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Biomedical subjects

Y Wada

Publications and source records attributed to Y Wada.

At least 73 records · Page 4Linked to original sources

A novel Gly35Ser mutation in the RDH5 gene in a Japanese family with fundus albipunctatus associated with cone dystrophy.

OBJECTIVE: To assess the clinical and genetic characteristics of a Japanese family with fundus albipunctatus with progressive cone dystrophy associated with a mutation in the RDH5 gene. DESIGN: Case report with clinical findings and results of fluorescein angiography, electroretinograms, kinetic visual field testing, dark adaptometry, and DNA analysis. SETTING: University medical center. PATIENTS: We studied the ocular findings in 6 members of a Japanese family with fundus albipunctatus with cone dystrophy and a guanine-to-adenine transversion at the first nucleotide in codon 35 of the RDH5 gene. The mutation resulted in a substitution of serine for glycine in amino acid 35 (Gly35Ser) of the RDH5 gene. RESULTS: Characteristic features included poor night vision, white dots in the retina, cone dystrophy, and a mottled appearance of the retinal pigment epithelium. Electroretinograms showed greater impairment of the rod-mediated responses than the cone-mediated responses. After 3 hours of dark adaptation, the a and b waves and scotopic b waves recovered. CONCLUSIONS: Although the mutation of the RDH5 gene has been known as a causative gene of fundus albipunctatus, the Gly35Ser mutation in the RDH5 gene may be related to the pathogenesis of progressive retinal degeneration. This phenomenon may provide evidence of gene phenotype caused by a mutation in the RDH5 gene. CLINICAL RELEVANCE: The Gly35Ser mutation causes fundus albipunctatus with cone dystrophy. This finding provides evidence that some kinds of mutations in the RDH5 gene are related, in part at least, to the pathogenesis of progressive retinal degeneration.

Alcohol Oxidoreductases↗

Identification of human antitumor cytotoxic T lymphocytes epitopes of recoverin, a cancer-associated retinopathy antigen, possibly related with a better prognosis in a paraneoplastic syndrome.

Cancer-associated retinopathy (CAR) is a rare paraneoplastic syndrome, and the recoverin-specific autoantibody is suggested to contribute to the pathogenesis of retinopathy, including apoptosis of retinal cells. Because it is known that CAR(+) cancer patients have a preferable prognosis, we hypothesized that aberrantly expressed recoverin in cancer cells can become a target of cytotoxic T lymphocytes (CTL). Here we tested nine recoverin-derived HLA-A24-binding peptides for their capacity to elicit antitumor CTL. We observed recoverin-specific CTL responses in two HLA-A24(+) CAR(+) cancer patients. In addition, the CTL responses were obtained from three of ten CAR(-) cancer patients and two of six healthy individuals. The CTL precursor frequency of CAR(+) cancer patients and that of CAR(-) cancer patients was higher than that of healthy individuals. Of nine recoverin peptides, R49 (QFQSIYAKF), R49.2 (QFQSIYAKFF), and R64 (AYAQHVFRSF) were discovered to induce the peptide-specific CTL. Taken together, our present data suggest that peripheral activation of recoverin-specific antitumor CTL is likely to contribute to the preferable prognosis of CAR(+) cancer patients. Moreover, in cases other than CAR(+) cancer patients, recoverin may offer the opportunity to design epitope-based immunotherapeutic approaches for treating HLA-A24(+) cancer patients with a recoverin-expressing tumor.

Antigens, Neoplasm↗

MRI white matter hyperintensities, (1)H-MR spectroscopy and cognitive function in geriatric depression: a comparison of early- and late-onset cases.

