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Biomedical subjects

M Mihara

Publications and source records attributed to M Mihara.

At least 127 records · Page 7Linked to original sources
PubMed1995

Renal refractoriness to phosphaturic action of parathyroid hormone in a patient with hypomagnesemia.

A 50-year-old tetanic woman with hypomagnesemia is described. She had partial resection of the stomach and the jejunum at the age of 20 years. Lack of parathyroid hormone (PTH) function was indicated by hypocalcemia, hyperphosphatemia and high tubular reabsorption of phosphate. However, both plasma concentration of PTH and nephrogenous cAMP were normal. Administration of magnesium sulfate completely normalized serum phosphate and tubular transport of phosphate with only a modest increase in nephrogenous cAMP. The present findings suggest that phosphaturic action of PTH is impaired in magnesium deficiency and that steps distal to cAMP production may be responsible for the renal refractoriness to the hormonal action.

Female↗
PubMed1994

Lichen sclerosus et atrophicus. A histological, immunohistochemical and electron microscopic study.

We studied three cases of genital lichen sclerosus et atrophicus (LSA) using histological, immunohistochemical and ultrastructural techniques to elucidate the characteristics of the collagen fibres, the elastic fibres and the interfilamentous matrix in the upper dermal homogeneous zone. In the early stages of LSA, the homogeneous zone caused elaunin fibres to push downwards and partially disappear, the collagen fibres were presumably phagocytosed by fibroblasts, and there were peculiar cells containing numerous vacuoles in the cytoplasm. In the advanced stages of LSA, the homogeneous zones showed newly formed collagen fibres and amorphous, dispersed, medium electron-dense substances that were probably composed of elastin or elastin-like substances and microfilaments originating from the collagen fibres. Immunohistochemically, there were numerous anti-aortic alpha-elastin-positive substances, but there was no positivity for anti-amyloid P component. These findings suggest that in advanced LSA a hybrid substance (elastocollagenous mass) between collagen fibres and elastic fibres may be formed in the homogeneous zone.

Aged↗
PubMed1994

Toxicity and chemical form of selenium in the liver of mice orally administered selenocystine for 90 days.

The subacute oral toxicity of selenocystine and chemical form of selenium in the liver following exposure to this compound were assessed in ICR male mice. Animals were dosed 6 days/week for 30, 60 or 90 days with 0, 5, 10 or 15 mg/kg per day. Body weight gain decreased with dosage. The activities of aspartate aminotransferase and alanine aminotransferase in plasma were significantly elevated at the highest dose level after 60 days and at the two higher dose levels after 90 days of exposure. However, the level of selenium content in the liver was the same at the two higher dosages at both 60 and 90 days of exposure. The subcellular distribution of selenium in the liver from mice treated with selenocystine showed that the major part of the total selenium content, 68.3-72.1%, existed in the cytosolic fraction. Sephadex G-150 chromatograms of liver cytosol of the animals administered selenocystine revealed three selenium-containing fractions which involve glutathione peroxidase (molecular weight 80,000) high molecular (molecular weight 55,000-60,000) and low molecular (molecular weight < 10,000) substances. Selenium content and acid-volatile selenium content in the high molecular weight fraction increased with exposure time to selenocystine. Thus, in a subacute toxicity study selenocystine given for 90 days caused hepatic damage in mice, depending on the acid-volatile selenium content in the liver cytosol.

Administration, Oral↗
PubMed1994

Psoriasis verrucosa showing peculiar histologic features.

A 60-year-old man had a 10-year history of linearly arranged verrucous papules on his left fingers in addition to psoriatic erythematosquamous papules and plaques on his trunk and extremities. The verrucous papules were clinically classified into two types: dome-shaped papules with a keratotic plug and crater-shaped papules with a central depression. Histopathologically, the former showed cup-shaped acanthosis with a parakeratotic column containing Munro's microabscesses, while the latter showed a cup-shaped epidermal invagination with Kogoj's spongiform pustule-like changes. Both types of papules were clinically diagnosed as psoriasis verrucosa, but their histologic features differed from those reported previously.

