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Biomedical subjects

G Kajiyama

Publications and source records attributed to G Kajiyama.

At least 19 recordsLinked to original sources

The level of a transcription factor Sp1 is correlated with the expression of EGF receptor in human gastric carcinomas.

The expression of the transcription factor Sp1 and EGF receptor (EGFR) was examined on human gastric carcinoma cell lines and gastric carcinoma tissues as well as corresponding normal mucosa in order to clarify the mechanism of overexpression of EGFR gene without gene amplification. All 7 carcinoma cell lines expressed Sp1 mRNA, the levels of which were closely correlated with the expression of EGFR mRNA except for one cell line. The gel retardation analysis revealed that the levels of Sp1 mRNA were parallel to its DNA binding activities. In 18 surgical cases, 12 tumors expressed Sp1 mRNA at higher levels than normal mucosa. The cases with overexpression of Sp1 showed the high level of EGFR mRNA. These results suggest that overexpression of Sp1 in tumor cells may induce overexpression of EGFR without gene amplification in human gastric carcinomas.

Adult

Flow cytometric DNA analysis of gastric smooth muscle tumors.

BACKGROUND: To better understand the malignant grade of gastric smooth muscle tumors, the DNA content of these tumors was studied. METHODS: In 43 patients with gastric smooth muscle tumors, the cellular DNA content was determined by flow cytometry and compared with the histologic classification and the prognosis. RESULTS: Flow cytometry indicated that all 21 leiomyomas and 9 of the 10 low-grade leiomyosarcomas were diploid; 10 of the 12 high-grade leiomyosarcomas were aneuploid. All patients with leiomyomas and 8 of the 11 patients with diploid leiomyosarcomas had neither local recurrence nor metastasis. By contrast, 8 of the 10 patients with aneuploid leiomyosarcomas died of their disease (mean survival, 41 months; range, 18-78 months). CONCLUSIONS: These results indicate that the DNA ploidy pattern shown by flow cytometry is related closely to the histologic classification and prognosis of gastric smooth muscle tumors.

Adult

Effects of organic anions on biliary lipid secretion in rats. Importance of association with biliary lipid structures.

This study was performed to determine the effects of various organic anions on biliary lipid secretion in rats. We infused bile-salt-pool-depleted rats with sodium taurocholate at a constant rate, with or without various organic anions: Indocyanine Green (ICG), bromosulphophthalein (BSP), BSP-glutathione and Phenol Red (PR). BSP decreased biliary secretion of cholesterol and phospholipids in a dose-dependent manner without affecting bile salt secretion (uncoupling), and this change was fully reversible. In contrast, ICG, BSP-glutathione and PR did not cause such an uncoupling of biliary lipids. In addition, the distribution pattern of each organic anion to various lipid particles was determined by gel-permeation chromatography. BSP was predominantly associated with bile salt micelles, whereas vesicular association was dominant for ICG, and both BSP-glutathione and PR formed only self-aggregations. From these data, we concluded that the uncoupling of biliary lipids from bile salt secretion by BSP resulted from the interaction between BSP and bile salt micelles in the bile canaliculus, and that this interaction inhibited the capacity of bile salts to induce the secretion of phospholipids and cholesterol.

Animals

Changes of colonic vasoactive intestinal peptide and cholinergic activity in rats with chemical colitis.

The vasoactive intestinal peptide concentration was examined in the colonic wall and portal venous plasma of rats with chemical colitis by radioimmunoassay, and the colonic localization was determined with immunocytochemistry. Colonic acetylcholine esterase activity was also measured, and the response of vasoactive intestinal peptide to acetylcholine administration was determined. Colitis was induced by administration of dextran sulfate for three months. The chemical colitis was histologically similar to active human ulcerative colitis. We observed a significant increase of immunostained neurons and nerve fibers and a significant rise in the colonic wall vasoactive intestinal peptide content in chemical colitis rats, while plasma concentrations of the peptide did not change significantly. Colonic acetylcholine esterase activity was significantly elevated in colitis rats compared with control rats. Systemic administration of acetylcholine significantly increased the colonic and plasma vasoactive intestinal peptide concentrations in colitis rats. These findings demonstrated a positive association between colitis activity and an increase of vasoactive intestinal peptide and suggested that increased vagal tone promoted the peptide's release.

Acetylcholine

Somatostatin in gastric juice in normal subjects and patients with duodenal ulcer.

Somatostatin in gastric juice was determined in normal subjects and patients with duodenal ulcer. Gel exclusion chromatography of gastric juice revealed that the main immunoreactivity existed at the position of somatostatin-14. A large amount of somatostatin was present in gastric juice, and the quantity increased following tetragastrin stimulation. Furthermore, there was a good inverse correlation between somatostatin concentration and acidity of gastric juice; however, there was no difference between normal subjects and patients with duodenal ulcer in the amount of somatostatin released into gastric juice.

Adult

Role of cholesterol-accumulating macrophages on vascular smooth muscle cell proliferation.

