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Biomedical subjects

M Kagaya

Publications and source records attributed to M Kagaya.

At least 19 recordsLinked to original sources

CD30+ large cell transformation of mycosis fungoides after psoralen plus ultraviolet A photochemotherapy.

Psoralen plus ultraviolet A (PUVA) photochemotherapy is widely used for the therapy of mycosis fungoides (MF). Clinical progression of MF is often associated with an increase in the size of tumour cells known as transformation. We report two patients with CD30+ large cell transformation that appeared after low-dose PUVA therapy for MF. Clinical data, histopathology, immunohistopathology and T-cell receptor gene rearrangement were studied. Nodules consisted of atypical large cells that expressed CD30. Monoclonal rearrangement of T-cell receptors was observed in one case. Low-dose PUVA therapy may be associated with CD30+ large cell transformation in patients with MF.

Aged↗

Idiopathic acquired generalized anhidrosis due to occlusion of proximal coiled ducts.

Idiopathic acquired generalized anhidrosis is a very rare disease of unknown pathogenesis. We report a 25-year-old man with acquired generalized anhidrosis due to occlusion of the coiled ducts. He did not have sweat secretion over the entire surface of the body, including the palms and soles. Sweat-inducing stimuli provoked tingling pain on the skin. Pilocarpine iontophoresis on the forearm did not induce sweat secretion. Neurological examination did not reveal any abnormality in the central or peripheral nervous system. Skin biopsy showed that the coiled ducts were occluded by an amorphous eosinophilic substance. This amorphous eosinophilic substance was positive with periodic acid-Schiff (PAS) staining and was resistant to digestion by diastase. Electron microscopy demonstrated that the coiled ducts were completely occluded by an amorphous substance. The substance occluding the coiled ducts contained fibrous structures. These findings suggested that the acquired generalized anhidrosis in this patient was caused by occlusion of the coiled ducts by a PAS-positive substance probably derived from dark cell granules.

Adult↗

Localized lymphomatoid papulosis.

A 50-year-old Japanese male visited our clinic in April 1999 with a 2-year history of self-healing, reddish papules on his right palm. On examination, there were grouped erythematous papules, 2-4 mm in size, which formed a relatively well-circumscribed erythematous plaque. A biopsy specimen showed a wedge-shaped, dense dermal infiltrate consisting of variously sized mononuclear lymphoid cells mixed with few large CD30-positive cells and inflammatory cells, suggesting the diagnosis of regional lymphomatoid papulosis (LyP). Analysis of the T cell receptor gene revealed a polyclonal pattern on lesional skin. Only 5 cases of LyP presenting in a regional distribution have been reported previously. Although the etiology of localized LyP remains unknown, considering that 2 of 5 reported patients developed widespread lesions regional LyP may be the initial presentation of typical LyP.

Administration, Topical↗

Exercise-induced nausea is exaggerated by eating.

This study was conducted to determine whether and under what circumstances exercise causes nausea. Twelve healthy volunteers (20-37 years), including six athletes, participated in the study. Subjects were studied on seven occasions. Each subject performed low and high-intensity exercise without eating, immediately after eating a beef patty and 60 min after eating. Besides these exercise experiments, effect of meal on nausea was studied in each subject for 180 min without exercise. Exercise was done on a bicycle ergometer for 60 min at 40-50% maximal heart rate reserve and 20 min at 70-80% maximal heart rate reserve. Subjects were tested for nausea by visual analogue scales. Both low and high-intensity exercise caused nausea. Scores for nausea were greater during exercise at fasting state and immediately after eating than those without exercise (p<0.05 during low-intensity exercise, and p<0.01 during high-intensity exercise). Immediately after eating, scores for nausea were greater during high-intensity exercise than during low-intensity exercise (p<0.05). During high-intensity exercise, scores for nausea were greater immediately after eating than without eating (p<0.05). There were no differences in ratings for nausea between the sexes in any of the experimental conditions. Training did not decrease exercise-induced nausea. In conclusion, exercise causes nausea, the severity of which is related to exercise intensity and food intake, but not sex differences nor physical training.

Adult↗

Cloning and characterization of the 5'-flanking region of human cytokeratin 19 gene in human cholangiocarcinoma cell line.

