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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 649 records · Page 36Linked to original sources

Results of pulmonary resection of metastatic colorectal cancer and its application.

A resection of pulmonary metastases from colorectal cancer was performed in 27 patients. The cumulative 5-year survival after thoracotomy was 41.1%. Patients with either one or two metastases had a significantly better survival, with a 5-year survival of 54.3%, than did those with a greater degree of metastases (p < 0.01). Other factors including the disease-free interval, size of metastases, type of pulmonary resection, and stage of primary cancer had no apparent influence on post-thoracotomy survival. Furthermore, the presence of controlled hepatic metastases had no adverse effect on survival and did not seem to contraindicate pulmonary resection. The lung and primary colorectal region were the major sites of recurrence. Therefore, the primary colorectal site should be explored thoroughly and the number of metastases should be carefully considered when pulmonary resection is considered for metastatic colorectal cancer.

Adult↗

Vascular anatomy of duodenal varices: angiographic and histopathological assessments.

Duodenal varices are a rare occurrence, and the diagnosis and control of related bleeding is problematic. The vascular anatomy of duodenal varices in four patients was examined angiographically. The incidence of these varices was 0.4% in the patients with portal hypertension seen in our clinics from 1982 to 1991. The transparent specimen obtained at autopsy and treated with methyl salicylate and portographies in the remaining three patients revealed that the duodenal varix consisted of a single vessel with afferent and efferent vessels, forming a portasystemic shunt in the retroperitoneum. The varix transversed the duodenum and was present in the submucosal layer of the posterior wall. The afferent vessel was the superior or inferior pancreaticoduodenal vein originating in the portal vein trunk or superior mesenteric vein. The efferent vein drained into the inferior vena cava. In view of these observations, devascularization or percutaneous transhepatic obliteration of the varix would be our first choice of treatment for patients with duodenal varices.

Duodenum↗

[A case of obstructive sleep apnea syndrome with increased lung water during sleep].

A 22-year-old man was admitted to the department of plastic surgery in our university with diagnosis of ankylosis and microgeniea. His complaints were snoring and somnolence in the daytime, so we performed a Respigraph (Chest) that showed obstructive apnea during sleep. We diagnosed obstructive sleep apnea syndrome. So we observed pulmonary circulation and measured lung water using the double indicator dilution method (Nihon Koden, MTV-1100) during sleep. During the period of apnea, arterial oxygen pressure and mixed venous saturation decreased, reversely, mean pulmonary arterial pressure rose, lung water (ETV) and central blood volume increased. We considered that the increase of lung water during sleep apnea is caused by hemodynamic change due to hypoxia and increase of venous return. After operation, the value of blood gas assay and apnea index were improved.

Adult↗

[Double blind controlled study of ubenimex (Bestatin) against squamous cell lung cancer--a multicenter cooperative study].

To investigate effects of the combination of ubenimex, chemotherapy, and radiotherapy against unresectable advanced squamous cell carcinoma of the lung, a placebo controlled double-blind study was performed. Of 365 registered cases, there were 258 cases in the complete radiation group in which the treatment as specified in the protocol (irradiation of 40 Gy or more to the thorax subsequent to chemotherapy) was conducted; the 50% survival time was 449 days and 363 days in the ubenimex group and the placebo group, respectively. A significant (p = 0.0473) prolongation of the survival time was noted in the ubenimex group, and the response rate was 60.9% and 50.0% (p = 0.087). From these results it was confirmed that ubenimex, when used in combination with chemotherapy and radiotherapy, not only enhances the tumor-reducing effect but also prolongs the survival time.

Aged↗

[Chemotherapy with cisplatin and daily administration of UFT for unresectable non-small cell lung cancer].

A combination chemotherapy of cisplatin and UFT was administered to fourteen patients with unresectable non-small cell lung cancer. To determine the maximum safety dose of UFT combined with CDDP (80 mg/m2), patients were assigned to three groups as follows: step 1: UFT (400 mg/m2) from day 1 to day 14; step 2: from day 1 to day 21; step 3: from day 1 to day 28. Cisplatin was administered on day 8 in each group. Myelosuppression with grade 3-4 and gastrointestinal toxicity of grade 3 were observed in one and two patients, respectively. The other toxicity was mild. There was no difference in the degree of toxicity among the three groups. The response rate of twelve evaluable patients was 50%; CR 0, PR 6, NC 4 and PD 2. Thus, chemotherapy using cisplatin 80 mg/m2 with daily administration of UFT 400 mg/m2 was considered to be well tolerated and effective in the treatment of non-small cell lung cancer.

