Biomedical subjects

F Watanabe

Publications and source records attributed to F Watanabe.

At least 19 recordsLinked to original sources

PubMed2006

Hepatocyte growth factor secreted by cultured adipocytes promotes tube formation of vascular endothelial cells in vitro.

OBJECTIVE: Adipose tissue is closely associated with angiogenesis, but the mechanisms are not fully understood. Some of the adipocyte-derived cytokines are hypothesized to play an important role in angiogenesis. We evaluated tube formation of human umbilical vascular endothelial cells (HUVECs) cultured in type I collagen gel when overlaid with the supernatant of 3T3-L1 cell culture, and expression of tube-forming factor(s) in 3T3-L1 cells with or without pioglitazone. We also studied plasma growth factor levels in patients with type 2 diabetes mellitus treated with pioglitazone. RESULTS AND METHODS: The supernatant of 3T3-L1 cells increased tube formation of HUVECs by 9.03-fold of control. Reverse transcription-polymerase chain reaction showed that hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) mRNA were expressed in 3T3-L1 cells. Western blot analysis also demonstrated HGF and VEGF protein expression. When 3T3-L1 cells were treated with 100 nM small interfering RNAs (siRNAs) for HGF, the HGF mRNA and protein were suppressed. The VEGF mRNA and protein in the cells were also suppressed by siRNA for VEGF. The supernatant of 3T3-L1 cells treated with HGF siRNA suppressed tube formation of HUVECs by 61% compared with the supernatant of cells treated with control siRNA. Addition of VEGF siRNA resulted in no significant changes. The supernatant conditioned with pioglitazone further promoted the tube formation. Pioglitazone enhanced HGF mRNA expression in 3T3-L1 cells. After 12 weeks of pioglitazone treatment, the changes of plasma HGF levels in patients treated with pioglitazone were significantly higher than those in control. CONCLUSION: These results suggest that HGF secreted from 3T3-L1 cells may be the major factor regulating the tube formation, and agents that enhance the differentiation of adipocytes may promote tube formation of HUVECs mediated by HGF secreted by adipocytes.

3T3 Cells↗

PubMed2005

Penetrance of adrenocortical tumours associated with the germline TP53 R337H mutation.

BACKGROUND: An inherited germline P53 mutation has been identified in cases of childhood adrenocortical carcinoma (ACT), a neoplasm with a high incidence in southern Brazil. The penetrance of ACT in carriers of the point mutation, which encodes an arginine-to-histidine substitution at codon 337 of TP53 (R337H), has not been determined. OBJECTIVE: To investigate the penetrance of childhood ACT in carriers of the R337H TP53 mutation. METHODS: The family histories of 30 kindreds of 41 southern Brazilian children with ACT were obtained. A PCR based assay was used to detect this P53 mutation in a large number of relatives of children with ACT. In all, 927 individuals were tested for the mutation, 232 from the non-carrier and 695 (including the 40 probands) from the carrier parental lines. RESULTS: 40 children with ACT carried the TP53 R337H mutation; the remaining child with ACT was not tested. There was no evidence of Li-Fraumeni syndrome in any of the kindreds; however, seven met the criteria for Li-Fraumeni-like syndrome. The carrier parental line was identified in each kindred. Of the 695 individuals tested in the carrier parental line, 240 (34.5%) were positive for the mutation, while none of the 232 individuals in the other parental line carried the mutation. The penetrance of ACT was 9.9% (95% confidence interval, 8.7% to 11.1%). CONCLUSIONS: The TP53 R337H mutation dramatically increases predisposition to childhood ACT but not to other cancers, and explains the increased frequency of ACT observed in this geographic region.

Adrenal Cortex Neoplasms↗

PubMed2005

Factors in maintaining long-term improvements in health-related quality of life after pulmonary rehabilitation for COPD.

