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Biomedical subjects

T Ohashi

Publications and source records attributed to T Ohashi.

At least 127 records · Page 7Linked to original sources
PubMed1997

Clival chordoma presenting as acute esotropia due to bilateral abducens palsy.

A case involving a 14-year-old girl having clival chordoma with symptoms of diplopia, acute esotropia, and bilateral abducens palsy is reported. Magnetic resonance imaging revealed a clival tumor invading the posterior edges of the bilateral cavernous sinuses. After removal of the tumor, no ocular manifestations were noted. The importance of acute esotropia as a sign indicating a possible brainstem mass is emphasized.

Abducens Nerve↗
PubMed1997

Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of [4-[1-(benzenesulfonamido)alkyl]phenyl]alkanoic acid derivatives.

In order to find new antiasthmatic agents with dual antagonistic activity against thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors, synthesis and pharmacological evaluation of various [4-[1-(benzenesulfonamido)-alkyl]phenyl]alkanoic acid derivatives were undertaken. TXA2 and LTD4 antagonistic activities in vitro were evaluated by measuring the inhibitory effects on L-46619-induced contraction of guinea-pig trachea and LTD4-induced contraction of guinea-pig ileum and trachea. Several compounds showed satisfactory dual antagonistic activities, and their effect (after oral administration) on LTD4-induced bronchoconstriction in guinea-pig in vivo was examined. The results demonstrated that both 4-[4-[1-(4-chlorobenzenesulfonamido)hexyl]phenyl]butyric acid (12e) and 4-[4-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]phenyl]bu tyric acid (12m) possessed good anti-LTD4 activities. Compounds 12e and 12m were then evaluated for other related pharmacological effects involving the arachidonic acid cascade. These compounds appear to be hybrid eicosanoids antagonists having antagonistic activity against contraction of guinea-pig trachea induced by prostaglandin D2 (PGD2) and PGF2 sigma, as well as TXA2 and LTD4 antagonistic activities.

Animals↗
PubMed1997

[Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of benzenesulfonamide derivatives].

In order to find dual antagonists against both thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors for a new antiasthmatic agent, various benzenesulfonamide derivatives were synthesized and evaluated for those pharmacological effects. TXA2 and LTD4 antagonistic activities in vitro were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced contraction of guinea-pig trachea. Furthermore, TXA2 and LTD4 antagonistic activities in vivo were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced bronchoconstriction of guinea-pig after oral administration of test compounds. It was found that 4-[5-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]-2-thi eny l]butyric acid and 4-[5-[1-(4-fluorobenzenesulfonamido)-5-methyl-hexyl]-2-thienyl]but yric acid possess good anti-LTD4 and anti-TXA2 activities by oral administration.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Studies on the novel antiallergic agent HSR-609: its penetration into the central nervous system in mice and guinea pigs and its selectivity for the histamine H1-receptor.

We studied the pharmacological characteristics of HSR-609 (3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11- ylidene)- piperidino]propionic acid dihydrate), a novel amphoteric antiallergic agent, on the central nervous system (CNS). Its selectivity for the histamine H1-receptor and its ability to penetrate into the CNS were compared with those of typical antiallergic agents and the nonamphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4-piperidylidene)benz[b]oxe pino- [4,3-b]pyridine), which has a chemical structure similar to that of HSR-609. In the in vitro study, HSR-609 had a high affinity for H1-receptors in the guinea pig cerebral cortex in comparison to affinities for muscarinic and serotonin 5-HT2-receptors in the rat cerebral cortex, while the selectivity of PY-608 for the H1-receptor was low. The inhibitory effects of these antiallergic agents on histamine-induced increase of vascular permeability in mice (ED50) were compared with the displacement of [3H]mepyramine binding to H1-receptors in mouse brain ex vivo (ID50). The ID50/ED50 ratio of HSR-609 was much larger than those of cyproheptadine, ketotifen and PY-608 and larger than those of terfenadine and cetirizine. HSR-609 was found to display selective displacement of the [3H]mepyramine binding to H1-receptors for lung vs cerebral cortex as found with terfenadine in guinea pigs ex vivo. These findings suggest that HSR-609 has high selectivity for the H1-receptor and poor ability to penetrate into the CNS in mice and guinea pigs due to its amphoteric chemical structure.

