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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 217 records · Page 12Linked to original sources

Interaction of opioids and vasopressin in central action of angiotensin II in conscious rabbits.

It has been demonstrated that opioids modulate the renin-angiotensin and sympathetic nervous system. To clarify the interaction of central angiotensin II (Ang II) and endogenous opioids, we studied the effects of naloxone, an opioid antagonist, on cardiovascular and sympathetic responses to intracerebroventricular (i.c.v.) Ang II in conscious rabbits. I.c.v. Ang II (20 ng/min) significantly increased mean arterial pressure (MAP), plasma epinephrine, and arginine vasopressin (AVP) levels, with no significant change in renal sympathetic nerve activity (RSNA) or heart rate. Pretreatment with intravenous naloxone (0.1 mg/kg) failed to alter the cardiovascular and neurohormonal responses to i.c.v. Ang II. To eliminate the effect of AVP on cardiovascular and sympathetic responses, [d(CH2)5Thy(Me)]AVP, a vasopressin V1-receptor antagonist, was given intravenously. Pretreatment with intravenous injection of the V1-receptor antagonist (30 micrograms/kg) augmented the maximum increase in RSNA caused by i.c.v. Ang II (8.9 +/- 2.2 vs. 16.2 +/- 0.7%, p < 0.05). Combined pretreatment with naloxone and V1-receptor antagonist further increased MAP and RSNA in response to ICV Ang II (20 +/- 1 vs. 16 +/- 2 mmHg, p < 0.05, and 30.9 +/- 3.7 vs. 16.2 +/- 0.7%, p < 0.01, respectively). These results suggest that opioids and AVP synergistically modulate sympathetic outflow so as to suppress the central pressor action of Ang II in conscious rabbits.

Angiotensin II↗

Familial isolated hyperparathyroidism due to multiple adenomas associated with ossifying jaw fibroma and multiple uterine adenomyomatous polyps.

We describe three siblings with hyperparathyroidism due to multiple parathyroid adenomas without evidence of other endocrinological abnormalities. A 22-year-old woman had two parathyroid adenomas complicated by multiple ossifying jaw fibromas. Her sister, aged 29, also suffered from primary hyperparathyroidism associated with two parathyroid adenomas one of which was also suspected to be a carcinoma. These two female patients had unusual multiple small uterine polyps, which were diagnosed as adenomyomatous polyps. Their brother, aged 17, had two parathyroid adenomas complicated by urolithiasis. These three patients are characterized by young adult-onset familial isolated hyperparathyroidism due to multiple adenomas with various complications including ossifying jaw fibroma and uterine adenomyomatous polyps. These clinical features are different from those of familial hyperparathyroidism associated with multiple endocrine neoplasia.

Adenoma↗

Simultaneous activation of Ca(2+)-dependent K+ and Cl- currents by various forms of stimulation in the membrane of smooth muscle cells from the rabbit basilar artery.

In smooth muscle cells isolated from cerebral blood vessels, histamine activates Cl- channels through an elevation of intracellular Ca2+. We investigated whether Cl- currents were also evoked by adenosine triphosphate (ATP) or caffeine in isolated smooth muscle cells from the rabbit basilar artery using the perforated patch-clamp technique. Bath application of 10 microM ATP or 1 mM caffeine (holding potential -60 mV) activated transient inward currents. With prolonged bath application of 10 microM ATP or 1 mM caffeine, oscillatory inward current were sporadically generated. At a holding potential of -40 mV, transient Cl- currents were induced by 10 microM histamine, 10 microM ATP, and 1 mM caffeine, following activation of a K+ current. At -10 or -20 mV, histamine predominantly activated the K+ current. A repetitively activated outward current was induced by membrane depolarization. These results suggest that oscillations in intracellular Ca2+ induced by histamine, ATP, and caffeine caused Cl(-)-current activation at the resting membrane potential. This Cl- current may depolarize the membrane and, thus activate voltage-dependent currents, including a Ca(2+)-dependent K+ current. Both the Ca(2+)-dependent K+ and Cl- currents induced by various stimuli may contribute to the modulation of Ca2+ influx by reinforcing membrane depolarization.

Adenosine Triphosphate↗

Serum leptin levels in smokers with type 2 diabetes.

