The vagina: effects of progesterone pretreatment and neonatal treatment with estrogen or androgen on [3H] estradiol retention

The paper deals with efficiency of sodium selenite in case of acute damage of the liver in rats as well as with its effect on main functions of the liver in norm and pathology, especially on biligenesis, synthesis and secretion of bile acids, bilirubin and cholesterol. The preparation in doses of 1 and 10 Mg per 100 g of weight is established to produce a normalizing effect of intensity of biliation synthesis and secretion of bile acids, secretion of bilirubin and excretion of cholesterol in the animals with the affected liver. The preparation has a cholagogic effect as well. In the healthy rats sodium selenite increases the intensity of bile secretion, intensifies synthesis and secretion of bile acids and bilirubin. A stimulating effect of the preparation on biligenesis is maintained with the liver dystrophy induced by carbon tetrachloride and polychlorines as well. Under these conditions it is manifested to a greater extent than in the healthy animals.     

Precocious mating in male rats following treatment with androgen or estrogen.

Conducted 5 experiments with 179 male Royal Victoria Hospital hooded rats. Daily subcutaneous injections of 1,000 MUg/100gm testosterone propionate of 5 MUg/100gm estradiol benzoate (EB) after postnatal Day 10 accelerated initial intromission and ejaculation in intact Ss. Precocious Ss continued to copulate after treatments were stopped. Age at the 1st display of intromission was unrelated to age at the 1st injection of EB. However, initiation of EB treatments before Day 11 was associated with rapid loss of intromission following cessation of treatment in adulthood. EB activated the 1st mating of prepuberally castrated and sham-operated Ss with nearly equal facility. Also, prepuberal castrates primed with EB subsequently intromitted after receiving fewer androgen replacement injections than control Ss. (24 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Paracrine regulation of talin mRNA expression by androgen in human prostate

The amino acid residue Asn141 of the restriction endonuclease EcoRI was proposed to make three hydrogen bonds to both adenine residues within the recognition sequence -GAATTC-. We have mutated Asn141 to alanine, aspartate, serine, and tyrosine. Only the serine mutant is active under normal buffer conditions although 1000-fold less than wild-type EcoRI. The alanine and aspartate mutants can be activated by Mn2+. At acidic pH the latter mutant becomes even more active than the wild-type enzyme in the presence of Mn2+. We conclude that Asn141 is essential for DNA recognition and that serine can partly substitute it.     

The effect of androgen deprivation on malignant and benign prostate tissue

The purpose of this research was to describe the changes in marker expression and histologic morphology following androgen deprivation in malignant and benign human prostates. Fourteen patients receiving pre-radical prostatectomy total androgen deprivation had pre- and post-androgen deprivation evaluation of marker expression and histologic morphology (both malignant and benign). Marker expression was significantly reduced for serum (p < 0.0001) and tissue (p < 0.004) PSA as well as bcl-2 expression (p < 0.008). There were significant histologic increases in vacuolization (p < 0.001), pyknosis (p < 0.04), fibrosis (p < 0.01) and lymphocytic infiltration (p < 0.008) in the malignant tissue. There were significant increases in squamous metaplasia (p < 0.0002), fibrosis (p < 0.0005), basal cell hypertrophy (p < 0.0005) and lymphocytic infiltration (p < 0.0002) in the benign tissue. Androgen deprivation therapy produces significant changes in marker expression and morphology in prostate specimens. At times these iatrogenic changes can be confusing. Clinicians and pathologists must be aware of these changes.     

The effects of LH-RH agonist alone or with flutamide in the treatment of stage D2 prostate cancer]

We compared the clinical efficacy of treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist alone to combined androgen blockade (CAB) with a LH-RH agonist and fiutamide. A total of 66 stage D2 prostate cancer patients were enrolled from Nov. 1992 to Mar. 1996 (n = 30: LH-RH agonist alone, n = 36 CAB). Serum PSA levels after 3 months of treatment and progression-free survival rates (Kaplan-Meier curves) were compared. Results were statistically evaluated by Wilcoxon's text. There were no differences in PSA levels between LH-RH agonist alone and CAB. Progression-free survival rates were longer in the patients treated CAB compared to LH-RH agonist alone (P = 0.041). Furthermore, in patients with poorly differentiated prostate cancers, longer survival rates were also observed with CAB (P = 0.030). However, there were no differences in high EOD (> or = 2) patients between the two treatments (P = 0.652).     

