Biomedical subjects
Publications and source records attributed to T Koyama.
We removed a cavernous angioma, making a tunnel between the fourth ventricle and tubercle using the traction-dissection method. Cavernous angioma with such a distribution is extremely rare, and we manipulated the mass differently to minimize surgical damage. Intraoperative findings and technical considerations are made.
The toxic dose of methamphetamine (METH) (5 mg/kg, s.c., x4, 2 hr intervals) decreased contents of dopamine, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in striatum, and decreased contents of serotonin (5-HT) in both striatum and nucleus accumbens. Administration of low doses of a non-selective endothelial and neuronal nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME) (5 and 10 mg/kg, i.p., x1) intensified the METH-induced decreases in contents of dopamine and its metabolites in striatum. NO substrate, L-arginine (500 mg/kg, i.p., x4) reversed these effects of L-NAME on the METH-neurotoxicity. L-NAME did not change the METH-induced hyperthermia. These findings, which are contrary to our previous study with a high dose of L-NAME, suggest that the inhibition of endothelial or neuronal NOS-mediated NO production by low doses of L-NAME enhanced the METH-induced neurotoxicity. The finding that L-NAME can have opposite effects on the METH-neurotoxicity according to the dosing is important, however, additional experiments should be performed to clarify which type of NOS is related to these effects.
Effects of lithium on the dopamine D2 receptor expression in the rat brain striatum were studied. Feeding the chow containing 0.2% LiCO3 for 6 days increased the level of the dopamine D2 receptor mRNA, and the transcription rate of the dopamine D2 receptor gene, indicating the stimulatory effects of lithium on the transcription of the dopamine D2 receptor gene. [3H] Spiperone binding to the striatal membranes increased in the rats treated with lithium, while the Western blotting analysis showed no change of the amount of the dopamine D2 receptors. These results suggested that lithium might induce the conformational changes of the dopamine D2 receptors. The methamphetamine-induced locomotor activity was enhanced by the pretreatment with lithium, whereas simultaneous increase in the methamphetamine concentration in the striatum was also observed. These observations suggested that the stimulation of methamphetamine-induced locomotor activity by lithium might be, at least partly, due to either increased sensitivity of the dopamine receptors, or increased concentration of methamphetamine in brain, or combination of both.
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BACKGROUND: Serotonin (5-HT)-stimulated platelet intracellular calcium (Ca) mobilization has been reported to be enhanced in unmedicated depressive patients compared to those of normal healthy subjects, which suggests increased 5-HT2A receptor function in these patients. It has not been ascertained whether this enhanced response is specific to some type of affective disorders among various mental disorders. METHODS: We examined 5-HT-induced platelet intracellular Ca response in 152 unmedicated outpatients with various psychiatric disorders including bipolar disorder (BD), major depressive disorder with melancholia (DM), major depressive disorder without melancholia (DN), schizophrenia (SCH), panic disorder (PD), obsessive-compulsive disorder (OCD), social phobia (SP) and bulimia nervosa (BN), and 30 normal controls. RESULTS: We observed no significant differences in basal intracellular Ca concentration among all patient subgroups and normal controls. While the 5-HT-induced Ca response was significantly and specifically higher in patients with BD than in normal controls, no significant differences were found in the Ca response to 5-HT between patients with DM, DN, SCH, PD, OCD, SP and BN, and normal controls. LIMITATIONS: The sample sizes of each group are still small. Therefore, they have to be enlarged in the continuation of the study so as to increase the power of the statistical tests. CONCLUSION: These results indicate the possibility that enhanced signal transduction, mediated by the 5-HT2A receptor, may be specific to bipolar disorder.
Pharmacological studies of bipolar disorder suggest that dysfunction of calcium mobilization via phosphatidylinositol-mediated transduction may be involved in its pathogenesis. The present study tests the hypothesis that dysfunction of calcium mobilization in bipolar disorder is due to the mutation of the nucleotide sequence in the FKBP12 binding site on the inositol 1,4,5-trisphosphate type-1 receptor (IP(3)R1). Nucleotide sequence analysis of the FKBP12 binding site on IP(3)R1 was performed using reverse transcription-polymerase chain reaction and DNA sequencing. The nucleotide sequence in this region was preserved in all subjects. This finding suggests that IP(3)R1 dysfunction through the FKBP12 binding site is not involved in the pathogenesis of bipolar disorder.