Administration, Oral↗
PubMed1997

Pharmacological studies on the novel antiallergic agent HSR-609: its effects on behavior in mice and electroencephalograms in rabbits.

We studied the central nervous system (CNS) effects of HSR-609 (3-[4-(8-fluoro-5,11-dihydrobenz[b]oxepino[4,3-b]pyridin-11- ylidene) piperidino]propionic acid dihydrate), a novel amphoteric antiallergic agent having antihistaminic activity. Its effects on the behavior of mice and the electroencephalograms (EEG) of unanesthetized and unrestrained rabbits after oral administration were compared with those of typical antiallergic agents and the non-amphoteric basic compound PY-608 (8-fluoro-5,11-dihydro-11-(1-methyl-4-piperidylidene)benz [b]oxepino[4,3-b]pyridine), which has chemical structure similar to that of HSR-609. HSR-609 (3-300 mg/kg) had no effect on general behavior, spontaneous locomotor activity, hexobarbital-induced sleeping time and reserpine-induced hypothermia in mice. HSR-609 (10-100 mg/kg) and terfenadine (100 mg/kg) had no effect on spontaneous EEG, sleep-wakefulness cycles and EEG power spectra in rabbits. On the other hand, cyproheptadine (3-30 mg/kg), ketotifen (30-100 mg/kg) and PY-608 (0.3-100 mg/kg) caused increases and/or decreases of spontaneous locomotor activity, prolongation of hexobarbital-induced sleeping time and antagonistic effects on reserpine-induced hypothermia in mice. These agents (30 mg/kg) increased slow wave sleep and enhanced EEG power spectra at low frequency bands such as delta and theta in rabbits. These findings suggest that HSR-609 has no inhibitory effect on the CNS due to its amphoteric chemical structure.

Animals↗
PubMed1997

[Effects of salicylate and quinine on cat primary auditory cortex--spontaneous firing rate].

The effect of salicylate and quinine on the spontaneous firing rate in the cat primary auditory cortex was investigated in 13 healthy cats. Spontaneous firing rates were calculated for each single unit. A dose of 200 mg of sodium salicylate per kg was administered intraperitoneally to six cats, and the findings from the same single unit were recorded prior to application and continuously up to, on average, 6 hours after application. A dose of 100 or 200 mg of quinine hydrochloride per kg was administered intramuscularly to seven cats, and the findings from the same single unit were recorded in the same manner as for the cats treated with sodium salicylate. Twenty one single units in salicylate-treated cats and 29 single units in quinine-treated cats were evaluated. All animals treated with salicylate showed a 20-30 dB threshold shift about 2 hours after application and showed no recovery during the course of the investigation. All animals treated with quinine showed a 10-40 dB threshold shift about 1 hour after application and recovered during the course of the investigation. There was no consistent difference in overall spontaneous firing rate before and after application in either salicylate-treated cats or quinine treated cats. In order to investigate a potential different effect on units with different spontaneous firing rates, we divided the cats into two groups, a high-firing rate group (pre-application firing rate > 1 spike/s) and a low firing rate group (pre-application firing rate < 1 spike/s). A significant decrease in the high-firing rate group (p < 0.05) and a significant increase in the low firing rate (p < 0.01) were observed in salicylate-treated cats. The same tendencies were observed in quinine-treated cats, but only the difference in the low firing rate group was significant (p < 0.05). The difference in the high-firing rate group was close to the significant level (p = 0.055). These changes in spontaneous firing rates in cat primary auditory cortex may be related to the generation of tinnitus.

