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Biomedical subjects

K Shimamura

Publications and source records attributed to K Shimamura.

At least 163 records · Page 9Linked to original sources

The relaxation and Ca-pump inhibition in mesenteric artery of normotensive and stroke-prone spontaneously hypertensive rats.

The influences of low temperature and vanadate, both of which have been known to inhibit the Ca-pump activity of membranous systems of smooth muscle cells, on the relaxation of mesenteric artery of stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were studied. Relaxation was induced by the removal of extracellular Ca in high-K-depolarized preparations, so that the involvement of receptor kinetics and changes in membrane potential could be excluded. Relaxation was significantly slower in the preparation from SHRSP than in that from SHRSP. Low temperature prolonged relaxation in preparations from both SHRSP and WKY. No difference in the effect of low temperature was observed between the preparations, which showed Q10 values between 2.8 and 3.5 for 50 and 80% relaxation time. Sodium vanadate also prolonged the time course of relaxation in both preparations. No difference in the effect of sodium vanadate was observed between the preparations from WKY and SHRSP. These results suggest that Ca-pump activity is involved in the relaxation of K-depolarized smooth muscle of mesenteric arteries from both WKY and SHRSP. However, the difference in the pump activity may not contribute greatly to the difference in the relaxation of K-depolarized preparations by the removal of extracellular Ca.

Animals↗

Inhibition of bacterial adherence by nasopharyngeal secretions.

The role of secretory immunoglobulin (Ig) A in nasopharyngeal secretions in the adherence of Streptococcus pneumoniae and Hemophilus influenzae to nasopharyngeal epithelial cells was investigated in vitro. The adherence was remarkably reduced by treating bacteria with nasopharyngeal secretions, and the antiadhesive activity was significantly greater in nasopharyngeal secretions having secretory IgA antibody activity against bacteria than in those having no activity. Noticeable changes were not observed in the antiadhesive activity caused by absorption of IgG from nasopharyngeal secretions. Results suggest that secretory IgA in nasopharyngeal secretions is related to bacterial adherence and adds to the prevention of nasopharyngeal infections.

Antibodies, Bacterial↗

Caffeine-induced contraction of rat portal vein and effects of K-depolarization, Na-removal and low temperature.

Contribution of Ca influx from extracellular pool and Ca-release from store sites in caffeine-induced contraction of rat portal vein longitudinal muscle were examined. At 37 degrees C caffeine induced a phasic contraction and the contraction was inhibited by verapamil or in the absence of Ca. Under low temperature, it was not decreased remarkably by verapamil or by the removal of extracellular Ca. Na-removal potentiated caffeine-induced contraction in the absence of Ca. Caffeine-induced contraction was also potentiated by high-K-depolarization. These contractions were at both temperature inhibited greatly by ryanodine. Caffeine induced the burst of the action potential at 37 degrees C but it was not remarkable at 17 degrees C. These results indicate that both extracellular Ca influx and release of stored Ca are involved in the caffeine-induced contraction. However, dependence of the contraction on Ca sources are influenced by temperature, extracellular Na and membrane potential.

Action Potentials↗

Absorption and disposition of epithiosteroids in rats (1): Route of administration and plasma levels of epitiostanol.

1. Absorption and disposition of epitiostanol (EP) were determined following intramuscular (i.m.), intravenous (i.v.) and oral administration of 14C-epitiostanol (14C-EP) to rats. 2. When 14C-EP was administered orally, radioactivity was absorbed from the gastrointestinal tract and appeared in the systemic circulation, but no unchanged EP was detected in the plasma. EP was extensively metabolized by first-pass metabolism in the intestinal mucosa and liver, and because of the low biological activity when given orally, EP should be given by injection. 3. The EP plasma concentration/time curve following i.m. administration is analysed by a flip-flop model (ka less than kel), because the ka for EP remaining at the i.m. injection site was less than the kel for i.v. injection.

Administration, Oral↗

Breast cancer developing after chemotherapy for osteosarcoma: a case report.

A 24-year-old patient who developed breast cancer 16 years after chemotherapy for osteosarcoma is presented. She had no family history of cancer. She had also not had radiotherapy. She had been given chemotherapy consisting of VAOMT (vincristine 10.2 mg, cyclophosphamide 900 mg, mitomycin C 15.2 mg, chromomycin A3 25.8 mg) pre- and post-operatively in the treatment of her osteosarcoma. Careful long-term follow-up is required after treatment of malignant neoplasms because there is a possibility of developing a second malignancy.

