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Biomedical subjects

E Morita

Publications and source records attributed to E Morita.

At least 19 recordsLinked to original sources

Environmental stress modifies glycemic control and diabetes onset in type 2 diabetes prone Otsuka Long Evans Tokushima Fatty (OLETF) rats.

This study was designed to investigate the effects of environmental stress on metabolic derangements and the expression of diabetes phenotype in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of human type 2 diabetes (NIDDM). Acute environmental stress, i.e., exposure to water with immobilization for 1 h, caused a transient increase in blood glucose with decreased insulin secretion, and the stress-induced hyperglycemia augmented with age. The increased glycemia was associated with increased plasma levels of catecholamines and corticosterone. Short-term stress, the same stress of 1 h/day for 10 days, caused a significant decrease of food intake, which led to weight reduction in OLETF rats, aged 50 weeks. Blood glucose and insulin responses in OGTT showed no change before or after the short-term stress, despite the weight reduction. In chronic stress experiments, i.e., exposure to the same kind of stress for 6 days/week from 8 to 75 weeks of age, stressed rats did not gain weight, compared to control rats. Blood HbA1c levels and the index of insulin resistance after a 4-h unfed period were significantly lower in stressed rats than in controls from 35 and 45 weeks of age on, respectively. The occurrence of diabetes, diagnosed by OGTT, was also significantly lower in the rats subjected to chronic stress than in controls. These results suggest that chronic stress from 8 weeks of age inhibited weight gain, probably due to changes in eating behavior, preventing the deterioration of insulin resistance in OLETF rats. Plasma leptin levels were not modulated by stress, and correlated with body weight in the rats under chronic stress and in controls. These results suggest that in type 2 diabetes, blood glucose derangement due to stress is presumably associated not only with changes in counterregulatory hormones involved in glucose metabolism, but also with stress-induced changes in eating behavior.

Animals↗

Production of tissue inhibitor of metalloproteinase-1 and -2 by cultured keratinocytes.

The imbalance between metalloproteinases and their inhibitors in tissue remodelling is likely to play an important role in various pathologic conditions. In order to understand the role of keratinocytes in regulating extracellular matrix degradation in skin, we analyzed the production of metalloproteinase inhibitors in keratinocytes. Tissue inhibitor of metalloproteinase-1 (TIMP-1) and tissue inhibitor of metalloproteinase-2 (TIMP-2) mRNA were detected in cultured human keratinocytes and mouse transformed keratinocyte cell line (KCMH-1) cells by RT-PCR. On several column chromatography separation steps of the KCMH-1 conditioned medium, two specific inhibitors for mammalian collagenase were purified showing an Mr of 29 kDa and an Mr of 22 kDa, respectively. The analysis of their N-terminal amino acid sequence revealed that two inhibitors were TIMP-1 and TIMP-2. The final preparation of TIMP-1 had a specific activity of 56000 U/mg and that of TIMP-2 had a specific activity of 26200 U/mg. Our results suggest that keratinocytes take part in tissue remodelling in skin in secreting both TIMP-1 and TIMP-2.

Animals↗

Hyperparathyroidism after thyroid surgery and autotransplantation of histologically normal parathyroid glands.

BACKGROUND: Parathyroid autotransplantation is a well-established method to prevent hypoparathyroidism during parathyroid and thyroid operations. The reported success rate of parathyroid autotransplantation ranges from 75% to 100%. Recurrent hyperparathyroidism may develop after parathyroid autotransplantation, especially after the transplantation of hyperplastic or adenomatous parathyroid tissue. Hyperparathyroidism recurs most frequently after subtotal parathyroidectomy or total parathyroidectomy and autotransplantation, in patients with renal failure and secondary hyperparathyroidism, and in patients with familial primary hyperparathyroidism or MEN I or MEN II syndrome. We report three patients who experienced primary hyperparathyroidism after autotransplantation of normal parathyroid tissue during thyroid operations (two patients) or after a long period of hypoparathyroidism. STUDY DESIGN: We reviewed our records from 1983 to May 1998 and identified three patients in whom hyperparathyroidism developed after thyroid operations. RESULTS: One patient had a thyroidectomy with left modified radical neck dissection for papillary thyroid cancer, followed by radioiodine ablative therapy. Two patients had thyroid operations for benign thyroid disease. One of these patients had a history of radiation exposure for acne, and in the other one secondary hyperparathyroidism arose 6 years after a thyroidectomy for hyperthyroidism. CONCLUSIONS: Our study documents that hyperparathyroidism may develop after autotransplantation of histologically normal parathyroid tissue and after a period of hypoparathyroidism after thyroid operations. For this reason, it is important to mark the site of the parathyroid transplantation.

