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Biomedical subjects

J Nakamura

Publications and source records attributed to J Nakamura.

At least 37 records · Page 2Linked to original sources
PubMed2003

Intraoperative location of small gastrointestinal cancers with a handheld gamma probe.

The location of a small lesion must be precisely identified during laparoscopic surgery. A gamma probe that is usually used for navigating sentinel lymph nodes was evaluated for its usefulness in locating small gastrointestinal lesions (14 gastric and 10 colonic). A total of 2 mCi of a Tc(99m)-labeled rhenium colloid was injected endoscopically around a tumor 16 h prior to surgery. During operation, the abdominal cavity was scanned using a handheld gamma probe (Navigator GPS, Tyco HealthCare, Norwalk, CT, USA). In all cases, the injection site was identified as the highest spot in the abdominal cavity, with 2585 counts per second on average (range, 910-8800 counts per second). The highest count in a lymph node was 637 per second on average. The gamma probe is a useful tool for identifying small gastrointestinal lesions during open and laparoscopic operations.

Colectomy↗
PubMed2003

Paroxetine as a 5-HT neuroendocrine probe.

RATIONALE: Acute administration of 40 mg paroxetine (a selective serotonin reuptake inhibitor) reportedly increases plasma cortisol in human subjects. This suggests that paroxetine may be a useful tool to probe brain serotonin function. OBJECTIVE: To investigate a dose-response relationship for paroxetine administration, and to determine whether a lower dose of paroxetine is sufficient to increase plasma ACTH and cortisol. METHODS: Twenty subjects were tested on three occasions in a double-blind, cross-over design receiving: (a) placebo, (b) paroxetine 20 mg and (c) paroxetine 40 mg administered orally at 8.00 a.m. In addition, five of the 20 subjects received paroxetine 20 mg plus cyproheptadine (a 5-HT(2) receptor antagonist) 4 mg and four subjects were given paroxetine 40 mg plus cyproheptadine 4 mg in an open manner. Plasma ACTH and cortisol levels were measured prior to administration and every hour for 6 h thereafter. RESULTS: Paroxetine, particularly 20 mg rather than 40 mg, significantly increased plasma ACTH and cortisol. Paroxetine 40 mg but not 20 mg caused significantly more nausea than the placebo. Cyproheptadine attenuated ACTH and cortisol responses to 20 mg but not to 40 mg paroxetine. CONCLUSIONS: Low-dose (20 mg) paroxetine has greater potential utility than larger doses as a neuroendocrine challenge test. The endocrine responses to paroxetine are probably mediated at least partially by 5-HT(2A/2C) receptors.

Adrenocorticotropic Hormone↗
PubMed2003

[Gastric cancer: an unusual presentation].

We want to introduce the case of an 18 year old male patient who consulted us because of proctorrhage, straining and rectal tenesmus. Diagnosis was rectal tumor which pathological anatomy revealed an adenocarcinoma of cells in seal ring shape, suggesting a probable gastric origin. The high endoscopy evidenced multiple polyps, less than a centimeter wide found in the cardiac orifice, body and antrum, with the same histology. All these findings were confirmed during the exploratory laparotomy. We thought it was interesting to report this case because of the clinical presentation, unusual in this type of gastric cancer.

Adolescent↗
PubMed2002

Allelic association of the neuronal nitric oxide synthase (NOS1) gene with schizophrenia.

Nitric oxide (NO) has been identified as a widespread and multifunctional biological messenger molecule in the central nervous system (CNS), with possible roles in neurotransmission, neurosecretion, synaptic plasticity, and tissue injury in many neurological disorders, including schizophrenia. Neuronal NO is widely produced in the brain from L-arginine catalyzed by neuronal NO synthase (NOS1). We therefore hypothesized that the NOS1 gene may play a role in the pathophysiology of schizophrenia. In the present study, we examined the genetic association between a novel single nucleotide polymorphism (SNP: a C-->T transition located 276 base pairs downstream from the translation termination site) of the human NOS1 gene, which is located in chromosome 12q24, and schizophrenia (215 Japanese patients with schizophrenia and 182 healthy controls). The allele frequencies of the polymorphism in exon 29 of the NOS1 gene differed significantly between patients with schizophrenia and controls (chi(2) = 20.10, df = 1, P = 0.000007; relative risk = 1.92; 95% confidence interval = 1.44-2.55). Our results suggest that the NOS1 gene polymorphism may confer increased susceptibility to schizophrenia.