We recorded single neuronal activities in the anterior cingulate cortex of monkeys while they were performing discriminative pain-avoidance and reward tasks: a prediction cue was presented for 0.5-1.5 s, followed by a red or green discrimination cue (1:1, random) for 1.0 s; painful stimuli were presented if the monkey failed to respond during the red cue; a reward was given, subsequent to a cued 1 s delay, if the monkey responded after the green cue. Among 775 neurons recorded, 196 neurons showed significant activity during one or more observation periods; 36 during the prediction period; 77 during the discrimination period; 41 during the delay period; 85 during the response period; 40 during the pre-reward period; and 15 during the reward-ingestion period. Of 77 neurons activated during the discrimination period, 47 showed exclusive activity either during the red (34) or during the green (13) cue: of 85 neurons activated during the response period, 64 showed exclusive activity either for pain-avoidance (37) or obtaining a reward (27). Control experiments confirmed that the neuronal activity could not be attributed to simple visual or motor processes. The results suggest that some anterior cingulate neurons are involved with anticipation of, and response selection for, imminent events.
1. Previously the authors have shown that acute citalopram treatment increased the dopamine D2 receptor expression in rat brain striatum (Kameda et al., 2000). In the present study, the authors attempted to determine whether these effects of citalopram influence the methamphetamine-induced locomotor activity. 2. The pretreatment with a single administration of citalopram (10 mg/kg, i.p.) resulted in the significant enhancement of the locomoter activity induced by methamphetamine treatment (1 mg/kg, i.p.). The enhancement was observed 30 min, 12 hours, 24 hours, but not 7 days after withdrawal of citalopram administration. 3. Then the authors determined the methamphetamine concentration in rat brain striatum by gas chromatography-mass spectrometry (GC-MS) The results showed that the concentration of methamphetamine wars significantly higher in the rats 24 hours, and also 7 days after withdrawal of citalopram administration, compared to the control rats. 4. These results emphasized the involvement of the high methamphetamine concentration, caused by the pretreatment with citalopram, in the enhancement of the methamphetamine-induced locomotor activity. However high methamphetamine concentration alone could not account for this enhancement, since the high concentration of methamphetamine observed 7 days after withdrawal of citalopram administration did not appear to enhance the methamphetamine-induced locomotor activity. Another mechanism through which the pretreatment with citalopram enhanced the methamphetamine-induced locomotor activity, such as the increased expression of the dopamine D2 receptors, could not be excluded.
Antigenic components of Malassezia furfur, M. globosa, M. restricta, M. slooffiae, and M. sympodialis were studied for immunoglobulin E antibodies in sera of patients with atopic dermatitis (AD). Antigenic components were extracted from Malassezia cells by treatment with beta-mercaptoethanol, referred to as 2-ME extract. CBB staining and lectin blots using Con A, LCA, PHA-E4, PNA or RCA120 showed that the 2-ME extracts contained several species-dependent components that differed quantitatively and qualitatively among the Malassezia species at the protein level. In the Western blot with the 2-ME extracts, of 54 sera of the patients with AD (54 patients), the patients' IgE antibodies most frequently recognized components showing molecular weights of 43-46 kDa for M. slooffiae, 12-22 kDa for M. sympodialis, 35-40 kDa for M. restricta, 45-50 kDa for M. globosa, and of 67-72 kDa for M. furfur, respectively. In the correlative study, in which the total band intensities generated for each extract in Western blot were compared among the Malassezia species, the intensity for M. globosa was well correlated with that for M. sympodialis (r=0.756). In the Western blot inhibition test, the 2-ME extract of M. globosa partially inhibited the reaction of the antigenic components of other Malassezia species with the patient's IgE antibodies. These results indicated that Malassezia species contained both species-specific and common antigenic components at the IgE antibody level.
BACKGROUND: FR167653 is a potent suppressant of tumor necrosis factor (TNF)-alpha and interleukin-1 (IL-1) production, and was shown to attenuate ischemia and reperfusion (I/R) organ injury in our previous experiment. Because p38 mitogen-activated protein (MAP) kinase has been reported to regulate the production of TNF-alpha and IL-1, we examined the effects of FR167653 in the rat lung I/R model and determined the expression and activation of p38 MAP kinase. METHODS: Experiment 1: After 1 hour of ischemia, p38 MAP kinase, phosphorylated p38 MAP kinase (active form), histologic changes of the lung, and serum levels of TNF-alpha and IL-1beta were examined. Experiment 2: After 2 hours of reperfusion, arterial oxygen content (PaO(2)) and saturation (SaO(2)), serum TNF-alpha and IL-1beta levels, and histologic changes in the lung were examined. Rats were divided into three groups in Experiment 1. In the control group, a saline solution was administered and, in the FR group, 0.1 mg/kg per hour of FR167653 was administered, intravenously throughout the experiment, beginning 30 minutes before ischemia. In the non-ischemic group, samples were taken soon after thoracotomy. The rats were divided into control and FR groups in Experiment 2. RESULTS: Experiment 1: One hour of ischemia induced almost no changes in the lung or serum cytokine levels. Meanwhile, FR167653 markedly attenuated the expression of phosphorylated p38 MAP kinase. Experiment 2: SaO(2) and PaO(2) were improved, serum cytokines were lower, and lung damage was less extensive in the FR group than in the control group. CONCLUSION: FR167653 attenuates I/R injury of the lung and this attenuation is associated with suppression of p38 MAP kinase activation.
