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S Arai

Publications and source records attributed to S Arai.

At least 379 records · Page 21Linked to original sources

[Clinical study of chemotherapy (PPM therapy) with cisplatin, peplomycin and mitomycin C in squamous cell lung cancer].

The effect of PPM therapy, consisting of cisplatin, peplomycin and mitomycin C, was evaluated in 15 cases of squamous cell lung cancer. Ten partial responses were achieved in primary cases and the response rate was 66.7%. Nephrotoxicity was well controlled with a continuous infused drip and FOM. The nausea and vomiting were reasonably well controlled with methylprednisolone and metoclopramide. Severe interstitial pneumonitis occurred in 5 cases (33.3%). PPM therapy is considered to be a very useful combination chemotherapy for squamous cell lung cancer but careful attention must be paid to pulmonary toxicity.

Aged↗

Mechanisms of in vivo generation of cytotoxic effector cells against tumor in tumor-bearing mice.

Our previous study showed that spleen cells from BALB/c mice bearing RL male 1 lymphoma inhibited the growth of RL male 1 lymphoma by the Winn-type adoptive transfer assay. Although this antitumor activity was mediated by the T-cell subset manifesting the surface phenotype of cytotoxic T-lymphocytes (CTLs), this antitumor activity of spleen cells was not detected by the in vitro cell-mediated cytotoxicity assay (4-h 51Cr release assay). The present study is concerned with the hypothesis that the maturation of the CTLs directed against RL male 1 may be arrested in spleens of the RL male 1-bearing mice and the differentiation into mature CTLs may occur at the tumor site; i.e., the immature CTLs (activated precytotoxic T-cells) may acquire the killing activity when they contact tumor cells at the tumor site. This report shows that BALB/c mice bearing the progressive RL male 1 lymphoma were able to generate CTLs against RL male 1 in the peritoneal cavities when the mice were inoculated i.p. with the irradiated RL male 1 cells. The cytotoxic activity of the peritoneal exudate cells of the RL male 1-bearing mice appeared 3 to 5 days after i.p. inoculation of the irradiated RL male 1 cells and rapidly decreased on day 7 after inoculation. In addition, spleen cells from the RL male 1-bearing mice after i.p. inoculation of the irradiated RL male 1 cells were not cytotoxic, suggesting a highly localized response. The cytotoxic effector cells induced in the peritoneal cavities consisted of T-lymphocytes and natural killer cells. Both cell types were simultaneously induced in the peritoneal cavities of the RL male 1-bearing mice. The T-cell subset mediating cytolytic activity against RL male 1 was shown to consist of Lyt-1+2+ T-cells which were defined by cytolysis with anti-Lyt-1 or anti-Lyt-2 antibody and complement. On the other hand, the normal BALB/c mice inoculated i.p. with the irradiated RL male 1 cells generated natural killer cells in the peritoneal cavities and spleens but the CTLs were not induced. The results from the present and previous studies suggest that precytotoxic or immature cytotoxic T-cells in spleens of the tumor-bearing mice migrate into the circulation and then mature CTLs develop at the tumor site.

Animals↗

A T cell leukemia line produces factor(s) that render rat neutrophils cytotoxic.

Proteose-peptone-induced intraperitoneal neutrophils from rats were activated in terms of tumor cytotoxicity by pretreatment with culture supernatants from a human T cell leukemia line, Jurkat (culture sup). Culture sup-treated neutrophils showed cytotoxicity against various tumor cell lines. The cytotoxicity of culture sup-treated neutrophils was dependent on the number of neutrophils and the concentration of culture sup. Cytostasis by activated neutrophils was observed very early in the assay incubation period (within 6 hr), but cytolysis first occurred at 24 hr after the start of incubation. Factor(s) in culture sup responsible for the activation of cytotoxic neutrophils were stable to temperature and pH treatments, and their molecular weight was higher than 10,000. The responsible factor(s) for activation of cytotoxic neutrophils were different from interleukin-2, serum-derived factor, and bacterial lipopolysaccharide.

Animals↗

Prediction of deformation in the potassium-arrested canine left ventricle using the finite element model.

A finite element model for the diastolic canine left ventricle based on large deformation theory has been developed. The myocardial stress-strain relation determined by the diastolic pressure-volume relation was used in this study. The ventricle was assumed as a homogeneous, isotropic, thick-walled solid of revolution with variable thickness. The predicted shapes based on the model were in close agreement with the shapes recorded by two-dimensional echocardiography. The stress calculated at the subendocardium was considerably larger as compared to that at the subepicardium. For example, at an intraventricular pressure of 10 cmH2O, the stress at the subendocardium was 80 g/cm2 and about four times larger than that at the subepicardium.

Animals↗

[Penetration of cefotaxime into human bone marrow blood].

Concentrations of cefotaxime (CTX) in bone marrow blood and venous blood were examined with the passage of time in 21 cases which received operations of bone and joint. Concentrations of CTX in bone marrow blood at 30 minutes of a single intravenous administration 2 g each of CTX were found to be 85.2 +/- 24.5 micrograms/ml. Concentration ratio of CTX in bone marrow blood to that in venous blood was reached the peak at 120 minutes after administration. Concentrations of CTX observed were higher than the MIC of CTX against major pathogens responsible for the postoperative infections in orthopaedic field. The CTX, therefore, is expected to have an effective antibiotic in prophylaxis.