OBJECTIVE: To elucidate the molecular mechanism of smoking cessation and its relationship to body weight gain, the effects of smoking on the serum levels of leptin were studied in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: The serum levels of leptin after an overnight fast in 37 adult male Japanese patients with type 2 diabetes (17 smokers and 20 nonsmokers) were assayed using radioimmunoassay. In addition, the serum leptin levels in four nondiabetic smokers were measured before and 2 weeks after quitting smoking. RESULTS: Smokers and nonsmokers did not differ in age, BMI, or levels of blood glucose and fasting insulin but did differ in HDL cholesterol levels (1.07 +/- 0.18 vs. 1.32 +/- 0.24 mmol/l for smokers and nonsmokers, respectively, P = 0.002). The mean serum leptin level of smokers did not differ from that of nonsmokers (3.8 +/- 1.9 vs. 3.8 +/- 1.6 ng/ml). The leptin level correlated with the fasting insulin level and BMI (r = 0.55 and 0.56, P < 0.001 and 0.001, respectively). The leptin levels in four heavy smokers showed no change after the subjects quit smoking (3.3 +/- 1.0 vs. 3.8 +/- 1.8 ng/ml, before and after quitting, respectively). CONCLUSIONS: Because smoking did not affect the leptin levels, the effects of quitting smoking on the fuel metabolism appear to be due to some other factors.

Adult↗

A case of microscopic polyarteritis nodosa with interstitial pneumonia successfully treated with steroid pulse therapy and immunosuppressive agents.

We report a patient with microscopic polyarteritis nodosa (mPN) and interstitial pneumonia, who was subjected to investigation by bronchoalveolar lavage (BAL), thoracic computerized tomography (CT) and gallium-67 citrate (67Ga) scintigraphy before and after administration of glucocorticoid and immunosuppressive agents. Renal function, renal histology, interstitial inflammation of the lung, and pulmonary function and histology improved cytoplasmic autoantibody (MPO-ANCA), which decreased with decreasing disease activity after starting treatment. Interstitial pneumonia may be associated with pulmonary capillaritis due to mPN. Methylprednisolone pulse therapy followed by oral prednisolone and immunosuppressive agents is considered to be an effective therapeutic strategy for combined mPN and interstitial pneumonia.

Anti-Inflammatory Agents↗

Comparative efficacies of a calcium antagonist and an alpha1 blocker in elderly hypertensive patients with stroke.

We compared the effects of nilvadipine, a calcium antagonist, and terazosin. an alpha1 blocker, on the hemodynamics and quality of life (QOL) in 12 elderly hypertensive patients with stroke. Following a washout period of 2 weeks. nilvadipine or terazosin was administered for 2 weeks in a randomized crossover manner. At the end of control and treatment periods, we measured the 24-hour-ambulatory blood pressure (BP) and postural change of BP, and interviewed QOL. Terazosin treatment did not show consistent decrease of casual BP, but was associated with a transient decrease of systolic BP and an increase of pulse rate after standing, and enhanced postprandial decrease in BP. Nilvadipine decreased casual BP in a dose-dependent manner, but showed neither postural nor postprandial change of BP. There was no difference in QOL scores with either treatment. Results suggest that nilvadipine is preferable to terazosin for the treatment of elderly hypertensive patients with stroke.

Adrenergic alpha-Antagonists↗

Thrombotic thrombocytopenic purpura accompanied by transient pure red cell aplasia and thymoma.

We describe a 64-year-old man with thrombotic thrombocytopenic purpura (TTP), transient pure red cell aplasia (PRCA) and thymoma. TTP in this case was thought to be idiopathic and was accompanied by microangiopathic hemolytic anemia. The patient, therefore, had an aplastic crisis due to PRCA. He was treated with peritoneal dialysis, plasma exchange with plasma infusion, red blood cell transfusion, methylprednisolone pulse therapy followed by maintenance dosing with intravenous prednisolone, gamma-globulin, vincristine, and dipyridamol. As a result, the patient's mental disorder, acute renal failure, anemia and thrombocytopenia improved; however, the haptoglobin level remained low. The pathogenesis of PRCA and thymoma indicates that these are immunological disorders often associated with each other. To our knowledge, there are no reports of TTP with transient PRCA and thymoma. Although such a combination is considered relatively rare, this case suggests that there is an immunological contribution to the pathogenesis of the association of these disorders.

Humans↗

B-cell monoclonality precedes the development of gastric MALT lymphoma in Helicobacter pylori-associated chronic gastritis.

Little is known about the temporal changes in Helicobacter pylori density and B-cell clonality during the evolution from chronic gastritis to gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Biopsied specimens from 28 patients with chronic gastritis who developed gastric MALT lymphoma (group A) and from 24 similar patients who did not (group B) during an equivalent follow-up period (mean, 42 months) were retrospectively scored for histological features of MALT lymphoma (0 to 5) and H. pylori density (0 to 3). B-cell clonality was analyzed by polymerase chain reaction (PCR). During the observation period, the H. pylori density in group A decreased significantly in comparison with group B; the mean change in H. pylori density (final minus initial density) per 1000 days was -1.4 for group A and +0.2 for group B (P < 0.005). Monoclonality was detected more frequently in group A (79%) than in group B (21%; P < 0.005), and it preceded the histological evidence of malignant transformation in 64% of those patients who showed monoclonality in group A. These results suggest that H. pylori is thus more closely associated with the precursor or initial phase in the genesis of gastric MALT lymphoma than with the later phase, as its density decreases as the tumor progresses. The detection of B-cell monoclonality by PCR is thus of possible use for predicting the histological genesis of gastric lymphoma.

