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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 307 records · Page 17Linked to original sources

Atrial and brain natriuretic peptide in adrenal steroidogenesis.

We elucidated the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human and bovine adrenocortical steroidogenesis. The urinary volume, sodium excretion and cyclic GMP (cGMP) excretion and plasma cGMP were markedly increased by the synthetic alpha-human ANP (alpha-hANP) infusion in healthy volunteers. Plasma arginine vasopressin (AVP) and aldosterone levels were significantly suppressed. Both ANP and BNP inhibited aldosterone, 19-OH-androstenedione, cortisol and DHEA secretion dose-dependently and increased the accumulation of intracellular cGMP in cultured human and bovine adrenal cells. alpha-hANP significantly suppressed P450scc-mRNA in cultured bovine adrenal cells stimulated by ACTH. Autoradiography and affinity labeling of [125I]hANP, and Scatchard plot demonstrated a specific ANP receptor in bovine and human adrenal glands. Purified ANP receptor from bovine adrenal glands identified two distinct types of ANP receptors, one is biologically active, the other is silent. A specific BNP receptor was also identified on the human and bovine adrenocortical cell membranes. The binding sites were displaced by unlabelled ANP as well as BNP. BNP showed an effect possibly via a receptor which may be shared with ANP. The mean basal plasma alpha-hANP level was 25 +/- 5 pg/ml in young men. We confirmed the presence of ANP and BNP in bovine and porcine adrenal medulla. Plasma or medullary ANP or BNP may directly modulate the adrenocortical steroidogenesis. We demonstrated that the lack of inhibitory effect of alpha-hANP on cultured aldosterone-producing adenoma (APA) cells was due to the decrease of ANP-specific receptor, which caused the loss of suppression of aldosterone and an increase in intracellular cGMP.

Adrenal Cortex↗

Cystic papillary carcinoma of the thyroid gland: a new sonographic sign.

Cystic thyroid lesions are generally considered to be benign and managed by repeated aspiration and/or biopsy. We report characteristic sonographic signs in eight cases of cystic papillary carcinomas of the thyroid gland. In all eight cases, ultrasonography (US) revealed mostly cystic lesions with solid excrescences protruding into the cyst. These nodules contained multiple punctate echogenic foci suggesting calcification. In three of these cases the initial fine needle aspiration biopsy was negative. The 'calcified nodule in cyst' sign was found to be very specific for cystic thyroid carcinoma in a review of the ultrasound findings in 115 patients with nodular thyroid lesions. Careful evaluation and/or surgery should be recommended in patients who have such characteristic sonographic findings even if the fine needle aspiration result is negative.

Adult↗

Pituitary hormone response to thyrotropin-releasing hormone in secondary amenorrheic women associated with simple weight loss.

OBJECTIVE: To investigate endocrine dysfunction in simple weight loss amenorrhea. DESIGN: We studied pituitary hormone responses to thyrotropin-releasing hormone (TRH) in 10 women with simple weight loss amenorrhea. SETTING: Department of Obstetrics and Gynecology, University Hospital, University of Tokushima at Tokushima, Japan. PATIENTS, PARTICIPANTS: Secondary amenorrheic women associated with simple weight loss who did not have anorexia nervosa. INTERVENTIONS: Intravenous injection of 500 micrograms of synthetic TRH. MAIN OUTCOME MEASURE: Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyrotropin, and prolactin were measured before and 15, 30, and 60 minutes after TRH injection. RESULTS: In normally menstruating women on day 7 of the cycle TRH did not affect serum LH and FSH levels. In women with simple weight loss amenorrhea, however, TRH raised serum LH and FSH levels significantly (P less than 0.01, respectively). Prolactin response to TRH was significantly (P less than 0.05) lower in women with simple weight loss amenorrhea than in normally menstruating women. CONCLUSIONS: These results indicate that TRH causes a significant rise in serum LH and FSH and the impaired prolactin response in women with simple weight loss amenorrhea.

