Biomedical subjects
Publications and source records attributed to S Karasawa.
Explore the source record for details and available documents.
4,4'-Bis(N-tert-butyloxylamino)-2,2'-bipyridine (4) and its 1:1 complexes with bis(hexafluoroacetylacetonato)manganese(II), -copper(II), and -zinc(II) were prepared. An X-ray structure analysis of free ligand 4 reveals that the molecule has a trans conformation with Ci symmetry and the aminoxyl radical center has a short contact of 2.36 A with one of the neighboring molecules. The three 1:1 complexes have mutually similar molecular structures in which the 2,2'-bipyridine moiety has a cis conformation and serves as a bidentate ligand and coordination geometry around the metal atom is a distorted octahedron. The EPR experiments for free ligand 4 and [Zn(hfac)2.4] in frozen solution suggested that the exchange couplings between the two aminoxyls (R) through the 2,2'-bipyridine rings are antiferromagnetic with JR-R/kB = -19.3 +/- 0.5 and -24.3 +/- 0.4 K, respectively. Isosceles triangular three-spin models were applied to the 1:1 magnetic metal complexes to give JR-M/kB = -19.1 +/- 0.2 K and JR-R/kB = -32.9 +/- 0.3 K for [Mn(hfac)2.4] and JR-M/kB = +73 +/- 18 K and JR-R/kB = -24.5 +/- 6.5 K for [Cu(hfac)2.4].
BACKGROUND: Intravenous administration of N-methyl-D-aspartate (NMDA) receptor antagonists and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor antagonists reportedly reduce the minimum alveolar anaesthetic concentration (MAC) for inhalation anaesthetics. If pain perception can be prevented by the intrathecal administration of antinociceptive receptor antagonists, these agents may reduce the requirements for inhalation anaesthetics. We studied the effect of intrathecal administration of an AMPA/kainate receptor antagonist, a metabotropic glutamate (mGlu) receptor antagonist and co-administration of NMDA and a neurokinin-1(NK-1) receptor antagonist drugs at low doses on the MAC. METHODS: After Wistar rats (n=36) were fitted with indwelling intrathecal catheters, the MAC of isoflurane was determined following intrathecal administration of a non-NMDA receptor antagonist (CNQX) at 10 microg, a mGlu receptor antagonist (AP3) at 10 microg, or a combination of NMDA receptor antagonist (APV) at 0.01 microg to 1 microg with NK-1 receptor antagonist (CP96345, CP) at 0.1 microg to 10 microg. Subsequently, a reversal dose of intrathecal NMDA with substance P (SP) was administered, and the MAC of isoflurane was redetermined. Conscious rats (n=15) were also examined for the presence of locomotor dysfunction following the intrathecal co-administration of APV and CP. RESULTS: Neither CNQX nor AP3 reduced the MAC of isoflurane. APV at 0.01 microg plus CP at 1 microg, as well as APV at 0.1 microg plus CP at 10 microg, reduced the MAC of isoflurane, with respective reductions of 7.6% and 14%; (P<0.05). Co-administration of NMDA plus SP reversed the decrease in the MAC of isoflurane. Locomotive activity was not changed. CONCLUSIONS: The NMDA receptor and the NK-1 receptor are important determinants of the MAC of isoflurane, exerting this influence by inhibition of pain transmission in the spinal cord, while mGlu and AMPA receptors have no effect on the MAC of isoflurane.
We examined the antinociceptive effect of intrathecally administered magnesium sulphate (MgSO4) in rats, using acute pain models including mechanical pressure, heat and subcutaneous formalin injection. According to the locomotion test 10 microliters of 6.2% MgSO4 did not produce motor paralysis. At the same dose, responses to pressure and heat were intact, compared with controls given saline. MgSO4 produced depression of pain responses only after the first 10 min in the formalin test. Our studies indicated that MgSO4 did not show remarkable antinociceptive effects in acute pain models.
