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Biomedical subjects

G Watanabe

Publications and source records attributed to G Watanabe.

At least 91 records · Page 5Linked to original sources

Bronchial sleeve resection with complete preservation of the lung for carcinoma.

Conservative sleeve resection with complete preservation of the lung parenchyma is very rarely applicable for the treatment of bronchial carcinomas. We used this surgical procedure in four patients with bronchial carcinoma in various sites of the central airway, and we obtained successful results. The pathological types were two squamous cell carcinomas and two low-grade malignant tumors (mucoepidermoid carcinoma and adenoid cystic carcinoma). If patients are properly selected, this operative procedure appears to be a safe and radical therapeutic option for the treatment of bronchial neoplasms arising from major bronchi.

Adult↗

Male reproductive defects caused by puromycin-sensitive aminopeptidase deficiency in mice.

Male reproductive performance is composed of two principal elements, copulation and spermatogenesis. A wealth of literature has described the intricate web of endocrine events underlying these biological processes. In the present study we show that puromycin-sensitive aminopeptidase (Psa)-deficient mice are infertile, lack copulatory behavior, and have impaired spermatogenesis. The reproductive deficits of the mutants are not restored by androgen administration, although no aberrant localization of the sex steroid receptors was detectable in their brains and testes. Considering the strong expression of the Psa gene in the brain and Sertoli cells and the degenerative morphology of Sertoli cells in Psa-deficient mice, Psa may participate in testosterone-mediated reproductive signal pathways in the brain and testis.

Aminopeptidases↗

Puromycin-sensitive aminopeptidase is essential for the maternal recognition of pregnancy in mice.

Maternal recognition of pregnancy in rodents requires semicircadian surges of hypophyseal PRL secretion during early gestation, which are required for the formation of the corpus luteum of pregnancy (CLP). Here we show that puromycin-sensitive aminopeptidase (Psa)-deficient mice display female infertility that results from impaired formation of CLP. Transplantation of mutant ovaries into normal females restored fertility but not vice versa. Psa-deficient females revealed no semicircadian surges of PRL induced after mating stimuli. Pregnancy in the mutant females was restored by grafting intact pituitaries to elevate circulating levels of PRL. Psa is thus required for the appearance of the semicircadian surges of PRL secretion that are crucial for maintaining pregnancy in rodents.

Aminopeptidases↗

Surgical treatment of primary cardiac tumors: 28 years' experience in Kanazawa University Hospital.

To examine the clinical features of primary cardiac tumors, 34 patients who underwent surgical treatment from 1973 to 2000 at the Kanazawa University Hospital were analyzed and the literature was reviewed. The 34 patients were divided into 3 categories: (i) myxomas; (ii) benign non-myxomas; and (iii) malignant tumors. Twenty-three patients (70%) were diagnosed with myxomas, including 22 left atrial myxomas and 1 right atrial myxoma. Seven patients (18%) were diagnosed with benign non-myxoma tumors, including 3 hemangiomas, 1 fibroma, 1 rhabdomyoma, 1 pheochromocytoma, and 1 lipoma. Four patients (12%) were diagnosed with malignant tumors, including 2 angiosarcomas, 1 rhabdomyosarcoma, and 1 malignant fibrous histiocytoma. Among the myxoma patients, in-hospital mortality was 9% (2/23), late mortality was 10% (2/21), and no recurrent myxomas have been identified. Among benign non-myxoma patients there were no perioperative deaths; however, 1 patient died 11 years after surgery, with no linked cause. No recurrent tumors have been identified. Among malignant tumor patients, 1 patient died the day following surgery and the rest died within 14 months. Early and late results of surgery were acceptable for those patients with benign tumors, while the prognosis for patients with malignant tumors was very poor.

Adolescent↗

Regulatory role of inhibin in follicle-stimulating hormone secretion and folliculogenesis in the guinea pig.

The effects of unilateral and bilateral ovariectomy and passive immunization against inhibin on follicle-stimulating hormone (FSH) secretions and follicular development in the guinea pig were investigated. Bilateral ovariectomy decreased plasma immunoreactive (ir-) inhibin rapidly and increased plasma FSH significantly. Unilateral ovariectomy decreased plasma ir-inhibin and increased plasma FSH temporarily, and doubled the number of ova released from the remaining ovary at the subsequent ovulation in guinea pigs. Injection of 1.0 ml inhibin antiserum significantly increased concentrations of plasma FSH at 6 hr onwards and the number of small follicles (100-200 microm in diameter) at 48 hr after the injection in guinea pigs bearing progesterone-containing implants. In vitro bioassay showed that inhibin antiserum could neutralize the suppression of ovarian homogenate on FSH secretion from cultured rat anterior pituitary cells. These results confirm the evidence that the ovary is the main source of inhibin secretion and both in vitro bioassay and passive immunization against inhibin show that the inhibin is a major regulator in the follicular development through FSH secretion in guinea pigs.