Animals↗
PubMed1997

[Functional changes in the cochlea of guinea pigs in chronic renal failure--electrocochleography. Effect of noise exposure].

An animal model of chronic renal failure (CRF) was created by the 5/6 nephrectomy procedure in guinea pigs. Levels of serum Cr and BUN were abnormally elevated at 1,2 and 3 months after the procedure. ECoG (CAP, CM) was recorded through a silver ball electrode placed on the round window 1,2 and 3 months after surgery. EP was measured with a glass microelectrode from the scala media via the round window membrane. Only slight ECoG changes were seen 1 month after surgery. On the other hand, moderate or profound changes were observed 2 and 3 months after-surgery. No significant decrease in EP was found in the post-surgery animals which distinctly showed abnormal CAP, CM, although a limited number of animals were studied. The above results indicate that CRF is one of the etiological factors of cochlear dysfunction and the sensory hair cells appeared to be the site of the lesion. To study the interaction between noise exposure and CRF, 1 month post-surgery animals with only a little change in ECoG were exposed to a broad band noise. Changes in the ECoGs were followed up for 6 hours after the noise exposure. In contrast to the controls, animals with CRF did not recover from the reduced ECoG which occurred immediately after the noise exposure. This suggests synergistic interaction between noise and CRF.

Animals↗
PubMed1997

[The serum zinc level in patients with tinnitus and the effect of zinc treatment].

We measured the serum zinc level in patients with tinnitus and evaluated the effectiveness of zinc in the treatment of tinnitus. Blood zinc levels were measured in 121 patients with tinnitus. All patients were examined between 1995 and 1997 at the outpatient clinic of otorhinolaryngology St. Marianna University Toyoko Hospital. Forty-seven patients who had received any drug such as a calcium channel blocker and others or had been affected by any diseases were excluded and therefore 74 patients consisting of 46 females (62%) and 28 males (38%) were investigated. Twenty two healthy volunteers served as a control group. The mean age and standard deviations for the tinnitus group and the control group were 47.8 +/- 17.1 and 31.4 +/- 8.2 years, respectively. There was a significant decrease (p < 0.0001) in serum zinc levels in patients with tinnitus compared with the control group. Because there was a significant difference (p < 0.0001) in age distribution between tinnitus and control groups, patients were selected by their age in order to neglect the effect of aging. In this situation, a significant difference (p < 0.01) was noted between the tinnitus group and control group. Low blood zinc level was defined by using the mean and standard deviation for the control group (mean-1 S.D.). We treated patients with low blood zinc levels. A total dose of 34-68 mg of Zn++ was administered daily for over 2 weeks. The degree of tinnitus was expressed on a numeric scale from 0 to 10 before and after treatment. Blood zinc levels were significantly elevated (p < 0.05) after treatment. We found a significant decrease (p < 0.01) in the numeric scale. These findings suggest that zinc is useful in at least some patients suffering from tinnitus. It is possible to classify patients with tinnitus by measuring serum zinc level and this leads to improvement of the overall treatment effect.

Adolescent↗
PubMed1997

Constitutive activation of Stat-related DNA-binding proteins in erythroid cells by the Friend spleen focus-forming virus.

The erythroleukemia-inducing Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein which allows erythroid cells to proliferate and differentiate in the absence of the erythroid hormone erythropoietin (Epo). In an attempt to understand how the virus alters the growth of erythroid cells, studies were carried out to determine if virus infection leads to the constitutive activation of the Jak-Stat pathway, one of the signal transduction pathways activated by Epo. Our data indicates that expression of SFFV in erythroid cells leads to the constitutive activation of the same Stat proteins that are transiently activated by Epo. While constitutive activation of Stat proteins by SFFV is associated with Epo-independent proliferation of splenic erythroid progenitor cells from Fv-2-sensitive mice and Epo-dependent HCD-57 cells, it is not sufficient to induce their differentiation. Although constitutive activation of the same Stat proteins is detected in erythroid cells from SFFV-infected Fv-2-resistant mice, it does not lead to their Epo-independent growth. It is also not required for transformation of erythroid cells by SFFV. Studies are in progress to identify the mechanism by which Stat proteins are phosphorylated in SFFV-infected cells in the absence of Epo. Although it has been shown that Epo activates Stat proteins through Jak2 kinase, our results suggest that the SFFV-induced Stat protein activation is Jak2-independent.