Humans↗
PubMed1994

Mechanism for macrophage activation against Corynebacterium parvum--participation of T cells and its lymphokines.

It is well known that Corynebacterium parvum activates macrophages to produce tumor necrosis factor (TNF). It is suspected that the activation of macrophages by C. parvum requires T-cell participation. The purpose of this study was to confirm that T cells participate in the activation of macrophages by C. parvum. TNF production in vitro from the spleen cells of BALB/c(-)+/+ mice was abrogated completely by the pre-treatment of spleen cells with anti-Ia antiserum and complement, indicating that Ia+ cells are the source of TNF. TNF production was not elicited at all in BALB/c-nu/nu mice. However, there was an increase in the number of Ia+ cells as well as an increase in the weight of spleen and liver. Supernatant from a culture of spleen cells stimulated with phytohemagglutinin-P (a PHA-induced lymphokine) made it possible for BALB/c-nu/nu mice to produce TNF, associated with an induction of Lyt-1+ cells and Lyt-2+ cells. However, treatment with the lymphokine did not augment the increases of Ia+ cells or liver and spleen weights. These results suggest that increasing the number of Ia+ cells is not sufficient to bring about TNF production; Ia+ cells must also be stimulated by T cells or T-cell lymphokines in order to produce TNF. These results suggest that T cells play an essential role in the activation of Ia+ cells against C. parvum.

Animals↗
PubMed1994

Sebaceous gland carcinoma of the eyelid presenting as a conjunctival papilloma.

A 70-year-old man complained of the sensation of having a foreign body in his left eye in June 1992. A papillary tumor was found growing from the palpebral conjunctiva of the left upper eyelid. On June 30, the conjunctival tumor was excised: the histopathologic findings indicated a malignancy. On August 18, full-thickness excision of the upper eyelid, including the rest of the tumor, was performed. Histopathologic findings showed a well-differentiated sebaceous gland carcinoma. We believe that sebaceous gland carcinoma presenting as conjunctival papilloma, as found in our patient, may be uncommon.

Adenocarcinoma, Sebaceous↗
PubMed1994

Distribution and chemical form of selenium in mice after administration of selenocystine.

To elucidate the relationship between chemical forms of selenium in tissues and subacute liver damage induced by selenocystine (T. Hasegawa et al., Arch. Toxicol., 68, 91 (1994)), the distribution and chemical form of selenium were investigated in ICR male mice treated with the chemical orally (50 mg/kg) and intravenously (5 mg/kg). The time-distribution of selenium in plasma, erythrocytes and liver after separate administration varied. However, Sephadex G-150 chromatograms of plasma, and stroma-free hemolysate from mice treated orally or intravenously with selenocystine, revealed that selenium exists mainly in the albumin and hemoglobin fractions, respectively, and is neither route- or time-dependent. Sephadex G-150 chromatograms of liver cytosol of the animals 1 h after oral administration or 1 and 6 h after intravenous administration showed two selenium-containing fractions, void volume and a low-molecular fraction (Kav = 0.85); 6 h after oral treatment, however, animals had an additional high-molecular fraction (Kav = 0.45). Levels of acid-volatile selenium and dialyzable selenium in the fraction with a Kav value of 0.45 were similar, being 31.2% and 30.3%, respectively. No acid-volatile selenium was recognized in the non-dialyzable high-molecular fraction. The present study demonstrated that when selenocystine is administered orally to mice, the selenium which produces acid-volatile selenium by acidification may bind to protein sulfhydryl groups in the liver cytosol; this was not seen in the case of intravenous administration.

Administration, Oral↗
PubMed1994

Aquaretic effect of the stable dynorphin-A analog E2078 in the human.

