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Biomedical subjects

B J Mills

Publications and source records attributed to B J Mills.

51 records · Page 3Linked to original sources
PubMed1984

Inhibition of tumor growth by magnesium depletion of rats.

In earlier studies tumor growth was inhibited in rats that first were made magnesium-deficient and subsequently implanted with tumors. The objective of this study was to determine if the reverse sequence is also effective. Namely, is tumor growth inhibited if tumors first are established and then a magnesium deficiency imposed? Rats with palpable mammary adenocarcinomas, or with sham implants were pair-fed either a control or magnesium-deficient diet for 32 days. Rats were then killed and tumors, plasma and several tissues analyzed. In tumors from magnesium-depleted rats, growth was inhibited 46%, magnesium concentration decreased 40% and necrosis was 50% greater. Magnesium depletion alone resulted in a 66% decrease in magnesium and a 29% increase in copper in plasma. Also, depletion caused a decrease in heart zinc and increase in kidney copper concentrations. As a result of tumor growth alone, concentrations of zinc in plasma decreased 40% and copper increased 37%. Rats with tumors also had decreased sodium and increased potassium levels in plasma. To our knowledge this is the first demonstration that the growth of an established tumor can be retarded solely by dietary magnesium depletion and thus may be significant for the nutritional management of tumor patients.

Animal Nutritional Physiological Phenomena↗
PubMed1984

Inhibition of tumor growth by zinc depletion of rats.

Tumors grow less rapidly when implanted into zinc-deficient rats. The objective of this study was to determine if tumor growth is also inhibited when tumors first are established and then a zinc depletion initiated. Therefore, rats with palpable mammary adenocarcinomas or with sham implants were pair-fed either a control or zinc-deficient diet for 32 days. Rats were then killed and tumors, plasma and several tissues analyzed. In three separate experiments tumor growth was inhibited 32, 35 and 35%, respectively. The extent of tumor necrosis and tumor zinc concentration were not different between control and deficient groups. However, there was a significant positive correlation between tumor zinc concentration and percent viable tumor tissue in both groups. Although zinc depletion in tumor-bearing rats resulted in a 10% loss of carcass weight, there was little effect on liver, kidney and heart weights. As a result of depletion alone, zinc concentrations decreased only in plasma and kidney. As a result of tumor growth alone, concentrations of liver zinc increased and kidney copper decreased. In plasma of tumor-bearing rats, levels of zinc decreased 40% while copper and magnesium increased 50 and 13%, respectively. To our knowledge, this is the first demonstration that growth of established tumors can be retarded solely by dietary zinc depletion.

Animal Nutritional Physiological Phenomena↗
PubMed1984

Meal intolerance in type 1 diabetes mellitus: influence of time interval between insulin therapy and meal intake.

Post-prandial hyperglycemia or meal intolerance has been documented in a majority of patients with Type I Diabetes Mellitus (IDDM) receiving conventional insulin treatment. It is most marked following the breakfast meal. We hypothesized that the abnormality might result from insulin insufficiency because of the short time interval between insulin therapy and meal ingestion. To test this hypothesis a standardized breakfast was fed 30 min. after insulin on one day and 90 min. after insulin on the alternate day. Plasma concentrations of glucose, free insulin and cortisol were measured at 30 min. intervals throughout the study period. A control population consisted of healthy children who were fed the same standardized breakfast. We observed that prolongation of the time period between insulin and meal did not alter the magnitude of the post-meal rise in glucose concentration in the IDDM group. Furthermore, meal intolerance persisted despite the significantly higher pre-meal levels of insulin in the IDDM group compared to the controls. We speculate that a defect in insulin action may be responsible for the phenomenon of meal intolerance in the Type I diabetics given subcutaneous insulin injections once or twice daily.

Adolescent↗
PubMed1983

Red blood cell and serum selenium concentrations as influenced by age and selected diseases.

Red blood cell and serum selenium concentrations were investigated to determine normal concentrations for our geographic area and if potential differences existed in patients with selected diagnoses (hepatic, renal, malignant, and chronic diseases). Selenium was quantified in samples of red blood cells, serum and urine by neutron activation analysis. The results were analyzed by comparing 1) pooled data from all ages for each disease with normal values, and 2) normal values with age-matched patients in each disease category. Decreases in red blood cell selenium concentrations (P less than 0.05) occurred in normal subjects over 60 years of age without concurrent significant decreases in serum selenium. Although differential results were noted in age-matched groups, overall results showed that decreased concentrations of selenium in both red cells and in serum occurred with alcoholic cirrhosis, malignancies, and chronic renal failure (P less than 0.025). Red blood cell selenium concentrations also were decreased in patients with stable chronic disease. Decreased serum selenium concentrations were positively correlated with albumin concentrations in patients with cirrhosis. There was no correlation between serum selenium and bilirubin concentrations in patients with liver disease or between serum selenium and creatinine concentrations in patients with chronic renal failure whose urinary excretion of selenium was far below control levels.

