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Biomedical subjects

Kenjiro Kikuchi

Publications and source records attributed to Kenjiro Kikuchi.

70 records · Page 4Linked to original sources
PubMed2003

A case of nephrotic syndrome associated with renovascular hypertension successfully treated with candesartan.

A sixty eight-year-old man was referred to our hospital for evaluation of hypertension and hypokalemia. His chief complaints were fatigability and weakness of the lower extremities. Atrophy of the right kidney was noted on computed tomography. The laboratory findings demonstrated massive proteinuria, markedly elevated plasma renin activity, hypokalemia, and renal insufficiency. Angiography showed total occlusion of the right renal artery. The patient was diagnosed as having nephrotic syndrome associated with renovascular hypertension. Treatment with candesartan, an angiotensin-II-receptor blocker (ARB), controlled both hypertension and proteinuria satisfactorily without worsening of his renal function. This is the first report on the effect of ARB on nephrotic syndrome associated with renovascular hypertension. Based on the results, ARB can be considered a promising agent for the treatment of patients with renovascular hypertension with massive proteinuria and renal insufficiency.

Aged↗
PubMed2003

Severe pulmonary hypertension associated with primary Sjögren's syndrome.

Severe pulmonary hypertension is one of the fetal complications in various connective tissue diseases. We report a case of severe pulmonary hypertension associated with primary Sjögren's syndrome. In a lung biopsy specimen, there were findings of intimal and medial hypertrophy with narrowing vessel lumina and plexiform lesions. Moreover, deposits of immunoglobulin M, immunoglobulin A and complement protein C1q were found in the pulmonary arterial walls. Although pulmonary hypertension was refractory to oral prostacyclin, steroid therapy improved the clinical and hemodynamic conditions. In the present case, the immunological etiology may be related to the mechanisms of pulmonary hypertension associated with Sjögren's syndrome.

Adult↗
PubMed2003

Effects of temocapril and olmesartan on myocardial sympathetic nervous activity and fatty acid metabolism in rats with chronic beta-adrenergic stimulation.

We investigated the effects of an angiotensin-converting enzyme inhibitor (temocapril) and an angiotensin II type 1 receptor blocker (olmesartan) on changes in myocardial sympathetic nervous activity, fatty acid metabolism and myocardial blood flow using 131I-meta-iodobenzylguanidine, 125I-beta-methyl-iodophenyl pentadecanoic acid and 99mTc-tetrofosmin, respectively, in rats with isoproterenol-induced cardiac hypertrophy. Male Sprague-Dawley rats underwent isoproterenol administration (3 mg/kg per day) for 1 week by osmotic mini-pump. The hearts were excised and analyzed for the uptake of meta-iodobenzylguanidine. Beta-methyl-iodophenyl pentadecanoic acid and tetrofosmin in 11 segments in four groups; sham group (saline), isoproterenol group (isoproterenol alone), angiotensin-converting enzyme inhibitor group (isoproterenol and temocapril), and angiotensin II type 1 receptor blocker group (isoproterenol and olmesartan). Isoproterenol significantly increased the heart weight compared with the sham group, whereas it was significantly blunted in the angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker groups. The ratio of the percent kilogram dose per gram of meta-iodobenzylguanidine to tetrofosmin, an index of myocardial sympathetic nervous activity, was significantly decreased in the isoproterenol group (0.18 +/- 0.01) compared with the sham group (0.41 +/- 0.03). Importantly, these changes were significantly improved in the angiotensin-converting enzyme inhibitor (0.28 +/- 0.01) and the angiotensin II type 1 receptor blocker groups (0.32 +/- 0.01). The ratio of the percent kilogram dose per gram of beta-methyl-iodophenyl pentadecanoic acid to tetrofosmin, an index of myocardial fatty acid metabolism, was significantly decreased in the isoproterenol group (1.30 +/- 0.03) compared with the sham group (1.60 +/- 0.10). In contrast, there were no significant differences in beta-methyl-iodophenyl pentadecanoic acid to tetrofosmin ratios between the sham and angiotensin-converting enzyme inhibitor groups, or the angiotensin II type 1 receptor blocker group. Cardiac hypertrophy induced by chronic beta-adrenergic stimulation is accompanied by impairment of sympathetic nervous activity and fatty acid metabolism. These abnormalities are effectively prevented by the angiotensin-converting enzyme inhibitor and the angiotensin II type 1 receptor blocker.

