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Biomedical subjects

Y Muto

Publications and source records attributed to Y Muto.

At least 37 records · Page 2Linked to original sources

A proposed mechanism for the potentiation of cAMP-mediated acid secretion by carbachol.

Acid secretion in isolated rabbit gastric glands was monitored by the accumulation of [(14)C]aminopyrine. Stimulation of the glands with carbachol synergistically augmented the response to dibutyryl cAMP. The augmentation persisted even after carbachol was washed out and was resistant to chelated extracellular Ca(2+) and to inhibitors of either protein kinase C or calmodulin kinase II. Cytochalasin D at 10 microM preferentially blocked the secretory effect of carbachol and its synergism with cAMP, whereas it had no effect on histamine- or cAMP-stimulated acid secretion within 15 min. Cytochalasin D inhibited the carbachol-stimulated intracellular Ca(2+) concentration ([Ca(2+)](i)) increase due to release from the Ca(2+) store. Treatment of the glands with cytochalasin D redistributed type 3 inositol 1,4,5-trisphosphate receptor (the major subtype in the parietal cell) from the fraction containing membranes of large size to the microsomal fraction, suggesting a dissociation of the store from the plasma membrane. These findings suggest that intracellular Ca(2+) release by cholinergic stimulation is critical for determining synergism with cAMP in parietal cell activation and that functional coupling between the Ca(2+) store and the receptor is maintained by actin microfilaments.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Systemic fusariosis after a preparative regimen including thiotepa, VP-16 and busulfan used for blood stem cell transplantation in Hodgkin's disease.

Fusarium infection is rare but important infection after bone marrow transplantation (BMT). A 27-year-old man developed systemic fusarial infection following severe skin damage probably caused by high-dose thiotepa administration. Systemic fusariosis rapidly progressed to a variety of organs despite antifungal treatment, and he finally died of this infection on day 75. Considering that this organism usually invades via damaged skin and that the penile lesion was the first manifestation of systemic fusariosis in this patient, careful examination of the skin might be helpful for early diagnosis of fusarial infection. His clinical course provided us with an important clue for diagnosis of fusarial infection.

Adult↗

Pneumocystis carinii pneumonia with an atypical granulomatous response in a patient with chronic lymphocytic leukemia.

We have recently seen a patient who developed Pneumocystis carinii pneumonia (PCP) in the course of treatment for chronic lymphocytic leukemia (CLL). This case showed uncommon pathological findings with extensive formation of granulomatous lesions. Despite advanced CLL associated with poor B-cell function, she responded well to anti-PCP treatment. In contrast to B-cell function, the T-cell functions were well preserved in vitro, and the numbers of peripheral CD4- and CD8-positive cells were normal, and T-cell functions were normal. These findings suggest that the production of granulomatous lesions to PCP may have been associated with the patients' immune status, and that it may constitute a good indicator in PCP infection in patients with underlying hematological malignancy.

Bronchoalveolar Lavage↗

Successful bone marrow transplantation for adult T-cell leukemia from a donor with oligoclonal proliferation of T-cells infected with human T-cell lymphotropic virus.

We describe a patient who underwent successful BMT from her sibling for the treatment of adult T-cell leukemia/lymphoma. Pre-transplant examination of the donor revealed oligoclonal integration of HTLV-I proviruses within the germ line, and our concern was that clinical sequelae of HLTV-I infection might become evident in the setting of post-transplant immunosuppression. However, the patient has been in complete remission for 14 months after transplantation, and no clonality of HTLV-I provirus was detected in the peripheral blood cells using southern blotting analysis. Our experience supports the possibility of transplantation from HTLV-I positive donors.

Bone Marrow Transplantation↗

Long-term results of hepaticojejunostomy for hepatolithiasis.

The results of a hepaticojejunostomy as a biliary-enteric bypass for benign disease are usually excellent. On the other hand, hepatolithiasis features a high rate of residual and recurrent stones with cholangitis after surgery. This study aims to evaluate the long-term results of a hepaticojejunostomy for hepatolithiasis regarding both the degree of the occurrence of postoperative cholangitis and the outcome. The clinical records of 159 patients with hepatolithiasis who underwent surgical treatment over a 23-year period were also retrospectively reviewed. Ninety-four of 159 patients underwent a hepatecetomy and 65 patients were subjected to liver-preserving surgery by means of intra- and postoperative endoscopic lithotripsy. In addition 72 patients underwent a hepaticojejunostomy. The rate of residual or recurrent stones was 31.4 per cent after complete stone removal. Twenty-two (30.6%) of the 72 patients developed some kind of cholangitis. This rate was significantly higher than that (three of 87 patients) of the non-biliary-enteric anastomosis group regarding the occurrence of biliary complications. We conclude that the use of a hepaticojejunostomy for patients with possible residual stones or intrahepatic bile duct lesions remains controversial.

Adolescent↗

High levels of serum interleukin-10 and tumor necrosis factor-alpha are associated with fatality in fulminant hepatitis.

