Biomedical subjects

T Ohashi

Publications and source records attributed to T Ohashi.

At least 181 records · Page 10Linked to original sources

PubMed1995

The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons.

We have identified a strong candidate cDNA for the mouse reeler gene. This 5 kb transcript encodes a 99.4 kD protein consisting of 881 amino acids and possessing two EGF-like motifs. We assayed two independent mutant alleles--'Jackson reeler', which has a deletion of the entire gene, and 'Orleans reeler' which exhibits a 220 bp deletion in the open reading frame, including the second EGF-like motif and resulting in a frame shift. In situ hybridization reveals that the transcript is detected exclusively in the pioneer neurons which guide neuronal cell migration along the radial array. Our findings offer an explanation for how the reeler mutant phenotype causes a disturbance of the complex architecture of the neuronal network.

Amino Acid Sequence↗

PubMed1995

Analysis of proteolipid protein (PLP)-specific T cells in multiple sclerosis: identification of PLP 95-116 as an HLA-DR2,w15-associated determinant.

Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95-116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to TCL selected against the peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.

Adult↗

PubMed1995

Effect of lansoprazole on peptic ulcers.

Lansoprazole is the first proton pump inhibitor developed in Japan. We studied the clinical efficacy of lansoprazole 30 mg q.d. on peptic ulcers and the subsequent relapse rates. The endoscopic healing rate of gastric ulcers (n = 86) after 8 weeks of treatment and duodenal ulcers (n = 52) after 6 weeks of treatment were 94.2 and 96.2%, respectively. The endoscopic S2-stage shift rates in gastric and duodenal ulcers were 45.5 and 65.4%, respectively. Factors affecting healing rates of gastric ulcers included colonization by Helicobacter pylori, the size and depth of the ulcers, pretreatment stage, and ulcer history, whereas those factors did not influence healing in duodenal ulcers. The clearance rates of H. pylori after lansoprazole treatment were 54.5% in patients with gastric ulcer and 66.7% in those with duodenal ulcer. The cumulative relapse rates after 1 year with standard maintenance therapy of H2-receptor antagonists (ranitidine, famotidine, and cimetidine) were 15.8% for gastric ulcer and 21.2% for duodenal ulcer. In conclusion, lansoprazole is highly effective in peptic ulcer disease and there are few relapses after treatment. Furthermore, it is suggested that lansoprazole is efficacious against H. pylori at usual clinical doses.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1995

Hurler syndrome with severe complication in post-bone marrow transplantation course: life threatening interstitial pneumonitis and hypertension.

Bone marrow transplantation (BMT) was performed in a 3 year old patient with Hurler syndrome. The post-BMT course was complicated by interstitial pneumonitis and severe hypertension, which were life threatening. The patient responded well to therapy and recovered. BMT in this patient resulted in significant clinical improvement in the signs and symptoms of Hurler syndrome. Biochemical improvement, including elevated alpha-L-iduronidase activity in white blood cells and decreased urinary glycosaminoglycan excretion was significant. However, skeletal and neurological impairment were not improved. We conclude that BMT for Hurler syndrome should be performed at an earlier stage, before severe neuronal damage has occurred. Moreover, BMT is a high risk procedure and there will always be a possibility that life threatening complications will occur, as in our case.

Bone Marrow Transplantation↗

PubMed1995

Surfactant treatment and ventilation effects on surfactant SP-A, SP-B, and SP-C mRNA levels in preterm lamb lungs.

The effects of exogenous surfactant treatment combined with postnatal ventilation on surfactant protein (SP)-A, SP-B, and SP-C steady-state mRNA levels were evaluated in preterm sheep at 120, 132, and 139 days gestation. Three groups were studied at each gestation period: animals ventilated and treated with 100 mg/kg natural sheep surfactant, animals ventilated and not treated with surfactant, and a comparison group of lambs that were neither ventilated nor treated with surfactant. In unventilated lambs, SP-A and SP-C mRNA levels measured by densitometry from Northern blots increased between 120 and 132 days gestation (P < 0.05). At 120 days gestation, no differences in SP-A, SP-B, or SP-C mRNA levels were noted among the three groups. At 132 days gestation, SP-A mRNA levels increased in both ventilated groups (P < 0.01), but no additional surfactant effect on SP-A mRNA expression was detected. There were no changes in SP-B or SP-C mRNA levels among the groups at 132 days gestation. At 139 days gestation, mRNA levels for both SP-A and SP-B increased after ventilation, compared with the unventilated groups (P < 0.05). Furthermore, an additional effect of surfactant treatment to increase SP-A mRNA levels relative to animals undergoing ventilation alone was noted (P < 0.05). We conclude that postnatal changes in mRNA levels for the surfactant proteins are gestationally regulated and protein specific.

