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Biomedical subjects

T Ohashi

Publications and source records attributed to T Ohashi.

At least 199 records · Page 11Linked to original sources
PubMed1995

Visual function in patients with optic neuritis associated with acute transverse myelopathy in multiple sclerosis.

The authors reviewed the records of 20 patients with optic neuritis, all of whom were diagnosed as having clinically definite multiple sclerosis (MS). They were classified into two subgroups: Group A, consisting of 9 patients who had shown acute transverse myelopathy (ATM); and Group B, 11 patients without ATM. Four patients (44%) in Group A had complete visual loss, but none in Group B. Six patients (67%) in Group A had less than 0.1 visual acuity in the affected eye, but only 2 patients (18%) in Group B. Four patients in Group A showed evidence of anticardiolipin antibodies. While both groups were diagnosed as having clinically definite MS, there were differences between them in the clinical features. We assume that the patients with ATM may constitute a different subgroup among MS patients.

Acute Disease↗
PubMed1994

In vivo isomerization of retinoic acids. Rapid isomer exchange and gene expression.

The in vivo isomerization of all-trans- and 9-cis-retinoic acids (RAs) was evaluated by high performance liquid chromatography after oral administration to rats. All-trans (2 ng/ml)- and 13-cis (1.8 ng/ml)-RAs, but not 9-cis-RA, were detected in the serum of normal rats. When an excess of either all-trans-RA or 9-cis-RA (100 micrograms/rat) was intragastrically administered to the retinoid-depleted rats, a rapid isomer exchange between 9-cis- and all-trans-RAs along with appearance of the administered RA occurred shortly after the dose (30 min). RA rapidly isomerized when an excess of either all-trans- or 9-cis-RA (1 mg/rat) was administered to normal rats. To examine whether the isomerized RAs elicit biological actions in vivo, the induction of target genes-[cellular retinol-binding protein type II (CRBP II) for 9-cis-RA and all-trans-retinoic acid receptor beta (RAR beta) for 9-cis- and all-trans-RAs] was determined. The degree of induction of the two genes did not differ 4 h after administration of either 9-cis-RA or all-trans-RA. However, unlike all-trans-RA, the RAR-specific synthetic retinoids did not induce the CRBP II gene. These results suggested that the apparent actions of 9-cis- and all-trans-RAs on gene expression in vivo may be mediated to some extent by the converted stereoisomer.

Animals↗
PubMed1994

Cloning of feline p53 tumor-suppressor gene and its aberration in hematopoietic tumors.

Alterations of the p53 tumor-suppressor gene have been observed in a variety of human and mouse tumors. For investigation of the role of this gene in tumors of cats, feline p53 cDNA was molecularly cloned from a feline lymph-node cDNA library. The cloned cDNA (FF53) contained the whole open reading frame of p53 gene encoding 386 amino acids. The amino-acid sequence of the feline p53 gene showed 82.1% and 74.9% similarities with those of the human and mouse counterparts, respectively, and had structural characteristics in common with the p53 genes of several other species. Aberrations of the p53 gene were investigated by RT-PCR and single-strand conformation polymorphism analyses. Of 10 primary hematopoietic tumors and 3 lymphoma cell lines examined, one lymphoma and one lymphoma cell line had a point mutation of the p53 gene, resulting in single amino-acid substitutions.

Amino Acid Sequence↗
PubMed1994

High-performance liquid chromatographic determination of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648) and its deacetyl metabolite in plasma, whole blood, urine and tissue samples in rats.

A reversed-phase high-performance liquid chromatographic method was developed for the determination of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl)benzoxazinorifamycin (KRM-1648, I), a new rifamycin derivative, and its 25-deacetyl metabolite (KRM-1671, II) in plasma, whole blood, tissues and urine from rats. I and II were coextracted with an internal standard from each sample matrix by solid-phase extraction (Bond Elut). Plasma and urine were directly loaded onto Bond Elut, while whole blood and tissues were homogenized and extracted with methanol or dichloromethane-chloroform prior to Bond Elut extraction. The extracts were chromatographed on Shim-pack CLC-ODS(M) using acetonitrile-0.02 M citrate buffer containing 0.1 M sodium perchlorate (2:1, v/v), and peaks were detected at 643 nm. The validation data showed that the assays for I and II in plasma, whole blood, tissues and urine were selective, accurate and reproducible.