Adrenergic Fibers↗
PubMed2003

[A case of pulmonary hamartoma and sclerosing hemangioma in the same lung].

A 49-year-old woman was referred to our hospital because abnormal masses had been found in the left lung on chest radiography. This examination and CT scanning on admission both revealed a 12 x 8 mm mass in the left S5 and a 31 x 25 mm mass in the left S8. Calcification was not found in the tumors. Bronchoscopy showed narrowing of the left B5 and B8 bronchi by irregularity of the mucous membrane. No malignant cells were found in the cytological specimens, which were obtained by brushing and washing of the bronchi. Although the radiological findings suggested benign tumors, surgical resection was performed to confirm the diagnosis. The tumor in the left S5 was diagnosed as a hamartoma because it contained cartilage, lipoid tissue and lymphatic follicles. The tumor in the left S8 was diagnosed as a sclerosing hemangioma because vasculo-capillary formation by the cells with epithelial origin was seen. The pathological diagnosis of the two tumors differed, but a similar mechanism of tumorigenesis was suggested.

Female↗
PubMed2002

Contribution of macrophage migration inhibitory factor to extracellular signal-regulated kinase activation by oxidative stress in cardiomyocytes.

In response to oxidative stress, the pathogenesis of a number of cardiovascular events and several genes are stimulated by extracellular signal-regulated kinases (ERK1/2). Biphasic (early, 10 min; and delayed, 120 min) ERK1/2 activation by H(2)O(2), a reactive oxygen species, was observed in cultured neonatal rat cardiomyocytes. We investigated the hypothesis that the delayed activation of ERK1/2 depends on a factor secreted by oxidative stress (FSO). The delayed activation was inhibited by calphostin C, a protein kinase C inhibitor. Conditioned medium (CM) obtained from cells stimulated with H(2)O(2) induced rapid and monophasic ERK1/2 activation, which was not inhibited by calphostin C. In contrast, calphostin C-pretreated CM did not activate ERK1/2. Macrophage migration inhibitory factor (MIF) was one of the candidate FSOs activating ERK1/2. The existence of MIF in CM, the recombinant MIF-stimulated ERK1/2 rapid activation, and anti-MIF neutralizing antibody-induced inhibition of the delayed activation implied that MIF could be the FSO. Pretreatment of cardiomyocytes with a mitogen-activated protein kinase/ERK kinase (MEK) inhibitor did not suppress the MIF secretion, although it prevented the ERK1/2 activation by H(2)O(2). These results indicate that MIF is secreted from cardiomyocytes as a result of oxidative stress and activates ERK1/2 through a MEK1/2-dependent mechanism, although the secretion is not regulated by ERK1/2 but by protein kinase C.

Animals↗
PubMed2002

Magnesium reduces myocardial infarct size via enhancement of adenosine mechanism in rabbits.

OBJECTIVES: Clinical impact of magnesium (Mg) therapy remains controversial in acute myocardial infarction. We investigated the infarct size limiting effects of Mg and its mechanism in rabbits. METHODS: Anesthetized rabbits underwent 30 min coronary occlusion and 3 h reperfusion in ten groups: (1) Control, (2) Low Mg, (3) Mg, (4) High Mg, (5) calcium (Ca), (6) Mg+Ca, (7) 8-phenyltheophylline (8PT), an adenosine receptor blockade, (8) 8PT+Mg, (9) alpha, beta-methylene-adenosine diphosphate (AOPCP), a selective inhibitor of ecto-5'-nucleotidase, and (10) AOPCP+Mg groups. Infract size (IS) to area at risk (AR) was measured by triphenyltetrazorium chloride method. RESULTS: The IS/AR ratio was significantly smaller in Mg, 27+/-3% (P<0.05) and High Mg, 24+/-2% (P<0.05) compared to Control, 50+/-3% and Low Mg, 42+/-4%. The IS limiting effects of Mg were abolished in 8PT+Mg, AOPCP+Mg and Mg+Ca. The IS/AR ratio correlated with neither rate-pressure products nor incidence of arrhythmia. CONCLUSION: Magnesium administration has an infarct size limiting effect independent of its effects on myocardial oxygen consumption and incidence of arrhythmia in rabbits. The infarct size limiting effect of magnesium is attributable, at least in part, to augmentation of adenosine mechanism.

5'-Nucleotidase↗
PubMed2002

Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells.