Animals↗
PubMed1997

[A study of MRI and clinical neurology in acute cerebellar infarcts].

We studied clinical manifestations of sixteen patients with cerebellar infarcts diagnosed by MRI. In fourteen of them, the stroke developed abruptly with vertigo, which continued for several days. At the early stage of illness, ataxia was obscure. But after vertigo and nausea disappeared, nine cases showed truncal ataxia, while limb ataxia was found in only five. Their vertigo was rotatory and aggravated by head movement. Gaze-evoked nystagmus was observed in only 5 cases. Four patients preferred to take unilateral posture since they experienced less vertigo. The side of their lesions was the lower side of their posture. Limb ataxia was more frequent in SCA-involving cases than in SCA-non involving cases (3 out of 6 vs 2 out of 10, respectively). On the other hand, headache was more frequent in PICA-involving cases than in PICA-non-involving cases (6 out of 11 vs 1 out of 5, respectively). Ataxic gait was seen more in medial branch-involving cases than medial branch non-involving cases (5 out of 6 vs 4 out of 10, respectively). One patient died due to obstructive hydrocephalus.

Adult↗
PubMed1997

A case of bilateral optic neuropathy and recurrent transverse myelopathy associated with perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA).

A case involving a 52-year-old man having bilateral optic neuropathy and recurrent transverse myelopathy is reported. His clinical features resembled multiple sclerosis, but neuroimaging failed to show evidence of demyelination or inflammation in the brain or the optic nerves. The patient experienced sudden visual loss despite massive steroid therapy. Positive perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) is suggestive that optic neuropathy and recurrent transverse myelopathy may have been caused by some common inflammatory processes associated with p-ANCA, however, having a different etiology from multiple sclerosis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

[The temperature dependency of the protective properties of the St. Thomas' Hospital cardioplegic solution, the University of Wisconsin solution, and Bretschneider buffered solution].

We studied three preservation solutions such as St. Thomas' hospital cardioplegic solution No. 2 (ST), the University of Wisconsin solution (UW) and Bretschneider's solution (BR) for protective properties, especially in terms of temperature dependence during the preservation. Rat hearts were studied and divided into three groups; ST. UW and BR. In each group, six hearts were carried out perfusion, cardioplegic infusion, ischemia and reperfusion for four different conditions. Using an isolated working rat heart model, the hearts were subjected to 5 minutes Langendorff perfusion followed by 20 minutes working perfusion. During this working period, cardiac functions such as aortic and coronary flow, aortic pressure, and heart rates were measured every 5 minutes. After working perfusion, 3 minutes of cardioplegic infusion was carried out either with UW, ST, and BR at 37, 20, 4, 1 degree C. The hearts were subjected to either 35 min at 37 degrees C, 120 min at 20 degrees C, 300 min at 4 degrees C, or 450 min at 1 degree C. The hearts were immersed in the same solution during ischemia. The hearts were reperfused at 37 degrees C, initially in the Langendorff mode for 15 min. Coronary effluent was collected for the measurement of CK leakage during reperfusion. The heart were then converted to the working mode for 20 minutes. During working reperfusion period, the variables of cardiac function were again measured and expressed as a percentage of their individual preischemic control values. Under conditions of 37 degrees C ischemia, % recovery of cardiac output (%CO) in ST group is 62.8 +/- 2.8%, although the hearts preserved with UW and BR were not recovered. Under conditions of 20 degrees C ischemia, %CO in UW, ST and BR were 46.8 +/- 2.7, 82.0 +/- 3.1 and 41.4 +/- 2.6%, respectively. Under conditions of 4 degrees C ischemia, %CO in UW, ST and BR were 66.2 +/- 8.0, 68.6 +/- 2.3 and 47.2 +/- 2.9%, respectively. Under conditions of 1 degrees C ischemia, %CO in UW, ST and BR were 70.6 +/- 3.3, 56.5 +/- 1.6 and 43.0 +/- 2.5%, respectively. In conclusions, ST revealed the best protective properties for the heart preservation between 37 degrees C and 20 degrees C ischemia. The properties of ST was similar to that of UW under conditions of 4 degrees C, although UW showed most excellent protective properties under conditions of 1 degrees C ischemia. These results suggested that, protective ability of preservation solution might be changed by the temperature during preservation period.

