982

Lysosome lipid storage disorder in NCTR-BALB/c mice. I. Description of the disease and genetics.

We describe a strain of BALB/c mice, designated NCTR-BALB/c, carrying a new genetic disorder characterized by excessive tissue deposition of cholesterol and phospholipid. The mice exhibit progressive incoordination, grow less rapidly, and die 80-120 days after birth. In comparison with control animals of the same age, organ weights in the affected animals are lower in absolute value but higher relative to body weight, except for the thymus, which is atrophied, and for the lung and testes, whose absolute weights are not changed. Vacuolated cells are found in many tissues, and large foam cells are present in reticuloendothelial system (RES)-rich organs. Compared with those of BALB/c controls, serum lipoproteins migrate more slowly on electrophoresis; the amount of beta-lipoproteins is increased, while alpha-lipoprotein content is decreased. Serum total cholesterol remains normal. The serum activities of aspartate aminotransferase, creatine phosphokinase, and N-acetyl-beta-glucosaminidase are elevated. Free cholesterol levels are increased 8-10-fold in liver, spleen, and thymus, and about 2-fold in other tissues; but esterified cholesterol levels are normal. The phospholipid content of several tissues is increased 50-100%, largely as a result of an increase in sphingomyelin content. Significant increases in phosphatidylcholine occur also in spleen and lung. The disorder is inherited, affecting both sexes equally, and appears to be transmitted as an autosomal recessive mutation.

Animals↗
PubMed1982

Lysosome lipid storage disorder in NCTR-BALB/c mice. II. Morphologic and cytochemical studies.

Electron-microscopic and cytochemical studies were carried out on tissues of NCTR-BALB/c mice. These mice are affected with a neurovisceral genetic disorder involving excessive tissue accumulation of lipid. Distinctive polymorphic intracellular inclusions, bounded by a membrane and containing lamellated bodies, were found in many cells of liver, spleen, lung, kidney, intestine, lymph nodes, and brain. The inclusions transformed reticuloendothelial cells into massive foam cells. Acid phosphatase cytochemical studies performed on sections of liver demonstrated that the inclusions were lysosomes. Fixation of liver in the presence of digitonin produced "spicules" in the inclusions characteristic of digitonin-cholesterol complexes. Clefts of cholesterol crystals were seen in the inclusions in liver, spleen, and lung. We conclude that the NCTR-BALB/c mice are affected by a lysosome lipid storage disease and that cholesterol is a major storage product.

Acid Phosphatase↗
PubMed1982

Feedback control of cholesterol biosynthesis in mice fed the liver carcinogens benzidine and 2-acetylaminofluorene.

Dietary feedback control (DFC) of hepatic cholesterol synthesis is absent or defective in hepatomas of trout, mouse, rat and man. DFC has also been shown to be defective in rats fed several liver carcinogens including 2-acetylaminofluorene (AAF). These studies have led to the hypothesis that loss of normal DFC is an early and consistent event in the development of liver cancer. To determine whether DFC was defective in "precancerous" mouse livers, we fed the liver carcinogens AAF (0.05% in chow) and benzidine (0.02% in drinking water) to male BALB/c and C57BL/6 mice for 3 or 6 weeks. We measured sterol synthesis as incorporation of 2-14C-acetate into digitonin-precipitable sterols by liver slices. DFC was tested by adding 2% cholesterol to the diet for 3 days prior to sacrifice. Benzidine (but not AAF) treatment enhanced sterol synthesis in C57BL/6, but not in BALB/c, mice. However DFC was normal in both strains with either carcinogen. The results indicate that defective DFC is not a consistent early finding in animals fed liver carcinogens. Since defective DFC has been a consistent finding in AAF-fed rats, additional research is needed to determine whether the same genetic factors which determine susceptibility to chemically-induced neoplasia are also important in influencing DFC in carcinogen-fed animals.

2-Acetylaminofluorene↗
PubMed1981

Resonance Raman spectra for flavin derivatives modified in the 8 position.

Spontaneous resonance Raman or resonance-enhanced AC-coupled inverse Raman spectra were obtained for 8-mercaptoriboflavin, 8-(dimethylamino) riboflavin, 8-hydroxyriboflavin, and 8-aminoriboflavin all free in solution. These Raman spectra were all similar to one another and markedly different from that of riboflavin. In addition, the Raman spectra of 8-mercaptoflavin bound to the apoproteins of old yellow enzyme, glucose oxidase, and L-lactate oxidase were determined. The Raman spectra of these protein-bound flavins were distinctly different from both those of the above 8-substituted riboflavins and that of riboflavin. An argument is presented in favor of assigning a quinonoid electronic structure to these protein-bound flavins.

Flavins↗
PubMed1981

Use of calendar and weather data to predict walk-in attendance.