Previously, we reported that human T cell leukemia virus type-1 env-pX region-introduced transgenic (pX-Tg) mice develop an inflammatory polyarthropathy. Although autoimmune pathogenesis was suggested, the detailed mechanisms remain to be elucidated. In this report, we examined effects of the MHC and fas genes on the development of the disease. When pX-Tg mice were backcrossed with different inbred strains, the incidence of arthritis differed among strains; 64% and 72% in BALB/cAn (H-2d), 25% and 46% in C3H/HeN (H-2k), and 0% and 2% in C57BL/6J (H-2b) background at 3 and 6 months of age, respectively. Rheumatoid factor levels in the serum correlated with the susceptibility to the disease, whereas IL-1beta and MHC gene expression were similarly elevated in all of these strains, suggesting involvement of immune regulatory genes in this strain difference. However, introduction of the H-2d locus into C57BL/6J pX-Tg mice did not increase the incidence of arthritis, and substitution of the BALB/cAn H-2 locus with the H-2b did not decrease it. The results indicate that the H-2 locus is not the major determinant of the disease. Then, since previous study indicated a defect in Fas-mediated apoptosis of transgenic T cells, the effects of fas gene modification on the disease were examined. The incidence increased when these pX-Tg mice were crossed with lpr/lpr mice, while it decreased when crossed with fas-transgenic mice. These observations suggest that aberration of Fas-mediated apoptosis of peripheral lymphocytes, rather than negative selection in the thymus, is involved in the development of autoimmune arthropathy in pX-Tg mice.
4-Hydroxyestrone N-acetylcysteine conjugate (4-OHE1-2SR) is considered to be an important compound for monitoring the in vivo formation of catechol estrogen quinones, an intermediary in estrogen carcinogenicity. This article describes the selective synthesis of isomeric monomethyl ethers of 4-OHE1-2SR utilizing the formation of a seven-membered ring lactone by dehydration with acetic anhydride. Using these authentic specimens, enzymic and chemical O-methylation were examined. Enzymic O-methylation, using a rat liver cytosolic fraction, of 4-OHE1-2SR gave its 3-methyl ether as the sole product, while preferential O-methylation of 4-hydroxyestrone (4-OHE1) at the C-4 position was confirmed under the same conditions. Methylation of 4-OHE1-2SR with diazomethane gave initially carboxylate methylation, then the corresponding 3-methyl ether almost exclusively, while methylation of 4-OHE1 also gave its 3-methyl ether preferentially. However, much more rapid formation of the 3-methyl ether was observed with 4-OHE1-2SR than with 4-OHE1 itself. These results show that the hydroxy group at the C-3 position of 4-OHE1-2SR is more reactive than that at the C-4 position, both chemically and enzymatically.
Somatosensory evoked potential, locomotion and vocalisation upon tail pinch in rats was studied in order to determine whether intrathecal magnesium sulphate administration causes spinal anaesthesia. In Wistar rats with indwelling intrathecal catheters, cortical somatosensory evoked potential was recorded following stimulation via electrodes inserted into the hind paw under chloral hydrate anaesthesia before and after intrathecal administration of 10 microliters of either magnesium sulphate (12.3% or 24.6%) or lignocaine (4% or 8%). Locomotion and vocalisation after tail pinch were tested following intrathecal administration of the same two drugs in conscious rats. Somatosensory evoked potential amplitude was diminished after administration of lignocaine (p < 0.05) but did not change after magnesium sulphate. Latency of P1 was increased by lignocaine and by magnesium sulphate 12.3% (p < 0.05). Although lower extremity paralysis was observed in both groups, its duration with magnesium sulphate was much longer than with lignocaine. Vocalisation was recognised after magnesium sulphate 12.3%, but was not observed after lignocaine 8% during paralysis (p < 0.05). We believe that magnesium sulphate caused motor paralysis, but not complete analgesia.
Transgenic mice carrying the env-pX region of human T lymphocyte virus type I (HTLV-I) develop autoimmune arthropathy in high incidence. Adopting the approach that Fas-mediated apoptosis has a critical function in the elimination of self-reactive T cells, we examined the involvement of this apoptosis in the induction of autoimmunity in HTLV-I transgenic mice. Splenic T cells derived from the transgenic mice were more resistant to apoptosis induced by anti-Fas mAb than those of the nontransgenic mice, whereas no appreciable difference in apoptosis was detected for thymocytes from either mouse's type. The resistance of transgenic T cells may be due to Tax coded in the pX region, since Tax mediates the inhibition of anti-Fas- induced apoptosis in mature T cell line, Jurkat. Among the transgenic mice, the extent of the resistance to Fas-mediated apoptosis was further enhanced in transgenic T cells with disease. These results suggest that the escape of self-reactive T cells from Fas-mediated apoptosis in the periphery, is critical for the development of autoimmune arthropathy in HTLV-I transgenic mice.
