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Biomedical subjects

S Hattori

Publications and source records attributed to S Hattori.

At least 19 recordsLinked to original sources

v-Src requires Ras signaling for the suppression of gap junctional intercellular communication.

Cell transformation by v-Src causes suppression of gap junctional intercellular communication (GJIC). Although tyrosine phosphorylation of connexin43 (Cx43), a gap junctional component, appears to be necessary for the suppression, involvement of other signaling remains unclear. We investigated the role of Ras signaling in the suppression of GJIC by v-Src. Conditional expression of either S17N Ras or mtGap1m dramatically recovered GJIC in v-Src-transformed cells. Although expression of S17N Ras or mtGap1m substantially decreased the levels of active Ras, tyrosine phosphorylation of cellular proteins including Cx43 remained unchanged. Similarly, treatment of v-Src-transfomed cells with a Ras farnesyltransferase inhibitor, manumycin A, restored GJIC, whereas tyrosine phosphorylation of Cx43 remained unchanged. Thus, these results strongly suggest that, in addition to Cx43 phosphorylation, constitutive activation of Ras signaling is required for the suppression of GJIC by v-Src.

Animals↗

Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus.

Altered expression of Disrupted-In-Schizophrenia-1 (DISC1) and dysbindin (DTNBP1), susceptibility genes for schizophrenia, in schizophrenic brain has been reported; however, the possible effect of antipsychotics on the expression levels of these genes has not yet been studied. We measured the mRNA expression levels of these genes in frontal cortex and hippocampus of mice chronically treated with typical and atypical antipsychotics by a real-time quantitative RT-PCR method. We found that atypical antipsychotics, olanzapine and risperidone, in a clinically relevant dose increased DISC1 expression levels in frontal cortex, while a typical antipsychotic, haloperidol, did not. No significant effect on dysbindin expression levels was observed in either brain region. These data suggest that prior evidence of decreased expression of dysbindin in postmortem brain of schizophrenics is not likely to be a simple artifact of antemortem drug treatment. Our results also suggest a potential role of DISC1 in the therapeutic mechanisms of certain atypical antipsychotics.

Actins↗

Angiotensin-II-induced oxidative stress elicits hypoadiponectinaemia in rats.

AIMS/HYPOTHESIS: Hypertension, endothelial dysfunction and insulin resistance are associated conditions that share oxidative stress and vascular inflammation as common features. Adiponectin is an abundant plasma adipokine that plays a physiological role in modulating lipid metabolism and exerts a potent anti-inflammatory activity. We hypothesised that adiponectin levels decrease in response to oxidative stress and that this may promote the development of hypertension, endothelial dysfunction and insulin resistance. METHODS: Rats were infused with angiotensin II (AngII) or its vehicle, either alone or in combination with tempo1 (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl), a membrane-permeable metal-independent superoxide dismutase mimetic, or tetrahydrobiopterin (BH4), one of the most potent naturally occurring reducing agents and an essential cofactor for nitric oxide synthase activity. Heart rate, systolic blood pressure, body weight and serum levels of adiponectin were measured on day 7 of treatment, and then the animals were killed. Vessel tone and superoxide production were measured ex vivo in thoracic vascular rings. The expression of adiponectin mRNA in adipose tissue was assessed by Northern blotting, and in 3T3-L1 adipocytes exposed to H2O2 by real-time PCR. The expression of NAD(P)H oxidase subunit mRNAs in the rats was assessed by RT-PCR and real-time PCR. RESULTS: Hypertension and endothelial dysfunction were induced in rats by infusion of AngII and reversed by administration of tempol. Plasma concentrations of adiponectin and adipose tissue levels of adiponectin mRNA were decreased in AngII-infused rats, and this effect was prevented by cotreatment with tempol or BH4. The production of superoxide anions (O2-) was significantly increased in the aortae of AngII-treated rats, and this increase was prevented by the administration of tempol or BH4. Levels of mRNAs that encode NAD(P)H oxidase components, including p22phox, gp91phox, p47phox and Rac1, were similarly increased in adipose tissue, aortae and hearts of AngII-infused rats. Cotreatment of rats with tempol or BH4 reversed AngII-induced increases in NAD(P)H oxidase subunit mRNAs. Fully differentiated 3T3-L1 adipocytes, also exhibited diminished adiponectin mRNA levels when exposed to low concentrations of H2O2. CONCLUSIONS/INTERPRETATION: Our results demonstrate that AngII-induced oxidative stress and endothelial dysfunction are accompanied by a decrease in adiponectin gene expression. Since antioxidants were observed to prevent the actions of AngII, and H2O2 on its own suppressed adiponectin expression, we conclude that adiponectin gene expression is negatively modulated by oxidative stress. Plasma adiponectin levels may provide a useful indicator of oxidative stress in vivo, and suppressed levels may contribute to the proinflammatory and metabolic derangements associated with type 2 diabetes, coronary artery disease and the metabolic syndrome.