Animals↗
PubMed1994

Single exon mutation in arylsulfatase A gene has two effects: loss of enzyme activity and aberrant splicing.

The arylsulfatase A gene of a Japanese patient who has the juvenile form of metachromatic leukodystrophy, and who has been previously reported as a heterozygote of the 1070A mutation, was investigated. Nucleotide sequence analysis revealed the presence of a previously unreported C-to-T substitution (designated 2330T), 22 nucleotides downstream from the exon 8 splice acceptor site. Although the 2330T mutation itself results in a single amino acid substitution of Thr409 by Ile, the analysis of the patient's cDNA fragments amplified by the reverse transcription-polymerase chain reaction revealed that transcripts of the 2330T allele were spliced both normally and aberrantly. The aberrant splicing produced a 27-nucleotide deletion from the usual exon 8 splice acceptor site. These results indicate that the new mutation is a rare case of an exon mutation affecting splice site selection. The mechanism of this aberrant pre-mRNA splicing is discussed.

Adolescent↗
PubMed1994

Type C Niemann-Pick disease fibroblasts and their transformed cell lines are hypersensitive to HMG-CoA reductase inhibitors.

The deficiency of exogenous cholesterol transport within fibroblasts of Niemann-Pick disease type C (NPC) has been addressed. In this report we confirmed that the endogenous synthesis of cholesterol within cells was markedly increased in NPC fibroblasts and those transformed by origin-defective simian virus 40. The transformed fibroblasts and those of the primary culture were hypersensitive to 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors as a consequence of their dependence on endogenous cholesterol biosynthesis. The transformed fibroblasts should help further biochemical and genetic research in this condition.

Cell Line, Transformed↗
PubMed1994

Identification and characterization of a major bovine serum tyrosine-O-sulfate-binding protein as a complement factor H.

A major tyrosine-O-sulfate (TyrS)-binding protein present in bovine serum was purified to electrophoretic homogeneity using a combination of TyrS-Affi-Gel 10 affinity chromatography, DEAE-Bio-Gel A ion-exchange chromatography, and hydroxylapatite chromatography. The purified TyrS-binding protein migrated as doublet protein bands with apparent molecular weights of ca. 160,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. N-termini of the two forms of purified TyrS-binding protein contain most likely identical sequence for the first fifteen amino acids residues, which displays a high degree of homology to those of human and mouse complement factor H. Furthermore, the purified TyrS-binding protein exhibited immunologic cross-reactivity with anti-human complement factor H. These results indicate the identity of the purified TyrS-binding protein being bovine complement factor H. The two forms of the purified bovine factor H were investigated with respect to the sensitivity to limited trypsin digestion. The high-molecular weight form was cleaved into two fragments with apparent molecular masses of, respectively, 45 kD and 125 kD. The low-molecular weight form was cleaved in a different manner to generate three major fragments with molecular masses of 25 kD, 45 kD and 100 kD, respectively. Limited V8 protease mapping of the two forms yielded similar, yet unidentical, peptide band patterns. Purified bovine factor H appeared to bind agarose-bonded heparin through its anion-binding domain and the binding was inhibited by the presence of free heparin or dextran sulfate.

Amino Acid Sequence↗
PubMed1994

Effects of chemical deactivation of the interstitial nucleus of Cajal on the vertical vestibulo-collic reflex induced by pitch rotation in alert cats.

The basic circuitry for the vestibulo-collic reflex (VCR) is a three-neuron arc, and this reflex requires the temporal and spatial transformation of vestibular signals to activate the appropriate neck muscles. Signals carried by vestibulo-collic neurons are insufficient to explain the responses of neck muscles. However, it is still unknown as to where the additional signal conversion is performed in the vertical VCR. We examined the effects of chemical deactivation of the interstitial nucleus of Cajal (INC) on the responses of biventer cervicis EMG induced by pitch rotation in the dark in alert head-fixed cats, and compared the results with the vertical vestibulo-ocular reflex (VOR) and also with the VCR and VOR induced by horizontal rotation. Muscimol infusion into the bilateral INC resulted in phase advance and gain drop in both the vertical VCR and the VOR, although the change was smaller in the VCR. The response phases of the horizontal VCR and VOR were not affected. Muscimol infusion outside the INC did not affect the phase of the vertical VCR or VOR. These results suggest that the INC is partially involved in temporal conversion of vestibular signals in the vertical VCR as well as in the VOR evoked by pitch rotation in alert cats.

