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Biomedical subjects

T Kuroda

Publications and source records attributed to T Kuroda.

At least 19 recordsLinked to original sources

Expression of allograft inflammatory factor-1 in kidneys: A novel molecular component of podocyte.

Our comprehensive gene expression profiles of the kidneys in an anti-glomerular basement membrane (GBM) nephritis model using DNA arrays revealed that allograft inflammatory factor-1 (AIF-1) was one of the highly expressed genes. Here, we explored the pathological significance of AIF-1 expression in the kidneys. The expression pattern of AIF-1 mRNA and protein in the kidneys of normal and diseased rats, such as anti-GBM nephritis and puromycin aminonucleoside nephrosis, was investigated by in situ hybridization, immunohistochemistry, and immunoelectron microscopy. Furthermore, the expression of AIF-1 in human kidneys and urinary sediments was examined. AIF-1 was expressed at both mRNA and protein levels in podocytes of normal and diseased rats, and in infiltrating cells in anti-GBM nephritis kidneys. The expression of AIF-1 in podocytes was constitutive; positive in podocytes of both normal and diseased rats. In humans, AIF-1 was expressed in podocytes and infiltrating inflammatory cells, similarly. Moreover, it was detected in urinary podocytes from patients with immunoglobulin A nephropathy. These data document for the first time that AIF-1, a constitutively expressed protein in rat and human podocytes, is a novel molecular component of podocytes, and that the upregulation of AIF-1 in an anti-GBM nephritis model may mainly be a consequence of its expression in infiltrating cells.

Adult↗

Fetal pleuroamniotic shunting for bronchopulmonary sequestration with hydrops.

Bronchopulmonary sequestration (BPS), a non-functional pulmonary tissue mass, when complicated by fetal hydrops, carries a high risk of perinatal mortality. However, a limited number of cases of BPS complicated by fetal hydrops with an informative clinical course have been reported. We report here on three cases of BPS complicated by fetal hydrothorax and hydrops that were successfully treated by pleuroamniotic shunting, which should be considered as a treatment option for fetal hydrothorax and hydrops associated with BPS.

Adult↗

S-2474, a novel nonsteroidal anti-inflammatory drug, rescues cortical neurons from human group IIA secretory phospholipase A(2)-induced apoptosis.

The elevated level of group IIA secretory phospholipase A(2) (sPLA(2)-IIA) activity contributes to neurodegeneration in the cerebral cortex after ischemia. The up-regulation of cyclooxygenase-2 (COX-2) is also relevant to cerebral ischemia in humans. Studies of ischemia with COX-2 inhibitors suggest a clinical benefit. In the present study, we investigated effects of S-2474 on sPLA(2)-IIA-induced cell death in primary cultures of rat cortical neurons, which was established as an in vitro model of brain ischemia. S-2474 is a novel nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 and contains the di-tert-butylphenol antioxidant moiety. S-2474 significantly prevented neurons from undergoing sPLA(2)-IIA-induced cell death. S-2474 completely ameliorated sPLA(2)-IIA-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA. sPLA(2) also generated neurotoxic prostaglandin D(2) (PGD(2)) and free radicals from neurons before cell death. S-2474 significantly inhibited the sPLA(2)-IIA-induced generation of PGD(2). The present cortical cultures contained few non-neuronal cells, indicating that S-2474 affected neuronal survival directly, but not indirectly via non-neuronal cells. The inhibitory effect of S-2474 on COX-2 might contribute to its neuroprotective effect. In conclusion, S-2474 exhibits neuroprotective effects against sPLA(2)-IIA. Furthermore, the present study suggests that S-2474 may possess therapeutic potential for stroke via ameliorating neurodegeneration.

Animals↗

Prenatal diagnosis of fetal hydrometrocolpos secondary to a cloacal anomaly by magnetic resonance imaging.

