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Biomedical subjects

O Nishimura

Publications and source records attributed to O Nishimura.

At least 73 records · Page 4Linked to original sources

[Experimental study of pumpless ECMO during 24 hours using extracapillary blood flow type polypropylene membrane oxygenator].

To remove carbon dioxide in acute respiratory failure, pumpless ECMO (extra-corporeal membrane oxygenation) experiment was carried out using extracapillary blood flow type membrane oxygenator, which was developed by our department and which has many advantages, compact, small priming volume and low pressure drop. The oxygenator is consisted with 17 cm in length, 200 microns in inner diameter, made of polypropylene with micropores. And it has 0.7 m2 of surface area and 60 ml of priming volume. In 14 canines, acute respiratory failure were made by hypoventilation (T.V. = 10 ml/kg, R.R. = 5 times/min). We compared with hypoventilation group (group 1, n = 5) and pumpless ECMO group (group 2, n = 9). Pumpless ECMO circuit is A-V bypass between femoral artery and femoral vein. The following results were obtained. 1. In group 1 severe hypoxia and hypercapnea were observed, and all 5 canines were dead within 4 hours. 2. In group 2 hypoxia and hypercapnea were improved by pumpless ECMO, and 4 in 9 lived for 24 hours. 3. Function in CO2 transfer with the P.H.O. is maintained in satisfactory condition for 24 hours. 4. The oxygenator seems to be available for long-term pumpless ECMO. 5. Degeneration of mitochondria in the acute respiratory failure was observed by electron microscopic examination. 6. Further examinations about the intracellular respiration and metabolism in pumpless ECMO should be needed.

Animals↗

Escherichia coli-derived human interferon-gamma with Cys-Tyr-Cys at the N-terminus is partially N alpha-acylated.

Purified preparations of recombinant human interferon-gamma (rIFN-gamma) with Cys-Tyr-Cys at the N-terminus ([ Cys-Tyr-Cys]IFN-gamma) derived from Escherichia coli gave two closely migrating bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and two peaks on reversed-phase high-performance liquid chromatography (rpHPLC). In contrast, rIFN-gamma without Cys-Tyr-Cys and rIFN-gamma in which both Cys-1 and Cys-3 were substituted with serine behaved as a single species on both SDS-PAGE and rpHPLC. These results suggest that the N-terminal portion of rIFN-gamma is heterogeneous. To elucidate the structure of the N-terminal portion, the N-terminal peptide preparation was obtained by binding rIFN-gamma to thiopropyl-Sepharose 6B gel with disulfide linkage followed by trypsin digestion and elution with 2-mercaptoethanol. The preparation gave four peaks (NT-1, NT-2, NT-3, and NT-4, in order of elution) on rpHPLC; all four were found to be Cys-1-Lys-9 by amino acid analysis after acid hydrolysis. Various analyses indicate that NT-1 is the intact nonapeptide, that NT-3 and NT-4 are N alpha-formyl and N alpha-acetyl forms of NT-1, respectively, and that NT-2 may be S-blocked at Cys-1. It is concluded that E. coli-derived [Cys-Tyr-Cys]IFN-gamma is partially N alpha-acylated. The data also suggest that N alpha-acylation does not affect the biological activity of [Cys-Tyr-Cys]IFN-gamma.

Amino Acid Sequence↗

Administration of human leukocyte interferon to patients with subacute sclerosing panencephalitis.

Between 1979 and 1982, fifteen patients with SSPE were treated with human leukocyte interferon (HuIFN-alpha). They were administered interferon (IFN) in doses ranging from 25 x 10(6) IU to 126 x 10(6) IU by various routes in regimens that ranged for 20 days to 14 months. In 3 of the 5 cases with rapid deterioration, HuIFN-alpha did not alter the course of the disease; however, 6 cases with mild progression showed various degrees of clinical improvement during the IFN therapy. In 3 of the 4 cases in remission, HuIFN-alpha caused no significant changes in clinical courses. No severe adverse reactions were seen during IFN administration. These results suggest that HuIFN-alpha has a potentially beneficial effect on the course of SSPE.

Adolescent↗

[Clinical evaluation of surgical treatment of lung cancer involving the chest wall].