The purpose of this study was to reveal predictors for the long-term effects of pulmonary rehabilitation for chronic obstructive pulmonary disease (COPD) patients, in terms of health-related quality of life (HRQoL). We investigated the long-term effects of pulmonary rehabilitation in 53 COPD patients who had completed the outpatient program and could be evaluated continuously for 1 year. We also investigated factors related to long-term maintenance of HRQoL assessed by the St George's Respiratory Questionnaire (SGRQ). In the year following the program, the only items that retained a significant improvement compared with the pre-program levels were respiratory muscle strength and 6-min walking distance. Patients whose total SGRQ score showed improvements that were maintained above the minimal clinically important difference were placed in a maintained-improvements group (n = 18, 34.0%), and the others in a non-maintained group (n = 35, 66.0%). A comparison of the groups revealed that the maintained-improvements group had significantly lower forced vital capacity (FVC), inspiratory capacity (IC), and tidal volume (TV) at rest; higher PaCO(2); greater initial impairments in HRQoL; and more frequent attendance in a maintenance program. In a multiple logistic regression model, only PaCO(2) was identified as predictor for the maintenance of improvement in HRQoL over a long term. In conclusion, higher baseline PaCO(2) is predictor of maintained, long-term improvement in HRQoL after pulmonary rehabilitation. Frequent attendance in a maintenance program is another predictor.

Aged↗

PubMed2005

Health-related quality of life in patients with idiopathic pulmonary fibrosis. What is the main contributing factor?

The prognosis of patients with idiopathic pulmonary fibrosis (IPF) is generally considered to be poor. As the disease progresses, patients invariably become severely limited in their activities. Therefore, evaluating the health-related quality of life (HRQoL) in IPF patients is considered to be important. However, there have been few studies of this kind to date. We applied the St. George's Respiratory Questionnaire (SGRQ) to 41 consecutive IPF patients and examined various physiological variables to identify factors that were correlated with the HRQoL. Total lung capacity, transfer factor, arterial partial pressure of oxygen at rest, the lowest oxygen saturation during exercise test, and the baseline dyspnoea index (BDI) score were significantly correlated with the total SGRQ score. A similar tendency was observed in each component. Conversely, peak oxygen uptake, known as one of the important factors that determines HRQoL in chronic obstructive pulmonary disease (COPD), did not correlate with any SGRQ scores. In stepwise multiple regression analysis, the BDI score was selected as the only factor significantly contributing to the total SGRQ score. Dyspnoea was the most important factor determining HRQoL in IPF. The types of other variables that correlated with the HRQoL in IPF patients were different from those in COPD.

Carbon Dioxide↗

PubMed2004

Case report: internal and external jugular vein thrombosis with marked accumulation of FDG.

We report an unusual case of idiopathic internal and external jugular vein thrombosis. Positron emission tomography (PET) using (18)F-fluoro-2-deoxy-D-glucose (FDG), which was conducted to assess subclinical malignancy, revealed intense uptake of FDG, corresponding to thrombus within the left internal and external jugular veins. Although FDG-PET is widely used in differentiating between malignant and benign diseases, we should bear in mind that this benign entity can demonstrate high accumulation of FDG.

Fluorodeoxyglucose F18↗

PubMed2004

[A rational approach of limited resection for small peripheral lung adenocarcinoma with curative intent; analyses of multiple primary adenocarcinomas].

Hundred and forty-one small peripheral adenocarcinomas 2 cm or less in diameter were retrospectively studied to determine the rationale of limited resection with curative intent. We used a conventional computed tomography (CT) which used 2.5 mm thick sections to examine only the main tumor during from March 1985 to May 1999 and a spiral CT which produced 2.5 mm thick sections of the entire lung field during from June 1999 to July 2003. The incidence of small peripheral adenocarcinoma significantly increased from 12.6% to 29.1%, suggesting an increase in the rate of detection with spiral CTs. During the spiral CT era, the percentage of females, pathological stage I a tumors, predominant ground-glass opacity (GGO) tumors and limited resection were significantly higher. The incidence of multiple adenocarcinomas 2 cm or less in diameter significantly increased 2.6% to 14.1%. It increases to 21.9% in small adenocarcinomas and 63.6% in predominant GGO type, when minute GGO lesion which have been followed in 5 patients by a watch and wait policy would be bronchioloalveolar carcinoma (BAC). In conclusion, a paradigm shift of the treatment for small peripheral adenocarcinoma should be warrant, because localized BAC as noninvasive cancer is not rare and often found as multiple BACs.

Adenocarcinoma↗

PubMed2003

Radiofrequency ablation is useful for selected cases of pelvic recurrence of rectal carcinoma.