UNLABELLED: BACKGROUND AND OBJECTIVES Geriatric depression is often thought to differ from that at other times of adulthood. Recently, several studies have shown that the incidence of white matter hyperintense lesions identified by brain MRI is higher in patients with geriatric depression than in healthy elderly subjects, but a consensus has not yet been reached on the relationship between the severity of white matter lesions and either cognitive impairment or depressive symptoms. METHOD: Forty-seven patients aged 50 to 75 years with major depression were divided into two groups based on age at onset of depression: early-onset (< 50 years) group (20 patients; mean age, 62.7 +/- 6.7) and late-onset (> or =50 years) group (27 patients; mean age, 65.6 +/- 5.4). The severity of hyperintense white matter lesions on MRI was classified by region, then a proton magnetic resonance spectroscopy ((1)H-MRS) focusing on the white matter of the frontal lobes, multidimensional neuropsychological tests and evaluation of depressive symptoms were conducted. RESULTS: The severity of the deep white matter lesions, the deterioration of cognitive function related to subcortical/frontal brain system and clinician-rated depressive symptoms were all more pronounced in the late-onset group compared with those in the early-onset group. It was further observed that the more severe the deep white matter lesions, the lower the levels of N-acetylaspartate/creatine. With the age of onset as the covariate, the patients with moderate deep white matter lesions had more pronounced cognitive impairment and clinician-rated depressive symptoms than those with none and/or mild lesions. CONCLUSION: These results suggest that subcortical/frontal type cognitive impairment and the persistence of depressive symptoms in geriatric depression is related to moderate deep white matter lesions more often complicated in the late-onset group. The (1)H-MRS findings were suggested to be a useful indicator of neuronal/axonal loss in the white matter of the frontal lobes which precedes cognitive impairment.

Aged↗

Lymphocytic hypophysitis: its expanding features.

Lymphocytic hypophysitis is classically defined as an inflammatory disorder confined to adenohypophysis. However, it has recently been indicated that infundibuloneurohypophysitis underlies some subsets of central diabetes insipidus (DI). Therefore, lymphocytic hypophysitis can be considered a syndrome including disorders of both the anterior pituitary (lymphocytic adenohypophysitis) and the posterior pituitary (lymphocytic infundibuloneurohypophysitis). We describe a 77-yr-old woman with lymphocytic hypophysitis presenting with headache, diplopia, general malaise and appetite loss. Head magnetic resonance imaging (MRI) demonstrated pituitary swelling and dura mater thickening on the dorsum sella. Endocrinological investigations revealed both anterior and posterior pituitary dysfunction associated with primary hypothyroidism due to Hashimoto's thyroiditis. Headache and diplopia spontaneously disappeared, and anterior pituitary dysfunction, general malaise and appetite loss improved after taking 10 mg hydrocortisone daily, although ACTH hyposecretion persisted. Pituitary swelling was thereafter reduced but the dura mater thickening persisted. We suggest that this case may represent a variant of lymphocytic hypophysitis in which chronic inflammatory process involves both the anterior and the posterior pituitary gland, infundibulum, dura mater on the dorsum sella and cavernous sinus. Regarding expanding features of lymphocytic hypophysitis, it may be considered a syndrome including heterogeneous disorders, of which the pathogenesis remains to be elucidated.

Aged↗

Characterization of a SINE species from vicuna and its distribution in animal species including the family Camelidae.

Twenty-six sequences of a short interspersed repetitive element (SINE) with a size of approximately 150 base pairs (bp) were isolated from the genomic DNA of Vicugna vicugna (vicuna). RNA polymerase III split promoter sequence was observed in most of them, and many had direct repeats flanking to SINEs as well as a poly(A)-like structure. The SINE sequences were designated as "vic-1" sequences. Comparison of the vic-1 consensus sequence with sequences registered in the DNA database (DDBJ/ EMBL/GENBANK) revealed that the vic-1 sequence had a 79% homology with mouse ala-tRNA gene. In addition, the tRNA-related region of the consensus sequence was folded into a cloverleaf structure as with mouse ala-tRNA. These findings strongly indicated that vic-1 was a retroposon derived from ala-tRNA gene. The vic-1 sequences were used as a probe for dot-blot hybridization to examine the distribution of their homologous sequences in the genomes of various animal species spanning 14 orders, of which, homologous sequences were found only in the Camelidae family. In order to examine the phylogenetical relationship among vicuna, llama, and camel, vic-1 insertion analysis and homology analysis of vic-1 sequences were performed at each locus. The analyses indicated that vic-1 sequences were generated in a common ancestor of the animal species, and that camels first branched off from the clade Camelidae, followed by vicunas and llamas.

Animals↗

Evaluation of an Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system to predict postoperative risk: a multicenter prospective study.