Twenty-four patients with primary lung cancer involving chest wall underwent pulmonary and chest wall resections. All patients were males ranging from 38 to 74 years of age. Pain was the most frequent symptom. Twenty-three lobectomies and one pneumonectomy were performed. Resections of parietal pleura were performed in 4 patients and en block resections of chest wall were performed in 20 patients. After operation, postsurgical stage was pT3N0M0 in 16 patients, pT3N1M0 in 4 patients and pT3N2M0 in four. Operative mortality was 4.2%. Actuarial survival of 23 patients surviving operation was 45.7% at 1 year, 28.7% at 2 year and 17.2% at 3 and 5 year. Three patients who had no lymphnode metastases and no rib invasion survived more than 5 years. We concluded that long term survival can be expected in pN0 patients without invasion to the ribs.

Adenocarcinoma↗

[Assay of erythropoietin in plasma by enzyme-linked immunosorbent assay].

Using an enzyme linked immunosolvent assay kit supplied by Toyobo Co., erythropoietin (EPO) concentration in plasma was measured. Normal 100 samples showed a logarithmic distribution in EPO concentrations and normal range was between 5.4-32.5 mU/ml (mean +/- 2 SD). Coefficient variations (C.V.) of 3 samples continuously assayed were 3.8%, 6.5%, and 9.1% and C.V. of 3 samples assayed day by day were 3.6%, 7.2%, and 11.5%. Dilution test revealed that 3 samples diluted to 75%, 50%, and 25% were on each line which go through zero point. After the addition of 5.0, 15.0, and 35.0 mU/ml of EPO to the 3 samples, assay of EPO revealed 95.5 +/- 6.3% (mean +/- SD) of recovery. Assay of EPO in plasma from 19 patients with aplastic anemia revealed that all samples were higher than normal range and that 4 samples from the patients with severe aplastic anemia (less than 8.0 g/dl of hemoglobin) showed higher than 3,000 mU/ml. Furthermore, 67% (14/21) of samples from patients with leukemia showed higher than normal range in EPO concentration. EPO concentration in plasma from 17 patients with chronic renal failure were within normal range although the patients showed anemia.

Adult↗

[Gastroesophageal reflux after esophageal surgery--evaluations based on esophageal transit scintigram].

By means of esophageal transit scintigram using 99mTc-DTPA, 15 patients (13 esophageal carcinomas and 2 cardia carcinomas) were studied, in whom esophagogastric anastomosis was done according to the posterior invagination anastomosis technique we had devised. In all 8 patients with anastomosis at cervical region, gastroesophageal reflux was not seen on both scintigrams before and after meals, and the average pressure gradient of high pressure zone at anastomosis was 39.8 cmH2O. In 2 of 7 patients with intrathoracic anastomosis, the scintigram before meals showed severe reflex, and the endoscopic findings showed diffuse and moderate erosion in the esophageal mucosa. The average pressure gradient across the anastomosis was 6.5 cmH2O. In these 2 patients, the new fornix with a sharp angle of His was not formed. In the remaining 5 patients with intrathoracic anastomosis, reflux was not seen on the scintigram before meals. However, in 2 of them, the scintigram after meal and endoscopic examination revealed mild reflux and mild esophagitis respectively. Furthermore in one patient very mild reflux was observed only on the scintigram after meals but the endoscopic findings showed the normal esophageal mucosa. In these 5 patients, the average pressure gradient across the anastomosis was 17.0 cmH2O, which was significantly higher (p less than 0.01) than that in 2 patients with severe reflux and was significantly lower (p less than 0.01) than the mean value of high pressure zone in 8 patients with cervical anastomosis. In conclusion, it is presumed that the formation of a large fornix enough to store food and a sharp angle of His are important factors in maintaining an anti-reflux mechanism. The esophageal transit scintigram was proved to be an excellent technique in detecting and evaluating quantitatively gastroesophageal reflux.

Aged↗

Human interferon-gamma lacking 23 COOH-terminal amino acids is biologically active.

We constructed five mutated cDNAs encoding human interferon-gamma (IFN-gamma) derivatives lacking 19-23 COOH-terminal residues and expressed them in Escherichia coli. All the derivatives were purified to homogeneity. They showed substantially the same order of antiviral activity in vitro as the intact molecule, and behaved as a dimer. The far- and near-UV circular dichroism spectra of the derivatives were quite similar to those of the intact one. These results indicate that the 23 COOH-terminal amino acids at least are not essential for achieving the full antiviral activity and constructing the higher structure of human IFN-gamma.

Amino Acids↗

Serum zinc and copper changes after gastrectomy in aged patients with gastric cancer.

