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Biomedical subjects

Y Inoue

Publications and source records attributed to Y Inoue.

At least 397 records · Page 22Linked to original sources

Corneal guttata associated with the corneal dystrophy resulting from a betaig-h3 R124H mutation.

AIMS: To investigate the frequency of corneal guttata in patients with a corneal dystrophy resulting from an Arg124His (R124H) mutation of betaig-h3 gene. METHODS: Slit lamp examination was performed on 30 eyes with corneal dystrophy from a genetically confirmed betaig-h3 R124H mutation and on 50 age matched control eyes. The stage of the corneal dystrophy was classified as stage 0, I, or II and the degree of guttata was classified as none, mild, or severe. Specular microscopic examinations were performed to evaluate the morphology of the corneal endothelium. RESULTS: Slit lamp examination disclosed the presence of corneal guttata in 21 eyes (70%) of the 30 eyes with the corneal dystrophy, but in only one (2%) of the 50 eyes in the age matched control group (p<0.001, chi(2) with Yates's correction). Of the 12 eyes with stage I betaig-h3 R124H corneal dystrophy, seven had no corneal guttata and five had a mild degree of guttata. Of the 18 eyes with stage II, the degree of guttata was none in two, mild in nine, and severe in seven. The degree of corneal guttata was significantly related to the stage of the corneal dystrophy (p<0.0001, Kruskul-Wallis test ANOVA on ranks). There was no significant differences between eyes with betaig-h3 R124H corneal dystrophy and normal eyes in cell density, coefficient of variation, and cell hexagonality of corneal endothelium. CONCLUSION: Corneal guttata are one of the characteristics of the corneal dystrophy resulting from betaig-h3 R124H mutation.

Aged↗

Management of orbital lymphangioma using intralesional injection of OK-432.

AIM: To treat orbital lymphangioma with an intralesional injection of OK-432 (group A Streptococcus pyogenes of human origin). METHOD: A 14 year old boy had a right orbital cystic lymphangioma. The visual acuity in the eye was 20/28. In an initial treatment, 0.02 mg of OK-432, was injected into the tumour after aspiration of the fluid contents, but no effect was seen. The second treatment was performed with 0.04 mg of OK-432. RESULT: 4 months later, the lesion had totally shrunk to fibrous tissue. The side effects were fever, a local inflammatory reaction lasting 3 days, and increased intraocular pressure, which was managed by draining the fluid contents. Visual acuity improved to 20/15, and the visual field defect and restriction of eye movement seen before treatment disappeared. No recurrence was noted 1 year after treatment. CONCLUSION: An intralesional injection of OK-432 shrunk the lymphangioma without functional disturbance and scar in the facial skin. OK-432 may be useful for orbital lymphangioma, but further studies are still warranted to determine efficacy, complications, and the optimal dose for safe treatment.

Adolescent↗

Bax is downregulated in inflamed colonic mucosa of ulcerative colitis.

BACKGROUND AND AIMS: One form of epithelial cell injury in inflamed colonic mucosa in ulcerative colitis (UC) is reported to involve apoptosis of these cells. Bcl-2 family proteins Bax and Bcl-2 are the major regulators of apoptosis. The aim of this study was to elucidate the involvement of the Bax/Bcl-2 system in induction of apoptosis of the inflamed colonic epithelium in UC. METHODS: Colonic epithelium was isolated from colonic biopsy specimens. Expression of CD95, Bax, Bcl-xL, and Bcl-2 proteins was determined by western blotting. Bax gene expression was assessed by both reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern hybridisation and a real time PCR assay. RESULTS: Equal levels of expression of CD95, Bcl-xL, and Bcl-2 proteins were noted in normal and UC colonic epithelia. Equal levels of expression of Bax protein and mRNA were noted in epithelia of normal colon and inactive UC. Levels of expression of Bax protein and mRNA were markedly reduced in inflamed UC colonic epithelium. CONCLUSIONS: Our study showed for the first time downregulation of Bax in inflamed colonic epithelium of UC. The Bax/Bcl-2 system did not seem to be involved in induction of apoptosis of epithelial cells in the inflamed colonic mucosa of UC.