High dose combination radiotherapy for the treatment of localized prostate cancer

PURPOSE: We evaluate the efficacy of high dose combination radiotherapy for the treatment of localized prostate cancer. MATERIALS AND METHODS: A total of 212 patients with localized prostate cancer (T1-T3) were treated with transperineal radioactive seed implantation followed by 45 Gy. external beam radiation therapy. Patients with Gleason scores of 2-5 were treated with 125iodine at a minimum peripheral dose of 120 Gy., while 103palladium at a minimum peripheral dose of 90 Gy. was used for those with Gleason scores of 7-10. Patients with Gleason 6 diploid tumors were treated with 125iodine and those with aneuploid tumors were treated with 103palladium. Biochemical failure was defined as inability to achieve a prostate specific antigen nadir value of 0.5 ng./ml. or less. No patient was treated with androgen deprivation therapy. RESULTS: The 212 patients have a minimum of 24 months of followup (mean 33 months). Prostate specific antigen 0.5 ng./ml. or less was reached by 72% of the patients (152 of 212) and positive biopsies were detected in 13.9% (20 of 144). Using life table survivorship analysis the probability of initial biochemical success at 5 years was 91% (95% confidence interval, 83 to 97). The probability of subsequent failure following an initial success was 11% (95% confidence interval, 6 to 20) at 24 months. The complications of combination therapy included proctitis in 21.4% (47 of 212 men), impotence in 38% (38 of 100), urinary retention in 1.5%, incontinence in 2.8%, rectoprostate fistula in 2.4%, rectal wall breakdown in 0.5% and urethral stricture in 0.5%. Six patients (2.8%) required colostomy and urinary diversion. CONCLUSIONS: Short-term responses to high dose combination radiotherapy for localized prostate cancer are promising. The morbidity is acceptable. Further long-term followup is warranted to assess this treatment.     

Apoptosis and other mechanisms in androgen ablation treatment and androgen independent progression of prostate cancer: a review

Patients with advanced prostate cancer commonly present with disseminated disease. For these patients, androgen ablation is a first-line treatment. This mode of therapy usually has an initially palliative effect on tumor-related symptoms and slows growth, although virtually all tumors eventually relapse to an androgen-independent, more aggressively growing phenotype. However, surprisingly little is known about the actions mediating the initial palliative effect as well as the initiation of androgen-independent tumor growth. In this review, some current concepts on mechanisms of androgen ablation treatment and androgen-independent progression of prostate cancer is highlighted. Special attention is given to the involvement of apoptosis in these processes.     

Reevaluation and potential therapeutic effects of estrogen therapy to prostate cancer patients

Survival time of 65 patients with stage D2 prostate cancer who were treated by estrogen with or without antiplatelet drugs was examined. Survival time of 37 patients with antiplatelet drugs was significantly longer than that of 28 histological control ones. The frequency of death of cardiovascular disease in the former group decreased to 5.3%. Next, progression free time of the 37 patients was compared to the time of 37 patients treated by antiandrogen therapy. The former one was better than the latter. However, survival time after relapse of the estrogen group was shorter than the control. These results suggest that estrogen therapy improved by a combination of antiplatelet drugs has to be reevaluated and contains specific therapeutic effects differing from antiandrogen therapy.     

