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Biomedical subjects

G Watanabe

Publications and source records attributed to G Watanabe.

At least 19 recordsLinked to original sources

Loss of fragile histidine triad gene expression is associated with progression of esophageal squamous cell carcinoma, but not with the patient's prognosis and smoking history.

BACKGROUND: Recently, fragile histidine triad (FHIT) gene abnormality has been thought to be associated with several malignancies and smoking history. The authors previously discovered that methylation of the 5' CpG island of the FHIT gene was closely associated with transcriptional inactivation in esophageal squamous cell carcinoma (SCC); however, the clinical impact of the FHIT gene in esophageal carcinoma is still unknown. METHODS: In this article, the authors evaluated the clinical impact of the FHIT gene in 149 esophageal squamous cell carcinoma (SCC) patients retrospectively using immunohistochemical analysis. They also examined the correlation between FHIT protein expression and smoking history. RESULTS: Among 149 curative resection (R0) cases of esophageal SCC, normal FHIT protein expression was noted in only 33 cases (22.1%), whereas reduced FHIT protein expression was noted in 67 cases and there was no FHIT expression in 50 cases. When a tumor invaded the muscle layer, FHIT protein expression was markedly reduced. The cases with reduction or loss of FHIT protein expression tended to have poor prognoses (P = 0.069). However, Cox multivariate analysis revealed that FHIT protein reduction had no relation to prognosis. FHIT protein expression had no relation to smoking history. CONCLUSIONS: FHIT protein expression was associated with progression of esophageal SCC, however, it may not be associated with the patient's prognosis and smoking history.

Aged↗

Irreversible effects of neonatal exposure to p-tert-octylphenol on the reproductive tract in female rats.

It has been known for many years that administration of androgens or estrogens at critical periods of development in mammals causes severe long-term effects on the endocrine/genital systems. The environmental pollutant p-tert-octylphenol (OP) possesses a weak but clear estrogen agonist activity in in vitro and in vivo studies. In the present study, effects of neonatal exposure to OP on the reproductive tract of female rats were investigated. Newborn female pups were injected with 100 mg/kg OP subcutaneously within 24 h after birth. Administration was repeated every other day until postnatal day 15 (total of eight doses). Before weaning, serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) remained at low levels during OP exposure, although the serum FSH peak and the high LH level were obvious in the controls. Histologically, inhibition of uterine gland genesis was apparent. The day of vaginal opening was about 4 days earlier in OP-treated animals than in controls. Persistent estrus was consistently observed in OP-treated animals. Atrophic and polycystic ovaries without corpora lutea showed anovulation. In the endometrium, cell-proliferative activity and cell-death were increased and decreased, respectively, and expression of estrogen receptor alpha mRNA was apparent by in situ hybridization. Unexpectedly, endometrial hyperplasias appeared at 8 weeks of age. After ovariectomy, vaginal smears immediately became of castration type and the uterus was atrophied. These results suggested that neonatal exposure to a high dose of OP alters developmental hormonal secretion presumably due to a hypothalamo-pituitary-ovarian disorder, with accelerated vaginal opening, subsequent persistent estrus, and uterine endometrial hyperplasia. The changes in the uterus and vagina are ovary-dependent.

Animals↗

The suppression of small GTPase rho signal transduction pathway inhibits angiogenesis in vitro and in vivo.

Angiogenesis consists of multistep pathways such as the degradation of the matrix, proliferation of the endothelial cells, motility of the endothelial cells, formation of the cord structure and network formation of microvessels. The small GTPase Rho participates in cell motility through actin fiber polymerization. The role of the small GTPase Rho signal transduction pathway in regulating angiogenesis, however, is still unknown. In this study, we investigated the role of the small GTPase Rho signal transduction pathway in angiogenesis in vitro and in vivo using the exoenzyme, Clostridium botulinum C3 transferase, which specifically suppresses Rho and a compound, Y-27632, which suppresses p160ROCK (Rho-associated coiled-coil containing protein kinase). In this paper, we showed that the small GTPase Rho-p160ROCK signal transduction pathway played an important role in angiogenesis both in vitro and in vivo. These results suggest that inhibition of the small GTPase Rho signal transduction pathway by the p160ROCK inhibitor could be a possible new strategy for angiogenic diseases.

