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Biomedical subjects

I Inoue

Publications and source records attributed to I Inoue.

At least 235 records · Page 13Linked to original sources

Molecular basis of ornithine transcarbamylase deficiency lacking enzyme protein.

We report an ornithine transcarbamylase(OTC)-deficient male patient who had no detectable immunoreactive materials but did have active mRNA for OTC-related protein. The total absence of OTC activity in the liver of the patient was caused by a complete lack of immunoreactive material, as determined by Ouchterlony double immunodiffusion, single radial immunodiffusion, and sodium dodecylsulphate-polyacrylamide gel electrophoresis of immunoprecipitate and of liver homogenate. However, mRNA coding for the precursor of OTC was clearly detected in autopsy specimens of the patient's liver as well as of controls in a cell-free translation system consisting of rabbit reticulocyte lysates and [35S]methionine. The labelled precursor of OTC synthesized in vitro with mRNA from the patient could be transported into rat liver and kidney mitochondria and processed to form a protein with a molecular weight indistinguishable from mature OTC, suggesting that there was no defect in the protein structure necessary for its transport into mitochondria. These results suggest that the primary defect of the OTC deficiency was located in the structural gene and that the labile OTC-related protein, after being synthesized with its mRNA, was degraded too rapidly to be detected by the method used.

Amino Acid Metabolism, Inborn Errors↗

[Antitumor activity of cisplatin against malignant brain tumors].

Antitumor activity of Cisplatin (cis-diamminedichloroplatinum) against malignant brain tumors was investigated from both experimental and clinical points of view. With glioma and neuroblastoma cell lines we studied inhibition of cell growth was studied and DNA histogram analyzed with flow cytometry to determine its antitumor activity in vitro. At the concentration of 1.25 micrograms/ml, DNA accumulation is S or G1-S phase and mild inhibition of cell growth were demonstrated; at the concentration of 12.5 micrograms/ml, cessation of cell cycle was observed. In the clinical study, four glioma patients were treated by intravenous administration of Cisplatin 10 mg/sqm for 5 days q 4 weekly. There were one complete response, one minor and two stable responses. Three patient with intracranial embryonal carcinoma were treated by cisplatin. One patient showed partial response and the others were stable.

Adolescent↗

[Effect of MCNU on brain tumors. Part II: Clinical experience with MCNU on malignant brain tumors].

Ten patients with malignant brain tumor (8 cases with glioblastoma, 2 cases with medulloblastoma) were treated with a new water-soluble nitrosourea, MCNU. Objective tumor regression of tumor (CR & PR) on computerized tomography was observed in four patients (2 complete and 2 partial) after MCNU, chemotherapy showing a response rate of 40%. The major side effects of MCNU were mild or moderate myelosuppression, and some cases also showed gastrointestinal toxicities and impairment of hepatic function. However, all these side effects were mild and transient and soon recovered to normal levels. One patient with glioblastoma multiforme recurrence was treated with a high-dose chemotherapy of MCNU (400 mg) associated with autologous bone marrow transplantation. Myelosuppression began to appear from 15th day of MCNU administration and normalized within 30 days afterwards. These results suggest that MCNU therapy is effective for patients with malignant brain tumors.

Adolescent↗

Chromatographic differentiation of the mitochondrial and cytosolic fumarases of rat liver and Baker's yeast and differential induction of two fumarases of Baker's yeast.

The mitochondrial and cytosolic fumarases of rat liver could be separated from each other by Bio-Gel HTP column chromatography, showing that there are some conformational differences between the native proteins of the mitochondrial and cytosolic fumarases which have been indistinguishable by their physicochemical, catalytic, and immunochemical properties. The fumarase associated with the mitochondrial fraction of Baker's yeast could also be separated from that located in the cytosol by the Bio-Gel HTP column chromatography. By applying this chromatography to the differential determination of the fumarase activities in the Baker's yeast cultured under various conditions, it was shown that the mitochondrial and cytosolic fumarases in the cell are regulated by independent control systems.

Animals↗

[MCNU effectiveness on brain tumor. Part I: Antitumor activity in vitro on human glioma and neuroblastoma cell lines].

