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Biomedical subjects

S Kitagawa

Publications and source records attributed to S Kitagawa.

At least 163 records · Page 9Linked to original sources
PubMed1994

ACTH and phorbol ester stimulated redistribution of protein kinase C in human cortisol-producing adrenal adenoma.

We studied the steroidogenetic action and concomitant subcellular redistribution of protein kinase C (PKC) in cortisol hypersecreting adrenal adenoma cells obtained from two patients with Cushing's syndrome. Isolated adenoma cells were treated with 10(-9) M and 10(-6) M 12-O-tetradecanoyl phorbol-13-acetate (TPA) or 10(-6) M ACTH. Treatment of the isolated adenoma cells with TPA resulted in cortisol secretion equivalent to that with ACTH-treatment. Immunoblot analysis of PKC during treatment with ACTH or TPA showed that PKC beta translocated from cytosol to membrane. A small amount of PKC alpha, but not membrane-associated PKC alpha, was detectable in the cytosolic fraction. It appeared that TPA-induced cortisol secretion mimicked ACTH-induced cortisol secretion, and that PKC beta translocated from cytosol to membrane on stimulation by both ACTH and TPA. We suggested that ACTH-induced cortisol secretion in human cortisol hypersecreting adrenal adenoma is mediated by PKC beta activation.

Adenoma↗
PubMed1994

Preventive effects of magnesium on raised serum lipid peroxide levels and aortic cholesterol deposition in mice fed an atherogenic diet.

We examined the effects of various levels of magnesium intake on serum lipid levels and aortic cholesterol deposition in mice fed for 14 weeks on an atherogenic diet containing 10 per cent linoleic acid. During that time, the mice were given MgCl2.6H2O in drinking water at magnesium doses of 10, 50, 100, or 200 mg/kg/d. A magnesium dose of 50 mg/kg/d is approximately equivalent to the amount consumed in the normal daily diet. Throughout the experimental period, levels of both serum total cholesterol and lipid peroxides decreased relative to increases in the dose of magnesium, while levels of serum phospholipid, triglyceride, and high density lipoprotein (HDL)-cholesterol were unaffected. Levels of aortic cholesterol, particularly cholesteryl ester, decreased as the dose of magnesium increased. These findings indicate that adequate magnesium intake prevents cholesterol deposition in the aortas of mice fed an atherogenic diet, and that this was due to the inhibitory effect of magnesium on lipid peroxidation and its hypocholesterolaemic effect, suggesting in turn, that the antioxidative action of this element plays an important role in creating a defence against the development of atherosclerosis.

Animals↗
PubMed1994

[Prevalence estimation of urinary incontinence among non-institutionalized persons aged 60 and over in Japan].

In order to estimate the total number and the prevalence rate of persons experiencing urinary incontinence among the non-instutionalized, aged 60 and over in Japan, a questionnaire survey was conducted in 16 prefectures in December 1991. The questionnaires were distributed and collected by public health nurses in Health Centers. A total of 12,180 questionnaires were administered. There were 11,528 responses (response rate of 94.6%), of which 11,142 were analysed. The main results were follows; 1) Daily urinary incontinence occurred in approximately 4.1% of the men and 5.3% of the women living at home. 2) 6.2% of the men and 8.9% of the women living at home had regular urinary incontinence with at least one episode of leakage per month in the preceding 12 months. 3) The prevalence of urinary incontinence increased with age for both sexes. 4) The 95% confidence interval estimate for the number of non-institutionalized persons over 60 years old suffering from urinary incontinent incidents nearly daily was estimated to be from 305,000 to 351,000 in men and from 554,000 to 675,000 in woman. 5) The 95% confidence interval estimate for the number of non-institutionalized persons over 60 years old with urinary incontinence of at least one episode of leakage per 5 months was from 3,507,000 to 3,889,000 for both sexes. 6) In order to determine age-specific prevalence for urinary incontinence for all age groups, a sampling survey is needed. 7) Research emphasizing the assessment of preventive interventions necessary since incontinence is preventable and medical and surgical treatment options are available.

