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Biomedical subjects

H Latta

Publications and source records attributed to H Latta.

At least 19 recordsLinked to original sources

An approach to the structure and function of the glomerular mesangium.

The mesangium of the glomerulus is a connective tissue tree arising at the vascular pole of the glomerulus and supporting the glomerular capillaries. It is partly covered by a basement membrane that follows the epithelial cells from the peripheral glomerular capillary wall over the supporting tissue. The capillary endothelium does not normally have a separate basement membrane. The endothelium has fenestrations that open directly into the mesangium and allow blood plasma and tracers to flow into the mesangium. The fenestrations partially restrict (or sieve) particles over 405 A in mean length from entry. Tracers move in intercellular channels and are filtered and concentrated by the basement membrane at the sides of the mesangium or by mesangial matrix filaments in the channels between cells. The irregular distributions of flow, matrix, and concentrations of tracers may account for irregular lobular reactions in glomerular disease. Two main pathways of flow seem to be (1) through the basement membrane and between the epithelial foot processes to form part of the glomerular filtrate and (2) into the efferent capillaries through their mesangial fenestrations. Intrinsic mesangial cells can now be regarded as myofibroblasts associated with the production of the connective tissue matrix. These cells hold the basement membrane to maintain the shape of the glomerular capillaries, they swell readily, and they can constrict like smooth muscle cells with appropriate stimulation. These reactions may enable them to control the flow of blood through the capillary network in glomerular disease. Mesangial cells can take up large amounts of foreign material within 24 h. Intrinsic mesangial cells and monocytes can increase in numbers in disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Lymphomatoid granulomatosis and malignant lymphoma of the central nervous system in the acquired immunodeficiency syndrome.

While primary and secondary malignant lymphomas have been well-documented in the CNS of patients with the acquired immunodeficiency syndrome (AIDS), only one case of lymphomatoid granulomatosis (LG) involving the CNS has been reported. We present three AIDS patients with multiple grossly evident foci of necrosis in the cerebral hemispheres which, on histologic evaluation, were seen to contain angiocentric mixed chronic inflammatory infiltrates with atypical mononuclear cells, luminal thrombosis, and infarction, which is typical of LG. LG was also identified in sections of the lung in one case. Lymphoma was found in other regions of the brain in two cases, suggesting the evolution of LG into cerebral lymphoma. In addition, widespread perivascular multinucleate syncytial giant cells, associated with human immunodeficiency virus (HIV) infection of the CNS, were identified in all patients. The features of LG, its relationship to lymphoma, and the possible etiologic role of an immunodeficiency state or the HIV virus in the pathogenesis of LG are discussed.

Acquired Immunodeficiency Syndrome

Initial characterization of sheep T-cell growth factor and its species-restricted activity on human, rat, and mouse cells.

Sheep T-cell growth factor (TCGF) was prepared from concanavalin A-activated sheep peripheral blood cells and subsequently characterized by ammonium sulfate precipitation, gel exclusion chromatography, and isoelectric focussing. The TCGF was found in the 60-80% ammonium sulfate fraction and was shown to have an apparent molecular weight of 32,500 and an isoelectric point in the range pI 5.2-5.5. The ability of the sheep TCGF to promote proliferation of activated human, sheep, mouse, and rat cells was compared with that of human TCGF prepared by phytohemagglutinin stimulation of lymphocytes from multiple donors and TCGF prepared from concanavalin A-stimulated rat and mouse spleen cells. Human TCGF was found to act across all species barriers, rat TCGF supported the growth of cells of all species except human, and mouse only promoted the growth of activated mouse and rat cells. Sheep TCGF was unique in being unable to support the growth of any cells except autologous cells.

Animals

Mesangial fenestrations, sieving, filtration, and flow.

