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Biomedical subjects

S Arai

Publications and source records attributed to S Arai.

At least 361 records · Page 20Linked to original sources

Long-term results of open heart repair of ventricular septal defect.

Long-term follow-up results of 321 patients who underwent open heart repair of ventricular septal defect in our institute and have lived for more than five years were analyzed using questionnaires. The follow-up period was up to 24 years with an average of 12.9 years. The questionnaire mainly concerned the patient's state of health. Beside this, IQ was measured in 52 children, ECG was analyzed in 92 patients and heart catheterization was performed on 21 patients with preoperative severe pulmonary hypertension (PH). From this survey, it was ascertained that no deaths resulted from cardiac disorders; physical activity and development were satisfactory in nearly all patients; the scholastic achievement score was within the normal range in nearly all school children; among 30 live births from 24 adult female patients, two babies with simple cardiac anomalies were found and there remained very few patients suffering from residual PH, residual shunt or conduction disturbances. IQ as tested by individual intelligence tests was within the normal range in all children. On ECG, complete right bundle branch block with left anterior hemiblock was found in 9% and complete atrioventricular block in 7%. Amelioration of PH was achieved especially in those who underwent operations in their younger years.

Adolescent↗

Biochemical and hemodynamic changes in the hypertrophied dog heart subjected to chronic protein-calorie malnutrition.

Biochemical and hemodynamic changes were assessed in 13 dogs subjected to sub-coronary valvular aortic stenosis and chronic protein-calorie malnutrition (PCM). Red blood cell, hemoglobin, serum albumin, free fatty acids, blood glucose, cholinesterase and blood amino acid levels were measured. The dynamic geometry of the left ventricle (LV) was assessed with chronically implanted sonomicrometric piezoelectric crystals. Cardiac function was evaluated by mean velocity of circumferential fiber shortening (mean VcF) and the relationship between LV end-systolic pressure (LVESP) or LV wall stress (LVWst) and LV end-systolic diameter (LVESD). The following results were obtained: A decrease in body weight and increases in free fatty acids and 3-Methylhistidine were observed following long-term PCM. Mean VcF was not depressed in dogs subjected to PCM. The relationship between LVESP or LVWst and LVESD shifted downward and to the right after PCM, indicating reduced myocardial contractility. These findings suggest that the left ventricle in hypertrophied dog hearts subjected to PCM retains normal pump function, despite a low state in the myocardium.

Animals↗

Effect of paraquat on plasma fibronectin, serum free hydroxyproline, serum ceruloplasmin and lung collagen content in monkeys.

The purpose of this study was to characterize paraquat toxicity in monkeys and to determine the feasibility of using the monkey as an animal model for the study of paraquat-induced pulmonary fibrosis in humans. Sixteen Japanese monkeys (Macaca fuscata), more than 3.5 years of age, with bodyweight ranging from 3.2 kg to 10.2 kg, were randomly divided into two groups. They were administered paraquat dichloride (PQ) by injection (s.c.) at a dose of 2.0 mg/kg bodyweight (12 monkeys) or s.c. saline, at a dose of 0.2 ml/kg bodyweight (control group, 4 monkeys), every two days for a period of four to five times. Eight monkeys (66.7%) from the PQ treatment groups expired due to subchronic PQ toxicity from days 11 to 35. Four monkeys (33.3%) from the PQ treatment group and all four monkeys from the control group survived the observation period of 66 days. On day 66, all of the surviving monkeys were sacrificed and examined for possible histopathological changes and the lung hydroxyproline content was determined. Our results indicate that the concentration of free hydroxyproline and plasma fibronectin did not vary significantly. The serum ceruloplasmin for the monkeys of the PQ treatment groups was significantly increased from day 14 to 21, compared to the control group. Also the total lung collagen of both the expired and surviving monkeys in the PQ treatment groups was elevated significantly, compared to the control group. The monkeys can provide extensive opportunities for research on the mechanism and the treatment of PQ poisoning in man.

Animals↗

Distribution of cefodizime to exudate in the croton oil-induced rat granuloma pouch and its therapeutic effects on experimental infections in the pouch.