Adenocarcinoma↗

Hypotonic cisplatin treatment for carcinomatous pleuritis found at thoracotomy in patients with lung cancer. In vitro experiments and preliminary clinical results.

We have developed an intraoperative intrapleural treatment with the use of distilled water combined with cisplatin for carcinomatous pleuritis found at thoracotomy in patients with non-small-cell lung cancer. In the in vitro experiment, three different cell lines were used as a model of malignant pleural effusion. Cell growth was examined after a 3-day culture, which was preceded by exposure of the cells to cisplatin in either phosphate-buffered saline solution or distilled water for 1/2 to 5 minutes. The growth inhibition of tumor cells after hypotonic cisplatin treatment was significantly greater than after treatment with saline solution and cisplatin. Tumor that was obtained by resection of non-small-cell lung cancer was used as a model to demonstrate decreased viability of the tumor after exposure to hypotonic cisplatin. The viability of the tumor in a 6-day culture, preceded by exposure to hypotonic cisplatin (50 micrograms/ml) for 10 minutes, was markedly decreased. Intraoperative intrapleural hypotonic cisplatin was instilled in seven patients with pleural carcinomatosis without side effects and with control of pleural dissemination and pleural effusion for 6 to 29 months.

Aged↗

[The significance of HPV 16, 18 infection and the DNA ploidy associated with the progression of uterine cervical dysplasia].

We investigated the significance of HPV 16, 18 infection and DNA ploidy in the progression to malignancy of uterine cervical dysplasia. Formalin-fixed, paraffin-embedded surgical and biopsy specimens obtained from 59 women were examined. The 59 women were classified into two groups: one of progression cases and the other regression cases. Polymerase chain reaction (PCR) and dot blot hybridization (DBH) were used for the detection of HPV 16/18 DNA, while flow cytometry was used for the analysis of the relative cellular DNA content in samples prepared by Hedley's method. Eight out of 29 progression cases (27.6%) and 3 out of 30 regression cases (10.0%) exhibited HPV 16/18 DNA, whereas 14 out of 29 progression cases (48.3%) and 2 out of 30 regression cases (6.7%) involved a DNA aneuploid population, representing a DNA index in the former above 1.5 and in the latter below 1.5. The proportion of cases having a population of DNA aneuploid together with the presence of HPV 16/18 DNA was 20.7% (6/29) in the progression group and 0% (0/30) in the regression group. These results indicate that the DNA aneuploid population coupled with simultaneous HPV 16, 18 infection may be used as a marker for progression in uterine cervical dysplasia.

DNA, Viral↗

Is T factor of the TNM staging system a predominant prognostic factor in pathologic stage I non-small-cell lung cancer ? A multivariate prognostic factor analysis of 151 patients.

We attempted to clarify whether the T factor of the TNM staging system should be viewed as a predominant prognostic factor in patients with pathologic stage I non-small-cell lung cancer when analyzed together with various histopathologic factors and deoxyribonucleic acid ploidy pattern of tumors. We studied 151 patients who were in this stage. Histopathologic factors used in the analysis were as follows: histologic cell type (squamous or nonsquamous cell carcinoma), grade of differentiation, and tumor invasion of visceral pleura and vessels. Deoxyribonucleic acid ploidy pattern of tumors was analyzed by flow cytometry, and the tumors were classified as diploid or aneuploid tumors. Significant prognostic factors (p < 0.05) that were demonstrated by univariate analysis of survival curves were as follows: (1) T1 versus T2; (2) well versus moderately or poorly differentiated tumor; (3) the absence versus presence of tumor exposed on pleura, (4) artery invasion, (5) lymphatic vessel invasion; and (6) diploid versus aneuploid tumor. Multivariate prognostic factor analysis showed the grade of differentiation and deoxyribonucleic acid ploidy pattern to be predominant prognostic factors. The T2 tumor group had significantly more cases with tumor invasion of lymphatic vessels that did the T1 tumor group and included 18 cases with tumor exposed on pleura. When these two factors were excluded from multivariate analysis, the T factor was marginally significant (p = 0.08). These observations suggest that the T factor is not necessarily a predominant prognostic factor in pathologic stage I non-small-cell lung cancer.

