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Biomedical subjects

M Nagano

Publications and source records attributed to M Nagano.

At least 145 records · Page 8Linked to original sources
PubMed1994

Prolactin and the immune system.

Prolactin (PRL) is involved in a wide range of physiological effects in several species and its immunoregulatory role has already been well documented. The PRL receptor has been cloned from various species. There are at least two receptor isoforms (short and long) in rats and mice, which differ only in their cytoplasmic domains, generated by alternative splicing of a single gene, although in human only the long form exists. Using the reverse transcriptase-polymerase chain reaction (RT-PCR), we detected transcripts encoding both forms of PRL receptor in all lymphoid tissues examined in human, mouse, and rat, but in mouse and rat the ratio between the two forms was variable from animal to animal. Concerning the transcript encoding the PRL itself, a clear signal was always found in human lymphocytes and occasionally in rat thymus. We also developed a quantitative PCR (Q-PCR) in order to measure the absolute number of transcripts in thymus and spleen from rats at two stages of estrous cycle. The level of expression of the two forms was about equal. Finally, we identified the tyrosine kinase JAK2, which is constitutively associated with the PRLR, using the Nb2 rat lymphoma cell line as a model system with which to study the action of PRL on cell mitogenesis. We also showed that, after stimulation by PRL, the dimerization process is a prerequisite step for the phosphorylation of the PRLR and JAK2, which represents the earliest event in the signal transduction pathway.

Animals↗
PubMed1994

Antihypertensive effects of the neutral endopeptidase inhibitor SCH 42495 in essential hypertension.

The antihypertensive effects and safety of a novel neutral endopeptidase inhibitor, SCH 42495, were investigated in hypertensive patients. A multicenter, open clinical trial was conducted in 27 patients with essential hypertension, WHO Stage I or II. Mean age was 64 +/- 1 years. After 2 to 4 weeks of a placebo run-in, 50 mg twice daily, was started, with the dose increased to 100 mg twice daily, and 200 mg twice daily, every 2 weeks, if necessary, to achieve a predetermined response. Blood pressure and pulse rate were monitored every 2 weeks. Blood chemistry, plasma atrial natriuretic peptide (ANP), and plasma cGMP levels were determined before and after the 8-week treatment period. Blood pressure was significantly reduced, from 171 +/- 1/100 +/- 1 mm Hg to 146 +/- 3/84 +/- 2 mmHg (P < .001) at the end of the 8-week treatment period. No change in pulse rate was noted. Efficacy rate was evaluated in 25 patients treated for 4 weeks or more. Efficacy rate was 44% with 50 mg twice daily, 60% with 100 mg twice daily, and 80% with 200 mg twice daily. Adverse reactions such as headaches and palpitation were observed in six patients (22.2%), with treatment discontinued in five. Significant correlation was observed between increment in plasma ANP levels and blood pressure reductions (r = -0.53, P < .05). Increase in plasma cGMP was positively correlated with increments in plasma hANP (r = 0.80, P < .001). SCH 42495 has potent antihypertensive effect associated with an enhancement of endogenous hANP and may be clinically useful as a new class of antihypertensive drug.

Aged↗
PubMed1994

Differential control of vascular tone and heart rate by different amino acid neurotransmitters in the rostral ventrolateral medulla of the rat.