BACKGROUND: We evaluated radiofrequency ablation (RFA) as a new local treatment for pelvic recurrence of rectal carcinoma. METHODS: Fourteen lesions in 10 patients were treated by RFA. Four patients with a solitary recurrent tumor were treated curatively, while 10 lesions in the remaining 6 patients with distant metastases were treated palliatively mainly to control pain. RFA was performed under CT guidance and epidural anesthesia. It was carried out by a single insertion for tumors 3 cm or less in diameter or by multiple insertions for tumors greater than 3 cm. Ablation effectiveness was evaluated by magnetic resonance imaging. For palliative cases, severity of pain was assessed using a visual analogue scale. RESULTS: Needle placement and ablation were accomplished in all 14 lesions. Complications following RFA consisted of 2 cases of abscess formation, 2 cases of neuralgia and one case of bleeding. To obtain complete necrosis, the tumor should be under 4 cm in diameter and not involve any major iliac vessels. Three of 4 patients treated curatively met these conditions. Among these 4 patients, only one recurrence was observed after RFA (follow-up, 6-36 months). Five of 6 patients treated palliatively had tumours greater than 4 cm in diameter or involving iliac vessels. In none of the patients did we achieve complete necrosis and satisfactory analgesia. CONCLUSION: Although certain conditions must be met, RFA is a feasible and effective treatment, and it should be considered as one of the treatment options for pelvic recurrence of rectal carcinoma.

Carcinoma↗

PubMed2002

Mucosal immunoadjuvant activity of the low toxic recombinant Escherichia coli heat-labile enterotoxin produced by Bacillus brevis for the bacterial subunit or component vaccine in pigs and cattle.

A gene encoding the mature Escherichia coli heat-labile enterotoxin (LT) lacking the nick site in the A subunit by deleting tripeptides was introduced in a vector pNH301 and expressed extracellularly as mutant molecule of holotoxin at high levels in Bacilus brevis HPD31-S5 of the host bacterium. The mucosal adjuvant activities of the produced mutant LT (mLT) preparation were studied in pigs and cattle. Intranasal immunization of pigs with the recombinant subunit vaccine of Erysipelothrix rhusiopathiae or the component vaccine of Bordetella bronchiseptica mixed with the mLT resulted in a substantial enhancement of both mucosal and serum-specific antibody levels. The immunized pigs were also protected when challenge-exposed intradermally with a highly virulent E. rhusiopathiae strain or challenge-exposed intranasally with a highly virulent strain of B. bronchiseptica. The mLT intranasally administered with recombinant intimin (an outer membrane adhesin) of E. coli O157:H7 also induced an elevation of IgA-specific antibody in the nasal secretion and saliva of calves as well as an elevation of IgG1-specific antibody level against the intimin in the sera and colostrum of cows. The three kinds tested protein antigens were poorly immunogenic when antigen administered intranasally alone. The mLT intranasally administered at a higher effective dose did not induce local adverse reactions or diarrhea in pigs and cattle. The present study demonstrates that the recombinant mLT produced using the B. brevis expression system might represent promising immunoadjuvants for the potential application of intranasal vaccines directed against infectious diseases in pigs and cattle.

Adjuvants, Immunologic↗

PubMed2002

Synthesis and antiherpesvirus activities of 5-alkyl-2-thiopyrimidine nucleoside analogues.