Adult↗

Roles of renal and vascular renin in spontaneous hypertension and switching of the mechanism upon nephrectomy. Lack of hypotensive effects of inhibition of renin, converting enzyme, and angiotensin II receptor blocker after bilateral nephrectomy.

Inhibitors of angiotensin converting enzyme, renin, and the angiotensin II (Ang II) receptor lower the blood pressure of spontaneously hypertensive rats (SHR) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of renin in SHR, antirenin antibodies, the converting enzyme inhibitors delapril, enalapril, and the Ang II receptor antagonist DuP 753 were administered to intact and bilaterally nephrectomized SHR and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of renal origin is a dominant factor. Gradual but complete disappearance of antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin converting enzyme in the maintenance of the spontaneous hypertension.

Angiotensin II↗

Gastric cytoprotection by ornoprostil, a PGE1 analogue, in human subjects.

Ornoprostil, a methyl derivative of PGE1 developed in Japan, was tested for its effect on gastric mucosal damage caused by ethanol in human subjects. Sixteen healthy volunteers were given either ornoprostil or a placebo, followed by 20 ml of 70% ethanol instilled into the gastric antral mucosa. Fifteen minutes later, visible mucosal lesions were evaluated endoscopically. The biopsy specimens were obtained from mucosa that had been exposed to ethanol but looked normal. The specimens were assessed by light microscopy and scanning electron microscopy. The gross mucosal damage demonstrated endoscopically was significantly less (p less than 0.05) in the subjects receiving ornoprostil than those receiving placebo. Hyperemia and hemorrhage in the mucosa were also significantly less (p less than 0.05) in the subjects given ornoprostil pretreatment. Ornoprostil, however, failed to prevent the disruption of surface epithelial cells as assessed by scanning electron microscopy. These data suggest that ornoprostil protects gastric mucosa against damage caused by concentrated ethanol.

Adult↗

H2-receptor antagonist-refractory ulcer: its pathophysiology and treatment.

We assessed the intraluminal pH and mucosal prostaglandin E2 (PGE2) concentrations in patients (nonresponders) whose gastric ulcer did not heal after an initial 2 months and subsequent 3 months of treatment with one of five H2-receptor antagonists (H2RAs). The efficacy of misoprostol, a PGE1 analogue, or AG-1749, a proton-pump inhibitor, on ulcer healing in nonresponders was also tested. The percentage of time (24-h measurement) during which the pH was 3 or more was higher in the basal condition (no H2RA) in nonresponders than in good responders with healing in the first 2 months. H2RAs increased this percentage satisfactorily in nonresponders as well as in good responders. The mean mucosal PGE2 concentration in the ulcer rim was 26 ng/g of tissue in nonresponders, much lower than in good responders. Treatment with misoprostol combined with an H2RA resulted in 60% success for ulcer healing within the next 2 months in nonresponders, without affecting the intraluminal pH measured during treatment with an H2RA alone. AG-1749 raised the percentage of time with high pH to 99% from the 68% obtained with an H2RA and cured 88% of this type of ulcer. These results suggest that extremely low PGE2 levels in gastric mucosa are related to the effectiveness of the H2RA. In such a condition, the small amount of gastric acid that is still secreted even during treatment with an H2RA may interrupt ulcer healing. Therefore, treatment with a prostaglandin analogue combined with an H2RA or treatment with a proton-pump inhibitor may be useful for ulcer healing in nonresponders.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Role of vascular wall renin: intracellular and extracellular mechanism.

Inhibitors of angiotensin-converting enzyme, renin and angiotensin II receptor lower the blood pressure of spontaneously hypertensive rats (SHRs) used as a model of essential hypertension. Since their plasma renin levels were normal or subnormal, renin in the vascular tissue was considered to play a key role in the maintenance of the hypertension. To clarify the source and localization of vascular renin in SHRs, the effects on blood pressure of antirenin antibodies, the converting enzyme inhibitors delapril and enalapril, and the angiotensin II receptor antagonist DuP 753 were examined in intact and bilaterally nephrectomized SHRs and their normotensive controls. The efficient hypotensive action of the renin antibody indicated that renin of the renal origin is a dominant factor. The gradual but complete disappearance of the antihypertensive action of these inhibitors of the renin-angiotensin system upon bilateral nephrectomy indicated the importance of membrane-associated renin of the renal origin and angiotensin-converting enzyme in the maintenance of the spontaneous hypertension.