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This study was designed to examine the time-course changes in capillarity, especially the distribution of arteriolar and venular capillaries, in skeletal muscles during endurance training by running in young female Wistar rats. Exercise training by running started at the age of 5 weeks and lasted for 5 weeks at 25 m min(-1) on a 25% gradient, 10-60 min day(-1), 5 days per week. Morphological findings were obtained from the soleus (SOL) and deep portions of the medial gastrocnemius (GASd) muscles. In SOL, the training significantly increased the capillary-to-fibre ratio (C:F), total capillary density, and density of venular capillaries at Week 1. Significant increases in the C:F and total capillary density were also observed at Weeks 4 and 5. The capillary domain area (CDA) values for total capillary and arteriolar and venular capillaries were significantly decreased after 4 weeks of training. In GASd, the training significantly increased the C:F at Week 1 and from Week 3 onwards. It also significantly increased cross-sectional area of all fibre types. Total capillary density and the CDA values showed no significant difference between control and training groups at all points of time. Significant increases in succinate dehydrogenase (SDH) activity were first noted after 2 weeks in GASd and after 3 weeks in SOL. These findings suggest that, in young growing rats, adaptive changes in the oxygen transport system occurred within 1 week after the onset of training mainly in highly oxidative muscles. The changes in arteriolar and venular capillary densities may help to clarify the growth pattern of the capillary network associated with endurance running training.
The effects of lunchtime bright light exposure in patients of a geriatric hospital were investigated. Ten inpatients (six women and four men; mean age +/- SD: 81.2 +/- 8.8 years) with sleep disturbances were studied for 9 weeks. Nurses performed daily ratings for sleep-wakefulness disturbances. Approximately 8000 lx bright light exposure was performed for 3 weeks in the light therapy room. Before and after exposure, ocular function was evaluated. Clinical ratings of sleep-wakefulness improved in eight patients. The score of difficulty in falling asleep and drowsiness in the morning declined during the light exposure. The score of drowsiness in the afternoon decreased during the post-light exposure. Post-exposure ocular disturbances were not found.
Inpatients with sleep disturbances in a geriatric hospital received 1 h of exposure to approximately 8000 lx bright light per day for 3 weeks. Polysomnogram was recorded for four female patients. Two (aged 68 and 87 years) were non-demented patients with weak cataracts and the other two (aged 92 and 93 years) were demented patients with severe cataracts. Electroencephalogram results showed that light exposure decreased the proportion of Stage W, while increased the proportion of Stage 2, and these effects continued for at least 3 weeks after the cessation of light exposure. These results suggest that exposure to bright light is effective in improving the disturbed sleep of patients.
We investigated the effect of citalopram [a selective serotonin (5-HT) reuptake inhibitor; SSRI] and MKC-242 (a selective 5-HT1A agonist), following treatment with subchronic lithium (p.o., 1 week) on extracellular 5-HT concentrations in the medial prefrontal cortex (mPFC). Acute treatment with citalopram (3 and 30 mg/kg) led to significant increases in extracellular 5-HT concentrations. The subchronic lithium group showed significantly higher basal levels of extracellular 5-HT than normal diet controls. Acute citalopram (3 and 30 mg/kg) treatment together with subchronic lithium treatment showed significant increases in the extracellular 5-HT concentrations, compared with citalopram treatment alone. Acute MKC-242 (1 mg/kg) treatment showed significant decreases in extracellular 5-HT concentrations, in both the normal diet and lithium diet groups to the same extent. The addition of lithium did not change the effect of the 5-HT1A agonist on extracellular 5-HT concentrations. This study suggests that lithium augmentation of the antidepressant effect of SSRI is mediated by the additional increases in extracellular 5-HT concentrations following the co-administrations of lithium and SSRI.