Aged↗
PubMed1993

Depth-dependent change in membrane fluidity by phenolic compounds in bovine platelets and its relationship with their effects on aggregation and adenylate cyclase activity.

The effects of phenolic compounds on membrane fluidity of bovine blood platelets were investigated by studies on the fluorescence anisotropies of diphenylhexatriene (DPH) and its ionic derivatives to clarify the relationship of these effects with the inhibitory effects of the compounds on aggregation. Among the phenolic compounds tested, monohydric phenols (phenol and two monosubstituted derivatives) decreased the fluorescence anisotropy of DPH, which is thought to be located within the hydrophobic core of the membrane, in concentration ranges in which they inhibited platelet aggregation. On the other hand, they had little or no effects on the fluorescence anisotropies of the ionic derivatives of DPH, which are thought to be located in the interfacial region of the lipid bilayer. Consistent with their effects on the fluorescence anisotropy of DPH, these monohydric phenols increased the intracellular cAMP concentration. Thus, these monohydric phenols may inhibit platelet function by stimulation of adenylate cyclase mediated by perturbation of the central region of the membrane lipid bilayer. On the other hand, pyrocatechol and pyrogallol, which have two and three phenolic hydroxyl groups and have much larger electron donor activities than the monohydric phenols tested, inhibited platelet function by a different mechanism, because they did not cause increase in either membrane fluidity or the cAMP concentration of platelets.

Animals↗
PubMed1993

Activation of the respiratory burst and tyrosine phosphorylation of proteins in human neutrophils: no direct relationship and involvement of protein kinase C-dependent and -independent signaling pathways.

Human neutrophils maximally stimulated with the optimal concentration (100 ng/ml) of phorbol myristate acetate (PMA), a direct activator of protein kinase C (PKC), for 5 min at 37 degrees C did not respond with superoxide (O2-) release to the later addition of PMA itself or the Ca2+ ionophore ionomycin. However, these cells did respond with enhanced release of O2- to the later addition of N-formyl-methionyl-leucyl-phenylalanine (FMLP) or concanavalin A (Con A). In these PMA-pretreated cells, an increase in cytoplasmic free Ca2+ ([Ca2+]i) induced by ionomycin was unaffected, whereas that induced by FMLP was inhibited by 50-60% and that induced by Con A was completely abolished. A 42-kDa protein was predominantly and consistently tyrosine-phosphorylated by FMLP, PMA and ionomycin with the different kinetics according to the stimuli. The dose-response curves showed that tyrosine phosphorylation and O2- release were stimulated in parallel by PMA, whereas tyrosine phosphorylation and an increase in [Ca2+]i, but not O2- release, were stimulated in parallel by FMLP or ionomycin. The potency of inducing tyrosine phosphorylation was ionomycin > FMLP = PMA, whereas the potency of triggering of O2- release was PMA > ionomycin = FMLP. UCN-01, a PKC inhibitor, inhibited O2- release and tyrosine phosphorylation induced by PMA, but not by FMLP or ionomycin. In contrast, pertussis toxin inhibited O2- release and tyrosine phosphorylation induced by FMLP, but not by PMA. Tyrosine kinase inhibitors (erbstatin and genistein) inhibited O2- release induced by FMLP, but not by PMA. However, both tyrosine kinase inhibitors did not impair FMLP- or PMA-induced tyrosine phosphorylation of a 42-kDa protein. Increased tyrosine phosphorylation of a 42-kDa protein was also detected in immature myeloid cells (HL-60 cells) stimulated by PMA, but not by ionomycin. These findings suggest that FMLP and Con A trigger the respiratory burst in human neutrophils by activating the definite pathway which include other signals than activation of PKC and an increase in [Ca2+]i; tyrosine phosphorylation of a 42-kDa protein is induced by the PKC-dependent and independent mechanisms according to the stimuli, and the PKC-independent and ionomycin-sensitive mechanism is inoperative in HL-60 cells; and tyrosine phosphorylation of a 42-kDa protein is unlikely to be causally related to activation of the respiratory burst.