PURPOSE: To study the effects of intrathecal administration of a neurokinin-I(NK-I) receptor antagonist (CP96,345) on the minimum alveolar anaesthetic concentration (MAC) of isoflurane in anaesthetized rats, and on the locomotive activity of conscious rats. METHODS: Wistar rats (n = 36) were fitted with indwelling intrathecal catheters, and the MAC of isoflurane was determined following the intrathecal administration of saline (control group) or the NK-I receptor antagonist CP96,345 (CP) at 1, 10 and 100 micrograms. Subsequently a reversal dose of intrathecal Substance P (SP) at 1, 10 and 100 micrograms was administered and MAC isoflurane was redetermined. Conscious rats (n = 35) were also examined for the presence of locomotor dysfunction following intrathecal administration of CP and SP. Animals were randomly assigned to each treatment group and the investigators were blinded. RESULTS: CP at 10 and 100 micrograms reduced MAC isoflurane by 9.9% and 15.3%, respectively (P < 0.05). Intrathecal administration of SP reversed the decreases in MAC by CP; however, locomotive activity was not changed. CONCLUSION: These results suggest that the NK-1 receptor plays an important role in determining the MAC of isoflurane by inhibition of pain transmission in the spinal cord.
We have studied the effects of hydrocortisone and adrenaline on natural killer (NK) cell activity and on the distribution of circulating lymphocyte subpopulations in 30 patients undergoing elective partial laminectomy under general anaesthesia. The patients were allocated to receive adrenaline (group 1, n = 11), hydrocortisone and adrenaline (group 2, n = 11) or neither hydrocortisone nor adrenaline (group 3, n = 8). Group 1 and group 2 patients received local adrenaline infiltration during operation to reduce bleeding. The mean dose of adrenaline administered was 2.1 (SD 0.2) microgram kg-1. Group 2 received hydrocortisone 10 mg kg-1 i.v. after premedication. In groups 1 and 2, adrenaline produced an instantaneous increase in NK cell activity accompanied by a selective increase in circulating NK cells. The measurements returned to pre-infiltration levels within 120 min of administration of adrenaline. The effect of adrenaline in causing increased NK cell activity was not blocked by pre-administration of hydrocortisone. There was a significant decrease in the ratio of T-helper/inducer cells (CD4) to T-suppressor/cytotoxic cells (CD8) in all patients after induction of anaesthesia. In groups 1 and 3, the CD4/CD8 of anaesthesia. In groups 1 and 3, the CD4/CD8 cell ratio did not change significantly during operation. However, compared with groups 1 and 3, group 2 showed a significantly reduced CD4/CD8 cell ratio during operation. Therefore, these results suggest that even in cases of such severe stress that the immune response was depressed by increased serum cortisol concentrations, adrenaline-induced NK cell activity enhancement was preserved.
We have studied the effects of dobutamine on natural killer (NK) cell activity and the distribution of lymphocyte subpopulations in peripheral blood in 16 patients under general anaesthesia. Patients were allocated to receive either dobutamine (n = 9) or isotonic saline (n = 7) for 30 min. There was a significant decrease in the ratio of T-helper/inducer cells (CD4) to T-suppressor/cytotoxic cells (CD8) in all patients after induction of anaesthesia. Dobutamine infusion induced an increase in NK cell activity, accompanied by a selective increase in circulating NK cells. However, compared with preinfusion values, CD4:CD8 cell ratio did not change during and after dobutamine infusion. In the isotonic saline group, NK cell activity and CD4:CD8 cell ratio remained unchanged. These results suggest that dobutamine induced an increase in NK cell activity and alterations in lymphocyte subpopulations.
We report on a female patient with bilateral acoustic neurinomas and other tumors in the central nervous system (neurofibromatosis type 2: NF2) and the constitutional translocation, t(4;22) (q12;q12.2). The precise identification of the translocation breakpoint (q12.2) on chromosome 22 implies the refined localization of a gene responsible for NF2, and would provide a clue to its molecular characterization and to the isolation of the gene. Chromosomes of a paraspinal neurinoma from the patient were also analyzed, and the same karyotype as seen in cultured peripheral lymphocytes was found. The patient's father was also a carrier of the translocation, but he had no clinical symptoms of NF2, nor did other relatives. Several explanations are offered for the different expression of the translocation between the patient and her father.