The treatment of advanced ovarian carcinoma with high dose, intravenous cyclophosphamide

The equal environments hypothesis of twin methodology was examined for the variable of similarity of appearance as it affects the personality ratings of young twins. There were two separate samples, the first with 95 pairs of same-sex twins and the second with 111 pairs. The average age of the twins in both samples was 3-1/2 years. Mothers rated their twins on four personality traits and on confusability of appearance. Not surprisingly, identical twins were markedly more similar in appearance than fraternal twins. The effect of this inequality on the personality ratings of the two types of twins was examined by correlating ratings of similarity of appearance with the absolute difference on the four personality traits for each pair of twins. None of the correlations was significant for the identical twins, suggesting that greater resemblance in appearance in identical twins does not make them more similar in personality. Indeed, the data suggested a contrast effect in which identical twins who were easily mistaken in appearance tended to be rated as less similar in personality. Thus, although similarity of appearance may create unequal environments for the two types of twins, it does not appear to bias twin studies in the direction of inflated heritabilities, at least for rating studies of the personality of young twins.     

Restoration of the CCAAT box or insertion of the CACCC motif activates [corrected] delta-globin gene expression

Hemoglobin A2 (HbA2), which contains delta-globin as its non-alpha-globin, represents a minor fraction of the Hb found in normal adults. It has been shown recently that HbA2 is as potent as HbF in inhibiting intracellular deoxy-HbS polymerization, and its expression is therefore relevant to sickle cell disease treatment strategies. To elucidate the mechanisms responsible for the low-level expression of the delta-globin gene in adult erythroid cells, we first compared promoter sequences and found that the delta-globin gene differs from the beta-globin gene in the absence of an erythroid Krüppel-like factor (EKLF) binding site, the alteration of the CCAAT box to CCAAC, and the presence of a GATA-1 binding site. Second, serial deletions of the human delta-globin promoter sequence fused to a luciferase (LUC) reporter gene were transfected into K562 cells. We identified both positive and negative regulatory regions in the 5' flanking sequence. Furthermore, a plasmid containing a single base pair (bp) mutation in the CCAAC box of the delta promoter, restoring the CCAAT box, caused a 5.6-fold and 2.4-fold (P < .05) increase of LUC activity in transfected K562 cells and MEL cells, respectively, in comparison to the wild-type delta promoter. A set of substitutions that create an EKLF binding site centered at -85 bp increased the expression by 26.8-fold and 6.5-fold (P < .05) in K562 and MEL cells, respectively. These results clearly demonstrate that the restoration of either an EKLF binding site or the CCAAT box can increase delta-globin gene expression, with potential future clinical benefit.     

Withdrawal of [corrected] estrogen increases hypothalamic neuropeptide Y (NPY) mRNA expression in ovariectomized obese rat

We determined the changes in neuropeptide Y (NPY) mRNA expression of the arcuate nucleus (ARC) in sham-operated (SHAM) and bilaterally ovariectomized (OVX) rats with estradiol (E2) supplement. Ovariectomy increases body weight gain for 3 weeks, accompanied by an increase of daily food intake. Ovariectomy significantly reduced serum corticosterone levels. E2 supplement reversed the effects of ovariectomy on body weight gain, food intake and serum corticosterone levels. Ovariectomy significantly increased NPY mRNA expression in the ARC. E2 supplement decreased NPY mRNA expression in the ARC of OVX rats. The present findings indicated that hypothalamic NPY mRNA expression, which involves the regulation of feeding behavior, are in parallel with circulating estrogen levels. Hypothalamic NPY mRNA expression may be important in the induction of hyperphagia after the withdrawal of estrogen by bilateral ovariectomy.     

Acid phosphatases in the human testis after prolonged estrogen treatment

The testes of 2 autopsied adult men and 6 subjects, suffering from prostatic carcinoma, were analysed for acid phosphatase activities, Two of the prostatic patients had been receiving estrogen treatment at least for a year and had completely regressed testes. Testes of other subjects contained well-defined tubules with different spermatogenic cells in abundance. The total acid phosphatase activity, assayed in the homogenate, showed a marked reduction in the testes of estrogen-treated subjects. Enzymes were separated by cellulose chromatography or by gel filtration combined with cellulose chromatography. Three activity peaks were resolved by the former and four by the latter technique, when homogenates of the control testes were used. In contrast, two to three strongly reduced activities could be discerned from the testes of estrogen-treated subjects. The specific activity of each enzyme after fractionation was compared between control and regressed testes. No difference was observed in the activities of enzyme I. Enzyme II was markedly reduced in the regressed testes, but was clearly present. Enzymes III and IV were either totally absent or showed a marked reduction in the regressed testes. It is suggested that a correlation exists between the destruction of germ cells, as a consequence of estrogen treatment, and the marked reduction in the activity of enzymes III and IV.     