1. To test the hypothesis that a central mechanism may play a role in the minimal reflex tachycardia noted in response to peripheral converting enzyme inhibition, we compared the effects of intravenous (i.v.) ceronapril (CER) with nitroglycerin (NTG) on neurotransmitter release in the rostral ventrolateral medulla (RVLM), using an in vivo microdialysis method in pentobarbital anaesthetized rats. 2. CER (0.1 mg/kg, i.v.) caused a progressive decrease in glutamate (GLU) release (CER 65 +/- 7% vs NTG 83 +/- 3% of each baseline at 140 min, P < 0.05) and attenuated the increase in glycine (GLY) release (CER 100 +/- 8% vs NTG 122 +/- 9%, P < 0.05). 3. Prevention of blood pressure reduction due to i.v. CER by concomitant infusion of a subpressor dose of angiotensin II (AII) attenuated the progressive reduction of GLU release (87 +/- 4%, P < 0.05 compared with NTG group), whereas GLY release was not affected (106 +/- 5%, NS compared with NTG group). 4. Perfusion of GLU into this area at approximately physiological concentrations resulted in a sustained tachycardia with an attenuation of the depressor effect of i.v. CER and perfusion of GLY solely lowered blood pressure. 5. These results demonstrate that i.v. converting enzyme inhibitor reduces the release of GLU in the RVLM, which was specifically caused by reducing circulating AII, without any effect on GLY release, thus resulting in the reduction of blood pressure with minimal effect on the heart rate.

Anesthesia↗
PubMed1994

Chronic administration of angiotensin II receptor antagonist, TCV-116, in cardiomyopathic hamsters.

We examined whether specific blockade of the renin-angiotensin system is beneficial for the treatment of cardiac dysfunction in heart failure. The angiotensin II type-1 (AT1) receptor antagonist TCV-116 (10 mg.kg-1.day-1) or its vehicle was given orally to UM-X 7.1 cardiomyopathic (CM) and normal Golden Syrian (GS) hamsters for 8 wk. Plasma and cardiac angiotensin II levels were significantly higher in CM than in GS hamsters. The CM heart showed a smaller response of left ventricular (LV) pressure and first derivative of maximal LV pressure (+dP/dtmax) to the elevation of perfusion pressure (from 60 to 120 cmH2O) in Langendorff-perfused than in GS heart. Treatment with TCV-116 did not affect LV function in GS but significantly improved cardiac contractility in CM hamsters. These results suggest that the renin-angiotensin system plays an important role in the development of cardiac dysfunction due to cardiomyopathy. Blockade of this system by the AT1 antagonist TCV-116 appears to be useful in the prevention of heart failure.

Angiotensin II↗
PubMed1994

Effects of age and hypertension on autonomic nervous regulation during passive head-up tilt.

To study the effects of age and hypertension on autonomic nervous function with passive postural change, we examined 31 normotensive subjects (25 to 85 years old) and 31 hypertensive patients (21 to 71 years old) without any cardiac disease, diabetes mellitus, or neurological disorders. Subjects were passively placed in a 60 degrees head-up tilting position after 15 minutes in the supine position. Autonomic nervous function was evaluated by frequency domain analysis of heart rate with the autoregressive method. Using low-frequency (0.1 Hz) and high-frequency (0.25 Hz) peaks, the ratio of low- to high-frequency power (L/H) was calculated as an index of sympathetic activity and the ratio of high to total power (%HF) as that of parasympathetic activity. With the patient in the supine position, total power spectral density declined logarithmically with age in normotensive subjects and hypertensive patients, but %HF and L/H showed no changes. In response to passive tilting, L/H was increased and %HF was decreased in the normotensive subjects, and these responses declined with age logarithmically. In contrast, hypertensive patients exhibited less autonomic response to postural change regardless of age. These results suggest that autonomic neural response to tilt is decreased with age; however, attenuation of the response by hypertension is not associated with an increase in age.

Adult↗
PubMed1994

Role of glucose intolerance in cardiac diastolic function in essential hypertension.

