In Vitro Contraction of the Canine Corpus Cavernosum Penis by Direct Perfusion with Prolactin or Growth Hormone

Purpose

It is well established that hyperprolactinemia, most typically seen in prolactinoma patients, causes hypogonadism and impotence. There seem to be a good possibility that hyperprolactinemia causes impotence, at least partially via some intrinsic property of prolactin (PRL), rather than through its suppressive effects on the hypothalamic-pituitary-gonadal testosterone dynamics. In the present investigation, we used an in vitro canine model to attempt to clarify whether direct action of PRL on the corpus cavernosum penis may lead to erectile insufficiency. Growth hormone (GH) and placental lactogen (PL), both having close structural and functional homologies to PRL, were also studied.

Materials and Methods

Isometric tension measurement with cavernous strips was performed in the presence or absence of 10 sup -5 to 10 sup -9 M. PRL, GH, or PL in the perfusion medium. The tension change induced by the test substances was normalized relative to that induced by 120 mEq KCl.

Results

Both PRL and GH produced dose-related elevations (p less than 0.01) of the cavernous tension, whereas PL and thiol-cleaved PRL in comparable doses were without effect (p greater than 0.05). When the tension rise produced by 120 mEq KCl was taken as 100 percent, the maximum contractions produced by PRL and GH were 80 percent and 110 percent. The minimum effective concentration was 10 sup -8 to 10 sup -7 M. for both PRL and GH. Pretreatment with indomethacin (10 sup -5 M.), but not tetrodotoxin (10 sup -5 M.), partially suppressed (p less than 0.05) the effects of PRL.

Conclusion

These results suggest that PRL and GH directly and specifically produced contraction of the corpus cavernosum penis, resulting in erectile insufficiency, and that the effect of PRL is partially mediated by prostaglandin.     

The effect of cadmium on vitamin A metabolism

It has been reported that a number of toxic agents impair normal vitamin A (VA) metabolism (A. D. Bruin, 1976, In Biochemical Toxicology of Environmental Agents, pp. 937–980. Elsevier, Amsterdam). A study was conducted to explore the effect of cadmium chloride (CdCl₂) on VA metabolism. Female rats of the Wistar strain were given drinking water containing 50 ppm of cadmium (Cd) for 237 days. Cadmium ingestion did not affect the food intake and body weight, but a significant decrease in serum VA was observed, concurrently with an increase in liver VA. In studying ingestion of tritiated VA alcohol (all trans-[15-³H]retinol), it was found that the absorption of VA alcohol from the intestine, the release of newly absorbed VA from the liver to serum, and the conversion of VA to water-soluble metabolites in the liver were not influenced by Cd. These findings suggest that Cd interfered with the release of VA, especially stored VA, to serum.     

Effects of pirarubicin,an antitumor antibiotic,on the cardiovascular system

Summary In the present study we examined the effects of pirarubicin [(2R)-4-0-tetrahydropyranyladriamycin, THP] on a cardiovascular system. An injection of THP (0.39–3.13 mg/kg, i. v.) reduced the mean blood pressure and caused an increase in the respiratory air rate in anesthetized rats. At 1.5×10^–6–1.5×10^–5 m, THP markedly relaxed a contraction induced by 10^–7 m norepinephrine in rat aorta with endothelium but not in that without endothelium. At a dose of 0.02–0.5 mg, THP produced an increase in the contractile force and the perfusion flow of isolated perfused guinea pig hearts. At a higher concentration (4.5×10^–5–1.5×10^–4 m), it produced a slight increase in the contractile force of the left atria in guinea pigs. This positive inotropic action of THP was inhibited by diphenhydramine (10^–6–5×10^–5 m), chlorpheniramine (3×10^–7–3×10^–5 m), and tripelennamine (3×10^–7–3×10^–5 m) but not by propranolol (10^–6 m), cimetidine (10^–5 m), diltiazem (10^–6 m), or ryanodine (10^–8 m). THP given i. v. at 2.5 mg/kg elevated the plasma histamine level in anesthetized dogs. From these data, we conclude that THP mainly relaxed the rat aorta in the presence of endothelium and that at higher concentrations, it increased the contractile force in the cardiac muscle, probably mediated through the release of histamine.     

Binaural advantage on usage of hearing aid together with cochlear implant--examination on speech perception (Japanese monosyllable word list 67-S and Japanese HINT)]

Six cochlear implant recipients with hearing aids in the opposite ear were studied to survey binaural advantage. They were examined in separate tests by using a hearing aid alone, cochlear implant alone, and by using both devices (bimodal condition). Test items used were the Japanese monosyllable word list 67--S and Japanese HINT. Statistically significantly results were obtained in the bimodal condition, three out of six subjects were successful in the monosyllable word test and all successful in the Japanese HINT. We conclude that all subjects enjoyed binaural advantage in speech perception in bimodal condition with no conflict at the recognition level; even when different sounds from cochlear implant and contralateral hearing aid were received. The plasticity of the brain is thought to be of importance in the bimodal condition.     

Effect of graft-versus-host disease on the outcome of bone marrow transplantation from an HLA-identical sibling donor using GVHD prophylaxis with cyclosporin A and methotrexate.