Adiponectin↗

Helicobacter pylori infection influences symptomatic response to anti-secretory therapy in patients with GORD--crossover comparative study with famotidine and low-dose lansoprazole.

BACKGROUND AND AIM: Helicobacter pylori infection was reported to affect gastric acid secretion. We investigated the heartburn symptoms of patients with gastro-oesophageal reflux disease during sequential treatment with 40 mg of famotidine or 15 mg of lansoprazole to clarify whether H. pylori infection influences symptomatic response to anti-secretory therapy. SUBJECTS AND METHODS: The subjects were 33 gastro-oesophageal reflux disease patients, who had already been treated with a full dose of H2 receptor antagonist. First, famotidine at 20 mg b.i.d. was administered to the patients for 8 weeks. Second, famotidine was replaced with 15 mg of lansoprazole once in the morning for 8 weeks. Finally, 20 mg of famotidine was administered b.i.d. for 8 weeks instead of lansoprazole. Gastro-oesophageal reflux disease symptoms were assessed using an original visual analogue scale. RESULTS: The sequential symptomatic responses to famotidine and lansoprazole administration indicated that gastro-oesophageal reflux disease symptoms of patients during low-dose lansoprazole treatment were significantly less than those during famotidine treatment. Remission of symptoms was obtained significantly more often by famotidine therapy in patients with H. pylori infection than in patients without H. pylori infection. CONCLUSION: Low-dose lansoprazole is more effective than full-dose famotidine for the control of symptoms in patients with gastro-oesophageal reflux disease, and H. pylori infection influences the symptomatic response to H2 receptor antagonists.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Tetraparesis due to exostotic osteochondroma at upper cervical cord in a patient with multiple exostoses-mental retardation syndrome (Langer-Giedion syndrome).

STUDY DESIGN: Case report of a severe upper cervical cord compression and tetraparesis by a massive cervical exostotic osteochondroma in a patient with multiple exostoses-mental retardation syndrome (Langer-Giedion syndrome; LGS). OBJECTIVE: To describe this very rare pathological condition and the results of surgical intervention. SETTING: Gifu, Japan. METHODS: A 23-year-old man was referred to our clinic because of progressing tetraparesis. He had previously been diagnosed with hereditary multiple exostoses and mental retardation. As he had not complained of any symptoms, his family only noticed the tetraparesis after advanced deterioration. His face possessed the pathognomic features of LGS. A postmyelogram CT scan demonstrated an exostotic mass arising from the left-side C2 pedicle with associated severe spinal cord compression. He was diagnosed with LGS. Hemilaminectomy on the left side and resection of the osteochondroma were performed. RESULTS: At 5 years postoperatively, a neurological examination showed the full return of all motor functions. The CT scan revealed no intracanalar recurrence of the tumor. CONCLUSION: In this case of severe tetraparesis due to cervical osteochondroma, decompression by hemilaminectomy provided excellent results. In patients with LGS and intracanalar osteochondroma, the neurological deficit may be masked by mental retardation. Hence, awareness of this pathological condition will help clinicians diagnose it at an early stage.