Serum pro- and anti-inflammatory mediators in patients with acute liver diseases were assessed to clarify the clinical significance of these measurements in relation to disease severity. Concentrations of circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, IL-12, and soluble TNF receptors (sTNFR) p55 and p75 were measured at admission in patients with fulminant hepatitis (FH; n=19), severe acute hepatitis (AHS, n=15), or acute hepatitis (AH, n=7). Serum concentrations of TNF-alpha, IL-10, and sTNFR-55 were significantly higher in patients with FH than in those with AHS (P<.05, <.05, and <.01, respectively) or AH (P<.05). Serum IL-10 and TNF-alpha levels were higher in patients who died of FH (n=13) than in FH survivors (n=6; P<.05). The ratios between TNF-alpha and IL-10 and sTNFR-55 or sTNFR-75 were not valuable in predicting mortality and disease severity. However, both proinflammatory cytokine TNF-alpha and anti-inflammatory cytokine IL-10 levels at admission were associated with fatal outcome among patients with FH.

Adult↗

NMR studies on functional structures of the AU-rich element-binding domains of Hu antigen C.

Hu antigen C (HuC) has three RNA-binding domains (RBDs). The N-terminal two, RBD1 and RBD2, are linked in tandem and bind to the AU-rich elements (AREs) in the 3'-untranslated region of particular mRNAs. The solution structures of HuC RBD1 and RBD2 were determined by NMR methods. The HuC RBD1 and RBD2 structures are quite similar to those of Sxl RBD1 and RBD2, respectively. The individual RBDs of HuC, RBD1 and RBD2 in isolation can interact rather weakly with the minimal ARE motif, AUUUA, while the didomain fragment, RBD1-RBD2, of HuC binds more tightly to a longer ARE RNA, UAUUUAUUUU. Chemical shift perturbations by the longer RNA on HuC RBD1-RBD2 were mapped on and around the two beta-sheets and on the C-terminal region of RBD1. The HuC RBD1-RBD2 residues that exhibited significant chemical shift perturbations coincide with those conserved in Sxl RBD1-RBD2. These data indicate that the RNA-binding characteristics of the HuC and Sxl didomain fragments are similar, even though the target RNAs and the biological functions of the proteins are different.

Adenosine↗

RNA-binding proteins: TRAPping RNA bases.

In Bacillus subtilis, tryptophan biosynthesis is regulated by a mechanism called attenuation. The new crystal structure of the 'trp RNA binding attenuation protein', TRAP, in complex with RNA has provided new structural insights into how proteins can bind RNA to regulate transcription and translation.

Bacillus subtilis↗

Adjuvant-induced improvement of glucose intolerance in type 2 diabetic KK-Ay mice through interleukin-1 and tumor necrosis factor-alpha.

We reported that administration of complete Freund's adjuvant (CFA) improved glucose tolerance test (GTT) results in obese diabetic KK-Ay mice. In this study, we investigated its mechanism. An injection with CFA remarkably improved GTT for more than a week in KK-Ay mice, although insulin response was not changed compared with saline controls. The hypoglycemic effect of insulin was significantly, but partially, potentiated in the CFA-treated mice compared with the controls, suggesting that CFA stimulated insulin-mediated and non-insulin-mediated glucose disposal. Improvement in the GTT with CFA was partially transferable to nontreated mice by peritoneal exudative cells, but not spleen or lymph node cells. Pretreatment with anti-interleukin (IL)-1 alpha and -1 beta antibodies or anti-tumor necrosis factor (TNF)-alpha antibody significantly abrogated the improvement in the GTT with CFA. The results indicate that CFA-induced improvement in glucose intolerance in KK-Ay mice was mediated at least by IL-1 and TNF-alpha.

Animals↗

Successful resection for advanced hepatoblastoma, combined with perioperative chemotherapy.

The aim of this study was to evaluate our results of surgical treatment with intensive perioperative chemotherapy for hepatoblastoma in infants and children. Seven patients (mean age, 30 months; range 1 month to 6 years) with hepatoblastoma who were followed-up for more than 3 years were reviewed. All patients underwent hepatectomy, performed using a microwave tissue coagulator, after they had received neoadjuvant chemotherapy comprising up to four cycles of cisplatinum and doxorubicin. The main outcome criteria were the clinical response rates to neoadjuvant chemotherapy and the overall survival. Neoadjuvant chemotherapy markedly reduced the tumor volume on computed tomography (mean regression rate, 73%). Alpha-fetoprotein (AFP) levels also decreased, from a mean value of 138 x 104 to 990 ng/ml (excluding values for one patient with tumor thrombus in the portal vein). The surgical procedures included extended right lobectomy in one patient, extended left lobectomy in two patients, hepatic left trisegmentectomy in one patient, and hepatic subsegmentectomy in three patients. The postoperative clinical courses in all seven patients were good, and no serious complications were observed. No relationship was observed between the DNA ploidy pattern and the histopathological findings of the resected specimens regarding survival. Six patients (excluding the patient with a tumor thrombus in the portal vein) who underwent complete resections survived without any signs of recurrence during a follow-up period ranging from 47 to 150 months. In conclusion, the perioperative chemotherapy greatly improved both the resection rate and overall survival in patients with hepatoblastoma. DNA ploidy pattern analysis may be useful when predicting the prognosis of patients with hepatoblastoma. The use of the microwave coagulator was safe for performing hepatectomy, even in infants.

