Cytogenetic and ploidy analysis of prostatic adenocarcinoma

The cytogenetic evaluation of prostatic adenocarcinoma has shown no consistent cytogenetic abnormalities. Despite manipulation of culture conditions, the majority of low-stage, untreated prostatic adenocarcinomas show a normal karyotype. We have performed cytogenetic analysis on eight primary prostate adenocarcinomas, using several control measures to increase the probability that any normal karyotype was derived from neoplastic cells rather than accompanying normal cells. Tumors were grown in media that encourages epithelial growth; DNA ploidy studies were performed before and after tissue culture; and immunohistochemical confirmation of the prostatic and epithelial nature of the cells was done following culture. Percentage of tumor on tissue sections adjacent to those submitted for culture was > 75% in all cases. Seven of eight cases were evaluable, and six cases showed no clonal abnormalities and were diploid. One tumor showed a population of tetraploid cells, without structural abnormalities. Three additional tumors showed evidence of tetraploidy by DNA analysis. One case showed nonclonal marker chromosomes and was aneuploid. This patient was pathologic Stage D. We conclude that the majority of prostatic adenocarcinomas at their inception may not show routinely detectable cytogenetic abnormalities. However, tetraploidy may play a role in the evolution of prostatic adenocarcinoma.     

Selective bladder preservation by combination treatment of invasive bladder cancer

BACKGROUND: For patients with invasive bladder cancer the usual recommended treatment is radical cystectomy, although transurethral resection of the tumor, systemic chemotherapy, and radiotherapy are each effective in some patients. We sought to determine whether these treatments in combination might be as effective as radical cystectomy and thus might allow the bladder to be preserved and the cancer cured. METHODS: We enrolled 53 consecutive patients with muscle-invading bladder cancer (stages T2 through T4, NXM0) in a trial of transurethral surgery, combination chemotherapy, and irradiation (4000 cGy) with concurrent cisplatin administration. Urologic evaluation of the tumor response directed further therapy: radical cystectomy in the 8 patients who had incomplete responses, additional chemotherapy and radiotherapy (6480 cGy) in the 34 patients who had complete responses or who were unsuited for cystectomy, and alternative care in the 11 patients who could not tolerate either irradiation or chemotherapy. RESULTS: After a median follow-up of 48 months, 24 of the 53 patients (45 percent) were alive and free of detectable tumor. In 31 patients (58 percent) the bladder was free of invasive tumor and functioning well, even though in 9 (17 percent) a superficial tumor recurred and required further transurethral surgery and intravesical drug therapy. Of the 28 patients who had complete responses after initial treatment, 89 percent had functioning tumor-free bladders. CONCLUSIONS: Conservative combination treatment may be an acceptable alternative to immediate cystectomy in selected patients with bladder cancer, although a randomized clinical trial that included a group for simultaneous comparison would be required to produce definitive results.     

Methods in the evaluation of medical students]

BACKGROUND: Delayed diagnosis, a high rate of histologically undifferentiated types of tumors, and rapid disease progression are frequently cited as the main reasons for the poor prognosis of gastric cancer in young patients. An improved prognosis has been anticipated for young gastric cancer patients because of recent improvements in digestive tract diagnostic techniques. This retrospective study was designed to determine whether these trends have had an impact on young Japanese patients with gastric cancer, and to further elucidate differences in clinicopathologic features between elderly and young patients. METHODS: From 1984 to 1995, 1654 patients with gastric cancer were admitted to our hospital. Of these, 86 patients (5.2%) were less than 40 years of age (young group). The clinicopathologic features of this young group were reviewed retrospectively, using hospital records, and compared with those of older patients (n = 499 [29.4%], 60 to 69 years of age). RESULTS: The young group contained significantly higher percentages of female patients, epigastric pain symptoms, depressed superficial type lesions, mucosal invasion, and poorly differentiated histology; percentages of hepatic metastasis and venous invasion were lower. Survival rates for all patients and for the resected cases were significantly better in the young group (p = 0.035 and 0.017 respectively). The percentage of early stage stomach cancers for the group less than 40 years of age was 49.0% in 1984-89, but had risen to 60.9% by 1990-95. CONCLUSIONS: Early diagnosis has improved the prognosis of young gastric cancer patients. Furthermore, these data show a recent shift in stage distribution; additional prognostic improvement is anticipated for young patients with early gastric cancer.     

