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Biomedical subjects

S Kishimoto

Publications and source records attributed to S Kishimoto.

At least 451 records · Page 25Linked to original sources

Therapy of congestive heart failure with orally administered taurine.

The clinical efficacy of 2 gm BID of oral taurine (2-aminoethane sulfonic acid) was studied in 24 patients with congestive heart failure (CHF). We expressed the severity of CHF by a score based on clinical signs and symptoms and on roentgenographic data. The maximum possible score, corresponding to the worst CHF, was 23 points. How much the 24 patients improved after receiving taurine for four or eight weeks was estimated by the difference between their pretreatment and posttreatment scores. In 19 of the 24 patients, taurine was effective. In the group as a whole, mean (+/- SEM) scores fell significantly, from 7.3 +/- 0.6 before treatment to 4.4 +/- 0.5 after treatment. Thirteen of the 15 patients who were designated as New York Heart Association (NYHA) functional class III or IV before receiving taurine could be designated as class II after they completed the study. This pilot study should prompt further investigation into the possible use of taurine in the treatment of patients with CHF.

Administration, Oral↗

Analysis of therapeutic effect in experimental chemoimmunotherapy for rat ascites tumor.

The lyophilized, squalene-treated Nocardia rubra cell wall skeleton (N-CWS) was confirmed to produce tumoricidal peritoneal macrophages resulting in inhibition of tumor growth when injected locally into the syngeneic ascites fibrosarcoma, AMC 60 in ACI/N rats. Furthermore, N-CWS was found to augment therapeutic effect when administered repeatedly after a single local injection of mitomycin-C (MMC). To analyze the effects, various in vitro cytolysis assays were performed using N-CWS-activated peritoneal macrophages. When tumor target cells were exposed in vitro to MMC, the resulting cytolysis in the presence of N-CWS-activated macrophages was similar to cytolysis of intact target cells. On the other hand, when N-CWS-activated macrophages were exposed to MMC, the tumoricidal activity was lost significantly, depending on exposure to MMC. When tumor target cells and N-CWS-activated macrophages were simultaneously exposed to MMC, tumor-cell cytolysis was strikingly depressed. In the final experiment, combined injection of MMC and N-CWS into the ascites tumor resulted in remarkable increases not only in peritoneal exudate cell number, but also in in vitro tumoricidal activity of peritoneal macrophages as compared to those induced by either agent alone. In addition, the production of tumoricidal macrophages by IP injection of MMC alone was also noticeable, as described previously. These results possibly indicate the involvement of macrophage activation in induction of therapeutic effect in chemoimmunotherapy.

Adjuvants, Immunologic↗

In vitro tumor cell killing by peritoneal macrophages from mitomycin C-treated rats.

The local cellular response induced by intraperitoneal injection of mitomycin C was examined in terms of cell-mediated cytotoxicity for tumor cells. An in vitro cytolysis assay involving 125I-iododeoxyuridine-labeled tumor target cells revealed that treatment of normal ACI/N rats (200 g) with a single intraperitoneal injection of mitomycin C (50, 100, or 200 micrograms) induced tumoricidal macrophages in the peritoneal cavity. The tumoricidal activity was dependent on the dose of mitomycin C injected and it was detectable as early as 1 day after the intraperitoneal injection of mitomycin C. In addition to the increased tumoricidal activity, the functional activities of the peritoneal macrophages were found to be increased with respect both to uptake of 2-deoxy-D-glucose and to phagocytosis of latex beads. Additional experiments excluded the possibility that the tumor cell cytolysis was the result of direct cytotoxicity by mitomycin C that might have been incorporated in the peritoneal macrophages or of nutrient depletion in the medium during the cytolysis assay. Furthermore, endotoxin contamination of the mitomycin C, which might have produced the activated macrophages, was not detected. The mechanism by which mitomycin C injected intraperitoneally induced the tumoricidal macrophages locally remains uncertain; however, it is possible also in clinical situations.

Animals↗

Gastric acid secretion, serum gastrin and parietal cell histology in hyperthyroidism.

