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Biomedical subjects

M Yamakado

Publications and source records attributed to M Yamakado.

At least 37 records · Page 2Linked to original sources

Corticotropin-releasing hormone, proopiomelanocortin, and glucocorticoid receptor gene expression in adrenocorticotropin-producing tumors in vitro.

To differentiate between ectopic ACTH syndrome and Cushing's disease, gene expression of corticotropin-releasing hormone (CRH), proopiomelanocortin (POMC), and glucocorticoid receptor was examined in 10 pituitary adenomas (Cushing's disease) and in 10 ectopic ACTH-producing tumors. CRH increased plasma ACTH levels in all patients with Cushing's disease and in five patients with ectopic ACTH syndrome whose tumors contained CRH and CRH mRNA. In five CRH nonresponders, CRH was not detected in tumors that contained no CRH mRNA or that contained only long-size CRH mRNA. Dexamethasone (Dex) decreased plasma ACTH levels in all patients with Cushing's disease and in three patients with ectopic ACTH-producing bronchial carcinoid. These tumors contained glucocorticoid receptor mRNA. CRH increased and Dex decreased ACTH release and POMC mRNA levels in pituitary adenoma and bronchial carcinoid cells. PMA increased POMC mRNA levels only in carcinoid cells. These results reveal characteristics of ectopic ACTH-producing tumors: long-size CRH mRNA and PMA-induced POMC gene expression. In addition, there are two ectopic ACTH syndrome subtypes: tumors containing ACTH with CRH (CRH responder) and tumors without CRH. Dex decreases ACTH release and POMC mRNA levels in some bronchial carcinoids. Therefore, CRH and Dex tests have limited usefulness in differentiating between Cushing's disease and ectopic ACTH syndrome.

8-Bromo Cyclic Adenosine Monophosphate↗

Comparing postgraduate medical education at university and non-university hospitals in Japan.

In 1988 the authors surveyed all the teaching hospitals in Japan to evaluate the present status of postgraduate medical education (PGME); they received responses from 67 (84%) of the university and 172 (89%) of the non-university teaching hospitals. It was found that a large proportion of residents had spent two years in a residency without having had a single experience of some of the basic clinical skills. Consequently the residents' confidence in their abilities to perform these skills was low. The residents at the university hospitals, in particular, had had fewer experiences and were less confident about their clinical skills than were the residents at the non-university hospitals. The lack of standard and minimum requirements for PGME in Japan may be the cause of the poor level of acquisition of clinical skills of residents during PGME. Other possible causes are the tendency in Japanese medical society to attach greater importance to academic attainment than to clinical competence and the excessive gravitation of residents toward university hospitals. The authors suggest their results show the necessity to improve the training in basic clinical skills in PGME in Japan, especially in university hospitals.

Clinical Competence↗

A patient with a prolactinoma associated with an aldosterone producing adrenal adenoma: differences in dopaminergic regulation of PRL and aldosterone secretion.

A patient with a rare combination of prolactinoma and aldosterone producing adrenal adenoma (APA) was reported in relation to studies concerning dopaminergic regulation of PRL and aldosterone secretion. The patient is a 38-year-old female with plasma PRL and aldosterone concentrations (PAC) of 563 ng/ml and 54 ng/dl, respectively. A bolus of 10 mg of metoclopramide significantly increased plasma PRL in 6 normal subjects and in 4 patients with APA, whereas the responses were blunted in 7 patients with prolactinoma and in our patient. The response of aldosterone to metoclopramide was less than that of PRL, but similar in all studied subjects, indicating that the dopaminergic inhibition of aldosterone secretion is less than that of PRL in normal subjects and did not change in patients with APA or prolactinoma. Oral administration of 2.5 mg of bromocriptine suppressed plasma PRL significantly in all the subjects studied, but did not produce any consistent changes in PAC. Discrepancies in the response of PRL and aldosterone to metoclopramide and to bromocriptine suggest a difference in the dopaminergic regulation of PRL and aldosterone secretion in both normal subjects and patients with prolactinoma and APA. It is unlikely that reduced dopaminergic inhibition is the basis for hypersecretion of PRL and aldosterone in our patient.

Adenoma↗

Pathophysiological role of endothelin in renal transplantation.