Alleles↗
PubMed2002

The effect of cigarette smoking on soluble adhesion molecules in middle-aged patients with Type 2 diabetes mellitus.

AIMS: To investigate the effect of smoking on soluble adhesion molecules in middle-aged diabetic patients. METHODS: One hundred out-patients with Type 2 diabetes and 100 age- and sex-matched non-diabetic subjects without clinical macrovascular disease were selected. Soluble serum levels of adhesion molecules were analysed using enzyme immunoassay. Carotid atherosclerosis was assessed using an ultrasound system. RESULTS: When compared with non-diabetic subjects, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and sE-selectin were found at significantly high levels in diabetic patients and significantly higher levels of sICAM-1, sE-selectin, and sP-selectin were observed in current smokers than never-smokers among diabetic or non-diabetic subjects, respectively. The combined, but not enhanced, effects of diabetes mellitus and smoking were observed in sICAM-1 and sE-selectin levels. Additionally, levels of sICAM-1 (P < 0.05) and sE-selectin (P < 0.01), but not sP-selectin, were high in ex-smokers when compared with never-smokers among diabetic patients. Diabetic smokers were also found to have marked carotid atherosclerosis, which was related to increased levels of sICAM-1. CONCLUSIONS: Our present study shows that levels of adhesion molecules were higher in diabetic smokers than diabetic non-smokers or non-diabetic smokers, and that cessation after chronic smoking did not restore the levels of sICAM-1 and sE-selectin, though sP-selectin levels were restored. These data suggest a possible mechanism for accelerated atherosclerosis induced by smoking in patients with diabetes.

Aged↗
PubMed2002

Characteristic patterns of circadian variation in plasma catecholamine levels, blood pressure and heart rate variability in Type 2 diabetic patients.

AIMS: To investigate whether Type 2 diabetic patients exhibit characteristic patterns of circadian variation in plasma levels of catecholamines, blood pressure (BP) and heart rate variability (HRV). METHODS: Ten Type 2 diabetic and eight control in-patients were studied. Blood for catecholamine measurement was collected every 4 h, and non-invasive ambulatory BP and heart rate were monitored throughout the day. HRV was determined using frequency domain methods. RESULTS: Diabetic patients showed a different pattern of circadian variation in BP and HRV from that of controls, the diurnal-nocturnal differences (D-N) being significantly smaller. The mean 24-h HRV levels were reduced in diabetic subjects. The mean 24-h plasma noradrenaline level of 1.36 +/- 0.12 nmol/l in diabetic patients was significantly lower than the 2.03 +/- 0.20 nmol/l in controls (P < 0.01). In contrast, no significant difference in adrenaline levels was observed. The mean 24-h plasma noradrenaline level demonstrated a significant positive correlation with D-N in systolic BP (r = 0.49, P = 0.0153). CONCLUSIONS: The present study demonstrated distinctive patterns of circadian variation in plasma noradrenaline level, BP and HRV in Type 2 diabetic patients, associated with an abnormal circadian pattern of sympathovagal modulation.

Blood Pressure↗
PubMed2002

Plasma levels of catecholamine metabolites predict the response to sulpiride or fluvoxamine in major depression.

We investigated the relationships between the changes in plasma catecholamine metabolites obtained from depressed patients before and after administration of sulpiride, a benzamide compound, or fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), and between clinical responses to treatment with each of these drugs. Responders to sulpiride had significantly lower plasma homovanillic acid (pHVA) levels before administration of sulpiride than did non-responders or controls (responders: 4.5 +/- 3.1 ng/ml, non-responders: 11.1 +/- 5.9 ng/ml, controls: 10.9 +/- 5.3 ng/ml). Positive relationships were observed between changes in pHVA levels and improvement rates in the 17-item Hamilton Depression Rating Scale (Ham-D). In contrast, responders to fluvoxamine had significantly higher plasma free 3-methoxy-4-hydroxyphenylglycol (pMHPG) levels before administration of fluvoxamine than did non-responders or controls (responders: 8.5 +/- 1.8 ng/ml, non-responders: 5.9 +/- 2.I ng/ml, controls: 5.2 +/- 2.9 ng/ml). Negative relationships were observed between changes in pMHPG levels and improvement rates in Ham-D. These results suggest that lower pretreatment pHVA levels and higher pretreatment levels of pMHPG might be predictors of response to sulpiride and fluvoxamine, respectively, and that sulpiride might produce a functional increase in the dopaminergic system, resulting in improvement in some depressive symptoms; fluvoxamine, on the other hand, might produce a functional decrease in the noradrenergic system via serotonergic neurons, resulting in improvement of those symptoms.