Animals↗
PubMed1994

Molecular cloning and expression of canine interleukin 8 cDNA.

Molecular cloning of canine interleukin-8 (IL-8) was performed to establish a basis for its investigation in the canine immune system. From a cDNA pool constructed from LPS-stimulated popliteal lymph node cells, canine IL-8 cDNA covering the whole coding region was amplified by polymerase chain reaction. The nucleotide sequence of a canine IL-8 clone, designated pcIL-8#38, was highly similar to those of human, rabbit and porcine IL-8, and comprised 353 bp with an open reading frame that encoded 101 amino acids. Analysis of the deduced amino acid sequence of insert DNA in pcIL-8#38 showed 76.5, 80.2, and 87.0% similarities with human, rabbit and porcine IL-8 proteins, respectively. Insert DNA of pcIL-8#38 was transferred to a mammalian expression vector, pcDL-SR alpha 296, and transfected into Cos7 cells. The supernatant of the transfectant had neutrophil chemotactic activity when it was examined by the neutrophil migration assay, suggesting that our cloned cDNA was biologically active. The cloned canine IL-8 cDNA will be useful for canine inflammatory disease and comparative immunology research.

Amino Acid Sequence↗
PubMed1994

Ontogeny and effects of exogenous surfactant treatment on SP-A, SP-B, and SP-C mRNA expression in rabbit lungs.

The aims of the present study were to first characterize the ontogeny of mRNAs encoding the principal surfactant proteins SP-A, SP-B, and SP-C in rabbit lung tissues, followed by an evaluation of the effect of exogenous surfactant administration on endogenous expression of mRNA levels. Lung tissues were collected from New Zealand White rabbits on days 19, 21, 24, 26, 28, 30 of gestation, 1 day and 10 days after birth, and as adults. SP-A, SP-B, and SP-C mRNAs were first detected on gestational days 26, 24, and 19, respectively. The specific levels of these mRNAs generally increased to gestational day 28 and decreased transiently on 1 day of life. Adult values remained lower than those noted at 30 days gestation. For the second study, 29-day-gestation preterm rabbits were given either one or two treatment doses of natural surfactant or an organic solvent extract of natural surfactant, and mRNA levels were measured 10 or 24 h later. No effect of surfactant treatments, type of surfactant, or dosage (1 or 2 treatments) was noted on SP-A, SP-B, or SP-C mRNA expression. These data indicate that the mRNA expression for the three major surfactant proteins was highest late in gestation in developing rabbits and that exogenous surfactant treatment was not associated with significant changes in SP-A, SP-B, or SP-C mRNA levels.

Animals↗
PubMed1994

A case of neuroretinitis associated with long-standing polyarteritis nodosa.

We reported a 45-year-old man suffering from neuroretinitis with long-standing polyarteritis nodosa and anterior uveitis. Fluorescein angiography, made at the stage when optic disk swelling developed, demonstrated a hypofluorescent area at the temporal part of the optic disc presenting exudates in its prelaminar region. When the swelling of the optic disc had resolved as verified ophthalmoscopically, and the hypofluorescence was angiographically undetectable, a macular star was observed, showing a configuration corresponding to Henle's layer.

Humans↗
PubMed1994

Changes in alveolar surface area, surfactant protein A, and saturated phosphatidylcholine with postnatal rat lung growth.

