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Biomedical subjects

Y Miyachi

Publications and source records attributed to Y Miyachi.

At least 73 records · Page 4Linked to original sources

Acute mild hypothermia caused by a low dose of X-irradiation induces a protective effect against mid-lethal doses of X-rays, and a low level concentration of ozone may act as a radiomimetic.

Acute changes in core body temperature following exposure to a low dose of X-rays were assessed in unanaesthetized and unrestrained mice. Radiotelemetry techniques were used to monitor core body temperature continuously. Following exposure to a 20 cGy dose of X-rays, the mice displayed a rapid and significant reduction in core body temperature relative to the sham-treated (non-irradiated) control animals. The present studies, and those by others, showed that pre-exposure to X-rays at doses as low as 20 cGy may result in a reduced mortality rate following subsequent exposure to X-rays at mid-lethal dose levels. This indicates an increased tolerance to radiation. An additional experiment was conducted to examine whether the reduction in the mortality rate following exposure to mid-lethal doses of radiation could be found when mice were subjected to a stressor, ozone inhalation, which induced a suppression in body temperature. The results showed that following inhalation of ozone at a concentration of 0.5 ppm, 93% of the treated animals survived a mid-lethal dose of radiation, whereas 50% of the sham-control animals died within 30 days. These results suggest that low-dose-induced tolerance to radiation may be dependent on a brief exposure to ozone, and a reduction in core temperature may be necessary to obtain tolerance effects in response to a mid-lethal dose of radiation.

Acute Disease↗

Serum concentrations of 20K human growth hormone in normal adults and patients with various endocrine disorders. Study Group of 20K hGH.

The 20K hGH isoform is produced by alternative splicing of GH mRNA, and comprises approximately 10% of all GH in the pituitary. The physiological role of 20K hGH remains to be determined partly because of the lack of a simple and specific assay. We have established sensitive enzyme-linked immunoadsorbent assays (ELISAs) specific to 20K and 22K hGH. The serum levels of 20K hGH after overnight fasting was 118 +/- 178 pg/mL (N=282) in normal women, significantly higher than in normal men (64 +/- 170 pg/mL, N=226). However, there was no difference in the proportion of 20K hGH to 20K plus 22K hGH between men (6.3 +/- 2.6%, N=176) and women (6.3 +/- 2.1%, N = 263). No correlation was detected between the ratio of 20K hGH and age, body height, body weight or body fat mass in normal subjects. The proportion of 20K hGH was significantly (P < 0.001) higher in patients with active acromegaly (9.2 +/- 2.2%, N=33) and in patients with anorexia nervosa (9.0 +/- 1.9, N=8), both of which are characterized by chronic elevation of circulating GH levels. The proportion of the 20K hGH in successfully treated acromegalic patients did not differ from that in normal subjects, suggesting that GH-producing pituitary tumors secrete a higher proportion of 20K hGH, or chronic excess of 22K hGH altering the metabolic clearance rate of 20K hGH. The values in patients with adult growth hormone deficiency (GHD), hyperthyroidism, primary hypothyroidism, or GH-independent short stature did not differ from those in normal subjects. The 20K ratio did not change after acute GH provocative tests such as insulin tolerance test and GRH test. These results suggest that secretion of 20K hGH from the pituitary is under the same control as that of 22K hGH.

Acromegaly↗

[Enzyme induction of cytochrome P450 and their roles in endocrine disruption].

Cytochrome P450(CYP) comprises a large superfamily of hemoproteins that plays a vital role in the biotransformation of variety of xenobiotics as well as endobiotics. CYPs 1-4 metabolize foreign compounds such as drugs, environmental pollutants and carcinogens influencing drug-drug interactions, drug or carcinogen activation and detoxification, and in addition, xenobiotics induce CYP genes. CYPs 1-4 also metabolize endogenous compounds, including steroid hormones, retinoid, bile acids, prostagrandins, and thus have roles in not only elimination but also production of endobiotic signaling molecules. Some of the orphan receptors may function as the receptors of these signaling molecules.

