Relation of the White Blood Cell Count to Obesity and Insulin Resistance: Effect of Race and Gender

PRATLEY, RICHARD E, CHARLTON WILSON AND CLIFTON BOGARDUS. Relation of the white blood cell count to obesity and insulin resistance: effect of race and gender. Obes Res. Recent reports suggest that the white blood cell (WBC) count is related to plasma insulin concentrations and insulin resistance in healthy individuals. The present study examines whether these relations are independent of obesity and the pattern of body fat distribution and tests whether race and gender affect these relations. WBC counts, insulin responses to a 75 gram oral glucose tolerance test (OGTT) and glucose disposal during a two-step hyperinsulinemic euglycemic clamp were measured in 300 men and women (149 Pima Indians, 100 whites, and 51 blacks) with a wide range of obesity. WBC counts were lower in blacks than Pima Indians or whites and tended to be higher in women than men. The subgroups were comparable in age and body weight, but percent body fat and plasma insulin concentrations were higher and glucose disposal during the glucose clamp was lower in Pima Indians than in blacks or whites. In the group as a whole, the WBC count correlated with obesity (body mass index and percent body fat), the waist to thigh ratio (an index of the pattern of body fat distribution), and plasma insulin concentrations and was negatively related to age and glucose disposal during the clamp. In multiple regression analyses, only age, race and obesity were significantly associated with the WBC count. When the analyses were restricted to Pima men, in whom correlations between the WBC count and the metabolic variables appeared the strongest, the WBC count remained significantly associated with plasma insulin concentrations, but not glucose disposal, after controlling for age and obesity. The results of this study indicate that age, race, and obesity are significantly associated with the WBC count in healthy individuals. Plasma insulin concentrations, but not insulin resistance per se, may also be weakly associated with the WBC count, but this may be population specific.     

Differential control of alveolar and ductal development in grafts of monodispersed rat mammary epithelium.

Multicellular secretory alveolar units (AU) develop in grafts of monodispersed mammary cells in intact recipient rats co-grafted with mammotropic hormone-secreting pituitary tumor (MtT). The cumulative evidence is consistent with a postulated clonal origin of these structures. Small numbers of multicellular structures of a second type, mammary ductal units (DU), were found in mammary cell grafts in intact Wistar/Furth recipients co-grafted with MtT W10 but not in intact F344 recipients co-grafted with MtT F4. Studies in (Wistar/Furth x F344) F1 hybrid recipients grafted with mammary cells from either parent strain demonstrated that this difference in DU formation is dependent on the strain of grafted MtT, and is not a genetic characteristic of the rat strain. DU formation is stimulated and AU formation is inhibited by elevation of mammotropic hormones from MtT coupled with glucocorticoid deficiency induced by adrenalectomy. cortisol treatment reverses this effect. Finally, in mammary glands in situ in intact rats, the total numbers of AU-forming clonogens decrease during 6 weeks after MtT transplantation. In contrast, during the same period, elevated mammotropins from grafted MtT coupled with glucocorticoid deficiency from adrenalectomy cause an increase in the total number of cells that are capable of AU formation when transplanted to intact recipients co-grafted with MtT. Thus, the same hormonal combination that stimulates DU formation in mammary cell grafts and has previously been shown to promote cancer in mammary glands in situ also stimulates an increase in the glandular content of assayable AU-forming cells in situ.     

Pattern formation inDrosophila melanogaster: The effects of mutations on polarity in the developing leg

Summary The effects of the mutations eyeless dominant (ey ^D) and shibire (shi) on bristle pattern in the legs ofDrosophila melanogaster were examined. Both mutations cause gaps in the intersegmental membranes which separate leg segments and often alter the position of these membranes. It was observed that pattern disturbances including reversed bristle polarity and duplication of structures such as sex combs and transverse rows were associated with defects in the intersegmental membranes. The alterations in bristle polarity and most of the duplication of structures could be accounted for by a segmentally reiterated gradient in the legs which controls bristle polarity and which requires the integrity of the intersegmental membrane. A computer simulation of this gradient model was devised which accounted for the observed results. The possible role of cell death as a cause of the gaps in the intersegmental membrane and of some of the pattern disturbances was examined.     

The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis

There are three major structural classes of mycolic acids in the cell envelope of Mycobacterium tuberculosis (MTB): alpha-, methoxy- and ketomycolate. The two oxygen-containing classes are biosynthetically related through a common α-methyl hydroxymycolate intermediate. BCG strains that fail to produce methoxymycolate and instead produce only keto- and alpha-mycolic acids show apparent defects in the O -methyltransferase MMAS-3. Overproduction of MMAS-3 from MTB resulted in a complete replacement of ketomycolate by methoxymycolate in both BCG and MTB. In vitro growth of these recombinant strains lacking ketomycolate was impaired at reduced temperatures but appeared to be normal at 37°C. Glucose uptake was significantly decreased in such strains, but uptake of chenodeoxycholate and glycine was unaffected. Although sensitivity to INH remained unchanged, these cells were found to be hypersensitive to ampicillin and rifampicin. Infectivity of BCG and H37Rv wild type or MMAS-3 overproducers in THP-1 cells was somewhat affected, but the ability of the strains lacking ketomycolate to grow within this macrophage-like cell line was severely compromised. In vivo labelling of mycolic acids during growth of H37Rv within THP-1 cells revealed a substantial increase in ketomycolate and alphamycolate synthesized by intracellularly grown mycobacteria. These results establish a critical role for mycolate composition in proper cell wall function during the growth of MTB in vivo .