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Biomedical subjects

M Mishina

Publications and source records attributed to M Mishina.

At least 91 records · Page 5Linked to original sources
PubMed1997

Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection.

The molecules of the collapsin/semaphorin gene family have been thought to play an essential role in axon guidance during development. Semaphorin III/D is a member of this family, has been shown to repel dorsal root ganglion (DRG) axons in vitro, and has been implicated in the patterning of sensory afferents in the spinal cord. Although semaphorin III/D mRNA is expressed in a wide variety of neural and nonneural tissues in vivo, the role played by semaphorin III/D in regions other than the spinal cord is not known. Here, we show that mice homozygous for a targeted mutation in semaphorin III/D show severe abnormality in peripheral nerve projection. This abnormality is seen in the trigeminal, facial, vagus, accessory, and glossopharyngeal nerves but not in the oculomotor nerve. These results suggest that semaphorin III/D functions as a selective repellent in vivo.

Afferent Pathways↗
PubMed1997

High-resolution HLA-DRB1 and DQB1 genotyping in Japanese patients with testicular germ cell carcinoma.

We report for the first time the frequency distributions of HLA-DRB1 and -DQB1 genes in 55 patients with testicular germ cell carcinoma (TGC) using the modified PCR-RFLP method and compare the results with those for 1216 healthy Japanese control subjects. The modified PCR-RFLP method produced accurate, reproducible cleavage patterns that are easily discriminated. HLA-DRB1*0410 was the susceptibility allele (RR = 3.26, P = 0.006) and DQB1*0602 appears to be a candidate protective allele (RR = 0.26, P = 0.02) for TGC in the Japanese. None of the HLA-DRB1 and -DQB1 alleles showed a specific tendency for histological type or clinical stage of the tumours. Previous studies based on serotyping methods failed to show these allelic associations. High-resolution genotyping is essential because the peptide-binding domain of MHC class II molecules is determined more precisely by their genotypes than by their serotypes. In addition, inherent technical difficulties and typing errors of up to 25% make serotyping inefficient. Our results suggest that high-resolution genotyping is a useful genetic marker to determine risk for TGC.

Female↗
PubMed1997

Absence of prostaglandin E2-induced hyperalgesia in NMDA receptor epsilon subunit knockout mice.

1. We have previously found that intrathecal administration of prostaglandins E2 (PGE2) and D2 (PGD2) into conscious mice induced hyperalgesia by the hot plate test. The present study investigated the involvement of N-methyl-D-aspartate (NMDA) receptor in the prostaglandin-induced hyperalgesia by use of mice tacking NMDA receptor epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunits. 2. PGE2 induced hyperalgesia over a wide range of doses from 50 pg to 500 ng kg-1 in wild-type mice. But PGE2 could not induce hyperalgesia in epsilon 1, epsilon 4, or epsilon 1/epsilon 4 subunit knockout mice. 3. The NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-AP5), the non-NMDA receptor antagonist 7-D-glutamylaminomethyl sulphonic acid (GAMS), and the nitric oxide synthase inhibitor N epsilon-nitro-L-arginine methyl ester (L-NAME) inhibited the PGE2-induced hyperalgesia in wild-type mice. 4. PGD2 induced hyperalgesia at doses of 25 ng to 250 ng kg-1 in both wild-type and epsilon 1/epsilon 4 subunit knockout mice. The substance P receptor antagonist OP 96.345 blocked the PGD2-induced hyperalgesia in wild-type and epsilon 1/epsilon 4 subunit knockout mice. 5. These results demonstrate that the pathways leading to hyperalgesia are different between PGD2 and PGE2, and that both epsilon 1 and epsilon 4 subunits of the NMDA receptor are involved in the PGE2-induced hyperalgesia.

Animals↗
PubMed1997

Idiopathic renal hematuria in a dog; the usefulness of a method of partial occlusion of the renal artery.

Exploratory laparotomy was performed on a dog suspected of having idiopathic renal hematuria. Two catheters were inserted into the bilateral ureters, and hematuria from the left kidney was confirmed. The blood flow was occluded in the ventral and dorsal rami of the left renal artery in order to localize the site of hemorrhage. As hematuria disappeared when the dorsal ramus was occluded, the site of renal hematuria was localized to the area dominated by the dorsal ramus of the renal artery. As a result of ligating the dorsal ramus of the left renal artery in this dog, renal hematuria subsided, and the dog has shown a favorable course, to date, one year after surgery.