Amides↗

Association between diabetic retinopathy and genetic variations in alpha2beta1 integrin, a platelet receptor for collagen.

Platelets might be involved in the pathogenesis of diabetic microangiopathy. Wide interindividual variations in the density of a platelet collagen receptor (alpha2beta1 integrin or glycoprotein Ia/IIa) are reportedly associated with polymorphism(s) in the gene encoding the alpha subunit of the receptor, including a Bgl II polymorphism in intron 7. The aim of the present study was to determine the relationship between the Bgl II polymorphism and the susceptibility to diabetic microangiopathy. A case-control study comparing 227 patients with type II diabetes mellitus (119 with versus 108 without diabetic retinopathy) as well as 169 nondiabetic subjects demonstrated that genotypes with Bgl II (+) allele had a significant increase in the risk for retinopathy. The odds ratio for Bgl II (+/+) to Bgl II (-/-) was 3.41 (95% CI, 1.49-7.78, P =.0036) when analysis was confined to those with a disease duration of diabetes of 10 years or more. The present study suggests that the presence of a Bg II (+) allele is a genetic risk factor for diabetic retinopathy. (Blood. 2000;95:1560-1564)

Alleles↗

Hepatic parenchymal cell volume and the indocyanine green tolerance test.

BACKGROUND: Precise evaluation of the hepatic function of preoperative patients with liver cirrhosis is controversial. Hepatic functional capacity cannot be evaluated easily because hepatic function is not based on morphological aspects. PURPOSE: The aim of this study was to evaluate hepatic function with a new procedure of the indocyanine green (ICG) tolerance test using an ICG clearance meter, and to compare liver parenchymal cell volume with hepatic function. PATIENTS AND METHODS: Sixteen patients (seven with histologically normal liver and nine with histologically proven liver cirrhosis) scheduled for liver resection were selected randomly for the study. Measurement of two blood disappearance rate constants of ICG, k(100-900) and k(100-300), and effective hepatic blood flow (EHBF) using an ICG clearance meter, as well as conventional ICG-k(5,10,15) and ICG-R15, was performed. We calculated k(100-300) and EHBF using the early disappearance rate of ICG with the ICG clearance meter. Liver parenchymal cell volume was measured using CT volume and the liver parenchymal cell ratio with computer-aided image analysis. RESULTS: The value of ICG-k(100-300) was mostly proportional to liver parenchymal cell volume. EHBF per liver parenchymal cell volume did not differ between normal and cirrhotic subjects. CONCLUSIONS: ICG-k(100-300) and EHBF are good indices of liver function and are proportional to liver parenchymal cell volume. Hepatic dysfunction in cirrhosis is due to a decrease in liver parenchymal cell volume.

Carcinoma, Hepatocellular↗

DXS10011: a hypervariable tetranucleotide STR polymorphism on the X chromosome.

The locus DXS10011 is a polymorphic system with a tetranucleotide repeat sequence located on the human X chromosome. The distribution of allele frequencies was examined in 334 Japanese and 171 German individuals and a total of 36 alleles was detected in the two population groups. This STR polymorphism will be a useful marker for linkage analysis.

Alleles↗

Follicle selection in cyclic guinea pigs with active immunization against inhibin alpha-subunit.

Experiments were conducted to elucidate the mechanisms of active immunization against inhibin on ovarian follicular development and selection in guinea pigs. Estrous cycle was synchronized in experimental guinea pigs by implanting progesterone containing tubes. Antibodies that bound 125I-labeled bovine inhibin were produced by all guinea pigs receiving the inhibin vaccine (recombinant ovine alpha-subunit in oil emulsion) without any effects on duration of the estrous cycle. Active immunization against inhibin increased the plasma concentrations of progesterone during the luteal phase and the plasma concentrations of estradiol but failed to increase the plasma concentration of follicle-stimulating hormone (FSH) during preovulatory period. The treatment also increased the number of corpora lutea (from 1.3+/-0.3 to 7.0+/-1.6 per each ovary), and preovulatory sized follicles (from 1.8+/-0.6 to 7.0+/-1.6 per each ovary), and follicles stained positively for inhibin alpha-subunit (from 2.3+/-0.5 to 6.3+/-1.3 per each ovary) significantly. The results indicate that active immunization against inhibin enhances ovulation rate by affecting the follicle selection and only dominant follicle can be stained for inhibin alpha-subunit in guinea pigs. This study is firstly to provide direct evidence that inhibins play important role in follicle selections in guinea pigs.