Adult↗

Electron microscopic identification of the intracellular secretion pathway of human G-CSF in a human tumor cell line: a comparative study with a Chinese hamster ovary cell line (IA1-7) transfected with human G-CSF cDNA.

Using monoclonal antibodies specific for human granulocyte colony-stimulating factor (G-CSF), intracellular localization of G-CSF in a G-CSF-producing human tumor cell line (CHU-2) and its ultrastructural characters were described and compared with those of a Chinese hamster ovary cell line (IA1-7) transfected with human G-CSF cDNA. The CHU-2 line, which was derived from a poorly differentiated squamous cell carcinoma of the oral cavity, preserved the character of a poorly differentiated squamous cell carcinoma. In the CHU-2 cell line, there were few cells immunohistochemically positive for G-CSF under light microscopic analysis despite the high transcription level of G-CSF cDNA and secretion of G-CSF that were comparable with cDNA-transfected IA1-7 cells. Using electron microscopy, the reaction products were localized mainly in the perinuclear space (PNS) and rough endoplasmic reticula (RER) without dilation of the cisternae, but they were very rarely found in the Golgi complex and not at all in other intracellular organelles. In contrast, most cells were positive for G-CSF in the IA1-7 cell line. Reaction products in this cell line were also demonstrated in the PNS and RER without dilation of the cisternae. These immunohistochemical findings, in conjunction with the results of Western and Northern blot analysis, suggested that G-CSF was secreted via the PNS and RER without intracellular retention.

Animals↗

[Immunohistochemical Study of 3-methylcholanthrene inducible cytochrome P-450 in the stomach and liver--a guide of postoperative chemotherapy in gastric cancer].

Immunohistochemical determination of 3-methylcholanthrene (MC) inducible cytochrome P-450 (MC-P-450) was investigated in rat and human tissue, and its clinical availability was discussed. Induced by MC, MC-P-450 in rat liver and stomach was well stained immunohistochemically, showing clear contrast against control without induction. The staining intensity in the tissue was correlated with the amount of tissue MC-P-450 which was determined previously by electrophoretical and biochemical technics. By the same immunohistochemical method MC-P-450 in human liver and stomach was also detectable. The staining grade of MC-P-450 in human liver and stomach was different from each person. However, its intensities in liver and stomach in the same individual showed clear correlation with p less than 0.02. Since MC-P-450 in liver plays a major role in drug metabolism, the proof of correlation between staining degree of the resected stomach and hepatic tissue would provide useful clue in gastric cancer for postoperative administration of masked compounds activated by MC-P-450.

Animals↗

The role of bacterial adherence in otitis media with effusion.

Adherence of nontypable Haemophilus influenzae and Streptococcus pneumoniae to nasopharyngeal epithelial cells was investigated in vitro. Both strains had higher affinity to the epithelial cells of children than to those of adults. In children, the adherence was significantly greater in patients with otitis media with effusion than in normal subjects. Secretory IgA in nasopharyngeal secretions was found to have antibody activity against the bacteria. Adherence of both bacteria was significantly smaller in the group having secretory IgA antibody activity than in the group having no activity. These results suggest that bacterial adherence to the nasopharynx may play an important role in the pathogenesis of otitis media with effusion in children, and that secretory IgA in nasopharyngeal secretions may be related to the decrease of adherence.

Adult↗

Effects of Bay K 8644 on the spontaneous electrical and mechanical activities of the rat portal vein.

Effects of Bay K 8644 on the spontaneous electrical and mechanical activities of the rat portal vein were studied. Bay K 8644 enhanced contractions in amplitude and duration. Bay K 8644 prolonged the duration of the spontaneous spike potential bursts and increased the number of spike potentials in a burst. These results indicate that the increase in the amplitude and duration of spontaneous contractions of the rat portal vein induced by Bay K 8644 are mediated mainly by the facilitation of the membrane electrical activity.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

An autopsy case of a cystic variant of thymic carcinoma mimicking a thymic cyst.