Insulin resistance and glucose intolerance have been suggested to be involved in the pathogenesis of various cardiovascular diseases. We examined the role of glucose intolerance in cardiac performance and cardiac hypertrophy in 33 patients with essential hypertension (28 to 71 years of age, mean +/- SD: 53 +/- 13 years) who had never been treated. Patients with obesity (body mass index > 30 kg/m2) or overt diabetes were excluded. Plasma glucose and insulin were measured after oral administration of 75 g glucose. The incremental areas of glucose and insulin were used as indices of glucose intolerance and insulin resistance, respectively. Patients with impaired glucose tolerance according to World Health Organization criteria (n = 12) showed a significantly higher ratio of peak velocity during atrial contraction to early left ventricular filling phase (A/E ratio) than those with normal glucose tolerance (n = 21) despite similar age, blood pressure, and left ventricular mass index. By regression analysis, left ventricular mass index positively correlated with systolic blood pressure (r = .392, P < .05) but not with any parameters of glucose and insulin metabolism. A/E ratio determined by a Doppler system significantly correlated with age ( r = .776) and fasting and peak levels and incremental area of plasma glucose (r = .529, r = .468, and r = .634) but not with those parameters of insulin. In contrast, ejection fraction was not related to blood pressure, glucose tolerance, or insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Risk factors related to the wall thickness of carotid artery assessed by ultrasonography].

Progression of atherosclerotic lesion of the carotid artery is suggested to induce the development of cerebrovascular events. We evaluate the risk factors related to carotid artery, wall thickness by ultrasonography. A total of 159 patients, who had received no medication for hypertension or hyperlipidemia were enrolled in this study. The wall thickness of carotid artery was evaluated as an intima-media (IM) complex measured by B-mode ultrasonography with a 7.5 MHz probe. Simple regression analysis demonstrated significant correlation between the IM complex and both age and systolic blood pressure, but not with fasting levels of plasma glucose, hemoglobin A1c, total and HDL cholesterol, triglyceride or gender. Stepwise regression analysis showed age and systolic blood pressure contribute to IM thickness (r = 0.623). However, in patients aged 60 or over, blood pressure did not contribute to the IM wall thickness. Smoking was not a risk factor for IM thickness, but the Brinkman Index (daily consumption of cigarettes x years smoking) was significantly higher in patients with plaques in the carotid artery than those without it. These results suggest that high blood pressure is a risk factor for mild atherosclerotic lesions of the carotid artery for those aged under 60. Smoking may contribute to the formation of plaque, which may consequently lead to the ischemic cerebrovascular disease.

Aged↗
PubMed1994

Role of the renin-angiotensin system in hypertension in the elderly.

Although the activity of the renin-angiotensin system is known to decrease with age, the antihypertensive efficacy of angiotensin-converting enzyme (ACE) inhibitors has been demonstrated in the elderly. To examine the role of the renin-angiotensin system in hypertension in the elderly, we evaluated the antihypertensive response to enalapril and to TCV-116, an angiotensin II type-1 receptor antagonist, in elderly patients with essential hypertension. A single oral dose of enalapril (10 mg) increased plasma renin activity (PRA) and reduced the angiotensin II concentration, whereas a single oral dose of TCV-116 (4 mg) increased both PRA and the angiotensin II concentration. Blood pressure was significantly reduced by these drugs from 4 h after administration. Basal levels of PRA and angiotensin II declined with age. However, the changes in blood pressure produced by either TCV-116 or enalapril did not correlate with age. These results suggest that the activity of the renin-angiotensin system in plasma declines with age, and that the extrarenal renin-angiotensin system may play a role in hypertension in the elderly.

Adult↗
PubMed1994

Effects of delapril hydrochloride on the myocardium of spontaneously hypertensive rats.