Animals↗

Changes in concentrations of plasma immunoreactive follicle-stimulating hormone, luteinizing hormone, estradiol-17beta, testosterone, progesterone, and inhibin in heifers from birth to puberty.

This study was designed to clarify the characteristics of changes in plasma concentrations of reproductive hormones in heifers from birth to puberty. Weekly or daily hormonal changes were observed in 39 heifers. Daily changes in the concentration of follicle-stimulating hormone (FSH) demonstrated a consistent cycle of hormone changes over a 7- to 8-day period in heifers from approximately 10 days to 9 months old. Weekly changes in reproductive hormones showed that there were three brief periods in heifers between birth and puberty in which dramatic changes occur. The first period was the first week after birth, during which a reciprocal relationship between steroid hormones and gonadotropins was observed. At birth, the concentrations of steroid hormones were higher than those at any other age. These hormone levels rapidly decreased within the first week after birth. Gonadotropin levels, however, increased from birth to 1 week of age. The second period of major change was at approximately 4 weeks of age when there was an increase in the concentrations of luteinizing hormone (LH), estradiol-17beta, testosterone, and immunoreactive inhibin. The third period was the last 5 weeks before the first ovulation, when there was an increase in the concentrations of estradiol-17beta followed by an increase in (LH). These results suggest that regular hormone changes start from 10 days after birth and that the periods from birth to 4 weeks of age and the last 5 weeks before the first ovulation in heifers are important to the development of reproductive functions before puberty.

Animals↗

Histological response of cisplatin predicts patients' survival in oesophageal cancer and p53 protein accumulation in pretreatment biopsy is associated with cisplatin sensitivity.

The aim of this study was to evaluate whether cisplatin sensitivity relates to patient's prognosis in oesophageal squamous cell carcinoma and to find a useful chemosensitivity molecular marker. 59 oesophageal squamous cell carcinoma (SCC) patients received cisplatin 30 mg/m2/week treatment of two to five cycles, followed by oesophagectomy. We analysed retrospectively whether the histological effect was related to patient's prognosis. Furthermore, to evaluate the relationship between the effect of preoperative cisplatin treatment and p53 and cyclin D1 expression, we investigated p53 and cyclin D1 expression in pretreatment biopsy samples using an immunohistochemical analysis and compared the results with the histological effect to cisplatin in the resected oesophagus. The cases that showed immunohistochemical p53 staining in the pretreatment biopsy samples were resistant to cisplatin (P = 0.032). However, there was no relationship between cyclin D1 expression and histological effect (P = 0.230). Nevertheless, combined analysis of p53 and cyclin D1 can predict histological effect (P = 0.032). The prognosis of cisplatin-sensitive cases was significantly better than that of cisplatin-resistant cases (P = 0.041). Cox's multivariate analysis revealed that the histological effect was an independent prognostic factor. In contrast, p53 protein accumulation and cyclin D1 were not. Histological response after neoadjuvant cisplatin treatment is a prognostic factor for oesophageal SCC and cisplatin chemotherapy may be selected according to the findings of p53 and cyclin D1 expression.

Antineoplastic Agents↗

Evaluation of tracheo-bronchial wall invasion using transbronchial ultrasonography (TBUS).

