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Biomedical subjects

K Abe

Publications and source records attributed to K Abe.

At least 541 records · Page 30Linked to original sources

Dopamine D1 receptor gene polymorphism and schizophrenia in Japan.

We studied the relationship between schizophrenia and the DdeI polymorphism in the 5' untranslated region (5'UTR) of the dopamine D1 receptor (DRD1) gene. This polymorphism is an A (A1 allele) to G (A2 allele) transition in the 5' UTR of exon 2 at bp -48 (A-48G). One hundred forty-eight schizophrenics and 148 control subjects were investigated. No significant differences in genotypic counts and allele frequencies between schizophrenics and controls were found. Although a significant difference between the patients classified as disorganized type and the controls was discovered both in genotypic counts and allele frequencies, neither association proved significant when a Bonferroni correction was used. Moreover, there were no differences in scores of main symptoms of schizophrenia based on the Manchester Scale between patients with A1/A1 genotype and those with A1/A2 genotype. These findings suggest that this gene may not be involved in the pathogenesis of schizophrenia.

Adolescent↗

Association study of the 5-HT6 receptor gene in schizophrenia.

Serotonergic (5-hydroxytryptamine; 5-HT) transmission may play an important role in the treatment and/or pathogenesis of schizophrenia. Previous studies reported that several atypical antipsychotic agents have high affinities for the 5-HT6 receptor. The 5-HT6 receptor gene polymorphism might contribute to the genetic background of this disorder. One hundred and fifty unrelated patients with schizophrenia and 150 unrelated healthy controls were genotyped for a biallelic polymorphism (267C/T) at the 5-HT6 receptor gene. No significant positive association between the 5-HT6 receptor genotype and schizophrenia was observed. Our results suggests that the 267C/T polymorphism of the 5-HT6 receptor gene may not be involved in the susceptibility to schizophrenia.

Adult↗

Expression of cyclin-dependent kinase 5 and its activator p35 in rat brain after middle cerebral artery occlusion.

Cyclin-dependent kinase 5 (cdk5) is a homologue of cell division cycle 2 (cdc2)-like protein kinase. It is mainly expressed in neurons, and supposed to be involved in the dynamic change of neurocytoskeleton structure seen in the brain after ischemia. In the present study, we investigated immunoreactivity for cdk5 and its critical regulatory subunit p35 in rat brain after 90 min of middle cerebral artery (MCA) occlusion. In the control brain, immunoreactive cdk5 was present in some neurons, while p35 was evident in almost all neurons. At 1 h after blood flow restoration, both of them were remarkably increased in the MCA territory. At 3 h, both immunoreactivities were decreased in the ischemic core region, while they became stronger in neurons at the boundary zone of the MCA territory, which decreased thereafter. These results might suggest that increased cdk5 activity in the brain after ischemia caused depolymerization of neurocytoskeletons, which resulted in neuronal cell death.

Animals↗

Regional differences in genetic subgroup frequency in hereditary cerebellar ataxia, and a morphometrical study of brain MR images in SCA1, MJD and SCA6.

Molecular genetic assessments of 69 individuals in 44 families with hereditary cerebellar ataxia (HCA) were made to determine the relative frequencies of subtypes of HCA in Yamagata, Japan. Fifteen families (34%) had SCA1, none had SCA2, nine (20%) had MJD, five (11%) had SCA6 and nine (20%) had DRPLA. These findings differ markedly from those in other regions of Japan and the rest of the world. A morphometrical study of the brain MR images also was made on 38 individuals with SCA1 (n = 14), MJD (n = 8) or SCA6 (n = 16). In SCA1, the ventral pons was atrophic in proportion to the amount of cerebellar atrophy. In MJD, both the pons and the cerebellum were atrophic, cerebellar atrophy being less pronounced than that in SCA1 and SCA6. While both the major and minor axes of the ventral pons were proportionally decreased in SCA1, the minor axis was more decreased than the major axis in MJD. In SCA6, a mild reduction in the ratio of the ventral pontine area to the posterior fossa area (Pv/PF) was observed as well as obvious cerebellar atrophy. These findings indicate that in MR images SCA1, MJD and SCA6 show different atrophic features of the cerebellum and brainstem.