Dynorphin-A is an endogenously released hormone that is now recognized as a kappa-opioid receptor agonist. Because kappa-agonists have been reported to induce water diuresis through negative modulation of antidiuretic hormone release and/or action, in the present study we investigated the aquaretic effects and safety of E2078, a metabolically stable dynorphin-A analog, in 21 healthy subjects after single (1.0, 2.0, 3.0, 5.0, 7.5 and 10.0 mg, i.m.) and repeated (5.0 mg t.i.d. for 4 and 1/3 days) administration. E2078 dose-dependently increased the 0 to 4-hr urine volume, which plateaued between 1032.4 +/- 130.1 and 1286.2 +/- 113.0 ml/4 hr (mean +/- S.E.M.) at doses of between 5.0 and 10.0 mg. The drug decreased urine osmolality (Uosm) markedly, by 17 to 27%, and the free-water clearance (CH2O) became positive, changing from -1.8 +/- 0.2 (placebo) to 0.8 +/- 0.3-2.8 +/- 0.4 ml/min after a single E2078 administration (P < .01). In the repeated-dose study, the first dose of E2078 increased the 0 to 5-hr urine output (1256 +/- 164.9 ml/5 h), lowered Uosm (151.8 +/- 13.3 mOsm/kg) and brought about a positive CH2O (1.9 +/- 0.2 ml/min). These values were similar to those seen after the single dose, but after the subsequent doses these aquaretic effects were attenuated, although the ranges of these same parameters were still significantly greater (P < .01-0.05) (441.4 +/- 102.4-585.3 +/- 131.9 ml/5 hr, 322.8 +/- 21.9-378.2 +/- 47.7 mOsm/kg and -0.2 +/- 0.2-(-)0.6 +/- 0.2 ml/min, respectively) than the day -1 base line (164.1 +/- 41.3 ml/5 hr, 992.0 +/- 80.6 mOsm/kg and -1.2 +/- 0.2 ml/min, respectively). Urinary excretion of electrolytes (Na, K and Cl) was not altered during either study period. A single E2078 administration reduced plasma antidiuretic hormone dose-dependently. On repeated dosing, the plasma concentration had rebounded to approximately 3 pg/ml by the time of the first dose on days 3 and 5, which lowered it again. The present results suggest that E2078 is a safe and effective aquaretic and could be a useful therapeutic tool for patients with water-retaining diseases.

Adult↗
PubMed1993

Comparison of the pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy young and elderly subjects.

E2020, a central-acting cholinesterase inhibitor, is now under clinical development as a potential therapeutic agent for senile dementia of Alzheimer type. In the current study, the authors compared the pharmacokinetics of this drug after single oral administration in 12 healthy young volunteers (20-27 years of age) and 6 elderly volunteers (65-82 years of age). The subjects received a single 2-mg oral dose of E2020 after a meal. Blood samples for determination of the drug level were collected over 168 hours after drug administration and were measured by specific high-pressure liquid chromatography methods with ultraviolet detection. E2020 was generally well tolerated by all subjects of both groups. The plasma elimination half-life of the beta-phase (t 1/2 beta) and time to maximum peak plasma concentration (tmax) were significantly longer in the elderly than in the young: t 1/2 beta, 103.8 +/- 40.6 versus 59.7 +/- 16.1 hours; and tmax, 5.2 +/- 2.8 versus 3.4 +/- 1.5 hours, respectively. There were no statistically significant differences in maximum peak plasma concentration and area under the curve between the two groups. The mean (+/- standard deviation) oral clearance (Cl/F) in the elderly (9.1 +/- 2.4 L/h) was similar to that in the young (10.6 +/- 2.7 L/h). The volume of distribution in the steady state (Vdss/F) was significantly larger in the elderly than that in the young: 1217.2 +/- 223.2 versus 852.5 +/- 147.7 L, respectively. These results suggested that the drug was absorbed more slowly and distributed more widely and thoroughly, but that its clearance from the body is essentially unaffected by age.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Detection of human papillomavirus type 2a DNA in verrucae vulgares by electron microscopic in situ hybridization.

Electron microscopic in situ hybridization (EMISH) of common warts (verrucae vulgares) of the hands was performed using a biotinylated human papillomavirus type 2a (HPV-2a) DNA probe and immunogold labelling of ultrathin sections of 2% glutaraldehyde-fixed, Lowicryl K4M-embedded tissues. It was first established that the warts contained HPV-2a DNA by light microscopic in situ hybridization. The HPV-2a probe chiefly labelled cells in the horny, granular and upper spinous layers of the epidermis, and labelling decreased towards the basal cell layer. The gold particles were located precisely on the viral particles in the nuclei of granular cells. The lower limit of detection by EMISH was found to be the keratinocytes of the third cellular layer above the basal cells. These keratinocytes showed evidence of a viral cytopathic effect, suggesting that vegetative DNA replication in infected keratinocytes occurs at least as early as this level of the epidermis.