NT-3 has a tropic effect on process outgrowth by postnatal auditory neurones in vitro

CONFOCAL analysis of early postnatal auditory neurones in a bicompartmental culture system was used to test for chemoattractant properties of NGF, BDNF and NT-3 on neuronal process outgrowth. NT-3 exerted a strong tropic effect on neuritic outgrowth from auditory neurones in this system. BDNF and NGF did not have any tropic activity that directed processes outgrowth from auditory neurones. However, BDNF was important for the support of neuronal survival in NGF-treated cultures and for neuritogenesis in NT-3-treated cultures. Since NT-3 has been identified as both a survival factor and a chemotropic agent for auditory neurones, it is likely that this neurotrophin will be a useful therapeutic agent in the treatment of damaged cochleae for the recovery of hearing.     

Pathological and immunocytochemical changes in chronic calcium oxalate nephrolithiasis in the rat

In the present study, we exposed rats to a crystal-inducing diet (CID) consisting of vitamin D3 and 0.5% ethylene glycol (EG), and we investigated histologically the kidney damage induced by the deposition of calcium oxalate (CaOx) crystals. After 28 days, 50% of the animals had renal CaOx crystals, of which 60% also had small papillary stones. Most crystals were present in the cortex. The occurrence of these crystals coincided with morphological and cytochemical changes: glomerular damage, tubular dilatation and necrosis, and an enlargement of the interstitium. The number of epithelial and interstitial cells positive for the proliferating cell nuclear antigen (PCNA) was increased. Tamm-Horsfall protein (THP) was not only demonstrable in the thick ascending limb of the loop of Henle (TAL), but also frequently in glomeruli, in the proximal tubular epithelium, and in the papilla. In the lumen of the tubular system, it was associated with urinary casts. Reflection contrast microscopy (RCM) showed that the crystals were coated with a thin layer of THP. In spite of the high urinary oxalate concentrations, the above described cellular changes were not observed in CID-fed rats without renal crystals. We conclude, therefore, that in the kidney, the retained CaOx crystals rather than the urinary oxalate ions are responsible for the observed morphological and immunocytochemical changes.     

Androgens markedly stimulate the accumulation of neutral lipids in the human prostatic adenocarcinoma cell line LNCaP

Microscopic evaluation of LNCaP cells stained with the lipophilic dye Oil red O revealed that androgens induce a marked stimulation of lipid droplet accumulation. As determined by quantitative analysis of the Oil red O extracted from the stained cells, stimulatory effects of the synthetic androgen R1881 became apparent at concentrations as low as 10(-11) M. Maximal induction (15-fold) was reached at 10(-8) M. Increases were observed 2 days after hormone addition and were maximal 1 day later. Accumulation of lipid droplets was also induced by mibolerone (another synthetic androgen) and by the natural androgens testosterone and dihydrotestosterone. In agreement with the aberrant ligand specificity of the mutated androgen receptor in LNCaP cells, stimulation of lipid accumulation was also apparent after treatment with progesterone and estradiol. Cortisol and the synthetic glucocorticoid dexamethasone were ineffective. The androgen antagonist Casodex (bicalutamide) abolished the stimulatory effect of R1881, further supporting the involvement of the androgen receptor. In agreement with this conclusion, no changes in lipid accumulation were observed after androgen treatment of the androgen receptor-negative prostate tumor lines PC-3 and DU-145. To investigate the nature of the lipids affected by androgens, lipid extracts were analyzed by TLC, complemented with enzymatic lipid analyses. Androgens were shown to have major effects on the content of triglycerides and cholesterol esters (33- and 7-fold stimulation, respectively), the two main classes of lipids stained by Oil red O. Phospholipid and cholesterol contents were increased by a factor of 2. Incorporation studies with [2-14C]acetate revealed that androgens caused a major stimulation of 2-14C incorporation into triglycerides and cholesterol esters (11- and 13-fold, respectively), suggesting that androgens act at least in part at the level of lipid synthesis. Taken together, these findings indicate that androgens, besides affecting proliferation and protein secretion, also markedly stimulate the production and accumulation of neutral lipids, revealing a novel interesting aspect of androgen regulation of LNCaP cells.     