Animals↗

PubMed1995

Discharge characteristics of vestibular and saccade neurons in the rostral midbrain of alert cats.

1. The interstitial nucleus of Cajal (INC) is involved in generation of vertical eye movements. To further explore the neural substrates of INC involvement in eye movements, we examined the discharge characteristics of neurons in the rostral midbrain that discharge for vestibular stimulation and saccades in alert cats. We analyzed 75 vestibular and saccade neurons (VSNs) that showed characteristic discharge during pitch rotation. Of these, 50 exhibited gradually increasing activity during upward slow phases and burst of action potentials during downward fast phases induced by downward pitch. The remaining 25 cells showed the opposite response pattern: gradually increasing activity during downward slow phases and a burst during upward fast phases induced by upward pitch. We classified these cells as downward VSNs and upward VSNs, respectively. The effects of electrical stimulation of the contralateral vestibular nerve were tested for 13 downward VSNs and 2 upward VSNs; all of them were activated at short latencies. 2. All vertical VSNs also showed burst activity associated with spontaneous saccades. The preferred direction for the burst was always the same for saccades and vestibular fast phases. The onset of burst activity preceded the onset of fast eye movement by an average of 35 +/- 14 ms (mean +/- SD). During fast eye movement in other directions, many of these cells also showed an inconsistent burst and the burst often began after the onset of saccades. Half of the upward VSNs examined showed a pause in activity during downward fast eye movement. 3. Burst parameters in the preferred directions were correlated with saccade parameters in half of the vertical VSNs examined, although the correlation coefficients were typically 0.5-0.6. 4. All vertical VSNs had irregular resting activity. Half of the downward VSNs examined showed eye-position sensitivity toward the direction opposite to the preferred direction for the burst activity but only if the period of analysis was restricted to discharge shortly before and after saccades. 5. All downward VSNs examined during sinusoidal rotation in several vertical planes received strong excitatory input from the contralateral anterior canal. Three of four upward VSNs examined received contralateral posterior canal excitation; the exception received ipsilateral posterior canal excitation.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

PubMed1995

Expression of paternal and maternal mitochondrial HSP70 family, hsc74, in preimplantation mouse embryos.

We have investigated the regulation of gene expression of a novel mitochondrial HSP70 family, hsc74 in preimplantation mouse embryos. We used a monoclonal antibody, anti-CSA, which reacts with only one of strain variants of the hsc74. By immunostaining with anti-CSA antibody, the hsc74 protein was constitutively detected in C3H embryos from 1-cell to blastocyst stage, but no signals were detectable in C57BL/6 embryos. To know the timing of paternal genome expression, we examined the expression of hsc74 in (C57BL/6 x C3H)F1 embryos. No positive signals were detectable in embryos before 8-cell stage. In early 8-cell stage weakly positive signals appeared in the peripheral region of the blastomeres. From late 8-cell stage, the protein was intensively detectable and was persistently expressed in all types of cells. We have also applied a sensitive methodology to distinguish genetic variants of hsc74 from C3H and C57BL/6 by reverse transcription polymerase chain reaction followed by single strand conformation polymorphism analysis. In (C57BL/6 x C3H)F1 embryos, the paternal transcripts were first detected in 4-cell embryos, while the maternal transcripts were constantly detectable. These results indicate that the transcripts and proteins of hsc74 were derived only from the maternal gene from 1-cell to 4-cell stages, and that from 4-cell stage the paternal gene is also transcribed, and the significant increase of the paternally derived protein occurred around late 8-cell stage.

Animals↗

PubMed1995

Overexpression of arylsulfatase A gene in fibroblasts from metachromatic leukodystrophy patients does not induce a new phenotype.

We tested the influence of overexpression of arylsulfatase A (ASA) on the activity of other sulfatases in fibroblasts from patients with metachromatic leukodystrophy (MLD). We demonstrated that the overexpression of ASA reduces the activity of various sulfatases by a small amount but does not induce an accumulation of glycosaminoglycan. Our results indicate that influence of ASA overexpression on other sulfatases is different from that of N-acetyl-galactosamine-4-sulfatase overexpression reported by Anson et al. We conclude that gene therapy for MLD based on the transfer of a normal ASA gene to mutant cells will be feasible because the overexpression of ASA peptides in cells does not lead to profound deficiency of other sulfatases or result in a new phenotype.

Cells, Cultured↗

PubMed1995

Successful transduction of oligodendrocytes and restoration of arylsulfatase A deficiency in metachromatic leukodystrophy fibroblasts using an adenovirus vector.

