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Biomedical subjects

B Holmes

Publications and source records attributed to B Holmes.

At least 163 records · Page 9Linked to original sources
PubMed1972

Development of bactericidal capacity and phagocytosis-associated metabolism of fetal pig leukocytes.

Evidence that the bactericidal ability and the stimulated oxidative metabolism of leukocytes appear in parallel during fetal development of the Minnesota Miniature pig has been obtained by application of the techniques applied to studies of human cells. It was demonstrated that leukocytes from 87- to 90-day fetuses were fully capable of ingesting Staphylococcus aureus but greatly diminished in bactericidal capacity as compared to leukocytes of older fetuses and adults. Although resting levels of oxygen consumption and hexose monophosphate pathway activity of leukocytes from the younger fetuses compared well with those of leukocytes from older animals, the phagocytosis-stimulated increments of metabolism were much less at 87 to 90 days of gestation than at later developmental stages. Both bactericidal capacity and increased metabolism of leukocytes reach adult levels by 100 days of gestation (normal gestation period of 115 to 120 days). Acrylamide gels stained for reduced nicotinamide adenine dinucleotide (NADH) and NADH phosphate (NADPH) diaphorase activity after disc electrophoresis of leukocyte extracts revealed normal mobility and intensity of NADH diaphorase bands. Three NADPH diaphorase bands were present in adult leukocyte extracts. Only the fast-migrating NADPH diaphorase band of 87- to 90-day cells stained with decreased intensity. This "deficiency" was no longer present at the later fetal period. The fast-migrating NADPH diaphorase band may represent an electron transfer protein which functions in cyanide-insensitive respiration of the leukocytes of the pig.

Acid Phosphatase↗
PubMed1971

Opsonic defect in patients with cystic fibrosis of the pancreas.

Cystic fibrosis of the pancreas is one of the most common inborn errors of metabolism. The high incidence of morbidity and mortality in these patients is primarily due to severe and frequent pulmonary infection. To date, no immune deficiency has been found in cystic fibrosis patients. Their sera contain normal quantities of immunoglobulins and hemolytic complement. In an assay of phagocytosis by alveolar macrophage, six out of nine sera from cystic fibrosis patients failed to support normal phagocytosis of Pseudomonas aeruginosa. This deficiency could be corrected by increasing the concentration of serum used in the assay. By contrast, their sera supported normal phagocytosis of Pseudomonas by blood polymorphonuclear leukocytes and continued to support normal phagocytosis when serum dilutions were used. Two patients with severe isolated deficiences of serum immunoglobulin A were found to have a similar defect in the alveolar macrophage assay, but normal phagocytosis by polymorphonuclear leukocytes. It is postulated that cystic fibrosis patients may have a quantitative and (or) functional defect of IgA antibodies, specific for Pseudomonas, and possibly of importance in the pathogenesis of their pulmonary disease.

Adolescent↗
PubMed1968

Some factors influencing carbon dioxide production by Leuconostoc citrovorum.

This study was undertaken to determine whether Leuconostoc citrovorum plays a role in carbon dioxide production in milk. The ability of L. citrovorum strains to produce gas was studied by two methods. A qualitative method, in which an agar plug was forced up the neck of a volumetric flask, measured gas visually. This method demonstrated that 0.25% yeast extract, in a milk medium at 30 C, stimulated the production of at least 10 ml of gas. Studies using a Gilson Differential Respirometer revealed that L. citrovorum produced 500 to 900 muliters of CO(2) in 6.5 hr, whereas 800 to 1,500 muliters of CO(2) was produced in nonfat milk which contained 0.33% yeast extract. Cell extracts of Streptococcus cremoris, S. lactis, Lactobacillus lactis, L. casei, and L. helveticus also enhanced gas production of L. citrovorum from 20 to 70%. Autolysates of these bacteria, present during the ripening or ageing of certain cheeses, may stimulate L. citrovorum, a common organism in starter cultures, to produce gas, causing, for example, the slit-open defect of cheddar cheese. Yeast extract caused an increase in acid and gas production per cell but did not cause an increase in growth. Experiments indicated that one metabolic source of carbon dioxide was the decarboxylation of pyruvate produced during catabolism of citric acid. Yeast extract stimulated this reaction by 16%.