A new water-soluble nitrosourea ( MCNU ) was tested for its antitumor activity against fourteen human glioma cell lines and two neuroblastoma cell lines. Four experiments were performed to determine its antitumor activity: inhibition of cell growth, comparison with ACNU, morphological observation, and analysis of DNA histogram with flowcytometry . Seven out of 14 gliomas (50%) and one neuroblastoma cell lines showed more than 50% inhibition of cell growth in vitro, appearance of giant multinucleated cell morphologically, and DNA accumulation in G2+M and/or S phase of cell cycle in the medium of 10 micrograms/ml MCNU . Antitumor activity and spectrum of MCNU against human brain tumors were almost the same as with ACNU.

Antineoplastic Combined Chemotherapy Protocols↗

Distribution of histaminase in human tumor tissues. An immunohistochemical study.

Tissue samples from 125 cases of a variety of human malignancies and benign conditions were examined for the presence of histaminase by the immunoperoxidase method on conventional pathological specimens. Histaminase was found diffusely in the cytoplasm of cancer cells of primary and metastatic tumors of lung, thyroid gland, pancreas, stomach, esophagus, ovary and pharynx. Histaminase-positive cases were also found in carcinoids, dysgerminomas and in melanoma. The incidence of positive histaminase staining in epithelial malignancies overall was 28/84, and those in sarcoma as well as in benign conditions were 1/22 and 0/19, respectively, excluding placental decidual cells and eosinophils intermingled in the tissues. No significant difference in the incidence of histaminase was found by histological type or by degree of cellular differentiation. The present results thus provided another direct evidence for the production of histaminase by many kinds of tumor cells.

Amine Oxidase (Copper-Containing)↗

[Postoperative chemotherapy of perforating appendicitis in children; with special reference to latamoxef therapy].

We employed latamoxef (LMOX) as antibiotic therapy subsequent to the performance of appendectomies in children. Fifteen patients, consisting of 8 cases of catarrhal appendicitis and 7 cases of gangrenous appendicitis, were administered LMOX at 50 mg/kg/day, while 13 patients with peritonitis due to a perforated appendix were treated with a dosage of 90 mg/kg/day. Both of these dosages were administered in 3 equally-divided doses, as one shot intravenous injections. All of the cases of catarrhal and gangrenous appendicitis showed good, steady recovery after the surgery, and there were no instances of complications. With regard to the 13 cases of perforating appendicitis, a clinical efficacy of at least "good" was obtained in 12 patients, for an efficacy rate of 92.3%. In addition, bacteriologically, 35 out of 36 strains that were isolated initially could no longer be detected after the LMOX therapy, indicating an eradication rate of 97.2%. Complications consisted of 1 case of dehiscence of the wound, and 1 case of adhesive ileus. Comparison of the values of the laboratory tests before and after the LMOX therapy revealed no development of abnormalities. Moreover, with regard to side effects, with the exception of 1 case of transient diarrhea, there were no side effects which presented clinical problems. It was found that the causative microbes involved in these cases of appendicitis--especially in the perforative appendicitis cases--were Gram-negative bacilli such as E. coli, and an anaerobic bacterium, B. fragilis.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Cerebral vasospasm evaluated by computed tomography in a patient with ruptured cerebral aneurysm. A case report.

Low density areas on computed tomography were correlated with changes in the neurological state of a patient who had cerebral vasospasm after subarachnoid hemorrhage from a ruptured anterior communicating aneurysm. No aneurysm was revealed on repeated angiograms initially because of vasospasm, but a low density area was found in the inferior part of the left frontal lobe. Following an attack of low blood pressure on the 12th day his neurological state deteriorated and CT disclosed low density areas in the inferior part of both frontal lobes. The aneurysm was finally disclosed and operated successfully on the 49th day when cerebral vasospasm had disappeared completely.

Adult↗

[Over diagnosis of the biopsy: from the analysis of the extirpated uterus after radical hysterectomy (author's transl)].

