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Biomedical subjects

H Hatakeyama

Publications and source records attributed to H Hatakeyama.

At least 37 records · Page 2Linked to original sources
PubMed1999

11beta-hydroxysteroid dehydrogenase in cultured human vascular cells. Possible role in the development of hypertension.

11beta-Hydroxysteroid dehydrogenases (11beta-HSD) interconvert cortisol, the physiological glucocorticoid, and its inactive metabolite cortisone in humans. The diminished dehydrogenase activity (cortisol to cortisone) has been demonstrated in patients with essential hypertension and in resistance vessels of genetically hypertensive rats. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) catalyzes only 11beta-dehydrogenation. However, a functional relationship between diminished vascular 11beta-HSD2 activity and elevated blood pressure has been unclear. In this study we showed the expression and enzyme activity of 11beta-HSD2 and 11beta-HSD type 1 (which is mainly oxoreductase, converting cortisone to cortisol) in human vascular smooth muscle cells. Glucocorticoids and mineralocorticoids increase vascular tone by upregulating the receptors of pressor hormones such as angiotensin II. We found that physiological concentrations of cortisol-induced increase in angiotensin II binding were significantly enhanced by the inhibition of 11beta-HSD2 activity with an antisense DNA complementary to 11beta-HSD2 mRNA, and the enhancement was partially but significantly abolished by a selective aldosterone receptor antagonist. This may indicate that impaired 11beta-HSD2 activity in vascular wall results in increased vascular tone by the contribution of cortisol, which acts as a mineralocorticoid. In congenital 11beta-HSD deficiency and after administration of 11beta-HSD inhibitors, suppression of 11beta-HSD2 activity in the kidney has been believed to cause renal mineralocorticoid excess, resulting in sodium retention and hypertension. In the present study we provide evidence for a mechanism that could link impaired vascular 11beta-HSD2 activity, increased vascular tone, and elevated blood pressure without invoking renal sodium retention.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

[Superior vena cava reconstruction combined with resection of mediastinal-pulmonary malignant tumors].

From 1988 to 1997, we experienced 5 cases of the superior vena cava (SVC) replacement with expanded polytetrafluoroethylene (ePTFE) grafts combined with resection of mediastinal or pulmonary malignant tumors. Two patients had lung cancer and three had invasive thymoma. Resection and reconstruction of the superior vena cava (SVC) were performed by application of a bypass graft between the innominate vein and the right atrium in two cases and a temporary bypass using a heparin-coated tube in three cases. Except in one patient who died of acute respiratory failure, no complication or occlusive symptom were observed postoperatively. Two patients remain healthy for 5 years 4 months and 2 years 7 months after operation. Three died 9 years, 5 months, and 110 days after operation respectively. In conclusion, ePTFE graft replacement or patch angioplasty of the SVC should be part of planning and execution of radical excision with curative intent of mediastinal or pulmonary malignant tumors.

Adult↗
PubMed1998

[Probability of leaving cancer tissue unresected by limited operation in patients with peripheral, stage I non-small cell lung cancer].

To study the probability of leaving metastatic lymph nodes or intralobar metastasis unresected by limited surgery, we reviewed histopathologically 189 patients who had major pulmonary resection and complete lymph adenectomy for peripheral, p-T 1 or T 2 non-small cell lung cancer from 1975 to 1997 at our hospital. Lymph node involvements and or intralobar metastasis were found in 25 (26.0%) of 96 cases with tumor smaller than 3.0 cm and 44 (47.3%) of 93 cases with tumor larger than 3.0 cm. There was no difference between histological types of lung cancer. From this result, it was suggested that the risk of leaving cancer by limited operation would not be low. In conclusion, we believe that limited operation is not an alternative to the standard resection in patients with peripheral, stage I non-small cell lung cancer.

Aged↗
PubMed1997

Vascular aldosterone in genetically hypertensive rats.