Hospital emergency rooms frequently provide routine health care to inner-city residents. Operating costs for such "walk-in" services might be reduced if staffing levels could be tailored to patient flow. To determine how calendar and meteorological factors affect attendance, we matched the daily visit records of a large ambulatory care center with concurrent calendar and weather data. Stepwise regression analysis resulted in a predictive equation that allows the projection of future attendance. In our facility, patient flow peaked on Monday and declined steadily during the remainder of the week. Fewer visits occurred during autumn and winter than during summer months. Higher temperatures were associated with more visits and daytime rainfall and glaze with fewer, once calendar variables were accounted for. The prediction equation has its greatest usefulness in projecting trends in walk-in attendance. Staffing levels can be adjusted to the predicted patient flow, allowing more cost-efficient operation.

Community Health Centers↗
PubMed1981

Glycogenosis type IB: possible membrane transport defect.

We have described a 20-month-old child with type IB glycogen storage disease, based on clinical and biochemical manifestations. Functional testing data were similar to those found in glucose-6-phosphatase deficiency, but in vitro studies showed normal hepatic glucose-6-phosphatase activity. Disruption of membranes with deoxycholic acid was followed by an increase in enzyme activity compared to a control liver tissue, suggesting "latency" of enzyme. We suggest that this patient had glycogen storage type IB and that this disorder may represent a specific glucose-6-phosphate transport defect.

Adult↗
PubMed1981

Effect of microsphere size on apparent intramural distribution of intestinal blood flow.

Microspheres were used in earlier studies to determine the distribution of blood flow within the intestinal wall, but the selection of microsphere size was not systematic. In one study, a 5-micrometers difference in mean diameter markedly altered the submucosal vs. mucosal distribution of microspheres. Therefore, we examined the effect of size on microsphere distribution within the gut wall. Loops of canine small bowel were perfused at constant pressure, and microspheres were injected in the following order: 9 +/- 1, 15 +/- 1, and 26 +/- 2 micrometers. Gut segments were separated into mucosal, submucosal, and muscularis tissues. The microspheres were recovered from digested tissues and venous blood. The number and diameter of spheres in an aliquot of resuspended spheres were determined by digital image analysis. The ratio of mucosal to submucosal accumulation varied 60-fold for sphere diameters from 8 to 20 micrometers. The muscularis' share did not vary systematically with sphere size. Approximately 20% of spheres less than 11 micrometers reached venous blood, whereas few (less than 1%) of larger sizes did. We conclude: 1) sphere distribution within the gut wall is size dependent, 2) correction for microsphere shunting will be difficult, because the route taken by untrapped spheres is unknown, and 3) fractionating intramural flow among the three layers is not practical with commercially available spheres. However, under control conditions 15-micrometers spheres seem to distribute independently of size between muscularis and a lumped mucosal-submucosal compartment.

Animals↗
PubMed1981

Feedback control of cholesterol biosynthesis in rats fed the liver carcinogens benzidine and 2-acetylaminofluorene.

Dietary feedback control (DFC) of hepatic cholesterol synthesis is absent in hepatomas of trout, mouse, rat and man. DFC has also been shown to be defective in rats fed several liver carcinogens, including 2-acetylaminofluorene (AAF). These studies have led to the hypothesis that loss of normal DFC is an early and necessary event in the development of liver cancer. To test this hypothesis, we fed the liver carcinogens benzidine (0.006% in drinking water) or AAF (0.05% in chow) to male Sprague-Dawley rats for either 3 or 6 weeks. We measured cholesterol synthesis as the incorporation of 2-14C-acetate into digitonin-precipitable sterols by liver slices. DFC was tested by adding 2% cholesterol to the diet for 3 days prior to sacrifice. DFC was defective in the AAF-fed rats but was normal in the benzidine-treated rats. These results are at variance with the previously stated hypothesis and, for the first time, suggest that defective DFC is not a consistent finding in the early stages of liver carcinogenesis. Additional research is necessary to explain why DFC is altered by exposure to some liver carcinogens such as AAF but unaffected by exposure to others such as benzidine.

2-Acetylaminofluorene↗
PubMed1980

Resonance Raman spectra of flavin derivatives containing chemical modifications in positions 7 and 8 of the isoalloxazine ring.

The resonance Raman spectra of riboflavin, 7,8-dichlororiboflavin, 8-chlororiboflavin, 8-bromoriboflavin, 8-(methylmercapto)riboflavin, 7-chlorolumiflavin, 8-norlumiflavin, 7,8-norlumiflavin, and 3-CH2COOH-lumiflavin were measured in complex with riboflavin binding protein, which was used as a fluorescence quenching agent. Shifts in the positions of Raman bands in the vicinity of 1250, 1405, 1550, and 1585 cm-1 were observed in the spectra of many of these flavin derivatives. Comparable shifts were found in the IR spectra (solid KBr) of the uncomplexed flavins. The perturbed bands have been previously assigned to reasonably localized stretching modes in the isoalloxazine system, which are well removed from the 7 and 8 positions. Thus, a direct effect on these bands due to modification of the substitutents at positions 7 and 8 is precluded. These observations have led us to conclude that these Raman bands are associated with highly delocalized aromatic framework vibrations.

Carrier Proteins↗