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Biomedical subjects

G Kajiyama

Publications and source records attributed to G Kajiyama.

At least 145 records · Page 8Linked to original sources

Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension.

Endothelial function has been shown to be impaired in patients with essential hypertension. The purpose of the present study was to determine whether antihypertensive drug therapy improves impaired endothelium-dependent renal vasorelaxation in essential hypertensive patients without atherosclerosis. We evaluated the effects of intravenous infusion of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 27 patients with mild to moderate essential hypertension who were randomly assigned to treatment with either the angiotensin-converting enzyme inhibitor imidapril or the calcium antagonist amlodipine for 12 weeks in a double-blind fashion. After the 12 weeks, the decrease in blood pressure was similar in the imidapril (n=14) and amlodipine (n=13) groups. The increase in renal plasma flow was also similar in both groups. L-Arginine-induced renovascular relaxation was increased by imidapril (renal plasma flow, 9.6+/-5.1% to 14.4+/-7.4%; renal vascular resistance, -10.4+/-8.1% to -16.7+/-9.2%, P<0.05, respectively) but not by amlodipine. Urinary excretion of nitrite/nitrate in response to L-arginine was significantly increased by imidapril (90+/-29% to 134+/-63%, P<0.05) but remained unchanged by amlodipine. These findings suggest that angiotensin-converting enzyme inhibition improves the impaired endothelium-dependent renovascular relaxation in patients with essential hypertension due to the increase in nitric oxide production and that the reduction in blood pressure with a calcium antagonist does not play a major role in the potentiation of L-arginine/nitric oxide-mediated effects.

Adult↗

Effect of adenosine triphosphate on human coronary circulation.

We investigated in humans the effects of adenosine triphosphate (ATP), administered by intracoronary bolus (4-16 microg) or intravenous infusion (25-200 microg/kg/min), on coronary and systemic hemodynamics and electrocardiogram (ECG) variables. All patients had normal epicardial coronary arteries. The maximal coronary blood flow velocity (CBFV) was determined with intracoronary bolus of papaverine. A 12 microg bolus of ATP (n=12) caused maximal coronary hyperemia similar to that caused by papaverine. Intracoronary boluses caused a small brief decrease in arterial pressure but no significant changes in HR or ECG variables. Intravenous infusion of ATP at 150 microg/kg/min (n=15) caused a decrease in the coronary resistance index similar to that caused by papaverine, but the rate of increase in CBFV by ATP was smaller than that caused by papaverine. No patients had a significant change in ECG variables, but some patients (40%) had a serious decrease in arterial pressure. These studies suggest that maximal coronary vasodilation can be achieved safely with intracoronary ATP administration and that intravenous infusions at 150 microg/kg/min cause near-maximal coronary hyperemia in most patients.

Adenosine Triphosphate↗

Expression of interleukin-8 correlates with vascularity in human gastric carcinomas.

Interleukin (IL)-8 is a multifunctional cytokine that can stimulate the division of endothelial cells. We examined the expression of IL-8 mRNA using Northern blot analysis and in situ mRNA hybridization (ISH) and protein production using enzyme-linked immunosorbent assay and immunohistochemistry in 8 human gastric carcinoma cell lines and 39 gastric carcinomas and corresponding normal mucosa (34 surgical specimens and 5 biopsy specimens). Of the 8 human gastric carcinoma cell lines, 6 expressed 1.8-kb IL-8 mRNA and secreted various levels of IL-8 protein. The expression of IL-8 by TMK-1 cells was induced by exposure to IL-1 alpha, epidermal growth factor, and transforming growth factor-alpha, shown previously to be autocrine growth stimulators for human gastric carcinoma cells. In tumor tissues, most of the tumors (28 of 34 surgical specimens and 4 of 5 biopsy specimens) expressed IL-8 at higher levels than the corresponding normal mucosa. ISH and immunohistochemical analyses revealed that IL-8 mRNA and protein were localized in the cytoplasm of tumor cells. The number of blood vessels in the gastric carcinomas was determined by using antibodies against CD34. The level of IL-8 mRNA in the neoplasms strongly correlated with vascularization (Spearman correlation, r = 0.812; P = 0.001). The data suggest that IL-8 produced by tumor cells may regulate neovascularization and, hence, the growth and spread of human gastric carcinoma.

Adult↗

Structural characteristics of Koch's triangle in patients with atrioventricular node reentrant tachycardia.