We have reported that aldosterone is synthesized and cytochrome P450aldo mRNA exists in the vasculature. To clarify the pathophysiological role of vascular aldosterone in hypertension, we compared aldosterone production in the mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats (WKY). The expressions of mRNA of cytochrome P450aldo, mineralocorticoid receptor, and alpha 1, Na,K-ATPase in the mesenteric arteries were compared between the two groups. Aldosterone concentration in the perfusate of the vasculature was measured by radioimmunoassay after purification with high-performance liquid chromatography. Cytochrome P450aldo and mineralocorticoid receptor mRNA levels were quantified by Southern blot analysis of the products of reverse-transcribed polymerase chain reaction. Levels of alpha 1 Na,K-ATPase mRNA were measured by Northern blot analysis. Vascular aldosterone and cytochrome P450aldo mRNA levels of 2-week-old SHRSP were significantly increased compared with those of age-matched WKY. However, vascular aldosterone in 4- and 9-week-old SHRSP did not differ from that in age-matched WKY. Expression levels of mineralocorticoid receptor mRNA in the vasculature of 4- and 9-week-old SHRSP were significantly increased compared with those in age-matched WKY. Concentrations of vascular alpha 1 Na,K-ATPase mRNA of 2-, 4-, and 9-week-old SHRSP also were significantly higher than those in age-matched WKY. These results suggest that vascular aldosterone contributes to the pathophysiology of hypertension in SHRSP in the early stage.

Aldosterone↗
PubMed1997

[Results of surgical treatment of T4 lung cancer].

A total of 381 patients with primary lung cancer including 30 cases of T4 lesion, were surgically treated at our hospital from June 1975 through July 1996. Extended resection was performed in 11 patients. The 5-year survival rate after operation for all cases of T4 lung cancer, including one with operative death was 15.2%. Six patients who had curative operation showed no significant prolonged survival when compared to 24 patients who resulted in non-curative operation, but the median survival time of the former was longer than that of the latter. Six patients survived over 3 years; malignant pleurisy and/or intrathoracic dissemination of lung cancer were existed in 3 cases of those patients. In conclusion, extended resection for patients with T4 lung cancer should be limited to patients who are expected to have curative operation.

Adenocarcinoma↗
PubMed1997

[A case of primary malignant melanoma of the esophagus].

A case of primary and malignant melanoma of the esophagus was reported. A 64-year-old male complaining of discomfort of anterior chest pain was admitted to our hospital for operation. Findings of upper G-1 X-ray and endoscopic examination revealed suspiciously malignant melanoma. Subtotal thoracic esophagectomy with R III dissection was performed. Operative findings included A0 N2 Pl0 M0 Stage III. Macroscopically it showed black-grayish colored polypoid tumors, 7 cm in size. The typical finding of junctional activity adjacent to the tumor mass and melanocytes were microscopically found. The patient received postoperative systemic chemotherapy, but was died of multiple liver and bone metastases 125 days after surgery. Malignant melanoma of the esophagus has extremely poor prognosis and none of effective therapies has been reported.

Esophageal Neoplasms↗
PubMed1997

Changes in bradykinin and prostaglandins plasma levels during dextran-sulfate low-density-lipoprotein apheresis.

The negative charges of dextran-sulfate (DS) used for low-density-lipoprotein (LDL) apheresis initiate the intrinsic coagulation pathway in which plasma kallikrein acts on the high-molecular-weight kininogen to produce large amounts of bradykinin. This study was undertaken to assess whether bradykinin generated during DS LDL apheresis has any physiologic effects in vivo. The plasma levels of bradykinin, prostaglandins and cyclic guanosine monophosphate (cGMP) were compared. when either of two anticoagulants, heparin or nafamostat mesilate (NM), was used during DS LDL apheresis. Although anticoagulative action by NM depends on the inhibition of thrombin activity this substance also inhibits the activity of plasma kallikrein. During apheresis using heparin, the plasma levels of prostaglandin E2 (PGE2) increased significantly (5.6 +/- 1.2 (mean +/- SE, n = 4) pg/ml before apheresis and 33.4 +/- 13.2 after apheresis, p < 0.05) in association with an increase in bradykinin levels (17.9 +/- 2.6 pg/ml before apheresis and 470 +/- 135 after apheresis, p < 0.01). Interestingly, these changes were suppressed during apheresis using NM. There were no appreciable changes in cGMP during DS LDL apheresis with either of the anticoagulants. This finding suggests that bradykinin generated during apheresis has some pathophysiological effects via activation of the prostaglandin system. Our results support the view that in patients taking angiotensin-converting-enzyme inhibitors, the anaphylactoid reaction occurring during apheresis may be caused by an excessive rise in the bradykinin levels.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

The expression of steroidogenic enzyme genes in human vascular cells.