Serum zinc and copper levels were evaluated in patients with gastric cancer who had undergone gastrectomy. These patients were divided into two age categories; namely, the aged group, comprising 39 patients over the age of 70 years, and the younger group, comprising 23 patients younger than 50 years. The data before and after surgery were compared between the two groups. Serum zinc levels in the aged group were significantly lower than those in the younger group, both before and after surgery. Serum copper levels, however, did not differ significantly between the two groups. The serum Cu/Zn ratio was also analyzed according to the histological stages of cancer (stages I to IV), and compared between the two age-classified groups. The aged group showed a higher Cu/Zn ratio at all stages, whereas in the younger group, the ratio was significantly higher at stage IV than in the earlier stages. Preoperative serum zinc, copper, and the Cu/Zn ratio were studied in relation to the complication of anastomotic leak after surgery. The Cu/Zn ratio in the aged patients with this complication was significantly higher than that in the aged patients without it. These results suggest that the Cu/Zn ratio may be an important factor in determining nutritional parameters in the aged.

Adult↗

The effects of diet on the residual small intestine following massive resection.

The midportions of rat small intestines were resected by 90 per cent, and the residual intestines studied for the effects of diet on mucosal morphology, nutrition and gastrointestinal hormones. Groups of rats were fed chow, an elemental diet (ED), or an ED + dietary fiber (EDF) for 1 or 3 weeks. Nonresected rats which were fed chow or ED for 3 weeks were used as controls. Nutritional parameters, such as concentrations of serum total protein, albumin and transferrin were favorable but gain in body weight was not. The parameters indicated that resected rats fed EDF fared better than resected rats fed ED. Mucosal villous height in the residual jejunum, similar in all the resected groups after 1 week, was significantly increased in the resected rats fed chow or EDF after 3 weeks, but did not differ between 1 and 3 weeks in the resected rats fed ED. Changes in the number of villous epithelial cells and villous width were also examined. The level of plasma enteroglucagon was high in the rats fed chow or EDF after both 1 and 3 weeks, and was positively correlated with the increases in villous height. Levels of serum gastrin were not affected by dietary change. Luminal nutrients were significantly associated with the adaptive changes in the mucosa of the residual intestine, and mucosal morphology was also considerably influenced by dietary change.

Adaptation, Physiological↗

Brain energy metabolism in two kinds of total asphyxia: an in vivo phosphorus nuclear magnetic resonance spectroscopic study.

Brain energy metabolism was studied in vivo by means of 31P-NMR spectroscopy in newborn mice during and after 20-minutes exposure to either pure carbon dioxide gas or nitrogen gas. In the N2 group, the brain ATP concentration remained almost normal throughout the experiment, while it showed a 30% reduction in the CO2 group. The brain concentration of phosphocreatine dropped to about 20% of the control value during the asphyxia in both groups, and its recovery was significantly delayed in the CO2 group compared to in the N2 group. Tissue acidosis and Pi accumulation were more remarkable and prolonged in the CO2 group.

Adenosine Triphosphate↗

Oral contraceptives and intrahepatic biliary cystadenoma having an increased level of estrogen receptor.

We report a case of intrahepatic biliary cystadenoma in a young woman who had no prior history of liver disease and who had taken oral contraceptives for one year. A 27-year-old woman was admitted to our hospital with a firm epigastric mass. At laparotomy, a large cystic mass was resected from the left hepatic lobe, and diagnosed as biliary cystadenoma. In the tumor tissue, the estrogen receptor content was 14.0 fmol/mg cytosol protein, which was much higher than the 3.0 fmol/mg cytosol protein in the surrounding liver tissue. This is the first case of biliary cystadenoma in which the estrogen receptor content was increased.

Adult↗

Importance of disulfide linkage for constructing the biologically active human interleukin-2.

Recombinant human interleukin-2 (rIL-2) produced in Escherichia coli possesses a free thiol group at Cys-125 and a disulfide linkage between Cys-58 and Cys-105, as in the case for natural human interleukin-2. Treatment of rIL-2 with 200 mM dithiothreitol resulted in the cleavage of the Cys-58-Cys-105 disulfide bond. The reduced form of rIL-2 thus obtained retained only 10% of the in vitro biological activity of the native form, as measured by the ability to stimulate the growth of an IL-2-dependent mouse natural killer cell line, NKC3. Far-uv circular dichroism studies indicated that the cleavage of the disulfide bond results in a decrease of alpha-helix content. Near-uv circular dichroism studies suggested that the native molecule is folded into a rigid tertiary structure, while the reduced form showed a spectrum similar to that of rIL-2 denatured in the presence of 6 M guanidine.HCl. The once-reduced molecule was readily reoxidized in the presence of 10 microM Cu2+ to form the native molecule with full biological activity. These results strongly demonstrate that the Cys-58-Cys-105 disulfide linkage in the IL-2 molecule is essential for constructing a rigid and biologically active form of IL-2.