Metachromatic leukodystrophy (MLD) is an inherited metabolic disease which is characterized by deficient activity of arylsulfatase A (ASA). This deficiency causes progressive accumulation of cerebroside sulfate (CS) in oligodendrocytes (OLs) in the brain resulting in dysmyelination. We are developing approaches for treating MLD based on direct delivery of ASA genes to brain. In this paper, we report a recombinant adenovirus (Adex1SRLacZL) that efficiently transduces OLs. Moreover, transduction and expression of the human transgene was efficient in primary fibroblasts from MLD patients exposed to similar recombinant adenovirus carrying the ASA gene (Adex1SRASA) In addition, the expressed ASA protein was correctly targeted to lysosomes and was immunoreactive to anti-ASA antibody. The enzymatic activity of ASA in MLD patient cells is corrected from the deficient state to 2.3 to 5.0 times the activity of normal control cells. These results demonstrate the correction of ASA deficiency by a recombinant adenovirus that is potentially useful for transferring the gene to brain.

Adenoviridae↗

PubMed1995

[The effects of Ebselen upon post-ischemic functional recovery in rat heart].

The effects of Ebselen (DR-3305) upon cardiac function and CK leakage with or without ischemia reperfusion insults were investigated in this isolated working rat heart study. In order to evaluate the effects of Ebselen upon cardiac function, it was administrated to the isolated rat heart with Langendorff perfusion for 15 min at 100 cmH2O. Cardiac functions such as aortic and coronary flow, heart rate and aortic pressure, before and after Ebselen treatment, were measured and expressed as percent of the control value. The coronary resistance was significantly reduced in 100 nM, 500 nM and 1000 nM of Ebselen pretreatment with dose dependent manner. However pretreatment with 1000 nM of Ebselen significantly decreased cardiac output with significant increase of CK leakage. The myocardial protective effects of Ebselen in the cardioplegia or reperfusate were investigated under conditions of normothermic ischemia. After measuring preischemic cardiac functions, the St. Thomas' Hospital cardioplegic solution was infused for 3 min followed by 35 min of global ischemia at 37 degrees C. Hearts were then aerobically reperfused for 15 min in the Langendorff mode. Subsequently, cardiac function was measured and expressed as percent of the preischemic control value. Ebselen addition to the St. Thomas' cardioplegic solution did not possess any myocardial protective effects, although addition to reperfusate possess the protective abilities at a concentration of 10 nM. From these data, Ebselen, which was one of the free radical scavenger, had the myocardial protective effects if it was added to reperfusate at a concentration of 10 nM.

Animals↗

PubMed1995

[Two cases of inferior branch palsy of the oculomotor nerve in children].

Two cases of inferior branch palsy of the oculomoter nerve in children are reported. A Six-year-old and a 14-year-old child had diplopia. Adduction and depression were restricted and mydriasis of the affected eye were observed. There were no restrictions on elevation. Ptosis was absent. They were diagnosed as having inferior branch palsy of the oculomotor nerve. Neurological examinations and diagnostic imagings showed no other abnormalities. Herpes simplex and influenza antibody titer were high in both cases. Oral steroid treatment was given. The eye position and movement recovered within 3 months in both cases. But the light reflexes of the affected eye remained diminished and light-near dissociation were observed. These findings have not changed for two years.

Adolescent↗

PubMed1995

[Long-term prolongation of direct pupillary light reflex latency and P100 latency of pattern visual evoked potential in unilateral optic neuritis].

We evaluated the visual functions of visual acuity, color sense, direct pupillary light reflex and pattern visual evoked potentials (P100) in five patients with unilateral optic neuritis whose visual acuity improved to 1.0 or better in order to assess the recovery of the impaired optic nerve fibers from the inflammatory process. During follow-up periods the direct light pupillary reflex was electropupillographically recorded and the P100 latency of visual evoked potentials was examined in both eyes. The temporal course of their differences showed a biphasic curve: the acute stage showed a rapid decrease of the differences and the chronic stage showed a flat line analysis of Pearson's correlation coefficient revealed that latency differences were mutually altered although there was a tendency for differences of direct pupillary reflex latency to decrease more rapidly at the acute stage than those of P100 latency. The present study demonstrated that the two different classes of the optic nerve fibers originating from the retinal ganglion cells, pupillary reflex-related fibers and form vision-related fibers, were damaged to the same degree by the inflammation, in spite of their morphological differences.

Adult↗

PubMed1995

[Neuron group of rostral midbrain associated with selective vertical gaze palsy in alert cats].

The neural and anatomical basis for selective vertical gaze palsy (isolated failure of upward or downward gaze) is still not completely understood. To study a new class of cells which is possibly related to selective vertical gaze near or in the INC (Interstitial-nucleus of Cajal), single cell recordings were performed in the vicinity of the INC of alert cats. We found 25 upward and 50 downward burster-driving neurons (BDN), which have very similar characteristics as those of previously reported horizontal BDNs. The activity of these vertical BDNs gradually increased during the downward slow phase and the upward slow phase, respectively, and this increased activity was further followed by a burst discharge shortly before and during the quick phase. These cells also showed burst discharge shortly before and during on-direction saccade. Downward BDNs were recorded mainly in the INC. Upward BDNs were found in the surrounding area of the INC. Deactivation by GABA agonist of each of the recorded sites produced selective upward and downward gaze palsy. Taken together, these results suggest that the deactivation of vertical BDNs involve some aspect of the selective vertical gaze palsy.