Recently, we demonstrated that aldosterone is produced by human vascular cells, and that vascular aldosterone is linked to angiotensin II-induced hypertrophy of vascular smooth muscle cells. We therefore examined whether genes encoding steroidogenic enzymes responsible for aldosterone biosynthesis from cholesterol are expressed in vascular cells. Using polymerase chain reaction after reverse transcription, type I and II 3 beta-HSD (3 beta-hydroxysteroid dehydrogenase), P-450c21 (21-hydroxylase), and P-450c18 (18-hydroxylase/oxidase) genes were found to be expressed both in endothelial cells and smooth muscle cells cultivated from human pulmonary arteries. However, P-450scc (cholesterol side chain cleavage enzyme) and P-45011 beta (11 beta-hydroxylase) mRNAs could not be detected. These findings suggest that the enzyme system responsible for aldosterone production in human vascular cells is different from that found in the adrenal cortex and that vascular aldosterone may be synthesized from metabolic intermediates which originate from the circulation. Extra-adrenal 3 beta-HSD and steroid 21-hydroxylase occur in a wide variety of tissues. Thus, human vascular cells can retain the ability to produce aldosterone by expressing the P-450c18 gene.

3-Hydroxysteroid Dehydrogenases↗
PubMed1996

Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis.

The hypothesis that dietary branched-chain amino acid (BCAA) supplementation improves the impaired protein turnover in male Donryu rats with carbon tetrachloride-induced liver cirrhosis was tested. We supplemented cirrhotic rats orally for 2 wk with BCAA solution [26.67 mg BCAA/(100 g body weight . d)], a conventional amino acid mixture [4.25 mg BCAA/(100 g body weight . d)] or saline and fed these three groups the AIN76 basal diet to have similar intakes of total energy and total nitrogen. Normal rats without liver cirrhosis were fed the basal diet similar to the above (noncirrhotic controls). After supplementation, rats were fed intravenous transthyretin (thyroxine-binding prealbumin) doubly labeled with 125I-tyramine-cellobiose and 131I. Kinetic indices including production rate of transthyretin were analyzed from plasma transthyretin disappearance curves. Tissue sites of transthyretin degradation were assayed using a trapped ligand technique by measuring 125I-tyramine-cellobiose levels. The production rate of transthyretin was significantly lower in cirrhotic rats supplemented with saline (mean 25.46 X 10(-3) . h(-1)) compared with noncirrhotic controls (45.08 X 10(-3) . h(-1)) (P < 0.05). This was corrected by supplementing cirrhotic rats with BCAA (37.05 X 10(-3) . h(-1), P < 0.05) but not with conventional amino acid mixture (22.49 X 10(-3) . h(-1)). The accelerated degradation of transthyretin in muscles of cirrhotic rats was improved by BCAA (P < 0.05). In conclusion, dietary supplementation with BCAA improves the impaired transthyretin turnover in rats with liver cirrhosis.

Administration, Oral↗
PubMed1996

Endogenous renal 11 beta-hydroxysteroid dehydrogenase inhibitory factors in patients with low-renin essential hypertension.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and is important in blood pressure control. The excretion of renal 11 beta-HSD (ie, NAD(+)-dependent isoform) is thought to protect renal mineralocorticoid receptors from cortisol. To examine whether endogenous renal 11 beta-HSD inhibitory factor(s) may be involved in the pathophysiology of hypertension, we studied the urinary excretion of such inhibitors in 30 patients with low-renin essential hypertension and 20 normotensive control subjects. The effect of sodium restriction on the urinary excretion of the inhibitors wa also evaluated in six normotensive control subjects. Urine was extracted with Sep-Pak cartridges and high-performance liquid chromatography. Endogenous renal 11 beta-HSD inhibitors were measured by the inhibition of 11 beta-HSD bioactivity in microsomes from the human kidney. The urinary excretion of the inhibitors was significantly increased in patients with low-renin essential hypertension (1280 +/- 88 nmol/d, mean +/- SEM) compared with normotensive control subjects (704 +/- 56 nmol/d) (P < .05). Ratios of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone did not differ significantly. Sodium restriction reduced the urinary excretion of the endogenous renal 11 beta-HSD inhibitors but did not affect the ratio of urinary tetrahydrocortisol+allo-tetrahydrocortisol to tetrahydrocortisone. Endogenous renal 11 beta-HSD inhibitory factors may contribute to the pathogenesis of low-renin essential hypertension by modulating the activity of 11 beta-HSD. Sodium intake may directly or indirectly regulate the inhibitory factors.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1996