Cefodizime was compared with cefotaxime (CTX) in regard to its distribution to an inflammatory site (exudate in croton oil-induced granuloma pouch) of rats and its therapeutic effects on experimental infections in such pouches after intravenous injection. Cefodizime levels in rat serum and pouch exudate were higher than those of CTX, and the former compound disappeared from the serum and pouch exudate far more slowly than the latter. In the tests for therapeutic effects, cefodizime showed almost the same degree of inhibitory activity as CTX against growth in pouch exudate of Escherichia coli Ec-7, Proteus mirabilis Pm-428, and Serratia marcescens Sm-390 for which the minimum inhibitory concentrations (MICs) of cefodizime were equal to or greater than the CTX values, and such activity of cefodizime lasted for a longer period than that of CTX. These results suggest that the above pharmacokinetic features of cefodizime compensate for its MICs against organisms displaying lower values for CTX.

Animals↗

[Experience of cefuzoname in pediatric patients. Fundamental and clinical investigations].

Cefuzoname (CZON) was administered to 50 pediatric patients with infections, and the efficacy was investigated in 49 patients. The efficacy rate was 83.7% and the drug was evaluated to be highly effective for diseases in the pediatric field. The activity of CZON was especially good against Staphylococcus aureus, and the efficacy rate for 13 clinical isolates was 69.2%, which was comparable to that of cefotiam or cefazolin. CZON appeared to be useable alone in Gram-positive infections. It might be very powerful in the control of infections in secondary immunodeficiency.

Adolescent↗

In vitro antimicrobial activity of cefpirome, a new cephalosporin with a broad antimicrobial spectrum.

The in vitro activity of cefpirome (HR 810), a new cephalosporin antibiotic having a 2,3-cyclopentenopyridine group in the 3-position side chain, was compared with in vitro activities of 5 other cephalosporins. HR 810 showed a broad spectrum of antimicrobial activity against Gram-positive and Gram-negative bacteria when tested using 71 standard strains and 876 clinical isolates. HR 810 inhibited 70% of the clinically isolated Staphylococcus aureus and Staphylococcus epidermidis strains when used at 0.59-0.84 microgram/ml, 2- to 25-fold lower than values of reference antibiotics, and the compound was also highly effective against Enterococcus faecalis which is relatively resistant to most of the existing cephem antibiotics. The activity of HR 810 against Enterobacteriaceae members (11 species), based on its minimal inhibitory concentrations inhibiting 90% of bacterial growth (MIC90S), was the highest among the cephalosporins used. Especially against Enterobacter species and Citrobacter freundii, the MIC90S of the compound were 4- to 64-fold lower than the values of the other antibiotics. Against Pseudomonas aeruginosa, HR 810 was as active as cefoperazone, an antipseudomonal agent. The minimal bactericidal concentrations (MBCs) of HR 810 were equal to or only 2-fold greater than the MICs for most of 12 standard strains tested. The compound markedly decreased viable bacterial counts at its MICs, thus showing strong bactericidal activities. The in vitro activity of HR 810 was not affected by pH or human serum content of agar media, but the activity against Gram-negative bacteria was lowered as the inoculum size increased.

Cephalosporins↗

Quantifiable morphologic evaluation of paraquat pulmonary toxicity in rats.

The intent of this study was to detect paraquat (PQ)-induced, dose-dependent variations, in rat lungs, by analyzing several quantifiable morphologic parameters. Male Wistar rats (6-week old) received single doses (0, 7, 10, 25 or 40 mg/kg body weight) of PQ dichloride by sc injection. The parameters examined were number of alveolar type II cells, number of intra-alveolar free cells, total number of cells constituting the pulmonary interstitium, and alveolar wall thickness. Our maximum dose produced a marked decrease, 3 days post-injection, in the number of alveolar type II cells in contrast to the observed increases in all other dosage groups. These increases in other groups were inversely proportional to the increasing PQ dosages. All rats that received the maximum dose died within 4 days after injection and therefore could not be compared to the control group for our parameters after 6 days. After 9 days, the number of type II cells had decreased significantly in the 25 mg/kg group. The two highest dosage groups, on the third day, had significantly more intra-alveolar free cells. The total number of cells constituting the pulmonary interstitium in all groups increased in proportion to the increasing dosages from 3 to 9 days post-injection. In the 10 and 25 mg/kg groups, alveolar wall thickness was notably increased from days 6 to 9. PQ dosing produced dose-dependent variations in all of the parameters examined. This model of PQ-induced pulmonary toxicity may be useful in evaluating prophylactic or therapeutic agents.