Animals↗
PubMed1968

The pattern of genetic transmission of the leukocyte defect in fatal granulomatous disease of childhood.

The leukocyte-phagocytic function test which was found to be abnormal in boys with fatal granulomatous disease of childhood has been found to be abnormal to an intermediate extent in their mothers. Nine of nine mothers were shown to be abnormal, whereas none of eight fathers and none of five healthy brothers exhibited a defect. 10 of 16 female siblings were abnormal to the same degree as their mothers, as were all three maternal grandmothers available for study. Assuming that this intermediate functional defect represents the heterozygous state, the nine family pedigrees are entirely compatible with the concept that the trait is transmitted on the X-chromosome.A tetrazolium dye-phagocytosis histochemical test was also abnormal in the carrier females and provided independent confirmation of the selection of the female siblings suspected of being carriers for the trait. In addition, this procedure gives indirect evidence that the gene in question is subject to the random inactivation that appears to affect many X-linked genes in mammalian females. The family members were also studied with two of the metabolic assays that have been shown to be abnormal in the cells of affected boys. One assay, the oxidation of the first carbon of glucose-1-(14)C by the isolated leukocytes, was significantly abnormal in the cells of carrier females. The other assay, the oxidation of formate-(14)C by leukocytes of heterozygotes was not significantly different from control values. The practical problem of diagnosing patients would appear to be best solved with a tetrazolium dye procedure, whereas the more subtle abnormality in carrier females is best detected with the leukocyte function test. Improved methods for the function test are being developed.

Adult↗
PubMed1967

In vitro bactericidal capacity of human polymorphonuclear leukocytes: diminished activity in chronic granulomatous disease of childhood.

Diminished bactericidal capacity was found to be characteristic of polymorphonuclear leukocytes (PMN) from five children with the clinical syndrome of granulomatous disease of childhood. The PMN from these children demonstrated nearly normal phagocytic capacity, and the majority of viable bacteria, after 2 hours of incubation in the phagocytosis system, were found associated with leukocytes. The morphology of the unstimulated polymorphonuclear leukocytes from patients with chronic granulomatous disease was similar to those from normal persons of similar ages by light and electron microscopy. In addition, the total lysozyme and phagocytin activity of leukocyte extracts from these patients was similar to those from equal numbers of leukocytes from controls.A striking difference in the cytoplasmic response after phagocytosis characterized the PMN of the patients with granulomatous disease. Whereas degranulation, vacuole formation, and rapid bacterial digestion were the rule in the PMN from controls, little degranulation and persistence of intact bacteria in the cytoplasm characterized disease. The deficiency of bactericidal capacity and the minimal degranulation after active phagocytosis by the PMN of these children with an inherited syndrome suggest that separate metabolic processes are involved in phagocytosis and in intracellular digestion. Continuing study of the metabolic function of leukocytes from these children should provide an opportunity for increased understanding of the metabolic basis for degranulation and intracellular digestion in phagocytic cells.

Bacteria↗
PubMed1967

Studies of the metabolic activity of leukocytes from patients with a genetic abnormality of phagocytic function.

Polymorphonuclear leukocytes from patients with chronic granulomatous disease respond to the phagocytosis of latex particles with normal increments in glucose consumption, lactate production, Krebs' cycle activity, and lipid turnover. The leukocytes of these patients fail to show normal increments in respiration, direct oxidation of glucose, and hydrogen peroxide formation during particle uptake. It appears that the stimulation of respiration with the formation of hydrogen peroxide and stimulation of the direct oxidative pathway of glucose metabolism are closely linked to degranulation and intracellular killing of bacteria by polymorphonuclear leukocytes.

Citric Acid Cycle↗