Twenty 5-alkyl-2-thiopyrimidine nucleosides were newly synthesized and examined for antiviral activities against herpes simplex virus (HSV), varicella-zoster virus (VZV) and human cytomegalovirus (HCMV). In this study, 2'-deoxy-5-alkyl-2-thiocytidine analogues had lower 50% effective concentration (EC50) values against HSV-1, and 2'-deoxy-5-alkyl-2-thiouridine analogues showed lower EC50 against VZV than their congeners of arabinoside form. Among the compounds examined, 2'-deoxy-5-ethyl and 5-propyl-2-thiocytidine (TN-53 and TN-54) were most potent and selective anti-HSV compounds. Their EC50s were 0.04 and 0.15 microM, and selectivity indexes were more than 7,215 and 1,849, respectively. On the other hand, 2'-deoxy-5-propyl-2-thiouridine (TN-51), 5-bromovinyl-2-thiouracil arabinoside (TN-65) and 5-styryl-2-thiouracil arabinoside (TN-67) were most potent and selective anti-VZV compounds. Their EC50s were 3.1, 3.8 and 2.6 pM for CaQu strain of VZV, respectively, and 2.1 to 3.0 times lower than that of acyclovir. All 2-thiopyrimidine nucleoside analogues did not show antiviral activities against thymidine kinase (TK) negative strains of HSV-1 and VZV. Only three 2-thiocytosine arabinoside compounds showed marginal anti-CMV activities (EC50s were 57-159 pM). All of the five alkyl-2-thio-pyrimidine nucleoside analogues examined were not cytotoxic to human lymphoblastoid cells (RPM18226) and human embryonic fibroblast cells (MRC-5) at 240 microM (100 microg/ml) or more. Regarding the structure-activity relationship of 5-alkyl-2-thiopyrimidine nucleoside analogues, the following remarks will be noted. Elongation of 5-alkyl chain (methyl to ethyl) of 2-thiocytosine in both deoxyribosyl and arabinosyl nucleosides increased anti-HSV-1 activity but not anti-VZV activity. Furthermore, elongation of the same chain (ethyl to propyl) of 2-thiodeoxyuridine increased anti-VZV activity whereas it did not in the case of 2-thiouracil arabinosides.

Antiviral Agents↗

PubMed2002

[Analyses of multiple primary lung cancers; recent trend].

We studied multiple primary lung cancers (MPLCs) in 921 patients who had undergone operation for primary lung cancer since March 1979 in Mie University Hospital. There were 14 synchronous and 5 metachronous MPLCs. Combination of synchronous MPLCs were adenocarcinoma (ADC)/ADC in 7, squamous cell carcinoma (SCC)/SCC in 3, and ADC/adenosquamous cell carcinoma, ADC/small cell carcinoma, ADC/large cell carcinoma and multiple AAH in one. The incidence of synchronous MPLCs was 0.7% (6/815 pts) before May 1999 and 7.5% (8/106 pts) after June 1999 when HRCT was introduced for preoperative evaluation and postoperative follow-up. Six cases with multiple bronchioloalveolar carcinomas (BACs) have undergone operation for last 5 years. Most of them were roentgenographically occult and the operative outcome was good in spite of limited resection. In summary, we need new strategy of diagnosis and operative procedure for peripheral small adenocarcinoma, because multiple MPLCs of BAC are not rare.

Adenocarcinoma↗

PubMed2001

Cobalamin deficiency results in severe metabolic disorder of serine and threonine in rats.

Dietary cobalamin (vitamin B12; Cbl) deficiency caused significant increases in plasma serine, threonine, glycine, alanine, tyrosine, lysine and histidine levels in rats. In particular, the serine and threonine levels were over five and eight times, respectively, higher in the Cbl-deficient rats than those in the sufficient controls. In addition, some amino acids, including serine and threonine, were excreted into urine at significantly higher levels in the deficient rats. When Cbl was supplemented into the deficient rats for 2 weeks, in coincidence with the disappearance of the urinary excretion of methylmalonic acid (an index of Cbl deficiency), the plasma serine and threonine levels were normalized. These results indicate that Cbl deficiency results in metabolic disorder of certain amino acids, including serine and threonine. The expression level of hepatic serine dehydratase (SDH), which catalyzes the conversion of serine and threonine to pyruvate and 2-oxobutyrate, respectively, was significantly lowered by Cbl deficiency, even though Cbl does not participate directly in the enzyme reaction. The SDH activity in the deficient rats was less than 20% of that in the sufficient controls, and was normalized 2 weeks after the Cbl supplementation. It is thus suggested that the decrease of the SDH expression relates closely with the abnormalities in the plasma and urinary levels of serine and threonine in the Cbl-deficient rats.

Animals↗

PubMed2001

Hypothermia reduces glutamate efflux in perilymph following transient cochlear ischemia.