Fetal female urogenital anomalies are often difficult to evaluate by ultrasonography, especially in late gestation. We report a case of fetal hydrometrocolpos detected at 35 weeks of gestation. Ultrasonography revealed a large retrovesical septate hypoechogenic mass in the fetal abdomen, however the sonographic findings were inconclusive. Magnetic resonance imaging (MRI) confirmed that the abdominal mass was fluid-filled with a mid-plane septum in the midline posterior to the bladder, and showed a connection to the dilated uterus that was duplicated. These findings were consistent with a diagnosis of hydrometrocolpos with septate vagina and uterus didelphys. The neonate showed abdominal distension, ambiguous genitalia and anal atresia with a single perineal opening. Hydrometrocolpos was secondary to a urethral type of cloacal anomaly. Aspiration of the mass and a colostomy were performed on the first postnatal day, followed by anorectoplasty at 19 months of age. MRI is a useful complementary tool for assessing fetal urogenital anomalies when ultrasonography is inconclusive.

Adult↗

Exciton localization in vertically and laterally coupled GaN/AlN quantum dots.

Near-field and time-resolved photoluminescence measurements show evidence of exciton localization in vertically and laterally coupled GaN quantum dots (QDs). The binding energies in multiple period QDs (MQDs) are observed to be stronger by more than six times compared to single period QDs (SQDs). Excitons in MQDs have a short (450 ps) lifetime and persist at room temperature, while SQDs exhibit extraordinarily long (>5 ns) lifetime at 10 K due to reduced spatial overlap of electron and hole wave functions in strained QDs.

Aluminum Compounds↗

Exercise and aspirin increase levels of circulating gliadin peptides in patients with wheat-dependent exercise-induced anaphylaxis.

BACKGROUND: Food-dependent exercise-induced anaphylaxis (FDEIA) is an allergic reaction characteristically induced by intense exercise combined with the ingestion of causative food. Recent reports have shown that aspirin intake is a contributing factor in some patients with FDEIA. Wheat is known to be the most frequent causative food, and the IgE-binding epitopes of a major wheat allergen (omega-5 gliadin) in wheat-dependent exercise induced anaphylaxis (WDEIA) have already been clarified. However, the mechanism of eliciting the symptom in WDEIA remains not fully understood. OBJECTIVES: The aim of this study was to examine the relationship of serum gliadin levels and allergic symptoms induced by exercise or aspirin in patients with WDEIA. METHODS: Six patients with a history of recurrent anaphylaxis associated with wheat ingestion were diagnosed as having WDEIA by the provocation test, which included wheat ingestion, exercise, aspirin intake and a combination of these challenges. During the tests, serum levels of gliadins were monitored by gliadin-specific sandwich ELISA. The effects of exercise and aspirin on serum gliadin levels were also investigated in four healthy subjects. RESULTS: Immunoreactive gliadins appeared in the sera of patients during the provocation test with both wheat-exercise and wheat-aspirin challenges in parallel with allergic symptoms. Serum gliadin levels also increased under the two same challenge conditions in the healthy subjects, although they exhibited no allergic symptoms. However, low levels of gliadin were detected in the sera of both patients and healthy subjects when challenged with wheat alone. CONCLUSION: We demonstrated for the first time that blood gliadin levels correlate with clinical symptoms induced by exercise and aspirin in patients with WDEIA. These findings suggest that exercise and aspirin facilitate allergen absorption from the gastrointestinal tract.

Adolescent↗

Combined fibrolamellar carcinoma and cholangiocarcinoma exhibiting biphenotypic antigen expression: a case report.

Fibrolamellar carcinoma (FLC), a variant of hepatocellular carcinoma (HCC), very rarely occurs in association with cholangiocarcinoma (CC). This report describes the first case of FLC coexisting with CC (FLC-CC) from Japan. Although the major part of the tumour located in the right lobe of the liver showed the typical features of FLC, CC was admixed with the FLC, not only in the primary hepatic tumour, but also in the lymph node metastases. Immunohistochemical analysis revealed that, although carcinoembryonic antigen (CEA), which can be detected with monoclonal antibodies in the cytoplasm and the cell surface of CC cells but not HCC cells, was expressed in only the CC cells in the primary tumour, it was expressed extensively in the cytoplasm of both CC and FLC cells in the metastatic and recurrent tumours. Furthermore, Hep Par 1, a hepatocyte specific antigen, was also expressed in both the FLC and CC cells. These findings suggest that, in this case, both FLC and CC were possibly derived from the same cancer stem cell with the capacity to differentiate into both hepatocytes and bile duct epithelium, and that both the cellular components, therefore, exhibited biphenotypic antigen expression.

Adolescent↗

Chloride channel function in the yeast TRK-potassium transporters.