We previously reported generating a scoring system termed E-PASS that predicted postsurgical risk. This study was undertaken to evaluate the usefulness of this system. A consecutive series of 902 patients who underwent elective gastrointestinal operations in six national hospitals in Japan were prospectively assessed for a comprehensive risk score (CRS) of the E-PASS, which was compared with their postoperative course. The postoperative morbidity rates linearly increased as the CRS increased. The postoperative mortality rate was only 0.13%, when the CRS was below 0.5; however, it increased to 9.7% when the CRS ranged from 0.5 to <1.0, and to 26.9% when the CRS was > or =1.0. The CRS correlated significantly with the severity of postoperative complications (rs = 0.527, P < 0.0001) and the costs of hospital stay (rs = 0.810, P < 0.0001). When the CRS-adjusted mortality rate at the CRS of > or =0.5 was compared among the hospitals, it was related to the hospital volume of operations, being 44.2% at the volume of <100 cases per year, 20.6% at the range of 100-199 cases, and 8.6% at the volume of > or =200 cases. These results suggest that E-PASS may be useful for predicting postsurgical risk, estimating medical expense, and comparing surgical quality.

Adolescent↗

A novel (Pro79Thr) mutation in the FKHL7 gene in a Japanese family with Axenfeld-Rieger syndrome.

PURPOSE: To report the ocular and genetic findings of a Japanese family with Axenfeld-Rieger syndrome associated with a novel Pro79Thr mutation in the FKHL7 gene. METHODS: Observational case series. Genomic DNA of patients from a family with Axenfeld-Rieger syndrome was extracted from leukocytes, and exons of the FKHL7 gene were amplified by polymerase chain reaction for direct sequencing. RESULTS: Molecular genetic analysis disclosed that one Japanese family with Axenfeld-Rieger syndrome had a heterozygous C to A transversion in the first nucleotide at codon 79, designated Pro79Thr mutation in the FKHL7 gene. CONCLUSION: Considering this novel Pro79Thr mutation together with previously reported findings, it is indicated that the clinical features of Axenfeld-Rieger syndrome may depend on the portion of the FKHL7 gene affected by the mutation, although more case reports are needed to clarify genotype-phenotype correlations of the FKHL7 gene.

Adult↗

Expression of very low density lipoprotein receptor mRNA in circulating human monocytes: its up-regulation by hypoxia.

Although very low density lipoprotein (VLDL) receptor expression by macrophages has been shown in the vascular wall, it is not clear whether or not circulating monocytes express the VLDL receptor. We investigated the expression of VLDL receptor mRNA in human peripheral blood monocytes and monocyte-derived macrophages by reverse transcriptase polymerase chain reaction (RT-PCR) and nucleotide sequencing after subcloning of PCR product. VLDL receptor mRNA was detected both in peripheral blood monocytes and monocyte-derived macrophages. Expression of VLDL receptor mRNA was upregulated by hypoxia in monocytes, whereas treatment with oxidized LDL, interleukin-1beta or monocyte chemoattractant protein-1 did not affect the levels of VLDL receptor mRNA in monocytes and macrophages. The present study shows a novel response of VLDL receptor mRNA to hypoxia, suggesting a role for VLDL receptor in the metabolism of lipoproteins in the vascular wall and the development of atherosclerosis.

Adult↗

Optical imaging reveals cation--Cl(-) cotransporter-mediated transient rapid decrease in intracellular Cl(-) concentration induced by oxygen--glucose deprivation in rat neocortical slices.

In brain slices from young (postnatal day (P) 10--15) rat somatosensory cortex, real-time neuronal intracellular Cl(-) concentration ([Cl(-)](i)) recordings were made by an optical technique measuring 6-methoxy-N-ethlquinolinium iodide (MEQ) fluorescence. Oxygen--glucose deprivation (in vitro model of ischemia) induced a long-lasting [Cl(-)](i) increase preceded by a rapid, transient [Cl(-)](i) decrease that could not be inhibited by blockers of Cl(-) pumps, Cl(-) channels, or Cl(-) antiporters, but was sensitive to cation-Cl(-) cotransporter inhibitors (bumetanide and furosemide). Use of low external Na(+) or high external K(+) revealed that the Na(+),K(+)-2Cl(-) cotransporter was inhibited by bumetanide and furosemide, whereas the K(+)-Cl(-) cotransporter was preferentially inhibited by furosemide under our experimental conditions. With a reduced inward driving force for Na(+) (reducing Na(+),K(+)-2Cl(-) cotransport), the transient [Cl(-)](i) decrease was only rarely induced by oxygen-glucose deprivation. In contrast, with a reduced outward driving force for K(+) (reducing K(+)-Cl(-) cotransport), the transient [Cl(-)](i) decrease still occurred. These results suggest that the transient [Cl(-)](i) decrease was primarily mediated by a rapid inhibition of the inwardly directed Na(+),K(+)-2Cl(-) cotransporter. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments suggested that the isoform involved is NKCC1. We hypothesize that the initial rapid Cl(-) efflux might effectively delay the irreversible Cl(-) influx that mediates neuronal injury.