To assess the pathophysiological role of endothelin (ET) in the early post-transplantation period, we followed plasma ET concentrations for 2 months from 1 week prior to surgery in four renal transplant patients. Plasma ET concentrations were elevated before transplantation in all patients. In two patients who developed marked pretibial edema, plasma ET concentrations increased before the onset of edema and before the increase in plasma atrial natriuretic peptide (ANP) concentrations, and remained high while the edema persisted. In the other two patients without edema, plasma ET and ANP concentrations fell toward normal immediately after transplantation. Plasma ET concentration increased transiently again in one of these patients when acute rejection occurred. After recovery from this rejection episode, the plasma ET concentration again fell to the normal range. There were significant correlations between plasma ET concentrations and changes in body weight and urine volume. These results suggest that the plasma ET concentration may reflect the function of transplanted kidneys and that ET may modulate body fluid volume regulation after transplantation. In addition, ET may participate in the pathogenesis of acute rejection.

Adult↗

Mechanisms of hypertension induced by erythropoietin in patients on hemodialysis.

To investigate the mechanisms of hypertension induced by recombinant human erythropoietin (rHuEPO) in patients on hemodialysis (HD), mean blood pressure (MBP), plasma renin activity (PRA), whole blood viscosity, blood volume (BV), cardiac index (CI) and total peripheral resistance index (TPRI) were measured before and after treatment with rHuEPO for 3 months in 9 patients on HD. Pressor responsiveness to exogenous norepinephrine (NE) and angiotensin II (AII) were also compared before and after treatment. Four patients were 'responders' (R) whose MBP increased by more than 10 mmHg, and 5 patients were 'non-responders' (non-R) whose MBP was unchanged or increased by less than 10 mmHg. Initial PRA and TPRI were significantly higher and BV was significantly lower in R than in non-R. After treatment, TPRI was increased in both groups, but CI was decreased in non-R. There was a significant correlation between changes in MBP and blood viscosity to rHuEPO. Pressor responsiveness to NE and AII were significantly enhanced after rHuEPO treatment in responders. These results suggest that inappropriate cardiovascular responses to the correction of anemia, increased blood viscosity, and enhanced pressor responsiveness may participate in the development of rHuEPO-related hypertension.

Adult↗

Echocardiographic findings in hemodialysis patients treated with recombinant human erythropoietin: proposal for a hematocrit most beneficial to hemodynamics.

We investigated the hemodynamic effects of the correction of anemia with recombinant human erythropoietin (rHuEPO) in 28 hemodialysis patients with severe anemia. Echocardiograms were recorded before the administration of rHuEPO (period I) with a hematocrit of 19.2 +/- 1.5% (mean +/- SD) and repeated twice (periods II and III) when the hematocrit was increased to 25.7 +/- 1.1% and to 30.0 +/- 1.0%. Left ventricular end-diastolic dimension (LVDd) decreased from 51.0 +/- 6.1 to 48.8 +/- 5.8 and to 48.3 +/- 7.1 mm, but no changes were observed in left ventricular end-systolic dimension. Cardiac output (CO) decreased from 5.89 +/- 1.46 to 5.00 +/- 1.44 and to 4.67 +/- 1.33 l/min. The thickness of the interventricular septum and the left ventricular posterior wall remained unchanged. Blood pressure was kept rather constant, although antihypertensive therapy needed to be adjusted to prevent the occurrence or aggravation of hypertension. Total peripheral resistance increased from 1481 +/- 359 to 1832 +/- 487 and to 1946 +/- 493 dynes.sec/cm5. The decreases in LVDd and CO were significant between periods I and II, without further changes between periods II and III. More antihypertensive therapy was needed in period III than in period II. Similar echocardiographic results were observed in 10 patients in whom antihypertensive therapy was not required throughout the study. In conclusion, an increase in hematocrit to 25% would be appropriate in order to obtain an effective hemodynamic improvement with rHuEPO therapy in dialysis patients although a higher hematocrit level might be desirable in order to improve working capacity.

Adult↗

Expression of cellular retinoic acid binding protein in the developing nervous system of mouse embryo.

