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Biomedical subjects

T Okada

Publications and source records attributed to T Okada.

At least 181 records · Page 10Linked to original sources

Multirecording of Ca(2+) signals from inner retinal neurons evoked by light stimulation of photoreceptors.

We simultaneously monitored changes of intracellular free Ca(2+) concentration ([Ca(2+)](i)) following different light stimuli from different inner retinal neurons of the turtle retina slice preparation. [Ca(2+)](i) increased with an increase of the light stimulus intensity. Some of the cells also showed color opponent Ca(2+) signals. 2-Amino-4-phosphonobutyric acid (APB) blocked in particular [Ca(2+)](i) increases and picrotoxin enhanced the observed [Ca(2+)](i) changes. These data support the idea that the observed [Ca(2+)](i) changes result from light stimulation and subsequent retinal processing. Similar Ca(2+) signals were observed when the release of Ca(2+) from internal stores was blocked with caffeine and thapsigargin. These results indicate that retinal Ca(2+) signals evoked by light stimulation depend to a large extent on voltage-dependent Ca(2+) influx and might therefore reflect signal processing.

Animals↗

Endolymphatic hydrops induced by chronic administration of vasopressin.

Recently, many lines of evidence have supported the possibilities that vasopressin (VP) is closely linked to the formation of endolymphatic hydrops in Meniere's disease. In the present study, it was examined whether or not the chronic administration of VP might induce endolymphatic hydrops. For this purpose, histological studies and VP radioimmunoassay were independently performed in 20 and 40 guinea pigs, respectively. The degree of hydrops was quantitatively assessed by the increase ratio (IR) of the scala media area in the mid-modiolar sections of the cochlea. The IR was defined by the following equation: 100x(A-B)/B (A: the cross-sectional area of the bulging scala media; B: the no-bulging scala media, enclosed by an idealized straight Reissner's membrane). VP was administered at the rates of 200 microU/kg/min, 400 microU/kg/min and 1000 microU/kg/min for 1 week via the osmotic mini-pump. The IR of the total of the apical, second, third and basal turns (means+/-S.D.s) were 4.4+/-0.7, 10.4+/-1.8, 17.4+/-7.9 (n=10 ears, each) in respective doses of VP. Comparing with that of the control animals (5.2+/-1.7, n=10 ears), the area increased significantly in the VP dosage of 400 and 1000 microU/kg/min (Bonferroni's method, P<0.05). Plasma VP concentrations produced by the VP administration in these dosages were 2.2+/-0.4, 3.5+/-0.8 and 14.0+/-3.9 (n=10, each) pg/ml. Although 3.5 pg/ml is the upper limit of plasma VP concentration in normal human subjects, 14.0 pg/ml was almost the same concentration as those observed in the acute phase of Meniere's disease (Takeda et al., 1995). Therefore, the formation of endolymphatic hydrops in cases of Meniere's disease might be caused by high concentrations of plasma VP.

Analysis of Variance↗

Effect of adaptive plasticity of linear vestibulo-ocular reflex upon angular vestibulo-ocular reflex.

OBJECTIVE: The vestibulo-ocular reflex (VOR) produces compensatory eye movements during head movements. The VOR consists of the angular VOR and the linear VOR. The VOR is under adaptive control that corrects VOR performance when visual-vestibular mismatch arises during head movements. Most experiments concerning plasticity of the VOR have used the angular VOR. So far, there has been no investigation on the effect of adaptive plasticity of the linear VOR on the angular VOR. In this study, using a linear sled, we tested the hypothesis that the angular VOR is altered by changes in the linear VOR. METHODS: To modify the linear VOR, we used an adaptation paradigm. Eight subjects were translated sinusoidally at 0.125 Hz and 0.16 g peak acceleration along their inter-aural axis for 40 min, while viewing earth-fixed vertical stripes on the wall while wearing the binocular magnifying lenses. Six of the eight subjects showed an increase in linear VOR sensitivity after adaptation. Each of the six subjects who showed an increase in linear VOR sensitivity after adaptation also showed an increased angular VOR gain at 0.125 Hz. CONCLUSION: These results suggest that the linear VOR and the angular VOR share common neural pathways in such a way that a change in the synaptic efficacy of one pathway is accompanied by a commensurate change in the other.

Adaptation, Physiological↗

Post-stimulus response in hemodynamics observed by functional magnetic resonance imaging--difference between the primary sensorimotor area and the supplementary motor area.