BACKGROUND/AIMS: The regulatory mechanism of cell-specific gene expression in cholangiocytes has not been sufficiently evaluated. In this study, we characterized the 5'-flanking region of the cytokeratin 19 gene expressed specifically in cholangiocytes. METHODS: We cloned a 2952-bp fragment in the 5'-flanking region of cytokeratin 19 and evaluated the regulatory mechanism of gene expression in this region by assaying transient expression of reporter gene and DNA footprinting. RESULTS: This segment of the 5'-flanking region of the human cytokeratin 19 gene shows an intense transcriptional activity in the cholangioma cell line KMBC, which was about 10 times its activity in the osteosarcoma cell line Saos-2, which does not express cytokeratin 19. From the results of reporter assays, important transcription regulatory elements are considered to be located in the segments from -2249 to -2050 bp and from -732 bp to the first ATG, and six protein-binding sites were detected in the segment from -732 bp to the first ATG by the DNA footprinting technique. CONCLUSIONS: Sp1 site, CCAAT box, and TATA box were present in the segment from -374 to the first ATG, and they are considered to constitute a cholangiocyte-specific promoter.

Base Sequence↗

The endogenous cannabinoid agonist, anandamide stimulates sensory nerves in guinea-pig airways.

The endogenous cannabinoid agonist, anandamide produced a modest contractile response in guinea-pig isolated bronchus compared with the vanilloid receptor agonist capsaicin. The contractile response to both anandamide and capsaicin was inhibited by the vanilloid receptor antagonist, capsazepine. Furthermore, the NK(2)-selective antagonist, SR48968 but not the NK(1)-selective antagonist, SR140333 inhibited contractile responses to anandamide. The contractile response to anandamide was abolished in tissues desensitized by capsaicin. However, anandamide failed to cross-desensitize the contractile response to capsaicin. The contractile response to anandamide was not significantly altered in the presence of the CB(1) receptor antagonist, SR141716A, nor the amidase inhibitor, phenylmethylsulphonyl fluoride (PMSF) but was significantly increased in the presence of the neutral endopeptidase inhibitor, thiorphan. The cannabinoid agonist, CP55,940 failed to significantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) response in guinea-pig airways. In contrast, the ORL(1) receptor agonist, nociceptin, significantly inhibited this response. The results demonstrate that anandamide induces a modest contractile response in guinea-pig isolated bronchus that is dependent upon the activation of vanilloid receptors on airway sensory nerves. However, cannabinoid receptors do not appear to play a role in this regard, nor in regulating the release of neuropeptides from airway sensory nerves under physiological conditions.

Animals↗

Successful treatment of a patient with lymphomatoid papulosis by methotrexate.

We report a case of lymphomatoid papulosis (LyP) that occurred in a 44-year-old Japanese male patient. Reddish papules with a small number of pustules and nodules were observed on the extremities, chest and upper back. Most lesions were also associated with central necrosis, ulceration and crusting, and regressed spontaneously within 4 to 6 weeks. Histopathological examination revealed wedge-shaped dense cellular infiltrate in the dermis, which was mixed with large atypical lymphoid cells, small lymphocytes, eosinophils and neutrophils. These large atypical cells expressed CD30 on their cell membrane and cytoplasm. Rearrangement of the T-cell receptor (TcR) beta-chain gene was detected in the skin lesion. Lymphadenopathy with histopathologic change similar to the skin lesions, but without TcR gene rearrangement, was found at the left inguinal area. Systemic administration of methotrexate (7.5-15.0 mg/week) was found to be dramatically effective in resolution of skin lesions and prevention of their recurrence.

Adult↗

[A case of bronchioloalveolar cell carcinoma with bilateral diffuse interstitial infiltrative shadow during the treatment of Takatsuki's disease].

A 54-year old man treated with Takatsuki's disease was referred to us complaining of cough and excessive sputum. A chest roentgenogram showed bilateral diffuse interstitial infiltrative shadow. Chest CT showed banding shadows around the bronchioles and lobule-septum thickening in the right middle and both lower lung fields, and many small nodules in both lower lung fields. The histological diagnosis was adenocarcinoma replaced with one layer of bronchiolar epithelium, and partly bronchiolo-alveolar carcinoma. The patient received 3 courses of combination chemotherapy with docetaxel and cisplatin. After chemotherapy, the chest CT showed no change. The clinicopathological characteristics of this rare case included adenocarcinoma mixed with bronchioloalveolar carcinoma, in which radiography showed bilateral diffuse interstitial infiltrative shadow.