A decrease in MAO by gastrin stimulation was observed in 13 of 20 hyperthyroid patients. Five of these 13 cases had achlorhydria. The decrease in gastric acid secretion had no relation to the duration of symptoms, serum T3 and T4 levels, serum antithyroglobulin antibody levels and serum antithyroid microsomal antibody levels. Gastroscopy with biopsy was performed in 17 cases. In patients with achlorhydria, macroscopic and histological atrophy was not observed in the body, and parietal cells were present and their succinic dehydrogenase activity was normal. Electron microscopy of the parietal cells of patients with achlorhydria showed that their cells were similar to those in the resting state of healthy subjects with the ability to secrete normal amounts of gastric acid. These findings demonstrate that the decrease in gastric acid secretion in hyperthyroidism is not caused by any structural changes in the gastric mucosa but by functional suppression. In the present experiment, this suppression was found resistant to gastrin. A rise in serum gastrin level was observed in 8 cases. Either achlorhydria or marked hypoacidity was found in 6 cases with the level more than 400 pg/ml. The HCl administration temporarily lowered elevated gastrin levels, and feedback inhibition by HCl was found to be maintained. A rise in gastric pH was considered to be one of the prerequisites for an increase in serum gastrin level.

Adolescent↗

Gastric acid secretion, serum gastrin and parietal cell histology in rat hyperthyroidism.

Experimental hyperthyroidism was produced in rats by thyroxin injection, and changes in gastric acid secretion and serum gastrin level were determined to analyze the relation between these changes and hyperthyroidism. Administration of thyroxin to two groups of rats-20 micrograms per 100 g of body weight for 20 days and 75 micrograms for 7 days-brought about significant increases in serum T3 level, gastric pH and serum gastrin level. An increase in gastric pH took place later than that in serum T3 level; this time lag implies that a decrease in acid secretion was not caused by an direct effect of thyroxin on the parietal cell but by its secondary effect. In the T4-injected rats with decreased gastric acid secretion, the parietal cell remained normal in form and succinic dehydrogenase activity was also normal. The electron microscopical observations showed nothing abnormal in the parietal cells. These findings suggest that a decrease in acid secretion was not due to any structural changes in the gastric mucosa but to functional suppression. The serum gastrin level rose in correlation with an increase in gastric pH and fell by HCl administration to the stomach. Feedback inhibition by pH remained in the G cell.

Animals↗

Induction of 19S IgM secretion in a murine pre-B cell line, 70Z/3, by cell hybridization with non-secreting myeloma cells.

Somatic cell hybrids were prepared between the TK-deficient variant of murine pre-B cell line, 70Z/3, cells and the HGPRT-deficient variant of non-secreting myeloma cells. Several hybrid clones which secreted IgM but did not express surface IgM were isolated. LPS stimulation did not induce the expression of surface IgM. SDS-PAGE analysis indicated that the IgM secreted by one of the hybrid clones was a 19S pentamer and that the size of its mu-chains was the same as that of mu-chains from MOPC 104E myeloma IgM. Two-dimensional gel electrophoresis of biosynthetically labeled immunoglobulin showed that the same pattern was obtained with kappa-chains from two hybrid clones and from the LPS-induced 70Z/3 cells. The result showed that cell hybridization could induce L-chain synthesis in the pre-B cell line. Anti-idiotypic antibody against the secreted IgM was prepared and it was shown that the surface IgM expressed on all LPS-stimulated 70Z/3 cells bore the same idiotype. Those results indicated that the specificity commitment has already occurred in 70Z/3 cells.

Animals↗

A glycopeptide containing 15 amino acid residues derived from hepatitis B surface antigen particles: demonstration of immunogenicity to raise anti-HBs in mice.

The major polypeptides composing hepatitis B surface antigen (HBsAg) particles are P-I and P-II. P-II shares the same amino acid sequence as P-I and contains an additional carbohydrate moiety of mol. wt approximately 5000. When a purified preparation of P-II was digested with Nagarse and then with Pronase P, it gave rise to a glycopeptide containing 15 amino acid residues and the carbohydrate moiety of P-II. The N-terminal amino acid sequence of the glycopeptide was determined to be Lys-Pro-Thr-Asp-Gly-Asn-. The polysaccharide moiety contained 5 moles of N-acetylglucosamine and was connected with Asn at the sixth position from the N-terminus. When mice were immunized against this HBsAg glycopeptide, they raised humoral antibodies which bound to each of three preparations of P-I derived from HGsAg particles of subtypes adw, adr and ayw, thereby indicating that the sequence of 15 amino acids in the glycopeptide would constitute a common antigenic structure of HBsAg.

Amino Acid Sequence↗

The regeneration of cholinesterase-positive structures in the process of burn wound healing in the skin of the guinea-pig.