Adult↗

Altered in vitro apoptosis of cultured mast cells prepared from an inbred strain of mice, NC/Kuj.

BACKGROUND: An inbred strain of mice, NC, develops dermatitis associated with highly elevated serum IgE and dermal mast cell hyperplasia. OBJECTIVES AND METHODS: To clarify the mechanisms for the dermal mast cell hyperplasia in NC, we prepared bone marrow-derived mast cells (BMMCs) from three strains of mice, NC/Kuj, C57BL/6 and BALB/c, and compare histamine contents, histamine release abilities, adhesive properties and apoptosis of the BMMCs. RESULTS: Compared with BMMCs obtained from C57BL/6 and BALB/c, NC/Kuj BMMC possessed higher histamine content and higher adhesive ability to plastic plates, although histamine release from BMMCs was found to be similar in the three strains. The most intriguing finding is the lack of apoptosis in the BMMCs from NC/Kuj upon growth factor deprivation as determined by DNA ladder formation and loss of membrane phospholipid asymmetry. CONCLUSION: The altered in vitro properties of mast cells in NC/Kuj partially account for an increase of dermal mast cells, which might be involved in the development of skin lesions in NC.

Animals↗

Correlation between deposition of immuno-components and infiltration pattern of polymorphonuclear leukocytes in the lesions of chronic urticaria.

Urticaria is often associated with perivascular infiltration of leukocytes into the lesions. Although mast cell-derived chemical mediators are considered to play crucial roles in the infiltration of leukocytes as well as in the dermal edema, other mechanisms for the leukocyte infiltration have not been well defined. This study revealed that approximately 25% of the cases of chronic idiopathic urticaria in whom wheals had continued for more than 12 h had deposition of immuno-components in the lesions, although histological examination of the lesions did not show leukocytoclastic vasculitis. In these lesions with deposition of immuno-components, both neutrophils and eosinophils had infiltrated at a constant ratio (approximately 2:1), whereas, in the lesions without deposition, a variable population of leukocytes was seen. This result suggests that activation of complements occurs in the lesions of a considerable percentage of patients with chronic idiopathic urticaria and that the complement fragments influence the infiltration patterns of polymorphonuclear leukocytes.

Adult↗

Discordancy between clinical predictions vs lymphoscintigraphic and intraoperative mapping of sentinel lymph node drainage of primary melanoma.

OBJECTIVE: To evaluate discordancy between clinical predictions and lymphatic drainage patterns of primary cutaneous melanoma as determined by preoperative lymphoscintigraphy and intraoperative lymphatic mapping of sentinel lymph nodes (SLNs). DESIGN: Before selective SLN dissection, 226 consecutive patients with melanoma underwent preoperative lymphoscintigraphy. SETTING: Teaching hospital tertiary care center. MAIN OUTCOME MEASURE: Correlation of lymphatic drainage patterns from the following 3 data sources: clinical predictions preoperatively based on anatomical location of primary melanoma, lymphatic drainage patterns as determined by preoperative lymphoscintigraphy, and identification of SLNs during surgery. RESULTS: Preoperative lymphoscintigraphy was successful in identifying at least 1 SLN in all 226 patients. In head and neck melanomas, at least 1 SLN was identified in an area outside what would have been clinically predicted in 11 (36.7%) of 30 cases. Discordancy for trunk melanomas was seen in 24 (25.3%) of 95 cases. Extremity melanomas showed drainage to unexpected SLNs in 6 (13.6%) of 44 and 3 (5.3%) of 57 patients for the upper and lower extremities, respectively. The overall rate of discordancy was 44 (19.5%) of 226. The SLNs were identified in surgery in all but 4 cases. CONCLUSIONS: Discordancy is most frequent in melanomas of the head and neck region, followed by that of the trunk. Preoperative lymphoscintigraphy identifies the occasional cases in the upper and lower extremities where drainage occurs to a basin that is not clinically predictable. Preoperative lymphoscintigraphy is a prerequisite for characterizing the lymphatic drainage pattern in patients with primary melanoma, especially for sites such as head and neck as well as trunk, before selective SLN dissection.

