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Biomedical subjects

M Gotoh

Publications and source records attributed to M Gotoh.

At least 73 records · Page 4Linked to original sources

Clinical significance of hepatic resection in hepatocellular carcinoma: analysis by disease-free survival curves.

HYPOTHESIS: The clinical significance of hepatectomy for hepatocellular carcinoma (HCC) is still controversial because of frequent intrahepatic recurrence, which results from either recurrence due to residual intrahepatic metastasis (Rim) or recurrence due to metachronous, multicentric liver carcinogenesis (Rmc). DESIGN: Retrospective review. Disease-free survival curves were obtained by the Kaplan-Meier method and the rates of Rim and Rmc were analyzed using 2 regression lines, based on the evidence that Rmc occurs at a constant rate throughout follow-up, whereas Rim occurs only in the early postoperative period. SETTING: University hospital. PATIENTS: From 1980 to 1996, 241 patients with HCC who underwent curative hepatic resection. MAIN OUTCOME MEASURE: Intrahepatic recurrence. RESULTS: Disease-free survival curves for all patients in the early (within 2 years) and late (4 years after surgery) follow-up were approximated by 2 regression lines, which represent both Rim and Rmc (Y(1) = -3.4X + 48) and only Rmc (Y(2) = -23.1X + 98). Using this approximation, the annual incidence of Rim within 2 years (a(1)-a(2)) was calculated as 19.7% and that of Rmc (a(2)) was 3.4%. The ratio of Rim in tumor recurrence (b(1)-b(2)) was 50%, and that of Rmc (b(1)) was 48%. The ratios of Rmc in patients with stages I and II HCC were 60% and 64%, respectively. In contrast, the values could not be calculated in patients with stages III and IVA because all but 2 patients showed recurrence within 4 years after surgery. CONCLUSION: Tumor recurrence is estimated to result from metachronous liver carcinogenesis in 48% of hepatectomized patients with HCC.

Carcinoma, Hepatocellular↗

Quality of micturition in male patients with orthotopic neobladder replacement.

We evaluated the quality of micturition in patients with orthotopic neobladder replacement. In the present study, 58 patients who had undergone orthotopic neobladder replacement following cystectomy were enrolled. The quality of micturition was evaluated by means of uroflowmetry, a self-administered questionnaire and a 24-h frequency-volume chart. The questionnaire consisted of 26 questions concerning storage (9 questions), evacuation of urine (9), patient's satisfaction with neobladder (3), limitations in daily life (3) and pain (2). In addition, 11 of the questions were followed immediately by a question concerning inconvenience to the patients. The mean follow-up period was 35 months (range 6-80). On uroflowmetry, the mean peak flow rate was 13.5 ml/s with a low average flow rate (mean: 5.7 ml/s), and the voiding time was considerably prolonged (mean: 70.2 s). According to the frequency-volume chart and questionnaire responses, although the frequency and tidal volume of micturition were normal, the majority of patients were conscious of retarded, intermittent, prolonged, and weak stream and of straining during voiding. Diurnal or nocturnal incontinence was noticed subjectively in as many as 69% of the patients. However, the degree of urine leakage was minimal. In spite of the fact that 66% of the patients replied that their micturition status was worse than before surgery and that 69% of the patients felt dissatisfied, the degree of inconvenience was low in every item and the limitations in daily life were minimal. Although micturition in patients with neobladder replacement appeared to be of lower quality than that in normal subjects and was considered by many to be unsatisfactory, most patients were able to adjust themselves to it without significant inconvenience.

Adult↗

New approaches for successful islet transplantation.

The long-term control of glucose metabolism is expected to be achieved with insulin-secreting pancreatic islets transplanted as the whole pancreas or isolated islet tissue. The current clinical outcomes of such procedures are unsatisfactory compared with that of whole organ transplantation or experimental islet transplantation, although the safety of the transplantation procedure itself is assured. In this review, we first describe the immunological characteristics of purified islets in an attempt to explain the differences between the results for human and experimental islet transplantation. We then introduce new approaches currently undertaken in our laboratory that could, we hope, make islet transplantation more successful.

Adjuvants, Immunologic↗

Presence of active hepatitis associated with liver cirrhosis is a risk factor for mortality caused by posthepatectomy liver failure.