The blood oxygen level dependency (BOLD) contrast is a useful tool for functional neuroimaging based on the hemodynamic response to neuronal activation. We observed different hemodynamic responses in the BOLD signal between the primary sensorimotor area (SM1) and the supplementary motor area (SMA) in the sequential finger movement task. In the SMA, a stronger initial overshoot and a post-stimulus overshoot were observed. It was hypothesized from the time course analysis that the stronger initial overshoot reflected the activation of the SMA for motor control programming in the initial phase. Although the post-stimulus overshoot may be partially explained by cerebral blood flow (CBF) cerebral blood volume (CBV) uncoupling, its mechanism remained unknown. In the SM1, only the initial overshoot was observed and the level of BOLD signal was almost constant after the initial overshoot during the task period. These observations suggested that the BOLD signal is characterized by both CBF-CBV uncoupling and the neuronal activation characteristics in each region.

Adult↗

Assessment of the marine toxins by monitoring the integrity of human intestinal Caco-2 cell monolayers.

The effects of marine substances with various cytotoxic mechanisms on the integrity of the human intestinal Caco-2 cell monolayer were examined by measuring the transepithelial electrical resistance (TEER). TEER was rapidly decreased by apical exposure of the monolayers to discodermin A, a membrane pore-forming substance. The decrease in TEER occurred in an earlier stage of incubation than the release of intracellular lactate dehydrogenase (LDH) which is commonly used as a parameter of cell damage or death. Mycalolide B (an actin-depolymerizing substance), calyculin A and okadaic acid (protein phosphatase inhibitors) also rapidly decreased the TEER value, although no cell membrane damage or resultant LDH release by these toxicants were detected. The TEER decrease caused by the toxicants was associated with the increased transepithelial permeability of the cell monolayer. Treatment with these toxicants, except calyculin A, caused morphological changes in the intracellular actin filament, suggesting that these toxicants altered the cytoskeletal structure, by which the tight junction was opened. Calyculin A was likely to loosen the cellular junctions rapidly and induce cell detachment from the monolayer. Although onnamide A, a protein synthesis inhibitor, did not cause any decrease in TEER, at least during a 90-min incubation, TEER sensitively reflects the cytotoxic effects of various types of toxicants with acute toxicity.

Actins↗

BCAP: the tyrosine kinase substrate that connects B cell receptor to phosphoinositide 3-kinase activation.

Tyrosine phosphorylation of adaptor proteins permits the B cell antigen receptor (BCR)-associated protein tyrosine kinases to regulate downstream effector molecules. Here, we report the identification of a novel B cell adaptor for phosphoinositide 3-kinase (PI3K), termed BCAP. Tyrosine phosphorylation of BCAP is mediated by Syk and Btk, thereby providing binding site(s) for the p85 subunit of PI3K. Disruption of the BCAP gene in the DT40 B cell line inhibits BCR-mediated phosphatidylinositol 3,4,5-trisphosphate generation, leading to impaired Akt response. Moreover, recruitment of PI3K to glycolipid-enriched microdomains (GEMs) is significantly attenuated in the absence of BCAP. Hence, these data suggest that BCAP bridges BCR-associated kinases to the PI3K pathway by regulating PI3K localization.

Adaptor Proteins, Signal Transducing↗

Nephrotic syndrome caused by protein thrombi in glomerulocapillary lumen in Waldenström's macroglobulinaemia.

Waldenström's macroglobulinaemia (WM) is described as a disorder of plasmacytoid lymphocytes. The renal complications of WM are less common and severe than those of multiple myeloma. We present a case of WM complicated by nephrotic syndrome. A biopsy specimen of the kidney revealed the intraglomerular thrombi of immunoglobulin M paraprotein. Corticosteroid pulse therapy and plasmapheresis were effective in improving proteinuria and reducing protein thrombi. The nephrotic syndrome caused by protein thrombi in WM may be reversible, at least in its early stage.

Aged↗

Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan.