Animals↗

Intradermal hepatitis B virus vaccination for low- or non-responded health-care workers.

Immune responses to hepatitis B virus (HBV) vaccine in six low- or non-responded health-care workers were tested with an intradermal low dose (5 micrograms) of the recombinant vaccine. The injection was repeated three or four times at fortnightly intervals. These successive doses of the vaccine induced a high concentration of antibodies with delayed-type hypersensitivity (DTH) skin reactions in all six subjects. A few minor temporary side effects, such as irritation and itching at the injection site, were reported by some of the vaccinees. The results suggest low-dose of intradermal HBV vaccinations for low- or non-responders are safe and readily effective.

Administration, Cutaneous↗

Decreased binding capacity for alpha-human atrial natriuretic peptide in aldosterone-producing adrenocortical adenoma.

The previous study demonstrated that the aldosterone secretion of aldosterone-producing adrenocortical adenoma failed to be suppressed by human atrial natriuretic peptide, based on the data in synthetic alpha-human atrial natriuretic peptide infusion in vivo and the effect on in vitro secretion from cultured adenoma cells. Using the membrane fractions prepared from human adrenal tissues and an aldosterone-producing adenoma tissues, we characterized the binding sites for [125I] alpha-human atrial natriuretic peptide by the binding study and affinity-labeling of [125I] alpha-human atrial natriuretic peptide. Both normal adrenal and adenoma tissue membrane fractions possessed specific binding sites, however the relative binding capacity for [125I] alpha-human atrial natriuretic peptide in the adenoma preparations was markedly lower than that in the normal adrenal tissue preparation. The specific binding sites for [125I] alpha-human atrial natriuretic peptide were detected at the region of 140 KD and 67-70 KD only in the normal adrenal membrane fractions. Our data suggest that the refractoriness to the effect of atrial peptide may be due to the reduced receptor sites in aldosterone-producing adenoma cells.

Adenoma↗

Mouse senile amyloidosis. ASSAM amyloidosis in mice presents universally as a systemic age-associated amyloidosis.

Amyloid deposition in 11 inbred strains of mice (A/J, SJL/J, DDD, C57BL/6J, B10.BR, C57BL/10, B10A/SgSn, C3H/HeMs, B10A(5R), DBA/2 and C57BL/6Cr5/c) was studied using the peroxidase antiperoxidase (PAP) method and antisera against ASSAM and murine protein AA. Among the 170 mice examined, in 77 (45.3%) from the nine strains other than C3H/HeMs and DBA/2, there was evidence of spontaneous amyloid deposits in routine histological sections. Immunohistochemical studies using 54 mice with amyloid deposition, demonstrated ASSAM deposition in 45 mice (83.3%) in all nine strains, although the incidence and intensity of the deposition differed somewhat between strains. SJL/J and A/J had ASSAM deposits from the age of 8 months and the incidence increased with advancing age. In the other seven strains, ASSAM was first deposited at an older age than in the SJL/J and A/J strains. In A J, C57BL/6J, C57BL/10, B10.BR, B10A(5R) and C57BL/6Cr5/c, protein AA often coexisted with ASSAM. The distribution pattern of the ASSAM deposits was similar to that observed among the SAM strains. Thus, ASSAM is an ubiquitously distributed senile amyloid protein in the mouse. Determination of the molecular type of apoA-II, a serum precursor of ASSAM, among all 11 strains using the polymerase chain reaction (PCR) revealed the SAM-P/1 type apoA-II variant in SJL/J and A/J strains with a high susceptibility to ASSAM deposition. We concluded from this study that amino acid substitution in precursor apoA-II may be responsible for the early onset and severe amyloid deposition in the mouse.

