Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 217 records · Page 12Linked to original sources

PubMed1999

[Drinking alcohol among junior high school students: reflecting drinking culture].

Using a data obtained from a junior high school students survey on drug use, perception of alcohol drinking for junior high school students and role of adults in drinking were examined. 78% of the junior high school students had ever drunk alcohol at least once. The results revealed that experience of drinking alcohol accompanied by family did not have a close relationship with regularity of daily life routine, school lives and family lives for the students. It was, however, strongly suggested that experience of drinking alcohol only with peers had a close relationship with undesirable daily life routine, school lives and family lives for the students. Furthermore, lifetime prevalence of cigarette smoking and that of solvent inhalation for the male students with experience of drinking only with friends were 11 to 13 times and 5 to 8 times higher, respectively, than the male students without experience of drinking only with friends. These were 22 times and 3 to 5 times, respectively, for female students. As for observance of the law which prohibits drinking alcohol for those under 20 years old, over a half of the students consider that alcohol drinking for minors was acceptable depending on the time and circumstances. This was greatly different from the observance of the laws against cigarette smoking and solvent inhalation. The author considers that this may reflect adult alcohol drinking culture in Japan.

Adolescent↗

PubMed1999

[Follow-up of children with early neonatal surgery of fetal hydrocephalus].

This is a retrospective study of patients with surgically treated antenatal diagnosed hydrocephalus. We conducted the study to elucidate the outcomes of the patients, as well as potential pitfalls in their care. A series of 51 patients underwent surgical intervention between 1987 and 1997. All lesions were diagnosed by antenatal ultrasound sonography. After the estimation of their lung maturation, they were delivered in early pregnancy stage and the operation had performed for hydrocephalus. 43 children could be followed-up. To estimate the morphological improvement from radiological examinations objectively, we compared cerebroventricular index (CVI) of pre-operation with that of post-operation. The result was that excellent improvement group was 18 cases, good improvement group was 13 cases, fair improvement group was 8 cases and poor improvement group was 4 cases. In 43 cases, 20 children also had myelomeningocele and in them the improvement of hydrocephalus was that excellent improvement group was 10 cases, good improvement group was 5 cases and fair improvement group was 5 cases. About motor function of 20 children with myelomeningocele, only 5 children were ambulatory with brace. Attending to the rest 23 children without myelomeningocele, 6 children in 8 excellent improvement cases and 6 children in 8 good improvement cases were ambulatory by themselves. But all 7 children belonging to fair and poor improvement groups were unambulatory. We concluded that it was necessary to improve dilated ventricle on the radiological examinations with surgical procedure in order to get better motor function, even semilobar and lobar holoprosencephaly.

Child Development↗

PubMed1999

[Urodynamic studies on the untethering of spinal lipoma in the children].

We performed conus untethering on 44 children with spinal lipoma. In this retrospective study, we studied urological examinations obtained in 36 consecutive patients. Urological examinations were ultrasonography of bladder and kidney, voiding cystourethrography (VCG), and urodynamic cystometry. In those of them, 6 patients had already had urinary dysfunction at preoperative stage, but 4 patients' spinal lipoma was one complication of cloaca exstrophy and 2 patients' spinal lipoma after repairment of their myelomeningocele. In the remaining 30 cases, 18 patients (60.0%) as the group 1 did not have urinary dysfunction and abnormality in any urological examinations. Another 7 patients (23.3%) as group 2 also did not have urinary dysfunction, but abnormal vesicoureteral reflux (VUR) was found out in their VCG examination. At postoperative stage, abnormal VUR resolved or improved in all these 7 cases, but one of them showed transient urinary retention. Two patients of 18 in the group 1 had to require clean intermittent self-catheterization at postoperative stage. These observations confirmed that children with spinal lipoma were more likely to present with urological findings, and so it was imperative that a diagnosis be made and treatment be instituted as early as possible.

Child, Preschool↗

PubMed1999

[The concept of "gateway drug"].