OBJECTIVES: To assess the time trends, morbidity and mortality of contemporary anatomical radical retropubic prostatectomy (RRP) in a multi-institutional study in Japan, where RRP has become more popular in the last decade. PATIENTS AND METHODS: Between January 1991 and August 1998, 638 patients underwent RRP at seven urological centres in Japan. Major complications (within 30 days of surgery) and the 30-day mortality were reviewed retrospectively. Of the patients, 12.9% were < 60 years old, 56.3% were 60-69 years old and 30.9% were >/= 70 years old (median age 67). Results The number of RRPs increased markedly, by more than sevenfold, from 1991-92 to 1996-97, mainly because there were more patients undergoing RRP in their sixth decade. The contribution of T1c disease increased in absolute and relative terms, from 13.9% in 1991-92 to 37.9% in 1997-98. Over time, the mean blood loss and the allogeneic transfusion rate decreased steadily. There was a trend toward more favourable outcomes for pathological variables (an increased percentage of organ-confined disease, decreased margin positivity and a decreased incidence of positive lymph node metastasis). The most common complications were wound-related (7.5%), or anastomotic leakage (4.1%). Major cardiopulmonary complications occurred in only two patients (0.31%, both pulmonary embolisms). One patient died from cerebral haemorrhage within 30 days of surgery, giving a mortality rate of 0.16%. CONCLUSION: s This study indicates a trend towards selecting patients most likely to benefit from RRP. Although the procedure is technically demanding, it can have an acceptably low rate of early complications, little mortality and need for allogeneic transfusion. The assessment of morbidity suggests a lower incidence of catastrophic thrombo-embolic and cardiac complications in Japanese patients than in Western men. The present data may be useful in decision-analysis models evaluating the role of therapy for Asian men with early-stage prostate cancer.

Adult↗

Effect of bilirubin UDP glucuronosyltransferase 1 gene TATA box genotypes on serum bilirubin concentrations in chronic liver injuries.

TATA box abnormality in the promoter region of the bilirubin UDP glucuronosyltransferase 1 gene has been reported to cause Gilbert's syndrome in white subjects. It has also been reported that the majority of Japanese patients with Gilbert's syndrome are heterozygous for Gly71Arg in the coding region of this gene. On the other hand, some patients with chronic hepatitis often show signs of unexpected hyperbilirubinemia. The aims of this study were to determine which of the genetic variations, TATA box genotype or codon 71 genotype, is most closely related to serum bilirubin concentrations, and whether the TATA box genotype has an effect on serum bilirubin concentrations in patients with hepatitis C-associated chronic liver diseases. In a sample of 300 individuals selected from among the general Japanese population, mean concentrations of total serum bilirubin differed significantly among TATA box genotypes, but not among codon 71 genotypes. Concentration of total serum bilirubin was significantly correlated with TATA box genotypes. In 211 patients with hepatitis C-associated chronic liver diseases, mean concentrations of total serum bilirubin also differed significantly among TATA box genotypes. In patients with chronic hepatitis C, concentration of total serum bilirubin was significantly correlated with TATA box genotypes. In summary, TATA box genotypes, but not codon 71 genotypes, are closely related to serum bilirubin concentrations. TATA box genotypes should therefore be considered when evaluating hepatic function by serum bilirubin concentrations in cases of hepatitis C-associated chronic liver diseases.

Adult↗

Polymyositis associated with primary cytomegalovirus infection.

A case of polymyositis associated with primary cytomegalovirus infection in a 17-y-old girl is reported. The girl exhibited fever, sore throat, progressive myalgia and muscle weakness with elevated creatine kinase, atypical lymphocytosis and myopathic features in the electromyogram. Histopathologically, biopsied muscle met the criteria for polymyositis. Primary cytomegalovirus infection was proven by seroconversion of IgG as well as IgM antibodies. This is the first report of an association between cytomegalovirus infection and polymyositis.

Adolescent↗

Essential role of the right superior parietal cortex in Japanese kana mirror reading: An fMRI study.

Functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates responsible for Japanese kana mirror reading. Japanese kana words, arranged vertically from top to bottom, were used in the mirror reading task in 10 normal right-handed Japanese adults. Since both mirror-reversed and normally oriented kana items are read in the same (top to bottom) direction, it was possible to minimize the oculomotor effects which often occur in the process of mirror reading of alphabetical language. By using the SPM96 random effect analysis method, a significant increase in the blood oxygen level-dependent signal during mirror reading relative to normal reading was detected in multiple brain regions, including the bilateral superior occipital gyri, bilateral middle occipital gyri corresponding to Brodmann area (BA) 18/19, bilateral lingual gyri (BA 19), left inferior occipital gyrus (BA 18), left inferior temporal cortex (BA 37), bilateral fusiform gyri (BA 19), right superior parietal cortex (SPC) (BA 7), left inferior frontal gyrus (BA 44/45) and an inferior part of the left BA 6. In addition to these cortical regions, the right caudate nucleus and right cerebellum were also activated. The activation found in the right SPC and the left inferior temporal region is consistent with the hypothesis that mirror reading involves both the dorsal visuospatial and ventral object recognition pathways. In particular, a significant correlation was found between the fMRI signal change in the right SPC and the behavioural performance (error index) in the task. This may reflect increased demand on the right SPC for the spatial transformation which is required for the accurate recognition of mirror-reversed kana items. This relationship between the haemodynamic response in a specific brain area and the behavioural data provides new evidence for the essential role of the right SPC in Japanese kana mirror reading.