Most previous studies of the relationship between surfactant and growth have correlated surfactant pool size with lung weight or body weight. We asked how the quantities of the surfactant components surfactant protein A (SP-A) and saturated phosphatidylcholine (Sat PC) recovered by alveolar wash changed with age in relationship to morphologic measurements of alveolar surface area in rats. We also calculated SP-A and Sat PC in total lung per surface area. In groups of three to 14 rats studied on d 1, 7, 14, 21, 50, and 100 of age, the ratio of alveolar surface area to body weight was highest at d 14 and lowest at d 100. Alveolar and total lung SP-A and Sat PC were higher relative to body weight and surface area on d 1 than at all other ages. Alveolar and total lung SP-A peaked relative to surface area at d 21 and subsequently decreased significantly at d 100. The alveolar Sat PC to surface area ratio also was highest at d 21 and decreased significantly at d 50 and 100. The SP-A to Sat PC ratio in alveolar washes was not constant across this age range, being highest at d 21 and 50. These measurements demonstrate age-dependent changes in alveolar and total lung SP-A and Sat PC in the rat that continue beyond the newborn period.

Age Factors↗
PubMed1994

Amphoteric drugs. I. Synthesis and antiallergic activity of [4-(diphenylmethoxy)piperidino]-, [4-(diphenylmethyl)piperazinyl]- and [4-(diphenylmethylene)piperidino]alkanoic acid derivatives.

A simple method of transforming classical antihistaminics into nonsedative antiallergic agents with strong effects in rat models is described. Various [4-(diphenylmethoxy)piperidino]- (series A), [4-(diphenylmethyl)piperazinyl]-(series B) and [4-(diphenylmethylene)piperidino]alkanoic acid derivatives (series C) were synthesized and examined for antiallergic activities and effects on the central nervous system (CNS), in comparison with the corresponding N-methyl derivatives (1a--c). N-Alkylcarboxylic acids (5a--c) showed stronger inhibitory effects on compound 48/80-induced lethality in rats than the corresponding N-methyl derivatives (1a--c). In particular, N-alkylcarboxylic acids (5a) in series A exhibited approximately 100-fold stronger inhibitory effects than 1a, and were the least effective in prolonging the sleeping time on hexobarbital-induced anesthesia in mice in all series. As a result of chemical modification in series A, it was found that introduction of a methyl group at the para-position on one benzene ring in the (diphenylmethoxy)piperidine system effectively reduced CNS side-effects without reducing antiallergic activity. (+)-3-[4-[(4-Methylphenyl)phenylmethoxy]piperidino]propionic acid ((+)-5l), an optically active isomer of 5l, exhibited a stronger antiallergic effect (ED50 = 0.17 mg/kg, p.o.) than ketotifen and terfenadine in the 48 h homologous passive cutaneous anaphylaxis (PCA) test, and moreover exhibited no CNS side-effects, such as prolongation of the sleeping time on hexobarbital-induced anesthesia, at an oral dose of 30 mg/kg. Compound (+)-5l was thus proved to be a promising candidate as a nonsedative antiallergic agent.

Animals↗
PubMed1994

[Studies on zwitter-ionization of drugs. III. Synthesis and pharmacological activities of N-alkylcarboxylic acid derivatives of 1,2,3,4,10,14b-Hexahydrodibenzo[c,f]-pyrazino[1,2-a]azepine and 2,3,4,9-tetrahydro-1H-dibenzo[3,4: 6,7]cyclohepta[1,2-c]pyridine].

The N-alkylcarboxylic acids of 1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-alpha]az epi ne (6a) and 2,3,4,9-tetrahydro-1H-dibenzo[3,4: 6,7]cyclohepta[1,2- c]pyridine (6b) were synthesized and examined for pharmacological activities in vitro: an inhibitory effect on the monoamine [noradrenaline (NA) and 5-hydroxytryptamine (5-HT)] uptake into the rat crude synaptosome, an inhibitory effect on the 5-HT- and NA-induced contraction in the isolated rabbit aorta and on the histamine- and acetylcholine-induced contraction in the isolated guinea-pig ileum, and binding affinity for alpha 2-adrenoceptor and D2-receptor. The in vitro tests indicated that zwitter-ionization was capable of maintaining antihistaminic activity while greatly reducing other pharmacological activities such as effects on central nervous system. 3-[2,3,4,9-Tetrahydro-1H-dibenzo[3,4: 6,7]cyclohepta[1,2- c]pyridin-2-yl]propionic acid (6b-2), selected as a candidate antiallergic agent having equally potent activities in rats and guinea-pigs, exhibited strong inhibitory effects on 48 h homologous passive cutaneous anaphylaxis (PCA) in rats (ED50 = 0.012 mg/kg, p.o.) and on histamine-induced bronchoconstriction in anesthetized guinea-pigs (ED50 = 0.0088 mg/kg, p.o.).