Adult↗

Suppressive effect of topically applied CX-659S, a novel diaminouracil derivative, on the contact hypersensitivity reaction in various animal models.

BACKGROUND: The T-cell-mediated contact hypersensitivity reaction (CHR) is thought to be involved in the pathogenesis of clinical cutaneous disorders including atopic dermatitis. A novel diaminouracil derivative, CX-659S, has been reported to have an inhibitory activity against picryl chloride (PC)-induced CHR when administered either orally or percutaneously. The inhibitory effect of topical CX-659S was assessed in three CHR models in the present study. In addition, to elucidate the mechanism of action of this compound, we examined the effect of CX-659S on the expression of messenger RNAs for proinflammatory cytokines after elicitation in PC models. METHODS: For the in vivo evaluation of the efficacy of CX-659S, we used PC- or oxazolone-induced CHR in mice and 2,4-dinitrochlorobenzene (DNCB)-induced CHR in guinea pigs. CX-659S was topically applied immediately after the hapten challenge in each model. To assess the effect on gene expression of cytokines, we used the reverse transcriptase-polymerase chain reaction (RT-PCR), a semiquantitative technique with specific primers. RESULTS: Topical CX-659S dose-dependently inhibited ear swelling at 24 h after the challenge in the two mouse models. This inhibitory effect was histologically confirmed in the PC model. Topically applied CX-659S also inhibited erythema and edema formation 24 h after challenge in the guinea pig model. CX-659S inhibited the expression of mRNA for proinflammatory cytokines IL-1 beta and TNF-alpha in vivo. CONCLUSIONS: Topically applied CX-659S showed significant inhibitory activities against CHR models both in mice and in guinea pigs. Inhibition profiles of CX-659S toward mRNA expression for proinflammatory cytokines corroborated these findings. CX-659S thus could be a useful therapeutic agent for allergic cutaneous disorders such as allergic contact dermatitis and atopic dermatitis.

Administration, Topical↗

Mast cell basic fibroblast growth factor in silicosis.

To investigate the role of mast cells (MC) and their fibrogenic growth factors in silicosis, we performed quantitative immunohistochemistry for MC tryptase and for basic fibroblast growth factor (bFGF) in lung tissue from silicotic and control subjects. Anti-bFGF antibody was bound to lung MC, basement membrane, endothelial cells, and smooth-muscle cells. Morphometric analysis revealed that the volume density (V(v)) of MC was increased in silicotic lung and that the V(v) of bFGF-positive (bFGF(+)) cells was significantly higher than normal in silicotic lung. Most MC contained bFGF (rho = 0.88, p < 0.001). The V(v) of collagen/reticulin fibers was increased in silicosis and correlated with the V(v) of bFGF(+) cells (rho = 0.81, p < 0.001). Immature silicotic nodules contained bFGF(+) MC throughout the loose array of collagen/reticulin fibers. In large, mature nodules, the density of collagen/reticulin fibers was higher, and bFGF(+) MC were found only in the nodule periphery. Because of this circumferential MC alignment in silicotic nodules, we observed a negative correlation between the V(v) of bFGF(+) MC and the density of collagen/reticulin fibers in silicotic nodules (rho = -0.80, p < 0.001) and between the V(v) of all other nodule-associated cells and the density of collagen/reticulin fibers in the hypocellular nodule centers (rho = -0.84, p < 0.001). We conclude that MC that produce bFGF may play an important role in the development of silicosis.

Aged↗

Serological diagnosis of idiopathic pulmonary alveolar proteinosis.

