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Biomedical subjects

Toshiaki Watanabe

Publications and source records attributed to Toshiaki Watanabe.

At least 109 records · Page 6Linked to original sources
PubMed2003

The effects of dietary vitamin B12 deficiency on sperm maturation in developing and growing male rats.

To evaluate the role of vitamin B12 on spermatogenesis, the effects of dietary vitamin B12 deficiency on sperm maturation in developing rat fetuses and young growing rats were examined. The vitamin B12-deficient diet was given to all the animals for three different periods: whole period (gestation to mature), gestation period (gestation to weaning), or immature period (3-12 weeks postnatal). Sperm examination revealed that the sperm count was markedly lower in male progeny (F1) that were vitamin B12-deficient during the whole period. In addition, a significantly higher number of abnormal sperm, such as tailless and amorphous sperm, was observed. In male rats that were vitamin B12-deficient during the immature period, the incidence of abnormal sperms was 14.4% and 4.8% for tailless and short tail, respectively. The motion rates, such as path velocity and straight line velocity, were decreased to 20-40% of the control value in rats that were vitamin B12-deficient both during the whole and gestation periods. However, no effects of vitamin B12 deficiency on sperm motility were observed during the immature and mature periods. From these findings, we suggest that dietary vitamin B12 deficiency during pregnancy may induce irreversible damage in the germ cells of embryos and affect the maturation of spermatozoa.

Animal Feed↗
PubMed2003

Structure-activity relationship of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone).

This paper describes the discovery of a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone, 1), as a potent antioxidant agent against lipid peroxidation. The structure-activity relationship of edaravone indicated that lipophilic substituents were essential to show its lipid peroxidation-inhibitory activity. In vivo studies revealed that edaravone showed brain-protective activity in a transient ischemia model.

Animals↗
PubMed2003

Effects of oyster extract on the reproductive function of zinc-deficient mice: bioavailability of zinc contained in oyster extract.

Zinc is a vital nutrient in the normal reproductive function and embryonic development of mammals, and it is well known that oyster extract contains significant amounts of zinc. The effects of oyster extract on reproductive function, such as embryonic development, serum levels of zinc and sperm maturation were examined in zinc-deficient mice. Zinc deficiency in dams during pregnancy induced a decrease in the successful pregnancy rate, maternal weight gain, the number of live fetuses and fetal body weight. Zinc deficiency for 12 weeks in male mice induced a decrease in body weight, testis weight and sperm count in the epididymis. However, reproductive failure, embryonic defects and decreased sperm motility in zinc-deficient mice were improved by supplementation with oyster extract. Some nutrients contained in oyster extract, such as taurine and glycogen, may be related to the recovery of reproductive function. There were significantly lower serum concentrations of zinc in dams fed a zinc-deficient diet. However, the serum zinc concentration was normal in the oyster extract-supplemented group. No difference in the concentration of serum zinc was observed between the oyster extract- and zinc carbonate-supplemented groups. From these findings, it is suggested that oyster extract is a useful supplement that can prevent reproductive defects from zinc deficiency, and the bioavailability of zinc may be identical to zinc carbonate.

Animals↗
PubMed2002

Poorly differentiated adenocarcinoma and mucinous carcinoma of the colon and rectum show higher rates of loss of heterozygosity and loss of E-cadherin expression due to methylation of promoter region.

Previous studies have reported that poorly differentiated adenocarcinoma and mucinous carcinoma of the colon and rectum (Por & Muc) show a low incidence and poor prognosis. However, genetic alterations and tumourigenesis of Por & Muc remain unclear. In our study, we analyzed the genetic and epigenetic alterations of Por & Muc to clarify the difference from those of well-differentiated adenocarcinoma (WD). First, we evaluated the loss of heterozygosity (LOH) on 4 chromosomes (2p, 5q, 17p, 18q) frequently observed in colorectal cancer. Second, to determine large-scale allelic losses, we performed wide-ranging allelotyping study. Using 27 microsatellite markers spanning every 10 cM on chromosome 17 and 18, we defined the LOH ratio as the proportion of markers that exhibit LOH out of 27 markers. Third, we evaluated the methylation of E-cadherin. With respect to LOH of 4 loci, higher rates of LOH were observed in Por & Muc and a statistical significance was found on the markers adjacent to MSH2 and SMAD4/DCC. Moreover, as the evidence of large-scale allelic imbalance, the average LOH ratio was higher in Por & Muc (0.70) than in WD (0.24) (p = 0.01). Methylation analysis showed that 54.5% of Por & Muc demonstrated hypermethylation of E-cadherin. In immunohistochemistry, 77.8% of Por & Muc exhibited abnormal expression of E-cadherin. Hypermethylation of E-cadherin correlated significantly with abnormal expression (p = 0.047). These results suggest that the higher rates of LOH contribute to Por & Muc tumourigenesis and most of Por & Muc lose normal E-cadherin expression, partly because of the methylation of promoter region.