Animals↗

Prepubertal changes in immunoreactive inhibin concentration in blood serum and testicular tissue in Holstein bull calves.

Age-related changes in immunoreactive inhibin (ir-inhibin) levels and the relationship among ir-inhibin, gonadotropins and testosterone were examined in 53 Holstein bull calves from neonates to 8.6 months old. Serum levels of ir-inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone, as well as ir-inhibin levels in testicular extracts, and testicular sizes were measured. All hormones were measured by specific radioimmunoassays. The concentrations of ir-inhibin in serum and testicular tissue were high in neonatal calves and tended to decrease with age. In contrast, serum concentrations of gonadotropins did not show any age-related changes within the experimental period. Serum testosterone levels and testicular sizes (length, width and weight) were positively correlated with age. Furthermore, a positive immunostaining to antiserum for the inhibin alpha-subunit was immunocytochemically observed only in Sertoli cells of the seminiferous tubules from neonates to calves less than 6 months old. These results indicate that the immature bovine testis produces and secretes high levels of ir-inhibin and that the Sertoli cells are a major source of ir-inhibin in prepubertal bull calves.

Age Factors↗

Dynamic changes in plasma concentrations of gonadotropins, inhibin, estradiol-17beta and progesterone in cows with ultrasound-guided follicular aspiration.

To elucidate the effects of ultrasound-guided transvaginal follicular aspiration, plasma concentrations of FSH, LH, inhibin, estradiol-17beta and progesterone, and folliculogenesis were examined in Holstein cows. Four clinically healthy cows with regular estrous cycles were scanned by ultrasound per rectum once a week for 9 weeks before the commencement of follicular aspiration. All visible follicles were divided into 3 categories based on their sizes (2 < or = small < 5 mm; 5 < or = medium < 10 mm, large > or = 10 mm). The follicular aspiration was started at random during the estrous cycle and conducted under epidural anesthesia induced with 5 ml of 2% lidocaine once a week for 6 weeks. The average number of total visible follicles > or = 2 mm in diameter at 7 days after aspiration (21.7 +/- 7.4, n = 24) was similar to that before starting aspiration (26.7 +/- 10.5, n = 36). Plasma inhibin and estradiol-17beta declined and fell to a trough on 1.5 days and returned to pre-aspiration values by 5 days after aspiration. Plasma concentrations of FSH increased and reached peak levels between 1 and 1.5 days after aspirations. Plasma concentrations of LH also increased and reached peak levels between 0.5 and 1.5 days after aspirations. Both plasma FSH and LH had returned to pre-aspiration levels by 5 days after aspirations. Plasma concentrations of progesterone did not change with the follicular aspiration. These results demonstrate that follicular aspiration decreases plasma concentrations of inhibin and estradiol-17beta, which in turn leads to a rise in plasma concentrations of FSH and LH. It is suggested that marked increases in plasma concentrations of FSH and LH after the aspiration stimulate the development and maturation of a new cohort of follicles within one week in cows.

Animals↗

Immunohistochemical detection of inhibin-alpha, -betaB, and -betaA chains and 3beta-hydroxysteroid dehydrogenase in canine testicular tumors and normal testes.

Immunohistochemical detection of inhibin-alpha, -betaA and -betaB chains and 3beta-hydroxysteroid dehydrogenase (HSD) was carried out on primary testicular tumors from 15 dogs and normal testes from three adult dogs. Histopathologically, the tumors were composed of three types: Leydig cell tumors in five dogs, Sertoli cell tumors in five dogs, and seminoma in five dogs. In normal testes, immunostaining against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD revealed positive reactivity in the cytoplasm of Leydig cells. In testicular tumors, immunoreactive cells against inhibin-alpha, -betaA, and -betaB chains and 3beta-HSD were localized in all Leydig cell tumors but not in any Sertoli cell tumors or seminomas. The results of radioimmunoassay for plasma inhibin in dogs with Leydig cell tumors showed higher concentrations than those in dogs with Sertoli cell tumors and seminomas and those in normal dogs. The concentration of inhibin in the plasma was markedly decreased by the surgical removal of the Leydig cell tumor in one dog. Our findings suggest that inhibin is synthesized by normal and neoplastic Leydig cells in the canine testis, and the secreted inhibin may be inhibin A and inhibin B.