Aging↗

[A case report of esophageal liposarcoma].

We report the first case of esophageal liposarcoma in Japan. A 46-year-old female was admitted to our hospital with chief complaint of protruding tumor out of the mouth. She had two episodes of protruding tumor after nausea in last 6 months. Barium swallow showed a large polypoid lesion of approximately 16cm in length with a stalk. By endoscopic examination, it was the polyp originated from the anterior wall of the cervical esophagus. It was covered with intact squamous epithelia, which had slight redness and erosion in the apex. Under general anesthesia the tumor was cut off at the base through the oral cavity. Specimen was 11 x 4 x 3cm in size and had yellowish cut surface. Histologically, the tumor composed of mature adipocytes and many atypical lipoblasts with spider web shaped cytoplasm. We diagnosed this tumor as well differentiated liposarcoma.

Esophageal Neoplasms↗

Kinetic analysis of amyloid fibril polymerization in vitro.

We investigated the polymerization kinetics of murine senile amyloid fibrils (fASSAM) in vitro. When sonicated murine senile amyloid fibrils was incubated with its constituent monomer protein, the extension of amyloid fibrils was observed in an electron microscopic analysis. Quantitative fluorometric analysis with thioflavine T (Naiki H, Higuchi K, Hosokawa M, Takeda T: Anal Biochem 177:244, 1989) revealed that (a) extension of amyloid fibrils occurred by a pseudo-first-order exponential increase in the fluorescence of thioflavine T; (b) the rate of extension was maximal around pH 7.5, and was inhibited with the increase in KCl or NaCl concentration in the reaction mixture; (c) the rate of polymerization was proportional to the product of the murine senile amyloid fibrils number concentration and the constituent monomer protein concentration; (d) the net rate of extension was the sum of the rates of polymerization and depolymerization with the equilibrium association constant K of 5 x 10(7) M-1. These results show that amyloid fibril formation can apparently be explained by a first-order kinetic model: that is, extension of amyloid fibrils proceeds by consecutive association of precursor proteins onto the ends of existing fibrils.

Aging↗

[Cardiac operation in patients older than 70 years].

To clarify the predictors of operative risk in the elderly, preoperative clinical features and postoperative short term outcome were retrospectively evaluated in 328 consecutive patients. Patients underwent coronary artery bypass or valvular surgery from July 1988 to December 1990 in our hospital: 78 patients were 70 years or older (elderly group) and 250 were younger than 70 years old (control group). Preoperative renal and respiratory function were slightly depressed in the elderly group than in the control group. Prolonged ventilatory support and the administration of inotropic agent were required in some elderly patients with renal or respiratory dysfunction. Neurological complications occurred more frequently in the elderly group than in the control group. Prolonged ventilatory support was needed in almost all the elderly patients with neurological complications. The operative mortality rate was similar in the two patient groups. In contrast, the hospital mortality rate was significantly higher in the elderly group than in the control group. The main causes of the higher hospital mortality in the elderly group was pulmonary infection and sepsis. These results suggest that the prolonged intensive care induces lethal infection and high hospital mortality in the elderly patients undergoing cardiac surgery.

Age Factors↗

[Acute nephrotoxicity by CDDP (on tubular damage)].

Cisplatin (CDDP) is known to cause a nephrotoxic side effect. By using urinary trehalase which is localized renal tubular brush border, we examined an acute cisplatin nephrotoxicity. 1) With less than 300 mg of CDDP, urinary trehalase activity in the 1st day was significantly increased than preadministration. And urinary beta 2-MG was significantly increased in the 2nd day. But urinary NAG was not significantly increased. 2) With 300 mg or more of CDDP, urinary trehalase, beta 2-MG and NAG were more increased than preadministration. Urinary trehalase and beta 2-MG were inclined to increment. But urinary NAG was not inclined to decrement. Above all, renal tubular damage is reversible with less than 300 mg of CDDP, but is irreversible with 300 mg or more of CDDP.

Acetylglucosaminidase↗