Concanavalin A↗
PubMed1993

Tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor.

Tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) primed human neutrophils for enhanced release of superoxide in time- and dose-dependent manners. The priming effects of these cytokines were detected at 3 min and maximal at 10 min of preincubation. The potency of the maximal effect was TNF > GM-CSF > G-CSF. Exposure of human neutrophils to TNF, GM-CSF and G-CSF resulted in tyrosine phosphorylation of a 42-kDa protein and intracellular alkalinization in a dose-dependent manner. The dose-response curves for triggering of tyrosine phosphorylation and intracellular alkalinization by each cytokine were similar to those for priming the cells. The potency of the maximal effect on tyrosine phosphorylation was TNF > GM-CSF > G-CSF, whereas that on intracellular alkalinization was GM-CSF > TNF > G-CSF. Tyrosine phosphorylation was detected at 3 min and maximal at 5-10 min after stimulation with each cytokine. Tyrosine phosphorylation induced by TNF declined at 20-40 min, whereas that induced by GM-CSF or G-CSF was maintained for at least 40 min. Intracellular alkalinization induced by each cytokine required a lag time of 3-5 min and was sustained for at least 40 min. Tyrosine phosphorylation preceded or occurred concomitantly with intracellular alkalinization and priming of the cells. These findings indicate that tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by TNF, GM-CSF and G-CSF, and that these early events may, at least in part, mediate activation or priming of human neutrophils by these cytokines.

Dose-Response Relationship, Drug↗
PubMed1993

Immunohistochemical analysis of gastrointestinal carcinoids.

Clinicopathological and immunohistochemical analyses were performed on ten samples of gastrointestinal carcinoids resected in Ishikawa Prefectural Central Hospital. All samples showed positive reaction to chromogranin A. Serotonin was detected in 8 samples, somatostatin in 4 samples, gastrin in 2 samples. Glucagon/Glicentin in 1 sample, and PYY production in 2 samples. CEA production was detected in 8 samples, and microvascular invasion was observed in 6 of these 8 patients. The PCNA/cyclin labeling index (L.I.) of the cases with metastases was significantly higher than those without metastases. In conclusion, the expression of CEA and the PCNA/cyclin L.I. may be useful markers of the malignant potential of carcinoid tumors.

Antigens, Neoplasm↗
PubMed1993

Enhancement of aortic cholesterol deposition by dietary linoleic acid in cholesterol-fed mice: an animal model for primary screening of antiatherosclerotic agents.

We tried to develop an experimental model using mice for the primary screening of antiatherosclerotic agents. Male ICR strain mice were given a high-cholesterol diet supplemented with 10% linoleic acid for 14 weeks. Throughout the experimental period, weight gain of these mice was significantly inhibited as compared to that of control mice given a basal diet, but displayed a steady increase comparable to that of the high-cholesterol diet without linoleic acid. The cholesterol and linoleic acid-fed mice showed increased serum cholesterol and phospholipid levels, and decreased serum triglyceride and high-density lipoprotein-(HDL) cholesterol levels and lecithin/cholesterol acyltransferase (LCAT) activity, as well as a markedly increased lipid peroxide level which was a characteristic appearance in the serum of this mouse model. At the end of the experiment, uniform and significant increases in cholesterol, notably cholesteryl ester, were observed in the aorta. Also found were marked decreases in the aorta contents of desmosine and isodesmosine, which are cross-linking amino acids present only in the elastin. Histological observations showed accumulations of fatty droplets in the intima. These changes were much less in mice receiving a high-cholesterol diet without linoleic acid. In this mouse model, probucol prevented elevation of serum cholesterol, phospholipid, and cholesterol accumulation in the aorta. Increases in lipid peroxide level and decreases in LCAT activity were also prevented. These findings indicate that this mouse model is useful for primary screening of antiatherosclerotic agents with antioxidative activity.

Animals↗
PubMed1993

Suppression of allograft responses by combining donor alloantigen-specific intravenous presensitization with suboptimal doses of FK506.