The aim of this study is to investigate whether patients with atrioventricular node reentrant tachycardia (AVNRT) present different structural characteristics of Koch's triangle from patients with atrioventricular (AV) reentrant tachycardia and other control patients. Fifty-eight patients with arrhythmia or chest pain underwent selective coronary sinus angiography so that the diameter of the coronary sinus could be measured. The patients with arrhythmia also underwent electrophysiological study and measurement of the height of Koch's triangle. Patients with AVNRT had large coronary sinus ostial diameters compared with patients with AV reentrant tachycardia and those with chest pain (13.6 +/- 2.2 mm vs. 10.6 +/- 2.7 mm [p < 0.005] and 10.0 +/- 2.1 mm [p < 0.002], respectively), while there were no differences in distal diameter. The ostial diameter in patients with dual AV node pathways but noninducible AVNRT (11.8 +/- 1.5 mm) tended to be smaller than that in patients with AVNRT. No differences in the height of Koch's triangle and electrophysiological characteristics, including AV node properties, were found among the study groups. In conclusion, an increased size of the coronary sinus ostium (the base of Koch's triangle) is a structural characteristic in patients with AVNRT and may be the substrate needed for the appearance of AVNRT.

Adolescent↗

Living related partial liver transplantation for primary biliary cirrhosis--a case report.

An adult living related partial liver transplantation was performed on a 49 year old female with terminal hepatic failure due to primary biliary cirrhosis (PBC). The donor was her 53 year-old sister. A sufficient volume of graft tissue was obtained, which comprised 1.5% of the body weight of the recipient. The recipient had an excellent recovery without any major complications, and was discharged 35 days after the operation. At 15 months after the operation, the patient has shown no signs of rejection while using FK506 and prednisolone as immunosuppressants. The progression of symptomatic PBC can be predicted, and the timing of the transplantation can be easily determined. In addition, the results of liver transplantation for PBC are good. Therefore, adult living related partial liver transplantation is an excellent treatment for primary biliary cirrhosis.

Bilirubin↗

[Telomerase activity in pancreatic juice for the preoperative diagnosis of pancreatic cancer].

Although many diagnostic challenges have been tried in pancreatic cancer, its prognosis still remains poor. One of the reason that it is difficult to diagnose using present diagnostic procedure in early stage of pancreatic cancer. Therefore, we tried new procedure using telomerase activity from pancreatic juice. In this study, telomerase was assayed by use of pancreatic duct cells obtained preoperatively from 32 cases with pancreatic duct abnormalities. Telomerase activity was undetectable in all 17 subjects with benign pancreatic diseases, whereas 13 (87%) of 15 subjects with pancreatic cancer had detectable telomerase activity. Interestingly, we also detected telomerase activity in the case of carcinoma in situ. If future studies confirm, the detection of telomerase activity of pancreatic duct cells may become an useful tool for diagnosis of pancreatic cancer, perhaps at early stages.

Adult↗

[Telomere length and telomerase activity in hepatocellular carcinoma].

Telomerase activity and terminal restriction fragment (TRF) length were examined in hepatocellular carcinoma (HCC). Telomerase activity was assayed by telomeric repeat amplification protocol (TRAP) connected with an internal telomerase assay standard (ITAS). The incidence of strong telomerase activity (highly variable level compared with the activity of non-cancerous liver tissue) was 79% in well, 84% in moderately, and 100% in poorly differentiated HCC, while 0% in non-cancerous liver tissues. The incidence of TRF length alteration (reduction or elongation) was 53% in HCC. The incidence of TRF alteration was significantly higher in HCC exceeding 3 cm in diameter, moderately or poorly differentiated in histology. Telomerase activity was not associated with TRF length alteration in HCC. In conclusion, strong telomerase activity and TRF length alteration increased with HCC tumor progressions.

Carcinoma, Hepatocellular↗

Significance of vessel count and vascular endothelial growth factor in human esophageal carcinomas.