The effect of graft-versus-host disease (GVHD) on relapse incidence and survival has been analyzed in several studies, but previous studies included heterogeneous patients. Therefore, we analyzed the data of 2114 patients who received unmanipulated bone marrow graft from an HLA-identical sibling donor with a GVHD prophylaxis using cyclosporin A and methotrexate. Among the 1843 patients who survived without relapse at 60 days after transplantation, 435 (24%) developed grade II-IV acute GVHD. Among the 1566 patients who survived without relapse at 150 days after transplantation, 705 (47%) developed chronic GVHD. The incidence of relapse was significantly lower in patients who developed acute or chronic GVHD, but disease-free survival (DFS) was significantly inferior in patients who developed acute GVHD. A benefit of 'mild' GVHD was only seen in high-risk patients who developed grade I acute GVHD. The strongest association between GVHD and a decreased incidence of relapse was observed in patients with standard-risk acute myelogenous leukemia/myelodysplastic syndrome. In conclusion, the therapeutic window between decreased relapse and increased transplant-related mortality due to the development of GVHD appeared to be very narrow.     

Methylenetetrahydrofolate Reductase Genotypes, Dietary Habits and Susceptibility to Stomach Cancer

OBJECTIVE To study the relation among methylenetetrahydrofolate reductase (MTHFR) C677T genotypes, dietary habits and the risk of stomach cancer (SC).METHODS A case-control study was conducted with 107 cases of SC and 200 population-based controls in Chuzhou district, Huaian, Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects..MTHFR genotypes were detected by PCR-RFLP. RESULTS (1) The prevalence of the MTHFR C/T or T/T genotypes was found to be significantly different between controls (68.5%) and SC cases (79.4%,P=0.0416), the increased risk had an adjusted OR of 1.79 (95?:1.01-3.19). (2) Among subjects who had a low intake of garlic or Chinese onion, MTHFR C/T or T/T genotypes significantly increased the risk of developing SC. Among non-tea drinkers or among subjects who had a frequent intakeof meat, the carriers of the MTHFR C/T or T/T genotypes had a higher risk of SC than individuals with the C/C type MTHFR. CONCLUSION The polymorphism of MTHFR C677T was associated with increased risk of developing SC, and that individuals with differing genotypes may have different susceptibilities to SC, based on their exposure level to environmental factors.     

Subjects with <Emphasis Type="Italic">TNF-A-857TT</Emphasis> and <Emphasis Type="Italic">-1031TT</Emphasis> genotypes showed the highest <Emphasis Type="Italic">Helicobacter pylori</Emphasis> seropositive rate compared with those with other genotypes

Background A possible association between Helicobacter pylori seropositivity and tumor necrosis factor (TNF) A G-308A has been reported in Korea. The present study examined the associations of H. pylori with functional polymorphisms, TNF-A G-308A, C-857T, and T-1031C, and TNF-B A252G in Japanese subjects.Methods The total of 1374 study subjects included 241 outpatients who participated in an H. pylori eradication program (HPE), 679 first-visit outpatients (FVO) at a regional cancer hospital, and 454 local residents who received a health checkup examination (HCE).Results The frequency of the TNF-A -308A allele was only 1.3% of 480 chromosomes in the HPE group, so the FVO and HCE groups were not genotyped for that polymorphism. The genotype frequency of TNF-A C-857T was 69.2% CC, 27.7% CT, and 3.1% TT; that of TNF-A T-1031C was 69.4% TT, 28.1% TC, and 2.5% CC; and that of TNF-B A252G was 36.8% AA, 48.2% AG, and 15.0% GG. TNF-A -857T was tightly linked to TNF-A -1031T and TNF-B 252A. No significant associations between H. pylori seropositivity and polymorphisms of TNF-A C-857T and TNF-B A252G were observed. However, a reduced odds ratio adjusted for sex, age, and recruitment source was observed for TNF-A -1031CC (0.43; 95% confidence interval, 0.20–0.91) relative to TNF-A -1031TT. Subjects with TNF-A -857CC and -1031CC showed the lowest seropositivity (38.2% of 34 participants), while those with TNF-A -857TT and -1031TT showed the highest (66.7% of 42 participants).Conclusions This study suggests that the possibly high expression genotype of TNF-A may increase susceptibility to persistent H. pylori infection.     

Alterations of theTP53 gene and TP53 protein expression in epithelial ovarian cancer before and after chemotherapy

Background A role for theTP53 (alias p53) tumor-suppressor gene in chemoresistance has recently been discussed, but little is known about the clinical relevance of theTP53 gene to chemoresistance. To elucidate the relevance ofTP53 status to chemoresistance, we investigated theTP53 gene and TP53 protein expression in tumors from the same patients, before and after chemotherapy. Methods Twenty-one patients with ovarian cancer, who had residual disease after primary surgery, were studied. These patients received chemotherapy consisting of cisplatin, doxorubicin, and cyclophosphamide, and then underwent a second surgery. Polymerase chain reaction-single strand conformation polymorphism analysis and cycle sequencing were performed to determineTP53 mutation. TP53 protein was detected by Western blot analysis. Results Of the 21 patients studied, 9 responded to chemotherapy. Mutation of theTP53 gene was seen in 7 patients (2 responders and 5 nonresponders) before chemotherapy. After chemotherapy, another mutation of the gene was observed in 5 patients, all of whom were nonresponders. TP53 protein was detected in 10 patients (3 responders and 7 nonresponders) before chemotherapy. After chemotherapy, the expression of TP53 protein increased in these 3 nonresponders, and became positive in 2 other nonresponders. Conclusions This study showed for the first time in clinical investigation that alterations toTP53 could develop in association with chemotherapy, and thatTP53 status may relate to the mechanisms of chemoresistance in patients with epithelial ovarian cancer.