Comparative rates of androgen production and metabolism in Caucasian and Chinese subjects

Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western countries than in Chinese in the Far East. Prior studies demonstrated diminished facial and body hair and lower levels of plasma 3 alpha-androstanediol glucuronide and androsterone glucuronide in Chinese than in Caucasian men. Based upon these findings, investigators postulated that Chinese men could have diminished 5 alpha-reductase activity with a resultant decrease in prostate tissue dihydrotestosterone levels and clinically apparent prostate cancer. An alternative hypothesis suggests that decreased 3 alpha-androstanediol glucuronide and androsterone glucuronide levels might reflect reduced production of androgenic ketosteroid precursors as a result of genetic or environmental factors. The present study examined 5 alpha-reductase activity, androgenic ketosteroid precursors, and the influence of genetic and environmental/dietary factors in groups of Chinese and Caucasian men. We found no significant differences in the ratios of 5 beta-:5 alpha-reduced urinary steroids (a marker of 5 alpha-reductase activity) between Chinese subjects living in Beijing, China, and Caucasians living in Pennsylvania. To enhance the sensitivity of detection, we used an isotopic kinetic method to directly measure 5 alpha-reductase activity and found no difference in testosterone to dihydrotestosterone conversion ratios between groups. Then, addressing the alternative hypothesis, we found that the Caucasian subjects excreted significantly higher levels of individual and total androgenic ketosteroids than did their Chinese counterparts. To distinguish genetic from environmental/dietary factors as a cause of these differences, we compared Chinese men living in Pennsylvania and a similar group living in Beijing, China. We detected a reduction in testosterone production rates and total plasma testosterone and sex hormone-binding levels, but not in testosterone MCRs in Beijing Chinese as a opposed to those living in Pennsylvania. Comparing Pennsylvania Chinese with their Caucasian counterparts, we detected no significant differences in total testosterone, free and weakly bound testosterone, sex hormone-binding globulin levels, and testosterone production rates. Taken together, these studies suggest that environmental/dietary, but not genetic, factors influence androgen production and explain the differences between Caucasian and Chinese men.     

Measurement of intravariceal pressure by fine needle direct puncture in hepatitis B surface antigen-positive cirrhotic patients: the effect of vasopressin

A trp E fusion protein containing a C-terminal portion of the rat substance P receptor (SPR) was expressed in bacteria and used to produce an antibody. The antibody specifically reacted with SPR expressed in a mammalian cell line and rat striatum. Light and electron microscope analyses of the rat striatum revealed intense SPR-like immunoreactivity in neuronal somata and dendrites. These immunoreactive neurons constituted approximately 3% of the total population of striatal neurons; they were putative interneurons of large and medium-sized aspiny type.     

The whispered voice: the best test for screening for hearing impairment in general practice?

Hearing loss is an important health problem in the elderly which sometimes leads to social isolation. In a study with 62 patients, the diagnostic value of four simple tests for screening for hearing loss in general practice was examined. When paying attention to the loudness of the whispering, the whispered voice test can be a valuable test for assessment of hearing loss in general practice.     

Mycoplasma pneumoniae pneumonia in a mouse model

To investigate the pathogenesis of acute Mycoplasma pneumoniae infection, BALB/c mice were anesthetized with metofane, and M. pneumoniae was introduced intranasally on days 0, 1, and 2. Mice were sacrificed on days 0-15. A histopathologic scoring system defined inflammatory changes in the lungs on a scale of 0-26 (least to most severe). Broth cultures were positive for all nasal passage and bronchoalveolar lavage (BAL) specimens. Histopathologic scores ranged from 0 to 21. The mean log10 (cfu/mL) were 4.1-6.4 on days 1-10 and >/=1.7 on days 13-15 for nasal passage and BAL specimens. Serum polymerase chain reaction was negative. ELISA for serum IgM and immunoblots for M. pneumoniae antibody were positive in 21 (62%) of 34 and 33 (97%) of 34 infected animals, respectively, at days 8-15. ELISA for IgG antibody was negative. This mouse pneumonia model can be used to study the immunologic and therapeutic responses to acute M. pneumoniae infection.     

Structure-activity relationships for 1-phenylbenzimidazoles as selective ATP site inhibitors of the platelet-derived growth factor receptor

1-Phenylbenzimidazoles are shown to be a new class of ATP-site inhibitors of the platelet-derived growth factor receptor (PDGFR). Structure-activity relationships (SARs) are narrow, with closely related heterocycles being inactive. A systematic study of substituted 1-phenylbenzimidazoles showed clear SARs. Substituents at the 4'- and 3'-positions of the phenyl ring are tolerated but do not significantly improve activity, while substituents at the 2'-position abolish it. Substituents in the 2-, 4-, and 7-positions of the benzimidazole ring (with the exception of 4-OH) also abolish activity. Most substituents at the 5- and 6-positions maintain or increase activity, with the 5-OH, 5-OMe, 5-COMe, and 5-CO2Me analogues being >10-fold more potent than the parent 1-phenylbenzimidazole. The 5-OMe analogue was both the most potent inhibitor, and showed the highest selectivity (50-fold) between PDGFR and FGFR isolated enzymes, and also a moderately effective inhibitor (IC50 = 1.9 microM) of PDGF-stimulated PDGFR autophosphorylation in rat aorta smooth muscle cells.     

Frequency of bilateral tumours and primary retroperitoneal localization in tumours of the testicles

Report on 4 patients with bilateral testicular tumours (out of a total number of 181 cases) and the problems arising with a second course of irradiation. The question of histogenesis and therapeutic course in 4 patients with a primary retroperitoneal tumour localization are discussed in the second part.