Effects of the prostanoids on the growth of cultured aortic vascular smooth muscle cells (VSMCs) were examined using mice lacking prostanoid receptors. Proliferation of VSMCs was assessed by measuring [(3)H]-thymidine incorporation and the cell number, and their hypertrophy by [(14)C]-leucine incorporation and protein content. In VSMCs from wild-type mice, expressions of mRNAs for the EP(4) and TP were most abundant, followed by those for the IP, EP(3) and FP, when examined by competitive reverse transcriptase-PCR. Those for the EP(1), EP(2) and DP, however, could not be detected. AE1-329, an EP(4) agonist, and cicaprost, an IP agonist, inhibited platelet derived growth factor (PDGF)-induced proliferation of VSMCs from wild-type mice; these inhibitory effects disappeared completely in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. In accordance with these effects, AE1-329 and cicaprost stimulated cAMP production in VSMCs from wild-type mice, which were absent in VSMCs from EP(4)(-/-) and IP(-/-) mice, respectively. Effects of PGE(2) on cell proliferation and adenylate cyclase were almost similar with those of AE1-329 in VSMCs from wild-type mice, which disappeared in VSMCs from EP(4)(-/-) mice. PGD(2) inhibited PDGF-induced proliferation of VSMCs from both wild-type and DP(-/-) mice to a similar extent. This action of PGD(2) was also observed in VSMCs from EP4(-/-) and IP(-/-) mice. In VSMCs from wild-type mice, I-BOP, a TP agonist, showed potentiation of PDGF-induced hypertrophy. I-BOP failed to show this action in VSMCs from TP(-/-) mice. The specific agonists for the EP(1), EP(2) or EP(3), and PGF(2)alpha showed little effect on the growth of VSMCs. These results show that PGE(2), PGI(2) and TXA(2) modulate PDGF-induced proliferation or hypertrophy of VSMCs via the EP(4), IP and TP, respectively, and that the inhibitory effect of PGD(2) on PDGF-induced proliferation is not mediated by the DP, EP(4) or IP.

Animals↗
PubMed2002

Downregulation of nitric oxide accumulation by cyclooxygenase-2 induction and thromboxane A2 production in interleukin-1beta-stimulated rat aortic smooth muscle cells.

BACKGROUND: Cytokines from inflammatory cells do not produce nitric oxide, but stimulate the production of nitric oxide in vascular smooth muscle cells (VSMC). Thromboxane A2 (TXA2) has been believed to have a key role in atherosclerogenesis and post-angioplasty restenosis. OBJECTIVE: To determine whether cytokine-induced nitric oxide production is regulated by the TXA2/prostaglandin H2 (PGH2) receptor. METHODS AND RESULTS: We studied the interleukin-1beta (IL-1beta)-induced production of nitric oxide in rat VSMCs using the TXA2/PGH2 receptor antagonists, seratrodast and Bay-u3405, and an agonist, U-46619. Nitrite formation was measured colorimetrically. IL-1beta increased nitrite formation in a time-dependent manner. The nitrite concentration was 1.7 times greater in the presence of seratrodast than that without it. Nitrite accumulation was increased by Bay-u3405, but was decreased in the presence of U-46619, to 44% of that in its absence. Western and Northern blotting showed that seratrodast increased the levels of expression of inducible nitric oxide synthase (iNOS) protein and mRNA in a dose-dependent manner, whereas U-46619 decreased them. We speculated that VSMCs produced TXA2, thereby decreasing nitric oxide production; therefore we measured the accumulation of TXB2 using an enzyme immunoassay. Untreated VSMCs produced about 20 pg/mg protein of TXB2. This was increased by the addition of IL-1beta, to 152.1 +/- 43.0 pg/mg protein after a 24 h incubation; the expression of cyclooxygenase-2 (COX-2) protein was also increased, but there was no effect on the expression of COX-1 and TXA2 synthase. U-63557A, a TXA2 synthase inhibitor, increased the accumulation of nitrite to 1.3-fold that in its absence. CONCLUSIONS: These data suggest that the expression of iNOS and the production of nitric oxide are regulated by the TXA2/PGH2 receptor in IL-1beta-stimulated VSMCs. The endogenous production of TXA2 by the induction of COX-2 from IL-1beta-stimulated VSMCs probably downregulated the production of nitric oxide in VSMCs. TXA2/PGH2 receptor inhibitors may contribute to the reduction in formation of atherosclerosis in lesions with vascular injury by enhancing the production of nitric oxide by VSMCs.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Ambient oxygen regulates epithelial metabolism and nitric oxide production in the human nose.