The purpose of this study was to determine the angiogenic profile of human esophageal carcinomas. The expression of vascular endothelial growth factor (VEGF) was examined in 6 esophageal carcinoma cell lines and 119 human esophageal carcinoma tissues by Northern blot analysis and immunohistochemistry, respectively. Immunohistochemistry using antibodies against CD34 (endothelial cell specific) was carried out on archival specimens, and microvessels were quantitated by counting vessels in a x200 field in the most vascular area of the tumor. All of the cell lines constitutively expressed VEGF mRNA at various levels. A total of 71 of 119 (59.7%) tumors showed intense VEGF immunoreactivity in the cytoplasm of cancer cells. Vessel count was significantly higher in the VEGF-positive tumors than it was in the VEGF-negative tumors. VEGF expression correlated with the depth of tumor invasion, tumor stage, venous invasion, and lymphatic invasion. The survival rate of patients with high vessel density in the tumor was significantly worse than that of patients with low vessel density in the tumor. There was a tendency for poorer prognosis in the group with VEGF-positive tumors compared with that of the group with VEGF-negative tumors. Overall, these results suggest that VEGF is associated with tumor progression by stimulating angiogenesis in human esophageal carcinoma.

Blotting, Northern↗

Lack of effect of transmembrane gradient of magnesium and sodium on regulation of cytosolic free magnesium concentration in rat lymphocytes.

The regulation of the intracellular concentration of Mg2+ ([Mg2+]i) is not fully understood. The level of Mg in lymphocytes is a good predictor of total body Mg status. We measured [Mg2+]i and total Mg in rat lymphocytes by using, respectively, the fluorescent Mg2+ indicator mag-fura-2 and atomic absorption spectrophotometry. The basal [Mg2+]i in rat lymphocytes was 328 +/- 23 micromol/l. An elevation to 5 mmol/l or the removal of extracellular Mg2+ did not affect [Mg2+]i. A reduction in extracellular Na+ did not influence [Mg2+]i for 60 min. The total Mg concentration in lymphocytes also remained stable. Results suggest that the permeability of the plasma membrane to Mg2+ is very low, and that Na+/Mg2+ exchange is not involved in the regulation of [Mg2+]i in rat lymphocytes.

Animals↗

Coronary segmental responses to acetylcholine and bradykinin in patients with atherosclerotic risk factors.

This study was designed to elucidate the nature of coronary endothelial dysfunction in patients with hypertension and/or hypercholesterolemia and normal smooth coronary arteries by evaluating the coronary vascular responses to acetylcholine and bradykinin. The study included 19 patients (10 men; age [mean +/- SD] 61 +/- 9 years) with angiographically normal smooth coronary arteries and either hypertension (n = 7) and/or hypercholesterolemia (n = 13). Patients received acetylcholine (3 or 30 microg/min) infusions followed by bradykinin (0.5, 1.5, 2.5 microg/min) and nitroglycerin (200 microg/min) infusions into the left coronary ostium. Epicardial coronary artery diameters were measured by quantitative angiography. Angiography detected both vasoconstricted and dilated segments following acetylcholine infusion. Bradykinin significantly dilated both types of segments (p <0.001, respectively). However, bradykinin-induced dilation was significantly greater in segments exhibiting acetylcholine-induced vasodilation than in those exhibiting vasoconstriction (p <0.01 in the proximal portion and p <0.02 in the distal portion). Nitroglycerin-induced dilation was similar in all segments. These results suggest that coronary endothelial dysfunction may be a heterogeneous process in patients with coronary risk factors. Moreover, the mechanism underlying diminished endothelium-dependent dilation involves not only the muscarinic receptor, but also B2-kinin receptor.

Acetylcholine↗

Chromosome assignment of aberrant NotI restriction DNA fragments in primary hepatocellular carcinoma.

DNA aberrations in human hepatocellular carcinoma (HCC) were studied by two-dimensional DNA electrophoresis analysis. Five intensified and 60 dwindling spots were detected recurrently in the two-dimensional profile which showed about 3000 restriction DNA fragments as distinctive spots. We assigned these aberrant spots to chromosomes, using the chromosome-assigned two-dimensional profile. Four of the five intensified, and 53 of the 60 dwindling spots were given chromosome assignments. Intensified spots were assigned to chromosomes 5, 6, 9 through 12, 16 and 18. Among the dwindling spots, the highest incidence of aberrations was found on chromosome 16, followed by 9 through 12 and chromosome 2. No aberrations were detected in chromosomes 7, 21, 22 or Y.

Carcinoma, Hepatocellular↗

Immunocytochemical detection of p53 protein as an adjunct in cytologic diagnosis from pancreatic duct brushings in mucin-producing tumors of the pancreas.