The expression of cellular retinoic acid binding protein, CRABP, in developing mouse embryos was immunohistochemically analyzed. Differentiating young neurons and neuronal fibers in the myelencephalon, metencephalon, mesencephalon and spinal cord in 10.5- and 12.5-day embryos showed intense expression of CRABP, but undifferentiated cells in the neural tube did not. Neural tissue in 16.5-day embryos expressed less amount of binding protein than the tissues of the younger stages. These expressions of CRABP suggest that retinoic acid participates in neurogenesis at early developmental stages via expression of cellular retinoic acid binding protein.

Animals↗

Regulatory mechanisms of erythropoietin levels in dialysis patients.

We described a radioimmunoassay system for measuring blood erythropoietin (Epo) levels using recombinant human Epo and evaluated the regulatory mechanisms of Epo in dialysis patients. A satisfactory dose-response relationship for Epo levels was observed within the wide range of 3-250 mU/ml with a sensitivity of approximately 5 mU/ml. The Epo levels were found to be 16.1 +/- 8.6 mU/ml (m +/- SD) in 422 uremic patients on maintenance dialysis and 17.1 +/- 7.2 mU/ml in 86 normal subjects. The Epo levels were not statistically different between the two groups, although the hematocrit was significantly lower in the dialysis patients. No correlation was observed between the Epo levels and hematocrit in the dialysis patients. Patients with polycystic kidneys had higher hematocrits and Epo levels than patients with chronic nephritis. No changes in Epo levels were observed with age and with the period of dialysis. Diurnal variations in the Epo levels revealed a significant increase after hemodialysis, and an acute reduction in hematocrit following massive hemorrhage raised the Epo levels up to 3,180 mU/ml. These findings indicate that the Epo levels in dialysis patients are inappropriately low for the severity of anemia and suggest that a negative feedback mechanism of the hematocrit on the Epo secretion may exist in uremic patients as well as in normal subjects and that the threshold for Epo secretion might be 'reset' at a low hematocrit level.

Erythropoietin↗

Clinical significance of cerebral aneurysm in renovascular hypertension due to fibromuscular dysplasia: two cases in siblings.

Two cases, in siblings, of renovascular hypertension caused by fibromuscular dysplasia (FMD) of the renal artery associated with cerebral aneurysms are reported. Both of the cases were found to have cerebral aneurysm, as well as multiple stenotic or occluded lesions in arteries such as renal, mesenteric, celiac, and internal carotid arteries. One case died of subarachnoid hemorrhage and the other case was successfully operated on for the aneurysm. This report suggests that FMD should be considered to be a systemic angiopathy including the cerebral artery, as well as the renal artery. Thus, cerebral angiography is recommended to detect the association with cerebral aneurysm, at least, in cases with multiple lesions of FMD. Occurrence of FMD in siblings also indicates that a genetic factor might be involved in the pathogenesis of FMD.

Adult↗

[Plasma beta-endorphin in patients on maintenance hemodialysis].

A sensitive and specific radioimmunoassay for beta-endorphin without gel filtration of plasma extracts has been developed by using newly raised antibody. The minimal detectable quantity was 5 pg, and ED 50 was 23 pg/ml. The crossreactivity of antibody with beta-lipotropin was 3.3%, but not showed crossreaction with other fragments of beta-lipotropin, beta-MSH and ACTH. The inter-assay coefficient of variation was 2.7% to 17.4%, and the intra-assay coefficient of variation was 4.5% to 26.4%, respectively. The mean recovery for unlabeled beta-endorphin added to plasma and extracted was 92.1% to 110.4%. Plasma levels of beta-endorphin in 40 normal subjects was 14.7 +/- 3.1 pg/ml and 14.8 +/- 1.1 pg/ml in 10 patients with chronic glomerulonephritis whose renal function was normal. There was no significant difference between the two groups. On the other hand, plasma levels of beta-endorphin in 16 patients on maintenance hemodialysis was significantly increased of 56.3 +/- 6.3 pg/ml than the other two groups. Physiological role of this high beta-endorphinemia in patients on maintenance hemodialysis still remains to be resolved.

Adult↗

Dosage regimen of ranitidine in patients with renal impairment.

The validity of the Giusti-Hayton method for dosage regimen adjustment in patients with renal impairment was investigated using ranitidine. Five normal healthy volunteers received a single ranitidine recommended dose of 150 mg, and 20 patients with renal disease received single administration in doses individually calculated by the Giusti-Hayton method from each patient's creatinine clearance level, and the various pharmacokinetic parameters were compared. As a result, the area under the time-concentration curve 0----infinity (AUC0----infinity) in the renal disease patients was almost comparable to that in the normal healthy volunteers. The Giusti-Hayton method was considered useful to keep both the AUC0----infinity constant and the mean blood level of the drug in a steady state, in any degree of renal impairment.