3-Hydroxysteroid Dehydrogenases↗

Superovulation, fertilization and in vitro embryo development in mice after administration of an inhibin-neutralizing antiserum.

The present study was conducted to investigate the effect of immunoneutralization against endogenous inhibin on oocyte and embryo production in adult and immature mice. At 12:00 h on day 2 of oestrus (day 1 of dioestrus), a single i.p. injection of inhibin antiserum (50, 100, 200 or 400 microl per animal) or equine chorionic gonadotrophin (eCG; 10 or 20 iu per animal) or control goat serum (100 microl per animal) was administered to adult female mice. After 48 h, the mice in each of the three groups were given a single i.p. injection of hCG (10 iu per animal). At 42 h after hCG injection, ova were collected from oviducts and cultured in KSOM solution. Treatments with both inhibin antiserum-hCG and eCG-hCG induced superovulation in all the animals tested. The number of oocytes in animals treated with inhibin antiserum was significantly higher (P < 0.05) compared with the control group, and the number of oocytes ovulated in animals treated with 200 or 400 ml inhibin antiserum was significantly (P < 0.05) higher than that in animals treated with 10 or 20 iu eCG. The superovulated oocytes that were fertilized normally in vivo were able to form blastocysts in vitro. The rate of blastocyst development for animals treated with 50-200 ml inhibin antiserum was significantly (P < 0.05) higher than that of the eCG-treated animals. Irrespective of the day of the oestrous cycle, 200 microl inhibin antiserum administered at 12:00 h on each of 4 days induced superovulation in all the animals tested. The rates of oocyte and embryo production by these animals were significantly (P < 0.05) higher than in the control groups. Furthermore, administration of inhibin antiserum at doses of 50, 100, 200 or 400 ml produced similar results in 26-day-old immature mice. These results indicate that passive immunoneutralization of endogenous inhibin alpha-subunit induces superovulation in immature and adult mice. The superovulated oocytes obtained by administration of inhibin antiserum have normal embryonic developmental competence. Thus, it is concluded that this inhibin antiserum method is a new practical alternative for induction of superovulation in mice instead of the more commonly used eCG-hCG protocol.

Animals↗

Ultrasonic vocalization responses in genetically high- and low-emotional rats.

Tsukuba High Emotional (THE) and Tsukuba Low Emotional (TLE) strains of rats have been congenitally bred for use in studies of emotionality. The current study investigated THE and TLE strain differences in the footshock-induced ultrasonic vocalization responses of adult male rats. Ultrasonic vocalization response inducibility (ratio of rats emitting ultrasounds) and vocalization activity in THE rats were statistically higher than in TLE rats. We next examined the causal relation between the ultrasonic vocalizations and the activation of the pituitary-adrenocortical axis in response to footshocks in these two strains of rats. Rats were sorted into two groups, vocalizing and non-vocalizing, after being exposed to the shock regimen daily for 5 successive days. Basal plasma concentrations of ACTH and corticosterone were not different between THE and TLE rats. After receiving footshocks, significant increases in plasma concentrations of ACTH and corticosterone were induced in both strains of rats. These increases in plasma concentrations of ACTH and corticosterone were significantly higher in THE than in TLE rats. However, in vocalizing and non-vocalizing rats of both strains, no statistical differences in plasma concentrations of ACTH and corticosterone were observed after footshocks. These findings suggest that the high emotionality of the adult male rats was reflected in the emission of ultrasounds, and that the emission of ultrasonic vocalizations might not be related to the activation of the pituitary-adrenocortical axis.

Adrenocorticotropic Hormone↗

Secretion of inhibin A and inhibin B throughout pregnancy and the early postpartum period in chimpanzees.