DNA, Viral↗
PubMed1993

Initial rapid decrease in visual acuity in siblings with Stargardt's disease.

Two siblings with Stargardt's disease who had an initial rapid decrease in visual acuity were reported. The 8-year-old boy and his 5-year-old sister experienced a bilateral visual decrease within a period of 3 months. Their parents had a consanguineous relationship. Macular changes and blocked choroidal fluorescence were noted bilaterally in both children. Normal color vision, normal or subnormal electroretinographic findings, and subnormal electro-oculographic responses were found. Stargardt's disease should be included in the list of conditions showing rapid decrease in visual acuity.

Child↗
PubMed1993

Pharmacokinetics of E2020, a new compound for Alzheimer's disease, in healthy male volunteers.

E2020 is a new cholinesterase inhibitor with a novel chemical structure, which is under clinical investigation for use in Alzheimer's disease in Japan and the USA. Three separate studies were conducted to evaluate the safety and to establish the pharmacokinetic profile of E2020 after oral administration to healthy male subjects. E2020 was administered as: (1) single oral doses (0.3 mg, 1 mg, 2 mg, 5 mg, 8 mg and 10 mg) in a fasting condition, (2) a single oral dose (2 mg) after a meal and (3) repeated oral doses (2 mg once daily for 21 days). The concentrations of E2020 and its metabolites in plasma, serum, urine and feces were determined by HPLC methods with UV detection. E2020 was generally well tolerated by all subjects. In the single-dose study, there was a linear relationship between dose and mean AUC. The mean plasma half-life was about 50 hours and was dose-independent. The total clearance and renal clearance of E2020 were also dose-independent and the mean values after 10 mg dosing were 9.7 l/hour and 0.86 l/hour, respectively. The cumulative total urinary and fecal excretion of the sum of unchanged E2020 and its metabolites at 264 hours after the administration of the single 10-mg-dose was 36.1% and 8.6% of the dose, respectively. The mean serum protein binding was 92.6%. No effect of food intake on the pharmacokinetics was observed. Evaluation of the mean trough levels and AUC0-24 of E2020 indicated that a steady-state was achieved after approximately 2 weeks of daily dosing.

Adult↗
PubMed1993

Regulation by cytokines of eosinophilopoiesis and immunoglobulin E production in mice.

Certain clinical disorders are associated with eosinophilia and hyperimmunoglobulinaemia of the immunoglobulin (Ig) E class, but others give rise to eosinophilia without hyperimmunoglobulinaemia. To investigate why there are two such patterns, we immunized BALB/c mice with ovalbumin plus tetanus toxid with aluminium hydroxide gel (alum) as adjuvant, which caused eosinophilopoiesis and hyperimmunoglobulinaemia, and also immunized mice with the same antigens and complete Freund's adjuvant (CFA), which caused only eosinophilopoiesis. The difference in the adjuvant brought about the two different patterns. Monoclonal antibodies to four cytokines were used to find that eosinophilopoiesis was mediated by interleukin-5 (IL-5), whichever the adjuvant, and that IgE production in mice treated with alum was regulated by both IL-4 and IL-5. The lack of increase in IgE production was not due to suppression by interferon-gamma (IFN-gamma) or by CD8+ T cells. By the polymerase chain reaction, both IL-4 and IL-5 mRNA were detected in cells from mice given alum, but only IL-5 mRNA was found in cells from mice given CFA. Thus, alum used as the adjuvant resulted in both eosinophilopoiesis and IgE production, but CFA resulted in eosinophilopoiesis alone. The dissociation between eosinophilopoiesis and IgE production shown in the mice given CFA could be due to the dissociation between the expression of mRNA of the cytokines IL-4 and IL-5 in vivo.

Adjuvants, Immunologic↗