Recertification and peer review in the United States.
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Biomedical subjects
Publications and source records attributed to J C Rose.
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We critically evaluated the major techniques for measurement of intramyocardial pressure (IMP) (closed, perfusion, open, microtransducer). Each technique demonstrates a gradient in systolic IMP increasing with depth from the epicardium. The estimated magnitude of this gradient varies with the technique employed. Indirect methods (closed, perfusion) estimate a higher value for the systolic IMP gradient. The open and microtransducer methods, which measure a direct hydrostatic pressure within the myocardium, are less invasive and reflect more reliably the magnitude of IMP. The results for the open and microtransducer methods were comparable and indicate that normalized systolic IMP increases linearly from the epicardium. In the inner half of the myocardium systolic IMP approaches the level of systolic LVP and in the subendocardial layer it exceeds the systolic LVP by about 8%. A reverse IMP gradient occurred in late diastole ranging from 5 mmHg in the subendocardial region to 25 mmHg in the subepicardium.
Enkephalin immunoreactive material from adrenal glands was characterized both in maternal and fetal sheep at various gestational ages. Whole gland extracts from both maternal and fetal sheep contained three major peaks of Enk immunoreactivity corresponding to apparent molecular weights of 10,000, 2800, and less than 1200 daltons. The majority of maternal adrenal Enk immunoreactivity was found in medullary tissue, although cortex also contained low but detectable amounts. This was also the case in newborn lambs and 139 day fetuses, where adrenal cortex was sufficiently developed to allow extraction and quantitation of opioid material. In fetuses at mid-gestation (70-80 days), adrenal medullary Enk immunoreactivity was approximately 75% of maternal values. Met-Enk and Leu-Enk content in 139 day fetal medulla were 70 and 76% of maternal values respectively, while newborn Met- and Leu-Enk medullary content were similar to maternal values. The molar ratio of Met-Enk to Leu-Enk was approximately 4:1 in both maternal and fetal adrenal medulla, and 2:1 in adrenal cortex, suggesting different synthetic processing of opioid peptides in the two tissues. The early appearance of significant levels of adrenal medullary Enk immunoreactivity and subsequent development paralleling that of catecholamines suggest a predominant role for adrenal enkephalins in regulation of fetal cardiovascular function early in gestation.
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The formation of adrenocortical zonation occurs in rats during late gestation. Since adult cortical function is modulated by neural mediators, it is possible that the development of differentiated function is dependent on cortical innervation. The goal of this study was to compare the pattern and timing of rodent and ovine adrenal innervation during late organogenesis by staining with antibodies directed against the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide tyrosine (NPY) and the catecholamine biosynthetic enzyme, tyrosine hydroxylase (TOH). Rat adrenals were collected from fetal days 17-21 (term=21 days) and ovine adrenals from fetal days 101-136 (term=145 days). Adrenals were fixed, cryosectioned at 100 microns and immunostained using Cy3-conjugated secondary antibodies. In both species, staining of VIP, CGRP, NPY and TOH fibers was observed in the capsule and subcapsular layers of the cortex during gestation. In late gestation, VIP- and NPY-positive ganglions cells were observed near the medulla extending processes toward the outer cortex; in ovine adrenals, fibers from ganglion cells appeared to surround nests of outer cortical (presumably, zona glomerulosa) cells. These data show that phenotypically distinct neural elements appear at different stages of adrenocortical development. The presence of neural elements in contact with adrenal cortical cells supports the possibility for neural control of adrenocortical development.