Animals↗

Interleukin-1beta induces the expression of lipocortin 1 mRNA in cultured rat cortical astrocytes.

Lipocortin 1 (LC1) has been shown to increase in neuronal damage and act as a neuroprotectant and a neurotrophic factor. IL-1beta acts as a mediator of inflammation and has been reported as a potent inducer of various neurotrophic factors including nerve growth factor and fibroblast growth factor. In this study, we investigated the relationship between LC1 and IL-1beta in cultured rat astrocytes. Time-and dose-dependent experiments of IL-1beta on rat cortical astrocytes in culture revealed that the expression of LC1 mRNA was significantly augmented by IL-1beta at 8 h, 10 ng/ml. In addition, IL-1beta evoked an extracellular secretion of LC1 without its cytotoxic effects. The effect of IL-1beta was completely abolished when we treated cells with inhibitor of mitogen-activated protein kinases (MAPKs) (PD98059) (25 microM), phospholipase A(2) inhibitor mepacrine (30 microM) and protein synthesis inhibitor cycloheximide (CHX) (10 microg/ml). This suggests that induction of LC1 by IL-1beta is through a MAPKs and phospholipaseA(2) pathway and requires protein synthesis. These results indicate that IL-1beta released in the central nervous system (CNS) injury can stimulate the transcription of the LC1 gene. Subsequent synthesis and release of LC1 may provide trophic support to neurons and modulate the action of IL-1beta in brain damage.

Animals↗

Quantitative examinations for multi joint arm trajectory planning--using a robust calculation algorithm of the minimum commanded torque change trajectory.

In previous research, criteria based on optimal theories were examined to explain trajectory features in time and space in multi joint arm movement. Four criteria have been proposed. They were the minimum hand jerk criterion (by which a trajectory is planned in an extrinsic-kinematic space), the minimum angle jerk criterion (which is planned in an intrinsic-kinematic space), the minimum torque change criterion (where control objects are joint links; it is planned in an intrinsic-dynamic-mechanical space), and the minimum commanded torque change criterion (which is planned in an intrinsic space considering the arm and muscle dynamics). Which of these is proper as a criterion for trajectory planning in the central nervous system has been investigated by comparing predicted trajectories based on these criteria with previously measured trajectories. Optimal trajectories based on the two former criteria can be calculated analytically. In contrast, optimal trajectories based on the minimum commanded torque change criterion are difficult to be calculated, even with numerical methods. In some cases, they can be computed by a Newton-like method or a steepest descent method combined with a penalty method. However, for a realistic physical parameter range, the former becomes unstable quite often and the latter is unreliable about the optimality of the obtained solution. In this paper, we propose a new method to stably calculate optimal trajectories based on the minimum commanded torque change criterion. The method can obtain trajectories satisfying Euler-Poisson equations with a sufficiently high accuracy. In the method, a joint angle trajectory, which satisfies the boundary conditions strictly, is expressed by using orthogonal polynomials. The coefficients of the orthogonal polynomials are estimated by using a linear iterative calculation so as to satisfy the Euler-Poisson equations with a sufficiently high accuracy. In numerical experiments, we show that the optimal solution can be computed in a wide work space and can also be obtained in a short time compared with the previous methods. Finally, we perform supplementary examinations of the experiments by Nakano, Imamizu, Osu, Uno, Gomi, Yoshioka et al. (1999). Estimation of dynamic joint torques and trajectory formation from surface electromyography signals using a neural network model. Biological Cybernetics, 73, 291-300. Their experiments showed that the measured trajectory is the closest to the minimum commanded torque change trajectory by statistical examination of many point-to-point trajectories over a wide range in a horizontal and sagittal work space. We recalculated the minimum commanded torque change trajectory using the proposed method, and performed the same examinations as previous investigations. As a result, it could be reconfirmed that the measured trajectory is closest to the minimum commanded torque change trajectory previously reported.