Adenocarcinoma↗
PubMed2002

The expression pattern of Ku correlates with tumor radiosensitivity and disease free survival in patients with rectal carcinoma.

BACKGROUND: Preoperative radiotherapy reduces the rate of local recurrence and improves the chance of survival in patients with resectable, advanced rectal carcinoma. However, because not all tumors respond similarly to radiation, sorting out suitable patients is required to irradiate tumors rationally. The authors examined the possible role of Ku protein in determining tumor radiosensitivity and disease free survival in patients with rectal carcinoma. METHODS: The authors studied 96 patients with advanced rectal carcinoma. In preradiation biopsy specimens of tumor samples, the number of cells that were stained positive for Ku protein was evaluated by immunohistochemistry. The expression pattern of Ku protein was examined for an association between tumor radiosensitivity (which was determined according to T classification downstaging, complete pathologic response, or Response Evaluation Criteria in Solid Tumors) and disease free survival. RESULTS: There was a high degree of correlation between the percentage of cells that expressed the 70-kDa Ku protein (Ku70) and the 86-kDa Ku protein (Ku86) in the tumor sections (correlation coefficient = 0.85; P < 0.001). The expression pattern of Ku protein was correlated not only with tumor radiosensitivity but also with disease free survival. Pathologic TMN classification, histopathologic grade, and Ku70 expression were significant prognostic variables for disease free survival in a multivariate analysis (P = 0.0031, P = 0.030, and P = 0.023, respectively). CONCLUSIONS: Ku70 and Ku86 raise the predictive possibility of tumor radiosensitivity. Ku may be a useful parameter for selecting patients with rectal carcinoma for preoperative radiotherapy.

Adult↗
PubMed2002

Isolation and characterization of a novel gene, hRFI, preferentially expressed in esophageal cancer.

hTID1, a human homologue of Drosophila tumor suppressor, I(2)tid regulates the release of cytochrome c from mitochondria and subsequent alteration of caspase-3 activity on apoptosis induced by exogenous stimuli, such as tumor necrosis factor-alpha and mitomycin C. To search for an interacting molecule with hTid1, we applied two-hybrid yeast screening and isolated a novel gene, which encodes a 46 kDa protein of 373 residues. Within the deduced amino acid sequence, a region showing homology to the Ring Finger domain of X-linked inhibitor of apoptosis protein was identified and the gene was designated as hRFI, standing for human Ring Finger homologous to IAP type. A 2.0 kb hRFI transcript was ubiquitously expressed in all human tissues as well as several cancer cell lines examined. Northern blot analysis showed that in 70% (14 out of 20) of esophageal cancer patients, expression of hRFI in cancerous regions was two or more times higher than in the corresponding normal tissues. HeLa cells transfected with hRFI construct exhibited a tendency to resist TNF-alpha induced apoptosis, suggesting an anti-apoptotic function of the hRFI product. Finally, hRFI protein was shown to be cleaved within the DEDD sequence spanning residues 230-233 by caspase-3 during the apoptotic induction.

Amino Acid Sequence↗
PubMed2002

Caspase-8 gene transduction augments radiation-induced apoptosis in DLD-1 cells.