The proliferation of vascular smooth muscle cells (VSMC) was stimulated by co-incubation with macrophages. Further stimulation was observed when co-incubated macrophages were supplied with LDL or cholesterol. However, the stimulation of VSMC proliferation did not result from co-incubation with macrophages supplemented with acetylated LDL or delipidated LDL. The addition of anti-PDGF antibody partially abolished the stimulation of VSMC proliferation induced by co-incubation with macrophages supplemented with LDL or cholesterol. A high concentration of prostaglandin E2 inhibited the proliferation of VSMC stimulated by PDGF and plasma-derived serum when they were at the G0/G1 stage. However, the inhibitory effect of prostaglandin E2 on proliferation was not observed when cells were incubated with macrophages supplemented with LDL or cholesterol in spite of the promotion under these conditions of prostaglandin E2 production. These results suggest that cholesterol-accumulating macrophages may exert a regulatory effect on the proliferation of VSMC through the synthesis and secretion of platelet-derived growth factor (PDGF) and prostaglandin E2, besides foam-cell formation.

Animals

Lack of effect of parathyroid hormone on calcium homeostasis in rat platelets.

The in vitro effects of parathyroid hormone on Ca2+ handling by fura-2 loaded rat platelets were studied. The incubation of these platelets with rat parathyroid hormone (1-34) for 10 min had no effect on intracellular fura-2 metabolism or [Ca2+]i in the resting state. The [Ca2+]i response to 0.1 U/mL thrombin was unaffected by preincubation with parathyroid hormone in the presence or absence of extracellular Ca2+. Furthermore, the recovery rate of [Ca2+]i after the thrombin-induced peak in Ca(2+)-depleted media was not altered with parathyroid hormone. These data indicate that parathyroid hormone may not have a significant effect on Ca2+ homeostasis in rat platelets in unstimulated and stimulated conditions.

Animals

Heterotopic pancreas diagnosed by endoscopic ultrasonography and endoscopic injection of ethanol to make a histologic diagnosis.

A gastric submucosal tumor in a 56-year-old man was presumed to be heterotopic pancreas on the basis of endoscopy and endoscopic ultrasonography. To obtain a histologic diagnosis we injected ethanol at the tumor site to create an artificial ulcer. This facilitated the removal of endoscopic biopsy specimens from the submucosal layer so that histologic examination could confirm the presence of heterotopic pancreatic tissue.

Choristoma

Inhibitory effects of pravastatin, a competitive inhibitor of hydroxymethylglutaryl coenzyme A reductase, on cholesterol gallstone formation in prairie dogs.

The effects of pravastatin on cholesterol gallstone formation were determined in prairie dogs. We fed 10 prairie dogs 1% cholesterol with or without 0.05% (w/w) pravastatin (n = 5, each) for 4 weeks. In addition, another 5 prairie dogs were fed a standard rodent chow as a control. Only the animals fed 1% cholesterol without pravastatin treatment formed cholesterol gallstones. Gallbladder bile from cholesterol-fed animals contained cholesterol monohydrate crystals, whereas those treated with pravastatin contained no crystal. Furthermore, marked increases in tissue cholesterol levels (serum, liver and bile), and in biliary mucous glycoprotein levels were evident in cholesterol-fed animals, whereas pravastatin treatment normalized these levels. These findings raise the possibility that such inhibitors might have a future role to play in the prevention of cholesterol gallstone formation and/or recurrence.

Animals

Immunoreactive transforming growth factor-alpha and epidermal growth factor in colorectal adenomas and carcinomas.

A total of 117 colorectal tissue specimens were examined immunohistochemically for the production of immunoreactive (IR-) transforming growth factor (TGF)-alpha and IR-epidermal growth factor (EGF). IR-TGF-alpha was detected in 26/32 (81.3%) invasive cancers, 14/27 (51.9%) carcinomas in situ, and 14/58 (24.1%) adenomas. IR-EGF was detected in 14/32 (43.8%) invasive cancers, 12/27 (44.4%) carcinomas in situ, and 12/58 (20.7%) adenomas. The staining intensity of IR-TGF-alpha was related to the histologic grade of malignancy, but that of IR-EGF was not. These suggest that IR-TGF-alpha plays a more important role than IR-EGF in the growth of colorectal neoplasms, and that further study of these growth factors would be helpful in understanding the biology of colorectal carcinoma.

Adenoma

Can high blood pressure alone increase erythrocytic intracellular sodium concentration?

In order to clarify the direct effects of high blood pressure on erythrocytic intracellular sodium concentration ([Na+]i) and sodium transport systems, a static pressure of 2.5 atm was applied to whole blood in plastic syringes at room temperature for 5 and 24 h. In the control samples, 5 h incubation under atmospheric pressure produced a significant decrease in ouabain-sensitive Na(+)-K+ pump activity and plasma pH, but no change in other parameters. After 24 h incubation, [Na+]i and mean corpuscular volume were significantly increased and intracellular potassium concentration, ouabain-sensitive Na(+)-K+ pump activity, and plasma pH were decreased. The change in [Na+]i during incubation under atmospheric pressure may be due to the increased permeability of the cell membrane and the decrease in ouabain-sensitive Na(+)-K+ pump activity. The pressure load did not increase erythrocytic [Na+]i but did decrease it relative to the control. The pressure load had no apparent effects on sodium transport systems, mean corpuscular volume and pH of plasma relative to the control. Although the mechanisms of the effect of pressure load on [Na+]i were not determined, we did find that high blood pressure alone was unable to increase erythrocytic [Na+]i.