C57BL/6 (B6) mice were injected i.v. with class I H-2-disparate B10.QBR spleen cells (10(7)/mouse). This regimen, termed "donor alloantigen-specific i.v. presensitization" (DSP), induced almost complete elimination of anti-B10.QBR mixed lymphocyte reaction/IL-2 production but did not affect the generation of CTL responses. Repeated (5 or 11 times) administration in vivo (over 7 or 18 days) of FK506 at suboptimal doses (0.75-1.0 mg/kg/day) failed to eliminate the capacities to exhibit MLR/IL-2 production and to generate CTL responses. Prolongation of skin graft survival was not induced by either of a single DSP or FK treatment (0.75-1.0 mg/kg/day, 11 times during 18 days) alone, but by the combination of these. Such combined treatment also resulted in almost complete reduction of CTL responses before (5 rounds of FK injection) or after (11 rounds of FK injection) recipients were engrafted with B10.QBR skin grafts. Under conditions in which lymphoid cells from mice receiving both treatments failed to generate CTL responses, the addition of recombinant IL-2 to cultures restored the CTL generation, suggesting that CTL precursors themselves are not attenuated by the combined treatment. Both prolongation of graft survival and suppression of CTL responses were obtained when the administration of FK506 was started before but not after DSP. Prolongation of graft survival could also be obtained in class I and II MHC-disparate combinations when the combined treatment was performed in a particular protocol. These results indicate that (1) DSP alone fails to prolong graft survival in class I and class I and II MHC-disparate combinations; (2) such failure is ascribed to the induction of CTL responses by CTL precursors and CTL helpers, both of which are DSP-resistant; (3) the administration of suboptimal doses of FK506 is not sufficient for the suppression of CTL responses, but is effective selectively for suppressing DSP-resistant CTL helpers; and (4) the combination of DSP with FK506 treatment in an appropriate protocol can thus prolong graft survival through the suppression of CTL-involved as well as CTL-independent graft rejection pathways.

Animals↗
PubMed1993

Effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on respiratory burst activity of neutrophils in patients with myelodysplastic syndromes.

The superoxide (O2-)-releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on FMLP-induced O2- release were investigated in neutrophils from 14 patients with myelodysplastic syndromes (MDS). The O2(-)-releasing capacity in MDS neutrophils varied from patient to patient. As compared with normal neutrophils, the O2(-)-releasing capacity in MDS neutrophils was increased in 9/14 patients, normal in three patients and decreased in two patients. There was no close relationship between the O2(-)-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The priming of neutrophils by rhG-CSF was not observed in five patients, whereas rhGM-CSF primed neutrophils from all patients. The priming effect of rhGM-CSF was consistently greater than that of rhG-CSF in each patient. The intravenous administration of rhG-CSF (300 micrograms/body) to two MDS patients showed an increase in the peripheral blood neutrophil count and enhancement of neutrophil O2- release. These findings demonstrate that the neutrophil O2(-)-releasing capacity in MDS varies from patient to patient and is not always impaired, and that rhGM-CSF is able to prime neutrophils which never respond to rhG-CSF.

Adult↗
PubMed1993

Altered vasoconstrictor responsiveness in vitamin D-induced arteriosclerotic rat aortas.

This investigation was undertaken to characterize the vasoconstrictor responsiveness in aortas isolated from a rat model of arteriosclerosis induced by vitamin D2 (VD) administration followed by feeding with a high-cholesterol diet. Cumulative contractile responses to KCl, noradrenaline and serotonin in thoracic aortic strips isolated from arteriosclerotic rats were slightly augmented in concentrations lower than the EC50 value of each agent and rather attenuated in their higher concentrations as compared with those from normal rats. Maximum contractions to the agonists were markedly attenuated in arteriosclerotic aortas; the degree of attenuation was greater in rats treated with a combination of VD and cholesterol than in those treated with VD alone. There was a significant negative correlation between the maximum contraction to KCl, noradrenaline or serotonin and the content of calcium or cholesterol ester in aortas. Removal of endothelium markedly enhanced sensitivity and contractility to the agonists in aortic strips from normal rats, whereas the same procedure only slightly enhanced them in aortic strips from arteriosclerotic rats. These results indicate that in arteriosclerotic rat aortas, contractile responsiveness to agonists of vascular smooth muscle cells is impaired with deposition of calcium and cholesterol, and they suggest that augmentation of contractile responses to the agonists in lower concentrations is due to impairment of endothelial function.