BACKGROUND: Whereas accurate evaluation of tumor invasion into the tracheo-bronchial wall is a critical factor in decision-making of therapy for intra-thoracic malignancies, it is sometimes difficult with usual thoracic imaging techniques such as computed tomography. As recent progress in technology of ultrasonography is marked, usefulness of transbronchial ultrasonography (TBUS) in evaluation of tracheo-bronchial wall invasion was assessed. METHODS: Following routine fiberoptic bronchoscopy, an ultrasound probe (20 MHz) covered with a balloon sheath was inserted through the bronchoscope. After air present between the ultrasound probe and the tracheo-bronchial wall was eliminated with filling the balloon with distilled water, TBUS imaging was taken. RESULTS: With TBUS, normal tracheo-bronchial wall was represented as a five-layer structure at the cartilagenous portion and a three-layer structure at the membranous portion. Based on this normal TBUS imaging, tumor extent was judged in 35 patients with intra-thoracic malignancies. Among 25 patients with extra-wall tumor including esophageal cancer (n=15) and metastatic lymph nodes (n=7), tracheo-bronchial wall invasion was clearly demonstrated in nine patients, and no invasion was demonstrated in the other 16 patients. Among ten patients with tumor originating from the tracheo-bronchial wall, tumor extent beyond outer border of the wall was demonstrated with TBUS in five patients. These diagnoses were examined pathologically in 15 patients who underwent the operation, and the accuracy was 93.3%. CONCLUSIONS: It is suggested TBUS can be a useful diagnostic tool in evaluation of tumor invasion to the tracheo-bronchial wall.

Adult↗

Monotypic epithelioid angiomyolipoma of the liver.

AIMS: Monotypic epithelioid angiomyolipoma is a recently recognized renal tumour, which is composed purely of epithelioid cells coexpressing markers of both smooth muscle differentiation and melanogenesis (HMB45). We report here the first case of monotypic epithelioid angiomyolipoma arising in the liver. CASE DETAILS: A 30-year-old woman without tuberous sclerosis complex (TSC) was incidentally found to have a hepatic mass by ultrasonography. Grossly, the resected tumour showed a nodule-in-nodule appearance, with large areas of haemorrhagic necrosis. Microscopically, the tumour was composed of pleomorphic epithelioid cells with clear, eosinophilic cytoplasm. Neither adipocytes nor abnormal vessels were recognized in the tumour. Immunohistochemically, the tumour cells were strongly positive for HMB45 and S100 protein, focally positive for desmin, vimentin and smooth muscle actin, and negative for epithelial markers (cytokeratins, EMA). Ultrastructural analysis showed numerous dense granules with some striated ones resembling melanosomes, myofilaments and pinocytic vesicles in the cytoplasm. Molecular analysis showed no allelic loss of the TSC2 region or 12 other chromosomal regions. The patient is free of disease over 1 year after the operation. CONCLUSION: We consider that this hepatic tumour is closely related to angiomyolipoma, and a counterpart of renal monotypic epithelioid angiomyolipoma.

Adult↗

Duodenal somatostatinoma: a case report and review of 31 cases with special reference to the relationship between tumor size and metastasis.

Somatostatinomas are rare functioning neoplasms usually arising in the pancreas and duodenum. We report a case of somatostatinoma in a 42-year-old male with neither neurofibromatosis nor somatostatinoma syndrome. A large tumor in the descending duodenum had given rise to multiple lymph node metastases. An additional 31 duodenal somatostatinoma cases were also reviewed. Most originated in the descending part of the duodenum, with the ampulla and peri-ampullary area as the most common sites (60%). Frequent manifestations were abdominal pain (25%), jaundice (25%), or cholelithiasis (19%), the latter two reflecting obstruction of the bile duct by tumors. Only two cases showed a possible somatostatinoma syndrome (6%). The tumors with metastases, lymph nodes (10) and liver (2), were significantly larger than average than those without (2.91 +/- 1.49 cm vs 1.36 +/- 0.71 cm, P < 0.05). With a cut-off point of 2.0 cm, diagnostic accuracy for metastasis was 77.78% with 87.50% specificity and 63.64% sensitivity. The smallest tumor with metastases was 0.8 cm and the largest without metastases was 3.0 cm. These results indicate that duodenal somatostatinomas are malignant by nature and the risk of metastasis significantly increases with tumors larger than 2.0 cm.

Adult↗

Detection of lymph node metastasis of oesophageal cancer by RT-nested PCR for SCC antigen gene mRNA.