Animals↗

[Synthetic glucocorticoid therapy--recent progress].

Synthetic glucocorticoids are administered systematically in the treatment of a large number of nonendocrine and endocrine diseases. Efforts have been made to reduce the side effects and to increase the pharmacological effects of these glucocorticoids. To avoid complications compartmental administration(topical, inhaled, suppository, ophthalmic, intra-articular) and alternate-day administration of intermediate acting glucocorticoids are recommended. Careful monitoring of the patients under therapy and gradual reduction of glucocorticoids should be performed to avoid adrenal insufficiency or reactivation of the disease. The understanding of molecular mechanisms of glucocorticoid actions may lead to the development of novel glucocorticoids, which are more active in anti-inflammatory actions than endocrine and metabolic actions(adverse effects of glucocorticoids).

Glucocorticoids↗

Response to cyclosporin and low-dose methylprednisolone in aggressive systemic mastocytosis.

BACKGROUND: There is no effective treatment for aggressive systemic mastocytosis. OBJECTIVE: The purpose of this study was to investigate the effect of cyclosporin and low-dose methylprednisolone in a 64-year-old man with aggressive systemic mastocytosis. METHODS: Immunohistochemical studies were done on biopsy specimens from the skin and other organs. Mast cells, predominantly containing tryptase, were derived from human umbilical cord blood cells cultured in the presence of stem-cell factor and IL-6. IgE-sensitized cultured human mast cells were activated by anti-IgE, and the effect of cyclosporin on histamine release was investigated. In addition, blood and urine levels of various mediators were measured in the patient before and after therapy. RESULTS: Biopsy specimens of the patient's skin lesions showed an increase of mast cells; cells containing tryptase (but not chymase) comprised 20% to 50% of the skin mast cells. Histamine release from activated cultured mast cells was inhibited by cyclosporin in a concentration-dependent manner. When the patient was treated with cyclosporin and low-dose methylprednisolone, he showed a good response. CONCLUSION: Cyclosporin combined with low-dose methylprednisolone may be a reasonable therapy for aggressive systemic mastocytosis.

Bone Marrow Cells↗

Influences of keratinocyte-fibroblast interaction on the expression of epimorphin by fibroblasts in vitro.

Epimorphin was demonstrated to be a mesenchymal signal factor modulating epithelial morphogenesis of skin, lung and liver in vitro. Most of the previous studies were performed biochemically and functionally. In the present study, expression of epimorphin was immunohistochemically compared between cultured fibroblasts and cocultured fibroblasts with keratinocytes obtained from normal skin. Cultured fibroblasts revealed a low level of epimorphin expression. In contrast, the expression by fibroblasts was greatly enhanced in skin explant culture where both fibroblasts and keratinocytes were present. In three-dimensional coculture of fibroblasts and keratinocytes, the expression of epimorphin was enhanced. The staining pattern of epimorphin in three-dimensional coculture was similar to that in human skin. These results suggest that dermal fibroblasts are manufacturers of epimorphin, and keratinocyte-fibroblast interaction may play important roles in the expression of epimorphin in vitro.

Adult↗

Using transgenic models to study the pathogenesis of keratin-based inherited skin diseases.

In the past decade, the production of transgenic animals whose genome is modified to contain DNA transgenes of interest has significantly contributed to expand our understanding of the molecular etiology and pathobiology of several inherited skin diseases. This technology has led to the discovery that mutations affecting specific keratin genes are responsible for a wide spectrum of inherited bullous diseases, which are collectively characterized by blistering after minor trauma. Type I and type II keratin proteins are restricted to, and very abundant in, epithelial cells, where they occur as a pancytoplasmic network of cytoskeletal filaments. Although it had long been suspected that a primary function of keratin filaments may be to contribute to the physical strength of epithelial sheets, a formal demonstration came from studies of transgenic mouse models and patients suffering from keratin-based blistering diseases. Here we review the basic characteristics of keratin gene and their proteins and relate them to the molecular pathogenesis of relevant inherited skin blistering diseases. A particular emphasis is placed on the role of transgenic mouse models in the past, current, and future studies of these genodermatoses.