Algorithms↗

Early growth-response factor 1 and basic transcriptional element-binding protein 2 expression in cardiac allografts.

Early growth-response factor 1 (Egr-1) and basic transcriptional element-binding protein 2 (BTEB2) are transcriptional factors that regulate multiple genes involved in phenotypic changes of smooth muscle cells (SMCs), one of the outstanding pathologic features of chronic cardiac allograft rejection. In this study, we used a heterotopic abdominal heart transplant model in monkeys to evaluate the roles of these molecules in graft coronary vasculopathy. We demonstrated that Egr-1 and BTEB2 are induced in vascular SMCs of rejected cardiac allografts well before morphologic changes, such as intimal thickening. These findings suggest that expression of Egr-1 and BTEB2 is one of the initial events in allograft angiopathy.

Animals↗

Multilocular spermatocele: a case report.

We describe a case of a multilocular spermatocele. Ultrasound examination revealed several cystic spaces at the head of the left epididymis. Epididymal tumor could not be excluded, and therefore surgical exploration was performed. Histopathological examination of the specimen revealed a multilocular spermatocele arising from the rete testis. Most spermatoceles remain small and rarely present marked clinical problems. but they are occasionally large, and may simulate a solid tumor.

Humans↗

Expression of V-ATPase proteolipid subunit of Acetabularia acetabulum in a VMA3-deficient strain of Saccharomyces cerevisiae and its complementation study.

The function of the translation products of six different cDNAs for Acetabularia V-ATPase proteolipid subunit (AACEVAPD1 to AACEVAPD6) was examined using a Saccharomyces cerevisiae VMA3-deficient strain that lacked its own gene for one of the proteolipid subunits of V-ATPase. Expression of the cDNAs in the strain revealed that four cDNAs from the six complemented the proton transport activity into the vacuole, visualized by fluorescence microscopy. The vacuolar-membrane-enriched fractions from the four transformants showed cross-reactivity with antibodies against the subunits a and A of S. cerevisiae V-ATPase. Two translation products from the other two cDNAs were demonstrated not to be localized in vacuolar membranes, and thus could not complement the function of the VMA3-deficient strain. As the primary structures deduced from the former four cDNAs are similar but clearly different from those of the latter two, the latter two translation products may not be able to substitute for theVMA3 gene product.

Acetabularia↗

Ethanol effect on sleep electroencephalogram by the correlation dimension.

The influence on sleep of alcohol (ethanol) was investigated in nine males using the correlation dimension (CD). Polysomnography (PSG) was recorded on a baseline night (BL-N) and on an ethanol (0.8 g/kg) night (Et-N). The mean correlation dimensions on Et-N, as well as on BL-N, significantly decreased from sleep stage 'awake' to sleep Stages 1, 2 and 3 and increased during rapid eye movement (REM) sleep. The mean correlation dimensions of the sleep EEG during sleep Stage 2 and those for the second sleep cycle on the Et-N were significantly higher than those on the BL-N. The changes in the correlation dimensions between sleep cycles were reduced on Et-N as compared to BL-N.

Adult↗

The manual zero potential shifting method in dipole analysis: comparison with neuroimagings in a patient with epilepsy.

We previously introduced the manual zero potential shifting (MZPS) method into dipole analysis to reduce the influence by error potential at the analytical stage. The source localizations of epileptic spikes as an equivalent current dipole (ECD) were estimated in a patient with symptomatic epilepsy and contrasted with findings obtained by magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT). When spikes were analyzed by the MZPS method, ECDs had high values of dipolarity, an indicator of ECD reliability. Moreover, their locations corresponded with lesions shown by MRI and SPECT. When the same spikes were analyzed by the conventional method, dipolarity values were declined and the locations did not correspond with lesions. These results provide further evidence that the MZPS method is of clinical utility in evaluating the electric source generator of epileptic spikes.

Adult↗