The regeneration of acetylcholinesterase-positive structures was studied during the process of third-degree burn wound healing in the skin of guinea-pigs. The procedure in this study generally followed the histochemical thiocholine technique of Karnovsky and Roots (1964) with slight modification. Acetylcholinesterase activity in the skin was found to disappear from the burn wound including its margin within 14 days post burn. True regeneration of acetylcholinesterase activity became visible after 21 days post burn. The cholinergic fibres reinnervating arterioles became visible on the twenty-first day, and thereafter gradually increased in number and staining intensity at the deep region of scar margins. The cholinergic fibres detected at the upper region of the scar centre on the twenty-first day disappeared on the twenty-eighth day. Such denervation of the cholinergic fibres may be elicited by the absence of the target organs or by a dense collagenous scar which induces degenerative changes in regenerated nerves. The denervation of cholinergic nerve fibres occurred in association with degeneration of the target organs. On the other hand, the regeneration of the cholinergic nerve fibres was not always associated with the regeneration of the target organs, but occurred later than that of the target organs.

Acetylcholinesterase↗

The regeneration of the sympathetic catecholaminergic nerve fibers in the process of burn wound healing in guinea pigs.

In the present study, morphological alterations of cutaneous catecholaminergic nerve fibers in the process of burn wound healing have been investigated by using glyoxylic acid induced fluorescence histochemistry. The sympathetic denervation is detected within 48 hr after burns as well as in various excisions. The regenerating sympathetic fibers are observed on the 7th day after burns. These regenerating fluorescent fibers seem to develop in accordance with the regeneration of blood vessels in the wound margins at various stages of healing. Regenerating sympathetic fibers gradually increase in number and the maximum density of these fibers is found approximately at 2 weeks after burns. Thereafter, the density of the fibers gradually decreases to less than that of sympathetic innervation of intact skin. On the 14th day after burns, dense regenerating fibers are observed around the regenerated arterial vessels in the deep granulation tissue of the wound margins. These fibers may correlate with the degeneration of regenerated blood vessels in the center of the wound because of contracting the blood vessel of the wound margins. Moreover, dense collateral sprouting of regenerating fibers is observed around the degenerative blood vessel in the center of the wound on the 16 day after burns. This sprouting occurs not because of searching after a new target organ following the degeneration of the target organ but because of playing important roles in certain functions during wound healing.

Animals↗

Apparent heterogeneity of human megakaryocyte colony- and thrombopoiesis-stimulating factors: studies on urinary extracts from patients with aplastic anaemia and idiopathic thrombocytopenic purpura.

Megakaryocyte colon-stimulating factor (MEG-CSF) in the urinary extracts from patients wit aplastic anaemia (AA) revealed two distinct peaks of activity on Sephadex G-200 gel filtration with apparent molecular weights of 155,000 and 76,000. Both fractions induced significant thrombocytosis in peripheral blood and megakaryocytosis in the spleen of rats. Heterogeneity of MEG-CSF was also found in the extracts from the urine of patients with idiopathic thrombocytopenic purpura. The higher molecular weight MEG-CSF was significantly reduced when the gel filtration was performed under the dissociating conditions. Ion-exchange chromatography indicated that the higher molecular weight MEG-CSF had a different charge from the lower molecular weight MEG-CSF. These results suggest that the apparent heterogeneity of MEG-CSF is due to interaction of MEG-CSF with other proteins in the urinary extracts.

Anemia, Aplastic↗

IgD-plasma cell leukemia associated with pyroglobulinemia and pyroglobulinuria. New types of pyroglobulin and cytoplasmic fibrils.

New pyroglobulin variants were found in a patient with a typical plasma cell leukemia. One was found in the urine and proved to be a variant of Bence-Jones' protein with a molecular weight of approximately 68,000. The other was found in the serum and appears to be the myeloma protein of IgD. Furthermore, an ultrastructural study disclosed myeloma cells in both peripheral blood and bone marrow to have cytoplasmic fibrils which might be unique for plasma cell leukemia.

Bence Jones Protein↗

Bile acid synthesis by long-term cultured cell line established from human hepatoblastoma.

Bile acids in the spent medium for the cell culture were analyzed by gas-liquid chromatography and gas-liquid chromatography-mass spectrometry to determine whether human hepatoblastoma cell line could synthesize bile acids. Cholic, chenodeoxycholic, and lithocolic acids were found in the culture medium, and a portion of chenodeoxycholic acid and all of lithocholic acid were sulfated. Since the cells had been cultured in serum-free medium, it is clear that the bile acids were newly synthesized and sulfated by the cultured cells. Chenodeoxycholic acid was the main bile acid in the medium, suggesting that the cell line might predominantly synthesize chenodeoxycholic acid. On the other hand, the cells had fetal or hepatoma characters such as marked alpha-fetoprotein production. These results suggest that fetal or hepatoma type bile acid metabolism might occur in the cell line, and that the established cell line could be an useful in vitro model for the study of bile acid metabolism in hepatoma.

Animals↗