Adenocarcinoma↗

Sesamin and alpha-tocopherol synergistically suppress lipid-peroxide in rats fed a high docosahexaenoic acid diet.

Docosahexaenoic acid (DHA) is an essential nutrient for human health, but has extremely high oxidative susceptibility. We examined the suppressing effect of sesamin, a sesame seed lignan, on lipidperoxides in rats fed a low alpha-tocopherol and high DHA containing diet. Groups of rats were fed four experimental diets: low alpha-tocopherol (10 mg/kg diet) control diet, low alpha-tocopherol + 0.2% sesamin diet, low alpha-tocopherol + 0.5% DHA diet and low alpha-tocopherol + 0.5% DHA + 0.2% sesamin diet. TBARS concentrations in plasma and liver were significantly increased by DHA, but were completely suppressed by sesamin. Alpha-tocopherol concentrations in plasma and liver decreased by addition of DHA, but with sesamin recovered to the control level. The addition of DHA into the diets caused remarkable increases of DHA concentrations in plasma and liver lipids. Sesamin caused a significant increase of DHA concentrations in the triacylglycerol of plasma.

Animals↗

Cold pain prolongs gastric emptying of liquid but not solid meal: an electrical impedance tomography (EIT) study.

Stressful stimuli are reported to affect gastric emptying. However, methods for measuring gastric emptying are, in themselves, stressful. Electrical impedance tomography (EIT) is a method for measuring gastric emptying noninvasively. We used EIT to measure gastric emptying of liquid and solid meals to determine the effect of cold pain stress on gastric emptying. EIT (DAS-01P APT system; University of Sheffield, UK) was carried out in six healthy women (age, 21.6 +/- 0.4 [mean +/- SD] years) who had ingested a liquid (potage, 263 g; 139 kcal) or solid (beef patty, 205 g; 435 kcal) test meal. Cold pain stimuli consisted of repeated immersions of the subject's non-dominant hand into ice water (4 degrees C) for 1 min, with a 15-s recovery period between immersions, for a total of 20 min. For the control stimulus, water at 37 degrees C was used. The cold pain stimulus was applied immediately after the ingestion of a test meal. All studies were carried out randomly in each subject at intervals of more than 1 week. With cold pain, the half emptying time of the liquid meal was significantly greater than that with the control stimulus (47.6 +/- 26.1 min vs 28.1 +/- 10.8 min, P < 0.05). For the solid meal, the half emptying time did not differ between stimuli (101.9 +/- 44.8 min with cold pain vs 92.6 +/- 30.5 min with control stimulus). There were no significant differences in lag time between the liquid and solid meals. Cold pain stress delayed gastric emptying of liquid but not solid meals.

Adult↗

Differential regulation of metalloproteinase production, proliferation and chemotaxis of human lung fibroblasts by PDGF, interleukin-1beta and TNF-alpha.