Adult↗

Detection and characterization of blocking-type anti-acetylcholine receptor antibodies in sera from patients with myasthenia gravis.

We developed a highly sensitive, convenient assay for measuring blocking-type anti-acetylcholine receptor antibodies, which inhibit the binding of 125I-labeled alpha-bungarotoxin (alpha-BuTx) to the acetylcholine receptor (AChR). This procedure detected inhibitory activities in sera from 76% of patients with myasthenia gravis. Results of an experiment done with synthetic peptide corresponding to the alpha-BuTx binding region in the alpha-subunit of Torpedo AChR suggested that this inhibition is due to nonspecific steric hindrance caused by the binding of antibodies to a region other than the alpha-BuTx site, rather than by direct binding to the latter site. The inhibitory activities of the blocking-type antibodies and the titers of non-blocking-type antibodies were correlated. Moreover, the blocking-type antibodies could dissociate 125I-labeled alpha-BuTx from 125I-labeled alpha-BuTx-human AChR complex, and their dissociation activities showed good correlation with the inhibitory activities.

Amino Acid Sequence↗

Adjuvant chemotherapy for completely resected stage III non-small-cell lung cancer. Results of a randomized prospective study. The Japan Clinical Oncology Group.

Two hundred nine patients with completely resected stage III non-small-cell lung cancer were randomized to receive postoperative cisplatin and vindesine chemotherapy or no further treatment. Before randomization, patients were stratified by the histologic characteristics of their tumors (squamous versus nonsquamous cell carcinoma). Prognostic variables such as histology, performance status, extent of operation, and tumor and nodal status of the eligible patients in chemotherapy (n = 90) and control groups (n = 91) were equally distributed. There was no statistically significant difference in disease-free and overall survival between the two groups. The 3-year disease-free survivals of the chemotherapy and control groups were 37% and 42%, respectively. The median survival times (5-year survival) were 31 months (35%) in the chemotherapy group and 37 months (41%) in the control group. These was no different pattern in the first site of recurrence (local versus systemic) between the two groups. This study failed to demonstrate the therapeutic benefits of postoperative cisplatin and vindesine chemotherapy.

Adenocarcinoma↗

Effect of Ca++ channel blockers on energy level and stimulated insulin secretion in isolated rat islets of Langerhans.

To investigate the effect of calcium channel blockade on intracellular energy levels and stimulated insulin secretion in isolated rat pancreatic islets, five different blockers of calcium channels were used. Insulin secretion stimulated with 16 mM glucose, 40 mM KCl or 20 mM alpha-ketoisocaproic acid was inhibited dose dependently by nifedipine, diltiazem, flunarizine and verapamil, albeit with different potencies. Nifedipine and flunarizine were more potent than diltiazem and verapamil. omega-Conotoxin GVIA (100 nM) had no significant effect on insulin release with all stimuli tested, although it caused approximately 20% inhibition of the late phase of secretion stimulated with high glucose. The doses of L-type channel antagonists and of flunarizine chosen for the measurements of cellular energy levels gave 60 to 80% inhibition of total stimulated insulin release. The [ATP]/[ADP] ratio, with 5 mM glucose in the perifusion medium, was greater when these channel blockers were present than in controls, whereas it was smaller with omega-conotoxin. The rises in the nucleotide ratio elicited by 16 mM glucose were not affected by any of the antagonists tested. Thus, influx of Ca++ and a consequent rise in its intracellular level are unlikely to be the primary causal event in stimulation of energy synthesis which occurs upon addition of high concentrations of metabolic secretagogues.

Adenosine Diphosphate↗

Laparoscopic ligation of splenic artery aneurysm.