Adenosine↗
PubMed1996

Identification of an alternatively spliced transcript of equine interleukin-1 beta.

Using lipopolysaccharide (LPS)-stimulated equine peripheral blood mononuclear cell (PBMC) cDNA as a template, we performed polymerase chain reaction (PCR) amplification with equine interleukin-1 beta (IL-1 beta) specific primers. Electrophoresis of the PCR product on agarose gel revealed an additional smaller fragment that hybridized with an equine IL-1 beta cDNA probe. Sequencing of this fragment demonstrated that it was shorter than normal equine IL-1 beta cDNA by 162 nucleotides, which corresponded to exon 5 of the human and murine IL-1 beta genes. The deletion of 162 nucleotides did not result in a frame shift but spliced out the putative exon 5 of the IL-1 beta gene which includes the cleavage site for the IL-1 beta converting enzyme (ICE) in human and murine IL-1 beta. Expression of the alternatively spliced IL-1 beta transcript in PBMC was also detected after stimulation with other compounds. These results clearly indicate the existence of an alternatively spliced IL-1 beta transcript in equine PBMC.

Alternative Splicing↗
PubMed1996

Potent inhibition of spontaneous rhythmic contraction by a novel beta 2-adrenoceptor agonist, HSR-81, in pregnant rat uterus.

We examined the effect of HSR-81 ((-)-(R)-alpha-[(tert-butylamino)methyl]-2-chloro-4-hydroxybenzyl alcohol L-tartrate), a newly developed, potent and selective beta 2-adrenoceptor agonist, as well as ritodrine and isoproterenol, on the spontaneous rhythmic contraction in uteri isolated from late pregnant, middle pregnant and non-pregnant (dioestrous and oestrous) rats. The three agonists inhibited the spontaneous rhythmic contraction at all the stages in a concentration-dependent manner. The pD2 value for HSR-81 was greater in late pregnancy than in dioestrus and oestrus. In the uterine preparations of late pregnancy and dioestrus, ICI-118,551 (1-(7-methylindan-4-yloxy)-3-isopropyl-aminobutan-2-ol , a selective beta 2-adrenoceptor antagonist) and atenolol (a selective beta 1-adrenoceptor antagonist) produced a parallel rightward shift of the concentration-response curves for HSR-81. The pKB values for ICI-118,551 and atenolol suggest that the inhibitory effect of HSR-81 was mediated through beta 2-adrenoceptors in the two stages. In the membranes prepared from rat uteri in late pregnancy and dioestrus, the equilibrium dissociation constant for [125I]iodocyanopindolol binding was not significantly different between the two stages. The three beta-adrenoceptor agonists and the two antagonists competed for the specific [125I]iodocyanopindolol binding and the pKi values were not significantly different between the two stages. However, the maximum number of binding sites was significantly greater in late pregnancy than in dioestrus. The configuration of the competition curves and the pKi values for the two antagonists confirmed the fact that these membranes contain predominantly beta 2-adrenoceptor subtype. These results indicate that the potent inhibition of the spontaneous rhythmic contraction by HSR-81 in the pregnant uterus may be due to the increased number of beta 2-adrenoceptors.