The effects of ambient O(2) tension on epithelial metabolism and nitric oxide (NO) production (VNO) in the nasal airway were examined in nine healthy volunteers. Nasal VNO, O(2) consumption (VO(2)), and CO(2) production (VCO(2)) were measured during normoxia followed by gradual hypoxia from 21 to 0% O(2) concentration. Nasal VO(2), VCO(2), and respiratory quotient during normoxia were determined to be 1.19 +/- 0.04 ml/min, 1.60 +/- 0.04 ml/min, and 1.35 +/- 0.04, respectively. Hypoxia exposure to the nasal cavity significantly decreased both VCO(2) and VNO [VCO(2): 1.60 +/- 0.04 to 0.96 +/- 0.03 ml/min (P < 0.01), VNO: 530 +/- 15 to 336 +/- 9 nl/min (P < 0.01)]. VNO was reduced commensurately with gradual decline in O(2) tension, and the apparent K(m) value for O(2) was determined to be 23.0 microM. These results indicate that the nasal epithelial cells exchange O(2) and CO(2) with ambient air in the course of their metabolism and that nasal epithelial cells can synthesize NO by using ambient O(2) as a substrate. We conclude that air-borne O(2) diffuses into the epithelium where it may be utilized for either cell metabolism or NO synthesis.

Adult↗
PubMed2002

Methylenetetrahydrofolate reductase gene polymorphism, hyperhomocysteinemia, and cardiovascular diseases in chronic hemodialysis patients.

Cardiovascular disease (CVD) is the principle cause of death in patients with end-stage renal disease. Some gene polymorphisms and hyperhomocysteinemia have been implicated in the pathogenesis of CVD. The aim of this study was to assess the relationships between angiotensin-converting enzyme genotype, endothelial nitric oxide synthase genotype, and methylenetetrahydrofolate reductase (MTHFR) genotype and CVD in patients on hemodialysis and to clarify the determinants of plasma homocysteine level. One hundred and sixty-eight patients on hemodialysis (87 males and 81 females, mean age 60.7 +/- 13.1 years) were included. A history of CVD was present in 25% of the patients. There was a significant difference in the distributions of MTHFR non-VV genotype and MTHFR VV genotype between patients with a CVD history and patients without a CVD history, but no difference in the distributions of angiotensin-converting enzyme genotypes and endothelial nitric oxide synthase genotypes. The plasma homocysteine concentration was significantly higher in patients with MTHFR VV genotype than in patients with MTHFR non-VV genotype. The plasma homocysteine concentration was negatively correlated with plasma vitamin B12 concentration and plasma folate concentration. On stepwise multiple-regression analysis for the predictors of plasma homocysteine concentration, MTHFR VV genotype and gender were significant. In conclusion, MTHFR polymorphism may be a risk factor for CVD in patients on hemodialysis, and MTHFR VV genotype and gender may be strong determinants of the plasma homocysteine level.

Adult↗
PubMed2002

Effects of right stellate ganglion block on the autonomic nervous function of the heart: a study using the head-up tilt test.

The effect of peripheral sympathetic block on the autonomic nerve function of the heart was studied using the head-up tilt test (HUTT) and right stellate ganglion block (RSGB). Blood pressure (BP), heart rate (HR) and the parameters of power spectral analysis of HR variability recorded during the HUTT were measured in 8 patients with chronic pain syndrome before and after RSGB. In the control state, the mean HR and the LF/HF component recorded during HUTT significantly increased whereas the HF component markedly decreased. Conversely, the mean HR and LF/HF and HF components during HUTT did not significantly alter after the RSGB procedure. There were no significant differences between the BP values before and after RSGB. These results suggest that RSGB suppresses cardiac sympathetic function without significantly affecting BP and thus may be a safe and effective therapy for the chronic pain syndrome.

Adult↗
PubMed2002

An autopsy case of amyotrophic lateral sclerosis accompanied by syndrome of inappropriate secretion of antidiuretic hormone.