Adult↗
PubMed2001

Association between three functional polymorphisms of dopamine D2 receptor gene and tardive dyskinesia in schizophrenia.

The dopamine D2 receptor (DRD2) gene is considered one of the candidate genes contributing to the development of tardive dyskinesia (TD). In the present study, we investigated the genetic association between three functional polymorphisms (Ser311Cys, -141C Ins/Del and TaqI A) in the DRD2 gene and TD (200 patients with schizophrenia: 44 with TD and 156 without TD). No significant difference in the allelic and genotypic distribution between patients with TD and those without TD was observed. However, we found a slightly significant association between the -141C Ins/Del polymorphism and the total Abnormal Involuntary Movement Scale (AIMS) score (P = 0.037). The significant association between the -141C Ins/Del polymorphism and the total AIMS score did not remain after the regression analysis was taken into account (P = 0.14). Our results suggest that that three functional polymorphisms in DRD2 may not play a major role in the occurrence of TD.

Alleles↗
PubMed2001

Characteristics of fluvoxamine-induced nausea.

We investigated the association between fluvoxamine and nausea from various viewpoints. The incidence of nausea induced by fluvoxamine was 29% (12/41). Plasma 5-hydroxyindoleacetic acid (p5-HIAA) levels after fluvoxamine administration were significantly higher in patients with nausea (6.6+/-3.4 ng/ml) than in those without nausea (3.5+/-2.7 ng/ml). On the other hand, no significant differences were found between patients with and patients without nausea in terms of sex, age, initial and maximum dosages of fluvoxamine and its plasma concentrations, and clinical response to fluvoxamine. However, the incidence of nausea in patients who were initially administered fluvoxamine at under 50 mg/day was significantly lower than in those who were started at above 50 mg/day. In addition, mosapride, a member of the benzamide family, was effective in alleviating fluvoxamine-induced nausea. These results suggest that fluvoxamine-induced nausea is associated with hyperactivity in serotonergic neurons.

Adult↗
PubMed2001

Controlled release and ocular absorption of tilisolol utilizing ophthalmic insert-incorporated lipophilic prodrugs.

To control ocular drug delivery, the O-butyryl ester prodrug of tilisolol (BUTL) and the O-palmitoyl ester prodrug of tilisolol (PalTL) were incorporated into an ophthalmic insert. The released TL from BUTL inserts and PalTL inserts in pH 7.4 phosphate-buffered saline until 5 h were approximately 25% and 3% of that from TL inserts, respectively. In addition, BUTL was also released from BUTL inserts. However, PalTL was not released from the PalTL insert. The release of drugs from TL inserts and BUTL inserts was little affected by the addition of bovine serum albumin (BSA) in pH 7.4 phosphate-buffered saline. In contrast, the release of drugs from PalTL inserts were enhanced by the addition of BSA. After application of TL, BUTL, and PalTL inserts to the rabbit eye, the aqueous humor concentration of TL was prolonged compared with TL instillation, and the plasma concentration of TL was much lower than that of TL instillation. The ratios of the area under the TL concentration-time curve (AUC) in the aqueous humor to AUC in the plasma (AUC(aqueous)/AUC(plasma)) after application of BUTL until 8 h were 3.1-fold and 3.8-fold higher than those of the TL insert and PalTL insert, respectively.

Absorption↗
PubMed2001

Leukemia inhibitory factor induces nociceptin mRNA in cultured rat cortical neurons.

The effects of leukemia inhibitory factor (LIF) on the expression of neurotransmitter synthetase and neuropeptide mRNAs in cultured rat cortical neurons were examined by reverse transcription-polymerase chain reaction. Nociceptin mRNA expression was increased by treatment with 20 or 80 ng/ml LIF for 24 h, but choline acetyl transferase, glutamic acid decarboxylase, enkephalin, dynorphin, substance P, somatostatin and galanin mRNA expression were not altered by LIF. These observations indicated a specific effect of LIF on nociceptin gene regulation in cultured cortical neurons.