Adult↗
PubMed1982

Elevated plasma beta-hydroxybutyrate concentrations without ketonuria in healthy insulin-dependent diabetic patients.

Plasma beta-hydroxybutyrate (beta-OHB) concentrations and simultaneous urine tests for ketonuria (nitroprusside reaction) were evaluated every 4 h throughout a 24-h study in 10 healthy insulin-dependent diabetics who had poor control based on home urine tests and elevated hemoglobin A1C. Concurrent measurements of the major carbohydrate regulatory hormones were made in the diabetic group and in a control population of 20 age-matched subjects. In the diabetics, 73% of the beta-OHB measurements were elevated. Only 43% of the abnormal beta-OHB values were associated with ketonuria. The diabetic subjects also showed exaggerated diurnal patterns for plasma beta-OHB and cortisol. There were no significant differences for the other regulatory hormones in the diabetic and normal groups. We conclude that 1) abnormal plasma beta-OHB levels without ketonuria are prevalent in poorly controlled diabetics; 2) negative nitroprusside tests for ketonuria underestimate the presence of ketonemia due to increased beta-OHB concentrations; 3) both insulin deficiency and glucocorticoid excess may influence ketone body metabolism in insulin-dependent diabetic patients.

3-Hydroxybutyric Acid↗
PubMed1981

A specific dietary zinc requirement for the growth of Walker 256/M1 tumor in the rat.

To determine the specific effect of zinc status on the growth of Walker 256/M1 carcinosarcomas young male rats were pair-fed either a control or zinc-deficient diet for 14 days, were implanted with tumors and killed 7 days later. Half of the deficient rats were repleted with zinc for the 7 days after tumor implantation. In deficient rats, tumor weights were decreased 70% (p less than 0.005), tumor necrosis was 3-fold greater (p less than 0.05) and tumor zinc concentrations were decreased 23 to 37% (p less than 0.005). A specific zinc effect was observed by a 2-fold increase in tumor weights in repleted rats (p less than 0.05) with marked decreases in tumor necrosis (p less than 0.05) and 29 to 84% increases in tumor zinc concentrations (p less than 0.005). Since there were no decreases in organ weights of zinc-deficient animals and no correlation between final tumor weights and postimplant changes in carcass weights, the results indicate a specific inhibitory effect of zinc deficiency independent of a nonspecific malnutrition.

Animals↗
PubMed1981

Effect of zinc deficiency on blood glutathione levels.

The specific effect of zinc deficiency on blood glutathione (GSH) concentrations has not been clearly demonstrated, for earlier results could have been due to differences in dietary intake. To clarify this, we determined blood GSH concentrations over a 17-day period in young, mature rats fed a zinc-deficient diet and compared them with pair-fed controls. Glutathione concentrations based on hemoglobin content increased in both groups but a different rates. After 17 days, the GSH levels increased 20% in deficient rats and 29% in control rats (P less than 0.005). The GSH levels in deficient rats were 11% lower than in controls by 10 days (P less than 0.025) and remained significantly lower thereafter. These results indicate that the decrease in blood GSH levels was a specific result of zinc deficiency.

Animals↗
PubMed1981

Differences in blood glutathione levels of tumor-implanted or zinc-deficient rats.

Previously we found that blood glutathione (GSH) levels were decreased in rats that were both zinc-deficient and tumor-bearing. In this study the separate effects of zinc deficiency and tumor were investigated. Young, male rats were pair-fed either a complete, control diet or a zinc-deficient diet, and some of each group were implanted intramuscularly (i.m.) with Walker 256/Ml carcinosarcoma. Then half of the tumor-implanted, zinc-deficient rats were repleted with zinc. All rats were killed 7 days after tumor implantation. Zinc deficiency was validated by poor growth, low food efficiency and decreased concentrations of zinc in liver, kidney and plasma. Relative to controls rats, the blood GSH level increased 21% as a result of tumor alone (P less than 0.005) and decreased 19% with zinc-deficiency alone (P less than 0.025). In rats that were both tumor-bearing and zinc-deficient, the GSH level was 16% higher than the controls (P less than 0.005). Zinc repletion of the tumor-bearing rats restored GSH levels to control values. These results indicate that the marked and opposite changes in blood GSH levels as a result of tumor implantation or of zinc deficiency occur by different mechanisms.