Caspase-8 is a member of the cysteine protease family that plays a critical role in death receptor-mediated apoptosis. We previously demonstrated that adenovirally transduced caspase-8 efficiently induced apoptosis in tumor cells (Shinoura et al. (2000) Hum. Gene Ther. 11, 1123-1137). However, to ensure safety in clinical applications some devise for minimization of the dose of adenoviral vector required for sufficient antitumor effect is needed. In this study, we evaluated the proapoptotic effect in DLD-1 colon cancer cells of a combination of low-dose infection with an adenoviral vector expressing caspase-8 and X-ray irradiation. Under these conditions, X-ray irradiation strongly induced apoptosis whereas irradiation without transduction only had a trace proapoptotic effect. Overexpression of bcl-xL strongly blocked the activation of caspase-8 and induction of apoptosis, suggesting that adenovirally transduced caspase-8 was activated at a point downstream of mitochondria. This combination strategy may be a useful modality for gene therapy of colorectal cancer.

Adenoviridae↗
PubMed2002

FDG-PET after radiotherapy is a good prognostic indicator of rectal cancer.

UNLABELLED: In the management of rectal cancer after the combined therapy of the radiation and surgical operation, the evaluation of the prognosis is important. Although fluoro- 18-deoxyglucose positron emission tomography (FDG-PET) is considered as a useful tool for evaluation of therapeutic effect of this cancer as well as the other cancers, however, there are few articles that clearly describe the appropriate procedure of the FDG-PET in order to obtain the best prognostic value. The purpose of the present study is to compare several variations of a semi-quantification method, the Standardized Uptake Values (SUV) and to determine the most appropriate parameter, for the prognostic prediction and to propose the quantitative guideline of the FDG-PET. Especially, the authors focused on the SUV after radiotherapy, which had not been considered as a key quantitative value, as it was rather taken as a mere indicator of the therapeutic (radiotherapeutic) effect, not a direct indicator of the prognosis for the cancer itself. METHODS: Forty patients with rectal cancer in the lower rectal region underwent two series of FDG-PET study before and after pre-operative radiotherapy. Their SUVs were calculated from FDG-PET data and compared with the results of the long-term follow-up of the patients as well as with histopathological outcomes. RESULTS: All 40 patients had high FDG uptake before radiotherapy. The mean value of SUV before radiotherapy (SUV1) was 7.6. After radiotherapy, the mean value of SUV (SUV2) decreased to 4.2. There was a significant difference in SUV2 between the groups with and without recurrence (p < 0.05), however, SUVI or SUV ratio (SUV2/SUV1) displayed no significant difference with the incidence of recurrence. CONCLUSION: SUV2 was considered to be a good prognostic indicator for long-term prognosis of rectal cancer patients. SUV1 nor SUV ratio SUV2/SUV1 did not have the equivalent prognostic usefulness. Subsets of patients with SUV2 greater than 3.2 should be observed closely.

Adult↗
PubMed2002

Interferon inhibits progression of liver fibrosis and reduces the risk of hepatocarcinogenesis in patients with chronic hepatitis C: a retrospective multicenter analysis of 652 patients.

A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P < 0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.

Alanine Transaminase↗
PubMed2002

Histogenesis and morphogenesis of depressed-type early colorectal carcinoma.

The aim of this study was to elucidate the histogenesis and morphogenesis of depressed-type early colorectal carcinomas (DECas). Eighty-seven DECas were selected for examination. The 87 DECas included 23 (26.4%) absolutely depressed (ABS) types (depressed mucosa being thinner than the normal mucosa; histologically true depression), 40 (46.0%) relatively depressed (REL) types (the thickness of the depressed mucosa being the same or greater than that of normal mucosa, with depression being relative compared to marginal elevation) and 24 (27.6%) ulcerated (UL) types (no remnant intramucosal component in the depressed area). The rates of residual adenomatous components were 0/23 (0%) for ABS type and 12/40 (30%) for REL type, indicating that the ABS type was thought to have arisen de novo and the REL type was thought to have arisen de novo and via an adenoma-carcinoma sequence. In 13 of the 23 (56.5%) ABS types, carcinoma was located within the depressed area alone, suggesting that many ABS types show a depression from their initial stage. While 33 of the 40 (82.5%) REL types accompanied by marginal elevation consisted of neoplastic mucosa, in 19 of the 33 (57.6%) cases, the depressed area showed a higher grade of atypia than the area of marginal elevation. This suggested that the depression in the REL type was generated secondarily at the center of a pre-existing, superficially elevated tumor due to progression of its histological grade of atypia. ABS type was speculated to be the precursor of UL type since the two types showed similarity (no statistical significant difference) in percent depression (69.6 vs 64.3%), grade of atypia of carcinoma (52.2 and 79.2% consisted of carcinoma with high-grade atypia alone), and frequency of being accompanied by non-neoplastic reactive marginal elevation (56.5 vs 70.8%).