An autopsy case of thymic carcinoma is reported. The surgically excised cystic tumour from a 38-year-old Japanese male mimicked a thymic cyst pathologically. After a clinical course of 6 years, postmortem examination disclosed extensive metastases, including cystic lesions lined by benign-looking squamous epithelium. This evidence suggested that the present tumour was not of the specific variants of thymic carcinoma and not a thymic cyst with malignant transformation.

Adult↗

Cadherin-mediated cell-cell adhesion and neurogenesis.

Cadherins constitute a molecular family which confers adhesive specificities on cells. Their expression is spatio-temporally regulated in embryos and the multiple types of cadherins are expressed in the nervous system. The inhibition of cadherin action with antibodies resulted in the perturbation of the histogenesis of neural tissues. The sites for determining the binding specificities of cadherins reside in their amino terminal 113 amino acid region. Possible roles of cadherins associated with these properties in neurogenesis are discussed.

Animals↗

Cadherin subclasses: differential expression and their roles in neural morphogenesis.

Cadherins homophilically bind cells. Thus, cells expressing identical cadherins adhere selectively to each other, and they do not randomly intermix with the cells expressing other types of cadherins in vitro. Neural tissues express multiple types of cadherins, and the expression of each cadherin type is spatiotemporally regulated within a tissue during development. This molecular family therefore could operate for the sorting of different cell types in the nervous system. The regulation of N-cadherin expression is also important for the early development of the neural tube. The ectopic expression of N-cadherin in Xenopus embryos, which was induced by mRNA injection, led to the disorganization of neural tube structures or the fusion of the neural tube to the epidermis. These results suggest that the precise regulation of cadherin expression at the quantitative as well as at the qualitative level si crucial for neural morphogenesis.

Animals↗

Relaxation of mesenteric artery of stroke prone spontaneously hypertensive rats by calcium removal.

1. The time courses of the relaxation, induced by removal of extracellular Ca2+, of K-depolarized mesenteric artery preparations from stroke prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were compared. 2. The time course of the decline in extracellular Ca2+ was estimated from the time course of the relaxation and the concentration-response curve of K(+)-depolarized preparations to Ca2+. The time course of the decline in the intracellular free Ca2+ concentration was also estimated from the reported relation between Ca2+ concentration and the contraction of skinned vascular smooth muscle. 3. The time course of relaxation was exponential, the curve being made up of three components. The time course was slower in preparations from SHRSP, especially the first component of the relaxation curve. 4. The time courses of the decline in the intracellular and extracellular Ca2+ concentrations were also exponential, being made up of three components and were also slower in the preparation made from SHRSP. 5. The wall and muscle layer of the mesenteric arteries used in the present experiments were significantly thicker in the SHRSP preparations. 6. Calculation of the half relaxation time, based on the diffusion of Ca2+ across the blood vessel wall, suggested that the slower relaxation in preparations from SHRSP is due largely to the thicker muscle layer, although differences in Ca2+ sequestration by the smooth muscle cells may also be involved.

Animals↗

Intranephron PGE2 production in stroke-prone spontaneously hypertensive rats.

To investigate whether intranephron prostaglandin E2 (PGE2) production in stroke-prone spontaneously hypertensive rats (SHRSP) differs from that in Wistar-Kyoto rats (WKY), we measured PGE2 accumulation rates in microdissected nephron segments from 4- to 6- and 12- to 14-wk-old male rats by radioimmunoassay. In both young and adult WKY, PGE2 accumulation was highest in the papillary collecting duct (PCD) and outer medullary and cortical collecting tubules, intermediate in the glomerulus (Glm), medullary and cortical thick ascending limbs of Henle's loop, and distal tubule, and negligible in the proximal tubule. PGE2 accumulation in adult WKY was severalfold higher than that in young WKY. PGE2 accumulation in adult and prehypertensive young SHRSP was significantly lower than that of respective WKY in most segments, whereas urinary PGE2 excretion was significantly higher in SHRSP than in age-matched WKY. Plasma arginine vasopressin concentrations in adult SHRSP were significantly higher than in WKY. PGE2 accumulation stimulated by 5 microM arachidonic acid was significantly lower in SHRSP than in WKY in most segments of young rats but was lower only in Glm and PCD of adult rats. PGE2 accumulation stimulated by 2 microM Ca2+ ionophore A23187 was significantly lower in most segments of adult and young SHRSP. These results indicate that a decrease in renal tubular PGE2 productive activities in SHRSP might not be caused by secondary adaptation to hypertension.