To develop drug abuse prevention for adolescents in Japan, the author reviewed concepts of "gateway drug" and "stepping-stone hypothesis". Firstly, results obtained from high school students in New York State (Kandel, D., 1975) were introduced as a standard model of "stepping-stone hypothesis". Secondly, results obtained from serious drug abusers in New York City (Golub, A. et al., 1994) were introduced as an example that shows the importance of defining clearly which cohort a study refers to when we use "gateway drug". Thirdly, results of a junior high school students survey in Japan were introduced and discussed to consider whether alcohol and cigarette for junior high school students in Japan are "gateway drugs" to solvent. The author concluded: 1) that cigarette smoking in junior high school students in Japan has a strong relationship with solvent inhalation, and 2) that drinking alcohol, however, depends on the presence of adults. Lastly, the author emphasized the need for doing more research on drug abuse in Japan.

Adult↗

PubMed1999

[Vein of Galen aneurysmal malformation: multi-staged feeder clipping in two neonatal cases with intractable heart failure].

The authors reported the surgical experience of two cases of vein of Galen aneurysmal malformation in the newborn, whose congestive high-output cardiac failure was intractable. Along with the intensive care to clinical manifestations of the heart failure, multi-staged feeder clipping was carried out to decrease the high-flow shunt of the malformation. As stages going on, heart failure was relieved gradually and cathecolamines were weaned. Although certain retardation became apparent in both cases, they are showing satisfactory development in the long-term follow up. By the recent advancement of the embolization technique, the embolization appears to have already taken place the treatment of choice for this malformation. According to the neonatal evaluation score of Lasjaunias, the embolization would no longer be recommendation in neonates, whose general condition scored less than eight points. The authors believe, based on our two cases, that multi-staged feeder clipping is one of the effective modality of treatment in neonates of the vein of Galen aneurysmal malformation with severe multiorgan failure.

Cardiac Output, High↗

PubMed1999

[Nationwide survey on alcohol use among junior and senior high school students in Japan].

We conducted the first nationwide survey on alcohol use by Japanese junior and senior high school students using a representative sampling procedure. Sample schools were selected by stratified cluster sampling. Response rates for self-administered anonymous questionnaires sent to sample schools for all students to fill out were 65.6% for junior high schools and 67.0% for senior high schools. A total of 117,325 students responded and 115,814 questionnaires were subjected to analysis. The proportion of current alcohol use (drank alcohol on > = 1 of the 30 days preceding the survey) among seventh graders was 26.0% for boys and 22.2% for girls, and it increased with age to reach 54.9% for boys and 43.4% for girls in the twelfth grade. The experience rate of alcohol drinking on ceremonial occasions was much higher than for any other modes of drinking. However, the experience rates of drinking with peers at parties, in bars, and drinking alone increased with age. The proportion of heavy drinkers also increased with age. The cumulative experience rate of drinking with peers was dramatically increased in senior high school students. The most popular alcohol drink among boys was beer, whereas it was liquor with sweet taste among girls. Most important routes of purchase of alcohol were convenience stores, bars, liquor shops, and vending machines.

Adolescent↗

PubMed1999

[Rhythmic involuntary movement of the neck in a patient with brainstem encephalitis].

A 36-year-old Japanese woman was admitted to our hospital, because of facial palsy, ophthalmoplegia, cerebellar ataxia, and rhythmic myoclonus of the neck. About a few weeks before admission, she developed symptoms of common cold and general fatigue. Her laboratory data were unremarkable, and her CSF was normal. Serum levels of antibodies to gangliosides were within normal limits. Her MRIs of the brain and neck were normal. Both somatosensory evoked cortical potential study and auditory evoked brainstem response study were normal. She was diagnosed as postinfectious brainstem encephalitis, and the administration of corticosteroid was started. After the treatment, her symptoms improved. To our knowledge, it is rare to see myoclonus to the neck without palatal tremor in patients with brainstem encephalitis.

Adult↗

PubMed1998

Using sensory and instrumental data to interpret the effect of storage at elevated temperatures on aroma of Chardonnay wines.