Adult

Hemodynamic changes due to afterload reduction as a predictor of exercise capacity in patients with dilated cardiomyopathy.

Sixteen patients with dilated cardiomyopathy were examined hemodynamically in order to clarify the relationship between the exercise capacity and the effects of afterload reduction at rest using supine graded bicycle exercise testing before and after sublingual administration of 10 mg nifedipine. 1) The integration of work loads was weakly correlated with the stroke index (r = 0.64), heart rate (r = -0.58) and plasma norepinephrine concentration at rest (r = 0.49), but not with the left ventricular ejection fraction, cardiac index, pulmonary arterial diastolic pressure or the mean arterial pressure at rest. 2) Changes in stroke index and heart rate after administration of nifedipine correlated well with the integration of work loads (r = -0.84, r = 0.81, respectively). Thus, in patients with dilated cardiomyopathy changes in stroke volume and heart rate due to afterload reduction at rest were better predictors of exercise capacity than the baseline left ventricular hemodynamic parameters.

Adult

Rapid growth and difficulty of early detection of scirrhous carcinoma of the stomach.

We report six cases of scirrhous carcinoma of the stomach in which we were able to observe the natural history of serial radiographs. All the patients developed scirrhous carcinoma of the stomach in an observation periods ranging from 2 to 15 months (mean: 5.8 months). No abnormalities or obvious findings indicative of a carcinoma were detectable, on the prior radiographs, even when they were reviewed. Endoscopy was also performed in two patients during the observation period, and no lesions were detected. At the time of diagnosis, two patients were inoperable because of metastases and died of the disease 2 and 5 months later. Three patients died of the disease 5, 8, and 26 months after gastrectomy, respectively. Only one patient is free of disease 16 months after gastrectomy. Our findings suggest that the difficulty of detection and the rapid growth of this tumor may explain why it is seldom detected at an early stage and has a very poor prognosis.

Adenocarcinoma, Scirrhous

Familial influence upon NaCl sensitivity in patients with essential hypertension.

OBJECTIVE: The role of genetic factors in the pathogenesis of essential hypertension has not been fully clarified. In order to characterize the relation between NaCl sensitivity and genetic features of hypertension, the responses to dietary Na manipulations were examined in essential hypertensive patients with and without a family history of hypertension. METHODS: Fifteen essential hypertensive patients, both of whose parents were hypertensive, were compared with 25 hypertensive patients in whom a family history of hypertension was known to be absent in first- and second-degree relatives. There were no differences in gender distribution, age, blood pressure or duration of hypertension between the two groups. Subjects were studied as inpatients on a daily diet of 170 mmol NaCl for 1 week, followed by 1 week on a low-NaCl diet (50 mmol/day) and then by 1 week on a high-NaCl diet (340 mmol/day). RESULTS: Plasma renin activity on a low-NaCl diet was lower, and the erythrocyte Na+ concentration on both diets higher, in hypertensive patients with than in those without a family history. The elevations in mean blood pressure and in erythrocyte Na+ concentration with a high-NaCl diet were greater in patients with a family history. A significant correlation between the change in mean blood pressure and the change in erythrocyte Na+ concentration was found in patients with a positive family history, but not in those with a negative family history. CONCLUSIONS: Essential hypertensive patients with an apparent hereditary component of hypertension can be characterized as the low-renin and Na-sensitive subgroup with intracellular Na+ accumulation. Genetic features may underlie, at least in part, the heterogeneity of essential hypertension.

Blood Pressure

Therapeutic effects of oral rebamipide and in combination with cimetidine on experimental gastritis in rats.

The present study evaluated the therapeutic effects of rebamipide alone and in combination with cimetidine on experimental gastritis established by the administration of 5 mM sodium taurocholate (TCA) for 6 months in rats. Morphological and biochemical analyses were performed to determine the effects of rebamipide, administered alone or in combination with cimetidine, on chronic, atrophic and erosive gastritis. Rebamipide and cimetidine were administered to rats as a dietary admixture for 4 weeks after withdrawal of TCA. Rebamipide dose-dependently reduced the total length of the erosion, normalized the mucosal thickness and increased the number of parietal and total cells, and tended to reduce interstitial infiltration of inflammatory cells and proliferation of collagenous fibers. Moreover, histochemical and biochemical studies also showed rebamipide to be effective. Rebamipide increased the PAS-positive mucus and normalized the reduced gastric mucosal SOD activity. The therapeutic effect of rebamipide on the experimental gastritis was enhanced by the combined use of cimetidine. These results suggest that rebamipide has a therapeutic effect on chronic atrophic erosive gastritis induced by TCA, and that the mechanism of the therapeutic effect is partially due to the increase in PAS-positive mucus and gastric mucosal SOD activity. Furthermore, the enhanced effect of the combination therapy of rebamipide with cimetidine was considered to be due to the actions of both cimetidine and rebamipide.

Administration, Oral