Adolescent↗

Prevalence of hepatitis C virus antibody in patients on chronic hemodialysis.

Hepatitis C virus antibody (anti-HCV) was studied in 267 patients undergoing maintenance hemodialysis using an anti-HCV enzyme-linked immunosorbent assay. Furthermore, both hepatitis B virus core antibody (anti-HBc) and human T cell leukemia virus type 1 antibody (anti-HTLV-1) were determined in these patients to compare their prevalence rates. Seventy one patients (27%) had positive anti-HCV, 134 patients (50%) positive anti-HBc and 40 patients (15%) positive anti-HTVL-1. Among the 183 patients who had received blood transfusion, the prevalence of these antibodies was 34% for anti-HCV, 56% for anti-HBc and 17% for anti-HTLV-1, respectively. A significance between those with and without blood transfusion was recognized for anti-HCV (p < 0.001) and anti-HBc (p < 0.01). Of 56 patients who had received hemodialysis for over 15 years, the positive antibody was found in 63% for anti-HCV (p < 0.001), 73% for anti-HBc (p < 0.001) and 25% for anti-HTLV-1 (p < 0.05), which was significantly higher than that of patients receiving a less than 15 years hemodialysis. The prevalence rates of anti-HCV and anti-HTLV-1 did not increase with age, while that of anti-HBc increased. These findings suggest that blood transfusions during hemodialysis play a very important role in the infection of hepatitis C virus.

Adolescent↗

Regression of carotid wall thickening after corticosteroid therapy in Takayasu's arteritis evaluated by B-mode ultrasonography: report of 2 cases.

We describe 2 young Japanese female patients with active Takayasu's arteritis whose diagnosis was mainly based on the characteristic ultrasonographic finding, that is, a circumferential vascular wall thickening in common carotid arteries. Following corticosteroid therapy, serial ultrasonographic examination documented the improvement of their thickened carotid walls (in Case 1 from 1.4 to 0.5 mm after 2 months of therapy, in Case 2 from 1.5 to 0.9 mm after 9 months of therapy). These cases emphasize that ultrasonography is useful for evaluation of the therapeutic effect as well as for the diagnosis of Takayasu's arteritis in its early stage.

Adrenal Cortex Hormones↗

Central and peripheral mechanisms involved in hypertension induced by chronic inhibition of nitric oxide synthase in rats.

OBJECTIVE: To study the possible central and peripheral mechanisms involved in hypertension induced by chronic inhibition of nitric oxide synthase. METHODS: We evaluated neurohormonal and renal responses of Wistar rats to chronic oral administration of 20 and 100 mg/kg per day NG-nitro-L-arginine methyl ester (L-NAME). Effects of intracerebroventricular and intravenous injections of NO donors (NOC-18 and FK-409) and an angiotensin II type 1 receptor antagonist CV-11974, and intravenous injection of alpha-adrenergic receptor antagonist phentolamine after chronic treatment with 100 mg/kg per day L-NAME were also studied. RESULTS: The chronic treatment with L-NAME induced a sustained dose-dependent hypertension with a decrease in heart rate. Urinary levels of norepinephrine and epinephrine decreased with no changes in plasma catecholamine levels, renin activity, and vasopressin level. Serum nitrate/nitrite levels in the rats treated with the high dose of L-NAME decreased. The intracerebroventricular and intravenous injections of the NO donors reduced arterial pressure in L-NAME-treated rats to a significantly greater extent than they did that in control rats. The intravenous but not intracerebroventricular injection of CV-11974 produced a sustained decrease in arterial pressure of L-NAME-treated rats. The depressor responses to intravenous injection of phentolamine of L-NAME-treated and control rats were similar. CONCLUSIONS: Results indicate that L-NAME-induced hypertension is associated with a deficiency of nitric oxide, both peripherally and centrally. Circulating angiotensin II could contribute to the maintenance of hypertension via angiotensin II type 1 receptor while the sympathetic nervous system seems to be suppressed.

Acute Disease↗

Na+-dependent glucose uptake and collagen synthesis by cultured bovine retinal pericytes.