Adult↗

Globular adiponectin upregulates nitric oxide production in vascular endothelial cells.

AIMS/HYPOTHESIS: Adiponectin, also called ACRP30, is a novel adipose tissue-specific protein that has been shown to improve insulin sensitivity and to exert anti-atherogenic effects. It is known that knockout mice lacking endothelial NO synthase (eNOS) develop hypertension, insulin resistance, hyperlipidaemia, and show augmented ischaemia-reperfusion damage. Thus, we examined whether globular adiponectin activates eNOS to produce NO. METHODS: To analyze NO production in bovine aortic endothelial cells (BAE), NOx (nitrite and nitrate) was measured in the medium with an automated NO detector/high-performance liquid chromatography system. eNOS activation was assessed by phosphorylation of the enzyme and its activity was evaluated by citrulline synthesis in human umbilical vein endothelial cells (HUVEC). eNOS mRNA and protein expressions in HUVEC were evaluated by Realtime PCR and Western blot analysis. RESULTS: Gobular adiponectin increased NO production in BAE. It also caused eNOS phosphorylation and potentiated eNOS activity in HUVEC. In addition, globular adiponectin up-regulated the eNOS gene to increase protein expression in HUVEC. CONCLUSION/INTERPRETATION: Globular adiponectin increases NO production through two mechanisms, namely, by activation of eNOS enzyme activity and via an increase in eNOS expression. Activation and up-regulation of eNOS could explain some of the observed vasoprotective properties of globular adiponectin, as well as its beneficial effects on the cardiovascular system.

Adiponectin↗

Heat sensitivity of human parvovirus B19.

BACKGROUND AND OBJECTIVES: To date there has been no published report on a systematic evaluation of the heat sensitivity of human parvovirus B19 (B19) and the related safety of the plasma-derived fractionated products. In this study, we examined the heat sensitivity of B19 by using the infectivity assay with cultured cells. MATERIALS AND METHODS: The heat sensitivity of B19 was examined by measuring the reduction in viral infectivity titres after heating liquid containing B19 at 60 degrees C. Viral infectivity was assayed by detection of viral antigens or viral mRNA in infected cells. As a control, canine parvovirus (CPV) was also heat-treated. RESULTS: B19 displayed quite different inactivation kinetics to CPV when both were heated in liquid at 60 degrees C. In sharp contrast to the latter, B19 was rapidly inactivated within 1 h when the virus was suspended in 5% or 25% human serum albumin solution, phosphate-buffered saline, or complete medium. However, B19 appeared to be resistant to heat inactivation in liquid containing 60% sucrose. CONCLUSIONS: The heat sensitivity of B19 in liquid was clearly different from that of CPV. Significantly, the efficiency to inactivate B19 and reduce its infectivity following heating in liquid was mainly affected by the composition of the solutions used for virus suspension.

Antigens, Viral↗

Effect of parathyroidectomy on bone mineral density in hemodialysis patients with secondary hyperparathyroidism: possible usefulness of preoperative determination of parathyroid hormone level for prediction of bone regain.

