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Biomedical subjects

P G Phillips

Publications and source records attributed to P G Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1986

Alpha 2U-globulin: measurement in rat kidney following administration of 2,2,4-trimethylpentane.

Hyaline droplet formation was stimulated markedly in the kidneys of post-puberty male rats 24-48 h after a single oral dose of 12/24 mmol/kg 2,2,4-trimethylpentane [TMP]. Renal hyaline droplet formation could not be detected in female rats or in pre-puberty male rats following similar doses of TMP. A dose-dependent increase in the renal concentration of the androgen-dependent low molecular weight protein, alpha 2U-globulin was observed in post-puberty male rats 24 h after a single oral dose of TMP, over the range 0.3-12.0 mmol/kg. After administration of a single dose of 12 mmol/kg TMP to male rats, the renal concentration of alpha 2U-globulin rose steadily up to a peak after 48 h and then returned slowly to near normal after 7 days. Renal alpha 2U-globulin could not be detected in female rats and in pre-puberty male rats. An immunocytochemical assay was developed to examine the distribution of alpha 2U-globulin within the kidney. alpha 2U-Globulin was localised primarily in the S2 segment of renal proximal tubules in untreated male rats. Rats which received a single dose of 12 mmol TMP/kg showed not only a greater staining intensity, due to the presence of a higher concentration of alpha 2U-globulin, but also staining in adjacent segments of the renal cortex. Several urinary biochemical indicators of nephrotoxicity were measured daily in male rats for up to 72 h following a single dose of 12 mmol TMP/kg. Renal proximal tubular function was unimpaired by TMP treatment. On the basis of studies in untreated and TMP-treated rats, a strong association has been found between the presence of renal hyaline droplets and the occurrence of renal alpha 2U-globulin. The findings in the present study provide an explanation for the occurrence of renal hyaline droplets only in adult male rats, but do not, as yet, establish the toxicological significance of increases in renal hyaline droplet formation.

Alpha-Globulins↗
PubMed1984

Mechanism of inhibition of granulopoiesis by ethanol.

The mechanism of inhibition of neutrophilic granulopoiesis by ethanol has not been well characterized. Possible mechanisms investigated include: (a) a direct toxic effect on the granulocyte-macrophage cluster-colony forming unit (CFU-GM), and/or (b) inhibition of production of CFU-GM proliferation stimulating factor activity (CSA) from T lymphocytes (T cells). Addition of as much as 600 mg% ethanol to T-cell- and monocyte-depleted light-density marrow (TMoDLDBM) cells from humans in soft agar cultures which were stimulated with an exogenous source of CSA did not inhibit the CFU-GM proliferation, suggesting that ethanol has no direct toxic effect on the CFU-GM. T cells obtained from the blood of normal humans were cultured in the presence of phytohemagglutinin with 100 to 600 mg% ethanol. Cell-free conditioned media (CM) from these cultures were tested for CSA concentration by their capacity to stimulate proliferation of CFU-GM from human TMoDLDBM or rat whole bone marrow cells. The results indicated that ethanol at a concentration greater than 100 mg% inhibited CSA production from T cells. There was no evidence for production of an inhibitor of CFU-GM proliferation from T cells in the presence of ethanol. These results suggest that the neutropenia which occurs in relation to alcohol abuse may in part be related to decreased CSA production from T cells.

Adult↗
PubMed1984

Regulation of normal human blood neutrophilic, macrophagic, and eosinophilic committed stem cell proliferation by autologous blood T lymphocyte subsets.

The influence of T lymphocyte (T cell) subsets on the proliferation of the blood neutrophilic, macrophagic, and eosinophilic cluster and colony (aggregate) forming cells (CFC) was evaluated. The T cells and the CFC-enriched B-null cells (mononuclear cells depleted of monocytes and T cells) and null cells (B-null) cells depleted of B lymphocytes) were separated from the blood of normal individuals. The population enriched for OKT4 (T4 cells) monoclonal antibody-binding T helper/inducer cells and for OKT8 (T8 cells) monoclonal antibody-binding T suppressor/cytotoxic cells were separated from the T cells or mononuclear cells depleted of monocytes by negative enrichment using an immunoadherence "panning" method. These separated cell populations were cultured separately, and the B-null or null cells were cocultured with the T, T4, and T8 cells in agar medium in the presence and absence of an exogenous source of colony-stimulating activity (CSA). The cultures were evaluated at day 14. The B-null and null cells, but not the T cells or subsets, contained CFC. The number of CFC proliferated from the B-null or null cells increased significantly (p less than 0.001) in cocultures with unseparated T and T8 cells in a dose-dependent manner. The T4 cells neither promoted nor inhibited the CFC growth. The T8 population was a better promoter (p less than 0.01) of CFC growth than the unseparated T cells. This suggests that the CFC promoting effect of the unseparated T cells is probably due to the influence of the T8 subset present within the T cells. The proportion of the neutrophilic, macrophagic, and eosinophilic CFC that proliferated in these cultures was comparable under the influence of the T and T8 cells. The results of these studies indicate that the T8 population, which is the suppressor in the classical immune system, promotes the growth of the blood CFC. We speculate that the T cells are involved in the regulation of granulopoiesis in vivo.

Cell Division↗
PubMed1983

A triple stain technique to evaluate monocyte, neutrophil, and eosinophil proliferation in soft agar cultures.

A useful cytochemical technique has been developed which facilitates the identification of the types of cell aggregates which proliferate in soft agar cultures of hematopoietic stem cells. Staining of fixed agar discs for alpha-naphthyl acetate esterase (ANAE), naphthol AS-D chloroacetate esterase (CAE) and with Luxol fast blue (LFB) in sequence results in permanent preparations in which monocytic, neutrophilic and eosinophilic aggregates can readily be distinguished on the same slide. This represents an improvement over the currently used technique which relies on the removal of a representative sample of aggregates from the agar discs for cell typing. Whole plate staining results in more accurate estimates of eosinophil growth since the frequency of occurrence of these cell aggregates is low under many of the culturing conditions used. The technique provides a useful tool for studying normal and abnormal hematopoiesis.