The effect of elevated temperatures during storage on the aroma of commercial Chardonnay wines was monitored by sensory and instrumental methods. Aromas of wines stored at 40 degrees C for 0, 15, 30 and 45 days were profiled by descriptive analysis by a trained panel. Heated storage decreased intensity of fruity and floral notes, while increasing attributes such as honey, butter/vanilla, oak, and rubber. Volatiles recovered by solvent extraction from the same wines were separated by gas chromatography (GC) and identified by GC-mass spectrometry (MS). Principal component analysis of instrumental variables (PCAIV) was used to reduce the initial set of 67 quantified GC peaks. Six compounds, selected by PCAIV to yield the configuration closest to that of the principal component analysis of the sensory data, provided a highly significant fit with the sensory configuration, as shown by a permutation test. This solution was the statistically optimal one, but was not unique, as demonstrated by significant fits between the sensory and instrumental spaces upon use of other GC peaks, which were highly correlated with the original six variables.

Female↗

PubMed1998

The stereo-specific effect of D-serine ethylester and the D-cycloserine in ataxic mutant mice.

Spinocerebellar ataxia is one of the most common neurological disorders. However, few therapeutics are effective for the treatment of this disorder. In the present study, we investigated the efficacy of d-serine ethylester and a related substance, d-cycloserine, as therapeutic agents for ataxia in a murine model. Both compounds are known to stereospecific modulate N-methyl-d-aspartate type glutamate receptors, and impaired glutamate-mediated signaling has been implicated in spinocerebellar ataxia. Using a microdialysis method, we found that intraperitoneal administration of d-serine ethylester increases the extracellular content of endogenous d-serine in the mouse cerebellum for at least 3 h. Maximum elevation of the extracellular d-serine was observed at 40 min after injection. An open-field study was used to assay the effect of the d-serine derivatives on movement and ataxia. In mice exhibiting cytosine arabinoside-induced ataxia, d-serine ethylester reduced the falling index in a dose-dependent manner. The effect of d-serine ethylester was stereo-specific in that l-serine ethylester had no effect on the falling index at the maximum doses tested, and was partially inhibited by 5,7-dichlorokynurenate, an antagonist that binds to the glycine-binding site. Locomotor activity was not changed by the d-serine ethylester treatment. d-cycloserine also significantly reduced the falling index of the mice. Both d-serine ethylester and d-cycloserine had longer lasting effects than other potential therapeutic reagents for ataxia. Growing evidence suggests the essential involvement of endogenous d-serine in mammalian brain function, and our results suggest that d-serine derivatives may represent an effective new therapeutic for the treatment of spinocerebellar ataxia.

Animals↗

PubMed1998

An activity in rat tissues that modifies nitrotyrosine-containing proteins.

Homogenates from rat spleen and lung could modify nitrotyrosine-containing BSA. With incubation, nitrotyrosine-containing BSA lost its epitope to a monoclonal antibody that selectively recognized nitrotyrosine-containing proteins. In the presence of protease inhibitors, the loss of the nitrotyrosine epitope occurred without protein degradation and hydrolysis. This activity was found in supernatant but not particulate fractions of spleen homogenates. The factor was heat labile, was sensitive to trypsin treatment, and was retained after passage through a membrane with a 10-kDa retention. The activity was time- and protein-concentration dependent. The activity increased about 2-fold in spleen extracts with endotoxin (bacterial lipopolysaccharide) treatment of animals, suggesting that the activity is inducible or regulatable. Other nitrotyrosine-containing proteins also served as substrates, while free nitrotyrosine and some endogenous nitrotyrosine-containing proteins in tissue extracts were poor substrates. Although the product and possible cofactors for this reaction have not yet been identified, this activity may be a "nitrotyrosine denitrase" that reverses protein nitration and, thus, decreases peroxynitrite toxicity. This activity was not observed in homogenates from rat liver or kidney, suggesting that there may also be some tissue specificity for the apparent denitrase activity.