PURPOSE: To examine longitudinal changes of bone mineral density (BMD) after parathyroidectomy (PTx) in patients undergoing maintenance hemodialysis (HD) with severe secondary hyperparathyroidism (HPT) to determine which factor contributes most to bone changes. METHODS: Fifteen Japanese HD patients who had been refractory to medical therapy were subject to PTx with autotransplantation. We measured BMD by dual energy X-ray absorptiometry (DXA) at the lumbar spine (L2 - 4 BMD) and the distal 1/3 region of the radius (1/3R BMD) at 1, 3, 6, 12, 24, and 36 months after PTx. RESULTS: Baseline Z-score of BMD was markedly low at 1/3R (- 3.07) and slightly low at L2 - 4 (-0.59) in this group. A significant increase in L2 - 4 BMD was observed as early as one month after PTx, which was sustained afterwards. Annual percent changes in L2 - 4 and 1/3R BMD were + 15.6 % and + 6.4 %, respectively. The annual percent changes in BMD at both sites were positively associated with preoperative intact PTH levels (L2 - 4; r = 0.642, p = 0.010, 1/3R; r = 0.884, p < 0.001) and total alkaline phosphatase (ALP) levels (L2 - 4; r = 0.663, p = 0.007, 1/3R; r = 0.858, p < 0.001). Stepwise multiple regression analysis revealed that serum levels of intact PTH and ALP were the best predictors of both percentage and net changes in radial BMD with high determination coefficients (r 2 > 0.8). CONCLUSION: Successful PTx following appropriate supplementation with vitamin D and calcium provides a marked increase in lumbar BMD and a modest increase in radial BMD in HD patients with secondary HPT. Preoperative levels of PTH and ALP are useful for predicting postoperative changes in bone mass.

Absorptiometry, Photon↗

Safety and efficacy of glucagon as a premedication for upper gastrointestinal endoscopy--a comparative study with butyl scopolamine bromide.

BACKGROUND: Glucagon inhibits digestive motility and is used for endoscopic premedication; however, its effect on cardiopulmonary function during endoscopy has not yet been fully investigated. AIM: To clarify the efficacy and safety of glucagon compared with butyl scopolamine bromide as upper gastrointestinal endoscopy premedication. METHODS: Two hundred and forty consecutive patients over 40 years of age, referred for upper gastrointestinal endoscopy, without any complications, were studied. These patients were randomly premedicated with butyl scopolamine bromide (SC group) or glucagon (G group). Time course changes in blood pressure, arterial oxygen saturation, heart rate and the number of retching episodes during endoscopy were examined. The efficacy of glucose tablets after upper gastrointestinal endoscopy to prevent hypoglycaemia caused by glucagon was evaluated. Cardiopulmonary parameters were also examined in 77 complicated patients with glucagon premedication (GC group). RESULTS: A continuous increase in heart rate during upper gastrointestinal endoscopy was observed in the SC group, but not in the G and GC groups. Blood pressure, arterial oxygen saturation and number of retching episodes were not different between the groups. Hypoglycaemia-related symptoms were frequent in the G group without glucose tablets, but were prevented by the administration of glucose. CONCLUSIONS: Glucagon has a weaker effect on cardiopulmonary function during upper gastrointestinal endoscopy than butyl scopolamine bromide. Glucose administration prevents hypoglycaemia-related symptoms caused by glucagon.

Aged↗

Requirement of Ras for the activation of mitogen-activated protein kinase by calcium influx, cAMP, and neurotrophin in hippocampal neurons.

Mitogen-activated protein (MAP) kinase plays important roles in the establishment of long-term potentiation both in vitro and in living animals. MAP kinase is activated in response to a broad range of stimuli, including calcium influx through NMDA receptor and L-type calcium channel, cAMP, and neurotrophins. To investigate the role of Ras in the activation of MAP kinase and cAMP response element-binding protein (CREB) in hippocampal neurons, we inhibited Ras function by overexpressing a Ras GTPase-activating protein, Gap1(m), or dominant negative Ras by means of adenovirus vectors. Gap1(m) expression almost completely suppressed MAP kinase activation in response to NMDA, calcium ionophore, membrane depolarization, forskolin, and brain-derived neurotrophic factor (BDNF). Dominant negative Ras also showed similar effects. On the other hand, Rap1GAP did not significantly inhibit the forskolin-induced activation of MAP kinase. In contrast to MAP kinase activation, the inactivation of Ras activity did not inhibit significantly NMDA-induced CREB phosphorylation, whereas BDNF-induced CREB phosphorylation was inhibited almost completely. These results demonstrate that Ras transduces signals elicited by a broad range of stimuli to MAP kinase in hippocampal neurons and further suggest that CREB phosphorylation depends on multiple pathways.