Animals↗
PubMed1993

Effects of cholesterol loading on autoimmune MRL-lpr/lpr mice: susceptibility to hypercholesterolemia and aortic cholesterol deposition.

Autoimmune MRL-lpr/lpr (MRL/l) mice, with a systemic lupus erythematosus-like disease, were shown to spontaneously develop hyperlipidemia and yet be susceptible to diet-induced hypercholesterolemia and aortic cholesterol deposition. Control animals on a basal diet showed significant increases in the serum total cholesterol, phospholipids, triglycerides, high density lipoprotein (HDL)-cholesterol and lipid peroxide levels, but a significant decline in the serum lecithin: cholesterol acyltransferase (LCAT) activity compared to those of 5-week-old mice. Animals on the high-cholesterol diet showed a rapid rise in serum total cholesterol to a plateau level (800 mg/100 ml) that was approximately 2.5 times higher than that in the control animals on a basal diet. However, the levels of serum triglycerides, HDL-cholesterol and lipid peroxides significantly decreased (by 61%, 23% and 53%, respectively) compared to those of the control animals, whereas LCAT activity and phospholipid level were not affected. The aortic contents of total cholesterol, free cholesterol and cholesteryl ester were significantly higher (by 35%, 36% and 31%, respectively) in animals fed the high-cholesterol diet than the control animals. These findings suggest that MRL/l mice are susceptible to diet-induced hypercholesterolemia and aortic cholesterol deposition.

Animals↗
PubMed1993

Transient wheeze. Eosinophilic bronchobronchiolitis in acute eosinophilic pneumonia.

The clinicopathologic features of five patients with acute eosinophilic pneumonia who presented with transient wheeze as well as acute onset of high fever, severe hypoxemia, and diffuse pulmonary infiltrates are described. Eosinophilic pneumonia was diagnosed by bronchoalveolar lavage and transbronchial lung biopsy. The illness resolved rapidly with or without corticosteroid therapy. No relapse occurred. To characterize the transient wheeze, a transbronchoscopic bronchial biopsy and pulmonary function tests were performed. Specimens of bronchial wall revealed eosinophil infiltration into the bronchial mucosa. Pulmonary function tests demonstrated reduced diffusing capacity and small airway dysfunction. These findings suggested that eosinophil infiltration into the bronchial mucosa might temporarily cause transient wheeze, different from bronchial asthma, due to small airway dysfunction in acute eosinophilic pneumonia.

Acute Disease↗
PubMed1993

Colonic submucosal tumors: a new classification based on radiologic characteristics.

