Propofol suppressed electromyographic fibrillation potentials in a patient with amyotrophic lateral sclerosis.
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Biomedical subjects
Publications and source records attributed to T Saitoh.
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The effects of hirsutine, an indole alkaloid from Uncaria rhynchophylla MIQ. JACKSON with antihypertensive, negative chronotropic and antiarrhythmic activity, and its C3 structural epimer, dihydrocorynantheine, on membrane potentials of rabbit sino-atrial node and guinea-pig right ventricle and left atrium were studied with microelectrode techniques. In sino-atrial node preparations, hirsutine and dihydrocorynantheine (0.1 microM to 10 microM) concentration-dependently increased cycle length, decreased slope of the pacemaker depolarization (phase 4 depolarization), decreased maximum rate of rise and prolonged action potential duration. In atrial and ventricular preparations, both compounds (0.1 microM to 30 microM) concentration-dependently decreased maximum rate of rise and prolonged action potential duration. These results indicate that hirsutine and dihydrocorynantheine have direct effects on the action potential of cardiac muscle through inhibition of multiple ion channels, which may explain their negative chronotropic and antiarrhythmic activity.
The active-oxygen scavenging activity of 70 traditional herbal medicines used in China and Japan as nourishing tonics were evaluated by electron spin resonance (ESR) technique, in order to evaluate their effectiveness for anti-aging and to search for new active-oxygen scavengers from natural resources. Most of the 70 herbal medicines showed scavenging activity with various intensities. Areca catechu (methanol extract), Dendrobium plicatile (methanol extract), Juglans regia (water extract), Paeonia lactiflora (methanol extract), Psychotria serpens (water and methanol extracts), Rhodiola sacra (water and methanol extracts) and Uncaria rhynchophylla (water extract) especially showed strong scavenging activity against superoxide anion radical (*O2-), while J. regia (water and methanol extracts), Morus alba (water extract) and Schisandra chinensis (water extract) revealed strong scavenging activity against hydroxyl radical (HO*). In addition, the active-oxygen scavenging activities of 19 compounds isolated from R. sacra were also examined, and hydroquinone (1), caffeic acid (3), protocatechuic acid (6), gallic acid (7), (-)-epigallocatechin 3-O-gallate (8), 3-O-galloylepigallocatechin-(4beta-->8)-epigallocatechin+ ++ 3-O-gallate (10), heterodendrin (17) and gallic acid 4-O-beta-D-glucopyranoside (19) were found to show mild or strong inhibitory activity against superoxide anion radical (*O2-), while 4-hydroxybenzoic acid (2), 3, 4-hydroxycinnamic acid (4), 6-8 and 19 inhibited hydroxyl radical (OH*). These active-oxygen scavengers may contribute, to different extents, to their anti-aging action.
Thromboxane (TX) A2 is an important bronchoconstrictor in the pathogenesis of asthma. Seratrodast, known as AA-2414, is a new oral TXA2 receptor antagonist which is currently prescribed in asthma therapy in Japan. However its clinical effects have been very different in individual subjects. To assess whether the clinical efficacy of TXA2 antagonist is predictable on the basis of urinary arachidonic acid metabolites in urine of patients with asthma, an open and multicentre trial was conducted. Fifty adult asthmatic subjects (women/men = 28/22) were enrolled [resting mean forced expiratory volume in 1 sec (FEV1)% was 82%; range, 50-96%]. Urinary levels of 11-dehydro-TXB2, leukotriene (LT) E4, 2,3-dinor-6-keto-prostaglandin F1alpha and creatinine in 3-h urine collected in the morning at the start of seratrodast (80 mg day(-1), once a day at evening for 4 weeks) were measured. Responders were defined by improvements of asthma symptoms score and peak expiratory flow rate (PEFR). Of the 50 subjects, 45 completed this study. Eighteen patients were responders and the other 27 were nonresponders. There were no significant differences between the two groups in patients' characteristics, baseline lung functions, treatments and baseline urinary eicosanoids. The 11-dehydro-TXB2/LTE4 ratio of responders was significantly higher (P = 0.0091) than that of non-responders (mean +/- SE, 7.49+/-0.71 vs. 5.09+/-0.67). Eleven patients out of 18 responders agreed to continue this drug for 6 months, the 11-dehydro-TXB2/LTE4 ratio decreased during this period, but not significantly. Our data demonstrated that responders and non-responders to TXA2 receptor antagonist existed in patients with asthma, and it suggests that the ratio of urinary eicosanoids might be a possible predictor of the effects of TXA2 receptor antagonist.