Previously, we reported the specific occurrence of neutralizing autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchoalveolar lavage fluid from 11 Japanese patients with idiopathic pulmonary alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all 5 I-PAP patients examined. To determine that the existence of the autoantibody is not limited to the Japanese patients, we examined sera from 24 I-PAP patients in five countries and showed that the autoantibody was consistently and specifically present in such patients. Thus, detection of the autoantibody in sera can be used for diagnosis of I-PAP. To establish a simple and convenient method for diagnosis of I-PAP, we developed a novel latex agglutination test using latex beads coupled with recombinant human GM-CSF. GM-CSF binding proteins isolated from the sera using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2). The titer of the autoantibody determined by this test correlated with that determined by ELISA. Agglutination was positive in 300-fold diluted sera from all 24 I-PAP patients, but negative in sera from four secondary PAP patients, two congenital PAP patients, 40 patients with other lung diseases, and 38 of 40 normal subjects. These results establish that the latex agglutination test is a reliable method for serological diagnosis of I-PAP with high sensitivity (100%) and specificity (98%).

Adult↗

Percutaneous transluminal coronary angioplasty performed 24-48 hours after the onset of acute myocardial infarction improves chronic-phase left ventricular regional wall motion.

The authors investigated the capacity of percutaneous transluminal coronary angioplasty (PTCA) performed 24-48 hours after the onset of acute myocardial infarction (AMI) to improve regional left ventricular wall motion. Twenty-four patients were divided into two groups: a PTCA group who received successful PTCA (14 cases) and a non-PTCA group (10 cases) who did not receive PTCA. Left ventricular end-diastolic volume (LVEDV) increased significantly (p<0.01) from 57+/-14 mL/m2 during the acute phase to 83+/-16 mL/m2 during the chronic phase in the non-PTCA group, whereas no significant change in LVEDV was seen in the PTCA group (69+/-26 vs. 76+/-16 mL/m2). In addition, in patients with 99% stenosis/thrombolysis in myocardial infarction (TIMI) grade 3 flow, increases in regional left ventricular wall motion (delta(sd)/chord) at the infarcted site between the acute and chronic phases were significantly greater in the PTCA group than in the non-PTCA group (2.49+/-1.05 vs. 0.67+/-0.65, p<0.01). PTCA performed 24-48 hours after the onset of AMI improved wall motion at the infarcted site.

Aged↗

Cytokine profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated ophthalmopathy.

Eye muscle (EM) and retroorbital fat tissue are two major sites of involvement in thyroid-associated ophthalmopathy (TAO). Lymphocytic infiltration in these tissues is a prominent histological feature of TAO. We have investigated the cytokine gene profiles in EM and orbital fat (OF) tissues from patients with TAO. Total RNA was isolated from EM tissue of 14 patients and from OF tissues of 29 patients with TAO. Cytokine gene expression was assessed by RT-PCR using paired primers for interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, CD4, CD8, and glyceraldehyde-3-phosphate dehydrogenase. IFNgamma, TNFalpha, IL-1beta, and IL-6 messenger RNA (mRNA) were mainly detected in EM tissue, whereas IL-4 and IL-10 mRNA were detected in only one patient. On the other hand, in OF tissue, IL-4 and IL-10 mRNA were detected in 24% and 38% of the patients, respectively, and IFNgamma, IL-1beta, and IL-6 mRNA were less often detected compared with EM tissue. The enlargement of EM tissue as assessed by computed tomography correlated significantly with TNFalpha mRNA expression in EM tissue. The orbital volume was positively correlated with IL-6 mRNA expression and negatively correlated with IL-4 mRNA and IL-10 mRNA expression in OF tissue. These results suggest that T helper (Th) 1-like cytokines predominate in EM tissue in most patients and that the predominant cytokine profile in OF tissue varies from patient to patient. Both Th1-like and Th2-like immune responses may play roles in the development of two components of ophthalmopathy.

Adipose Tissue↗

Correlation of diversity of leg morphology in Gryllus bimaculatus (cricket) with divergence in dpp expression pattern during leg development.