Fibroblast migration, proliferation, extracellular matrix protein synthesis and degradation, all of which play important roles in inflammation, are themselves induced by various growth factors and cytokines. Less is known about the interaction of these substances on lung fibroblast function in pulmonary fibrosis. The goal of this study was to investigate the effects of PDGF alone and in combination with IL-1beta and TNF-alpha on the production of human lung fibroblast matrix metalloproteinases, proliferation, and the chemotactic response. The assay for MMPs activity against FITC labeled type I and IV collagen was based on the specificity of the enzyme cleavage of collagen. Caseinolytis and gelatinolytic activities of secreted proteinases were analyzed by zymography. Fibronectin in conditioned media was measured using human lung fibronectin enzyme immunoassay. Cell proliferation was measured by 3H-Thymidine incorporation assay. Cell culture supernatants were tested for PGE2 content by ELISA. Chemotactic activity was measured using the modified Boyden chamber. Matrix metalloproteinase assay indicated that IL-1beta, TNF-alpha and PDGF induced intestitial collagenase (MMP-1) production. MMP assay also indicated that IL-1beta and TNF-alpha had inhibitory effects on MMP-2,9(gelatinaseA,B) production. Casein zymography confirmed that IL-1beta stimulated stromlysin (matrix metalloproteinase 3; MMP-3) and gelatin zymography demonstrated that TNF-alpha induced MMP-9 production in human lung fibroblast, whereas PDGF alone did not. PDGF in combination with IL-1beta and TNF-alpha induced MMP-3 and MMP-9 activity, as demonstrated by zymography. PDGF stimulated lung fibroblast proliferation in a concentration-dependent manner, whereas IL-1beta and TNF-alpha alone had no effect. In contrast, the proliferation of human lung fibroblasts by PDGF was inhibited in the presence of IL-1beta and TNF-alpha, and this inhibition was not a consequence of any elevation of PGE2. PDGF stimulated fibroblast chemotaxis in a concentration-dependent manner, and this stimulation was augmented by combining PDGF with IL-1beta and TNF-alpha. These findings suggested that PDGF differentially regulated MMPs production in combination with cytokines, and further that MMP assay and zymography had differential sensitivity for detecting MMPs. The presence of cytokines with PDGF appears to modulate the proliferation and chemotaxis of human lung fibroblasts.

Cell Division↗

Effect of heparin and related glycosaminoglycan on PDGF-induced lung fibroblast proliferation, chemotactic response and matrix metalloproteinases activity.

Fibroblast migration, proliferation, extracellular matrix protein synthesis and degradation are the key events in various biological and pathological processes in pulmonary fibrosis. In addition, biopsy specimens from the lungs of patients with pulmonary fibrosis show increased numbers of mast cells which have metachromatic granules containing heparin, histamine and proteases. Little is known about how these products influence pulmonary fibrosis. In the present study, we investigated the effect of heparin and related glycosaminoglycans on PDGF-induced lung fibroblast proliferation and chemotactic response in vitro. In addition, we examined the effect of heparin on both the induction of matrix metalloproteinases (MMPs) and MMPs activity in lung fibroblasts in vitro. Heparin, de-N-sulphated heparin but not heparan sulphate inhibited PDGF-induced lung fibroblast proliferation. In contrast, only heparin inhibited PDGF-stimulated human lung fibroblast chemotaxis. Negatively charged poly-L-glutamic acid had no effect on either fibroblast proliferation or chemotaxis. Thus the negative charge alone cannot account for the ant-proliferative and anti-chemotactic effects of heparin. Furthermore, heparin and heparan sulphate also had no inhibitory effect on induction of MMPS, including MMP-1 (interstitial collagenase), MMP-2 (gelatinase A) and MMP-9 (gelatinase B). Only heparin inhibited both MMP-1 and MMP-2/MMP-9 activity. Additionally, tissue inhibitor of metalloproteinase type 1 (TIMP-1) and type 2 (TIMP-2) inhibited PDGF-stimulated human lung fibroblast chemotaxis. The ability of heparin to inhibit fibroblast chemotaxis may account for the inhibitory effect of heparin on MMP activity. The above results suggested that heparin and related glycosaminoglycans differentially regulate PDGF-induced lung fibroblast proliferation, chemotaxis and MMPs activity and further that these effects may have a key role in extracellular matrix remodeling in inflammatory lung disease.

Becaplermin↗

UVB photosensitivity due to ranitidine.

We describe a 62-year-old male with photosensitivity due to ranitidine. An oral challenge test after taking ranitidine with UVB irradiation was positive. Ranitidine-induced UVB photosensitivity was persistent even after cessation of the medication.

Dermatitis, Photoallergic↗

Effects of aging and gastric lipolysis on gastric emptying of lipid in liquid meal.