The effect of hypothermia on ischemic injury of the cochlea in gerbils was studied with particular regard to glutamate efflux in the perilymph. Under normothermic conditions interruption of the blood supply to the cochlea for 15 min caused a remarkable elevation of the compound action potential (CAP) threshold, and an increase in perilymphatic glutamate. The CAP threshold recovered to some extent with reperfusion, but not to preischemic levels. CAP thresholds, under hypothermic conditions and with reperfusion, recovered promptly to near pre-ischemic levels, while glutamate concentration did not change. These results, together with electron microscopy studies, suggest that hypothermia prevents hearing loss primarily through reduction of glutamate efflux at the synopses between inner hair cells and primary afferent auditory neurons.

Animals↗

PubMed2001

Alternative splicing of novel exons of rat heart-type fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase gene.

Three C-terminal sequences (VSIPVV, VCKWT, and LTLLS) of rat heart-type fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase have been reported. To elucidate the mechanism of generating the heterogeneity of the enzyme, we carried out reverse transcriptase PCR using three pairs of specific primers. The existence of mRNAs encoding VSIPVV and LTLLS was confirmed but not that of VCKWT. In addition to these cDNAs, we found four novel mRNAs that encode the C-termini of the enzyme. The genomic sequence reveals that the heterogeneity is generated by alternative splicing of exon 15 and four novel exons (exon 16a-d).

Alternative Splicing↗

PubMed2001

Experience with radiofrequency ablation in the treatment of pelvic recurrence in rectal cancer: report of two cases.

PURPOSE: The aim of this study was to assess the efficacy of radiofrequency ablation in the treatment of pelvic recurrent rectal cancer. METHODS: Computed tomography-guided percutaneous radiofrequency ablation was performed by placing a LeVeen needle electrode into the tumor. Radiofrequency ablation was performed on three lesions in two patients with pelvic recurrent rectal cancer, where the tumors were unresectable and associated with poorly controllable pain despite local treatment consisting of chemoradiotherapy. RESULTS: There were no major complications during the radiofrequency ablation procedure, although one patient complained of a sensation of warmth in the pelvic region, which was reasonably tolerated. Case 1: Each of two lesions of pelvic recurrence, 3 or 4 cm in diameter, was treated once by radiofrequency ablation with placement of a needle electrode into the tumor mass. After the procedure, magnetic resonance imaging confirmed nearly complete necrosis of the tumors, and there was a sufficient relief of pain enabling discontinuation of an opioid. Serum carcinoembryonic antigen returned to normal and there was no evidence of relapse six months after the treatment. Case 2: Radiofrequency ablation was performed by placing a needle electrode at two sites of a recurrent tumor 6 cm in diameter. Postradiofrequency ablation imaging showed viable tissue remnants along the tumor margin, but the treatment produced relief of pain. The procedure was effective in opioid dosage reduction and pain control within a limited time span. CONCLUSION: Radiofrequency ablation is a relatively readily maneuverable and safe local treatment for pelvic recurrence in rectal cancer and is considered a procedure worth applying with further accumulation of experience in clinical cases.

Catheter Ablation↗

PubMed2001

Thiazolidinedione derivative improves fat distribution and multiple risk factors in subjects with visceral fat accumulation--double-blind placebo-controlled trial.

BACKGROUND: It has been clarified that visceral fat accumulation leads to atherosclerosis through multiple risk factors such as insulin resistance, glucose intolerance, hyperlipidemia and hypertension. So far, it has been reported that a thaizolidinedione derivative, troglitazone, improves the insulin resistance in subjects with diabetes, glucose intolerance and obesity. However, it has not been reported yet that troglitazone affects fat distribution in subjects concomitant with visceral fat accumulation and multiple risk factors. METHODS: Twenty-nine subjects with visceral fat accumulation who had at least two risk factors including glucose intolerance, hyperlipidemia and hypertension were investigated. They were randomly assigned to receive either 200 or 400 mg per day of troglitazone or placebo for 12 weeks. A 75 g oral glucose tolerance test (OGTT) was performed before and after the treatment for 12 weeks. Fasting plasma glucose, insulin, HbA(1c), total serum cholesterol (T-chol), triglyceride (TG), HDL-cholesterol (HDL-C), and blood pressure, as well as the number of risk factors were measured periodically during the treatment. The change of the abdominal fat distribution was evaluated using computed tomographic scanning (CT scan) at the umbilicus level. RESULTS: After the treatment for 12 weeks, the area under the curve (AUC) of plasma glucose from a 75 g OGTT decreased dose-dependently. HbA(1c) and TG decreased significantly in the high-dose troglitazone group (400 mg per day) compared with the placebo group (P<0.05). Systolic blood pressure was significantly lower in subjects with hypertension in the pooled troglitazone group than in the placebo group (P<0.05). Therefore, the number of risk factors decreased with the troglitazone treatment. The ratio of visceral fat area (VFA) to subcutaneous fat area (SFA) (V/S ratio) decreased in the troglitazone groups due to decreased VFA and increased SFA. CONCLUSION: These results suggest that thiazolidinedione derivative may be a useful drug to improve multiple risk factors by changing the fat distribution in subjects with visceral fat accumulation.