OBJECTIVE: To investigate the effect of renal denervation on renin mRNA levels in fetal and nonpregnant adult ovine renocortical tissue and in isolated juxtaglomerular cells under basal conditions and after stimulation. METHODS: The left kidney was denervated and the right kidney subjected to a sham procedure in nine ovine fetuses (136-141 days' gestation) and 20 nonpregnant ewes. After 5-7 days the denervated and intact kidneys were obtained, and renin-containing renal cortical cells were isolated and cultured overnight. Then cells were treated with isoproterenol, forskolin, or isomethylbutyl xanthine (IBMX) for 4 hours. Total RNA was isolated and renin mRNA measured by RNase protection assay. Cyclic adenosine monophosphate (cAMP) levels were measured in the incubation medium with a competitive enzyme immunoassay. RESULTS: In adults, basal renin mRNA levels were significantly lower in denervated than in sham-operated kidneys. No difference was noted between denervated and intact fetal kidneys. Renin mRNA levels were significantly higher in fetal than in adult kidney tissue, and cells from fetuses had greater increases in renin mRNA after stimulation than did cells from adults. Fetal cells also released more cAMP into the incubation medium, and there was a correlation between cAMP and renin mRNA levels. CONCLUSIONS: The data indicate the effects of renal denervation on renin mRNA expression in the kidney are age dependent and that the fetus in late gestation has a mechanism for maintaining renin mRNA levels after denervation, which is absent or nonfunctional in the adult.
A peptidyl fluoromethyl ketone (Z-Phe-Ala CH2F) was found to be an effective compound in a time dependent inactivation of cathepsin B isozymes from a number of tissues including human tumors. The effect was visualized by employing an activity-specific fluorescent print technique preceded by isoelectric focusing. The technique could yield additional information of selective inhibition of isozymes as observed with rat pancreas. The fluoromethyl ketone is 30-fold more potent than the known inhibitor of cathepsin B, Z-Phe-AlaCHN2 in parallel evaluation. Furthermore, the fluoromethyl ketone may have in vivo potential in the inhibition of cathepsin B, in view of the results of toxicological studies. The findings demonstrate that the application of enzyme-directed overlay membranes, impregnated with specific substrates, following isoelectric focusing could be very useful in the study of proteases and their involvement in the oncogenic process.
Circadian rhythms of plasma immunoreactive insulin and skin surface temperature were demonstrated in a group of African green vervets. Alteration in the timing of a single daily meal of fixed calorie content resulted in an acrophase shift of plasma immunoreactive insulin for the group of animals and in an acrophase shift of skin surface temperature in 7 or the 8 animals studied. The acrophase shift of skin surface temperature was considerably less then the shift of acrophase of plasma immunoreactive insulin, which closely approximated the shift in meal timing. The results of this study are compared with results of similar studies in human beings.
OBJECTIVE: To determine if the increase in intrarenal renin content that occurs in late gestation in the fetal lamb results from an increase in the proportion of cells containing renin, an increase in the amount of renin per renin-containing cell, or both. METHODS: Kidney cells with a density of 1.062 g/mL were isolated from ovine fetuses at 100-104 days gestation (n = 6, immature) and at 131-139 days gestation (n = 6, mature). This fraction was enriched with renin-containing cells. Total renin (TR) and active renin (AR) were measured by their ability to generate angiotensin I (AI). Renin mRNA was measured by RNase protection assay. The presence of renin in cells and the capacity to release it were identified by immunocytochemistry and cell immunoblot analyses. Data were analyzed by analyses of variance. RESULTS: The TR and AR in isolated cells increased from 3.7 +/- 0.3 and 2.5 +/- 0.2 micrograms AI/microgram protein . hr-1 in immature fetuses to 6.2 +/- 0.7 and 5.0 +/- 0.6 micrograms AI/microgram protein . hr-1 in mature fetuses (P < .01). The percentage of immunopositive renin cells (PC) was greater in mature (40.6 +/- 4.3) than in immature fetuses (15.2 +/- 1.2) (P < .01). The TR/PC and AR/PC were also higher in mature (8.2 +/- 0.6 and 6.6 +/- 0.4 ng AI/h . pc-1) than in immature animals (6.5 +/- 0.6 and 4.4 +/- 0.4 ng AI/h . pc-1) (P < .01). CONCLUSIONS: The data indicate that the increase in TR and AR occurring during development in fetal lamb kidney results from an increase in both the number of renin-containing cells and in the renin content per cell.