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Biomedical subjects

D S Folse

Publications and source records attributed to D S Folse.

At least 19 recordsLinked to original sources

Lack of effectiveness of antiestrogens RU 39,411 or keoxifene in the prevention of estrogen-induced tumors in Syrian hamsters.

As part of a search for an effective and safe antiestrogen to be used as adjunct therapy in the treatment of breast cancer, we examined the potential of RU 39,411 and keoxifene to inhibit the incidence of estradiol-induced kidney tumors in Syrian hamsters. Groups of 10 hamsters were chronically treated with implants of either keoxifene, RU 39,411, estradiol plus keoxifene, or estradiol plus RU 39,411 for 8 months. Five hamsters received only estradiol and 5 control animals remained untreated. There was a 100% kidney tumor incidence in estradiol-treated hamsters, which was not statistically different from that in animals co-treated with estradiol plus keoxifene (3 of 4 hamsters with tumors) or estradiol plus RU 39,411 (7 of 8 hamsters with tumors). Rodents treated only with antiestrogen remained tumor free. In addition to kidney tumors, testicular cancer was also found in animals cotreated with either estradiol plus keoxifene (2 of 4 hamsters with tumors) or estradiol plus RU 39,411 (3 of 8 hamsters with tumors). Two animals of this latter group also developed liver tumors. Testicular or liver neoplasms were not observed in hamsters implanted only with estradiol or only with antiestrogen. The lack of inhibition of estrogen-induced carcinogenesis in hamsters by RU 39,411 or keoxifene suggests that these two antiestrogens are not as effective as previously tested substances in inhibiting the appearance of this cancer. However, their concentrations were sufficient to induce, in combination with estradiol, the development of testicular tumors in these hamsters.

Animals↗

Edema resulting from experimental filariasis.

Domestic cats and patas monkeys were infected with Brugia malayi so that the worms localized in the regional lymphatics of the hind legs. Reaction to the filarial parasites resulted in visible local edema in cats and disruption of normal lymph flow in the monkeys. Edematous tissue was examined grossly and by light and electron microscopy. Lymph flow patterns were examined by direct observation following injection of lymph staining dye and reflection of the skin, by X-ray following injection of radio-opaque contrast media, and by lymphscintigraphy after subcutaneous injection of radioisotopes. Clinical edema occurred in cats but not in monkeys. However, disruption of normal lymph flow in monkeys infected with Brugia could be demonstrated by lymphscintigraphy.

Animals↗

Quantitative glomerular morphology of the normal and diabetic baboon kidney.

This is a study of quantitative glomerular morphology in 14 normal and 6 long-term diabetic female baboons between 3 and 25 years of age. In the normal female baboon, peripheral glomerular capillary basement membrane thickness increased until around 10 years of age, reached a plateau between 10 and 20 years of age, and possibly decreased at 25 years of age. Mean value for young (3 to 7 years of age) and older (10 to 25 years of age) controls were 266 nm and 329 nm respectively. Fractional volumes of mesangial matrix (8.9%) and mesangial cells (6.8%) were not affected by age. Glomerular basement membrane thickness and the volume of mesangial matrix increased progressively in female baboons with poorly controlled pancreatectomy-induced diabetes, while the volume of mesangial cells remained unchanged. After 106 to 145 months of diabetes, glomerular basement membrane thickness and the volume of mesangial matrix were 558 nm and 18.7% respectively. These values were significantly greater than those of the age-matched controlled (p = less than 0.05). By light and electron microscopy, the normal baboon glomerular morphology, morphometric measurements and changes with age were similar to those in man. The renal changes in diabetic baboons were also similar in morphology and rate of development to those of mild to moderate diffuse diabetic glomerulosclerosis in humans, indicating that the baboon is an ideal model for the long-term study of diabetic glomerulosclerosis. The presence of considerable interanimal variability in the degree of glomerulosclerosis attained after prolonged diabetes suggested that glomerulosclerosis progressed at different rates in these models. The reason for this was not apparent.

Aging↗

Perturbation of lymphatic endothelial cells in experimental Brugia malayi infections.

Infection with filarial nematodes induces lymphatic dysfunction in many individuals in endemic areas. The present morphometric study describes changes in lymphatic endothelial cells of Brugia-infected cats. Transmission electron microscopy revealed a decrease in the number of cytoplasmic vesicles in endothelial cells from lymphatic vessels harboring filarial nematodes (4.9 vesicles per micron 2 cytoplasm) when compared with similar cells from the contralateral uninfected control vessels (9.0 vesicles per micron 2). The size of the vesicles and their location within the cytoplasm was not changed. Irregular large vacuoles, often containing degenerating organelles, were common in endothelial cells lining Brugia-infected lymphatic vessels. These studies suggest that damage of cells by living or dead worms or worm products may have a direct effect on the endothelial lining of lymphatic vessels. This may compromise the efficiency of vessels that collect and transport edematous fluid in affected limbs.

Animals↗

Use of 99mTc-sulfur colloid to assess lymphatic dysfunction in filarial infection.