We report an autopsy-confirmed case of amyotrophic lateral sclerosis (ALS) accompanied by syndrome of inappropriate secretion of antidiuretic hormone (SIADH). A 67-year-old man was admitted to our hospital with muscle weakness, dysarthria and dysphagia. During hospitalization, respiratory insufficiency was ingravescent, and hyponatremia, hypo-osmolarity, elevated osmotic pressure of urine, and elevated urinary sodium excretion were noted. Based on these findings we diagnosed ALS with SIADH, and treatment with infusion of concentrated NaCl was started. However, the patient died of respiratory failure on day 50. We assumed that severely restrictive ventilatory impairment was the cause of SIADH in this case.

Aged↗
PubMed2002

[Pulmonary sarcoidosis in a case of dermatomyositis under long-term steroid therapy].

Pulmonary sarcoidosis in association with dermatomyositis has rarely been reported. A 52-year-old woman was admitted for evaluation of a previously unrecognized bilateral hilar lymphadenopathy on a chest radiogram in August 1995. She had been receiving oral corticosteroids for dermatomyositis, which was confirmed by the typical skin rash and the myogenic changes on an electromyogram in 1977. She had no respiratory symptoms at the time of admission. Chest computed tomography showed hilar and mediastinal lymphadenopathy with reticular shadows in the peripheral lung parenchyma. A 67gallium-citrate scintigram apparently revealed accumulation in bilateral hilums. The tuberculin skin reaction was negative. Flowcytometry of bronchoalveolar lavage fluid indicated a CD4/CD8 ratio of 5.37. Thoracoscopic biopsy specimens sampled from the mediastinal lymph nodes and the lung demonstrated non-caseating granulomas. A definitive diagnosis of pulmonary sarcoidosis was made from these findings. The chest radiographic findings were spontaneously resolved after three years with no increase in the dosage of oral corticosteroids. It is well known that an abnormal immune response playa an important role in development of dermatomyositis and sarcoidosis. This case suggested close associations in both diseases.

Anti-Inflammatory Agents↗
PubMed2002

[Saccharomyces-induced hypersensitivity pneumonitis in a dairy farmer: a case report].

A 58-year-old man, a dairy farmer, was admitted to Engaru Kosei Hospital because of cough, fever and dyspnea following repeated exposure to moldy silage in a silo. Chest radiography showed ground-glass opacity and tiny nodules in both lung fields. Arterial blood gas analysis showed severe hypoxia (PaO2, 30.8 torr). The patient was referred to Asahikawa Medical College Hospital for a diagnostic evaluation. At the time of admission, his symptoms were slightly resolved and the lung density on the chest radiograph was decreased. Pulmonary function tests revealed restrictive ventilatory impairment with a reduction in diffusing capacity. Bronchoscopic examination revealed mild lymphocytosis in the bronchoalveolar lavage fluid (BALF). Neither bacteria nor fungi were cultured from the BALF. Transbronchial lung biopsy specimens showed alveolitis with lymphocyte infiltration. The symptoms and signs disappeared spontaneously without any specific treatment, such as corticosteroids or antibiotics. A provocation test consisting of silage handling elicited recurrence of his symptoms, a decrease in diffusing capacity, and hypoxia. A definitive diagnosis of hypersensitivity pneumonitis (HP) was made from these findings. Samplings from the silage revealed a gross growth of the yeast Saccharomyces cerevisiae. A serum-precipitating antibody gave a positive reaction for an extract of S. cerevisiae. These results suggested that repetitive exposure to S. cerevisiae had led to sensitization through the patient's occupational environment, resulting in the development of HP.

Agriculture↗
PubMedDate not supplied

Renal artery stenosis emerged after angiotensin-converting enzyme inhibitor treatment for myocardial infarction: a case report.

A 76-year-old woman with acute myocardial infarction underwent percutaneous coronary angioplasty followed by treatment with an angiotensin-converting enzyme (ACE) inhibitor, lisinopril. Her renal function deteriorated after the administration of lisinopril, so it was changed to another ACE inhibitor, temocapril. Renography suggested a complication of severe right renal artery stenosis, and renal angiography revealed bilateral renal artery stenoses. Her renal hemodynamics were assessed by (99m)Tc-Mercaptoacetyltriglycine ((99m)Tc-MAG(3))-renography before and after withdrawal of temocapril. The authors concluded the patient had essential hypertension complicated by atherosclerotic renovascular disease. In the treatment of elderly patients with heart disease, hypertension, or both, with ACE inhibitor, the possibility of coexisting renal artery stenosis should be considered. Renography is recommended as a reliable tool for detecting renal artery stenosis.

Aged↗