This study was performed to clarify the presence of sodium-dependent glucose uptake and its role in the synthesis of type IV and type VI collagen by cultured bovine retinal pericytes. The glucose uptake by retinal pericytes and retinal endothelial cells was measured using 3H-D-glucose in the presence or absence of sodium. Glucose uptake in the presence of sodium was twice as high as that observed in the presence of phlorizin and sodium or in the absence of sodium. Sodium-dependent glucose uptake was observed at different sodium concentrations, and its half-maximal stimulation occurred at 48 mM. These findings were not observed in retinal endothelial cells. Levels of type IV and type VI collagen produced by retinal pericytes were significantly increased at glucose concentrations higher than 20 mM. Phlorizin decreased both collagen synthesis and glucose consumption by retinal pericytes incubated with 30 mM of glucose to the levels observed with 5 mM of glucose. These data suggest that sodium-dependent glucose uptake is present in retinal pericytes and that excessive glucose entry into the cell is an important factor for overproduction of collagen. Phlorizin normalized the synthesis of type IV and type VI collagen with decreasing glucose consumption under high glucose conditions.

Animals↗

Polymorphism of the angiotensin-converting enzyme (ACE) gene in patients with thrombotic brain infarction.

The relationship between cerebrovascular disease and an insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is still being debated. We examined its role as a risk factor in patients with thrombotic brain infarction. The association between ACE polymorphism and ischemic stroke was examined in 181 patients with thrombotic brain infarction and 271 controls without strokes. The I/D polymorphism was examined using the polymerase chain reaction. Distributions of the ACE genotypes and alleles did not differ between the infarcted patients and the controls. Both distributions in patients with onset at age 60 years or younger were significantly higher than those in younger controls (genotype: chi 2 = 7.6, P = 0.02; allele: chi 2 = 5.6, P = 0.02). There were no significant differences in the distributions of ACE genotypes and alleles between the patients with lacunar infarcts and with cortical infarcts in all ages. There were also significant differences in the distribution of ACE genotypes and alleles between the younger and the elderly subgroup of patients with brain infarction (genotype: chi 2 = 12.9, P = 0.002; allele: chi 2 = 11.1, P = 0.0009). Furthermore, there was a significant decline in the frequency of the ACE D allele with increasing age in all patients with thrombotic brain infarction. These observations demonstrated a significant association between the ACE gene polymorphism and thrombotic brain infarction in patients age 60 years or younger in a Japanese population. Furthermore, there may be an association between the ACE D allele and mortality after cerebral infarction.

Aged↗

Effects of CP-060S on membrane channels in vascular smooth muscle cells from guinea pig.

The newly developed cardioprotective drug, CP-060S, (-)-(S)-2-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]-3-[3-[N-methyl-N- [2-(3,4-methylenedioxyphenoxy) ethyl] amino] propyl]-1,3-thiazolidin-4-one hydrogen fumarate, is reported to possess a vasodilating action. Our objective was to examine the effects of CP-060S on the membrane channels in mesenteric arterial cells from guinea pigs, using whole-cell patch-clamp techniques. CP-060S inhibited the Ca2+ channel current in a concentration-dependent manner (ED50 = 1.7 microM at a holding potential of -80 mV and a stimulation frequency of 0.1 Hz). The inhibition was potentiated by a more depolarized holding potential and a higher stimulation frequency. These effects of CP-060S resembled those of diltiazem and gallopamil more than to those of nifedipine; the inhibition was more frequency dependent and less holding-potential dependent than with nifedipine. Higher concentrations of CP-060S also inhibited the delayed K+ channel currents (ED50 = 18 microM). The present observations suggest that CP-060S exhibits the profile of a Ca2+ channel antagonist, similar to that of diltiazem and gallopamil.

Animals↗

Stretch-activated whole-cell currents in smooth muscle cells from mesenteric resistance artery of guinea-pig.

1. Stretch-activated (SA) channels were studied in smooth muscle cells isolated from mesenteric resistance arteries using the whole-cell patch-clamp method. Membrane stretch was achieved by cell inflation after application of positive pressure through a patch electrode. 2. In the voltage-clamp configuration, cell inflation increased and cell deflation decreased the membrane conductance. Conductance of the evoked current depended on the increase in cross-sectional area of the cell. The current-voltage relationship was linear between -80 and 0 mV, while further hyperpolarization showed a slight inward rectification. 3. The reversal potential of the SA current depended on the extracellular Na+ concentration, suggesting that the inward SA current was carried predominantly by Na+. The SA current was also carried by other cations, suggesting that the channel responsible for this current is a non-selective cation channel. The permeability sequence of cations as assessed by reversal potential was as follows: K+ > or = CS+ > or = Na+ > Li+. The channel was also permeable to Ca2+. 4. Extracellular Ca2+ and Gd3+ inhibited the SA current carried by monovalent cations in a concentration-dependent manner with IC50 (concentration giving 50% of maximal inhibition) values of 0.9 mM and 14 microM, respectively. 5. In the current-clamp configuration, membrane stretch depolarized the cell, and 100 microM Gd3+ inhibited the stretch-induced depolarization. 6. The results suggest that SA cation channels exist in arterial smooth muscle cells. Activation of the channels may modify membrane potential and intracellular ionic environment, and promote stretch-mediated cell responses.

Animals↗