Human glioma cell line, Onda 10 produces TGF-beta1. TGF-beta1 has a biological role for the immunosuppression of the host. We have investigated whether suppression of TGF-beta1 on human glioma cell enhanced the susceptibility to lymphokine-activated killer (LAK) cells. In vitro, susceptibility to LAK cells on Onda 10 cell is augmented by retroviral gene transfection with antisense TGF-beta1. Nude mice bearing Onda 10 cells transduced with antisense TGF-beta1 gene has a longer life span compared to mice carrying that of sense TGF-beta1 gene or vector alone. The cytotoxic activity of LAK cells induced from spleen cells of mice carrying antisense TGF-beta1 gene transduced cells is higher against Onda 10 cell than that of LAK cells from mice carrying vector alone transduced cells. Also, antisense TGF-beta1 gene transduced cells are much more sensitive to LAK cells compared to Onda 10. These suggest that the augmented host systemic immunity in mice is one of the mechanisms of the reduced tumorigenicity of antisense TGF-beta1 gene transduced cells and that the increased systemic immunity could be ascribed to the increased immunogenicity of the tumor cells. The gene therapy for malignant glioma with antisense TGF-beta1 gene is expected to be promising.
It has been suggested that vitamin B12 (vit.B12) plays an important role in immune system regulation, but the details are still obscure. In order to examine the action of vit.B12 on cells of the human immune system, lymphocyte subpopulations and NK cell activity were evaluated in 11 patients with vit.B12 deficiency anaemia and in 13 control subjects. Decreases in the number of lymphocytes and CD8+ cells and in the proportion of CD4+ cells, an abnormally high CD4/CD8 ratio, and suppressed NK cell activity were noted in patients compared with control subjects. In all 11 patients and eight control subjects, these immune parameters were evaluated before and after methyl-B12 injection. The lymphocyte counts and number of CD8+ cells increased both in patients and in control subjects. The high CD4/CD8 ratio and suppressed NK cell activity were improved by methyl-B12 treatment. Augmentation of CD3-CD16+ cells occurred in patients after methyl-B12 treatment. In contrast, antibody-dependent cell-mediated cytotoxicity (ADCC) activity, lectin-stimulated lymphocyte blast formation, and serum levels of immunoglobulins were not changed by methyl-B12 treatment. These results indicate that vit.B12 might play an important role in cellular immunity, especially relativing to CD8+ cells and the NK cell system, which suggests effects on cytotoxic cells. We conclude that vit.B12 acts as an immunomodulator for cellular immunity.