Colorectal Neoplasms↗
PubMed2002

Extended lymphadenectomy and preoperative radiotherapy for lower rectal cancers.

BACKGROUND: Extended lymphadenectomy including lateral node dissection (EXT-L) contributes to a low incidence of local recurrence of lower rectal cancer. However, EXT-L is frequently associated with impairment of sexual and urinary function. We therefore compared the effectiveness of preoperative radiotherapy with that of EXT-L. METHODS: One hundred fifteen patients were studied. Seventy-eight patients underwent preoperative radiotherapy with a total dose of 50 Gy (Rad[+] group), and 37 did not (Rad[-] group). Seventy-five patients received EXT-L (EXT-L[+] group), and 40 did not (EXT-L[-] group). Patients were further divided into 4 subgroups (Rad[+]&EXT-L[-], Rad(+)&EXT-L[+], Rad[-]&EXT-L(+), and Rad[-]&EXT-L[-]), and clinicopathologic features were examined. In the Rad(+) group, the relation between the p53 gene and survival was also examined. RESULTS: There was a significant difference in disease-free survival between the Rad(+) and Rad(-) groups (5-year disease-free survival rate, 74.6% vs 45.9%; P =.006). However, there was no significant difference between the Rad(+)&EXT-L[-] and Rad[-]&EXT-L(+) groups. The p53 gene status did not affect survival in the Rad(+) group. CONCLUSIONS: This study suggests that in terms of curative effect, preoperative radiotherapy can be one alternative therapy in place of EXT-L for patients with lower rectal cancer.

Adenocarcinoma↗
PubMed2002

Not infrequent K-ras mutations in depressed-type early colorectal carcinomas larger than 10 mm.

The aim of this study was to elucidate whether K-ras (codons 12 and 13) mutations occur in depressed-type early colorectal carcinomas (DECas) larger than 10 mm in size. Thirty-four cases of DECas including 27 larger than 10 mm were examined for K-ras mutations by means of microdissection, PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism), and direct sequencing. Although K-ras mutation was infrequent (1/7, 14%) in small (less than 10 mm) DECas, 16/27 (59%) and 17/27 (63%) of DECas larger than 10 mm revealed codon 12, or either codon 12 or 13 mutations, respectively. None of the evaluated pathological factors except size showed a correlation with K-ras mutation. These data indicate that although K-ras mutation could not be involved in the early stage of the progression of DECas, it might play a role at a later stage when the tumor size is over 10 mm.

Colorectal Neoplasms↗
PubMedDate not supplied

Coil embolization of an arteriobiliary fistula caused by hepatic intra-arterial chemotherapy.

Arteriobiliary fistula is a rare complication of hepatic intra-arterial chemotherapy. We report successful coil embolization of an arteriobiliary fistula. An 80-year-old woman underwent percutaneous placement of an indwelling catheter into the replaced right hepatic artery for intra-arterial chemotherapy of liver metastases. Coil embolization of the left hepatic artery was not performed. The patient complained of abdominal pain during intra-arterial chemotherapy. Angiography revealed a fistula between the replaced right hepatic artery and the common bile duct. The fistula was successfully treated by coil embolization via the indwelling catheter, and the indwelling catheter was removed. Although such complications usually herald the termination of intra-arterial chemotherapy, the patient underwent percutaneous implantation of a new catheter-port system, and intra-arterial chemotherapy was restarted.

Abdominal Pain↗
PubMedDate not supplied

Ectopic thyroid in the adrenal gland: Computed tomography findings.

Ectopic thyroid in the adrenal gland is extremely rare, and its radiologic findings have not been reported in the radiologic literature. A case of ectopic thyroid in the adrenal gland is reported, and its imaging findings on computed tomography are discussed.

Adrenal Gland Diseases↗