Administration, Oral↗

Extrarenal role of aldosterone in the regulation of blood pressure.

To assess the hypothesis that aldosterone may have direct vasoconstrictive action, the acute effects of canrenoate potassium (Soldactone, S), an aldosterone antagonist, on hemodynamics and hormonal responses were determined before and after the intravenous administration of 2 mg/kg S in 11 patients with primary aldosteronism (PA), 9 patients with essential hypertension (EH), and 5 patients with renovascular hypertension (RVH). S caused a significant -12 +/- 2 mm Hg decrease in MBP in PA, -5 +/- 2 mm Hg in EH, and -4 +/- 1 mm Hg in RVH. Reduction in MBP was significantly higher in PA than in the others and there was a negative correlation between changes in MBP and basal PAC. The cardiac index did not change throughout the study in all groups, which led to a significant reduction in total peripheral resistance index (TPRI) in PA but not in the others. There was a significant correlation between changes in MBP and TPRI (r = 0.82, p less than 0.01). PRA did not change throughout the study, but PAC and cortisol were significantly elevated. There were no correlations between changes in MBP and hormonal responses. In conclusion, S resulted in a significant reduction of MBP mediated by a significant reduction of TPRI. These results suggest that aldosterone may have direct vasoconstrictive action and this extrarenal effect of aldosterone may be involved in the regulation of blood pressure.

Adult↗

Immunoreactive prorenin and its profragment peptide are present in human juxtaglomerular cells.

Although prorenin appears to be activated through the cleavage of its prosegment in the juxtaglomerular cells, the presence of prosegment peptide has never been demonstrated. We therefore studied prorenin in juxtaglomerular tumour cells, both by immunohistochemistry and by radio-immunoassay. Synthetic peptide covering the 14-carboxyterminal sequence of human renin prosegment was used to prepare both antibody and radiolabelled tracer. Intense immunostaining of prorenin was demonstrated in the tumour cells. By gel filtration, however, immunoreactive prorenin was shown to consist of two major components. The first peak, located at the elution position of activatable inactive renin, was regarded as prorenin. The other peak was located at an elution position with a smaller molecular weight, which was assumed to represent the profragment. These results suggest that both prosegment peptide and prorenin are present in the juxtaglomerular cells.

Adult↗

Hormonal and renal effects of atrial natriuretic peptide in patients with secondary hypertension.

To investigate the involvement of atrial natriuretic peptide (ANP) in secondary hypertension, we examined hormonal and renal responses to ANP infusion (0.025 microgram/kg/min) in 27 patients with renal parenchymal hypertension, 10 with primary aldosteronism, 8 with renovascular hypertension, and 15 normotensive subjects. The preinfusion plasma concentration of ANP was significantly higher in patients with renal parenchymal hypertension (120 pg/ml, p less than 0.01) and in patients with primary aldosteronism (98 pg/ml, p less than 0.05) than in the normotensive subjects (40 pg/ml), but it was not greater than in the patients with renovascular hypertension (73 pg/ml, NS). In the patients with renal parenchymal hypertension, plasma ANP correlated negatively with creatinine clearance (r = -0.76, p less than 0.001). Mean blood pressure (-5%, p less than 0.01) and plasma aldosterone (-40%, p less than 0.001) decreased to a similar degree in the four groups during ANP infusion. However, an increase in urinary sodium excretion caused by ANP was higher in the hypertensive than in the normotensive patients (+250% vs. +70%, p less than 0.01) and correlated positively with mean blood pressure during ANP infusion (r = 0.47, p less than 0.001). The removal of adenomas in the patients with primary aldosteronism significantly lowered both plasma levels of ANP and cyclic guanosine 2',3'-monophosphate and reduced an increase in sodium excretion during ANP infusion, whereas the responses of blood pressure and plasma aldosterone to ANP infusion were not altered by the operation. Thus, these results suggest that elevated ANP secretion and increased natriuretic responses to ANP may modify the blood pressure and body fluid volume status in some types of secondary hypertension.

Adrenal Gland Neoplasms↗