The TRK proteins-Trk1p and Trk2p- are the main agents responsible for "active" accumulation of potassium by the yeast Saccharomyces cerevisiae. In previous studies, inward currents measured through those proteins by whole-cell patch-clamping proved very unresponsive to changes of extracellular potassium concentration, although they did increase with extracellular proton concentration-qualitatively as expected for H(+) coupling to K(+) uptake. These puzzling observations have now been explored in greater detail, with the following major findings: a) the large inward TRK currents are not carried by influx of either K(+) or H(+), but rather by an efflux of chloride ions; b) with normal expression levels for Trk1p and Trk2p in potassium-replete cells, the inward TRK currents are contributed approximately half by Trk1p and half by Trk2p; but c) strain background strongly influences the absolute magnitude of these currents, which are nearly twice as large in W303-derived spheroplasts as in S288c-derived cells (same cell-size and identical recording conditions); d) incorporation of mutations that increase cell size (deletion of the Golgi calcium pump, Pmr1p) or that upregulate the TRK2 promoter, can further substantially increase the TRK currents; e) removal of intracellular chloride (e.g., replacement by sulfate or gluconate) reveals small inward currents that are K(+)-dependent and can be enhanced by K(+) starvation; and f) finally, the latter currents display two saturating kinetic components, with preliminary estimates of K(0.5) at 46 micro M [K(+)](out) and 6.8 m M [K(+)](out), and saturating fluxes of approximately 5 m M/min and approximately 10 m M/min (referred to intracellular water). These numbers are compatible with the normal K(+)-transport properties of Trk1p and Trk2p, respectively.

Biological Transport, Active↗

Chewing-side preference is involved in differential cortical activation patterns during tongue movements after bilateral gum-chewing: a functional magnetic resonance imaging study.

Contralateral dominance in the activation of the primary sensorimotor cortex (S1/M1) during tongue movements (TMs) has been shown to be associated with a chewing-side preference (CSP). However, little is known about its interaction with chewing-related cortical activation. Functional magnetic resonance imaging was performed before and after gum-chewing in six subjects who exhibited a left CSP to determine the relationship between the CSP and activation patterns in the S1/M1 during TMs. Before the subjects chewed the gum, activation foci were found in the bilateral S1/M1. In the left hemisphere, both signal intensity and the area of activation significantly increased during TMs within 10 min after subjects chewed gum. Moreover, this augmented activation significantly decreased within 20 min during tongue protrusion and leftward movement. In the right hemisphere, there were no marked changes during TMs. These results suggest that bilateral gum-chewing enhances activation of the S1/M1 ipsilateral to the CSP during TMs.

Adult↗

A case of dermatomyositis complicated with pneumomediastinum successfully treated with cyclosporin A.

We describe a rare case of a 46-year-old Japanese man with dermatomyositis (DM) and interstitial lung disease who developed spontaneous pneumomediastinum and subcutaneous emphysema. Relatively mild myositis, mild elevation of CK values and the absence of anti-Jo-1 antibody were observed and the case was similar to amyopathic DM. Treatment of this patient with oral prednisolone and cyclosporin A (CsA) was effective for the myositis and interstitial lung disease. The administration of CsA enabled rapid tapering of the dose of prednisolone without aggravating the disease. Pneumomediastinum and subcutaneous emphysema disappeared 5 months later without recurrence. The serum levels of KL-6 were monitored every 2 weeks to help determine whether this may have contributed to the recurrence of interstitial pneumonitis. This is a rare case of pneumomediastinum in a patient with DM.

Administration, Oral↗

Evidence for fibroblast growth factor receptors in myofibroblasts during palatal mucoperiosteal repair.

Fibroblast growth factors (FGFs) regulate cell growth and differentiation and play crucial roles in the process of tissue repair and remodelling. We have previously shown that basic FGF is widely expressed at the injured site. Since the presence of FGF receptors (FGFRs) determines cellular responsiveness, we examined the localisation of FGFR1, FGFR2 and FGFR3 expression by immunohistochemistry throughout the repair of full-thickness excisional wounds up to 28 days after wounding. Strong expression of FGFR1 was observed in the nuclei of myofibroblasts, which are characterised by alpha-smooth muscle (alpha-SM) actin expression. The weak expression of FGFR2 was also observed in the nuclei of myofibroblasts. In contrast, there was no staining for FGFR3 in fibroblasts through the wound healing process. In addition, transforming growth factor-beta1 (TGF-beta1), a potential inducer of myofibroblasts, enhanced the expression of FGFR1 and FGFR2 in the nuclei of palatal fibroblasts in vitro. These findings suggest that FGFR1 and FGFR2 in myofibroblasts may be responsible for the signal transduction of FGF during the wound healing process.