Small tracers in the circulation enter the rat mesangium rapidly and in large amounts that indicate a sizable plasma flow into the mesangium. Entrance is effected through mesangial fenestrations with a mean width in scanning electron microscopy of 376 A, a size similar to fenestrations in peripheral glomerular capillary walls. This is considerably smaller than the mean size of 678 A found with transmission electron microscopy, but the difference is probably due largely to the anionic surface coat on endothelial cells. Measurements of asymmetric thorium dioxide particles show that smaller ones with a mean length of 315 A enter the mesangium preferentially and that larger particles with a mean length of 405 A are partially restricted, supporting the idea that the measured width in scanning electron microscopy is close to the actual width in vivo. Fluid flow into the mesangium requires fluid flow out. The appearance time and accumulation of tracers suggest the following exit paths of flow from the mesangium: through the overlying epithelium into the urinary space contributing to glomerular filtration and concentrating large tracers beneath the basement membrane in the paramesangial region, into the efferent glomerular capillaries after tracers have been filtered out by the fibrillar matrix, and through the hilus into the juxtaglomerular apparatus (quantitatively small).

Animals

Effects of excessive sodium chloride on the juxtaglomerular apparatus and blood pressure of uninephrectomized rats.

To clarify the functions of the agranular cells in the polar cushion of the juxtaglomerular apparatus, the effects of drinking 1% NaCl or eating a diet containing 8% NaCl were examined on the numbers of granular and agranular cells in the polar cushions, the kidney weights, and the blood pressures of male Sprague-Dawley rats after uninephrectomy. Only 11.8% of the cells in the polar cushions of control rats in this study were granular; hence, 88.2% of the cells were agranular. After uninephrectomy of rats on a normal diet with tap water, the maximal increase in relative weight of the remaining kidney occurred within 2 weeks, and the degree of hypertrophy was estimated as 64%. Rats with a high salt intake after uninephrectomy had a similar increase, indicating that a high salt intake after uninephrectomy did not affect the degree of hypertrophy of the remaining kidney. The mean juxtaglomerular cell count (JGCC) showed moderate increases 2 weeks after uninephrectomy. Drinking 1% NaCl for 2 weeks after uninephrectomy produced about twice as much increase in the JGCC. Maximal initial increases in JGCCs occurred at 2 weeks, well before an increase in blood pressure. Drinking 1% NaCl had no significant effect on blood pressure within 2 weeks, but there was a definite hypertension at 8 weeks, with no further increase in JGCC. On an 8% NaCl diet hypertension developed between 8 and 16 weeks, when the JGCC was greater than previous levels. Clipping the renal artery of a solitary kidney produced hypertension but no increase in JGCC within 2 weeks. Uninephrectomy lowered the mean granular cell count, and drinking saline lowered it even more. Hence, the proliferation involved agranular cells. In summary, excessive NaCl intake was associated with a rapid proliferation of agranular cells which was maximal at 2 weeks and occurred before any significant increase in blood pressure. This suggests that the agranular cells in the polar cushion of the juxtaglomerular apparatus are concerned more directly with sodium chloride metabolism than with blood pressure regulation.

Animals

Acute hematogenous pyelonephritis in the rabbit. Electron microscopic study of Escherichia coli localization and early acute inflammation.

Injection of approximately 10(6) to 10(9) Escherichia coli into the renal arteries of rabbits resulted in retention of sufficient numbers of organisms in renal vessels to permit study of the mechanism of localization by electron microscopy. After injection of the bacterial suspension, perfusion fixation was used to maintain open vascular contours. Individual organisms were found to adhere to the endothelium of glomerular and intertubular capillaries, and ruthenium red staining demonstrated a close interaction between the largely polysaccharide bacterial microcapsule and the sialoglycoprotein endothelial surface coat. Thus, individual E. coli seem to localize in the rabbit kidney in this model by sticking to the endothelial surfact coat of the renal vessels. After localization, polymorphonuclear leukocytes and monocytes appeared in the capillaries and phagocytosed the bacteria. Phagocytosis of bacteria was evident at 10 minutes and was almost complete at 60 minutes and, although less frequent, were associated with small amounts of fibrin at 60 minutes. This acute inflammation and thrombosis may be mediated by activation of complement through the alternate pathway.