Adenoviridae↗

Effect of IL-12 encoding plasmid administration on tight-skin mouse.

The tight-skin (Tsk/+) mutant mice, a putative murine model of scleroderma, are characterized by the excessive deposition of collagen and the presence of antinuclear antibodies. Type 2 cytokines, such as IL-4 and IL-6, are capable of regulating the synthesis of various matrix molecules, including type I collagen, by fibroblasts. IL-12 is well known to induce type 1 cytokine production and to reduce type 2 activity. Here, we examined the effect of IL-12 encoding plasmid (pCAGGSIL-12) on the disease progression of Tsk/+ mice. pCAGGSIL-12 plasmid or pCAGGS parental vector was injected intramuscularly 7 times at 3 week intervals into Tsk/+ mice. One week after the last injection, pCAGGSIL-12 administered Tsk/+ mice exhibited a marked decrease in the skin thickness compared with the mice treated with pCAGGS vector. The serum levels of antinuclear antibodies were diminished in pCAGGSIL-12 treated mice. IL-4 production by spleen cells from pCAGGSIL-12 plasmid treated mice was significantly lower than that from vector treated mice. These results indicate that pCAGGSIL-12 administration into Tsk/+ mice had beneficial effects in preventing the collagen accumulation in the skin and suppressing the autoimmunity via improvement of Th1/Th2 balance. The present study suggests that the IL-12 encoding plasmid administration might have a therapeutic effect on systemic sclerosis.

Animals↗

Systematic separation and purification of elastase, gelatinase (matrix metalloproteinase 9), and collagenase (matrix metalloproteinase 8) from polymorphonuclear leukocytes in dialyzers previously used by patients with renal failure.

We developed a simple and effective method for the systematic separation and purification of human polymorphonuclear leukocyte (PMN) proteinases, elastase, gelatinase (matrix metalloproteinase 9, type IV collagenase), and collagenase (matrix metalloproteinase 8), derived from the extracts of hollow fiber dialyzers that had been utilized in the treatment of patients with renal failure. The fraction containing elastase was grossly separated from that containing gelatinase and collagenase by heparin-Sepharose chromatography and purified in an aprotinin column. The remaining two enzymes were then separated using the gelatin-Sepharose column after gel chromatography following ammonium sulfate precipitation. Gelatinase and collagenase were further purified by gelatin-Sepharose chromatography as a latent form and by collagen-Sepharose chromatography as an activated form. This novel method offers procedural advantages over existing methods that separate PMNs from the whole blood of volunteers for experimental research purposes.

Animals↗

Optimal doses of paclitaxel and carboplatin combination chemotherapy for ovarian cancer: a phase I modified continual reassessment method study.

BACKGROUND: A multicenter, phase I study of combination therapy with paclitaxel and carboplatin for epithelial ovarian cancer was conducted to determine the safety and recommended dosages for Japanese women. METHODS: Paclitaxel was administered intravenously over a 3-h period, followed by carboplatin administered intravenously over a 1.5-h period. A modified continual reassessment method (mCRM) was used in two treatment arms to establish the maximum tolerated dose (MTD) and recommended doses of the combination. In group A, the dose of paclitaxel (175 mg/m2) was constant and the dose of carboplatin was increased from 4 to 7 in terms of the target area under the plasma concentration-versus-time curve (AUC). In group B, the dose of carboplatin was constant (AUC 6) and paclitaxel was administered at two dose levels (160 and 175 mg/m2). In both groups, the carboplatin dose was limited to a maximum of 800 mg/body for each administration. RESULTS: Because the calculated probability of toxicity was greatest at a dose of paclitaxel 175 mg/m2 and carboplatin AUC 7, this dose was designated the MTD in group A. Based on this result, treatment in group B was initiated at doses of paclitaxel of 160 mg/m2 and carboplatin AUC 6. While the dose of paclitaxel was escalated to 175 mg/m2, the safety of the combination was confirmed. The most frequent adverse effect was neutropenia, which resolved promptly with the appropriate use of granulocyte-colony stimulating factor (G-CSF). No other severe hematologic or nonhematologic toxicities were observed. CONCLUSIONS: Our study demonstrated that the recommended dose for this combination regimen should be paclitaxel 175 mg/m2 plus carboplatin AUC 6 (maximum dose, 800 mg/body).

