Leukokinetic Studies. VII. Morphology of the Bone Marrow and Blood of Dogs Given Vinblastine Sulfate

The effect of a single injection of vinblastine sulfate was studied in 50mongrel dogs. Nine of 34 dogs given 0.2 mg./Kg. of VLB died with gastrointestinal toxicity and the mortality rate increased as the dosage of VLB wasincreased. The morphologic pattern of leukocyte suppression and recovery inthe bone marrow and blood was studied in detail in surviving animals.

The cells of the bone marrow were markedly affected by VLB. Within 4hours there was an increase in the number of cells in metaphase and, by day1, virtually all proliferating leukocytes and erythrocytes had disappeared. Anorderly repopulation of the bone marrow followed.

The neutrophils, eosinophils, lymphocytes and monocytes of the blood wereall markedly altered in concentration after VLB. Each type of cell first decreased to abnormally small numbers and then increased to abnormally largenumbers in the blood. The curve of disappearance from and reappearance inthe blood differed for each cell type.

The changes in blood neutrophil number and morphology were correlatedwith changes in the blood neutrophil precursor cells of the marrow. The following conclusions were reached concerning the neutrophils and the assumptions implicit to these conclusions were detailed.

1. In the dog, the marrow contains enough post-mitotic granulocytes toreplace those lost from the blood for at least 3 to 4 days.

2. The release of mature neutrophils from the bone marrow is a functionof the rate at which blood neutrophils are lost and proceeds normally evenwhen the marrow granulocyte reserve is partially depleted.

Submitted on March 27, 1963 Accepted on August 20, 1963     

Immunolocalization of fibroblast growth factor-1 and -2 in the embryonic rat kidney

Summary: Fibroblast growth factors (FGF) regulate cell proliferation, migration, differentiation and angiogenesis during morphogenesis in many different tissues. Recent evidence indicates that exogenous FGF-2 stimulates mesenchymal condensation in cultured rat metanephroi, a crucial epithelial-mesenchymal induction event in the developing nephron. the aim of the present investigation was to determine the in vivo distribution of FGF-1 and FGF-2 in developing rat metanephroi at embryonic days 14, 15, 16, 18 and 20. Avidin-biotin enhanced indirect immunohistochemistry was used to demonstrate that both FGF-1 and FGF-2 were co-localized in metanephroi at all ages studied. High levels of FGF-1 and FGF-2 were present in ureteric bud branches and in developing distal tubules. Fibroblast growth factor-1 and FGF-2 were colocalized in developing nephron elements, from vesicles to S-shaped bodies, and in the mesangium of capillary loop and maturing stage glomeruli. Both growth factors were present in the mesenchyme of the nephrogenic zone and in the interstitium of the developing cortex. However, immunostaining for FGF was not evident in mesenchymal condensates, endothelial cells, medullary interstitial cells, or in the thin undifferentiated epithelium of the immature loop of Henle. These findings indicate that the expression of both FGF-1 and FGF-2 is tightly regulated in the embryonic kidney and suggest a role for these molecules in kidney development.     

Reliability of a Timeline Method: assessing normal drinkers' reports of recent drinking and a comparative evaluation across several populations

Since alcohol research involves both clinical and non-clinical populations, it is important to evaluate drinking assessment methods across different subject populations. Over the past several years, the reliability of the timeline (TL) method of gathering retrospective reports of recent drinking has been evaluated in several studies, and this method has been shown to have generally high reliability with outpatient alcohol abusers, in-patient chronic alcoholics, and normal drinker college students. The present study examined the reliability of the TL method with normal drinkers in the general population. Similar to other populations, the test-retest reliability of male (n=31) and female (n=31) normal drinkers' reports of recent drinking behaviour was found to be generally high. Data gathered by the TL method were also compared to data gathered from the same subjects using a common quantity-frequency (QF) method. Consistent with earlier reports, QF categorization provided a relatively insensitive measure of individual differences in drinking behaviour as compared to TL-derived data. Since the TL method has now been shown to have fairly good reliability for assessing recent drinking across a broad range of drinkers, it can be used for comparative evaluations of drinking behaviour across studies with different subject populations.