Acute Disease

Granular and agranular cell counts in the juxtaglomerular apparatuses of rats with unilateral renovascular hypertension.

Counts were made of granular and agranular cells in the juxtaglomerular apparatuses of rats with unilateral renovascular hypertension, using light and electron microscopy. Both granular and agranular cells may appear binucleated; therefore, nuclear counts need to be corrected by 4 to 8 per cent to get true cell counts. The polar cushion (Polkissen) corresponds to the cells included in the juxtaglomerular cell count, which is really a nuclear count. Interstitial or inflammatory cells may lie close to the polar cushion and should be excluded from the counts. The polar cushions in sham-operated rats contained mostly agranular cells: less then 6 per cent of the cells were granular. Most of the granular cells lay outside the polar cushion in afferent and efferent arteriolar walls. With acute hypertension the cells in the polar cushion increased 26 per cent due to increases in both granular and agranular cells, with the result that 11 per cent of the cells were granular and 89 per cent agranular. The number of granular cells seemed to decrease with chronic hypertension while the number of agranular cells remained elevated. This suggests the agranular cells have a function which is independent of that of granular cells.

Acute Disease

Glomerular mesangial and endothelial cell swelling following temporary renal ischemia and its role in the no-reflow phenomenon.

The purpose of these experiments was to define changes in glomeruli of rats kidneys which could account for a marked reduction of blood flow immediately following temporary ischemia. After the renal artery had been clamped for 60 minutes, mesangial and endothelial cellular swelling was sufficiently severe to compress and trap intracapillary erythrocytes, obstruct capillary lumens, and prevent reflow of an isotonic carbon suspension. Perfusion of saline solution before the renal arteries were clamped washed blood from the kidney, and the resulting cellular swelling alone was not sufficient to block capillary lumens. Erythrocyte trapping did not occur after 15 minutes of ischemia. Swelling of glomerular and tubular epithelial cells produced some extrinsic capillary compression that could contribute to erythrocyte trapping, but this appeared to be of minor importance in producing the no-reflow phenomenon.

Animals

Unilateral renovascular hypertension in rats. Measurements of medullary granules, juxtaglomerular granularity and cellularity, and areas of adrenal zones.

To produce hypertension, the left renal artery was clipped in 20 rats. Six rats had a sham operation. After 4 months, some of the rats showed only a moderate increase in blood pressure, and a second clipping of the same artery was performed. When hypertension became severe in some of the rats, 2 to 4 weeks later, all rats were sacrificed. The "clipped" rats were divided into four groups depending on whether they had little change in blood pressure, acute hypertension, chronic hypertension, or chronic and superimposed acute hypertension. The average adrenal weights were increased in the two groups with acute hypertension. The area of the adrenal glomerular zone was increased in all three groups with hypertension. The groups with acute hypertension also showed increases in the combined areas of (1) the medullary and androgenic zones and possibly (2) the fascicular and reticular zones. The granules of the left juxtaglomerular apparatus were greatly increased in the group with acute hypertension, but were only slightly elevated in the group with chronic hypertension and the group with chronic and superimposed acute hypertension. An increased juxtaglomerular cellularity in the clipped kidney correlated best with hypertension. Renal medullary granular counts were decreased in the right and left kidneys of all clipped groups whether or not they had hypertension, but no changes were found in the amount of medullary interstitial space. The above results are consistent with the evidence in acute unilateral renovascular hypertension with the opposite kidney intact that the clipped kidney is responsible initially via a renin-angiotensin-aldosterone mechanism, with participation by the major adrenal zones. In chronic hypertension some other mechanisms, with participation by the major adrenal zones. In chronic hypertension some other mechanisms, which seem to be related to juxtaglomerular cellularity in the clipped kidney, are operating. Other evidence suggests that such mechanisms may depend on sodium retention, volume expansion, and increased sensitivity to vasoconstrictors.

Acute Disease