Animals↗

Nerve growth factor release with mast-cell-derived mediators in a patient with systemic mastocytosis after middle-wave ultraviolet irradiation.

BACKGROUND: The symptoms of a 56-year-old man with systemic mastocytosis became worse with exposure to sunlight. We evaluated mast-cell-derived mediators and cytokines before and after exposure to ultraviolet light in the patient. METHODS: The patient was irradiated with middle-wave ultraviolet light, so-called ultraviolet light B, and the levels of mediators and cytokines were measured serially. The point mutation Asp816Val in c-kit was investigated by analyzing polymerase chain reaction products from the complementary DNA of peripheral blood mononuclear cells. RESULTS: Before irradiation, the levels of mast-cell-derived mediators and metabolites were elevated. Among various cytokines measured, including soluble c-kit and stem cell factor, only the level of nerve growth factor was elevated. After irradiation, the nerve growth factor level was further increased along with the levels of mast-cell-derived mediators and metabolites. The point mutation Asp816Val in c-kit was not detected in peripheral blood mononuclear cells. CONCLUSIONS: Middle-wave ultraviolet light may activate mast cells to release nerve growth factor and mediators in systemic mastocytosis.

Cytokines↗

Cutaneous papules and nodules in the diagnosis of the antiphospholipid syndrome.

Of 11 patients with primary or secondary antiphospholipid syndrome (APS), four exhibited papules or nodules on the finger, sole or leg as the initial cutaneous manifestation. Histological examination demonstrated thrombosed vessels or vessels containing organized thrombi in the dermis or in the subcutaneous fat tissue. Cutaneous papules and nodules should be recognized as skin manifestations of APS. Screening tests for antiphospholipid antibodies and lupus anticoagulant are required in patients with cutaneous papules or nodules of unknown aetiology. In cases of positive antiphospholipid antibodies and/or lupus anticoagulant, histological examination is critical in the establishment of the diagnosis of APS.

Adolescent↗

Cord blood-derived human cultured mast cells produce transforming growth factor beta1.

BACKGROUND: Mast cells frequently accumulate at the site of fibrosis and their contribution has been suspected in the pathogenesis of fibrotic conditions. However, it still remains unknown whether human mast cells synthesize transforming growth factor beta1 (TGF-beta1). OBJECTIVE: We have investigated whether cord blood-derived human cultured mast cells express messenger RNA (mRNA) for TGF-beta and produce bioactive TGF-beta1. METHODS: Mast cells were obtained by culturing mononuclear cells from cord blood in the presence of stem cell factor and interleukin-6. Expression of mRNA for TGF-beta1 was examined by the method of reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemical staining for TGF-beta and growth-inhibitory assay using Mv1Lu cells were also performed. RESULTS: The cultured human mast cells constitutively expressed mRNA for TGF-beta1. With calcium ionophore A23187, the intensity of the PCR-amplified band for TGF-beta1 was not increased. Immunocytochemical staining showed that the cultured mast cells were positive for both latency-associated peptide and activated forms of TGF-beta. Bioassay with Mv1Lu cells and R 4-2 mutant cells showed that mast-cell conditioned medium had a bioactivity of TGF-beta1. CONCLUSION: Cord blood-derived human cultured mast cells constitutively express mRNA for TGF-beta1 and produce functional TGF-beta1. Because TGF-beta1 has been shown to be highly fibrogenic, these results may highlight a novel role for human mast cells in tissue fibrosis.

Animals↗

Herpes zoster in Japanese patients with systemic lupus erythematosus.