Adipose Tissue↗

PubMed2001

Hypothermia prevents hearing loss and progressive hair cell loss after transient cochlear ischemia in gerbils.

The effects of hypothermia on ischemia-reperfusion injury of the cochlea were studied in gerbils. Hearing was assessed by sequentially recording compound action potentials before, during and after the ischemia. The degree of hair cell loss in the organ of Corti was evaluated in specimens stained with rhodamine-phalloidin and the dye Hoechst 33342. Ischemic insult was applied to the animals by occluding the bilateral vertebral arteries for 15 min under normothermic or hypothermic (rectal temperature 32 degrees C) conditions. Interruption of the blood supply to the cochlea caused a tremendous increase in the compound action potential threshold, which usually recovered to some extent with reperfusion. In the ischemia/normothermic group, the threshold did not return to the pre-ischemic level. The average increase in the threshold seven days after ischemia was 20.0 dB. Histologically, the hair cell loss increased gradually until four days after the ischemic insult. On the seventh day, the mean loss of inner and outer hair cells at the basal turn was 31.1 % and 2.4 %, respectively. In the ischemia/hypothermic group, the threshold returned to the pre-ischemic level within 30 min after reperfusion and remained stable thereafter. The mean loss of inner and outer hair cells on the seventh day was 0.1 % and 0.2 %, respectively. These results indicate that hypothermia can prevent inner ear damage, which otherwise occurs after transient ischemia of the cochlea.

Animals↗

PubMed2001

Characterization of a vitamin B12 compound from unicellular coccolithophorid alga (Pleurochrysis carterae).

A unicellular coccolithophorid alga, Pleurochrysis carterae, contained 125.4 +/- 1.2 microg of vitamin B12 per 100 g dry cell weight of the lyophilized algal cells. A vitamin B12 compound was purified from the lyophilized algal cells and partially characterized. The silica gel 60 TLC and reversed-phase HPLC patterns of the purified pink-colored compound were identical to those of authentic vitamin B12, but not those of vitamin B12 analogues inactive for humans. When 22-week-old B12-deficient rats which excreted substantial amounts of methylmalonic acid (75.5 +/- 12.3 mg/day) in urine were fed the P. carterae (10 g per kg diet)-supplemented diet for 12 d, urinary methylmalonic acid excretion (as an index of vitamin B12 deficiency) of the rats became undetectable and hepatic vitamin B12 level of the rats was significantly increased.

Animals↗

PubMed2001

Inactive corrinoid-compound significantly decreases in Spirulina platensis grown in a cobalt-deficient medium.

Spirulina platensis NIES-39 was grown under open culture system in the presence or absence of CoSO(4) (12 microg/L) and/or vitamin B(12) (10 microg/L) to confirm whether CoSO(4) and/or vitamin B(12) stimulate or are essential for growth of the algal cells and for accumulation of vitamin B(12). The addition of CoSO(4) and/or vitamin B(12) could not affect both cell growth and cell yield of the alga. The amount of corrinoid-compound was increased significantly by the addition of CoSO(4) but not by vitamin B(12). A C18 reversed-phase HPLC pattern of the Spirulina corrinoid-compound increased by the addition of CoSO(4) was identical to that of authentic pseudovitamin B(12), which is inactive for human. These results indicate that the algal cells grown in the absence of CoSO(4) are suitable for use of human health foods because the inactive corrinoid-compound can be reduced significantly.

Chromatography, High Pressure Liquid↗