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Biomedical subjects

D A Henderson

Publications and source records attributed to D A Henderson.

At least 19 recordsLinked to original sources

Molecular analysis of spontaneous glomerulosclerosis in Os/+ mice, a model with reduced nephron mass.

Oligosyndactyly mice (ROP Os/+) are a radiation-induced mutant strain with reduced glomerular number and increased glomerular size. We found that they develop glomerulosclerosis. At 3 mo, ROP Os/+ mice had diffuse mesangial expansion by light microscopy, whereas their +/+ littermates did not. Electron microscopic morphometry revealed a twofold increase in mesangial areas but no changes in the thickness of glomerular basal laminae. Mean glomerular volume was increased 1.8-fold. Cell number and thymidine labeling index were increased 1.3- and 2.4-fold, respectively. The amount of glomerular type IV collagen and tenascin but not laminin was increased by immunofluorescence microscopy. mRNA levels in microdissected glomeruli were measured by competetive reverse transcription-polymerase chain reaction and corrected for cell number. alpha 1-Chain type IV collagen and tenascin mRNAs were increased 3.2-fold and 1.8-fold, whereas laminin B1 mRNA levels were not. The levels of 72-kDa collagenase mRNA were increased 1.6-fold. Transforming growth factor-beta 1 mRNA levels were elevated 1.8-fold, but platelet-derived growth factor-B mRNA levels remained normal. This is the first analysis of glomerular molecular and cellular changes in a model of congenital nephron reduction.

Actins

Electronmicroscopic diagnosis of human papilloma virus in verruca plantaris.

The purpose of this study was to identify the human papilloma virus in verruca plantaris by transmission electron microscopy and study the cellular effect of human papilloma virus at both the transmission electron microscopy and light histochemistry level. The authors discuss the cellular pathology in relation to early studies and keratin disorders. Features identified by transmission electron microscopy are consistent with characteristics of human papilloma virus-1.

Adolescent

Characterization of keratin densities in mitotic WISH cells.

Three dimensional (3-D) reconstruction of four mitotic WISH cells from ultrathin sections gave an informative representation of the spatial distribution of keratin densities in these cells. The correspondence between the densities as studied by transmission electron microscopy (TEM) and the keratin bodies initially revealed by immunoflourescent colabeling of cultures, was confirmed by immunoelectronmicroscopy. The smaller, and sometimes more elongated densities, were relatively abundant just beneath the subplasmalemmal microfilament band; and at certain levels of the mitotic cell they were observed to be connected to neighboring densities by intact intermediate filaments (IFs). The larger and more spherical densities appeared to be somewhat more discrete and randomly distributed. Other observed associations of the keratin densities included the telophase contractile ring of microfilaments, chromosomes, the reformed telophase nucleus, and desmosomal junctions with neighboring interphase cells. Cytochalasin D (CD) treatment of cells displaced the peripheral keratin densities toward the cell membrane. The density volume constituted 0.52% to 1.57% of the total cell volume, and the proportional density size was decreased in the cells that had progressed into anaphase and telophase. The observed formation and subsequent dissolution of keratin densities during mitosis may represent a dynamic mechanism of restructuring the keratin cytoskeleton in an unpolymerized form in order to allow for rapid reformation of interphase cell junctions. The physical associations observed between intact IFs and the keratin densities may provide support at certain depths of the mitotic cell, and the juxtaposition of densities with nuclear components suggests a possible source of and role for keratin IFs during nuclear events.

Actin Cytoskeleton

Cellular morphology in outer medullary collecting duct: effect of 75% nephrectomy and K+ depletion.

The present study was designed to determine, in rats, whether 75% nephrectomy and potassium depletion affect the principal and intercalated cells in the outer medullary collecting duct in the same manner as they affect the principal and intercalated cells in the cortical collecting duct. Ten days after a 75% reduction of renal mass, whole animal glomerular filtration rate decreased and the fractional excretion of potassium increased in rats. However, no morphological changes occurred in either the principal or intercalated cells of the outer medullary collecting duct after the reduction of renal mass. When 75% nephrectomized rats were placed on a diet deficient in potassium, the concentration of potassium in plasma and the absolute and fractional excretion of potassium decreased significantly. In addition, marked hypertrophy occurred in both the principal and intercalated cells in the outer medullary collecting duct. Previous findings from the same animals used in the present study show that 75% nephrectomy caused hypertrophic changes in principal cells of the cortical collecting duct, which could be inhibited by potassium depletion induced by the dietary restriction of potassium. The findings also show that the intercalated cells of the cortical collecting duct in 75% nephrectomized rats were unaffected by potassium depletion. On the basis of our findings, it appears there is an absence of hypertrophy in either the principal or intercalated cells in the outer medullary collecting duct of the rat after renal mass in the animal is reduced significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Defining global medical education needs.