With recent development in molecular biology, reverse transcriptase polymerase chain reaction (RT-PCR) has been applied to detect occult lymph node metastasis, but there have been few reports concerning oesophageal cancer. The objective of this study is to investigate the usefulness of the squamous cell carcinoma (SCC) antigen gene as a marker with RT-nested PCR to detect occult lymph node metastases of oesophageal cancer. The SCC antigen has been widely used as a serum tumour marker and was reported as a target gene to detect tumour cells in peripheral blood in cervical cancer. In this study, 620 lymph nodes from 14 oesophageal cancer patients were analysed. The results of RT-nested PCR were compared with that of pathological and immunohistochemical examinations. In the test of sensitivity, the RT-nested PCR detected 10(1) of SCC antigen producing cells in 10(7) peripheral blood mononucleocytes and was not found in 43 control lymph nodes. The pathological examination, immunohistochemical examination and the RT-nested PCR detected 36, 45 and 65 nodes respectively. The RT-nested PCR detected statistically more lymph nodes than the pathological or immunohistochemical examination. The sensitivity and specificity seem higher in squamous cell carcinoma cases. The SCC antigen gene is one of the more useful markers for RT-nested PCR to detect occult lymph node metastases of oesophageal cancer.

Antigens, Neoplasm↗

Effects of oral administration of L-arginine on renal function in patients with heart failure.

OBJECTIVES: Although the beneficial effects of L-arginine on systemic haemodynamics have been reported in patients with heart failure, its effect on renal function has not been examined. We evaluated the effects of oral administration of L-arginine on renal haemodynamics, sodium and water handling, and various hormonal factors in patients with chronic heart failure. SUBJECTS AND METHODS: A double-blind crossover trial was performed in 17 patients with chronic congestive heart failure (NYHA II-III, 56 +/- 12 years of age) who were randomly assigned to receive oral L-arginine (15 g/day) and placebo or placebo and arginine sequentially for 5 days each. Twenty-four hour creatinine clearance (Ccr), and 24-h urinary cyclic guanosine 5-monophosphate (GMP) excretion were determined. Saline loading was performed on day 5 of each treatment Renal blood flow, glomerular filtration rate (GFR), and urinary sodium excretion rate (UNa) were assessed before and after saline loading. RESULTS: Twenty-four hour GMP excretion (1.4 +/- 1.1 versus 0.8 +/- 0.5 micromol/day, P < 0.01) and Ccr (150 +/- 43 versus 125 +/- 42 ml/min, P < 0.05) were higher and plasma endothelin level (2.5 +/- 0.6 versus 3.1 +/- 0.8 pg/ml, P < 0.05) was lower with L-arginine treatment compared to placebo treatment In addition, the relative increase of UNa and GFR after saline loading were significantly higher in L-arginine treatment (UNa, 47 +/- 12%; GFR, 44 +/- 31%) than in placebo treatment (UNa, 34 +/- 9%; GFR, 22 +/- 29%) (P < 0.05). CONCLUSIONS: Oral administration of L-arginine has beneficial effects on glomerular filtration rate, natriuresis, and plasma endothelin level in patients with chronic congestive heart failure.

Administration, Oral↗

Cyclin D1 is required for transformation by activated Neu and is induced through an E2F-dependent signaling pathway.

The neu (c-erbB-2) proto-oncogene encodes a tyrosine kinase receptor that is overexpressed in 20 to 30% of human breast tumors. Herein, cyclin D1 protein levels were increased in mammary tumors induced by overexpression of wild-type Neu or activating mutants of Neu in transgenic mice and in MCF7 cells overexpressing transforming Neu. Analyses of 12 Neu mutants in MCF7 cells indicated important roles for specific C-terminal autophosphorylation sites and the extracellular domain in cyclin D1 promoter activation. Induction of cyclin D1 by NeuT involved Ras, Rac, Rho, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38, but not phosphatidylinositol 3-kinase. NeuT induction of the cyclin D1 promoter required the E2F and Sp1 DNA binding sites and was inhibited by dominant negative E2F-1 or DP-1. Neu-induced transformation was inhibited by a cyclin D1 antisense or dominant negative E2F-1 construct in Rat-1 cells. Growth of NeuT-transformed mammary adenocarcinoma cells in nude mice was blocked by the cyclin D1 antisense construct. These results demonstrate that E2F-1 mediates a Neu-signaling cascade to cyclin D1 and identify cyclin D1 as a critical downstream target of neu-induced transformation.

Animals↗

Inhibin is an important factor in the regulation of FSH secretion in the adult male hamster.