Adolescent↗

Renal hemodynamics in Otsuka Long-Evans Tokushima fatty rat, a model rat of spontaneous non-insulin-dependent diabetes mellitus with obesity.

Renal hemodynamic features in obese non-insulin-dependent diabetic rats remain unknown. We investigated renal hemodynamic and morphologic changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rats at the age of 5 and 10 months compared with age-matched lean nondiabetic control rats (LETO). OLETF rats showed obesity compared with age-matched LETO rats. Hyperglycemia was mild in 5-month-old OLETF rats and moderate in 10-month-old OLETF rats. The absolute value for glomerular filtration rate (GFR) was significantly higher in OLETF rats than in age-matched LETO rats at the age of 5 and 10 months. Ten-month-old OLETF rats had significantly higher absolute values for renal plasma flow (RPF) than age-matched LETO rats but not 5-month-old OLETF rats. Stepwise multiple regression analysis revealed that body weight was a powerful determinant of GFR and RPF. When factored for body weight, no difference in GFR was demonstrated between 5-month-old OLETF and LETO rats, whereas 10-month-old OLETF rats still had significantly higher GFR and RPF than age-matched LETO rats. Renal hypertrophy was demonstrated in both 5- and 10-month-old OLETF rats even when factored for body weight. Glomerular volume was significantly increased in 10-month-old OLETF rats, but the ratio of glomerular volume to body weight was not different among the groups. Both absolute value for glomerular capillary length free from mesangial area and the value factored for glomerular area were significantly longer in OLETF rats than in age-matched LETO rats. Mesangial matrix expansion was remarkable in 10-month-old OLETF rats, and the glomerular sclerosis index was significantly higher in 10-month-old OLETF rats than in age-matched LETO rats. Stepwise multiple regression analysis revealed that body weight, hemoglobin A1c, and hypertriglyceridemia were powerful determinants for kidney weight and glomerular volume. These data suggest that renal hyperfiltration and hypertrophy observed in 10-month-old OLETF rats are related to diabetic metabolic disorders and that obesity-related conditions may be involved in the renal hemodynamic and morphologic features in OLETF rats.

Animals↗

FR190997, a novel bradykinin B2 agonist, expresses longer action than bradykinin in paw edema formation and hypotensive response.

Biological actions of a novel non-peptide B2 receptor agonist, FR190997, were examined by comparing them with those of bradykinin. The paw edema was induced by subcutaneous injection of 30 microl of solution of bradykinin (0.3, 0.6, and 1.2 nmol) or FR190997 (0.1, 0.3, and 0.9 nmol) into the right hind paw of ICR male mice. Bradykinin caused a dose-dependent edema formation, which peaked at 15 min and ceased after 150 min. FR190997 also formed a dose-dependent edema, peaking at 15-30 min with a slight delay compared to bradykinin and this response continued over 200 min. The edema formed by bradykinin or FR190997 was inhibited by pretreatment with HOE140 (1 mg/kg) injected intraperitoneally 30 min before the injection of each agonist. A novel non-peptide B2 antagonist, FR173657 (30 mg/kg, i.p. 30 min before the agonist), also diminished these responses by bradykinin and FR190997 dose-dependently. Indomethacin (10 mg/kg, i.p. 30 min before) inhibited the response to FR190997, suggesting that release of prostaglandins induced by the B2 agonistic action might be involved in this inflammatory process induced by FR190997. The hypotensive action of FR190997 was also examined. Intravenously injected FR190997 caused the systemic hypotensive response in Sprague-Dawley male rats anesthetized with pentobarbital. The potency of FR190997 was weaker than that of bradykinin, when compared with the maximal hypotension. Duration of the hypotensive response of FR190997 was significantly longer than that of bradykinin. These results indicate that FR190997 has the B2 agonistic action similar to bradykinin and is also a good tool for in vivo examination of the B2 receptor.