Animals↗
PubMed1997

A clinical evaluation of blood pressure through non-invasive measurement using the oscillometric procedure in conscious dogs.

The oscillometric procedure was used to measure the heart rate as well as the systolic, mean, and diastolic blood pressures of 152 dogs (102 in the control group, 13 in the group with renal disease, 37 in the group with heart disease) who were brought to Azabu University of Veterinary Teaching Hospital. It was demonstrated that the blood pressure and heart rate of the control group lowered and tended to become stable as the number of measurements increased. No appreciable difference was identified in the measurements of either blood pressure or heart rate in the forelimbs and tail head. With regard to gender, males showed a significantly higher value than females (p < 0.05). No interaction was identified between age and blood pressure. No difference was identified in the heart rate in all groups. In an investigation of blood pressure in all groups, the renal disease group showed significantly higher values (p < 0.05) than either the control or the heart disease group in all values of systolic, mean and diastolic pressures. These results indicated that dogs with renal disease can manifest hypertension.

Aging↗
PubMed1997

[Neuroradiological findings on cerebral blood flow and metabolism of a case of adult onset sialidosis].

We examined a patient with adult onset sialidosis using N-isopropyl-p-123I-iodoamphetamine single photon emission computed tomography (SPECT) and 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (PET). A 41-year-old [correction of 47] man was admitted to our hospital because of the involuntary movement of his extremities and gait disturbance. On admission, he exhibited action myoclonus in his face and extremities with cerebellar ataxia. Ophthalmoscopy revealed cherry-red spots on his retina. Enzymological analysis of his leucocytes and skin fibroblasts revealed primary sialidase deficit. Brain MRI showed no abnormal findings. Brain SPECT showed decreased cerebral blood flow in the cortex of bilateral occipital lobes, and PET study revealed decreased glucose metabolism in the cortex of bilateral occipital lobes. This case is the thirteenth patient of adult onset sialidosis in Japan. As far as we know, there are no previous reports of SPECT or PET on sialidosis patients. Why the cerebral blood flow and glucose metabolism was decreased in the occipital lobe region remains obscure. From the literatures, we suppose that the onset time of neuronal tissue degeneration or the sensitivity to cumulative metabolites in the occipital region may be different from those in other regions. Further studies are required to confirm abnormalities of cerebral blood flow and metabolism in sialidosis.

Adult↗
PubMed1996

Functional correlation of NMDA receptor epsilon subunits expression with the properties of single-channel and synaptic currents in the developing cerebellum.

NMDA receptor (NMDAR) subunits epsilon 1-epsilon 4 are expressed differentially with respect to brain region and ontogenic period, but their functional roles still are unclear. We have compared an epsilon 1 subunit-ablated mutant mouse with the wild-type to characterize the effect of epsilon subunit expression on NMDAR-mediated single-channel currents and synaptic currents of granule cells in cerebellar slices. Single-channel and Western blot analyses indicated that the epsilon 2 subunit disappeared gradually during the first postnatal month in both wild-type and mutant mice. Concomitantly, the voltage-dependent Mg2+ block of NMDAR-mediated EPSCs (NMDA-EPSCs) was decreased. Throughout the developmental period studied, postnatal day 7-24 (P7-P24), the decay time course of NMDA-EPSCs in epsilon 1 mutant (-/-) mice was slower than in wild-type mice. We suggest that the expression of the epsilon 3 subunit late in development is responsible for a reduction in the sensitivity of NMDA-EPSCs to block by extracellular Mg2+ and that receptors containing the epsilon 1 subunit determine the fast kinetics of the NMDA-EPSCs.

Age Distribution↗
PubMed1996

Developmental changes in expression and distribution of the glutamate receptor channel delta 2 subunit according to the Purkinje cell maturation.

The glutamate receptor (GluR) channel delta 2 subunit is considered to be a functional molecule involved in motor coordination, Purkinje cell synapse formation and cerebellar long-term depression. We examined developmental changes in expression and distribution of the GluR delta 2 in the mouse cerebellum by in situ hybridization and immunohistochemistry. The GluR delta 2 mRNA was detected as early as embryonic day 15 (E15) in a cell mass consisting of Purkinje neuroblasts in the posterior cerebellum. During late embryonic and postnatal periods, the GluR delta 2 mRNA was expressed abundantly and specifically in Purkinje cells. By immunohistochemistry, immunoreactivity of the GluR delta 2 was found in both shafts and spines of Purkinje dendrites at early postnatal period. By P21, however, the intense immunoreactivity became restricted to the dendritic spines, especially along the postsynaptic membrane in contact with parallel fiber terminals. These findings suggested that the transcription of the GluR delta 2 subunit occurs in the Purkinje cells from fetal through adult stage, but the intracellular localization of the protein products undergoes an alteration from non-synaptic to synaptic site when active synaptogenesis takes place.