Lipid delays gastric emptying, and aging is associated with changes in gastric motor function and transit. However, little is known about the effect of lipid on gastric emptying time in the elderly. To determine the effect of aging on lipid gastric emptying, we used electrical impedance tomography (EIT) to study gastric emptying of liquid meals with or without lipid in five young (23.0 +/- 0.6 years, mean +/- SEM) and six elderly (73.3 +/- 1.6 years) healthy male volunteers. These subjects drank 400 ml of non-lipid soup (triglycerides, 0 g) or lipid soup (triglycerides, 24.6g) in liquid test meals. To study the effect of lipolysis in the stomach, a liquid test meal containing 240mg of lipase in the lipid soup was also administered. Plasma cholecystokinin (CCK) concentration was measured by specific radioimmunoassay before and 30 min after the ingestion of a test meal. The gastric emptying time of the lipid soup was longer in the elderly than in the young subjects, and the time was significantly longer for lipid soup than for nonlipid soup (P < 0.05) in both the young and elderly subjects. Gastric emptying time for non-lipid soup was not significantly different between the elderly and young subjects. The administration of lipase shortened the gastric emptying time for lipid in both the elderly and the young subjects. Basal CCK concentration was significantly higher in the elderly than in the young subjects. However, there was no relationship between gastric emptying time and plasma CCK concentration after the ingestion of a test meal in the subjects overall. In conclusion, the delaying effect of lipid on gastric emptying is increased in the elderly, and the administration of lipase accelerates the emptying of lipid from the stomach.

Adult↗

Adrenal insufficiency due to metastatic hepatocellular carcinoma.

A 73-year-old man with general malaise and nausea following a common cold diagnosed by a local physician was found to have multiple hepatocellular carcinomas with enlarged bilateral adrenal glands, combined with adrenal insufficiency. Hydrocortisone replacement improved the symptoms and laboratory findings. Autopsy findings revealed that each adrenal gland was completely replaced by the tumor measuring 11 cm in diameter, and no adrenal tissue was recognized. Histologically, the adrenal tumors, as well as the liver tumors, were moderately differentiated Edmondson type II hepatocellular carcinomas. This is a second report of adrenal insufficiency due to hepatocellular carcinoma as a primary site of metastatic adrenal tumor.

Adrenal Gland Neoplasms↗

[Goodpasture's syndrome initially presenting with alveolar hemorrhage].

A 17-year-old man was admitted to our hospital because of exertional dyspnea, fever, and hemoptysis. Chest X-ray films disclosed diffuse alveolar infiltrates and patchy shadows in both lungs. Laboratory data included a hemoglobin level of 6.7 g/dl and white blood cell count of 8,100/microliter. Urinalysis revealed microscopic hematuria with RBC cast. Bronchoalveolar lavage fluid from the right middle lobe bronchus was bloody. Anti-GBM antibodies were detected at low levels in serum (10 EU/ml) by ELISA procedures. Renal and lung biopsies were performed. Immunofluorescent studies revealed linear deposits of IgG along glomerular basement membrane of the kidney, but not in alveolar walls of the lung. This case fulfilled the criteria for Goodpasture's syndrome. The patient was treated with methylprednisolone (1,000 mg/day, for 3 days) and plasma exchange (for 2 days), and demonstrated a dramatic improvement in his clinical condition and chest X-ray findings. We were unable to identify autoantibodies to the NC domain of the alpha 3 chain of type IV collagen. Another conformational epitope may play a role in the disease.

Adolescent↗

Cold milk accelerates oro-cecal transit time during the luteal phase but not the follicular phase in women.

The effect of the menstrual cycle on oro-cecal transit time (OCTT) has been controversial. Since poor reproducibility of OCTT measurements by lactulose might be responsible for this controversy, we measured OCTT with either milk or a solid test meal during the luteal and follicular phases of the menstrual cycle. Nine healthy young women (21.9 +/- 0.42 years old) with regular menstruation were studied for 4 consecutive menstrual cycles. Control (37 degrees C) or cold (10 degrees C) milk was used as a liquid meal, and the OCTT measurements were taken 3 times at each milk temperature during each of the 2 phases for 3 consecutive menstrual cycles. OCTT after a solid test meal (cooked rice, miso soup, a boiled egg, and cooked soybeans with mixed vegetables) was studied twice in 1 menstrual cycle. Breath hydrogen was determined every 15 min for 6 h. OCTT was defined as the time when breath hydrogen showed a sustained rise of 3 ppm or more from baseline. OCTT was not different between the luteal and follicular phases when the test meal was control milk or the solid meal. When cold milk was used as the test meal, OCTT was significantly shorter during the luteal phase (134 +/- 15 min) than during the follicular phase (165 +/- 21 min). In conclusion, cold milk accelerates OCTT during the luteal phase but not the follicular phase of the menstrual cycle in women.

Administration, Oral↗