OBJECTIVE: To investigate the effects of long term treatment with delapril hydrochloride (an angiotensin-converting enzyme inhibitor) on myocardial contractility and ventricular myosin isoenzymes in spontaneously hypertensive rats (SHR). DESIGN: Delapril hydrochloride (10 mg/kg/day by mouth) was administered to 22- to 24-week-old male SHR for eight to 10 weeks. The isometric contractions of isolated left ventricular papillary muscles were observed while being perfused with Tyrode's solution (32 degrees C, pH 7.4, bubbled with 95% oxygen: 5% carbon dioxide, stimulation frequency 0.2 Hz). The left ventricular myosin isoenzymes were separated using pyrophosphate-gel electrophoresis. MAIN RESULTS: The mean systolic blood pressure of the delapril-treated group was significantly lower than that of the untreated control group. The mean ventricular weight was also lower in the delapril-treated than control group (mean +/- SD, untreated: 211 +/- 11 mmHg, n = 6; delapril-treated: 183 +/- 14 mmHg, n = 8, P < 0.01). The mean isometric developed tension (T) and +/-dT/dtmax of isolated left ventricular papillary muscles from the delapril-treated and untreated SHR did not differ significantly. The left ventricular myosin isoenzyme pattern obtained by pyrophosphate-gel electrophoresis, however, showed a significant shift towards VM-1 after long term delapril treatment. CONCLUSIONS: Long term treatment of SHR with delapril hydrochloride reduced blood pressure, which was associated with regression of cardiac hypertrophy, and changed the ventricular myosin isoenzyme pattern without significantly affecting myocardial contractility.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

[A case of Crow-Fukase syndrome associated with membranoproliferative glomerulonephritis].

Crow-Fukase syndrome is a rare multiorgan disorder. Although renal disorders, such as proteinuria, and renal impairment, have been observed in half the cases of this syndrome, there have been few reports describing the renal lesions. We report here a case of this syndrome associated with membranoproliferative glomerulonephritis. A 43-year-old woman was referred to our hospital because of hyperglycemia. She had also been suffering from hyperpigmentation, hepatosplenomegaly, lymphadenopathy, polyneuropathy and endocrine dysfunction, including diabetes mellitus and amenorrhea. Serum electrophoresis showed M protein and immunoelectrophoresis revealed IgA (lambda). Bone marrow aspiration showed a slight increase in the number of plasma cells. Urine protein was 30 mg/dl, BUN was 17 mg/dl and creatinine 0.8 mg/dl. Light microscopic examinations showed enlargement of glomeruli with proliferation of mesangial cells and matrix, a lobular pattern of the glomeruli and thickening of the glomerular basement membrane and associated double contour. Electron microscopic examinations showed thickened capillary walls, associated mesangial interposition and subendothelial dense deposits. Moreover, fine granular deposits of IgM, C3, and fibrinogen along the basement membrane were observed on immunofluorescent studies.

Adult↗
PubMed1994

[A case of sporadic acute type A hepatitis associated with acute renal failure].

We report a case of sporadic acute type A hepatitis associated with acute renal failure, due to mesangioproliferative glomerulonephritis and interstitial nephritis. A 42 year-old-man was admitted to Mitsui Memorial Hospital because of jaundice and oliguria with fever in February, 1989. His serum creatinine was 12.2 mg/dl, BUN 87 mg/dl, GOT 57 U/l and GPT 358 U/l. The serum IgM antibody to hepatitis A virus was positive, which indicated recent infection with hepatitis A virus. Hemodialysis and steroidal therapy were started, and the patient's acute renal failure and liver dysfunction ameliorated within one month. Light microscopic examinations showed an increased number of mesangial cells and an increased amount of mesangial matrix, and also showed inflammatory cell invasion in the interstitium. Electron microscopic examinations showed proliferation of mesangial cells and matrix, and a dense deposit along the basement membrane. On immunofluoresent studies, fine granular deposits of IgA and Clq were observed in the mesangium.

Acute Disease↗
PubMed1994

[Study on clinical effects of tosufloxacin (TFLX) and the long-term low dose therapy for the prophylaxis of recurrent urinary tract infection].

Forty five patients with complicated urinary tract infections were treated with tosufloxacin (TFLX) in the initial antibacterial treatment. Excellent and moderate responses were obtained in 39 patients (86.7%). No side effects were seen. Clinical efficacy and safety of long-term preventive administration of TFLX (150mg, a day) were also examined in 39 patients who showed an excellent or a moderate response in the initial treatment. The period of the administration ranged from 28 to 112 days (average; 55 days). The rate of preventing recurrence of urinary tract infection was 92.3% on the last day of treatment. These findings suggested that TFLX was useful not only in treating the patients with complicated urinary tract infections but also in preventing recurrence of urinary tract infection.