The acute phase response (APR) was induced by five separate intravenous (i.v.) injections of Escherichia coli lipopolysaccharide (LPS, 17 microg/kg each time) in rabbits, with intervals of 1 h. This model was used to study the effects of APR on the activities of hepatic microsomal cytochrome P450 (CYP)-dependent enzyme including drug metabolism. Five female rabbits were included in each of four groups, a control group and three LPS-treated groups (group I, II and III). The rabbits of the control, group I, II and III were killed at 1, 1, 3 and 7 days after saline (control only) or the LPS injection, respectively. The APR was confirmed by increases in rectal body temperature, plasma concentrations of interleukin-6 and C-reactive protein (CRP). Pharmacokinetics of antipyrine before death were examined in every group. Antipyrine was administered (5 mg/kg) at 24 h (control and group I), 3 days (group II) and 7 days (group III) after the first LPS injection. Total body clearance (Cl(tot)) of antipyrine tended to decrease in group I. All the livers were excised for measuring CYP-dependent activities. Total CYP content and several CYP-dependent activities (aminopyrine N-demethylation, aniline 4-hydroxylation and caffeine 3-demethylation) decreased in group I. The maximum velocity (Vmax) values of those enzymes, and the amount of CYP1A1/1A2 and CYP2E1 apoproteins appeared to decrease. Michaelis constant (Km) values of those enzymes were not affected by the APR. Rectal body temperature recovered to normal at 3 days after the first LPS injection in group II and III. The concentration of CRP, albumin, total CYP content and the plasma clearance of antipyrine returned to the control levels at 7 days after the first LPS injection. These results suggest that the metabolism of drugs, including CYP-dependent drug metabolizing activity, is suppressed markedly in incipient APR induction in rabbits, and the drug metabolizing capacity is returned to normal at 7 days after APR induction.
To simplify liver support using an ex vivo perfused liver, an isolated pig liver was perfused with arterial blood from the recipient pig while monitoring the metabolic capacity of the ex vivo perfused liver. It was possible to perfuse the isolated liver for more than 24 h using arterial blood from a pig with ischemic liver failure. The viability of the isolated liver during support from the liver failure pig was well maintained as evidenced by the high adenylate energy charge (0.815) and a constant ketone body ratio (KBR) of over 1.0 sampled from the hepatic vein. Oxygen consumption (mean, 29.0 microl/min/g of liver) and bile production (mean, 24.2 microl/h/g of liver) were significantly higher in the isolated liver connected to the liver failure pig than in the organ connected to the pig without liver failure (15.5 microl/min/g and 7.3 microl/h/g, respectively). These findings suggest that this liver support system has sufficient metabolic capacity to support a failed liver. Further studies may provide the experimental basis necessary for the clinical application of this device in treatment of patients with acute liver failure.
An N-acetylglucosamine (GlcNAc)/N-acetylneuraminic acid-specific lectin from the fruiting body of Psathyrella velutina (PVL) is a useful probe for the detection and fractionation of specific carbohydrates. In this study, PVL was found to exhibit multispecificity to acidic polysaccharides and sulfatides. Purified PVL and a counterpart lectin to PVL in the mycelium interact with heparin neoproteoglycans, as detected by both membrane analysis and solid phase assay. The pH-dependencies of the binding to heparin and GlcNAc5-6 differ. The heparin binding of PVL is inhibited best by pectin, polygalacturonic acid, and highly sulfated polysaccharides, but not by GlcNAc, colominic acid, or other glycosaminoglycans. Sandwich affinity chromatography indicated that PVL can simultaneously interact with heparin- and GlcNAc-containing macromolecules. Extensive biotinylation was found to suppress the binding activity to heparin while the GlcNAc binding activity is retained. On the other hand, biotinyl PVL binds to sulfatide and the binding is not inhibited by GlcNAc, N-acetylneuraminic acid, or heparin. These results indicate that PVL is a multi-ligand adhesive lectin that can interact with various glycoconjugates. This multispecificity needs to be recognized when using PVL as a sugar-specific probe to avoid misleading information about the nature of glycoforms.
The morphology of myeloma cells is reported to be one of the prognostic factors in multiple myeloma (MM) patients. We analyzed the prognostic factors, including morphological classification, in 292 patients with MM in order to select poor-risk patients who should be considered candidates for early intensive chemotherapy, including stem cell transplantation. Multivariate analysis was applied to 90 patients diagnosed between 1989 and 1996, because serum beta-2-microglobulin (beta2M) has been measured regularly since 1989, and showed that serum albumin, serum beta2M, and the morphology of myeloma cells predicted survival. According to these factors, patients were divided into 3 risk groups; a high-risk group (14%), a intermediate-risk group (46%) and a low-risk group (40%). There were significant differences between survival times in these 3 groups (median survival: high-risk, 16; intermediate-risk, 22; and low-risk, 44 months).