Effects of androgen deprivation on prostate alpha 1-adrenergic receptors

Twenty-four hour exposure to cycloheximide produced a concentration-dependent reduction in protein synthesis in mouse cortical cell cultures. Unexpectedly, a 24 h pretreatment with cycloheximide exposure also reduced neuronal vulnerability to subsequent oxygen-glucose deprivation-induced injury, measured both acutely (cell swelling) or after one day (cell lysis). This neuroprotective effect was attenuated if the period of cycloheximide pretreatment was shortened to 8 h, and lost if the pretreatment was shortened to 1 h. A comparable neuroprotective effect was also induced by 24 h pretreatment with another protein synthesis inhibitor, emetine. The neuroprotection induced by pretreatment with cycloheximide or emetine was probably not attributable to reduction of apoptosis: (i) neuronal death under these conditions occurs by N-methyl-D-aspartate receptor-mediated excitotoxic necrosis, not apoptosis; (ii) the same cycloheximide pretreatment did not block staurosporine-induced apoptosis. Also unlikely as an explanation is reduction in postsynaptic vulnerability to excitotoxicity, as death induced by exogenous addition of N-methyl-D-aspartate, kainate, or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate was little affected by cycloheximide pretreatment. Rather, the protective effect of cycloheximide pretreatment was probably explained, at least in part, by marked reduction in the glutamate release induced by oxygen-glucose deprivation.     

Plasma kinetics of an oral dose of [2H4]retinyl acetate in human subjects with estimated low or high total body stores of vitamin A

Hydrolysis of ATP bound to DnaA protein by its intrinsic ATPase activity negatively controls chromosomal DNA replication in Escherichia coli. We developed a new in vitro assay system for ATP hydrolysis, which makes feasible a search for factors affecting the ATPase activity of DnaA protein. A crude cell extract enhanced the hydrolysis of ATP bound to DnaA protein, in a dose-dependent manner. Gel-filtration analyses revealed a single entity of the stimulation factor for the ATP hydrolysis and an apparent molecular mass of 170 kDa. The stimulation activity for ATP hydrolysis coeluted with the inactivation activity for DnaA protein initiating an oriC DNA replication, as determined by anion-exchange and gel-filtration column chromatographies. Activity of the stimulation factor required DNA and ATP. These observations suggested that IdaA protein, a previously described negative factor for DnaA protein, inactivated DnaA protein through stimulation of the hydrolysis of ATP bound to DnaA protein.     

Differential expression and androgen regulation of the human selenium-binding protein gene hSP56 in prostate cancer cells

Low levels of dietary selenium are associated with increased risk of malignancy of several organs, including the prostate. Using a subtractive approach called linker capture subtraction, we have found that the human selenium-binding protein gene hSP56 is differentially expressed by the relatively slow-growing, androgen-sensitive prostate cancer cell line LNCaP but not by the more rapidly growing androgen-insensitive lines PC-3 and DU145. We confirmed this differential expression by Northern blot analysis. Importantly, hSP56 expression by LNCaP cells was reversibly down-regulated by exogenous androgen in a concentration-dependent manner. Marked differences in steady-state hSP56 mRNA levels were found in a variety of normal and neoplastic human cells that were examined. hSP56 expression was especially high in normal tissues that appear to benefit from the cancer-protective action of dietary selenium and was low in many neoplastic cells. The results suggest that hSP56 may play a role in determining the neoplastic phenotype.     