Animals↗

PubMed1998

Guinea pig liver Mu-class glutathione S-transferase M1-2 cross-reacts with antibodies to both rat Mu- and theta-class glutathione S-transferases.

Two novel major heterodimeric Mu-class glutathione (GSH) S-transferases (GSTs), designated M1-2 and M1-3*, were isolated from guinea pig (gp) liver cytosol and purified to homogeneity together with a known major homodimeric Mu-class gpGSTM1-1 (reported as GST b by R. Oshino, K. Kamei, M. Nishioka, and M. Shin, 1990, J. Biochem. 107, 105-110). These three gpGSTs were quantitatively retained on an S-hexyl-GSH affinity column and separated as homogeneous proteins by chromatofocusing. Subunits of the heterodimers were inseparable on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, but could be completely separated by reverse-phase partition high-performance liquid chromatography. A molecular cloning study demonstrated that the gpGST subunit M2 consisted of 217 amino acid residues with a calculated molecular mass of 25,562 and shared 84% identity in overall amino acid sequence with gpGSTM1-1. N-terminal amino acid sequences of peptides from the gpGST subunit M3* with a blocked N-terminus strongly suggested that it should belong to the Mu class. Western blot analysis using antisera raised against purified rat (r) GSTsA1-2 (Alpha), M1-1, P1-1 (Pi), and T2-2 (Theta) indicated that gpGSTsM1-1 and M1-3* cross-reacted only with anti-rGSTM1 antibody. However, gpGSTM1-2 cross-reacted intensely to almost the same extent with antibodies to both rGSTsM1-1 and T2-2. A homodimeric gpGSTM2-2, artificially constructed from native gpGSTM1-2 by treatment with guanidine hydrochloride followed by dialysis, intensely cross-reacted with antibodies to both the rat Mu- and Theta-class GSTs. Thus, the gpGST subunit M2 provided the first evidence for the double immuno-cross-reaction of a GST with polyclonal antibodies to two different classes of GSTs.

Amino Acid Sequence↗

PubMed1998

Light-induced retinal degeneration suppresses developmental progression of flip-to-flop alternative splicing in GluR1.

AMPA receptors are hetero-oligomers composed of subsets of four distinct subunits, termed GluR1, GluR2, GluR3, and GluR4. Using quantitative reverse transcription-PCR analysis, we have found that light-induced degeneration of rat retina dramatically suppresses developmental progression of the flip-to-flop alternative splicing switch of retinal GluR1 mRNA. When animals were raised under standard conditions of a 12 hr light/dark cycle (LD 12:12), the flop-to-flip ratio in GluR1 and GluR2 dramatically increased between postnatal day 10 (P10) and P28, and the ratios continued to increase gradually up to P84. When animals were raised in complete darkness, this increase was delayed in GluR1 between P21 and P42. In addition, the increase of the flop-to-flip ratio in GluR1 was strongly suppressed after P21 under conditions of continuous illumination from P2. This is significant because P21 is just after the eye opening and is the timing of the onset of light-induced retinal degeneration. This suppression of the increase of the flop-to-flip ratio was specific to GluR1 and was not observed in GluR2-4. Immunocytochemistry and immunoblot analysis suggested no changes in either the distribution or expression of GluR1 protein in the light-damaged retina measured at P84. When rats were raised under continuous illumination from P2 to P21 followed by LD 12:12 from P22 to P84, retinal degeneration did not progress after P22. In such animals the flop-to-flip ratio, once decreased to approximately 50% of the control (LD 12:12) at P21, was restored to the control level at P84. These findings demonstrate that developmental progression of the flip-to-flop exon switch in retinal GluR1 is affected by lighting conditions, and that light-induced retinal degeneration contributes to the mechanism of suppression of this splicing switch.

Alternative Splicing↗

PubMed1998

Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases.