Multiple subpial transection (MST) was applied to 12 cases with intractable epilepsy, the foci of which were located in unresectable essential areas. The result proved that MST is effective in controlling seizures, and no explicit neurological deficits have incurred postoperatively.
A clinico-statistical survey was carried out on dental treatment for children under general anesthesia who visited the clinic of Pedodontic Department, Matsumoto Dental College Hospital during the period of 1986 to 1989. The number of cases subjected in this survey was 108 (57 boys 51 girls), aged from one year and 5 months to 8 years and 9 months. All of these patients were admitted to the hospital for 3 days and were treated under general anesthesia, using GOE in 107 cases (in 80 cases by nasal intubation, in 27 cases by oral intubation). One case was administrated by intravenous anesthesia with Ketamine. The results were as follows: 1. The patient ages of the patients ranged from one year 5 months to 8 years 9 months. 2. Thirteen percent of the patients were handicapped. Fifty three percent of the patients had to visit hospitals in remote areas. 3. The number of restored teeth per patient was 15 on the average. The teeth were treated with composite resin filling in 8.5 teeth, composite resin crown in 2.6 teeth, metal crown 3.6 teeth and other material in 0.8 (extraction). 4. Pulpal treatment was carried out on 42 percent of the subjected teeth. 5. The average anesthesia administration time was 3 hours and 28 minutes. No serious trouble was observed although minor complications were seen post-operatively such as high fever or vomiting in some cases.
Xanthine and uric acid, products of purine metabolism, were measured by reversed-phase high-performance liquid chromatography (HPLC) with electrochemical detection in rat forebrain following focal cerebral ischemia. Focal cerebral ischemia was induced in the rat by permanent occlusion of the left middle cerebral artery (MCA). Sprague-Dawley rats were anesthetized with halothane inhalation and left MCA was occluded via trans-retro-orbital approach. Normal and sham-operated rats were used as control animals. The animals were decapitated 2 (MCA = 5, Sham = 5), 4 (MCA = 7, Sham = 6), 8 (MCA = 5, Sham = 5), and 16 (MCA = 6, Sham = 6) hours or 1 (MCA = 5, Sham = 5), 2 (MCA = 6, Sham = 6), 7 (MCA = 7, Sham = 6), 14 (MCA = 6, Sham = 5), and 28 (MCA = 7, Sham = 5) days after the operation. The brains were removed and divided into right and left hemisphere. Each hemisphere was homogenized and centrifuged. The supernates were filtered with membrane filter. An aliquot of the filtrate was used for measurement of xanthine and uric acid in both of the ischemic and contralateral hemisphere by a HPLC system. In the normal group, xanthine and uric acid in the brain was 12.4 +/- 0.4 and 2.2 +/- 0.1 nmol/g tissue (mean +/- SEM), respectively. In the ischemic hemisphere, xanthine increased up to 57.7 +/- 5.2 nmol/g tissue 2 hours after MCA occlusion and reached a maximum value of 59.42 +/- 4.91 nmol/g tissue 4 hours following the induction of ischemia. Xanthine level was still high 8 hours after ischemia and then rapidly decreased to the normal value at day 2.(ABSTRACT TRUNCATED AT 250 WORDS)
Changes of the xanthine and uric acid (UA) levels in rat forebrain following focal cerebral ischemia were studied by reversed-phase HPLC with electrochemical detection. Focal ischemia was induced by occluding the left middle cerebral artery in the rat. The xanthine level in the normal group was 11.50 nmol/g tissue. In the ischemic group, the xanthine concentration in the ischemic hemisphere progressively increased after occlusion and reached a maximum value of 59.42 nmol/g tissue 4 h after operation. The UA level in the normal group was 2.20 nmol/g tissue, whereas in the ischemic group the UA concentration in the ischemic hemisphere gradually increased after occlusion, reaching a value of 38.53 nmol/g tissue 24 h after ischemia. The concentration of UA remained elevated in the ischemic hemisphere until 48 h after occlusion, and reached a maximum value of 38.98 nmol/g tissue. The xanthine and UA levels in the contralateral hemisphere remained unchanged. The xanthine and UA concentrations in the sham-operated group did not show a significant increase after operation. The time course of xanthine and UA levels suggests that in ischemic forebrain UA is formed from xanthine as a product of purine metabolism.
Explore the source record for details and available documents.
Explore the source record for details and available documents.