We examined retrospectively the incidence of herpes zoster among 58 Japanese patients with systemic lupus erythematosus (SLE), 42 patients with systemic sclerosis (SSc) and 21 patients with autoimmune bullous diseases (AIBD). The incidence of herpes zoster was significantly higher in SLE (46.6%) than in SSc (9.5%) or AIBD (4.7%) (P < 0.001). The rate of positive delayed-type skin test with varicella zoster virus antigens was significantly lower in SLE than in SSc [4/16 (25.0%) vs. 11/12 (91.7%), P < 0.001]. In addition, the positive rate of skin test with purified protein derivatives of tuberculin was also low in SLE patients (3/16, 18.8%). These results reconfirm the general impairment in cellular immunity in SLE.

Adolescent↗

The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2'-deoxyguanosine in arsenic-related Bowen's disease.

Arsenic is widely distributed in nature in the form of either metalloids or chemical compounds, which cause a variety of pathologic conditions including cutaneous and visceral malignancies. Recently, reactive oxygen species have been hypothesized to be one of the causes of arsenic-induced carcinogenesis. 8-Hydroxy-2'-deoxyguanosine is one of the major reactive oxygen species-induced DNA base-modified products that is widely accepted as a sensitive marker of oxidative DNA damage. We studied the presence of 8-hydroxy-2'-deoxyguanosine by immunohistochemistry using N45.1 monoclonal antibody in 28 cases of arsenic-related skin neoplasms and arsenic keratosis as well as in 11 cases of arsenic-unrelated Bowen's diseases. The frequency of 8-hydroxy-2'-deoxyguanosine positive cases was significantly higher in arsenic-related skin neoplasms (22 of 28; 78%) than in arsenic-unrelated Bowen's disease (one of 11; 9%) (p < 0.001 by chi2 test). 8-Hydroxy-2'-deoxyguanosine was also detected in normal tissue adjacent to the arsenic-related Bowen's disease lesions. Furthermore, arsenic was detected by neutron activation analysis in the deparaffined skin tumor samples of arsenic-related disease (four of five; 80%), whereas arsenic was not detected in control samples. Our results strongly suggest the involvement of reactive oxygen species in arsenic-induced human skin cancer. Key word: neutron activation analysis.

8-Hydroxy-2'-Deoxyguanosine↗

A case of lipodystrophia centrifugalis abdominalis infantilis with morphea.

A 5-year-old female developed three depressed lesions sequentially on her left hip, left upper arm and left Achilles tendon; we diagnosed them as lipodystrophia centrifugalis abdominalis infantilis (LCAI). She also developed two sclerotic lesions, at almost the same time, on her left upper arm and left forearm; we diagnosed them as morphea. Clinical and histopathological examination revealed that the LCAI and morphea seen in our case were completely different. Although two other cases of co-existing LCAI and morphea have already been reported, they were not described in detail and their morphea lesions were adjacent to their LCAI lesions. We herein report a case of LCAI with morphea in which the lesions were not adjacent.

Biopsy, Needle↗

Clinical and immunological characterization of patients with systemic sclerosis overlapping primary biliary cirrhosis: a comparison with patients with systemic sclerosis alone.

Limited cutaneous systemic sclerosis (lSSc) or CREST syndrome is sometimes complicated by primary biliary cirrhosis (PBC). To characterize the clinical and immunological features of patients with SSc overlapping PBC (SSc-PBC), the clinical and laboratory data of 11 SSc-PBC were studied. Since all of the SSc-PBC were lSSc, the features of SSc-PBC were compared with those of 266 patients with lSSc alone. The sera from SSc-PBC showed a significantly higher positivity for anti-centromere antibody (ACA) (p < 0.0005) and higher reactivity to centromere protein-C. Although SSc-PBC more frequently exhibited calcinosis and telangiectasia (p < 0.05), there was no statistical difference in other features of CREST syndrome. There was no statistical difference in other scleroderma-related features either. SSc-PBC were more frequently complicated with Sjögren syndrome (p < 0.05). The most prominent feature of SSc-PBC was a higher incidence of ACA than in lSSc alone.

Adult↗