Animals↗

Fur mites induce dermatitis associated with IgE hyperproduction in an inbred strain of mice, NC/Kuj.

An inbred strain of mice, NC, has been introduced as an animal model for atopic dermatitis because the mice develop dermatitis associated with severe scratch preceded by elevated serum IgE level when kept in conventional conditions. Although hypersensitivity to some environmental factors is suggested to cause dermatitis, the precise factor remains unclear. As the mice maintained under conventional conditions were often infected with fur mites, we investigated whether an infection of fur mites induces skin lesions in NC. Infection with the fur mites induced NC to develop skin lesions associated with highly elevated serum IgE, whereas no obvious skin lesions were observed in BALB/c and C57BL/6, and the elevation of serum IgE level was minimal in these two strains of mice. The role of the fur mites in the manifestation of skin lesions and IgE hyperproduction was confirmed by eliminating the fur mites by treatment with ivermectin. In addition, the existence of specific IgE antibody to Myocoptes musculinus antigen in the sera of mite-infested NC was detected by the antigen-induced histamine release from bone marrow-derived cultured mast cells after sensitization with the serum. These results suggest that continuous exposure to fur mite antigen is a potential factor in the development of dermatitis in NC. We provide a new model system of antigen-induced dermatitis for investigating the role of IgE in eliciting dermatitis.

Animals↗

Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients.

BACKGROUND: Serum thyroglobulin determination has been reported to be a sensitive indicator of persistent or recurrent differentiated thyroid cancer of follicular cell origin (DTC) after total thyroidectomy. The purpose of this investigation was to determine the accuracy of serum thyroglobulin levels in predicting persistent or recurrent DTC in euthyroid and hypothyroid patients. METHODS: One hundred ninety consecutive patients with DTC of follicular cell origin who had 4 or more thyroglobulin levels measured after total thyroidectomy were retrospectively evaluated. One hundred fifteen patients had serum thyroglobulin levels measured when hypothyroid for radioiodine scanning or ablation. Serum thyroglobulin levels were determined by commercial assays. One hundred twenty-two patients less than 45 years old were considered at low risk, whereas 68 patients more than or equal to 45 years old were considered at high risk on the basis of TNM classification. The mean follow-up period was 62 months. RESULTS: After thyroidectomy with or without central or modified radical neck dissection 120 patients had normal thyroglobulin levels (< or = 3 ng/mL) while receiving thyroid hormone. One hundred thirteen of the 120 patients (94%) with normal serum thyroglobulin levels had no evidence of recurrent tumor, whereas 6% (7 patients) had persistent or recurrent disease. Among 76 patients with persistent (28 patients) or recurrent (48 patients) disease, 70 had a serum thyroglobulin level > 3 ng/mL while receiving thyroid hormone. Overall, 14 of 115 patients, including 2 of 61 (3%) in the high-risk group and 12 of 54 (22%) in the low-risk group, only had elevated serum thyroglobulin levels when hypothyroid with high serum thyroid-stimulating hormone (TSH) levels documenting persistent or recurrent disease. In 1 patient the serum thyroglobulin level (240 ng/mL) was falsely elevated probably as a result of interfering antibodies because no tumor was identified surgically or pathologically, and the thyroglobulin concentration was < 3 ng/mL when analyzed in 3 other laboratories. CONCLUSION: Serum thyroglobulin testing is sensitive (91%) and specific (99%) for identifying patients with persistent or recurrent differentiated thyroid cancer. Serum thyroglobulin levels are most precise when patients are hypothyroid (high TSH) and may be unreliable in patients with antithyroglobulin antibodies. We recommend TSH-stimulated thyroglobulin testing for all patients after total thyroidectomy for differentiated thyroid cancer of follicular cell origin regardless of patient age or risk group.

Adult↗

Identification of bilateral breast sentinel lymph nodes draining primary melanoma of the back by preoperative lymphoscintigraphy and intraoperative mapping.