After thoracotomy, patients often suffer from a persistent pain syndrome called post-thoracotomy pain. To elucidate morbidity, time course, and predictive factors for this syndrome, we analyzed follow-up data for 85 post-thoracotomy patients. We used a four-point scale to assess pain: none, slight, moderate and severe. Of 85 patients, 50 reported pain (39 slight, 11 moderate) one day after surgery. A year after surgery, the patients were polled using a simple questionnaire received by the mail. Sixty patients reported persistent pain (34 slight, 14 moderate, 12 severe) a month after surgery, and 35 patients reported persistent pain (33 slight, two moderate) around the time of the poll (1 year after surgery). Although pain deterioration was observed in 40% (34/85) of patients during month 1 after surgery, pain alleviation was seen in 48% (41/85) of patients during months 2-12. Stepwise regression analysis revealed that female gender and pain at postoperative day 1 were predictive for persistent pain both 1 month and 1 year after thoracotomy. Among 35 patients with persistent pain 1 year after surgery, 24 cases reported paresthesia-dysesthesia, and 14 cases reported hypoesthesia. The present data thus suggests that persistent pain is common and often severe 1 month after surgery but is alleviated after 1 year. Clinical time course and symptoms indicate that nerve impairment rather than simple nociceptive impact may be involved in this syndrome.
OBJECTIVE: To test the hypothesis that early and low doses of erythromycin reduce the incidence of early delayed gastric emptying (DGE) and induce phase 3 of the migratory motor complex in the stomach after Billroth I pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Delayed gastric emptying is a leading cause of complications after PPPD, occurring in up to 50% of patients. High doses of erythromycin (200 mg) accelerate gastric emptying after pancreaticoduodenectomy and reduce the incidence of DGE, although they induce strong contractions that do not migrate to the duodenum. METHODS: Thirty-one patients were randomly assigned to either the erythromycin or control groups. The patients received erythromycin lactobionate (1 mg/kg) every 8 hours, or H2-receptor antagonists and gastrokinetic drugs from days 1 to 14 after surgery. On postoperative day 30, gastroduodenal motility was recorded in 14 patients. RESULTS: Preoperative, intraoperative, and postoperative factors were comparable in the erythromycin and control groups. The erythromycin group had a shorter duration of nasogastric drainage, earlier resumption of eating, and a 75% reduction in the incidence of DGE. Erythromycin was an independent influence on nasogastric tube removal, and preservation of the right gastric vessels was a significant covariate. Low doses of erythromycin induced phase 3 of the migratory motor complex and phase 3-like activity, with the same characteristics as spontaneous phase 3, in 86% of patients: two had quiescent stomachs and the others had spontaneous phase 3 or phase 3-like activity. CONCLUSIONS: Low doses of erythromycin reduced the incidence of DGE by 75% and induced phase 3 of the migratory motor complex after Billroth I PPPD. Low doses of erythromycin are preferable to high doses in the unfed period after PPPD.
PURPOSE: The aim of this study was to investigate the clinical value of coregistration of interictal SPECT and magnetic resonance imaging (MRI) in patients with partial epilepsy. MATERIALS AND METHODS: Seventeen patients with partial epilepsy were examined with I-123 IMP or Tc-99m ethyl cysteinate dimer SPECT during the interictal phase. The SPECT images were automatically coregistered to axial T1 weighted MRIs. Asymmetry indexes (AIs) were calculated in both nonregistered images and coregistered images. RESULTS: SPECT images showed areas of decreased tracer uptake in 12 patients. In two patients, the relation between the tumor and the extent of decreased uptake became more accurate in the coregistered images. In five cases, the coregistered images clearly showed that the decreased uptake was located in the sulcus. The AIs were significantly reduced from 14.29 +/- 7.23 to 5.86 +/- 3.48 (P < 0.001) after the images were coregistered in these cases. In five cases, the coregistered images indicated that the decreased areas were in agreement with the cortical findings. No significant differences in the AIs were observed in these cases (16.50 +/- 6.19 versus 17.83 +/- 4.45). Thus, the coregistered images were useful not only to differentiate actual hypoperfusion from artificial hypoperfusion resulting from partial volume effects but also to improve the accuracy of AIs. CONCLUSION: The coregistration of interictal perfusion SPECT and MRI is useful not only to provide precise functional and anatomic mapping but also to improve the accuracy of calculations of the semiquantitative analysis of regional cerebral blood flow parameters during the interictal state of epilepsy.