BACKGROUND: In cases of mucin-producing tumor (MPT) of the pancreas, a new clinical entity of pancreatic tumor, it has been reported to be difficult to distinguish adenoma from carcinoma preoperatively. This observation caused the authors to develop a new method of p53 immunocytochemistry using cytologic samples obtained by endoscopic retrograde pancreatic duct brushing (ERPDB). METHODS: Fifteen cases of MPT (9 with carcinoma and 6 with adenoma) were examined. In all cases, histologic diagnosis was determined by surgery or autopsy. A wire with a small brush was pushed into the dilatated pancreatic duct detected by endoscopic retrograde pancreatography (ERP). Specimens obtained by brushing were prepared on slides and subsequently fixed with ethanol. Papanicolaou staining and p53 immunocytochemistry were performed simultaneously. The ability of conventional cytology to distinguish adenoma from carcinoma was compared with that of p53 immunocytochemistry. RESULTS: Five of 9 cases (56%) with carcinoma of MPT were correctly diagnosed by Papanicolaou staining. Two of four cases, classified as benign by Papanicolaou staining, expressed p53 protein. Overall, 7 of 9 cases (78%) with carcinoma MPT were correctly diagnosed by Papanicolaou staining associated with p53 immunocytochemistry. In the cases with adenoma MPT, all cases were classified as benign by Papanicolaou staining and no case positive for p53 protein was encountered. CONCLUSIONS: These results suggest that p53 immunocytochemistry as an adjunct in cytologic diagnosis using ERPDB may contribute to differentiating adenoma from carcinoma MPT of the pancreas preoperatively.

Adenocarcinoma, Mucinous↗

Extracellular Mg2+ inhibits capacitative Ca2+ entry in vascular smooth muscle cells.

BACKGROUND: Agonist-induced Ca2+ entry is thought to be mediated by capacitative Ca2+ entry other than L-type Ca2+ channels in vascular smooth muscle cells (VSMCs). The mechanism for capacitative Ca2+ entry has not been fully elucidated. Our objective was to examine the effect of external Mg2+ on capacitative Ca2+ entry in cultured rat aortic VSMCs. METHODS AND RESULTS: Three doses of external Mg2+ concentration (nominally 0, 1, and 5 mmol/L) were used. After exposure to 1 mumol/L, angiotensin II (Ang II) in Ca(2+)-free medium, addition of Ca2+ to the medium caused an increase in cytosolic free Ca2+ concentration ([Ca2+]i), indicating Ang II-induced Ca2+ influx. This Ca2+ influx was attenuated in cells preincubated with high external Mg2+ concentrations or with 1 mumol/L nifedipine. After VSMCs in Ca(2+)-free medium were exposed to 1 mumol/L thapsigargin, which inhibits the sarcoplasmic reticulum Ca(2+)-ATPase and depletes Ca2+ stores, addition of Ca2+ to the medium induced an increase in [Ca2+]i, indicating capacitative Ca2+ entry. This entry pathway was found to be independent of dihydropyridine-sensitive Ca2+ channels and inhibited by increased external Mg2+ concentration. External Mg2+ concentration did not influence Ca2+ efflux across the plasma membrane after stimulation with Ang II plus thapsigargin. CONCLUSIONS: Results suggest that in VSMCs, capacitative Ca2+ entry is reduced by external Mg2+. This mechanism may explain in part the inhibitory effect of external Mg2+ on Ca2+ handling.

Angiotensin II↗

Activation of MAP kinase cascade induced by human pancreatic phospholipase A2 in a human pancreatic cancer cell line.

We have found that the growth of human pancreatic cancer cells MIAPaCa-2, induced by human pancreatic phospholipase A2 group I (hPLA2-I), is mediated via its specific receptor but not via its catalytic property. The present study showed that the activation of mitogen-activated protein kinase (MAPK) cascade in MIAPaCa-2 cells is induced by hPLA2-I: this digestive enzyme induced phosphorylation of MEK1/2, p44/42 MAPK and ATF-2, and the phosphorylation in the MAPK cascade was inhibited after the cells were pre-incubated with a selective inhibitor of MEK, PD98059. In addition, this inhibitor dose-dependently blocked the hPLA2-I-induced MIAPaCa-2 proliferation, suggesting that activation of the MAPK cascade is essential for the hPLA2-I-induced MIAPaCa-2 proliferation.

Activating Transcription Factor 2↗