Animals↗

Suppressive effect of human natural killer cells on Epstein-Barr virus-induced immunoglobulin synthesis.

The suppressive effect of human natural killer (NK) cells on Epstein-Barr virus (EBV)-induced immunoglobulin (Ig) synthesis by autologous B cells was investigated. By Percoll discontinuous density gradient centrifugation, low-density fractions enriched for NK cells were isolated from human peripheral blood lymphocytes. These NK-enriched fractions were added to purified autologous B cells in the presence of EBV, were cultivated for 8 days, and were examined for their suppressive effect on Ig synthesis by an enzyme-linked immunosorbent assay. The fractions markedly suppressed both IgM and IgG synthesis induced by EBV. It was possible to reduce the suppressive effect of NK-enriched cells by complement-dependent lysis of NK cells and Leu-11, but not by OKT3 monoclonal antibody, indicating that NK cells may be responsible for the suppression of Ig synthesis. Upon close examination of interferon (IFN) activity, it was revealed that the co-cultures of NK-enriched cells and EBV-infected B cells generated production of IFN-alpha, which might be produced by NK cells in response to EBV-stimulated B cells. Addition of anti-IFN-alpha but not anti-IFN-gamma serum almost completely abrogated the suppressive effect of NK-enriched cells on Ig synthesis, indicating that IFN-alpha produced are required for the NK cell-mediated suppression of Ig synthesis. However, addition of IFN-alpha into purified B cells showed no direct suppressive effect on EBV-induced Ig synthesis by B cells in the absence of NK cells. Nevertheless, NK cells when previously incubated with IFN-alpha and added to B cells showed a suppressor activity on Ig synthesis to a level higher than that of untreated NK controls. These results strongly suggest the possibility that NK cells display an interaction with EBV-infected B cells and produce IFN-alpha, which in turn activates NK cells. These activated NK cells suppress the Ig synthesis by B cells, which undergo transformation induced by EBV.

Antibodies, Monoclonal↗

Enhancement of the expression of a rat neutrophil-specific cell surface antigen by activation with phorbol myristate acetate and concanavalin A.

A monoclonal antibody against rat neutrophils, RP-1, was produced by hybridizing a mouse myeloma (P3-X63-Ag8.653) with BALB/c mouse spleen cells sensitized with peritoneal neutrophils from Wistar-King-Aptakeman/Hok rats. RP-1 specifically reacted to neutrophils and bone marrow cells from rats of various strains. The expression of an antigen reactive to RP-1 on rat peritoneal neutrophils was enhanced by stimulation with phorbol myristate acetate and concanavalin A. The experimental result that the expression of an antigen reactive with another anti-neutrophil monoclonal antibody was not enhanced by stimulation with phorbol myristate acetate indicates that the antibody-binding capacity of stimulated neutrophils was not nonspecifically enhanced. The enhancement of antigen expression was temperature dependent. A glycolytic inhibitor, 2-deoxy-D-glucose, and an inhibitor of intracellular calcium mobilization, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester hydrochloride, which inhibited hydrogen peroxide release from stimulated neutrophils, did not inhibit enhancement of the expression of an antigen reactive with RP-1.

Animals↗

Heterogeneous profiles of a factor that renders neutrophils cytotoxic obtained from a concanavalin A-stimulated spleen cell culture in partial purification process.