Plasma concentrations of inhibin A and inhibin B during pregnancy and early lactation in chimpanzees were determined by enzyme-linked immunosorbent assay (ELISA). Plasma samples were taken from five pregnant chimpanzees at 6-9, 10, 20 and 25 weeks of pregnancy, and following parturition. Throughout pregnancy and the early postpartum period, circulating inhibin A and inhibin B concentrations remained low, at similar levels to those during the normal menstrual cycle in chimpanzees. Concentrations of inhibin A in the placental homogenate were high enough to be measured by the ELISA and by bioassay, whereas circulating inhibin bioactivities in late pregnancy were too low to be measured. Plasma concentrations of FSH remained low with no significant changes throughout pregnancy and the postpartum period. Plasma concentrations of oestradiol-17beta and progesterone at 25 weeks of pregnancy were much higher than normal menstrual cycle levels. It was concluded that in chimpanzees the levels of circulating inhibin A and inhibin B remained low throughout pregnancy and the early postpartum period, and that the concentrations of bioactive dimeric inhibin did not increase towards the end of pregnancy. The suppression of circulating FSH levels during pregnancy is suggested to be controlled by steroid hormones that increased significantly in late pregnancy, and the present findings further suggest that the secretory pattern and role of inhibin during pregnancy in chimpanzees may be different from that in human and other primates.

Animals↗

Effect of hyperprolactinemia induced by pituitary grafts or castration on porphyrin content of the mouse Harderian gland.

The histology and porphyrin concentrations of Harderian glands and plasma prolactin levels were examined in B6C3F1 mice castrated or isografted with pituitaries in combination with the administration of bromocriptine (2-bromo-á-ergocryptine), a potent suppressor of prolactin. Four pituitaries were transplanted underneath the bilateral kidney capsules of each mouse. Furthermore, we investigated Harderian porphyrins and plasma testosterone levels in mice that were castrated or treated with neuroleptic butyrophenone (timiperone), a potent accelerator of prolactin, and treated concurrently with bromocriptine. Light microscopically, pituitary grafts increased the concretion of porphyrin pigments within the Harderian gland lumina. Pituitary grafts or castration increased both Harderian porphyrin concentrations and plasma prolactin levels compared with the intact control mice. In pituitary-grafted or castrated mice, bromocriptine distinctly prevented the rise in both porphyrins and prolactin levels. Administration of butyrophenone did not result in any marked change in testosterone levels, although Harderian gland porphyrins were significantly increased. The present results indicate that in mice prolactin stimulates the porphyrin production of the Harderian gland and has an important role in the regulation of Harderian gland porphyrins.

Animals↗

Evidence of primary beta-cell destruction by T-cells and beta-cell differentiation from pancreatic ductal cells in diabetes associated with active autoimmune chronic pancreatitis.

OBJECTIVE: Diabetes associated with autoimmune chronic pancreatitis (ACP) is a subtype of diabetes that is responsive to corticosteroid treatment of progressive endocrine and exocrine dysfunction. However, little is known about pathological changes of islet and exocrine pancreas in ACP. RESEARCH DESIGN AND METHODS: We examined pancreatic specimens obtained on biopsy from four diabetic men with ACP (mean [range]: age 62 years [48-78], duration of ACP 3 months [1-5], duration of diabetes 1 month [0-3]) morphologically, immunohistochemically, and morphometrically. RESULTS: The pancreatic specimens in all cases exhibited inflammatory cell infiltration surrounding ductal cells and extensive fibrosis. Some islets were infiltrated with mononuclear cells with disrupted beta-cells. The subsets of T-cells infiltrated to the islets were mainly CD8(+). Islet beta-cell volume was decreased; the mean percentage area of beta-cells in the islets in four cases with ACP were 16% (range 13-20) (P = 0.0015 vs. type 2 diabetic patients, 48% [27-73], n = 8; P = 0.0002 vs. nondiabetic control subjects, 58% [39-77], n = 7). Preserved ductal cells were surrounded predominantly by CD8(+) or CD4(+) T-cells. Some cytokeratin 19-positive ductal cells contained insulin and glucagon, representing upregulated differentiation of islet cells from ductal cells. Insulin promoter factor-1 (IPF-1) was hyperexpressed in insulin-containing ductal cells. CONCLUSIONS: Diabetes associated with ACP is caused by T-cell-mediated mechanisms primarily involving islet beta-cells as well as pancreatic ductal cells. In ACP, ductal islet precursor cells were associated with IPF-1 hyperexpression, suggesting a critical role of IPF-1 on islet cell differentiation and eventual beta-cell restoration.

Acute Disease↗

Biological characteristics of carcinomatosa pleuritis in orthotopic model systems using immune-deficient rats.