Aging↗

Pharmacokinetics of flomoxef in mucosal tissue of the middle ear and mastoid following intravenous administration in humans.

The pharmacokinetics of flomoxef in serum and in the mucosal tissue of the middle ear and mastoid were studied in 9 patients undergoing tympanoplasties. All patients received 1 g of flomoxef intravenously. Flomoxef levels in serum and in mucosal tissue were determined by a bioassay method. The peak value of mean concentrations of flomoxef in the mucosal tissue was 30.3 +/- 11.7 micrograms/ml at 10 min after the administrations. Pharmacokinetic analyses showed that the concentration of flomoxef in the mucosal tissue was over 1.56 micrograms/ml (which is the MIC90 for the common pathogens of otitis media) for more than 2 h and decreased parallel with serum concentration with a half-life of about 40 min.

Adolescent↗

Establishment of specific monoclonal antibodies against recombinant human granulocyte colony-stimulating factor (hG-CSF) and their application for immunoperoxidase staining of paraffin-embedded sections.

Detection of granulocyte colony-stimulating factor (G-CSF), one of the substances responsible for proliferation and differentiation of granulocytes, has been performed up to the present by use of the granulocyte colony-formation assay, because of the lack of a specific anti-G-CSF antibody. This has prevented the advancement of biological investigations of cell dynamics linked to G-CSF, e.g., cell localization of G-CSF and its pathophysiological changes. In the present work, two monoclonal antibodies (MAb), 1E7 and 4A6, against recombinant human G-CSF (rhG-CSF) were developed by cell hybridization between NS-1 myeloma cells and splenocytes from a mouse immunized with rhG-CSF. 1E7 and 4A6 were shown to be reactive with hG-CSF but not with other CSF (hGM-CSF, hIL-3, and mouse GM-CSF) by Western blot analysis. An immunoperoxidase staining method using these MAb was then established. This method was applicable to frozen sections, paraffin-embedded sections, and cells fixed with 4% paraformaldehyde. Positive staining for G-CSF was observed in tumor cells secreting G-CSF and also in Chinese hamster ovary (CHO) cells transfected with hG-CSF cDNA. However, no staining was seen in tumor cells secreting no G-CSF, untransfected CHO cells, lung fibroblasts, or bone marrow stromal cells after short periods of culture. These results confirmed the immunospecificity of MAb 1E7 and 4A6 and the validity of their application to immunohistochemistry using paraffin-embedded sections.

Animals↗

Pharmacological studies on 6-amidino-2-naphthyl[4-(4,5-dihydro-1H-imidazol-2-yl)amino] benzoate dimethane sulfonate (FUT-187). I: Inhibitory activities on various kinds of enzymes in vitro and anticomplement activity in vivo.

FUT-187, a newly synthesized compound, was studied on its inhibitory activities mainly on proteolytic enzymes, in comparison with those of FUT-175 and FOY-305, known serine protease inhibitors. FUT-187, as well as FUT-175 and FOY-305, had selective inhibitory activities on serine proteases including Clr, Cls, kallikrein, trypsin, plasmin and thrombin; its activities on these enzymes except Clr and pancreatic kallikrein were relatively lower than those of FUT-175 and FOY-305. Further studies were conducted focusing on complement-mediated reactions. In spite of its lower activities against Clr and Cls, inhibitions by FUT-187 on the complement-mediated hemolysis in vitro and in vivo were only a little weaker than or equivalent to that of FUT-175. FOY-305 was ineffective in these tests. Forssman shock in guinea pigs is known to be initiated by the activation of the complement system. The protective effect of intravenous or oral FUT-187 against this shock was definitely superior to that of FUT-175. Furthermore, FUT-187 inhibited changes accompanied with Forssman shock, such as increase in lung weight, the decrease in platelet counts and CH50, and histopathological changes. These results suggested that FUT-187 should be a more potent oral therapeutic agent than FUT-175 for various inflammatory diseases attributed to the excessive activation of the complement system followed by platelet aggregation.

Amylases↗