Adrenergic beta-2 Receptor Agonists↗
PubMed1996

New method for evaluation of hard contact lens materials with regard to cell injury by dynamic contact.

To establish a new method for evaluation of contact lens materials, we studied the porcine endothelial cell injury caused by dynamic contact (rotatory rubbing) with three kinds of hard contact lenses (HCL). The HCLs used were 1) PMMA HCL, 2) oxygen-permeable HCL composed of a graft copolymer of dextran derivative and methylmethacrylate (MMA) (Suncon Mild II, 12 Dk), and 3) oxygen-permeable-HCL composed of a copolymer of a monomer containing silicone, a monomer containing fluorine, and MMA (RGPL-A, 216 Dk). Cell injury rates were significantly different among these HCLs (Suncon Mild II < PMMA < RGPL-A) although there were no differences in rotatory rubbing forces. The smoothness of HCL surface, the qualities of injured cell layers observed by scanning electron microscopy, and the water wettability of HCLs were not correlated with cell injury rate. These results suggest that physicochemical properties of materials other than rotatory rubbing force, smoothness, and water wettability were involved in the cell injury. Our evaluation method for biomaterials that injure the corneal endothelial cells by dynamic contact should be very useful for the development of biomaterials or medical devices, including HCLs and intracardiac and urethral catheters.

Animals↗
PubMed1996

Correlation between spinal cord blood flow and arterial diameter following acute spinal cord injury in rats.

Simultaneous measurements of spinal cord blood flow and arterial diameter at areas adjacent to a site of spinal cord injury were carried out to determine changes in CO(2) reactivity and autoregulation. The spinal cord injury was made at T10 level by the epidural clip compression method. A spinal window was drilled at an area either 7 mm caudal or 7 mm rostral to the injury site for the measurement of spinal cord blood flow and arterial diameter at the same time. Spinal cord blood flow was decreased at both spinal windows, especially at the rostral window. Arterial diameter was also decreased significantly at both sites. The ischaemic zone evaluated histologically tended to expand more diffusely in the rostral direction than in the caudal direction. In the pre-injury stage, both CO(2) reactivity and autoregulation were present in the spinal cord. Following the clip injury, CO(2) reactivity and autoregulation were both impaired in the areas 7 mm adjacent to the impact site. Correlation coefficients suggested that the rostral spinal cord tended to sustain more injury than the caudal spinal cord. The histologically proven spinal cord ischaemia following the injury may have resulted from the decreased arterial diameter and impaired CO(2) reactivity and dysautoregulation of the spinal cord.

Animals↗
PubMed1996

Transient reperfusion with acidic solution affects postischemic functional recovery: studies in the isolated working rat heart.

This isolated working rat heart study was designed to investigate the effect of duration of reperfusion and degree of acidity of the reperfusate on myocardial protection. The experimental time course was as follows: 20 minutes of perfusion with the heart working, 3 minutes of infusion with the St. Thomas' Hospital cardioplegic solution followed by global ischemia for 33 minutes at 37 degrees C, and 20 minutes of Langendorff reperfusion followed by 20 minutes of working perfusion. During the initial 3 minutes of Langendorff reperfusion, the pH of the reperfusate was changed to 5.6, 6.8, and 7.5 by addition of sodium hydroxide into Krebs-Henseleit nonbicarbonate HEPES buffer. A respiratory acidic reperfusate was used for the initial 0.5, 1, 2, 3, 5, and 15 minutes during reperfusion. The results were as follows: (1) Reperfusion with a mildly acidic solution (i.e., pH 6.8) yielded better recovery than reperfusion with solutions having pH levels of 5.8 or 7.5. (2) Reperfusion for less than 3 minutes with a reperfusate having a pH level of 6.8 provided better recovery, although reperfusion for longer than 3 minutes exacerbated reperfusion injury. In conclusion, the effects of reperfusion with acidic solution were influenced by degree and duration with biphasic response characteristics.

Analysis of Variance↗