Adenocarcinoma, Clear Cell↗

Characterization, amino acid sequence and evolution of edema-inducing, basic phospholipase A2 from Trimeresurus flavoviridis venom.

Two phospholipases A2 (PLA2s) were purified from the venom of Trimeresurus flavoviridis (Crotalinae) inhabiting Tokunoshima island, Japan, and named PLA-A and PLA-B in the order of elution on a cation-exchange column. Lipolytic activities of PLA-A and PLA-B toward mixed micelles and liposomes were substantially lower than that of PLA2 (an [Asp49]PLA2) which had been isolated from the same venom. Both PLA-A and PLA-B consisted of 122 amino acids and contained aspartate at position 49 (the numbering according to the aligned sequences of PLA2s in Fig. 8), thus belonging to an [Asp49]PLA2 subgroup. PLA-A and PLA-B were identical in sequence with an exception at position 79. PLA-B contained Asn-Gly at positions 79 and 80 which are located in the beta-sheet region. On the other hand, PLA-A had beta-Asp-Gly and alpha-Asp-Gly in high and low proportion, respectively, at the corresponding positions which were produced from Asn-Gly through the base-catalyzed formation and hydrolysis of the succinimide type intermediate. Thus, PLA-A is derived from PLA-B. PLA-B is similar in sequence to PL-X, which had been purified from the venom of T. flavoviridis inhabiting Amami-Oshima island, Japan, and to PL-X', whose cDNA had been cloned from Tokunoshima T. flavoviridis venom gland, rather than PLA2. PLA-B showed strong edema-inducing activity, while PLA-A exhibited rather lower activity. The sequence around position 79 which constitutes a beta-turn segment seems to be crucial for edema-inducing activity. Phylogenetic tree of Tokunoshima T. flavoviridis venom PLA2 isozymes indicated that PLA-B and PL-X' diverged from PLA2 after branching of [Asp49]PLA2 forms and [Lys49]PLA2 forms.

Amino Acid Sequence↗

Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen.

BACKGROUND: The cytoprotective agent, ecabet sodium, inhibits urease activity and growth of Helicobacter pylori. AIM: To evaluate the efficacy and safety of ecabet sodium-based eradication of H. pylori infection, compared with a lansoprazole-based regimen, in a randomized multicentre study. SUBJECTS AND METHODS: A total of 120 H. pylori-positive patients were assigned to one of two treatment regimens for 2 weeks: ecabet sodium 1 g b.d., amoxicillin 500 mg t.d.s. and clarithromycin 400 mg b.d. (EAC: 60 patients); or lansoprazole 30 mg (o.m.) with the same antimicrobial agents (LAC: 60 patients). Cure of infection was assessed by a 13C-urea breath test 1 month after completion of treatment. RESULTS: One patient in the EAC group and two in the LAC group did not complete therapy because of an adverse event, and three did not undergo the 13C-urea breath test. Cure rates for the intention-to-treat, all-patients-treated and per protocol analysis in the EAC group were 85%, 86% and 88%, respectively, whereas those in the LAC group were 85%, 88% and 91%. There were no significant differences in cure rate or adverse events between the two regimens. CONCLUSIONS: Ecabet sodium in combination with amoxicillin and clarithromycin is as effective as lansoprazole-based eradication therapy for H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

A prospective clinical study on inhaled nitric oxide therapy for neonates in Japan.