Insects can be grouped into mainly two categories, holometabolous and hemimetabolous, according to the extent of their morphological change during metamorphosis. The three thoracic legs, for example, are known to develop through two overtly different pathways: holometabolous insects make legs through their imaginal discs, while hemimetabolous legs develop from their leg buds. Thus, how the molecular mechanisms of leg development differ from each other is an intriguing question. In the holometabolous long-germ insect, these mechanisms have been extensively studied using Drosophila melanogaster. However, little is known about the mechanism in the hemimetabolous insect. Thus, we studied leg development of the hemimetabolous short-germ insect, Gryllus bimaculatus (cricket), focusing on expression patterns of the three key signaling molecules, hedgehog (hh), wingless (wg) and decapentaplegic (dpp), which are essential during leg development in Drosophila. In Gryllus embryos, expression of hh is restricted in the posterior half of each leg bud, while dpp and wg are expressed in the dorsal and ventral sides of its anteroposterior (A/P) boundary, respectively. Their expression patterns are essentially comparable with those of the three genes in Drosophila leg imaginal discs, suggesting the existence of the common mechanism for leg pattern formation. However, we found that expression pattern of dpp was significantly divergent among Gryllus, Schistocerca (grasshopper) and Drosophila embryos, while expression patterns of hh and wg are conserved. Furthermore, the divergence was found between the pro/mesothoracic and metathoracic Gryllus leg buds. These observations imply that the divergence in the dpp expression pattern may correlate with diversity of leg morphology.

Animals↗

Preparation and characterization of two crystalline forms of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrroli dinyl]benzamide (TKS159).

For 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrrolid inyl]benzamide (TKS159), two polymorphs, forms alpha and beta, were prepared and characterized by means of X-ray powder diffractometry, thermal analysis, infrared spectroscopy and 13C-NMR spectroscopy, both in the solution and solid phases. The X-ray powder diffraction analysis gave different patterns for forms alpha and beta. In the thermogravimetry and differential thermal analysis profiles, form beta exhibited characteristic endo- and exothermic peaks at 112.7 degrees C and 116.2 degrees C, respectively, due to the partial melting-induced phase transition to form alpha without accompanying weight loss, and these were followed by an additional endothermic peak at 138.2 degrees C due to fusion. For form alpha, only an endothermic peak at 137.8 degrees C due to fusion was observed. The IR spectroscopic analyses of forms alpha and beta gave different absorption bands assigned to N-H and O-H stretching, N-H bending, and C=O stretching vibrations. From the data obtained by thermal analysis, form alpha was shown to be thermodynamically more stable than form beta.

Benzamides↗

Interactions of cyclodextrins with dipalmitoyl, distearoyl, and dimyristoyl phosphatidyl choline liposomes. A study by leakage of carboxyfluorescein in inner aqueous phase of unilamellar liposomes.

The interaction of cyclodextrins (CDs) with L-alpha-dipalmitoyl phopsatidyl choline (DPPC), L-alpha-distearoyl phosphatidyl choline (DSPC), and L-alpha-dimyristoyl phosphatidyl choline (DMPC) unilamellar liposomes was investigated by the leakage of carboxylfluorescein (CF) entrapped in the inner aqueous phase of liposomes, at 25 degrees C (DPPC and DSPC liposomes) and at 5 degrees C (DMPC liposomes). The efficiency of CDs for CF leakage was remarkable in the order of heptakis (2,6-di-O-methyl)-beta-CD (DOM-beta-CD) > alpha-CD > heptakis (2,3,6-tri-O-methy)-beta-CD (TOM-beta-CD) from DPPC liposomes, in the order of DOM-beta-CD > TOM-beta-CD > alpha-CD from DSPC liposomes and in the order of alpha-CD > DOM-beta-CD > TOM-beta-CD from DMPC liposomes. The other CDs used in the present studies, beta-CD, 2-hydroxylpropyl beta-CD, and gamma-CD scarcely induced the CF leakage from above the three liposomes. From the profiles of % CF leakage, together with measurements of differential scanning calorimetry, it was found that hydrophobic DOM-beta-CD penetrates the matrix of the liposomes to interact with them as well as TOM-beta-CD, and that less hydrophobic alpha-CD exists at the surface of the membrane to interact with the liposomes. Further, it was found that the interaction of CDs with liposomes changes depending not only on the length of fatty acid chain of phospholipid (condensation force and hydrophobicity) but also the hydrophobicity and the cavity size of CD.

1,2-Dipalmitoylphosphatidylcholine↗

Vestibular schwannoma presenting as sudden deafness.