The histologic activity of associated hepatitis was examined in 285 patients who underwent hepatectomy for hepatocellular carcinoma (HCC), to determine if the histologic activity is an independent risk factor for postoperative mortality due to liver failure. The proportion of patients with liver cirrhosis who died due to liver failure (6/180, 3.3%) was not different from that of patients with chronic hepatitis (2/68, 2.9%). However, mortality was higher in patients with liver cirrhosis and active hepatitis (4/46, 8.7%) than in those with cirrhosis and inactive hepatitis (2/134, 1.5%, P < 0.05). Such difference was not observed in the chronic hepatitis group. Multivariate analysis showed that clearance of indocyanine green at 15 min (ICGR15) and activity of hepatitis were two independent risk factors for postoperative mortality due to liver failure. In conclusion, histologic activity of associated hepatitis should be taken into account in hepatic resection of HCC in cirrhotic liver, in addition to the functional reserve of the liver.

Adult↗

Advanced hepatocellular carcinoma with distant metastases, successfully treated by a combination therapy of alpha-interferon and oral tegafur/uracil.

We report a case of advanced hepatocellular carcinoma (HCC), successfully treated by a combination therapy of alpha-interferon (IFN-alpha) and tegafur/uracil (UFT). A 44-year-old Japanese man who underwent a partial hepatectomy for HCC developed tumor recurrence in the liver 10 months after surgery. Transcatheter arterial chemoembolization (TAE) was performed twice within 7 months, but was ineffective. Later, multiple metastatic lesions appeared in the liver, lung and spine. Following the third TAE, a combination therapy of IFN-alpha (10 x 10(6) units, i.m., t.i.w.) and UFT (300 mg, p.o.d.) was started. The treatment resulted in a fall in serum PIVKA-II (protein induced by vitamin K antagonism) levels from 906 mAU to normal levels and a complete resolution of all lung nodules within 6 months. At the latest follow up 24 months after the initiation of combination treatment, the patient was working full-time and showed no evidence of tumor relapse. A combination therapy of IFN-alpha and UFT may be promising for the treatment of advanced HCC.

Administration, Oral↗

A new class of neurotoxin from wasp venom slows inactivation of sodium current.

The effects of alpha-pompilidotoxin (alpha-PMTX), a new neurotoxin isolated from the venom of a solitary wasp, were studied on the neuromuscular synapses in lobster walking leg and the rat trigeminal ganglion (TG) neurons. Paired intracellular recordings from the presynaptic axon terminals and the innervating lobster leg muscles revealed that alpha-PMTX induced long bursts of action potentials in the presynaptic axon, which resulted in facilitated excitatory and inhibitory synaptic transmission. The action of alpha-PMTX was distinct from that of other known facilitatory presynaptic toxins, including sea anemone toxins and alpha-scorpion toxins, which modify the fast inactivation of Na+ current. We further characterized the action of alpha-PMTX on Na+ channels by whole-cell recordings from rat trigeminal neurons. We found that alpha-PMTX slowed the Na+ channels inactivation process without changing the peak current-voltage relationship or the activation time course of tetrodotoxin (TTX)-sensitive Na+ currents, and that alpha-PMTX had voltage-dependent effects on the rate of recovery from Na+ current inactivation and deactivating tail currents. The results suggest that alpha-PMTX slows or blocks conformational changes required for fast inactivation of the Na+ channels on the extracellular surface. The simple structure of alpha-PMTX, consisting of 13 amino acids, would be advantageous for understanding the functional architecture of Na+ channel protein.

4-Aminopyridine↗

Mucin ball-producing extrahepatic bile duct carcinoma.

The characteristic features of surgically curable mucin-producing extrahepatic bile duct carcinoma (MPEBC) have not previously been elucidated. Three (6.5%) of 46 patients who underwent surgery in our department for bile duct carcinoma between 1986 and 1997 had MPEBC. Clinicopathological features, diagnostic procedures and operative methods for patients with MPEBC were investigated. Tumors in the bile duct were identified by cholangioscopy combined with cholangiography after removal of mucin balls. Tumors were located close to the hepatic confluence in these patients. Two patients underwent hepatic lobectomy together with caudate lobectomy while the other underwent resection of the hepatic confluence. Absence of residual tumors was confirmed histologically in these patients. All three patients remain alive without evidence of recurrence, 22-54 months after surgery. MPEBC is a curable disease. Accurate localization in the biliary tree is essential and can only be obtained after, i) removal of mucin balls, and ii) extensive diagnostic work-up including cholangiography, cholangioscopy and intraoperative pathological examination.