We assessed the association of vascular endothelial growth factor (VEGF) on the formation of carcinomatosa pleuritis in orthotopic model systems. Immune-deficient rats were inoculated with PC-14 cells into i) a subpleural space of the parietal pleura after pneumonectomy or ii) into the thoracic cavity directly. The rats bearing tumor cells were randomly separated into two groups: non-treatment and treatment with anti-VEGF neutralizing antibody groups. At the time of the autopsy, all rats developed gross pleural dissemination with/without malignant effusions. In the first model, despite no significant difference in the mean volume of the subpleural tumors between the groups, the degree of dissemination was suppressed in the treatment group with less tumor vasculature and with reduced expression of autocrine motility factor receptor (AMFR) in tumor cells. In the second model, although the inhibitory effect on dissemination was not clear, the formation of pleural effusion was inhibited in the treatment group. In addition to the ability of vascular permeability, the results demonstrated here showed the possible association of VEGF with the development of pleural dissemination/metastasis in the context of blood/lymphatic routes and cancer cell motility affected by AMFR.

Adenocarcinoma↗

[Carinal resection for bronchogenic carcinoma].

The purpose of this study was to evaluate the results of carinal resection for bronchogenic carcinoma in our institute. From 1981 to 1999, 24 carinal resection were performed for squamous cell carcinoma (n = 19), adenoid cystic carcinoma (n = 2), small cell carcinoma (n = 1), adenocarcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). Nineteen underwent sleeve pneumonectomy, 2 had carinal resection without lung resection, 2 had carinal resection with right middle and lower lobectomy, and 1 had wedge pneumonectomy. In the patients with sleeve or wedge pneumonectomy, there were 5 operative death and 3 patients had survived for more than 3 years. Two patients with low-grade malignant tumors underwent carinal resection without lung resection and survived more than 10 years. We believe that limited carinal resection for low-grade malignant tumors are safe and valuable procedure. Careful selection of patients with sleeve or wedge pneumonectomy is mandatory.

Adult↗

[Evaluation of cases of off-pump CABG with mid-sternotomy].

Off-pump CABG was utilized on patients who had multivessel coronary artery disease and other organ diseases. A total of 79 patients who underwent off-pump CABG were evaluated. Of these, 66 suffered from OMI and AP, 4 form AP, 6 from u-AP, and 3 from AMI. LITA was used in 75 cases, RA in 48, GEA in 45, RITA in 13, IEA in 3, and SVG in 38. Revascularization was performed at # 2 in 3 cases, # 3 in 11, 4 PD in 37, 4 PL in # 7 or # 8 in 79, # 9 in 27, # 12 in 51, and # 14 in 17. A time of 10.3 min was spent on LAD revascularization, 9.8 min on D 1, 10.2 min on Cx, anf 11.5 on RCA. Seven patients were transferred to on-pump beating CABG because of hemodynamic instability. One patients suffered postoperative CVA, and 2 had wound infection. Complete revasculization was accomplished in 78 patients, and hospital death was not reported.

Aged↗

Different lengths of a polymorphic repeat sequence in the thymidylate synthase gene affect translational efficiency but not its gene expression.

PURPOSE: Thymidylate synthase (TS) is a target enzyme of 5-fluorouracil. Recently, the TS gene has been shown to contain a polymorphic tandem repeat sequence. The aim of this study was to determine whether differences in the number of tandem repeats could affect gene expression or mRNA translation. EXPERIMENTAL DESIGN: We quantified TS mRNA isolated from 130 colorectal cancer tissues by real-time reverse transcription-PCR and TS protein in 92 available samples by the fluoro-dUMP binding assay. These values were compared with TS genotypes of the samples determined by a PCR assay. RESULTS: There was no relation between TS genotype and mRNA expression level. On the other hand, cancer tissues with the 3R/3R genotype had a significantly higher TS protein expression level than did those with the 2R/3R genotype. These results suggest that the efficiency of TS mRNA translation is responsible for the genotype-dependent difference in TS protein expression. Further analysis using TS 5'-untranslated region-luciferase reporter constructs showed that the RNA with the three-repeat sequence was translated three to four times more efficiently than that with two-repeat sequence. CONCLUSIONS: From the results of both in vitro and in vivo study, we conclude that TS mRNA with a three-repeat sequence has greater translation efficiency than that with the two-repeat sequence. The results provide the rationale for comprehensive usage of TS genotyping with quantitation of TS mRNA or TS protein to predict the patient's response to 5-fluorouracil-based chemotherapy.

5' Untranslated Regions↗