Adolescent↗

Stimulation of procollagenase synthesis in human rheumatoid synovial fibroblasts by mononuclear cell factor/interleukin 1.

In order to define mechanisms regulating the synthesis of procollagenase in human rheumatoid synovial fibroblasts, the proteins synthesized by cultured cells were labeled with [35S]methionine. Labeled medium proteins were analyzed by SDS-PAGE directly and after immunocomplexing with a specific antibody to human fibroblast collagenase. Labeling of both the predominant form of the enzyme (Mr approximately 55 000) as well as a minor species (Mr approximately 61 000) was increased following incubation with the monokine, mononuclear cell factor/interleukin 1. The approximately 61 kDa form of the procollagenase appears to be a glycosylated form of the approximately 55 kDa precursor based on binding to Con A-Sepharose and decrease in the approximately 61 kDa form after culture in the presence of tunicamycin. Thus, mononuclear cell factor, homologous with interleukin 1, partially purified from monocyte conditioned medium increased incorporation of [35S]methionine into several medium proteins, including those complexed by the anticollagenase antibody. In the presence of mononuclear cell factor/interleukin 1, labeling of the procollagenase was increased 12-14-fold over control cultures incubated with medium alone. Therefore, one of the mechanisms involved in increase of collagenase activity in the medium of cultured synovial fibroblasts in the presence of mononuclear cell factor/interleukin 1 is a stimulation of enzyme protein synthesis.

Animals↗

Inhibition of mouse natural killer cytotoxicity by heparin.

The effect of heparin on mouse natural killer (NK) cytotoxicity was investigated. Heparin greatly inhibited NK activity at a concentration of more than 10 units/ml. Inhibition of NK cytotoxicity was observed only when heparin was present in the reaction mixture of the cytotoxicity assay. The results of kinetic study of NK inhibition and target-effector binding assay proposed the possibility that heparin inhibits NK cytotoxicity after the binding of effector cells to target cells. Dextran sulfate, the heparin analog, which has potent negative charge also had an inhibitory effect on NK activity. Fractionation of heparin on Sephadex A-25 column revealed the parallelism of the negative charge and the inhibitory effect of heparin on NK cytotoxicity. These results demonstrated that polyanion could modulate NK cytotoxicity.

Animals↗

Clinical usefulness of the (chloride-90)/phosphate ratio for distinguishing primary hyperparathyroidism from hypercalcemia due to other causes.

In order to obtain a good separation line between patients with primary hyperparathyroidism (1 degree HPT) and those with non-parathyroidal hypercalcemia (NPHC), serum chloride (Cl) and phosphate (P) concentrations were analyzed. Ninety-nine per cent of the patients with 1 degree HPT had a Cl/P ratio greater than or equal to 33, but 29% of patients with NPHC were also included in this range. When the (Cl-90)/P ratio was used to separate into two groups, 98% of the patients with 1 degree HPT had a ratio greater than or equal to 5.0, and 94% of the patients with NPHC had a ratio less than 5.0. From these results, while high sensitivity was achieved both with the Cl/P and (Cl-90)/P ratios, the (Cl-90)/P ratio provided higher specificity. Therefore we conclude that the (Cl-90)/P ratio was excellent in distinguishing 1 degree HPT from other types of hypercalcemia.

Adult↗

A heat-modifiable outer membrane protein carries an antigen specific for the species Yersinia enterocolitica and Yersinia pseudotuberculosis.

The outer membranes of gram-negative bacteria are considered to be of importance in host-bacteria interaction, in protective immunity, and occasionally in subclassification within a species. In this study, the outer membranes of several strains of Yersinia enterocolitica and Y. pseudotuberculosis were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). It was found that the appearance of the major proteins depended on the temperature at which they were solubilized in SDS. A protein was identified with the use of two-dimensional gels and preparative SDS-PAGE, which was equivalent to the "heat-modifiable protein" (protein II) of other Enterobacteriaceae species. A monoclonal antibody, 4G1, was generated against an isolated preparation of this Y. enterocolitica protein. This antibody was tested with whole cell bacterial antigens of 46 individual bacterial strains. The reactive strains included only Y. enterocolitica and Y. pseudotuberculosis. In addition, the reactivity of the 4G1 monoclonal antibody preparation could be absorbed only with Y. enterocolitica and Y. pseudotuberculosis, and not with other strains of bacteria. The reactivity of this 4G1 monoclonal antibody was also tested by the Western Blot technique. Six individual strains were tested: a Y. enterocolitica serotype 0:3, a Y. enterocolitica serotype 0:9, an Escherichia coli, a Salmonella typhimurium, a Shigella flexneri, and a Klebsiella pneumoniae. The 4G1 antibody reacted with only the proteins of the two Y. enterocolitica strains. In conclusion, the equivalent of the heat-modifiable protein was present in Y. enterocolitica and Y. pseudotuberculosis. Moreover, this protein also carried a species-specific antigenic determinant.