Adenocarcinoma, Mucinous↗

Creatol, an oxidative product of creatinine in hemodialysis patients.

Creatol (CTL) is a product resulting from the reaction of creatinine (Cr) with the hydroxyl radical and is identified as a precursor of methylguanidine (MG), a uremic toxin. In this study, we investigated serum CTL levels together with those of Cr and MG in 66 patients who were on maintenance hemodialysis (HD). Prior to dialysis, the mean serum levels of Cr, CTL and MG were 967 (= 11.1 mg/dl)+/-267 microM, 11.1+/-4.8 microM and 5.8+/-2.9 microM, respectively. The mean CTL level was about 1.1% that of Cr, and the CTL plus MG level was about 1.4% that of the Cr level. The reduction rates of Cr, CTL and MG by a single HD were 62.6 6.1%, 71.0+/-10.3% and 51.9+/-11.6%, respectively. The CTL level at 0.5, 1 and 6 h after HD increased rapidly by 20.7+/-8.7%, 31.7+/-14.7% and 80.1+/-27.3%, respectively. There was a significant correlation between CTL or CTL/Cr and parathyroid hormone in patients who had just undergone parathyroidectomy. No significant correlation was found between CTL or CTL/Cr and those factors which seems to be related to the predialysis levels of reactive oxygen. Therefore, because of the good clearance of CTL and its rapid conversion to MG, its usefulness for the estimation of hydroxyl radical generation in HD patients is limited.

Adult↗

Prevalence of Japanese dialysis patients with an A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene.

BACKGROUND: A high prevalence of an A-to-G mutation at nucleotide 3243 of the mitochondrial genome in patients with diabetes mellitus (DM) and/or deafness has been reported previously. We investigated the prevalence of this mutation in Japanese dialysis patients with associated DM and/or deafness. METHODS: We studied 106 dialysis patients with DM, 26 with DM and deafness, and 26 with deafness alone, using peripheral leucocytes to detect an A-to-G transition at nucleotide 3243 of the mitochondrial gene. RESULTS: We identified this transition in 1 of 26 patients with DM and deafness. None of the 106 DM or 26 dialysis patients with deafness but no DM was positive for this mutation. A 42-year-old male patient on continuous ambulatory peritoneal dialysis (CAPD) who carried this mutation had a 20-year history of sensory hearing loss as well as hypertrophic cardiomyopathy. CONCLUSION: We found that a mitochondrial gene mutation at nucleotide 3243 was present in one dialysis patient with NIDDM and deafness. The prevalence of this mutation was found to be below 1% in diabetic end-stage renal disease patients in Japan.

Adult↗

PTEN / MMAC1 mutation and frequent loss of heterozygosity identified in chromosome 10q in a subset of hepatocellular carcinomas.

Frequent allelic losses on chromosome 10q have been reported in several types of cancers, suggesting the presence of a putative tumor suppressor gene(s) on the chromosomal arm. We examined loss of heterozygosity (LOH) on chromosome 10q in 37 hepatocellular carcinomas (HCC) using eleven dinucleotide microsatellite markers, spanning the entire chromosome arm of 10q. Twelve (32%) out of 37 informative cases showed allelic losses of at least one locus on 10q and eight tumors showed a partial deletion of 10q. Analysis of deletion mapping of these eight cases identified two commonly deleted regions within the distal part of 10q (10q24-q26), a 20-cM interval flanked by D10S597 and D10S216 and a 24-cM interval flanked by D10S216 and D10S590. Moreover, we detected a somatic missense mutation (Met --> Val) of a candidate tumor suppressor gene PTEN / MMAC1, located at 10q23.3, in one HCC with LOH of 10q. Our findings indicated the presence of putative tumor suppressor gene(s) in the distal region of 10q that might be involved in the development and progression of HCC. Inactivation of PTEN / MMAC1 gene located outside the commonly deleted region of 10q might also play an important role in a subset of HCCs.

Carcinoma, Hepatocellular↗

Hemodialysis does not influence the peroxidative state already present in uremia.