Effects of chronic lithium and carbamazepine treatment on G-protein subunit expression in rat cerebral cortex

Although lithium and carbamazepine (CBZ) are effective in the treatment of bipolar affective disorder, their mechanism of action is still unknown. Recent evidence suggests that lithium and CBZ might exert their therapeutic effects by modulating the function of guanosine triphosphate (GTP)-regulatory (G) proteins associated with central nervous system second messenger systems. In the present study, we showed that chronic lithium administration decreases G alpha s, G alpha i1, and G alpha i2 messenger RNA (mRNA) abundance by 25%-30% in rat cerebral cortex. However, the levels of G alpha s, G alpha i1, and G alpha i2 mRNA were unaffected by chronic CBZ treatment. The effects of lithium on G alpha s, G alpha i1, and G alpha i2 mRNA levels appear to be selective, as the mRNA levels of G alpha o, G alpha x, G beta 1, G beta 2, and G beta 3 subunits remained unchanged. Two days after terminating chronic lithium treatment, changes in G alpha s, G alpha i1, and G alpha i2 mRNA levels were not demonstrable. Short-term administration of lithium (2 days), however, reduced only the G alpha i2 mRNA levels. Surprisingly, there was no significant difference in the amount of immunologically detectable G alpha s-s, G alpha s-1, G alpha i(1 + 2), G alpha 0, and G beta (1 + 2) in the cortex of rats chronically treated with lithium or CBZ, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bacterial and human cell mutagenicity study of some C18H10 cyclopenta-fused polycyclic aromatic hydrocarbons associated with fossil fuels combustion

Maximal activity of NADP.H-cytochrome c reductase was found in the liver, the lowest one--in the retina. On the contrary, the highest activity of aldose reductase was observed in the retina, the lowest one--in the liver. The activity of NADP.H-cytochrome c reductase in the retina of rats with hereditary degeneration of the retina increased to the 60th day of postnatal life by 33%, the increase reaching 273% to the 90th day. In the brain cortex, the increase in the activity to the 45-60th days amounted to 22-34%, whereas at the age of 90 days the difference between healthy and patient rats, as well as the difference between males and females became less significant. The activity of aldose reductase in the cortex and retina in patient rats at the 20th day was 35% lower than in healthy animals. In the liver of patient rats, to the age of 45 days, the activity of aldose reductase decreased by 38%. At other periods, no significant differences were observed between healthy and patient animals with respect to the activity of this enzyme.     

Antibody capture haemadherence tests for parvovirus B19-specific IgM and IgG

Repeated administration of benzodiazepines has been reported to produce tolerance in animals and humans. Using an elevated plus-maze test and an autoradiographic technique, we investigated whether repeated administration of chlordiazepoxide produced tolerance to its anxiolytic effects, and whether such repeated administration altered benzodiazepine and GABAA receptors. Tolerance to the anxiolytic effect of chlordiazepoxide was produced when it was administered at a dose of 30 mg/kg (i.p.) once a day for 10 and 14 days. In the quantitative autoradiographical study, although repeated chlordiazepoxide treatment had no effect on [3H]flunitrazepam and [3H]Ro 15-4513 binding to benzodiazepine receptors, such treatment reduced [3H]muscimol binding to GABAA receptors in the cortex, caudate putamen, and hippocampus. These results suggest firstly, the production of tolerance to the anxiolytic effects of chlordiazepoxide, and, secondly, that this tolerance may be due to the down-regulation of GABAA receptors, but not of benzodiazepine receptors.