Effect of adrenocorticotropin stimulation on the synthesis of 19-noraldosterone in man.

The hormone, 19-noraldosterone, which was recently shown to be synthesized and produced in the human adrenal gland, exhibits potent mineralocorticoid and hypertensinogenic activities. This hormone is controlled in part by the renin-angiotensin system. We studied the effects of ACTH stimulation on the synthesis of 19-noraldosterone in vitro and in six normal men. 19-Noraldosterone was measured by a specific RIA after the urine extract or incubation medium was purified by high performance liquid chromatography. The 24-h urinary excretion of 19-noraldosterone increased approximately 4-fold during the administration of ACTH (40 U, injected im twice daily for 3 days). Virtually identical responses were observed with aldosterone, 18-hydroxycorticosterone, 18,19-dihydroxycorticosterone, and 18-hydroxy-19-norcorticosterone. Glomerulosa cells isolated from human adrenals were incubated with angiotensin II (10(-7), 10(-8), and 10(-9) mol/L) or ACTH (10(-8), 10(-9), and 10(-10) mol/L). Angiotensin II and ACTH increased the production of 19-noraldosterone dose-dependently from isolated glomerulosa cells. The secretion of aldosterone, 18-hydroxycorticosterone, 18,19-dihydroxycorticosterone, and 18-hydroxy-19-norcorticosterone in response to angiotensin II and ACTH was identical to that of 19-noraldosterone. These observations suggest that 19-noraldosterone is stimulated by the renin-angiotensin system as well as ACTH.

18-Hydroxycorticosterone↗
PubMed1996

Regulation of aldosterone synthase in human vascular endothelial cells by angiotensin II and adrenocorticotropin.

Mineralocorticoids have been suggested to act on blood vessels, leading to increased vasoreactivity and peripheral resistance. Aldosterone is synthesized locally in blood vessels and participates in the hypertrophy of vascular smooth muscle cells. In this study we examined the effects of angiotensin II (ANG II), potassium, and ACTH on the production of aldosterone, the activity of aldosterone synthase, and the expression of CYP11B2 and CYP11B1 messenger ribonucleic acid (mRNA) in cultured human vascular endothelial cells. Human vascular endothelial cells were incubated with ANG II, potassium, or ACTH with or without [14C]deoxycorticosterone ([14C]DOC). Incubation medium was collected, and chromatography was preformed in a reverse phase high performance liquid chromatography system. The concentration of aldosterone in the incubation medium was measured using RIA after separation with the high performance liquid chromatography system. The activity of aldosterone synthase was estimated by the conversion of [14C]DOC to [14C]aldosterone. The levels of CYP11B2 and CYP11B1 mRNA were determined by competitive PCR. ANG II, potassium, and ACTH increased the production levels of aldosterone in a dose-dependent fashion. Both ANG II and potassium increased the conversion of [14C]DOC to [14C]aldosterone, but ACTH did not significantly increase the conversion. Both ANG II and potassium increased the concentration of CYP11B2 mRNA, but not that of CYP11B1 mRNA. Tumor necrosis factor reduced ANG II- and potassium-induced aldosterone synthesis and CYP11B2 mRNA levels. ACTH did not influence the expression of CYP11B2 mRNA. These results suggest that vascular aldosterone synthase is controlled by ANG II and potassium at the transcriptional level.

Adrenocorticotropic Hormone↗
PubMed1995

Induction of apoptosis by acyclic retinoid in the human hepatoma-derived cell line, HuH-7.