Amino Acids↗

Chemical characterization of recombinant human leukocyte interferon A using fast atom bombardment mass spectrometry.

Proteolytic digests of biologically active fractions of recombinant human leukocyte interferon A expressed in large quantities in Escherichia coli were analyzed by fast atom bombardment mass spectrometry and high-performance liquid chromatography. The values observed in the mass spectra of digests of the major fraction of recombinant human leukocyte interferon A with trypsin and Staphylococcus aureus protease V8 accounted for 93% of the amino acid sequences of human leukocyte interferon A predicted from the nucleotide sequence of the gene encoding the protein, indicating that the major fraction of recombinant human leukocyte interferon A was expressed with the same amino acid sequence as that translated from the nucleotide sequence of the gene encoding the protein. Mass spectrometry of proteolytic digests of two minor fractions of recombinant human leukocyte interferon A and mass and amino acid analyses of their high-performance liquid chromatography fractions showed that the amino group of the N-terminal amino acid residue of interferon was in part acetylated, and the Cys-1 and Cys-98 residues were oxidized to cysteic acid or linked to glutathione. These findings suggest that amino acid residues in recombinant proteins prepared in large quantities in E. coli are modified post-translationally.

Amino Acid Sequence↗

Proximal gastrectomy as the surgical procedure of choice for upper gastric carcinoma.

To assess the efficacy of proximal gastrectomy in the treatment of upper gastric carcinoma, we analyzed clinical data from patients with lesions confined to the upper third of the stomach (group 1) and from patients with lesions which, while primarily located in the upper portion of the stomach, showed spread to the body of the stomach (group 2). Patients in group 2 showed more metastatic lymph node involvement, particularly of the infrapyloric lymph nodes, which were not included in lymphadenectomy accompanying proximal gastrectomy. None of the group 1 patients demonstrated metastasis to the infrapyloric lymph nodes. The postoperative 5-year survival rate in curatively operated group 1 patients was not significantly different between those treated by proximal gastrectomy and those subjected to total gastrectomy. We conclude that proximal gastrectomy is indicated in patients with upper gastric carcinoma when it is confined to the upper third of the stomach.

Gastrectomy↗

An enzyme-immunoassay for human interleukin-2.

A highly sensitive enzyme-immunoassay (EIA) for human interleukin-2 (IL-2) has been established. The assay is based on a sandwich method that uses two kinds of anti-IL-2 antibodies raised against Escherichia coli-derived recombinant IL-2 (rIL-2). An affinity-purified-anti-IL-2 goat IgG was used as the first antibody and the Fab' fragment of an affinity-purified-anti-IL-2 rabbit IgG was used as the second antibody after being coupled with horseradish peroxidase (HRP). As little as 30 pg/ml of IL-2 was detected by the EIA, indicating that this method was about 100 times more sensitive than the bioassay using an IL-2-dependent murine natural killer cell line, NKC3. There was a good correlation between the EIA and the bioassay (r = 0.998).

Biological Assay↗

[Bone disorder in long-term survival after gastrectomy with reference to bone mineral content].

To investigate post-gastrectomy metabolic bone disorder, the radial bone mineral content (BMC) was measured with 125I-photon absorptiometry in 131 long-term survivors, the postoperative periods ranged 3 to 30 years. Sixty-eight patients (52 per cent) showed abnormally low BMC levels compared with healthy controls. The 43 patients with total gastrectomy manifested a higher incidence of decreased BMC levels than did the other 88 patients with partial gastrectomy. In females, patients subjected to the Billroth II procedure manifested low BMC values. The extent of the decline in BMC was much higher in females than in males, and higher in totally gastrectomized patients than in partial gastrectomy group. At more than 10 years postoperatively many patients manifested markedly low BMC levels; in totally gastrectomized patients this finding was made at less than 5 years postoperatively. A significant correlation was found between the extent of the decreased BMC levels and the postoperative periods. Of the patients with decreased BMC values, 30 per cent of them gave histories of osseous symptom after gastrectomy, however, 70 per cent of patients were asymptomatic. Based on the results, in long-term survival treated by total or partial gastrectomy, many patients present an osteopenic status, however, the number of those with clinically manifested bone disease such as osteomalacia may be low.

Age Factors↗