Adult↗
PubMed1993

Myocardial contractility and energetics in cardiac hypertrophy and its regression.

The changes in myocardial contractility and ventricular myosin isoenzymes were investigated in rats with pressure-overload cardiac hypertrophy as well as during its regression. Hypertrophic myocardium was obtained from rats with renovascular hypertension (Goldblatt rats), rats with abdominal aortic constriction (AC), and spontaneously hypertensive rats (SHR). Regression of cardiac hypertrophy was induced by lowering the blood pressure through nephrectomy on the affected side in Goldblatt rats, by opening the clip which constricted the abdominal aorta in AC rats, and by the administration of antihypertensive agents to SHR. The isometric developed tension of isolated left ventricular papillary muscles and the maximum rate of increase in the tension (dT/dtmax) were measured. Left ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis. Isometric developed tension remained unchanged, but dT/dtmax was decreased in hypertrophic myocardium, although it recovered along with the regression of cardiac hypertrophy. The left ventricular myosin isoenzyme pattern was shifted towards V3 in hypertrophic myocardium, and shifted back again towards V1 with the regression of cardiac hypertrophy. These results indicate that relief of hemodynamic overload is one of the most important elements in the regression of cardiac hypertrophy and the associated physiological or biochemical alterations. However, other factors such as neurohumoral influences must also be taken into consideration.

Animals↗
PubMed1993

Beneficial effect of ACE inhibitor in congestive heart failure.

The effects of captopril, an angiotensin-converting enzyme inhibitor, on congestive heart failure (CHF) were investigated in animal and clinical studies. Congestive heart failure was induced in rats by a combination of pressure and volume overload. Cardiac pressure overload was induced by constricting one renal artery (Goldblatt rat) and volume overload was induced by aorto-caval fistula. Captopril (100 mg/kg/day) was then administered for 14 weeks. Isometric contraction was assessed using isolated left ventricular papillary muscles. The maximum developed tension and the maximum rate of increase in tension (dT/dtmax) were decreased in untreated rats with CHF and improved in captopril-treated rats. The left ventricular myosin isoenzyme pattern was shifted towards V3 in untreated rats with CHF, and was shifted back towards V1 in the captopril-treated rats. In the clinical study, captopril (37.5-75 mg/day) was administered to patients with cardiomyopathy for 12 months. There was no effect on left ventricular mass in hypertrophic cardiomyopathy, although systolic anterior motion of the mitral valve disappeared in one patient. In dilated cardiomyopathy, however, left ventricular mass tended to decrease. These results indicate that captopril has a beneficial effect in congestive heart failure.

Animals↗
PubMed1993

A possible functional necklace formed by placental antigen X-P2-immunoreactive and intensely acetylcholinesterase-reactive (PAX/IAE) glomerular complexes in the rat olfactory bulb.

The relationship between placental antigen X-P2 (PAX)-immunoreactive glomeruli and intensely acetylcholinesterase-reactive (IAE) patchy regions was evaluated by comparison of neighboring cryostat sections of the rat olfactory bulb. Both groups of distribution show similar necklace patterns. Each IAE region consists of heterologous glomerulus-like structures with variable acetylcholinesterase reactivity: strongly and less-reactive (IAE-S and IAE-L) structures. The PAX-immunoreactive glomeruli were detected as parts of the IAE-L portions. Three heterologous PAX/IAE glomeruli or glomerulus-like structures (IAE-S, IAE-L/PAX and IAE-L/non-PAX structures) locally form a distinct glomerular complex, the 'PAX/IAE glomerular complex'. At the caudal end of the main olfactory bulb, nine to sixteen such complexes occur at intervals and form a circumferential 'necklace'. Since one of them corresponds to the 'modified glomerular complex' involved in rat suckling behavior, the entire 'necklace' may be associated with processing olfactory stimuli eliciting or suppressing the suckling response.