BACKGROUND: This is the first report about a prospective clinical investigation to study the efficacy and safety of nitric oxide (NO) inhalation in infants with persistent pulmonary hypertension of the newborn (PPHN) in Japan. METHODS: Patients in the present study had to meet the following entry criteria: (i) they had to be younger than 7 days of age; (ii) they had to have evidence of PPHN as defined by echocardiograph; (iii) they had to have severe systemic hypoxemia under mechanical ventilation at 100% oxygen supplementation; and (iv) they had to have a failure to respond to conventional therapies. Patients were excluded from this trial if they had any of the following: hypoplastic lung, structural cardiac lesions or severe multiple anomalies. RESULTS: Nitric oxide inhalation therapy was performed in 68 infants who had severe PPHN at 18 hospitals between May 1995 and May 1997. At birth, 21 of 68 infants (31%) weighed less than 1,500 g and 39 infants weighed more than 2,500 g. The diagnoses associated with PPHN were as follows: 27 infants had meconium aspiration syndrome, 15 infants had dry lung syndrome, nine infants had congenital diaphragmatic hernia, six infants had respiratory distress syndrome, three infants had pneumonia and eight infants had other diagnoses. The mean oxygenation index (OI) before NO inhalation therapy in 68 infants was 43.2; 55 infants (81%) had good responses. CONCLUSIONS: These results may be valuable for further randomized controlled and double-blind trials in Japan to evaluate whether NO inhalation therapy is more effective than conventional therapy in infants with severe PPHN.

Administration, Inhalation↗

A study of the relationship between metabolism using 1H-MRS and function using several neuropsychological tests in temporal lobe epilepsy.

Several investigators have reported on the relationship between metabolism, using magnetic resonance spectroscopy (MRS), and function, using neuropsychological tests in temporal lobe epilepsy (TLE) patients, but the opinions regarding the results remain in contention. The aim of this study is to examine the relationship between metabolism, using proton MRS ((1)H-MRS), and function using several neuropsychological tests in the temporal lobes of TLE patients. We studied 29 TLE patients at our hospital using(1)H-MRS and neuropsychological tests. We used a clinical 1.5 T MR unit. We conducted five neuropsychological tests to examine the function of the left or right temporal lobe. There were significant correlations between the N-acetylaspartate/creatine + phosphocreatine (NAA/Cr) ratios and the scores of almost all of the neuropsychological tests for the temporal lobe function ipsilateral to the spike focus. However, in two Wechsler Memory Scale-Revised (WMS-R) subtests we found no significant correlation in the ipsilateral side. These findings suggest that the NAA/Cr ratios, which reflect neural metabolism, are closely related to function in the temporal lobes of TLE patients. The disparity between the results in two subtests of WMS-R show that several tests may be necessary in order to assess temporal lobe function.

Adolescent↗

Trimeresurus flavoviridis (habu snake) venom induces human erythrocyte lysis through enzymatic lipolysis, complement activation and decreased membrane expression of CD55 and CD59.

Trimeresurus flavoviridis (habu snake) bites can be fatal to man because of its virulent venom, which is clinicopathologically classified as haemorrhagic, necrotic, and haemolytic toxins. Trimeresurus flavoviridis venom causes lysis of human erythrocytes in conditions where plasma is present as well as in plasma-free conditions in a dose-dependent manner. The haemolytic process requires Ca2+ and Mg2+ ions in the solution. Additionally, the venom initiates activation of the human complement cascade as evidenced by C3a and C5a releases, complement consumption indicated by CH50 and formation of soluble membrane attack complex. The insertion of membrane attack complex into the erythrocyte membranes is morphologically identified by electronmicroscopy. Immunofluorescence analysis reveals that incubation of erythrocytes with the venom decreased cell-surface expression of CD55 (decay accelerating factor) and CD59 (protectin), which renders erythrocyte more vulnerable to adherent C3 and C5 convertases and to polymerization of C9 into membranes, and may enhance autologous complement-mediated haemolysis triggered by the venom. Our data demonstrate that Trimeresurus flavoviridis venom induces haemolysis in the presence of plasma by three distinct mechanisms, direct lipolysis through PLA2 activity, activation of the human complement system, and cleavages of CD55 and CD59 from erythrocyte membranes.

Animals↗