Animals↗
PubMed1994

Electron microscopic studies on the inhibition of degranulation of rat mast cells by a novel anti-allergic agent, PTPC.

When rat mast cells sensitized by IgE antibody were exposed to antigen, transmission electron microscopy revealed alteration of the granules, cavity formation by fusion of the perigranular membrane and granule release by the fusion of the cavity membrane with the mast cell membrane. Scanning electron microscopy disclosed the extrusion of smooth and round bodies from pores formed on the cell surface. These changes were accompanied by the release of histamine. The inhibition of this degranulation by a novel anti-allergic agent, 6-(1-pyrrolidinyl)-N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamide (PTPC), was evaluated quantitatively as an inhibition of the granule alteration and cavity formation. At a concentration of 100 nM, PTPC inhibited the granule alteration and cavity formation as well as histamine release. In the same concentration, PTPC significantly increased the cyclic AMP content in the mast cells. These results suggest that the inhibition of the morphological changes in mast cells by PTPC might be due to the increased cyclic AMP caused by the agent and plays an important role in the suppression of chemical mediators release.

Animals↗
PubMed1994

Can plasma glucose and nonesterified fatty acid be regulators of glucose utilization in skeletal muscle?

The effect of plasma glucose and nonesterified fatty acid (NEFA) on basal and insulin-stimulated glucose utilization in skeletal muscle was assessed by perfused hindlimb preparations. Two-month-old male Wistar rats were divided into four groups: starved, glucose-loaded, hypoglycemic and control. Diabetic rats were made by means of streptozotocin, and divided into three groups: non-treated, insulin-treated normoglycemic and insulin-treated hyperglycemic. The effect of NEFA on glucose clearance was also investigated by adding palmitate to the perfusate. Basal glucose utilization decreased with a rise in plasma glucose concentrations, and increased with a fall in them in each group. The available data strongly support the view that plasma glucose levels play an important role in the control of basal glucose utilization by the hindlimb muscle. In contrast, continuous hyperglycemia in the diabetic state decreased insulin-stimulated glucose utilization by the skeletal muscle, whereas an acute rise in plasma glucose concentrations in the glucose-load state did not. Palmitate stimulated basal glucose utilization, while it decreased insulin-stimulated glucose uptake. It was also clarified that it increased the affinity for glucose in the skeletal muscle in the basal state. This finding seems to indicate that NEFA has some influence on an increase in basal glucose utilization in starvation.

Animals↗
PubMed1994

[T cell immunity to proteolipid protein (PLP) in multiple sclerosis (MS): identification of DR2-associated PLP determinants and conserved TCR CDR3 motifs].

Multiple sclerosis is assumed to be an autoimmune disease mediated by T cells specific for myelin protein, such as, myelin basic protein (MBP) and PLP. Several groups reported that PLP-specific T cells are activated in the cerebrospinal fluid and, to a lesser extent, in the peripheral blood of the patients. We identified seven T cell epitopes within PLP residue 85-159. The T cell responses to these epitopes were higher in MS than in healthy subjects. PLP 95-116 and 105-124 specific T cells were more frequently established from DR2 MS than from non-DR2 MS, indicating that the DR2 restricted T cells recognizing these determinants are involved in the pathogenesis of MS. It is found PLP-specific T cells preferentially use V beta 5 and V beta 2 families though the usage is not exclusive. TCR beta chain complementary determining region 3 (CDR3) amino acid motifs of some PLP-specific T cells were homologous to those of MS lesion T cells, so it is likely that PLP-specific T cells infiltrate MS lesions. To our surprise, the CDR3 motifs of PLP-specific clones resemble those of MBP-specific clones. According to these facts, some antigen-independent pressure might give a common structure to T cells involved in MS.

Amino Acid Sequence↗