Antineoplastic Combined Chemotherapy Protocols↗

Peptic ulcer recurrence during maintenance therapy with H2-receptor antagonist following first-line therapy with proton pump inhibitor.

We investigated the peptic ulcer recurrence rates during maintenance therapy with H2-receptor antagonists (H2RAs) following first-line therapy with a proton pump inhibitor (PPI). Patients with gastric ulcer (GU) or duodenal ulcer (DU) were enrolled in this study; 583 eligible patients (GU, 325; DU, 258) were administered lansoprazole (30 mg/day for 8 weeks for GU, and the same dosage for 6 weeks for DU) as first-line therapy, and a half dose of H2RA as maintenance therapy for 12 months. Endoscopic photographs were taken before administration and after 8 (GU) and 6 (DU) weeks of lansoprazole administration. Ulcer stage was evaluated using the classification of Sakita and Miwa. Endoscopic examinations were performed 6 months or 12 months after the start of maintenance therapy or when a recurrence was suspected because of the appearance of subjective symptoms. The healing rates for GU and DU patients after completion of lansoprazole therapy were 79% in both groups, while the S2-stage healing rates were 18% and 31%, respectively. At 1 year after the start of maintenance therapy, the recurrence rates were 25% for GU and 39% for DU patients. In DU patients, the recurrence rates from S1-stage and S2-stage were 49% and 20%, respectively (P = 0.004), but no significant difference was found between these rates in GU patients. The recurrence rates in H. pylori-positive patients before lansoprazole administration were 27% for GU and 43% for DU patients. We concluded that the maintenance therapy with a half-dose of H2RA following PPI therapy was insufficient to prevent recurrences of GU and DU.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Granular cell tumor of the rectum: a case report and review of the literature.

A 47-year-old Japanese woman with a 5-year history of alcoholism was admitted to the Ryukyu University Hospital for the treatment of the alcoholism. For evaluation of observed changes in her bowel habits, she underwent colonoscopy, which revealed seven small polyps spread throughout the entire large intestine. Six of the polyps were in the colon; one was an adenoma and five were hyperplastic polyps. The remaining polyp, in the rectum, was an 8-mm submucosal tumor. Pathological analysis of a biopsy of the lesion in the rectum indicated a possible diagnosis of adenocarcinoma. Endoscopic ultrasonography (EUS) demonstrated a submucosal hypoechoic nodule, involving the mucosa and the muscularis propria. Subsequently, the patient underwent a radical low anterior resection of rectum. The lesion was a submucosal tumor with ulceration. The tumor consisted of granular tumor cells which were positive for S-100 protein, neuron-specific enolase, and periodic acid schiff (PAS) stain, but negative for desmin and vimentin. Granular cell tumor is rare in the gastrointestinal tract. As a result, such tumors can be misinterpreted to indicate a possible malignancy on either a biopsy or EUS.

Biomarkers↗

Limitations of exogenous L-arginine in exerting a cytoprotective effect on hepatic ischemia/reperfusion injury.

To test whether or not the L-arginine/nitric oxide (NO) pathway induces a protective effect, we investigated the effect of exogenous L-arginine on hepatic ischemia/reperfusion (I/R) injury, using ex vivo perfusion of the isolated rat liver. The rat liver was removed and preserved in cold saline for 60 min, followed by 120 min of reperfusion with oxygenated perfusate at 37 degrees C. Either 600 mg/kg of L-arginine (groups 1 and 4), D-arginine (group 2), N(G)-nitro-L-arginine methyl ester (L-NAME) (group 3), or saline (group 5) were administered through the portal vein starting from 5 min before reperfusion to 5 min after reperfusion. In group 4, 600 mg/kg of L-NAME was preadministered at 10 min prior to the administration of L-arginine. The intrahepatic nitric oxide (NO) levels showed only a temporal elevation (227% +/- 70% of the pre-reperfusion levels at 5 min) after reperfusion in group 1. Pretreatment with L-NAME suppressed the elevation of the NO levels immediately after reperfusion in group 4. The lactate dehydrogenase release to the effluent perfusate significantly decreased and the histological findings showed that the sinusoidal damage observed after reperfusion was mitigated in group 1 more than in the other groups. These results thus suggest that exogenous L-arginine produced a relatively small amount of NO and therefore resulted in a slight decrease of hepatic I/R injury.

Animals↗