Adult↗

Participation of the left posterior inferior temporal cortex in writing and mental recall of kanji orthography: A functional MRI study.

To examine the neuropsychological mechanisms involved in writing kanji (morphograms), we used functional MRI (fMRI) in 10 normal volunteers, all right-handed, native Japanese speakers. The experimental paradigms consisted of kana-to-kanji transcription, mental recall of kanji orthography and oral reading and semantic judgement of kana words. The first two tasks require manual and mental transcription of visually presented kana words into kanji, respectively, whereas the last two tasks involve language processing of the same set of stimulus words without recall of kanji. The transcription and mental recall tasks yielded lateralized activation of the left posterior inferior temporal cortex (PITC). By contrast, neither oral reading nor semantic judgement produced similar activation of the area. These results, in good accordance with lesion data, provide converging evidence that the left PITC plays an important role in writing kanji through retrieval of their visual graphic images, and suggest language-specific cerebral organization of writing. The set of fMRI experiments also provides new neuroimaging data on the cortical localization of basic language functions in people using a non-alphabetical language.

Adult↗

In vivo trafficking and catabolism of IgG1 antibodies with Fc associated carbohydrates of differing structure.

We have now produced mouse-human chimeric IgG1 in wild-type Chinese hamster ovary (CHO) cell lines Pro-5 as well as in the glycosylation mutants Lec 2, Lec 8, and Lec 1. Analysis of the attached carbohydrates shows those present on IgG1-Lec 1 were mannose terminated. Carbohydrate present on IgG1-Lec8 was uniformly biantennary terminating in N-acetylglucosamine. The glycosylation profiles of IgG1-Lec 2 and IgG1-Pro-5 were heterogeneous. Only IgG1-Pro-5 was sialylated with sialic acid present on only a small percentage of the carbohydrate structures. When the in vivo fate of antibodies labeled with (125)I-lactotyramine was determined, it was found that the majority of all of the antibodies, irrespective of the structure of their attached carbohydrate, is catabolized in the skin and muscle. However, the attached carbohydrate structure does influence the amount that is catabolized in the liver and the liver serves as a major site for the catabolism of proteins bearing carbohydrate with the Lec2 (with terminal galactose) or Lec1(with terminal mannose) structure.

Animals↗

Retrovirus-specific random mutagenesis by a nucleoside 5'-triphosphate analogue, PTP.

In a retrovirus replication model system, which consists of in vitro transcription and reverse transcription cycles, 6-(beta-D-ribofuranosyl)-3,4- dihydro-8H-pyrimido[4,5-c][1,2]oxazin-7-one-5'-triphosphate (PTP) induced highly efficient random mutations and this was due to the ambiguous incorporation of PTP by RNA polymerases. The types of mutations were mainly C-to-U or U-to-C transition mutations and the frequency was about 4 x 10(-2)/nucleotide during four cycles of the replication. Since a high mutation rate is harmful to species, PTP may be new candidate for anti-retroviral drugs. N4-aminoCTP and N4-hydroxyCTP were also incorporated ambiguously by RNA polymerase. These compounds may have a potential to induce mutation by the same mechanism as PTP.

Mutagenesis↗

Expression of Bra r 1 gene in transgenic tobacco and Bra r 1 promoter activity in pollen of various plant species.

Bra r 1 encodes a Ca2+-binding protein specifically expressed in anthers of Brassica rapa. In this study, we isolated a genomic clone of Bra r 1 and found sequences similar to Pollen Box core motifs and LAT56/59 box, pollen-specific cis-acting element, in the 5' upstream region of Bra r 1. Reporter gene fusion revealed that the Bra r 1 promoter directs male gametophytic expression in Nicotiana tabacum, Arabidopsis thaliana and B. napus, showing strong expression in mature pollen grains similar to that of endogenous Bra r 1. Genomic DNA of Bra r 1 was introduced into tobacco plants and the highest accumulation of Bra r 1 protein was observed in mature pollen in the same manner as reporter gene expression. Using in vitro-germinated pollen tubes of transgenic tobacco, we firstly demonstrated the subcellular localization of Bra r 1 in pollen tubes. Bra r 1 protein was distributed throughout the pollen tube of transgenic tobacco and slightly intense signals of Bra r 1 were observed in the tip region. In long-germinated pollen tubes, Bra r 1 was detected only in the cytoplasmic compartments while no signals were observed in the empty part of the pollen tube, indicating that cytoplasmic movement toward the tube tip is accompanied by Bra r 1. Hence, we suggest that Bra r 1 is involved in pollen germination and pollen tube growth.