From January, 1973 to December, 1980, 396 cases of cervical cancer were treated with radical hysterectomy under the diagnoses of stage Ib, IIa and IIb. Precise postoperative pathological examinations about the extirpated uterus revealed that 63 of them had only early invasive cancer or less advanced lesions though they had been considered as frank invasive cancer by preoperatively performed biopsies. The major causes of the misinterpretations were, 1) misjudging the glandular involvements as frank invasive lesions, or 2) misjudging the tangentially sectioned lesions of the bulky outgrowth as frank invasions. Furthermore, it is sometimes difficult to identify the invasive lesions in the biopsy specimens whether they are early invasive or frank invasive. Colposcopic and cytological examinations were simultaneously performed to each cases. Either cytology or colposcopy did not suggest frank invasions in 44.2% of cases. Both of them did not suggest frank invasions in 37.2% of cases. At least, cone biopsy should have been performed to identify the degree of invasions of these 37.2% cases. The authors emphasize that the directed biopsies are not always accurate to diagnose the early invasions, and one should use colposcopy, cytology and directed biopsy to make an accurate diagnosis.

Adenocarcinoma↗

Activation-inactivation of potassium channels and development of the potassium-channel spike in internally perfused squid giant axons.

A spike that is the result of calcium permeability through potassium channels was separated from the action potential is squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution by blocking sodium channels with tetrodotoxin. Currents through potassium channels were studied under voltage clamp. The records showed a clear voltage-dependent inactivation of the currents. The inactivation was composed of at least two components; one relatively fast, having a time constant of 20--30 ms, and the other very slow, having a time constant of 5--10 s. Voltage clamp was carried out with a variety of salt compositions in both the internal and external solutions. A similar voltage-dependent inactivation, also composed of the two components, was recognized in all the current through potassium channels. Although the direction and intensity of current strongly depended on the salt composition of the solutions, the time-courses of these currents at corresponding voltages were very similar. These results strongly suggest that the inactivation of the currents in attributable to an essential, dynamic property of potassium channels themselves. Thus, the generation of a potassium-channel spike can be understood as an event that occurs when the equilibrium potential across the potassium channel becomes positive.

Action Potentials↗

[Bacteriological and clinical studies of cefoxitin with special reference to anaerobic infections in the patients of abdominal surgery (author's transl)].

Both bacteriological and clinical studies of the effectiveness of cefoxitin (CFX) in the treatment of infections associated with abdominal surgery have been carried out at Tokyo Metropolitan Toshima Hospital from September 1979 through August 1980. The results of these studies are summarized in the following: 1. The clinical isolates from the 29 surgical patients were studied and anaerobes were found in 16 patients (55% of the patients). B. fragilis was found in 11 of the 16 patients (69%) from whom anaerobes were isolated. In all of these patients, aerobes were also isolated--most frequently E. coli or K. pneumoniae. 2. The in vitro antibacterial activity of cefoxitin (CFX) against 83 clinical isolates was compared to that of cephalothin (CET), cefazolin (CEZ) and carbenicillin (CBPC). The activity of CFX against Gram-positive bacteria was generally slightly inferior to that of the other 3 antibiotics. Among the Gram-negative aerobic organisms, CEZ was the most active against E. coli and CFX and CEZ against K. pneumoniae. However, CFX, with MIC's of 0.78-12.5 micrograms/ml, showed the greatest activity against B. fragilis, followed by CBPC, CEZ and CET, in order of decreasing activity. 3. CFX was administered in a 1-hour drip infusion to 3 patients following abdominal surgery, and concentrations of CFX in the serum and the exudate were measured. Peak serum concentrations were obtained at the end of the infusion, with a mean peak level of 97.93 micrograms/ml. Peak concentrations in the exudate were observed 30 to 60 minutes later and varied from 21.10 to 56.25 micrograms/ml. 4. Of the 20 patients administered of CFX, complete clinical and bacteriological data of anaerobic infections were available in 8 patients. The clinical evaluation was 'good' in 7 patients and 'fair' in 1. The bacteriological evaluation was 'eradicated' in 5 patients and 'decreased' in 3. As for side effects, elevations of S-GOT and S-GPT were observed in 4 of the 20 patients received CFX, but these abnormalities might also be attributable to other factors such as underlying disease, surgical intervention etc. No other side effects were found in these patients.

Abdomen↗