Adult↗

A gustatory cyclic nucleotide-gated channels CNGgust, is expressed in the retina.

Cyclic nucleotide-gated (CNG) channels are essential proteins that contribute to the intracellular signal transduction of the senses of sight and smell. Recently, we found a novel CNG channel (CNGgust) in rat taste buds, and demonstrated its possible involvement in taste signal transduction. In the present study, we used RT-PCR and immunostaining to prove that this gustatory CNG channel is expressed in the outer segments of rat cone photoreceptor cells. The study strongly suggests that the senses of taste and sight share, at least in part, a common signal transduction pathway.

Animals↗

Selective impairment of fast anterograde axonal transport in the peripheral nerves of asymptomatic transgenic mice with a G93A mutant SOD1 gene.

Transgenic mice that express a mutant Cu/Zn superoxide dismutase (SOD1) gene have been provided a valuable model for human amyotrophic lateral sclerosis (ALS). We studied a possible impairment of fast axonal transport in transgenic mice carrying a Gly93-->Ala (G93A) mutant SOD1 gene found in human familial ALS (FALS). Left sciatic nerve was ligated for 6 h in transgenic (Tg) and age-matched wild-type (WT) mice. Immunohistochemical analyses were performed for accumulations of kinesin and cytoplasmic dynein on both sides of the ligation site. Clinical function and histology in the spinal cords, sciatic nerves and gastrocnemius muscles were also assessed. The mice were examined at an early asymptomatic stage (aged 19 weeks) and a late stage (30 weeks) just before the development of the symptoms. WT mice showed an apparent increase in immunoreactivities for kinesin and cytoplasmic dynein at proximal and distal of the ligation, respectively. In contrast, the young Tg mice showed a selective decrease of kinesin accumulation in the proximal of the ligation. The mice were asymptomatic with a mild histological change only in muscles. The old Tg mice showed a marked reduction of the immunoreactivity for kinesin and cytoplasmic dynein on both sides of the ligation. They had a significant loss of spinal motor neurons, relatively small myelinated fiber densities of sciatic nerves, and severe muscular changes. These results provide direct evidence that the SOD1 mutation leads to impaired fast axonal transport, particularly in the anterograde direction at an early, asymptomatic stage preceding loss of spinal motor neurons and peripheral axons. This impairment may contribute to subsequent selective motor neuron death in the present model implicated for human FALS.

Amyotrophic Lateral Sclerosis↗

Potent antiperoxidation activity of the bisbenzylisoquinoline alkaloid cepharanthine: the amine moiety is responsible for its pH-dependent radical scavenge activity.

The bisbenzylisoquinoline alkaloid cepharanthine, which has been considered to exhibit antiperoxidation activity due to its membrane stabilizing effect, was found to scavenge radicals such as .OH and DPPH (1,1-diphenyl-2-picrylhydrazyl) in solution, and to inhibit lipid peroxidation in mitochondria and liposomes by Fe2+/ADP. The antiperoxidation activity of cepharanthine in rat liver mitochondria initiated by Fe2+/ADP at pH 7.4 was much greater than that of alpha-tocopherol, its half-inhibitory concentration being about 23 microM. However, cepharanthine was effective only at neutral pH values such as pH 7.4, not in a moderately acidic pH region below pH 6.5. Accordingly, the neutral form of the deprotonated amine moiety in the tetrahydroisoquinoline ring is concluded to be responsible for the radical scavenging activity of cepharanthine. There are two amine moieties in the cepharanthine molecule, but we specified the effective amine moiety from the antiperoxidation activities of the imine analogs of cepharanthine.

Alkaloids↗

Effect of coenzyme Q10 in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): evaluation by noninvasive tissue oximetry.