Concanavalin A (Con A)-stimulated rat spleen cells were cultured in a serum-free conditioned medium. This culture supernatant contained a certain factor(s) that renders neutrophil cytotoxic for various tumor cells. The factor was tentatively termed neutrophil-activating factor (NAF). Rat NAF was partially purified from the serum-free culture supernatant by using ion exchange chromatography of DEAE-Sephadex A-50, gel filtration of Sephadex G-100, and affinity chromatography of Con A-Sepharose 4B. NAF activity was eluted in broad fractions by the ion exchange chromatography and the gel filtration. Moreover, on the Con A column, some NAF activities were bound to the column, but other activities passed through the column. These results showed the heterogeneity or polydispersity of NAF activity in both molecular size and charge-based separation properties. Monoclonal antibodies were produced by fusing BALB/c myeloma cells (P3-X63 Ag8.653) with spleen cells from syngeneic mice immunized with partially purified NAF (pNAF) obtained from the gel filtration. Absorbent beads which were linked with one monoclonal antibody (ANAF-10) partially absorbed NAF activity from supernatants of a Con A-stimulated spleen cell culture. Further purification of pNAF was performed with the use of affinity chromatography of ANAF-10-linked Sepharose. Through these procedures, the NAF activity was concentrated about 10,000-fold. Heterogeneity of NAF activity, however, did not disappear in even this affinity chromatography. On the other hand, 125I-labeled material of the final product migrated to one major band corresponding with an m.w. of about 20,000 as determined by SDS-PAGE analysis, and NAF activity was detected in the same band.

Animals↗

Mechanism of radiosensitizing effect of chloride ion on E. coli.

Cells of E. coli capable of repairing DNA damage are sensitized to radiation in the presence of NaCl. However, the enhanced radiolethality was suppressed by the addition of compounds such as an amino acid to the irradiation buffer. The protective efficiencies of these compounds depend on their reactivities with Cl-.2 or OH.. ATP synthesis in the cells irradiated in the presence of NaCl was severely inhibited depending on the dose of irradiation. This reduced rate of ATP synthesis can account for the inhibition of protein, RNA and DNA synthesis in the irradiated cells with NaCl.

Adenosine Triphosphate↗

Beta-lactamase stability of cefpirome (HR 810), a new cephalosporin with a broad antimicrobial spectrum.

Cefpirome was highly stable to hydrolysis by various beta-lactamases, although it was hydrolyzed to some extent by R plasmid-mediated penicillinase of Richmond-Sykes type Va/b and by chromosomal cephalosporinases from Bacteroides species. The compound had a very low affinity for cephalosporinases from Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, and Proteus vulgaris. Cefpirome showed strong antimicrobial activity against eight beta-lactamase (cephalosporinase)-producing strains which have become resistant to broad-spectrum cephalosporins; especially against E. cloacae and C. freundii, it had the highest activity among the cephalosporins used. Its activity against ampicillin-resistant R plasmid-containing transconjugant isolates of Escherichia coli was as high as that against the recipient strain E. coli chi 1037. The inducer activity of cefpirome in S. marcescens and P. vulgaris increased dose dependently, whereas cephamycin derivatives showed high inducer activity at low concentrations. A relatively low affinity of cefpirome for beta-lactamases is considered to be one of the reasons for its high antimicrobial activity against such enzyme-producing strains. In addition, other factors such as good penetration through the outer membrane and affinity for the target sites may also be involved in the high activity of cefpirome.

Anti-Bacterial Agents↗

Heart rate at onset and termination of paroxysmal atrial fibrillation in apparently healthy subjects.

Eighteen paroxysms were documented on Holter electrocardiogram both at the onset and the termination of paroxysmal atrial fibrillation in 14 apparently healthy subjects. There were large inter- and intraindividual variations and no definite trend was observed in the time and duration of paroxysms. Heart rate at the onset of paroxysms was consistently higher than that at sinus rhythm immediately before atrial fibrillation started. There were 2 patterns in the sequence of heart rate during paroxysms. One was an almost constant heart rate during paroxysms, and the other was a trend toward a decrease in heart rate from the onset to the termination of paroxysms. The duration of paroxysms was within 2 hours in the former group and more than 2 hours in the latter group. There was a reverse correlation between heart rate at the termination of paroxysms and their duration.

Adult↗