Three genes potentially encoding novel matrix metalloproteinases (MMPs) were identified by sequence similarity searching of Caenorhabditis elegans genome database, and cDNAs for these MMPs were cloned. The predicted gene products (MMP-C31,-H19 and -Y19) display a similar domain organization to human MMPs. MMP-H19 and -Y19 are unique in that they have an RXKR motif between the propeptide and catalytic domains that is a furin-like cleavage site, and conserved only in stromelysin-3 and membrane-type MMPs. The amino acid sequence homology with MMP-1/human interstitial collagenase at the catalytic domain is 45%, 34% and 23% for MMP-C31, -H19 and -Y19, respectively. Recombinant proteins of C. elegans MMPs cleaved an MMP peptide substrate with efficiency proportional to their amino acid homology with human MMPs. Digestion of gelatin was observed only with MMP-C31. Enzyme activity of MMP-C31 and -H19 was inhibited by human tissue inhibitor of MMPs (TIMP)-1, TIMP-2 and synthetic MMP inhibitors, BB94 and CT543, indicating that the catalytic sites of these C. elegans MMPs are structurally closely related with those of mammalian MMPs.

Animals↗

PubMed1998

Functions of the two glutamate transporters GLAST and GLT-1 in the retina.

In the retina, the glutamate transporter GLAST is expressed in Müller cells, whereas the glutamate transporter GLT-1 is found only in cones and various types of bipolar cells. To investigate the functional role of this differential distribution of glutamate transporters, we have analyzed GLAST and GLT-1 mutant mice. In GLAST-deficient mice, the electroretinogram b-wave and oscillatory potentials are reduced and retinal damage after ischemia is exacerbated, whereas GLT-1-deficient mice show almost normal electroretinograms and mild increased retinal damage after ischemia. These results demonstrate that GLAST is required for normal signal transmission between photoreceptors and bipolar cells and that both GLAST and GLT-1 play a neuroprotective role during ischemia in the retina.

ATP-Binding Cassette Transporters↗

PubMed1998

Levels of cyclooxygenase-1 and -2 mRNA expression at various stages of acute gastric injury induced by ischemia-reperfusion in rats.

Recently, the state of cyclooxygenase (COX) mRNA expression has been reported in an acetic acid-induced chronic gastric ulcer model of mice. However, the time course of COX expression during the developmental stage and the subsequent repair process of acute gastric injury is not well understood at present. In this study, we quantitatively investigated the time course of the level of COX-2 and -1 mRNA expression from the developmental stage through the healing stage in ischemia-reperfusion (I-R)-induced acute gastric damage. COX-2 mRNA was expressed at low or undetectable levels in the normal gastric tissues of control rats. The COX-2 expression between 6 and 48 h following I-R was higher than that of the control gastric tissues; the histological findings were erosion during 1-36 h and transitional appearance from erosion to ulcer at 48 h. The maximum expression of COX-2 mRNA was recorded at 24 h (approximately 200-fold elevation). The COX-2 message was very low or undetectable at 72 h (ulcer stage) and at 96 and 120 h (healing stage of ulcer) after I-R. The level of COX-1 mRNA remained stable through all stages of acute gastric damage. These results are potentially useful for understanding the role of COX and evaluating the effects of drugs on expression of COX at various stages of acute gastric injury.

Animals↗

PubMed1998

Development of genotoxicity assay systems that use aquatic organisms.

Our aim is to develop and evaluate monitoring systems that use aquatic organisms to assess the genotoxicity of water in the field and in the laboratory. In a field study, we have shown that the micronucleus assay is applicable to freshwater and marine fishes and that gill cells are more sensitive than hematopoietic cells to micronucleus-inducing agents. Gill cells from Carassius sp. (Funa) and Zacco platypus (Oikawa) collected upstream on the Tomio River (Nara, Japan), tended to have lower micronucleus frequencies than gill cells from fish collected at the midstream of the river. Leiognathus nuchalis (Hiiragi) and Ditrema temmincki (Umitanago), small marine fishes collected periodically at Mochimune Harbor (Shizuoka, Japan), showed seasonal differences in the frequencies of micronucleated gill cells and erythrocytes; they were highest in summer. For laboratory studies, we developed a method for analyzing chromosomal aberrations and micronuclei using Rhodeus ocellatus ocellatus (rose bitterling) embryos. One day after artificial insemination (gastrula stage), we observed structural chromosomal aberrations and micronuclei in the cells of embryos grown in water containing trichloroethylene. Although more work is needed to fully assess their sensitivity, these assays show promise as a means of detecting environmental genotoxins.