In this study, we analysed the clinical and audiological features of 24 vestibular schwannoma patients presenting with sudden deafness who visited our hospital within 10 days after its onset. The relationships between the prognosis of hearing loss and the clinical and audiological features including the pure-tone average (PTA), the presence of dizziness and/or vertigo, the tumour size and the auditory brain stem response (ABR) findings were evaluated. Hearing recovery depended on the PTA and tumour size, but even a small tumour induced sudden deafness. Impaired hearing completely recovered in five our of 24 patients. ABR findings indicated that the aetiology of sudden deafness in the vestibular schwannoma patients might vary in each patient.

Adult↗

Thyroid hyperactivity induced by methimazole, spironolactone and phenobarbital in marmosets (Callithrix jacchus): histopathology, plasma thyroid hormone levels and hepatic T4 metabolism.

To determine drug-induced hyperfunction of marmoset thyroids due to inhibition of synthesis or enhancement of metabolic elimination of thyroid hormones, males were orally administered 10 and 30 mg/kg/day methimazole (MMI), 30 and 100 mg/kg/day spironolactone (SPL), or 50 mg/kg/day phenobarbital (PB) for 4 weeks. MMI caused marked hypertrophy of follicular epithelial cells in accordance with a significant decrease in the plasma thyroxin (T4) level. Hypertrophied epithelial cells were filled with dilated rough endoplasmic reticulum and reabsorbed intracellular colloids, and the luminal surface was covered with abundant microvilli. The colloid included vacuoles positive to anti T4 immuno-staining. SPL and PB also caused similar histomorphological changes, although they were less severe than those due to MMI and were not clearly associated with decrease in the plasma T4 levels. Hepatic T4 UDPGT activities tended to increase due to SPL and PB treatment, however, which were not so significant as increases in microsomal cytochrome P-450 contents. Some animals treated with SPL and PB showed marked increases in thyroid weights due to inactive dilated follicles. In conclusion, hyperactivity of thyroid follicles was induced in marmosets not only due to inhibition of T4 synthesis produced by MMI but also because of enhancement of hepatic T4 elimination produced by SPL and PB. However, hypertrophic effects of SPL and PB were less severe than MMI, because plasma T4 levels were maintained at almost pretreatment or control levels after SPL or PB treatment.

Animals↗

Haemorrhagic lumbar synovial cyst. A cause of acute radiculopathy.

A total of 254 cases of synovial cysts of the spine have been reported in the English literature, but only eight have been associated with haemorrhage. We describe a 55-year-old man with acute radiculopathy resulting from haemorrhage involving a synovial cyst at a lumbar facet joint. Traumatic factors could have caused bleeding around or into the synovial cyst. Treatment by resection of the cyst and evacuation of the haematoma led to complete neurological recovery.

Acute Disease↗

Simple and rapid determination of Gtpase activity by capillary electrophoresis without radioisotope.

In order to determine guanosine-5'-triphosphatase (GTPase) activity, we developed a simple, rapid and reliable method that utilizes capillary electrophoresis without radioisotope. Tubulin-GTPase was used for simple measurement of GTPase activity utilizing capillary electrophoresis. Tubulin, a component of microtubules, was incubated with guanosine-5'-triphosphate (GTP) in 100 mM 2-(N-morpholino) ethanesulfonic acid (MES) buffer (pH 6.5). Guanosine-5'-diphosphate (GDP) was determined as the hydrolyzed product of GTP. Guanosine-5'-monophosphate, GDP and GTP in the filtrate of the mixture were clearly separated using 10 mM MES buffer (pH 6.5) (migration time, 3.8, 5.5 and 7.2 minutes, respectively) with a fused-silica capillary column. The quantification of GDP was based on the peak area, which increased linearly with the concentration of GDP from 1 to 50 microM (r2=0.995). The peak area and migration time had good reproducibility; the intra-assay coefficient of variation (n=6) was 1.3% for peak area and 0.6% for migration time. As an application of this method, we examined the effect of dimethylarsinic acid, an effective antimitotic agent, on tubulin-GTPase. Dimethylarsinic acid inhibited tubulin-GTPase activity in a dose-dependent manner. The inhibition was not complete and the maximum decrease of the activity was about 50% at 200 microM dimethylarsinic acid. Thus, since this method is clean, simple and rapid, its application to the study of various GTPase proteins is expected to be useful.