We evaluated the effect of coenzyme Q10 supplementation to two patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) by using noninvasive tissue oximetry with near-infrared spectra of hemoglobin from the quadriceps muscle during bicycle ergometer exercise. Patients showed distinct oxygen consumption patterns reflecting the defect in oxidative phosphorylation and the impairment in oxygen utilization during exercise. Based on the oxygen consumption pattern, we considered one patient as having severe mitochondrial disorder and another patient as having mild one. After coenzyme Q10 supplementation, the oxygen consumption pattern of the patient with the severe form shifted to the mild one, while that of the patient with mild form remained unchanged. The shift of the pattern to the mild form correlated well with reduction of the sum of the serum lactate and pyruvate content during exercise. Noninvasive tissue oximetry may be useful to evaluate the effect of coenzyme Q10 supplementation to patients with mitochondrial encephalomyopathy including MELAS.

Adolescent↗

Comments on the characteristics of incommensurate modulation in quartz: discussion about a neutron scattering experiment.

From analysis of the elastic neutron scattering data of Dolino et al. [J. Phys. (Paris) (1984), 45, 361-371], it is shown that, besides the well identified components u(x) and u(y) of the acoustic displacements in the incommensurate (IC) phase of quartz, there also exists a strong component of the u(z) vector of the modulation. The existence of the large u(z) is not consistent with the currently accepted model for the IC transition in quartz, since the long-period IC modulation observed in quartz cannot induce any noticeable acoustic component u(z). The need for a new model is keenly felt in order to understand the origin of the IC modulation in quartz.

Journal Article↗

Late acquired words in childhood are lost earlier in primary progressive aphasia.

The psycholinguistic nature of the dissolution of the mental lexicon in a primary progressive aphasic patient was investigated in light of the general regression hypothesis that language dissolution is the inverse of language acquisition. Four years after onset of the symptoms, the patient scored 60% correct on a picture naming test, exhibiting some effects of lexical and sublexical age-of-acquisition, but 7 years after onset, he scored only 15% correct. While even a weak form of the regression hypothesis is not fully supported, age-of-acquisition effects seem to be preserved throughout the course of the lexical dissolution. Some implications are briefly discussed for future research.

Age Factors↗

Localization of small bowel bleeding by arterial injection of Tc-99m-labeled RBC.

A 79-year-old man with melena was suspected of having small bowel bleeding because upper and lower endoscopic findings were negative. Technetium-99m-labeled red blood cell (Tc-99m-RBC) scintigraphy was performed by arterial injection of a radiotracer from the superior mesenteric artery (SMA) after angiography. Extravasation was seen in the ileum by scintigraphy although angiography was negative. Scintigram 2 minutes after arterial injection was consistent with the late capillary phase of balloon occluded angiography. This comparison provided a better anatomical distinction. Tc-99m-RBC scintigraphy by arterial injection through the SMA identified the bleeding site in the small bowel more accurately than conventional intravenous Tc-99m-RBC scintigraphy.

Aged↗

Effects of S-8510, a benzodiazepine receptor partial inverse agonist, on event-related potentials (P300) in monkeys.

The present study investigated the effects of a novel benzodiazepine inverse agonist, S-8510 [2-(3-isoxazolyl)-3, 6, 7, 9-tetrahydroimidazo [4, 5-d] pyrano [4,3-b] pyridine monophosphate monohydrate], on the P300 components of the event-related potential (ERP) in monkeys. Late positive potentials (P300-like potentials) from the cortex (Pz) and hippocampus recorded using the auditory oddball paradigm in combination with electrical reinforcement can be measured in rhesus monkeys. The latency of this P300-like potential recorded from the monkey cortex was 330 ms, and the amplitude was 13 microV. It was prolonged in both the cortex (Pz) and hippocampus by SC injection of 10 microg/kg scopolamine, a muscarinic receptor antagonist. Oral administration of S-8510 (3, 10 mg/kg) had no effect on the latency in normal monkeys. However, S-8510 reversed the scopolamine-induced prolongation of P300-like potentials on the cortex (Pz) and hippocampus. These results show that S-8510 can attenuate the effects induced by scopolamine on P300-like potentials associated with cognitive function in monkeys, suggesting that S-8510 may be useful as a therapeutic drug in disease-associated cognitive dysfunctions of the central nervous system.