OBJECTIVE: Despite advances in gastrointestinal radiologic techniques, findings from barium enema studies cannot be used reliably to predict the histologic nature of a colonic submucosal tumor. Therefore, we generated a new and comprehensive classification system for all colonic submucosal tumors based on a correlation between their radiologic characteristics and their histopathologic features. MATERIALS AND METHODS: Between 1978 and 1990, 89 patients had 95 colonic submucosal tumors diagnosed on the basis of barium enema studies and confirmed by biopsy or surgery. Of these, 39 patients (44%) were symptomatic and 50 patients (56%) were asymptomatic. Single lesions (82 cases) and multiple lesions (12 cases of lymphoma and one case of blue rubber bleb nevus) were observed. The 95 lesions included 21 carcinoids, 27 malignant lymphomas, 17 lipomas, 10 lymphangiomas, six leiomyosarcomas, five leiomyomas, and nine others. We analyzed the radiologic findings and classified these lesions according to their appearance. RESULTS: All tumors were classified on the basis of their morphologic appearance into five types: (1) wide-based sessile lesion with gradually sloping margin and smooth surface (17 cases); (2) wide-based sessile lesion, more polypoid than the first type, with a smooth surface, with or without a central depression (49 cases); (3) wide-based sessile lesion with lobulated surface (six cases); (4) pedunculated lesion with smooth or granular surface (17 cases); (5) unclassified, not any of the previously mentioned types, may be diffusely stenotic or aneurysmal (six cases). The most common finding was the wide-based sessile lesion with a smooth surface and a possible central depression; next most common was the wide-based sessile lesion with gradually sloping margin and smooth surface; next was the pedunculated lesion with a smooth or granular surface. Eighty-six percent of the lesions were single; 14% were multiple. Histologic confirmation revealed mainly lymphoma (29%) and carcinoid (22%), of which the most common finding was a wide-based sessile lesion with a smooth surface, with or without a central depression. CONCLUSION: This new classification based on radiologic characteristics covers all varieties of colonic submucosal tumors. It can serve as a guideline for predicting a specific diagnosis of a colonic submucosal tumor on the basis of radiologic findings.

Adolescent↗
PubMed1993

[Plasma exchange failures in two patients with thrombotic thrombocytopenic purpura].

We treated two patients with thrombotic thrombocytopenic purpura (TTP) with multiple plasma exchanges for a short period. Following 6 plasma exchanges during 11 days in patient 1 and the 8 exchanges during 13 days in patient 2, consciousness disturbance and thrombocytopenia improved with a decrease in serum lactate dehydrogenase (LDH) levels in both patients. However, thrombocytopenia rapidly progressed with a rise of serum LDH levels after a few days from cessation of the treatment. They received a few rounds of plasma exchange without beneficial effects and eventually died of massive hemorrhage. The clinical course of these patients indicates that some patients with TTP are refractory to repeated plasma exchanges for a short period. It seems important to determine the target point in blood chemistry values such as the LDH level for plasma exchange at which the treatment could be discontinued without causing relapse of TTP.

Aged↗
PubMed1993

Changes in cytoplasmic pH in platelets activated through the high- and moderate-affinity receptor pathways by highly purified human alpha-thrombin.

Platelets in plasma were loaded with the probe BCECF/AM, and changes in cytoplasmic pH levels induced by highly purified human alpha-thrombin (2900 NIH U/mg) were studied in washed platelets having high- and moderate-affinity receptors and in platelets from which the high-affinity alpha-thrombin receptor had been removed by treatment with Serratia marcescens protease. In intact platelets, cytoplasmic acidification reached a maximum within 2 minutes of -0.072 +/- 0.009 pH units at 0.3 nmol/L alpha-thrombin concentration (0.03 U/ml). Cytoplasmic pH values were higher at both lower and higher alpha-thrombin concentrations and were significantly (p = 0.018) higher at 2 nmol/L alpha-thrombin, which induced -0.037 +/- 0.013 pH units of acidification. Five nanomoles of alpha-thrombin, however, induced cytoplasmic alkalinization of +0.027 +/- 0.033 pH units. In platelets lacking the high-affinity receptor where there is a 10 to 20-fold reduction in sensitivity to alpha-thrombin, acidification reached a maximum of -0.175 +/- 0.033 pH units at 2 nmol/L alpha-thrombin, but alkalinization was observed at 5 nmol/L (+0.038 +/- 0.025) and 10 nmol/L (+0.042 +/- 0.007) alpha-thrombin. These results show that the transition from acidification to alkalinization occurs in the same range of alpha-thrombin concentrations (2 to 5 nmol/L) in both preparations, despite the rightward shift in sensitivity caused by the absence of the high-affinity receptor. However, the maximum acidification reached in control platelets (-0.037 pH units at 2 nmol/L) was much less than the value obtained in platelets lacking the high-affinity receptor (-0.175 pH units at 2 nmol/L alpha-thrombin).(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