Buffers↗

Gene expression of the three members of hepatocyte nuclear factor-3 is differentially regulated by nutritional and hormonal factors.

Hepatocyte nuclear factor-3 (HNF-3) belongs to a large family of forkhead transcription factors and is made up of three members (HNF-3alpha, -3beta and -3gamma). It has been shown that HNF-3 regulates a number of metabolically important genes. However, the mechanisms underlying this regulation of HNF-3 activity by hormones and nutrition have not yet been well elucidated. In attempting to explore the regulation of gene expression of HNF-3 members by physiological status, we analyzed the effects of insulin, dexamethasone and protein malnutrition on the hepatic mRNA level of each member. Male Wistar rats were fed on a 12% casein diet, 12% gluten diet (deficient in lysine and threonine) or a protein-free diet for 1 week. The protein-free diet and gluten diet caused a 3. 7-fold increase in HNF-3g mRNA in the liver and did not affect the mRNA level of either HNF-3alpha or HNF-3beta. Daily administration of dexamethasone caused the mRNA levels of HNF-3alpha and HNF-3beta to increase (2.3- and 1.4-fold, respectively), but had no effect on the HNF-3gamma mRNA level. In diabetic rats that had been injected with streptozotocin, an elevation of the hepatic mRNA levels of HNF-3beta and HNF-3gamma was observed (1.6-and 1.9-fold, respectively). Insulin replacement in the diabetic rats decreased both mRNA levels in a dose-dependent manner. HNF-3alpha mRNA was not affected by insulin status. These results show that the genes of the three members of the HNF-3 family respond differently to hormonal and nutritional factors suggesting that the activities of HNF-3 members are regulated, at least in part, by the levels of their gene expression.

Animals↗

Paragonimiasis miyazakii associated with bilateral pseudochylothorax.

A 37-year-old man who suffered from bilateral pleural effusions, subcutaneous abdominal induration and blood eosinophilia, was admitted to our hospital. He had ingested raw crabs at a pub-restaurant before the onset of his symptoms. His pleural effusions were chyliform containing cholesterol crystals, and a high level of immunoglobulin E (36,580 IU/ml) and anti-Paragonimus miyazakii antibody were detected. He was effectively treated with praziquantel. This case suggests that paragonimiasis should be strongly suspected if blood eosinophilia, pseudochylothorax, and a high level of immunoglobulin E in pleural effusion are detected.

Adult↗

[Pulmonary hypertension in a patient with primary Sjogren's syndrome, Hashimoto's disease, and primary biliary cirrhosis].

A 53-year-old woman was admitted to our hospital in May 1999, because of progressive dyspnea and liver dysfunction. She had been receiving the replacement therapy of thyroid hormone for thirteen years and suffering from Raynaud's phenomenon for 9 years. She experienced exertional dyspnea and sicca symptom for 3 years, and had an episode of syncope 4 months before admission. An echocardiogram showed dilation of the right ventricle, tricuspid regurgitation and the estimated mean pressure of the pulmonary artery was higher than 120 mmHg. She was diagnosed as having severe pulmonary hypertension (PH) complicated with primary Sjogren's syndrome and primary biliary cirrhosis without portal hypertension She was treated with anticoagulant (warfarin) and oral prostagrandin I2 (prostacyclin). However, right heart failure and jaundice gradually progressed and she suddenly died in December 1999. At autopsy, the heart was enlarged with right ventricular hypertrophy. Small arteries and arterioles in the lung showed concentric intimal proliferation and severe plexogenic vascular disease. Deposition of immunoglobulin was not observed in the pulmonary arteries. Since the prognosis of PH is poor, it is important to analyze the etiology of the disease for the development of the treatment.

Fatal Outcome↗