Acetylcholinesterase↗
PubMed1993

Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11 beta), but the salt-sensitive hypertensive rat does not.

Molecular cloning of cytochrome P450(11 beta) cDNAs from the adrenal glands of Dahl's salt-sensitive hypertensive (DS) and salt-resistant normotensive (DR) rats was performed using a combined technique of the first strand cDNA synthesis by reverse transcriptase followed by polymerase chain reaction. The cDNA sequence of P450(11 beta)-DS was identical to that of wild type P450(11 beta). In contrast, the clone obtained from the DR rat contained six nucleotide substitutions causing five amino acid alterations (Arg-127-->Cys, Val-351-->Ala, Val-381-->Leu, Ile-384-->Leu, and Val-443-->Met). When the two cDNAs were expressed in COS-7 cells and steroid conversion rates of the transformed cells were determined, a ratio of 18-hydroxylation to 11 beta-hydroxylation of 11-deoxycorticosterone by P450(11 beta)-DS-expressed cells was 0.58, whereas that by P450(11 beta)-DR-expressed cells was 0.23. Plasma levels of 18-hydroxy-11-deoxycorticosterone and corticosterone (the 11 beta-hydroxylation product of 11-deoxycorticosterone) in DS and DR rats well reflected the steroidogenic activities of the two P450s. These results suggest that the characteristic plasma steroid level of the DR rat is caused by the mutations in P450(11 beta) gene and may act to maintain the normotensive blood pressure in this rat strain during sodium loading.

Amino Acid Sequence↗
PubMed1993

An aromatase-associated cytoplasmic inclusion, the "stigmoid body," in the rat brain: II. Ultrastructure (with a review of its history and nomenclature).

The ultrastructure of aromatase-associated "stigmoid (dot-like) structures," which were detected in a previous study using light-microscopic immunohistochemistry (Shinoda et al.: J. Comp. Neurol. 322:360-376, '92), were examined in the rat medial preoptic region, bed nucleus of the stria terminalis, medial amygdaloid nucleus, and arcuate nucleus by pre- and post-embedding marking with a polyclonal antibody against human placental antigen X-P2 (hPAX-P2) for immuno-electron microscopic analysis. The immunoreactive stigmoid structure was identified as a distinct, non-membrane-bounded cytoplasmic inclusion (approximately 1-3 microns in diameter), which has a granulo-fuzzy texture with moderate-to-low electron density in non-immunostained preparations. It consists of at least four distinct granular and three distinct fibrillo-tubular elements forming a granulo-fibrillar conglomerate. This type of inclusions was formally termed the "stigmoid body" under the electron microscope. The stigmoid body is composed of the outer granulo-fibrillar and inner hyaloplasmic compartments. The immunoreactivity for hPAX-P2 is mainly localized to the former, especially to the low density granulo-fuzzy materials associated with the fibrillo-tubular elements. Identification of the ultrastructure of stigmoid body clarified their prevalence not only in the limbic and hypothalamic regions, but also in sex-steroid-sensitive peripheral tissues (e.g., peripheral sensory ganglia, ovary, testis) by consulting earlier electron-microscopic studies. Reviewing the history and nomenclature of this inclusion body, we reorganized the terminology of related neuronal cytoplasmic inclusions, the terms of which have often been confused, and discussed its functional significance on the basis of the present and previously accumulated data. In conclusion, we emphasized the importance of the stigmoid bodies in the sex-steroid-sensitive neural system because of their large size, high frequency, specific distribution in brains and peripheral tissues, effects of sex-steroids, and immunological and histochemical characteristics of the antibody marking the inclusion. The stigmoid bodies may provide a subcellular site for sex-steroid metabolism in their target tissues and play a critical role in cytosolic modulation of their actions (e.g., by aromatization) prior to their receptor binding.

Amygdala↗