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Biomedical subjects

V J Rosen

Publications and source records attributed to V J Rosen.

At least 19 recordsLinked to original sources

Experimental model of lead nephropathy. I. Continuous high-dose lead administration.

This study followed the progression of lead nephropathy in male Sprague-Dawley rats (E) administered lead acetate (0.5%) continuously in drinking water for periods ranging from 1 to 12 months. Control animals (C) were pair-fed. Observations included renal pathology by light and electron microscopy, wet and dry kidney weights, and glomerular filtration rate (GFR) to assess renal function. Urinary excretion of lead, the enzymes N-acetyl-beta-D-glucosaminidase (NAG) and glutathione-S-transferase (GST), and brush border antigens (BB50, CG9, and HF5) were utilized to explore possible markers of kidney injury. GFR was increased significantly after three months of lead exposure, but was decreased significantly after 12 months. Kidney wet weights were significantly greater in E than C from three months on. Kidney dry weight/wet weight ratio was constant up to three months, but decreased in E at 12 months. Glomerular diameters were normal at all time periods; the nephromegaly was related primarily to hypertrophy of proximal tubules. Lead inclusion bodies were found in nuclei of proximal convoluted tubules and pars recta at all times. Tubular atrophy and interstitial fibrosis first appeared at six months, and increased in severity thereafter. Brush borders of proximal tubules were disrupted at one and three months, but recovered thereafter. Focal and segmental glomerulosclerosis was observed in 2 of 10 rats at 12 months. Arteries and arterioles remained normal at all time periods. Urinary NAG was elevated in E above C after three months of lead exposure. However, urinary NAG in C also increased with age, obscuring changes in the 12 month E rats. GST was elevated after three months of lead administration in E, not without an attendant age-related increase in C rats. In three-month E rats, urinary brush border antigens were increased above C, but were decreased at six and 12 months, correlating with the morphologic changes in brush border. We conclude that a high dose of lead in rats may initially stimulate both renal cortical hypertrophy and an increase in GFR. Later, the adverse effects of lead on the tubulointerstitium predominate, and GFR falls. The urinary marker, NAG, was abnormal in the early stages of the disease, but age-related changes obscured its utility at later stages; urinary GST appeared to be a more consistent marker of injury.

Acetylglucosaminidase

Intrathoracic Hodgkin's disease. A case presentation with multiple pulmonary nodules in the absence of mediastinal or hilar node disease.

Patients with Hodgkin's disease (HD) most commonly present with peripheral lymph node enlargement. The finding of pulmonary parenchymal involvement is usually associated with hilar and/or mediastinal adenopathy; such instances are felt to represent spread to the lung by contiguity. Noncontiguous spread to peripheral lung parenchyma in the absence of hilar or mediastinal node involvement has rarely been reported. This is the first documented case report in a 32-year-old woman with nodular sclerosing HD. The unusual clinical presentation in this patient was associated with the histologic detection of vascular invasion in the lymph node and open-lung biopsy specimens.

Adult

Subchronic toxicity in rats administered oral 8-methoxypsoralen.

Scientists at the National Toxicology Program are studying the toxicologic properties of 8-methoxypsoralen (8-MOP) with and without 320-400 nm UV (UVA). The combination of psoralen and UVA is a promising treatment for psoriasis. In this study, 8-MOP was administered to male and female Fischer 344 rats without subsequent UVA exposure for the determination of toxic effects of the psoralen alone. The drug (in corn oil) was administered by gavage 5 days/week for 90 days at doses of 0, 25, 50, 100, 200, and 400 mg/kg. The effects of toxicity were seen primarily in the 200- and 400-mg/kg dose groups, which included mortality, decreased body weight gain, and dose-related increases in liver:body ratios. On histopathology, target organ toxicity was seen in the liver, testes, and adrenals. In this study, relatively high doses of 8-MOP were tolerated in comparison to the dose of psoralen used in combination therapy clinically.

Administration, Oral

Burn wound biopsy. Multiple uses in patient management.

It is often exceedingly difficult to initially evaluate the depth of a burn wound and thus inaugurate appropriate definitive therapy. The clinical picture of the burn would may not always correlate with the true histologic depth of the injury. For this reason we have undertaken a program of obtaining punch biopsies of burn wounds in patients where the depth of the burn wound is equivocal. In such cases the biopsy has proven to be useful in guiding subsequent therapy. In addition to establishing the anatomic depth of injury, there are several other valuable uses of burn wound biopsies. The other uses are: diagnosis of invasive infection, quantitative bacterial culture, medical-legal values, psychological values and forensic utility.

Biopsy

Electron microscopic studies of viral agents in Crohn's disease.

Viral agents isolated from ileal filtrates of patients with Crohn's disease have been successfully cultivated in continuous rabbit ileum tissue-culture and grown to titres sufficient to allow electron microscopic characterisation. Electron microscopic studies showed clusters of viral particles only in tissue-cultures inoculated with cultivated viruses originally obtained from tissues from patients with Crohn's disease. Control cultures showed no evidence of viral agents. The mean virus-particle diameter was 30 nm. An electron-dense central core was present and a spiculated coat was demonstrated. The physical chemical properties of this agent, as previously described, together with the electron microscopic appearance are consistent with the appearance of a picornavirus.

Cell Line

Silicon nephropathy.

A patient with excessive industrial exposure to silicon and an elevated silicon content in his renal tissue was found to have a distinctive nephropathy, characterized pathologically by changes in the glomeruli and proximal tubules, and manifested clinically by albuminuria and hypertension. Proximal tubular function was intact. From a biochemical standpoint, this finding correlates with the demonstration in vitro that, in contrast to cadmium, a known cause of Fanconi syndrome, silicon does not inhibit renal cortical sodium-potassium-adenosine triphosphatase (Na-K-ATPase).

Adult