Action Potentials↗

PubMed1995

C-fos gene expression in rat retinal cells after focal retinal injury.

PURPOSE: To examine the expression of c-fos proto-oncogene in the rat retina after focal retinal injury. METHODS: A penetrating wound was made by pushing a 22-gauge hypodermic needle through the retina into the vitreous. The retinas were analyzed by in situ hybridization using single-stranded RNA probes for c-fos transcripts and by immunocytochemistry using anti-S100 protein antibody. RESULTS: Thirty minutes after the penetrating wound, c-fos mRNA was expressed in the inner nuclear layer (INL) and the ganglion cell layer (GCL) of the retina. Immunocytochemistry before in situ hybridization demonstrated c-fos mRNA surrounding the S-100 protein immunoreactive cytoplasm in the middle layer of the INL. CONCLUSIONS: Focal retinal injury of the rat retina induced the expression of c-fos mRNA in retinal cells. In the INL, it is suggested that the major cells that express c-fos mRNA after focal retinal injury were the Müller cells. These results suggest that c-fos may be involved in the transcription in the Müller cells after injury to the retina.

Animals↗

PubMed1995

[A case of bilateral upper medial medullary infarction].

A clinical case of bilateral upper medial medullary infarction was reported. A 61-year-old woman was admitted to our hospital because of numbness of trunk and bilateral upper and lower limbs, aphonia and left-hemiparesis, which progressed to quadriplegia. Facial movements were intact. Her tongue was not fully protruded and deviated to the right side. Impairment of the position sense was noted in bilateral lower limbs. Respiratory failure was not observed. A brain MRI revealed a high-intensity area on T2-weighted imaging in the upper medulla oblongata. The lesion involved the medial medulla oblongata bilaterally. No lesions were present in the other brain parenchyma. According to the literature, respiratory failure was present in almost all patients with bilateral medial medullary infarction. The findings of our patient suggest that respiratory failure is not induced by the bilateral medial medullary infarction limited to the upper medulla oblongata.

Cerebral Infarction↗

PubMed1995

Optic neuropathy and acute transverse myelopathy in primary Sjögren's syndrome.

A case of Sjögren's syndrome with optic neuropathy and acute transverse myelopathy mimicking multiple sclerosis is described. The patient suddenly lost her visual acuity resulting in a permanent visual deficit in spite of the massive steroid therapy given. During the treatment the patient showed dry eye symptoms and was finally diagnosed as having primary Sjögren's syndrome. It is suggested that primary Sjögren's syndrome should be considered in the differential diagnosis of neurologic disorders that resemble multiple sclerosis.

Acute Disease↗

PubMed1995

[Gaucher disease].

Gaucher disease is an inherited metabolic disease characterized by deficient activity of lysosomal enzyme, known as a glucocerebrosidase. Three clinical phenotype were documented depends on the onset of disease and neuronal involvement. Deficient activity of glucocerebrosidase results in progressive accumulation of glucocerebroside mainly in bone marrow derived macrophages. Diagnosis was made based on enzymatic activity in various tissue including WBC and fibroblasts. Molecular diagnosis was also possible. However, it is difficult to differentiate the three phenotypes. Although bone marrow transplantation and enzyme infusion therapy are both effective, the inherent problems limits their application. Gene therapy based on transfer of the therapeutic gene to hematopoietic stem cells were started in this year in USA.

Bone Marrow Transplantation↗

PubMed1995

[Gene therapy for Gaucher disease].

Gaucher disease is a lysosomal storage disease which is characterized by deficient activity of lysosomal enzyme, known as glucocerebrosidase. This resulted in progressive accumulation of glucocerebroside only in bone marrow derived macrophages. This unique pathophysiology makes Gaucher disease an excellent candidate of gene therapy based on transferring therapeutic gene to hematopoietic stem cell. The extensive study based on transferring therapeutic gene to hematopoietic stem cell. The extensive study was already done using mouse in vivo system and human in vitro system. In mouse system, all of the macrophages from long term reconstituted mice were transduced. In human system, 40 approximately 60% of bone marrow progenitor cells were transduced. Because of this success, the clinical protocol for gene therapy for Gaucher disease was approved by RAC and FDA. The clinical trial was started in this year. The brief history of development and current limitation of gene therapy for Gaucher disease were discussed.

Animals↗