Actins↗

Hydrodynamics-based delivery of the viral interleukin-10 gene suppresses experimental crescentic glomerulonephritis in Wistar-Kyoto rats.

Gene therapy is expected to revolutionize the treatment of kidney diseases. Viral interleukin (vIL)-10 has a variety of immunomodulatory properties. We examined the applicability of vIL-10 gene transfer to the treatment of rats with crescentic glomerulonephritis, a T helper 1 (Th 1) predominant disease. To produce the disease, Wistar-Kyoto rats were injected with a rabbit polyclonal anti-rat glomerular basement membrane antibody. After 3 h, a large volume of plasmid DNA expressing vIL-10 (pCAGGS-vIL-10) solution was rapidly injected into the tail vein. pCAGGS solution was similarly injected into control rats (pCAGGS rats). We confirmed the presence of vector-derived vIL-10 mainly in the liver and observed high serum vIL-10 levels in pCAGGS-vIL-10-injected rats. Compared with the pCAGGS rats, the pCAGGS-vIL-10 rats showed significant therapeutic effects: reduced frequency of crescent formation, decrease in the number of total cells, macrophages, and CD4+ T cells in the glomeruli, decrease in urine protein, and attenuation of kidney dysfunction. Using quantitative real-time polymerase chain reaction, we also observed that this model was Th1-predominant in the glomeruli and that the ratio of the transcripts of CD4, interferon-gamma, tumor necrosis factor-alpha, and monocyte chemotactic protein-1 to the transcripts of glucose-6-phosphate dehydrogenase in the glomeruli were all significantly lower in the pCAGGS-vIL-10 rats than in the pCAGGS rats. These results demonstrate that pCAGGS-vIL-10 gene transfer by hydrodynamics-based transfection suppresses crescentic glomerulonephritis.

Animals↗

Pharmacoepidemiologic investigation of a clonazepam-valproic acid interaction by mixed effect modeling using routine clinical pharmacokinetic data in Japanese patients.

Non-linear Mixed Effects Modeling (NONMEM) was used to estimate the effects of clonazepam-valproic acid interaction on clearance values using 576 serum levels collected from 317 pediatric and adult epileptic patients (age range, 0.3-32.6 years) during their clinical routine care. Patients received the administration of clonazepam and/or valproic acid. The final model describing clonazepam clearance was CL = 144.0 TBW-0.172 1.14VPA, where CL is total body clearance (mL/kg/h); TBW is total body weight (kg); VPA = 1 for concomitant administration of valproic acid and VPA = zero otherwise. The final model describing valproic acid clearance was CL (mL/kg/h) = 17.2 TBW-0.264 DOSE0.159 0.821CZP 0.896GEN, where DOSE is the daily dose of valproic acid (mg/kg/day); CZP = 1 for concomitant administration of clonazepam and CZP = zero otherwise; GEN = 1 for female and GEN = zero otherwise. Concomitant administration of clonazepam and valproic acid resulted in a 14% increase in clonazepam clearance, and a 17.9% decrease in valproic acid clearance.

Adolescent↗

First night effect of an interocclusal appliance on nocturnal masticatory muscle activity.

The purpose of this study was to examine the effect of an interocclusal appliance on nocturnal masticatory muscle activities. Six healthy Japanese males (mean age: 26.8 years) participated in this study. Electromyographic (EMG) activities of the right anterior temporalis and masseter muscles were recorded using a portable EMG recording unit at night both with and without an interocclusal appliance. In both muscles, the maximal EMG activity and the number of bruxing events decreased significantly by wearing the appliance. Moreover, the duration of a higher level of muscle activity was decreased while that of a lower level of muscle activity increased by wearing the appliance in both muscles. These findings suggest that nocturnal masticatory muscle activity is significantly reduced by wearing an interocclusal appliance, and that the use of such an appliance at night could help to relax masticatory muscles.