Investigations of lymphatic dysfunction in animals infected with filarial parasites has been hampered by a paucity of techniques to measure efficiency of lymphatic drainage. In this study a 99mTc-sulfur colloid technique was used to assess the efficiency of lymphatic drainage in Patas monkeys infected with filarial nematodes. In all 15 uninfected hind limbs there was rapid and consistent appearance of labeled colloid in the primary lymph node (popliteal) and subsequently in the secondary nodes (abdomino-pelvic) in 11 of 15 limbs. In contrast, in all eight limbs tested 1-9 months after infection there was reduced rate of migration of the colloid and initial appearance in the abdomino-pelvic region: subsequent accumulation was seen in the popliteal region in only four of the limbs. This data indicated that lymphatic vessels were blocked and that collateral vessels channeled the colloid to the secondary lymph nodes. The lymph flow patterns demonstrated by the isotope technique were supported at autopsy.

Animals↗

The effect of t-butylated hydroxytoluene on glutathione linked detoxification mechanisms in rat.

When rats were fed a diet containing 0.4% (w/w) butylated hydroxytoluene (BHT), a three-fold increase in total glutathione (GSH) S-transferase activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was observed in liver but not in lung or kidney. Hepatic GSH S-transferase activities towards styrene oxide (SO) and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were also increased, but to a lesser extent. Isoelectric focusing studies indicated that the activities of most of the rat liver GSH S-transferase isoenzymes were induced. Immunoprecipitation studies of the native and induced enzymes suggested that de novo synthesis of these proteins caused the increase in GSH S-transferase activity in liver. A two-fold increase in glutathione reductase activity in liver upon dietary administration of BHT was observed. Kinetic and physical properties of the native and induced enzymes were similar which may indicate that the induction is due to the synthesis of this enzyme. A significant increase in reduced glutathione (GSH) content in liver and lung was also seen in rats treated with BHT.

Animals↗

Dominant lethal effects of n-butyl glycidyl ether in mice.

Using the dominant lethal assay, the ability of n-butyl glycidyl ether to induce mutations in male mice was investigated. No significant dose-related changes either in pregnancy rates or in average number of implants per pregnant female were found. However, while the results were not altogether conclusive, there was evidence of a significant increase in fetal death rates by the end of the first week after the highest dosage was administered.

Animals↗

Leprosy in wild armadillos (Dasypus novemcinctus) of the Texas Gulf Coast: epidemiology and mycobacteriology.

A significant prevalence of leprosy has been demonstrated in wild Louisiana armadillos. The Texas Gulf Coast still has endemic human leprosy, and recent mores in Texas have markedly increased armadillo-human contact. Armadillos were screened by physical examination, and by ear-snip and slit-scrape technique. Animals that screened "positive" were sacrificed and necropsied under aseptic conditions. Liver, spleen, gross lesions, and four groups of lymph nodes were cultured for mycobacteria and were studied histologically. Base ratios and DNA homology with Mycobacterium leprae were determined on mycobacteria from two armadillos (and two tissues from one of these); these studies indicate that the organism found in Texas armadillos is M leprae. Twenty-one of the armadillos were leprous--4.66%. The local prevalence varied from 1.0% to 15.4%. Epidemiologic implications of these findings and the occurrence of other concomitant mycobacterial infections are discussed.

Animal Diseases↗

Leprosy in wild armadillos (Dasypus novemcinctus) on the Texas Gulf Coast. Ultrastructure of the liver and spleen.

Recent studies have established that the "naturally-occurring leprosy-like disease of wild armadillos" is, indeed, caused by Mycobacterium leprae indistinguishable from M. leprae from human lepromatous leprosy. The present study reports the ultrastructure of the mycobacteria and host response in deep viscera, liver and spleen, in Texas armadillos with sylvatic leprosy. Evidence for acid-fast bacillary proliferation in these organs and penetration of hepatocytes is given. Acid-fast bacilli concentrated in activated macrophages in Billroth cords and sheaths of Schweigger-Seidel of the spleen and in Kupffer cells of the liver. Both mycobacteria and host response seen in lepromata of sylvatic leprosy, lepromatous lesions produced by injection of inocula from human lepromata and human lepromata, are compared.

Animal Diseases↗

Leprosy in wild armadillos (Dasypus novemcinctus) on the Texas Gulf Coast: anatomic pathology.

Recent studies of the "naturally occurring leprosy-like disease of wild armadillos" establish that the causative bacillus is genetically identical to M. leprae from human sources, and thus the disease is a zoonosis, sylvatic leprosy. A recent survey of 451 wild armadillos from the Texas Gulf Coast demonstrated sylvatic leprosy in 4.66%. This companion study reports the anatomic pathologic changes seen in the 17 leprous and 17 nonleprous armadillos necropsied in that survey. Findings support previous studies on the histopathology and pathogenesis of sylvatic leprosy, but a broader spectrum of histologic changes are noted.

Animal Population Groups↗

Smooth muscle in lymph node capsule and trabeculae.

This study focuses on the confusion in existing literature concerning the presence of smooth muscle in the capsule and trabeculae of lymph nodes. Human and bovine nodes from several anatomical areas and several individuals of each species were examined by conventional light, electron and fluorescence microscopy. Smooth muscle cells, independent of blood vessels, were demonstrated in the trabeculae and capsules of lymph nodes of both species examined by all three techniques. The need for further study on the function of these cells is indicated.

Animals↗

Femoral neuropathy and ischemic colitis associated with amyloidosis in hemodialysis patients.

Renal failure is often the presenting problem with amyloidosis and it portends a generally poor prognosis. Two of 121 patients in a home dialysis program were found to have amyloidosis after they developed unusual complications, ischemic colitis and femoral neuropathy. Both ultimately died as a result of their disease. From the limited experience that is reported, it appears that renal transplantation offers a better alternative for long term therapy than hemodialysis.

Adult↗