Hydrolysis of androgen receptor by cathepsin D: its biological significance in human prostate cancer

Risk factors, etiology, and outcome of 180 cases of infective endocarditis (IE) in the Slovak Republic for 5 years were prospectively studied in a national survey. According to the Duke Endocarditis Service Criteria (1994), 169 cases were considered definitive and 21 possible/probable. The aortic valve was infected in 46.7%, mitral in 47.2%, and tricuspidal/pulmonary in 6.1% of cases. The majority of endocarditis cases was caused by Staphylococcus aureus and coagulase-negative staphylococci (CNS) (33.3%); only 12.2% were due to viridans streptococci; 11.7% were due to Enterococcus faecalis; 6.1% due to Haemophilus spp.; 10.1% due to other organisms; and 26.7% were culture negative. Single positive cultures of CNS were not considered clinically significant. More than 25% of 180 patients were older than 60 years. Rheumatic fever was a risk factor in 35.5%, dental surgery in 20.5%, prior cardiosurgery in 7.8%, and neoplasia in 6.7%. All patients were treated with antimicrobials (average length of therapy was 29.5 days) and 33.3% of patients also had surgery (valvular prosthesis replacement). Forty (22.2%) died, and 140 (77.8%) survived at day 60 after the diagnosis of endocarditis was made. All 40 deaths were attributable to infection. Univariate analysis comparing deaths and survivors did not show significant differences in most of the recorded risk factors between both groups, except age > 60 (40.0% versus 21.4%, p < 0.05), staphylococcal etiology (55.0% versus 27.1%, p < 0.04), and antibiotic therapy < 21 days (without surgery) (65.0% versus 3.6%, p < 0.01). These risk factors were significantly more frequently associated with deaths. Viridans streptococcal IE and surgical therapy in addition to antibiotics were associated with lower mortality in comparison to staphylococcal endocarditis (p < 0.045) or to cases treated with antibiotics only (p < 0.05). In comparison to other nationally based surveys in Europe (Greece, Croatia, France), the percentage of culture-negative endocarditis and spectrum of pathogens differed significantly.     

Microsatellite mutation (CAG24-->18) in the androgen receptor gene in human prostate cancer

The androgen receptor (AR) gene contains a polymorphic CAG microsatellite that codes for a variable length of glutamine repeats in the AR protein. Microsatellite DNA sequences may be potential sites of genetic instability. Using the polymerase chain reaction (PCR), we screened 40 human prostate cancer specimens for expansions or deletions of this microsatellite. In one patient, nontumor DNA yielded a single PCR product, as expected for the AR, but the tumor DNA yielded two discrete products, one identical to normal, and a second smaller one. Direct sequencing revealed that the nontumor tissue contained 24 CAGs, whereas the tumor contained one fragment with 24 CAGs (wild-type) and a second fragment with 18 CAGs (mutant), representing a somatic contraction of the AR CAG repeat (CAG24-->CAG18) in the tumor. Interestingly, this patient manifested a paradoxical agonistic response to hormonal therapy with the antiandrogen flutamide.     

Acute and chronic single dose effects of LSD-25 on visual discrimination in rats

The concept of "accident proneness" is frequently discussed and rarely documented. We predicted that children who take more risks as judged by their behavior in gym class, or who have more stressful life changes as determined by their score on a Social Readjustment Rating Questionnaire (SRRQ), would be more likely to injure themselves. 103 junior high school boys were rated for these factors, and then followed for injuries by weekly telephone calls for five months. Boys having high SRRQ scores had significantly more accidents than those with low scores; risk-taking levels were not predictive. In this study, children undergoing stressful changes in their lives were more susceptible to accidents.     

The effects of impurities and heat treatment on the internal friction of tungsten at high temperatures

An improved internal friction technique was used to study the relaxation processes in pure tungsten and the following alloys: commercially doped tungsten (218W), W-1 pct ThO₂, 218W-3 pct Re, and 218W-20 pct Re. Internal friction experiments were performed on worked and recrystallized specimens in the temperature range of 300° to 3000°K. The effects of impurities and alloying additions on the damping and recrystallization behavior of tungsten are demonstrated. It is further shown that the internal friction curves can conveniently be used to determine the temperature of primary and secondary recrystallization. The important effect of impurities on the microstructure and high temperature strength is also revealed by the temperature dependence of shear modulus.