Efforts should be made to avoid splenectomy because host resistance is maintained by the spleen. We describe here a 50-year-old woman in whom laparoscopic ligation of a splenic artery aneurysm 3.0 cm in diameter was successfully performed, without major complications. Computed tomography performed 5 months later revealed no infarction in the spleen. For this patient with liver cirrhosis and cholelithiasis, laparoscopic cholecystectomy was performed at the same operation. Laparoscopic surgery is most feasible when the splenic artery is markedly tortuous and protrudes from the pancreas.

Aneurysm↗

Albumin inhibits hemolysis of erythrocytes induced by ethanolamine oleate during endoscopic injection sclerotherapy.

In attempts to avoid hemolytic nephropathy following injection of 5% ethanolamine oleate during endoscopic injection sclerotherapy for esophageal varices, the relationship between serum levels of albumin and hemolysis induced by ethanolamine oleate was investigated. The rate of hemolysis at various concentrations of ethanolamine oleate and albumin was examined using a spectrophotometer in ten cirrhotic patients and five healthy volunteers (controls). Hemolysis induced by ethanol-amine oleate increased in an ethanolamine oleate concentration-dependent fashion (p < 0.01) but was dose-dependently inhibited by albumin (p < 0.05). The state of liver function was unrelated to the rate of hemolysis. The relationship between hemoglobinuria and serum albumin levels in seventy-nine cirrhotic patients with esophageal varices treated by endoscopic injection sclerotherapy with ethanolamine oleate was also examined. Hemoglobinuria was evident in 20 out of 24 patients (83.8%) in whom the serum albumin level was less than 3.0 g/dl, and in 24 out of 55 (43.6%) in whom it exceeded 3.0 g/dl, the difference being statistically significant (p < 0.01). On the day after endoscopic injection sclerotherapy, creatinine clearance fell from 81.6 +/- 33.8 m/l min to 60.1 +/- 31.4 ml/min in the hemoglobinuria-positive patients (p > 0.01) and two went into acute renal failure. The creatinine clearance ranged from 79.5 +/- 27.9 ml/min to 83.0 +/- 39.9 ml/min in the hemoglobinuria-negative patients (p < 0.1). In the light of this evidence we correct the serum albumin level cut off point to 3.0 g/dl prior to endoscopic injection sclerotherapy in order to maintain renal function.

Aged↗

Defenestration of the sinusoidal endothelial cell in a rat model of cirrhosis.

We characterized the structural and immunohistological changes of sinusoidal endothelial cells that occur during cirrhosis in rats made cirrhotic with thioacetamide. Thioacetamide (200 mg/kg body wt) was injected intraperitoneally three times a week into male Wistar rats. Two, 4, 6 and 12 wk later, rat livers were observed under transmission and scanning electron microscopy and regular microscopy and immunostained with laminin and von Willebrand factor (factor VIII-related antigen) antibodies. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly after 2 wk in the thioacetamide-treated rats; however, they decreased within 4 wk after thioacetamide treatment. A basement membranelike structure in Disse's space was noted 6 wk after thioacetamide treatment. Laminin was detected in Disse's space after 4 wk. In vitro, in cultured sinusoidal endothelial cells, the diameter of sinusoidal endothelial fenestrations was significantly lower at 6 wk in thioacetamide-treated rats. von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 wk of thioacetamide treatment. These results suggest that as fibrosis develops in cirrhosis, the structural and immunohistochemical characteristics of sinusoidal endothelial cells change.

Animals↗

Structural elucidation of a novel phosphonoglycosphingolipid in eggs of the sea hare Aplysia juliana.

A novel phosphonoglycosphingolipid (AJPnGL) was isolated from eggs of the sea hare Aplysia juliana. The structure was determined to be Gal alpha 1-->2Gal beta 1-->4(2-aminoethylphosphonyl-->6)Glc beta 1-->1Cer by FAB/MS, 1H-NMR, hydrogen fluoride degradation, methylation analysis, partial acid hydrolysis and GC analysis of the component sugars, fatty acids and long-chain bases. The ceramide moiety of this lipid consisted of branched nonadeca-4-sphingenine and octadeca-4-sphingenine as main long-chain bases and palmitic acid and stearic acid as major fatty acids. Since the sugar chain (Gal alpha 1-->2Gal beta 1-->4Glc beta 1-->) and the ceramide moiety of AJPnGL were identical with those of the main neutral glycosphingolipid of eggs of A. juliana, the biosynthesis of AJPnGL may occur by the addition of 2-aminoethylphosphonate to the main neutral glycosphingolipid, Gal alpha 1-->2Gal beta 1-->4Glc beta 1-->1Cer.

