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Biomedical subjects

D S Wu

Publications and source records attributed to D S Wu.

8 recordsLinked to original sources

A human prostatic epithelial model of hormonal carcinogenesis.

The effects of stromal and hormonal environment on the immortalized but nontumorigenic human prostatic epithelial cell line BPH-1 were investigated in an in vivo model. BPH-1 cells were recombined with rat urogenital sinus mesenchyme (UGM), and the tissue recombinants were grafted to the renal capsule of adult male athymic mouse hosts. BPH-1 + UGM recombinants formed solid branching epithelial cords with a well-defined basement membrane. The cords canalized to form ductal structures. The mesenchymal cells formed thick sheets of well-differentiated smooth muscle surrounding the epithelium, reinforcing the idea that the epithelium dictates the patterning of prostatic stromal cells. When hosts carrying BPH-1 + UGM tissue recombinants were exposed to testosterone propionate and 17-beta-estradiol (T + E2), the tissue recombinants responded by forming invasive carcinomas, demonstrating mixed, predominantly squamous as well as adenocarcinomatous (small acinar and mucinous) differentiation. When either untreated or T + E2-treated hosts were castrated, epithelial apoptosis was observed in the grafts. When tumors were removed and regrafted to fresh hosts they grew rapidly. Tumors were serially regrafted through six generations. Histologically these tumors consisted largely of focally keratinizing squamous cell carcinoma with high-grade malignant cytological features. BPH-1 cells grown in the absence of UGM survived at the graft site but did not form tumors or organized structures. This behavior was not influenced by the presence or absence of T + E2 stimulation. These data show that an immortalized, nontumorigenic human prostatic epithelial cell line can undergo hormonal carcinogenesis in response to T + E2 stimulation. In addition, the data demonstrate that the stromal environment plays an important role in mediating hormonal carcinogenesis.

Animals↗

Indinavir urolithiasis.

Indinavir sulfate is a protease inhibitor that has been found to be extremely effective in increasing CD4+ cell counts and in decreasing HIV-RNA titers in patients with HIV and AIDS. However, patients receiving indinavir also have been noted to have a significant risk for developing urolithiasis. Published reports of indinavir urolithiasis estimate its incidence at between 4 and 13%. Indinavir has a high urinary excretion with poor solubility in a physiologic pH solution. Consequently, patients develop urinary stones that are principally composed of indinavir or of a mixture of indinavir and other substances, such as calcium oxalate. Similar to other forms of urolithiasis, acute flank pain and hematuria are the typical symptoms of indinavir urolithiasis. Indinavir urolithiasis is unique in that computed tomography, which was once thought to be efficacious in identifying all urinary calculi, is not useful in imaging stones that are composed of pure indinavir. Indinavir urolithiasis generally responds to a conservative regimen of hydration, pain control, and the temporary discontinuation of the medication. Only a minority of patients need surgical intervention. Approximately 10% of patients ultimately need to discontinue indinavir therapy altogether. Indinavir is an antiviral agent that has a significant role in the treatment of AIDS. Although urolithiasis is a significant side effect of indinavir use, limiting its clinical application is not the answer. Rather, physicians need to know more about indinavir urolithiasis to help their patients cope with its potential complications.

HIV Protease Inhibitors↗

Osteoporosis in Colles fracture.

Previous studies of bone density in patients with Colles fracture have been inconclusive. We measured bone density at the second metacarpal in 36 postmenopausal women with Colles fracture. The patients were found to have highly significant (P < 0.01) or significant (P < 0.05) differences in the parameters of bone density compared with controls matched for age. The results suggest that osteoporosis is of definite relevance to the etiology of Colles fracture in postmenopausal women.

Aged↗

Adaptative responses of tobacco callus cells to simulated microgravity by compensation.

Under the rotation-induced gravity compensation, growth rate of callus was repressed by about 44%. Its osmotic and water potential declined by about 22 and 27% respectively. The content of soluble sugar was enhanced by about 123% and that of K+ by about 25%. The permeability of plasmic membrane increased and the lipid peroxidation intensified. When the callus grown under clinostatting were subcultured and returned to stationary conditions, the growth rates and related physiological indications were restored again to or near to the level of the control (SC). Electron microscopic studies showed that nuclear membrane was invaginated so deeply that some of the nuclei were like a starfish. Rough endoplasmic reticulum was diminished. The smooth one observed on the surface of slices was lengthened by almost 8.9 times of the control (SC), the longest one reached to 42 micrometers. They were often concentrated in a corner of the cell. Some of them were rolled into tube-shapes. The amyloplasts were without starch grain. It is assumed that the responses of plant cell to microgravity may be a sort of tolerable unloading reaction on endomembrane system.

Adaptation, Physiological↗

Acute and chronic effects of the pesticide amitraz on alpha 2-adrenoceptors in mouse brain.

There is increasing evidence to suggest that several effects of the formamidine pesticide amitraz (AMZ) in mammals are mediated by its interaction with alpha 2-adrenoceptors. AMZ has been shown to inhibit the binding of [3H]clonidine, a specific ligand for alpha 2-adrenoceptors to mouse brain in vitro and after administration in vivo. In the present study we have further investigated and characterized the effects of acute and chronic administration of AMZ on brain alpha 2-adrenoceptors in mice. AMZ caused a dose-dependent inhibition of [3H]clonidine binding. This inhibition was long-lasting (more than 48 h) following a relatively high dose of AMZ (75 mg/kg), while it was of short duration (2 h) following low doses (7.5 and 12.5 mg/kg). The time course of inhibition of [3H]clonidine binding was correlated with the plasma levels of AMZ and/or its active metabolites, measured with a novel radioreceptor binding technique. The alteration of [3H]clonidine binding was due to a decrease in alpha 2-adrenoceptor affinity, with no change in the density of binding sites, and was reversible in vitro upon repeated washing of the membrane preparation. Repeated administration of 7.5 mg/kg or 12.5 mg/kg AMZ, to yield a total dose of 75 mg/kg, showed no evidence of a cumulative effect on brain alpha 2-adrenoceptors.

Animals↗

Formamidine pesticides and alpha 2-adrenoceptors: studies with amitraz and chlordimeform in rats and development of a radioreceptor binding assay.

The interaction of the formamidine pesticides chlordimeform (CDM) and amitraz (AMZ) with rat brain alpha2-adrenoceptors was investigated. Both compounds inhibited the binding of 3H-clonidine and 3H-yohimbine in vitro with IC50 values of 62-68 microM (CDM) and 95-110 nM (AMZ). In vivo administration of AMZ and CDM caused a dose-dependent inhibition of 3H-clonidine binding in rat forebrain. The inhibition was short-lasting (24 hr) following CDM administration, while after AMZ recovery of 3H-clonidine binding occurred only after 72 hr. Good correlations were found between inhibition of brain 3H-clonidine binding by the formamidines and "plasma equivalents" of these compounds and/or their biologically active metabolites, as measured by a new radioreceptor assay. These results suggest that 1) formamidines can interact in vivo with brain alpha 2-adrenoceptors when administered at doses previously shown to cause toxic effects on the central nervous system: and 2) this effect is reversible, both in vivo and in vitro, and appears to be linked to the presence of the formamidines and/or their active metabolites at the receptor sites.

Amidines↗