The graduates of medical education institutions should be, both in their numbers and in their acquired skills, appropriate to improving the health of the particular society they are intended to serve. Medical education should be tailored to deal with the diseases the physician is most apt to see--or at least apt to see in an academic medical center. Such logic does not prevail, however, in terms of either the numbers of physicians trained or the content of the medical curriculum. The Western model of a medical school curriculum has been adopted--but little adapted--for use by much of the Third World. Relevant subjects such as epidemiology, social sciences, and management are often either ineptly taught or omitted. A shift in attention from patient to community is recommended, accompanied by deliberate programs of education and health care to measure and improve the health of the community. Significant improvements in health in much of the world can be made only through community-based programs such as improved nutrition, education, sanitation, prevention of infectious diseases, and family planning. Two types of U.S. participation in international medical education are recommended: (1) specialty training of physicians from countries whose access to instrumentation and medical care support structures are similar to those in the United States, and (2) strengthening of institutions in developing countries in the areas of education, research, and practice appropriate to the particular needs of each of these countries.

Curriculum

Principles and lessons from the smallpox eradication programme.

The eradication of smallpox required a unique, fully collaborative international effort on the part of WHO and Member States. In the course of the programme, many lessons were learned in its organization, execution and evaluation which have implications for other international activities. Most important among these was the need to establish measurable objectives and to evaluate progress and performance in terms of these; to establish procedures for quality control both of vaccines and performance; to recruit the best possible personnel and support them; and to assure an on-going programme of problem-oriented research which can facilitate activities and resolve apparently paradoxical observations. The inherent capacities of national health services to execute their smallpox eradication programmes was gratifying. It encouraged the belief that other, more complex health measures could be undertaken. Although this would necessitate that adequate numbers of competent leaders be recruited and given delegated responsibility, such persons were usually found to be available although often inexperienced. WHO's roles in catalysing and orchestrating this great effort were critical. Its potential for promoting other efforts in disease prevention and health promotion was apparent although still only partially realized.

Communicable Disease Control

Delayed plasma clearance and hepatic uptake of lymph chylomicron 14C-cholesterol in marginally zinc-deficient rats.

Previously, chylomicrons from marginally zinc-deficient rats were shown to be abnormally large, with markedly reduced levels of apoproteins C and E. In the present study, effects of such changes on the plasma clearance and hepatic uptake of chylomicron cholesterol were investigated in rats fed 3 ppm of zinc (ZD), as compared with those fed 30 ppm of zinc (CT). The rate of plasma clearance was determined by plasma 14C-radioactivity at different intervals after intravenous injection of lymph chylomicrons labeled in vivo with 14C-cholesterol. The 14C-clearance curves were nonlinear, consisting of an initial rapid phase followed by a slow phase of clearance. The initial 14C-clearance was significantly (p less than 0.05) delayed whether the labeled chylomicrons from ZD donors were injected into ZD or CT recipients. The hepatic 14C-recovery in extracted lipids was also significantly lower in ZD rats. The present data provide first evidence that a marginal level of zinc deficiency produces a significant delay in the plasma clearance and hepatic uptake of chylomicron cholesterol. This may be attributable in part to the molecular alterations of chylomicrons induced by zinc deficiency.

Administration, Oral

Effect of marginal zinc deficiency on the morphological characteristics of intestinal nascent chylomicrons and distribution of soluble apoproteins of lymph chylomicrons.

Effects of marginal zinc depletion on the compositional and morphological characteristics of chylomicrons were investigated in adult male rats fed 3 ppm of dietary zinc, as compared with pair-fed and ad-libitum controls given 30 ppm of zinc for 6 to 8 wk. Lymph was collected by cannulating the intestinal lymphatic duct during infusion of a 1:1 mixture of Intralipid and 150 mM NaCl via a duodenal catheter. Lymph chylomicrons were isolated by ultracentrifugation and further purified by agarose column chromatography. A marginal level of zinc deficiency produced decreases in the relative concentrations of apolipoproteins C and E, with an increase in apoprotein A-I and no change in apoprotein A-IV and no significant alterations in the lipid components. Nascent chylomicrons in the intestinal absorptive cells were irregular and larger in shape and size, as determined by light and electron microscopy. The present results suggest that the changes in chylomicron apoproteins produced by zinc deficiency are due in part to postsynthetic modification of intestinal chylomicrons upon their release into the lymph.

Animals