A 30-year-old white woman with a primary malignant melanoma of her right back at the Sappey line, 4 cm from the midline at the L2 level, underwent preoperative lymphoscintigraphy and intraoperative mapping of the sentinel lymph node using lymphazurin injection at the primary site and a hand-held gamma probe. Lymphoscintigraphy showed one sentinel lymph node in each breast and another one in the right axilla. These three sentinel lymph nodes were accurately identified using a hand-held gamma probe during operation. An additional sentinel and one nonsentinel lymph node from the right axilla were harvested. All four sentinel lymph nodes were blue and showed significantly elevated radioactivity compared with background. Histologic analysis showed that all these lymph nodes were negative for metastatic melanoma. She has been followed for a period of 26.7 months since her selective sentinel lymphadenectomy and has been free of disease to date. This case illustrates the importance of preoperative lymphoscintigraphy in identifying in-transit sentinel lymph nodes in both breasts in addition to the clinically predictable sentinel lymph node(s) in the right axilla.

Adult↗

A case of acquired autoimmune bullous disease associated with IgM macroglobulinaemia.

A variety of autoimmune bullous dermatoses have been reported to develop in association with lymphoproliferative disorders. We report a patient with IgM macroglobulinaemia, who presented with a skin fragility similar to but somewhat milder than that seen in epidermolysis bullosa acquisita. Immunofluorescence detected circulating IgM autoantibodies reacting with the basement membrane zone, which reacted predominantly with dermal side of 1 M NaCl-split skin. Immunoblotting of the epidermal and dermal extracts with the patient's serum showed no specific reactivity. Further studies are needed to identify the antigenic molecules responsible for the IgM deposition.

Autoantibodies↗

An assessment of the role of Candida albicans antigen in atopic dermatitis.

An immediate hypersensitivity reaction to Candida albicans (C. albicans) antigen has been observed in patients with atopic dermatitis. Recent data from a comparative study of the immune response to C. albicans antigen in patients with atopic dermatitis and non-atopics suggest a shift form type 1 helper T cells to type 2 helper T cells in the immune response to C. albicans antigen in atopic dermatitis. To delineate the role of C. albicans in the pathogenesis in atopic dermatitis, we evaluated skin reaction of C. albicans antigen, as well as the serum IgE antibody level against C. albicans in patients with atopic dermatitis, patients with nasal allergy, and non-atopics. In addition, the clinical effect of antifungal drugs was evaluated in the patients with atopic dermatitis. As a result, we found that immediate hypersensitivity to C. albicans antigen is strongly correlated with the patients with atopic dermatitis. On the other hand, the delayed-type hypersensitivity to this antigen, which is highly prevalent in atopics without dermatitis as well as non-atopics, was reduced in most of these patients. Antifungal drugs markedly improved the skin manifestations in patients with atopic dermatitis that have IgE antibodies against C. albicans, and the serum IgE levels also decreased. These results suggest that C. albicans antigen is a potent intrinsic factor in inducing skin lesions in atopic dermatitis because of IgE-mediated hypersensitivity of C. albicans antigen.

Adolescent↗

Centrally administered murine leptin stimulates plasma arginine-vasopressin secretion and increases the level of mRNA expression in the supraoptic nucleus of conscious rats.

The product of the ob gene protein, leptin, has been suggested to function as an endogenous mediator of the cardiovascular system via sympathetic nerve activity. Moreover, extensive distribution of leptin receptor-like immunoreactivity has been demonstrated in the choroid plexus, cerebral cortex, hippocampus, thalamus and hypothalamus, especially in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, we have investigated the in vivo effects of leptin on plasma arginine-vasopressin (AVP) secretion and the level of AVP messenger ribonucleotic acid (AVP mRNA) in the SON of conscious rats. Intracerebroventricularly administered leptin increased plasma AVP concentration in a dose-dependent manner (0-400 pmol/rat). The maximal effect was obtained at 15 min after the administration of leptin. Furthermore, in Northern blot analyses, the levels of AVP mRNa in the SON increased approximately 2-fold from the basal level after the administration of leptin. AVP mRNA expression in the PVN was also increased by leptin. However, leptin had no effects on plasma oxytocin (OXT) secretion and OXT gene expression in the SON. In conclusion, leptin is involved in AVP secretion via the central nervous system, however, its physiological role is unknown.