Animals↗

In vitro proliferation and the cytotoxic specificity of a cryopreserved cytotoxic T cell clone reacting against human autologous tumor cells.

Proliferation and functional maintenance of CTL after cell cryopreservation often proves to be quite difficult. We developed an improved method for proliferating cryopreserved CTL, and for gaining their specific cytotoxic function. T cells were cryopreserved at -180 degrees C in RPMI 1640 containing 50% FCS and 10% DMSO. The cryopreserved T cells were well recovered by culturing in a medium containing the supernatant of primary cultures with TIL and autologous tumor cells, in addition to a high concentration (350 U/ml) of rIL-2. Furthermore, these cells were proliferated more efficiently when MMC-treated autologous tumor cells were used in vitro as a feeder and an antigenic stimulant. However, such a high dose IL-2 cultivation resulted in the loss of cytotoxic reactivity of CTL clone. In contrast, the withdrawal of rIL-2 from in vitro cultivation for 24 h prior to the cytotoxic assays conferred the specificity of cytotoxicity on CTL. By these methods, one can obtain a large number of CTL, and pursue the physiologic detail of the specific cytotoxic mechanism of CTL against autologous human tumor cells.

Antigens, Surface↗

A new member of the insulin receptor family, insulin receptor-related receptor, is expressed preferentially in the kidney.

Shier and Watt isolated human and guinea pig genomic DNA encoding a putative protein, insulin receptor-related receptor (IRR), the primary structure of which is similar to that of other members of the insulin receptor family, the insulin receptor and type-I IGF receptor (J. Biol. Chem. 264, 14605-14608 (1989)). However, the expression of the IRR gene remained unknown. In this paper, we isolated the IRR cDNA from the rat brain and examined the expression of the IRR mRNA in a variety of rat tissues, including the brain, heart, lung, liver, small intestine, kidney, thymus, spleen, muscle, adipose tissue and cartilage by polymerase chain reaction. In contrast to the wide distribution of the insulin receptor and type-I IGF receptor mRNAs, the IRR mRNA is expressed preferentially in the kidney, which indicates that IRR has unique functions as a member of the insulin receptor family.

Amino Acid Sequence↗

Transforming growth factor-beta inhibits phosphorylation of the retinoblastoma susceptibility gene product in human monocytic leukemia cell line JOSK-I.

Proliferation of the human monocytic leukemia cell line JOSK-I is inhibited by transforming growth factor-beta (TGF-beta). Growth inhibition by TGF-beta was not due to either a toxic effect or to induction of differentiation. TGF-beta induced a cell cycle arrest at late G1 phase and was not found to be inhibitory to JOSK-I cells in S phase or G2/M. This G1 cell cycle arrest was associated with an accumulation of the unphosphorylated form of the retinoblastoma susceptibility gene product (Rb) in good correlation with inhibition of DNA synthesis. In contrast to the effects of TGF-beta, two other agents which induced a G1 arrest of JOSK-I cells had a different effect on Rb. Aphidicolin blocked cells at G1/S but could not reduce Rb phosphorylation as great as that seen with TGF-beta. 12-O-Tetradecanoylphorbol-13-acetate, an inducer of differentiation, did reduce Rb phosphorylation, but not until 72 h, when differentiation had already occurred. The identities of the Rb kinases are unknown, but recent evidence suggests that the cdc2 gene product could participate in Rb phosphorylation. Although cdc2 mRNA and total protein levels were not affected, TGF-beta inhibited the rate of translation and kinase activity of cdc2 in JOSK-I cells. These results suggest that growth inhibition of hematopoietic cells by TGF-beta is linked to suppression of Rb phosphorylation to retain Rb in an unphosphorylated, growth-inhibitory state. The suppression of Rb phosphorylation is suggested to be mediated through inhibition of cdc2 kinase activity by TGF-beta.

Aphidicolin↗