Adult↗

Hemispheric dominance of tongue control depends on the chewing-side preference.

Blood-oxygenation-level-dependent (BOLD)-functional magnetic resonance imaging (fMRI) is known to be a non-invasive technique for studying human brain function. The purpose of this study was to apply BOLD-fMRI to identify brain areas responsible for producing tongue movements and their relation to chewing-side preference in 15 normal right-handed volunteers. A marked increase in BOLD signals was detected in primary sensorimotor cortices upon protrusion and in rightward and leftward tongue movements compared with at rest. In 10 subjects with an evident chewing-side preference, the BOLD signal change in the primary sensorimotor cortex was significantly greater on the side contralateral to the preferred chewing side. The results suggest that there is a relationship between hemispheric dominance and chewing-side preference in primary sensorimotor cortices responsible for tongue movements.

Adult↗

Comparison of gastroduodenal, renal and abdominal fat biopsies for diagnosing amyloidosis in rheumatoid arthritis.

The aim of the study was to determine the frequency of amyloidosis detected by gastroduodenal biopsy in rheumatoid arthritis (RA) patients, and to investigate correlations between the results of gastroduodenal biopsy and abdominal fat and renal biopsies. A total of consecutive 1006 RA patients underwent gastroduodenal biopsy. The 71 patients who tested positive for gastrointestinal (GI) amyloidosis were asked to undergo renal and abdominal fat biopsies, and 21 did so. Renal biopsies were also performed on 12 patients with no amyloidosis but indicators of drug-induced renal damage, and abdominal fat biopsies were performed on 50 RA patients with no indication of amyloidosis. The prevalence of GI amyloidosis was 7.1%. Urinary abnormalities and GI symptoms were common in GI amyloidisis, and inflammatory markers were elevated. Sixty-one (86%) had either depressed creatinine clearance or urinary symptoms. Nineteen of the 21 patients (91%) with GI amyloidosis who underwent renal biopsies also had renal amyloid deposits. Eleven of the 21 (52%) had amyloidosis on abdominal fat biopsy. None of the 12 patients without GI amyloidosis had renal amyloidosis on renal biopsy, and none of the 50 patients without GI amyloidosis had amyloidosis on abdominal fat biopsy. Gastroduodenal biopsy reveals a high prevalence of amyloidosis in RA patients. Amyloidosis is often associated with signs of renal impairment. Results of GI biopsy are highly correlated with those of renal biopsy, but the results of fat biopsy are not. We recommend GI biopsy for RA patients for the screening of systemic amyloidosis.

Abdominal Wall↗

Interleukin-2 levels are elevated in the bone marrow serum of patients with mutilans-type rheumatoid arthritis.

In order to investigate the pathogenesis of mutilans-type rheumatoid arthritis (RA), we measured cytokine levels in the bone marrow serum of patients with RA. We studied 35 patients with non-mutilans RA, 19 with mutilans RA, and 20 patients with osteoarthritis (OA) undergoing joint surgery. At the time of surgery, iliac bone marrow and peripheral blood were sampled from all 74 patients and cytokine levels measured. The serum levels of five cytokines (IL-1beta, IL-2, IL-3, IL-6 and GM-CSF) were measured by ELISA. Haematologic and inflammatory factors were also measured. Levels of IL-2, IL-6 and GM-CSF in bone marrow serum were significantly higher in all RA patients than in those with OA. Mean (+/-SD) IL-2 levels were significantly higher in patients with mutilans-type RA (309.8+/-686.3 pg/ml) than in patients with other types of RA (66.5+/-173.1 pg/ml; P<0.01). IL-2 was detected significantly more often in patients with mutilans-type RA than in patients with other types of RA (P < 0.01). Inflammatory factors were higher in all RA groups than in OA patients. However, the haematologic and immunologic variables were no different between mutilans RA and other types of RA. No correlations were observed between IL-1beta, IL-2, IL-3, IL-6 and GM-CSF levels and these laboratory variables. In patients with mutilans-type RA, IL-2 levels in the bone marrow serum were significantly higher than in patients with other types of RA or with OA. This elevation does not appear to be related to systemic inflammation, as there was no correlation with other inflammatory factors.

Aged↗