Absorption↗

Effects of changes in chamber geometry by chronic pressure-overload on wall stress and strain as studied in the potassium-arrested canine left ventricle.

We studied differences in stress and strain distributions within the left ventricular wall between the normal heart and the pressure-overload hypertrophied heart. Diastolic left ventricular pressure-volume (P-V) relations of both ventricles were recorded using isolated potassium-arrested heart preparations. The P-V relations thus obtained were analyzed based on the large deformation theory. In this study, the left ventricle was assumed to be a thick spherical shell and its wall was assumed to consist of a homogeneous elastic material. In the hypertrophied heart, the wall stress at every layer of the diastolic left ventricle was smaller than that of the normal heart except in the close vicinity of the endocardial surface when compared at the same left ventricular pressure. Therefore, we concluded that the occurrence of concentric hypertrophy under pressure-overload may contribute in reducing the preload of the hypertrophied ventricle. It was thus suggested that the preload reserve of the pressure-overload heart exceeded that of the normal heart.

Animals↗

Characterization of effector cells mediating antitumor activity in spleen cells of tumor-bearing mice.

Antitumor activity of spleen cells from BALB/c mice bearing RL male 1 lymphoma was studied. In the Winn assay spleen cells of the tumor-bearing mice inhibited the growth of RL male 1 lymphoma. This antitumor activity of spleen cells was not detected by the in vitro cell-mediated cytotoxicity assay (4-h 51Cr release assay). The effector cells in spleen cells were T-cells which manifested asialo GM1 on their cell surfaces and were radiosensitive (1000 rads). The analysis of T-cell subsets using Lyt markers showed that the effector cells expressed the Lyt-2 antigen with a small amount of the Lyt-1 antigen on their cell surfaces. In addition antitumor activity of spleen cells of the tumor-bearing mice was weak in the early stage of tumor growth, strong in the mid-stage, and disappeared in the late stage. The mechanisms of antitumor activity of spleen cells of the tumor-bearing mice are discussed.

Animals↗

[Fundamental and clinical studies on cefminox in the field of pediatrics].

Cefminox (CMNX, MT-141) is a new injectable cephamycin antibiotic, which was studied for its antibacterial activity, absorption and excretion after administration and clinical efficacy of patients with infections. The following results were obtained. Antibacterial activity The antibacterial activity of CMNX against 19 clinical isolates consisting of 11 species made the results that its activity against E. coli, P. vulgaris and C. jejuni was superior to CMZ and CEZ. Concentration in serum and urine CMNX was given intravenously to 3 groups at 20 mg/kg by one shot (2 cases), 40 mg/kg by one shot (2 cases) and 40 mg/kg by 1 hour drip infusion (1 case). The half-lives were between 1.15 to 1.80 hours. We obtained over 70% of its excretion to urine within 6 hours after injection. Clinical efficacy Clinical evaluation was made on a total of 18 patients with various infections, 11 of whom had underlying diseases. The result was excellent in 1 case, good in 11 cases, fair in 2 cases and poor in 4 cases, and the effective rate was 66.7%. Side effect Clinical and laboratory abnormal findings related to CMNX were not found. It is concluded that CMNX seems to be effective and safetive antibiotic in the field of pediatrics.

Abscess↗

Induction of interferon-gamma production by human natural killer cells stimulated by hydrogen peroxide.

Interferon (IFN)-inducing activity of hydrogen peroxide in human peripheral mononuclear cells was investigated. Among the mononuclear cells, purified nonadherent cells produced IFN, but not B cells and monocytes. The maximal titer of IFN by purified nonadherent cells was observed after a 72-hr cultivation in the presence of 10(-2) mM H2O2 without affecting their viability. Furthermore, the purified nonadherent cells, but not the unpurified mononuclear cells, showed an augmented cytotoxicity to K562 when stimulated with hydrogen peroxide. By using Percoll discontinuous density gradient centrifugation, peripheral blood nonphagocytic and nonadherent mononuclear cells were divided into the low and high density fractions for which natural killer (NK) cells and T cells were enriched, respectively. The NK-enriched low density fractions, but not the T cell-enriched high density fractions, showed IFN production by the stimulation of hydrogen peroxide. IFN production as well as large granular lymphocytes and HNK-1+, Leu-11+ cells of the NK-enriched fractions were abrogated by treatment of the cells with monoclonal antibody against human NK cells (HNK-1+) but not against T cells (OKT3) in the presence of complement. Moreover, hydrogen peroxide-inducing IFN production seems to be regulated by monocytes. The antiserum neutralizing IFN-alpha and IFN-beta failed to neutralize substantially IFN-produced NK cells. The treatment with either pH 2 or antiserum-neutralizing human IFN-gamma resulted in marked reduction, indicating that a major part of IFN was IFN-gamma. The purified nonadherent cells showed IFN production and augmented cytotoxicity when cultured separately from activated macrophages by opsonized zymosan; furthermore, both IFN production and enhancement of cytotoxicity were abrogated by catalase. These results suggest that both exogenous and endogenous hydrogen peroxide might be responsible for a part of immunoregulation.

Adult↗