Animals↗
PubMed1996

Age-dependent reduction of hippocampal LTP in mice lacking N-methyl-D-aspartate receptor epsilon 1 subunit.

The effects of targeted disruption of the N-methyl-D-aspartate (NMDA) receptor epsilon 1 subunit gene were studied during the postnatal development of epsilon 1-disrupted mutant mice. Using the mice at the ages of 2-3, 5-6 and 9-10 weeks, we examined NMDA receptor channel-mediated synaptic currents and long-term potentiation (LTP) in CA1 pyramidal neurons of hippocampal slices. NMDA receptor channel currents, expressed as the ratios to non-NMDA receptor channel currents, decreased with the age in both wild-type and mutant mice, but the values in the mutant mice was approximately half of those of the wild-type mice at all ages examined. The LTP in the mutant mice was also reduced, but in contrast to the NMDA receptor channel currents, the extent of the reduction in the LTP was age-dependent. The reduction was marginal at the age of 2-3 weeks, and became progressively prominent to adulthood, with the potentiation being 26% of that of the wild-type mice at 9-10 weeks.

Age Factors↗
PubMed1996

Gene structure and chromosomal localization of the mouse NMDA receptor channel subunits.

Multiple espilon subunits are major determinants of the diversity of the N-methyl-D-aspartate (NMDA) receptor channel. The four epsilon subunit mRNAs exhibit distinct expression patterns in the brain. In an attempt to elucidate the molecular basis of selective and characteristic expression of the NMDA receptor channel subunits, we have isolated the gene encoding the mouse NMDA receptor epsilon 3 subunit and have determined its structural organization. The epsilon 3 subunit gene spans 17.5 kb and consists of 14 exons. The major transcription start site is 439 bp upstream of the ATG initiation codon as determined by primer extension and S1 nucleas protection analyses. Two polyadenylation sites are 397 (or 398) and 402 bp downstream of the termination codon. The 5'-flanking region of the epsilon 3 subunit gene contains GC-rich segments including consensus sequences for binding of the transcription factors Spl and EGR-1. The murine chromosomal locations of the five NMDA receptor channel subunits, the epsilon 1 (Grin2a), epsilon 2 (Grin2b), epsilon 3 (Grin2c), epsilon 4 (Grin2d) and zeta 1 (Grinl) subunits, were determined using an interspecific backcross mapping panel derived from crosses of [(C57BL/6JxM. spretus) F1xC57BL/6J] mice. Each of these genes mapped to a single chromosome location. The mapping results assigned the five loci to five different mouse autosomes, indicating that they have become well dispersed among mouse chromosomes.

Amino Acid Sequence↗
PubMed1996

Impairment of suckling response, trigeminal neuronal pattern formation, and hippocampal LTD in NMDA receptor epsilon 2 subunit mutant mice.

Multiple epsilon subunits are major determinants of the NMDA receptor channel diversity. Based on their functional properties in vitro and distributions, we have proposed that the epsilon 1 and epsilon 2 subunits play a role in synaptic plasticity. To investigate the physiological significance of the NMDA receptor channel diversity, we generated mutant mice defective in the epsilon 2 subunit. These mice showed no suckling response and died shortly after birth but could survive by hand feeding. The mutation hindered the formation of the whisker-related neuronal barrelette structure and the clustering of primary sensory afferent terminals in the brainstem trigeminal nucleus. In the hippocampus of the mutant mice, synaptic NMDA responses and longterm depression were abolished. These results suggest that the epsilon 2 subunit plays an essential role in both neuronal pattern formation and synaptic plasticity.

Animals↗
PubMed1996

Equivalent parental distribution of frequently lost alleles and biallelic expression of the H19 gene in human testicular germ cell tumors.