Amino Acid Sequence↗

Influence of movement arousal on circadian rhythm of blood pressure in obstructive sleep apnea syndrome.

OBJECTIVE: To investigate the hypothesis that repeated arousals at the termination of apnea/hypopnea in obstructive sleep apnea syndrome (OSAS) are related to abnormal circadian rhythm of blood pressure (BP). DESIGN AND METHODS: We performed polysomnography (PSG) with pulse oximetry in 26 middle-aged patients with OSAS aged 42-58 years (mean age 51.8 years). The intensity of arousal on PSG was graded into two levels: grade 1 (EEG arousal, EA), an abrupt shift in EEG frequency, and grade 2 (movement arousal, MA), EEG arousal with an increase in electromyogram activity lasting at least 3 s. The number of apnea/hypopneas per hour (apnea/hypopnea index, AHI), and length of time during which nocturnal oxygen saturation decreased below 90% (oxygen desaturation time, ODT) were also evaluated. Percentage EA and %MA were assessed by the ratio of the number of apneas and hypopneas with EA or MA to the number of apneas and hypopneas in total. The 24 h systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured noninvasively. Multiple regression analysis was performed among AHI, ODT, %EA and %MA or among age, body mass index and %MA. RESULTS: The %MA was the most significant factor contributing to the elevated 24 h SBP (r= 0.46, P< 0.05); oxygen desaturation (r= 0.44, P< 0.05) was the next most important contributing factor. The level and pattern of 24 h BP differed significantly between the patients with %MA 85% and %MA < 85% (mean 24 h SBP: 147 +/- 16.8 versus 125 +/- 19.6 mmHg, P< 0.01; mean 24 h DBP: 97.5 +/- 14.3 versus 85.6 +/- 14.6 mmHg, P< 0.01), and also differed between those with severe OSAS, i.e. ODT > or = 130 min, and mild to moderate OSAS, i.e. ODT < 130 min, (mean 24 h SBP: 149 +/- 15.8 versus 132 +/- 20.6 mmHg, P < 0.01; mean 24 h DBP: 100 +/- 14.1 versus 87.4 +/- 14.0 mmHg, P < 0.01). CONCLUSION: Our findings suggest that MA and oxygen desaturation in OSAS make an important contribution to abnormal circadian rhythm of BP. We conclude that repeated end-apneic arousal and/or hypoxic asphyxia and the subsequent sleep fragmentation may contibute to nocturnal and diurnal elevation of BP.

Adult↗

Comparison of the effects of nifedipine and nisoldipine on coronary vasoconstriction in the Langendorff-perfused rat heart.

By using Langendorff-perfused rat hearts, we compared the relaxant effects of two dihydropyridine calcium antagonists (nifedipine and nisoldipine) on the coronary vasculature. Hearts were perfused at a constant flow rate (13 ml/min), and the coronary perfusion pressure was monitored to assess vasoconstriction and relaxation. Administration of 5 nM endothelin significantly increased the perfusion pressure within 5 min, and it did not decrease during the subsequent 10-min washout period. Washout with 1 nM nisoldipine or 10 nM nifedipine almost completely normalized the perfusion pressure. Administration of a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine (100 microM), elevated the perfusion pressure at 5 min. When 1 nM nifedipine was added to the perfusate, it failed to decrease the pressure, but 10 and 100 nM nifedipine partly decreased it (96.4+/-8.2 and 87.0+/-8.8 mm Hg for 10 and 100 nM, respectively). Nisoldipine alleviated the pressure elevation almost completely at 10 nM (60.0+/-5.2 mm Hg). The vasodilatory effect of nisoldipine was also approximately 10 times more potent than that of nifedipine when coronary vasoconstriction was induced by hypoxia-reoxygenation. These results suggest that nisoldipine has a stronger effect than nifedipine at the organ level, which does not depend on the cause of coronary vasoconstriction.

Animals↗