Animals↗
PubMed1980

Prolymphocytic leukemia: flow microfluorometric, immunologic, and cytogenetic observations.

Cells isolated from four patients with prolymphocytic leukemia were evaluated by surface markers, cytogenetics, and flow microfluorometric analysis of cell size and DNA content. All four patients had B-cell markers with a high density of IgM, kappa type, and Ia-like antigen. Less intense staining for surface IgD was also observed. In each patient studied, chromosomal modes were in the hypodiploid or near-diploid range. Despite the karyotypic abnormalities, the cellular DNA content, as determined by flow microfluorometry, was within the normal limits in all cases. This suggests that the variability in chromosome numbers seen in these patients may reflect an abnormality in DNA package rather than differences in total DNA content. The modal electronic cell size of the prolymphocytes, determined by light scatter, was readily distinguishable from that of normal peripheral blood lymphocytes and the lymphocytes of chronic lymphocytic leukemia. Fewer than 4% of the peripheral prolymphocytes had S-phase DNA content, a finding consistent with the chronic nature of this leukemia.

Chromosomes, Human↗
PubMed1979

Antibody-independent neutralization of vesicular stomatitis virus by human complement. II. Formation of VSV-lipoprotein complexes in human serum and complement-dependent viral lysis.

Vesicular stomatitis virus (VSV) is efficiently neutralized by normal, nonimmune human serum without the participation of antibody. Neutralization is complement- (C) dependent and requires the early-acting components of the classical pathway, C1, C4, C2, and C3, but not later-acting C components. In further studies, normal human serum was found to markedly increase the density of a variable but significant proportion of virus-associated RNA and to markedly decrease the density of the remainder of virus-associated RNA. The RNA of increased density was found to be dense ribonucleocapsid cores released from VSV by C-dependent viral lysis mediated through the classical pathway. The released ribonucleocapsid cores found at the bottom of sucrose density gradient after incubation of VSV with human serum were resistant to degradation by proteolytic enzymes. The VSV-derived RNA found floating on the tops of sucrose density gradients performed on serum-treated VSV was infectious virus. The decreased density was due to binding of VSV to human serum lipoproteins (LP), primarily very low density lipoproteins (VLDL). Binding of VLDL to VSV required the presence of the viral envelope and the external glycoprotein, G. Despite the binding of LP to VSV, LP did not neutralize VSV, and LP-depleted sera were fully active in neutralizing VSV. Thus, LP do not represent an accessory factor for the C-dependent neutralization of VSV.

Antibodies, Viral↗
PubMed1976

The biosynthesis of deoxyribonucleic acid during the life-span of the mosquito.

Previous results from this laboratory [Kao et al, (1976) Biochem. J. 154, 471-480] demonstrated that a low-molecular-weight DNA species, "sDNA", present in high concentrations during rapid larval growth of the yellow-fever mosquito, Aedes aegypti, may be an intermediate in DNA replication. We have now determined the life-span profiles of synthetic rates and the steady-state contents of sDNA and total DNA by radiometric and biochemical procedures and by using mosquitoes grown and maintained under defined and controlled conditions, including axenic culture and synchronization of stages. 2. Our results showed exponential increases in DNA contents and synthetic rates which paralleled the changes in weight during larval growth. Of special importance was the finding that in rapidly-growing larvae and newly-emerged adult mosquitoes high contents and rates of synthesis of sDNA were correlated with increases in total DNA/organism, which suggests that sDNA content may be an index of DNA replication. In senescent mosquitos a twofold increase in the synthetic rate of bulk DNA ("pDNA") without an increase in sDNA may reflect repair synthesis. 3. The significance of this investigation is that it may be the first quantitative and systematic description of the synthetic rates and contents of both DNA-replication intermediates and total DNA in an axenic, eukaryotic organism rather than a specific cell type. Equally important is that these findings describe DNA changes during growth and also during aging through senescence in an age-characterized organism.

Aedes↗
PubMed1976

Mutants of Pseudomonas aeruginosa that show specific hypersensitivity to aminoglycosides.

A class of mutants in Pseudomonas aeruginosa have been found that are tolerant to aeruginocin 41 and also hypersensitive to aminoglycosides. They do not show any changes in susceptibility to a wide range of other toxic agents, including antibiotics and surfactants. This tol locus, tolA, has been mapped at 10 min from the FP2 origin and linked to carA (carbamyl phosphate synthetase) by transduction and conjugation. By selecting for revertants of the hypersensitivity phenotype, revertants to tol(+) were found, indicating that it is the tolA locus that is responsible for this specific hypersensitivity. The results indicate that a specific mechanism exists for the intrinsic resistance of P. aeruginosa to aminoglycosides.

Aminoglycosides↗