Bone Marrow Cells↗
PubMed1983

Molecular heterogeneity of the concanavalin A tetramer: effects on binding to human red blood cells.

We have found that the distribution of the three main monomer species found in tetrameric concanavalin A was approximately 73% type A monomer (27,000 MW); 4% type B monomer (14,000 MW); and 23% type C monomer (12,000 MW). When this tetrameric concanavalin A was bound to human erythrocytes and the monomer distribution of the bound concanavalin A was examined, we found that it resembled that of the concanavalin A used in the binding reaction. However, when competing sugars were used, either to inhibit the binding of concanavalin A or to remove previously-bound lectin, examination of cell-bound monomer distribution revealed that there was a significant increase in type C monomers and a simultaneous decrease in type A monomers. The shifts in monomer distribution varied depending on experimental conditions and the particular competing inhibitor employed. These findings were taken to indicate that not all concanavalin A cell surface interactions are identical and that quantitative methods are available for studying this phenomenon.

Concanavalin A↗
PubMed1982

Differences in the sensitivity of normal human peripheral blood and bone marrow granulocytic-macrophagic and eosinophilic colony forming cells (CFC) to a source of colony stimulating factor.

The relative sensitivity of normal human peripheral blood (PB) and bone marrow (BM) granulocytic-macrophagic and eosinophilic committed stem cells (CFC) to a source of colony stimulating factor (CSF) was evaluated. In this study, PB and BM cells depleted of mature granulocytes, monocytes (Mo), thymus dependent lymphocytes (T cells), and, in some studies, bone marrow derived lymphocytes (B cells) were cultured in soft agar medium. Human placental conditioned medium (HPCM) was used as a source of CSF. The time sequence evaluation of cultures of PB and BM cells in the presence of a constant amount of HPCM confirmed the results of earlier culture studies of unseparated PB and BM nucleated cells which showed that the proliferation of PB CFC is maximum at or after days 14 to 15 and that of BM CFC at days 7 to 8. Culture of a constant number of PB and BM cells with variable amounts of HPCM indicated that PB CFC require an exogenous source of CSF for proliferation whereas BM CFC proliferate to a modest degree in its absence. The rate of increase in the number of CFC proliferated with the addition of increasing amounts of HPCM is higher for BM than for PB. These data indicate that the BM CFC are more sensitive to a source of CSF than are the PB CFC. Also, the results of this study, along with those in the literature, support the concept that the PB and BM CFC comprise distinct populations, and, further, suggest that the PB CFC is more primitive than the day 7 BM CFC.

B-Lymphocytes↗
PubMed1976

Endogenous nitrogen excretion and utilization of dietary protein.

1. The endogenous nitrogen losses of men of different ethnic, ecological and socio-economic backgrounds are similar when calculated per unit body-weight or per unit basal energy consumption. The hypothesis that endogenous N losses, adjusted upwards by a factor of 0-30 to equate them with N equilibrium, can be used to derive man's physiological requirements for proteins of high quality, e.g. those of egg and milk, was studied. 2. Men living in Nigeria, accustomed to eat diets which provided mixtures of protein only slightly higher than the 'safe level of intake' proposed by the Joint FAO/WHO ad hoc Expert Committee on Energy and Protein Requirements (FAO/WHO, 1973), were found to use absorbed N more efficiently than University of California students who habitually consume diets which supply a great excess of protein over that 'safe level'. 3. The greater protein-sparing effect of carbohydrates than of fats and oils may play a part in this more efficient use of protein by men living in developing countries. Also, man possesses mechanisms in intermediary metabolism which allow him to adjust to low levels of protein intake. 4. Thus it appears that all apparently healthy men cannot be considered equal in regard to their requirements for protein.

Adolescent↗
PubMed1976

The utilization of dietary protein by Nigerian men.

1. The excretion of urinary and faecal nitrogen by young Nigerian men of a low income group was found to vary significantly between subjects, but was not significantly different in the same subject, when they were given a mixed diet composed of rice, vegetables and fish on two separate occasions. At the levels of energy and protein supplied by this diet the men gained or lost small amounts of weight, mean values indicating N equilibrium, the variation around the mean being high. 2. The correlation between the urinary and faecal N of these men was significantly negative at and below the level of N equilibrium, becoming positive 2-3 weeks after they had consumed the above diet supplemented by 400 g of lean beef per day, and had already established considerable rates of gain in body-weight and N retention. The diets were made isoenergetic by adding the beef at the expense of cassava flour and red palm oil. 3. The physiological processes involved in the adaptation, by young Nigerian men of low income, to a highly efficient use of low-protein diets are discussed in relation to the biological value and true digestibility of those diets, and to the 'safe level of protein intake' and protein-energy ratios proposed by FAO/WHO (1973, 1975). 4. It is concluded that the protein requirements of apparently healthy men can only be established in the context of their ecological, socio-economic and nutritional backgrounds.

Adult↗
PubMed1971

Separation and identification of menaquinones from microorganisms.

Simple thin-layer chromatographic procedures are outlined for the separation, isolation, and characterization of a complex of lipophilic naphthoquinones. Procedures are also described for the quantitative recovery of naphthoquinones from thin-layer plates. The general usefulness of the described methods is demonstrated by their application in the analysis of menaquinones from several microorganisms. The methods allow distinction between menaquinones varying in side-chain length, degree of saturation, and geometry, as well as in the presence or absence of ring methyl groups.

Bacillus↗