Animals↗

PubMed1998

Selective hippocampal damage to hypoxia after mild closed head injury in the rat.

Our previous studies have shown selective neuronal damage in the CA3 region after mild closed head injury (CHI) combined with hypoxia. In the present studies, we examined (1) extracellular concentrations of neuroactive amino acids using in vivo microdialysis technique and (2) neuroactive amino acid binding to their receptors using quantitative autoradiography. Male SD rats were divided into five groups; sham control, mild CHI (sacrificed at 1 h or 24 h after CHI), mild CHI followed by hypoxia (1 h or 24 h). [3H]-Glutamate binding to NMDA receptors, [3H]-muscimol binding to GABAA receptors and [3H]-kainate binding to KA receptors were measured in hippocampus and cortex by quantitative autoradiography. With CHI alone, GLU and TAU levels were transiently increased by 15 min posttrauma. In the CHI with hypoxia, increases in GLU and TAU levels were sustained until 60 min following CHI. GABA level was also increased until 75 min posttrauma Pretreatment of MK-801 significantly diminished the prolonged elevation in GLU and TAU levels. (2) CHI alone did not produce prominent change in the measured receptor binding. When hypoxia was combined with CHI, significant increase in [3H] GLU binding to NMDA receptors and significant decrease in [3H]-muscimol binding to GABAA receptors were observed in CA1 and CA3 at 1 h and 24 h post-insult. These results demonstrate that selective hippocampal damage to hypoxia after mild CHI may be mediated through an increase in NMDA receptor activation and the further release of GLU and that NMDA antagonist may be beneficial in preventing secondary neuronal damage by hypoxia.

Animals↗

PubMed1998

Pharmacological characterization of YM087, a potent, nonpeptide human vasopressin V1A and V2 receptor antagonist.

The effects of YM087 (4'-[(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d] [1]benzazepin-6-yl)-carbonyl]-2-phenylbenzanilide monohydrochloride), a novel nonpeptide vasopressin (AVP) receptor antagonist, on [3H]AVP binding to human AVP receptors (V1A, V1B and V2) cloned and transiently expressed in COS-1 cells generated from monkey renal tissue were studied. Scatchard analysis of saturation isotherms for the specific binding of [3H]AVP to membranes, prepared from COS-1 cells transfected with human V1A, V1B and V2 receptors, yielded an apparent equilibrium dissociation constant (Kd) of 0.67 nM, 0.28 nM and 2.14 nM and a maximum receptor density (Bmax) of 2180 fmol/mg protein, 369 fmol/mg protein and 2660 fmol/mg protein, respectively. YM087 showed high affinity for AVP V1A and V2 receptors with Ki values of 6.3 and 1.1 nM, respectively, but had no effect on [3H]AVP binding to AVP V1B receptors. In COS-1 cells expressing either AVP V1A or V1B receptors, AVP caused a concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i). YM087 inhibited the AVP-induced increase in [Ca2+]i in COS-1 cells expressing AVP V1A receptors in a concentration-dependent manner with an IC50 value of 14.3 nM, but did not influence this increase in AVP V1B-receptor expressing cells. In contrast, stimulation of COS-1 cells expressing AVP V2 receptors resulted in an accumulation of cAMP. YM087 inhibited AVP-induced cAMP production in COS-1 cells expressing AVP V2 receptors in a concentration-dependent manner with an IC50 value of 1.95 nM. In all assays used, YM087 was devoid of any agonistic activity. These results suggest that YM087 is a potent nonpeptide dual human AVP V1A and V2 receptor antagonist, and that YM087 will be a powerful tool in investigation of the physiological and pathophysiological roles of AVP.

Animals↗