HuH-7 cells, a human hepatoma-derived cell line, underwent apoptosis in response to all-trans 3, 7, 11, 15-tetramethyl- 2, 4, 6, 10, 14-hexadecapentaenoic acid, or acyclic retinoid. The retinoid-induced apoptosis was verified by a characteristic step-wise fragmentation of genomic DNA and chromatin condensation. The induction of apoptosis was detected as early as 8 hrs after the addition of the retinoid and was concentration dependent (0.1-10 microM). Neither the natural retinoid all-trans retinoic acid nor 9-cis retinoic acid induced apoptosis. These data strongly indicate that the antitumor activity of the acyclic retinoid may be partly explained by the induction of apoptosis in tumor cells.

Apoptosis↗
PubMed1995

Vascular complications in patients with aldosterone producing adenoma in Japan: comparative study with essential hypertension. The Research Committee of Disorders of Adrenal Hormones in Japan.

The incidence of vascular complications in 224 patients with aldosterone-producing adenoma (APA) which was proven on adrenal surgery, was compared to that in 224 sex- and age-matched patients with essential hypertension (EHT). The incidence of cerebral hemorrhage was significantly higher (p < 0.05) in the patients with APA when compared to the EHT group. On the other hand, the incidence of myocardial infarction and/or congestive heart failure in the APA group was lower, although this difference did not reach statistical significance. Diastolic blood pressure in the APA group was significantly higher (p < 0.001) in the EHT group. However, a significant difference in diastolic blood pressure was not detected between the APA groups with and without vascular complications, whereas in the EHT group diastolic blood pressure was significantly higher (p < 0.001) in cases with vascular complications as compared to those without complications. As a possible factor contributing to the higher incidence of cerebral hemorrhage in the APA group, proteinuria was suggested. It was recommended that patients with primary aldosteronism should undergo operation when localization of the APA is established.

Adenoma↗
PubMed1995

Human papillomavirus type 16-positive esophageal papilloma at an endoscopic injection sclerotherapy site.

Human papillomavirus infection is important for both the development of papilloma and the progression of the papilloma-carcinoma sequence in the cervix, larynx, lung, and colon. Esophageal squamous cell papilloma is rare but important as a possible precancerous lesion. Esophageal papilloma has previously been thought to develop mainly as a result of chemical irritation by chronic gastroesophageal reflux. However, a few recent studies suggested a role for papillomavirus infection in esophageal tumorigenesis, although the exact route of transmission and invasion of the virus has not been fully elucidated. A case of esophageal squamous papilloma at the site of endoscopic injection sclerotherapy (EIS) for varices is reported. Papilloma development was followed up clinically during a 2-year period, and the papilloma was removed by endoscopic mucosal resection. Histological examination of the tissue confirmed the diagnosis of squamous cell papilloma. DNA analysis of the tumor showed integration of papillomavirus type 16 but not types 18 and 33. The surrounding normal mucosa did not contain any of the three virus types. Injury such as ulceration resulting from EIS may have provided a locus susceptible to the viral infection. The clinical course after EIS should be monitored carefully to detect papilloma formation.

Adult↗
PubMed1995

Aldosterone biosynthesis and action in vascular cells.

In view of the hypothetical possibility that the vascular renin-angiotensin system (RAS) might include aldosterone biosynthesis and action in the vasculature, we have undertaken a study to identify aldosterone released into the perfusion circuit from the rat mesenteric artery, and to investigate the effects of an angiotensin converting enzyme inhibition (ACEI) on aldosterone production from the vasculature. After 30 min equilibration, 240 mL of perfusate was collected and subjected to reverse-phase HPLC and subsequent mass spectrometry. Mass spectra corresponding to authentic corticosterone and aldosterone were obtained from the samples of mesenteric artery perfusate. Production of aldosterone in the mesenteric artery was not changed by adrenalectomy, although it was reduced in the arterial perfusate from rats pretreated with ACEI. By RT-PCR the expression of CYP 11B2 and mineralocorticoid receptor genes were demonstrated in both vascular endothelial and smooth muscle cells. These studies constitute indirect evidence supporting our hypothesis that locally produced aldosterone in the vascular tissue acts on vascular tone and remodeling via a paracrine or autocrine manner.

Aldosterone↗