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Although the use of corticosteroid (CS) eye drops of the use of eye washing by artificial tears was effective for the prevention of ocular toxicity such as keratitis and photophobia in the high-dose cytosine arabinoside (Ara-C) therapy, the toxicity was not prevented perfectly. We studied the effects of the rational use of CS eye drops, and the combined use of CS eye drops and eye washing by physiological saline in order to prevent the ocular toxicity. Before the study, the instillation of 0.1% sodium bethamethazone phosphate (BM) eye drops was carried out at 4-6 times per day during the high-dose Ara-C therapy, and continued for several days after the high-dose Ara-C therapy. However, the rational use of "eyelid closure" and "naso-lacrimal occlusion" after the instillation was not performed Consequently, the ocular toxicity was observed in 3 (19%) of 16 cases of the patients. When the instillation of BM eye drops at 4 times per day was carried out rationally according to the consultation of pharmacist during the high-dose Ara-C therapy and for additional 10 days after the therapy, no ocular toxicity was observed in all cases (0 of 6 cases). Furthermore, the combined use of eye washing by physiological saline and instillation of BM eye drops was effective for the decrease of the risk of ocular toxicity, because no ocular toxicity was observed in the high-dose Ara-C therapy (0 of 34 cases). Our procedure in this study would be effective for the prevention of ocular toxicity in the high-dose Ara-C therapy.
To clarify the mechanism and the predictors of the reduction in left ventricular mass (LVM) induced by antihypertensive drugs, forty hypertensive patients were classified according to the presence of left ventricular hypertrophy (LVH) as a defined by echocardiographic LVM findings (LVH group: 27 patients, non-LVH group: 13 patients) and according to the presence of negative U-waves (NU) (NU group: 10 patients, non-NU group: 30 patients). Negative U-waves appeared in the LVH group only (10 of 27 patients). The hemodynamic determinants were investigated as a mechanism of LVM reduction in 38 of these patients who were treated for 2 years with antihypertensive drugs. In the LVH group, thickness of interventricular septum (IVST), posterior wall thickness (PWT) and LVM increased significantly compared to the non-LVH group. In the NU group, the left ventricular end-diastolic dimension (LVDD) was significantly larger and the relative wall thickness was significantly smaller compared to the non-NU group in the LVH group, with no difference in LVM between the two groups. Negative U-waves disappeared in all cases after treatment. Significant decreases in LVDD and LV wall thickness were observed in the NU group and significant decrease in LV wall thickness in the non-NU group. LVM index was reduced by 24.0% in the NU group and 9.5% in the non-NU group. The disappearance of negative U-waves was an independent predictor of the reduction of LVH.
A case of a 66-year-old Japanese man developed therapy-related megakaryoblastic leukemia with pituitary involvement after chemotherapy for non-Hodgkin's lymphoma. Alkylating agents had been administered for the treatment of non-Hodgkin's lymphoma and 6 years later, megakaryoblastic leukemia with myelofibrosis and myelodysplasia developed. The blast cells expressed CD41, and immature antigens also. These findings were compatible with therapy-related megakaryoblastic leukemia. An autopsy revealed blast-cell infiltration into multiple organs including the posterior pituitary lobe. Therapy-related megakaryoblastic leukemia is very rare, and pituitary involvement may be associated with immaturity of blast cells.