Hemodialysis (HD) patients are exposed to high oxidative stress, however, the nature of this stress is still unclear. In this study, we employed a specific lipid peroxidative product, phosphatidylcholine hydroperoxide (PCOOH), and evaluated the peroxidative effect of end stage renal disease by measuring thiobarbituric acid reactive substances (TBARS) and PCOOH in both plasma and erythrocyte membrane. We also surveyed plasma TBARS and PCOOH before and after HD sessions thereby assessing oxidative stress by a single HD procedure. The plasma TBARS level of healthy controls was 2.9 +/- 0.4 nmol/ml. Those of HD patients before and after HD session were 5.1 +/- 1.4 and 3.1 +/- 0.5 nmol/ml, respectively, and the pre-HD plasma TBARS levels were significantly higher than those of controls and after HD. The plasma PCOOH concentration of patients before HD was 119.7 +/- 58.4 pmol/ml and was significantly higher than that of controls which was 88.6 +/- 14.3 pmol/ml. After HD, the plasma PCOOH level decreased to 103.2 +/- 36.0 pmol/ml, which was still significantly higher than that of controls. In erythrocytes, the PCOOH level of patients was 259.3 +/- 105.4 nmol/g RBC and was significantly higher than that of controls with 88.6 +/- 32.0 nmol/g RBC. Analyzed with respect to the cause of renal disease, the polycystic kidney disease patients showed significantly lower plasma PCOOH levels than the others. These results suggest that there is an increase of lipid peroxidation in both plasma and erythrocytes of HD patients, though this oxidative stress was not brought about by HD.

Erythrocyte Membrane↗

Estimation of the lethal toluene concentration from the accidental death of painting workers.

To determine the potentially lethal level of thinner concentration in the air, we measured the concentration of toluene in the blood and others of three patients who suffered severe acute thinner intoxication between 4 January 1996 and 21 April 1997 in Ube city. The concentration of toluene in blood were 30.2 mg/L in died patient, and 13.7 mg/L and 17.5 mg/L in recovered patients, respectively. By extrapolation from the results of our previous toxicokinetic research on toluene poisoning in anesthetized dogs, the fatal concentration of toluene was estimated to be approximately 1800 to 2000 ppm for 1-hour exposure.

Accidents, Occupational↗

Perforation of rotator cuff increases interleukin 1beta production in the synovium of glenohumeral joint in rotator cuff diseases.

OBJECTIVE: To study the hypothesis that perforation of the rotator cuff increases the degree of inflammation in the synovium of the glenohumeral joint in rotator cuff diseases. METHODS: Thirty-five synovial specimens in the glenohumeral joint of patients with rotator cuff diseases were examined. They were obtained during surgery and divided into 2 groups on the basis of the presence or absence of rotator cuff perforation, i.e., perforating and nonperforating tears. The expression levels of inflammatory cytokine mRNA of interleukin 1beta (IL-1beta) and 2 forms (secreted type and intracellular type) of IL-1 receptor antagonist (IL-1ra) were measured by reverse transcriptase polymerase chain reaction (RT-PCR). The protein level of IL-1beta was determined by Western blot analysis. IL-1beta producing cells were also identified by in situ RT-PCR and immunohistochemistry. RESULTS: In perforating tears cytokine mRNA in the glenohumeral synovium was more significantly expressed than in nonperforating tears. Also, higher levels of IL-1beta protein were detected in perforating tears. CONCLUSION: Perforation of the rotator cuff increases IL-1beta production in the glenohumeral joint, enhancing inflammatory intensity at the site. These findings suggest the possibility that glenohumeral synovitis in rotator cuff diseases may be a factor for the development of glenohumeral arthropathy.

Adult↗

Expression of procollagen alpha 1 type III mRNA in rotator cuff tears.

The purpose of this study was to investigate the relationship among expression of procollagen alpha 1 type III mRNA, subacromial adhesion, and limited shoulder elevation in rotator cuff tears. Procollagen alpha 1 type III mRNA was analyzed in the torn supraspinatus tendons and synovial tissue of 42 patients with rotator cuff tears. As a control, four normal supraspinatus tendons of patients who had undergone shoulder surgery other than rotator cuff repair served as controls. Cells stained positively for procollagen alpha 1 type III mRNA were more abundant in the adhesive synovium of the subacromial bursa and in the torn supraspinatus tendons than in controls. Patients with complete-thickness tears who had undergone surgery less than 10 months after trauma were found to have more signal-positive cells than those later than 10 months. We conclude that the adhesive synovium of the subacromial bursa contains abundant cells stained positively for procollagen alpha 1 type III mRNA. We suggest that the production of type III collagen by these cells could contribute to the limitation of shoulder motion in patients with rotator cuff tears, and recommend release and excision of the excess adhesive synovium during rotator cuff surgery.

Adult↗