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Biomedical subjects

K Higuchi

Publications and source records attributed to K Higuchi.

At least 37 records · Page 2Linked to original sources
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1991

[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↗
PubMed1990

In vitro adaptive cytoprotection in gastric cells isolated from rat stomach.

The effects of mild irritants (2-5% ethanol or water at 45-55 degrees C) on production of prostaglandins (PGs) in gastric cells isolated from rat stomach and the damage caused by 15% ethanol were assessed. Gastric cells were isolated by the method of Matuoka et al., by which a suspension rich in surface epithelial cells was obtained. Synthesis of PGE2 by the cells was stimulated by 3% ethanol or water at 50 degrees C. The damage caused by 15% ethanol was much less in the cells treated with 3% ethanol or 50 degrees C water beforehand than in untreated cells. This protective effect by 3% ethanol or 50 degrees C water was abolished when the cells were treated with 10(-4) M indomethacin. These results suggest that 3% ethanol or 50 degrees C water protects the gastric cells from damage caused by 15% ethanol, possibly via endogenous PGs.

Animals↗
PubMed1990

Extracellular collagenase, proteoglycanase and products of their activity, released in organ culture by intact dermal inflammatory lesions produced by sulfur mustard.

Peak (1 and 2 d) and healing (3, 6, and 10 d) inflammatory lesions were produced in rabbits by the topical application of the military vesicant, bis(2-chloroethyl)sulfide, commonly called sulfur mustard (SM). SM produces an acute sterile dermal inflammatory reaction with little or no necrosis, except in the epidermis, which dies during the first day. After an animal was killed, its lesions were excised intact, as full-thickness 1.0-cm2 explants. They were then organ-cultured for 3 d in order to maintain the viability of both local and infiltrating cells. The extracellular fluid in each lesion equilibrated with the culture fluid, which was collected daily and analyzed for collagenase and proteoglycanase activities. These metalloproteinase activities were measured after we had i) destroyed the alpha-macroglobulin inhibitors with KSCN, ii) destroyed the tissue inhibitor of metalloproteinases (TIMP) by reduction and alkylation, and iii) activated the latent proteinase activity with aminophenylmercuric acetate (APMA). Hydroxyproline-containing peptides and glycosaminoglycans (GAG) released into the culture fluids were also measured as indicators of local collagenase and proteoglycanase activity within the inflammatory lesions. In general, the levels of both the metalloproteinases and the products of their activity were higher in second- and third-day culture fluids than in first-day culture fluids, and higher in fluids from SM lesions than in those from normal skin. The activated fibroblast was apparently the major cell type producing the collagenase and proteoglycanase. The hydrolysis of collagen and ground substance occurs pericellularly. An excess of inhibitors exists outside the pericellular region. The daily change in culture fluids apparently decreased such inhibitors, so that by the second and third day of culture we could detect the changes in pericellular enzyme activity that were not detectable on the first day of culture. As the inflammatory lesions healed, the extracellular enzyme products (hydroxyproline and GAG) increased more than the enzymes that produced these products. With healing, a decrease occurs in the extravasation of all serum components, especially the large ones such as the alpha-macroglobulin inhibitors. We propose that during healing, the decrease in these inhibitors allows the metalloproteinases to begin the remodeling process, and that during the peak phase of inflammation, these same inhibitors protect extracellular matrix against hydrolysis by such proteinases.

Animals↗