Animals↗

Pseudomyxoma retroperitonei.

We report a rare case of pseudomyxoma retroperitonei in a 58-year-old woman with a past history of severe appendicitis. The imaging showed a multicystic mass similar to pseudomyxoma peritonei, but the tumor was located in the retroperitoneal space.

Diagnosis, Differential↗

Genomic organization and expression analysis of the mouse qkI locus.

qkI, encoding a KH domain-containing RNA binding protein, has been isolated as a candidate gene for the mouse neurological mutation quaking. Here, we describe detailed studies on its genomic structure and expression pattern. We isolated approximately 1 Mb of genomic region containing the quaking locus and determined its genomic organization. The qkI locus contains at least 9 exons spanning approximately 65 kb of DNA. It gives rise to six distinct transcripts encoding, theoretically, five different protein isoforms. Exons 1 through 4 are shared by all the transcripts, whereas coding exons and two distinct 3'-UTRs downstream to the exon 4 are differentially utilized. One isoform has a truncated KH domain and may act as an antagonist to the others. These findings and identification of a single transcription initiation site suggest that differential expression of each transcript is regulated by alternative splicing. Expression of each alternative transcript and protein product was also examined. Two types of transcripts, 5 kb-A and B, are most abundant in the brain of newborn mice and are gradually downregulated thereafter. In contrast, the other three messages, 6 kb, 7 kb-A and B, increase as myelination proceeds and peak at 2 weeks of age, corresponding to the most active stage of myelination. Although the qkI messages and their products are abundant in brain and heart, a lower level of expression was found in various other tissues tested. Alternative transcripts that share the same 3'-UTR showed very similar expression patterns, suggesting a regulatory role of the 3'-UTRs in qkI gene expression.

3' Untranslated Regions↗

Primary hepatic carcinoid tumor.

A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 x 12 x 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver.

Antineoplastic Agents↗

Heat shock protein 70 and heat shock cognate protein 70 messenger ribonucleic acid induction in the brains, hearts, and livers of neonatal rats after hypoxic stress.

OBJECTIVE: The aim of this study was to examine the production of 2 types of heat shock protein 70 in the organs of neonatal rats during an episode of mild hypoxic stress that was insufficient to produce histologic changes. STUDY DESIGN: Seven-day-old rats were subjected to hypoxia (inspired gas of 8% oxygen and 92% nitrogen) at 33 C for 2 hours (n = 5), 3 hours (n = 5), and 4 hours (n = 5). Control rats (n = 5) inspired room air for 4 hours. The brains, hearts, and livers were removed after 4 hours of recovery. The levels of heat shock protein 70 and heat shock cognate protein 70 messenger ribonucleic acid were measured by Northern blot analysis. Arterial pH, Pao 2, PACO 2, and brain temperature were measured before, during, and at 4 hours of hypoxia in another 16 animals. Histologic examinations were carried out in these 16 animals 7 days after hypoxic stress. RESULTS: PaO 2, PACO 2, and brain temperature decreased during the hypoxic stress and returned to prehypoxic values at recovery time. Arterial pH did not change. No histologic changes were observed in any areas of the brain. Heat shock cognate protein 70 messenger ribonucleic acid was normally expressed in the brain, heart, and liver and was further induced after hypoxia in the brain and the heart. There was, however, no additional increase of heat shock cognate protein 70 messenger ribonucleic acid in the liver. there were no increments of the stress-induced form of heat shock protein 70 messenger ribonucleic acid in these organs. CONCLUSION: Mild hypoxia selectively induced messenger ribonucleic acid of heat shock cognate protein 70, which may play an important role in protecting the brain and the heart against stress.

Animals↗