OBJECT: Cervical flexion myelopathy is a rare condition that mainly affects adolescent boys. In recent years, avoidance of neck flexion has been advocated as the treatment for cervical flexion myelopathy, and treatment with a cervical collar and surgery in which fusion of the cervical spine is performed have been found to be effective. However, previously reported series contained only a limited number of patients. The authors report their experience with treating 10 male patients in whom surgery was performed to correct cervical flexion myelopathy, and they evaluate the patients' surgical outcome. METHODS: The authors performed anterior decompressive surgery and fusion in the cervical spine by using a long bone graft after resection of one or two vertebrae in seven patients. The other three patients underwent posterior fusion of four or five laminae. After surgery, symptom progression was stopped in all patients, muscle strength improved in seven, and sensory disturbance was alleviated in another two. However, the muscular atrophy in the upper extremities, which was evident in nine patients preoperatively, improved in only two. CONCLUSIONS: Because some neurological improvement was seen in nine of 10 patients, it is believed that surgical fusion of the cervical spine is an effective treatment for patients with cervical flexion myelopathy.
The presence of mutations around the A beta sequence in APP provides strong argument for the involvement of APP, and A beta in particular, in pathogenesis of Alzheimer's disease (AD). In vitro studies demonstrated that A beta may cause neuronal death, supporting the hypothetical involvement of A beta in neurodegeneration in AD. However, concentrations of A beta required for neuronal death are nonphysiologically high. Nevertheless, the predominant idea in the field is that it is sufficient to postulate A beta as a major culprit in AD development. The question we pose is whether the potentially important involvement of A beta precludes the etiological (primary) involvement (not pathological, i.e., secondary) of APP functions. We do not have an adequate answer to this question. Current knowledge about APP functions indicates that APP is critically required for the maintenance of neuronal and synaptic structure and function. Because AD is a disease of neuronal and synaptic deterioration, APP may be involved during the course of AD pathogenesis, perhaps secondarily. To ponder the question whether APP may be etiologically involved in AD, much needs to be learned about APP functions. This article is intended to provide a foundation for this challenging task.
A 64-year-old woman had been given a diagnosis of Ph-positive chronic myelogenous leukemia (Ph+ CML) in October 1992 and accordingly treated with interferon-alpha busulfan, and hydroxyurea. She was admitted to our hospital with a one-day history of consciousness disturbance on May 30, 1993. Two weeks before admission, she had received chemotherapy consisting of vincristine and predonisolone because of progressive thrombocytopenia, basophilia, and leukocytosis accompanied by a heightened degree of cell immaturity in peripheral blood and bone marrow. Cranial computerized tomography on admission disclosed tumoral masses in the left frontal lobe and the right temporal lobe. Moreover, lumbar puncture ezinkns disclosed blastoid cells in cerebrospinal fluid. Based on these laboratory findings, the diagnosis was blastic crisis CML, 46XX t(9; 22; 17) (q34; q11; q23), cytogenetic aberration and extramedulary brain disease Although the patient underwent the same combined chemotherapy again, her unconsciousness did not resolve. She died of cerebellar herniation on the 7th hospital day. Post mortem examination revealed three extramedullary tumors localized in cranial dura. This was a rare case of CML presenting multiple extramedullary tumors localized in cranial dura.
We successfully anesthetized an 80-year-old female for Pringle maneuver which was applied at the time of liver transection and consisted of cross-clamping the hepatoduodenal ligament for 25 minutes and releasing the clamp for 2 minutes until the completion of the liver transection. Anesthesia chosen was total intravenous anesthesia with propofol, fentanyl and ketamine (PFK) in combination with epidural anesthesia. The plasma concentrations of propofol at pre-, intra-, and post-Pringle maneuver under the intravenous infusion of propofol at 3 mg.kg-1.h-1 were 0.84, 1.49, and 1.29 micrograms.ml-1, respectively. All operative procedures were done uneventfully and recovery from anesthesia was prompt after the end of propofol infusion. Transient increases in liver enzymes were seen during early postoperative period, but no signs of hepatic failure were observed. In this patient, PFK anesthesia was useful and safe for the liver transection with Pringle maneuver.