Epigenetic alterations such as genomic imprinting might play an important role in human tumorigenesis, in addition to specific genetic alterations. To clarify the role of genetic and/or epigenetic alterations in the tumorigenesis of testicular germ cell tumors (GCTs), we analyzed 40 primary and 3 metastatic testicular GCTs with regard to specific chromosomal losses and their parental origin. A high incidence of loss of heterozygosity (LOH) was demonstrated on chromosomes 1p, 3p, 11p, and 17p: 9/19 (47%), 18/39 (46%), 13/40 (33%) and 20/36 (56%), respectively. However, there was no correlation between the frequency of LOH on any chromosome and clinicopathological features. Regarding the parental origin of the lost allele at these chromosomes, preferential loss was not demonstrated in this study. To clarify the imprinting status in GCTs, we analyzed the allele-specific expression of the H19 gene, which is paternally imprinted on chromosome 11p. All of 11 tumors without LOH at this locus showed biallelic expression of H19. Based on previous work demonstrating the biallelic expression of H19 in primordial germ cells and spermatogonia in the mouse germ line, these results suggest that the biallelic expression of H19 in testicular GCTs reflects the characteristics of the original germ cells in which the imprinting marking has been erased and not established, rather than loss of imprinting during tumorigenesis. It is also possible that a failure to re-establish the imprinting might be an initial event which leads to testicular GCTs.

Alleles↗
PubMed1996

Role of the nondominant hemisphere and undamaged area during word repetition in poststroke aphasics. A PET activation study.

BACKGROUND AND PURPOSE: Although the resting regional cerebral blood flow (rCBF) in aphasic patients has been thoroughly investigated with positron emission tomography (PET) and single-photon emission CT, and PET studies in normal subjects have elucidated the functional localization of language processing, little is known about the activation pattern of language processing in aphasic patients. METHODS: We measured the changes in rCBF during a repetition task (hearing a single word and repeating it aloud) and the resting state using the H2(15)O PET activation technique in 6 normal subjects (mean +/- SD age, 58.3 +/- 8.1 years) and 16 aphasic patients: 10 fluent aphasics (age, 60.3 +/- 12.5 years) and 6 nonfluent aphasics (age, 50.5 +/- 8.3 years). RESULTS: In normal subjects, the posteroinferofrontal area (PIF) including Broca's area, the posterosuperotemporal area (PST) including Wernicke's area, the rolandic areas, and a few other areas were activated with left side dominance by the repetition task. In the resting state, the rCBF in the left PIF and the left posterotemporal area was reduced in both fluent and nonfluent aphasics. In aphasic patients, the magnitude of activation in the right PIF and PST by the repetition task was greater than in normal subjects. The increase in rCBF during the repetition task in the left PIF correlated with the Western Aphasia Battery score of spontaneous speech in the nonfluent aphasics with a left inferofrontal lesion. CONCLUSIONS: This study shows the importance in aphasic patients of the mirror regions of the left PIF and PST in the nondominant (right) hemisphere for performing the word repetition task. The results also show the importance for nonfluent aphasic patients of the recruitment of the undamaged PIF for spontaneous speech.

Adult↗
PubMed1996

[Molecular diversity and physiological roles of the NMDA-receptor channel].

Molecular cloning has elucidated the molecular diversity of the N-methyl-D-aspartate (NMDA)-receptor channel and has provided a solid basis for extensive studies of the structure and function of the NMDA-receptor channel. Mutational analyses have assigned functional domains and the transmembrane topology of the channel subunits. Identification of the multiple subunits with distinct distribution, properties, and regulation has suggested that NMDA-receptor channels are distinct in molecular architecture and functional characteristics in various brain regions at different developmental stages. The physiological significance of the NMDA-receptor channel diversity is presently under investigation by various techniques including gene targeting.

Animals↗
PubMed1996

Renal transplantation in cats with chronic renal failure.

Renal transplantation was performed on 6 cats with chronic renal failure. Clinical signs and the blood chemistry findings (BUN, Cr, IP) improved one week after renal transplantation. Renal anemia also improved 3-4 weeks after surgery. Two cases had the same complications, hydronephrosis and hydroureter within 1 or 2 weeks of surgery, evidenced by marked elevations of BUN and Cr, suggesting that ureteral obstruction at the site of ureterocystostomy is the main complication of renal transplantation in cats. As a new resolution for this problem, we transplanted the ureter with the intact ureteral opening of the bladder from the donor in the remaining 4 cats. Ureteral obstruction was not observed in them, thus the procedure was considered to be useful for avoiding this complication. Two cats died of pneumonia and other complications within 3 months. There were no acute rejections or side effects from the immunosuppressant during the observation period in the remaining four cats.

Animals↗