Animals↗

Phylogenetic position of the Phacotaceae within the Chlamydophyceaeas revealed by analysis of 18S rDNA and rbcL sequences.

Four genera of the Phacotaceae (Phacotus, Pteromonas, Wislouchiella, Dysmorphococcus), a family of loricated green algal flagellates within the Volvocales, were investigated by means of transmission electron microscopy and analysis of the nuclear encoded small-subunit ribosomal RNA (18S rRNA) genes and the plastid-encoded rbcL genes. Additionally, the 18S rDNA of Haematococcus pluvialis and the rbcL sequences of Chlorogonium elongatum, C. euchlorum, Dunaliella parva, Chloromonas serbinowii, Chlamydomonas radiata, and C. tetragama were determined. Analysis of ultrastructural data justified the separation of the Phacotaceae into two groups. Phacotus, Pteromonas, and Wislouchiella generally shared the following characters: egg-shaped protoplasts, a single pyrenoid with planar thylakoid double-lamellae, three-layered lorica, flagellar channels as part of the central lorica layer, mitochondria located in the central cytoplasm, lorica development that occurs in mucilaginous zoosporangia that are to be lysed, and no acid-resistant cell walls. Dysmorphococcus was clearly different in each of the characters mentioned. Direct comparison of sequences of Phacotus lenticularis, Pteromonas sp., Pteromonas protracta, and Wislouchiella planctonica revealed DNA sequence homologies of >/=98. 0% within the 18S gene and 93.9% within the rbcL gene. D. globosus was quite different from these species, with a maximum of 92.9% homology in the 18S rRNA and </=86.6% in the rbcL gene. It showed major similarities to the 18S rDNA of Dunaliella salina, with 95.3%, and to the rbcL sequence of Chlamydomonas tetragama, with 90.3% sequence homology. Additionally, the Phacotaceae sensu stricto exclusively shared 10 (rbcL: 4) characters which were present neither in other Chlamydomonadales nor in Dysmorphococcus globosus. Different phylogenetic analysis methods confirmed the hypothesis that the Phacotaceae are polyphyletic. The Phacotaceae sensu stricto form a stable cluster with affinities to the Dunaliellaes and possibly Haematococcus pluvialis. Dysmorphococcus globosus represented an independent lineage that is possibly related to Chlamydomonas moewusii and C. tetragama.

Chlorophyta↗

Histamine enhances UVB-induced IL-6 production by human keratinocytes.

Histamine, an important mediator in immediate-type hypersensitivity, is elevated in the skin of patients with atopic dermatitis and is considered to play a pathogenic role in atopic dermatitis. In this study, to elucidate the mechanism of sun exposure-induced exacerbation of skin lesions in atopic dermatitis, we examined the effect of histamine on proinflammatory cytokine production of keratinocytes induced by ultraviolet (UV) B irradiation. Cultured human keratinocytes were irradiated with 30 mJ/cm2 of UVB and incubated with histamine over the concentration range 10(-7) to 10(-4) M, and the IL-1alpha and IL-6 released into the medium were measured using an ELISA. Histamine weakly stimulated IL-6 production by itself. However, together with UVB, it synergistically enhanced IL-6 production and the amount of IL-6 mRNA as estimated by reverse-transcription polymerase chain reaction (RT-PCR). Histamine had a dose-dependent effect which was maximal at a concentration of 10(-5) M, and had no effect on the kinetics of IL-6 production. In contrast, histamine had no effect on IL-1alpha production by keratinocytes. The effect of histamine was completely blocked by pyrilamine, an H1 receptor antagonist, and mimicked by the H1 receptor agonist, 2-methylhistamine. Whereas the H2 receptor antagonist, cimetidine, slightly inhibited the effect of histamine and the effect of the H2 receptor agonist, 4-methylhistamine, was minute. These results show that histamine augments UVB-induced IL-6 production by keratinocytes predominantly via the H1 receptor at the level of transcription. This suggests a contributory role for histamine in the exacerbation of atopic dermatitis induced by sun exposure.

Adult↗