We investigated the importance of inhibin and testosterone in the regulation of gonadotropin secretion in adult male golden hamsters (Mesocricetus auratus). After castration, plasma concentrations of inhibin and testosterone were reduced to undetectable, whereas plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were increased. After hemicastration, plasma FSH and LH increased moderately and plasma inhibin decreased to one-half its initial level. Plasma testosterone levels in hemicastrated animals decreased 3 h after hemicastration but returned to those in sham-operated animals at 6 h. Plasma LH in the castrated hamster declined comparably to intact animals with testosterone treatment; plasma FSH also decreased but still remained at levels higher than those in intact animals. After treatment with inhibin in long-term-castrated animals, plasma FSH decreased, whereas plasma LH was not altered. Intact males treated with flutamide, an anti-androgen, showed a significant increase in plasma LH but not in FSH. On the other hand, treatment with anti-inhibin serum induced a significant elevation in plasma FSH, but not in LH. Using immunohistochemistry, we showed that the inhibin alpha-subunit was localized to both Sertoli and Leydig cells. The present study in adult male hamsters indicates that FSH secretion is regulated mainly by inhibin, presumably from Sertoli and Leydig cells, and that LH secretion is controlled primarily by androgens produced from the Leydig cells. This situation is more similar to that of primates than of rats.

3-Hydroxysteroid Dehydrogenases↗

Development of embryos in superovulated guinea pigs following active immunization against the inhibin alpha-subunit.

Embryo recovery and subsequent embryonic development from guinea pigs treated with or without inhibin vaccines were compared to determine the effect of active immunization against the inhibin alpha-subunit. Twenty female guinea pigs of the Hartley strain were injected 3 times either with 1 ml inhibin vaccine (recombinant ovine inhibin a-subunit in oil emulsion: 50 microg/ml, inhibin-immunized group), or 1 ml placebo (saline in oil emulsion; control group) at 4 week intervals. After one estrous cycle following the last injection, females were naturally mated and embryos were collected at 11:00 hr of day 6 of pregnancy (Day 1: sperm in the vaginal smear) for culture in vitro. Active immunization increased the number of corpora lutea (12.6+/-3.0 vs. 4.6+/-0.2, P<0.05), recovered embryos (9.8+/-1.9 vs. 3.6+/-0.4, P<0.01) and normal embryos (7.8+/-1.4 vs. 3.6+/-0.4, P<0.05), although estrous cycle length was not affected (P>0.05). During subsequent 8 day culture in vitro, most of the recovered embryos formed trophoblast outgrowth; 100% (14/14) and 88.2% (15/17) in control and immunized groups, respectively. High levels of inhibin antibody titers were sustained in the inhibin-immunized guinea pigs at least for 5 months after the last injection while no antibody titer was detected in the control animals. These results indicate that active immunization against the inhibin a-subunit is a long-acting and efficient method to induce superovulation with normal embryonic development in the guinea pig.

Animals↗

Effects of third ventricle injection of norepinephrine analogue on LH secretion of the non-laying SIJI goose.

The effect of norepinephrine analogue (NA) and norepinephrine antagonists on luteinizing hormone releasing hormone (LHRH) secretion in geese was investigated by monitoring serum levels of LH. Twenty non-laying geese were selected and randomly assigned to 4 groups of 5 each. The geese received a single intraventricular injection of saline (control), NA (12 microg/6 microl), phentolamine (1 microg/6l) plus NA or yohimbine (10 microg/6 microl). Phentolamine, a non-selective adrenoreceptor blocker was given 5 min before NA, but yohimbine, an alpha2-adrenoreceptor blocker, was delivered without NA injection. The results showed that serum levels of LH began to increase 20 min after injection of NA, and that high serum levels of LH were maintained until 105 min, followed by a decline to the basal level 125 min later. Significantly high levels of serum LH were observed at 50 and 105 min after the injection as compared with the respective control. Treatment with phentolamine completely blocked the stimulatory effect of NA on serum levels of LH in NA treated geese. Serum levels of LH increased by yohimbine treatment 5 min after the injection and the high levels of serum LH were maintained until 125 min later. Five out of 8 points were significantly high as compared with their respective control values. The present study also suggested that there is presynaptic modulation in the a-noradrenergic neural pathways which mediate the release of LHRH, and that this modulation may be carried out by alpha2-adrenoreceptor blocker.

Adrenergic alpha-Agonists↗