Aging↗
PubMed2001

STM images apparently corresponding to a stable structure: considerable fluctuation of a phase boundary of the Si(111)-(square root of (3) x square root of (3))-Ag surface.

We study scanning tunneling microscopy (STM) images near a phase boundary of the Si(111)- (square root of (3) x square root of (3))-Ag surface by using Monte Carlo simulations based on results of first-principles calculations. The boundary is found to fluctuate from snapshot to snapshot, and the feature of the simulated STM images differs distinctly from the observed one with a straightly extending honeycomb pattern of bright spots. Remarkably, statistical averages of the simulated images reproduce the observed feature. This study gives a warning of our tendency to relate STM images revealing clear arrangement of bright spots with some stable structure.

Journal Article↗
PubMed2001

Novel polymorphism in the 5'-upstream region of the human 5-HT6 receptor gene and schizophrenia.

The localization of 5-hydroxytryptamine6 (5-HT6) receptor in the limbic and cortical regions, and the high affinity of atypical antipsychotic drugs such as clozapine for the receptor, suggest the possible involvement of the receptor in the pathogenesis of schizophrenia. In this study, we searched systematically for polymorphisms in the 5'-upstream region of the human 5-HT6 receptor gene. We identified a trinucleotide repeat polymorphism, (GCC)2/3, at a nucleotide position between -1093 and -1085 bp upstream from the translation start site. Subsequent case-control association study did not demonstrate significant differences of genotype and allele frequency between 206 controls and 246 patients with schizophrenia. Our results suggest that the 5-HT6 receptor gene polymorphism does not confer increased susceptibility to schizophrenia.

Alleles↗
PubMed2001

Inhibition of adenylylcyclase activity in mouse cerebellum membranes upon hydrolysis of triacylglycerols by triacylglycerol lipase, but not phospholipids by phospholipase A(2).

We previously showed that arachidonic acid and related unsaturated free fatty acids (U-FFAs) inhibit the activity of adenylylcyclase in brain membranes of mice. The level of U-FFAs elevates when the hydrolysis of triacylglycerols (TAGs) and phospholipids is promoted. In this study, we examined whether activation of triacylglycerol lipase (TAG lipase) and phospholipase A(2) (PLA(2)) results in the inhibition of adenylylcyclase activity in cerebellum membranes of mice. Incubation of Intralipos with TAG lipase in the presence of membranes mainly released oleic acid and linoleic acid and caused > or =95% inhibition of adenylylcyclase activity. In contrast, PLA(2), though releasing substantial amounts of U-FFAs, increased the enzymatic activity. To account for this difference, we examined how by-products formed in U-FFA release by TAG lipase and PLA(2) operated on the arachidonic acid-induced inhibition. Lysophosphatidylcholne and some other lysophospholipids, produced by PLA(2), enhanced the adenylylcyclase activity and attenuated the inhibitory effect of arachidonic acid. On the other hand, no such effects were found with by-products of TAG lipase-mediated lipolysis. Rather, monoacylglycerols having U-FFAs, possibly formed by TAG lipase, potentiated the arachidonic acid-induced inhibition of adenylylcyclase. Bovine serum albumin, added into the mixture for the pretreatment of membranes with TAG lipase, prevented the inhibition of adenylylcyclase. These results indicate that by-products formed in U-FFA release have a crucial role for the U-FFA's action on adenylylcyclase and that U-FFAs released from TAG are an inhibitor of adenylylcyclase. It may be that albumin in plasma, and thus FFA-binding proteins within cells, are of importance in protecting adenylylcyclase upon U-FFA release.

Adenylyl Cyclase Inhibitors↗
PubMed2001

Structural and cohesive properties of a C60 monolayer.

We have explored the cohesive property of a monolayer of C (60) molecules (ML- C (60)) by means of total energy calculations with the density-functional theory. The total energy curve calculated for ML- C (60), which is obtained as a function of the lattice constant, has two minima and shows a hysteresis in the compression-tension stroke. These two minima in energy correspond to the different structural phases of ML- C (60): one is a monomer phase and the other is a polymer one. The energy band gap within the framework of the local density approximation varies from 1 eV (semiconducting phase) to 0 eV (metallic phase) with external pressure and without structural transition from the monomer phase to the polymer one.

Carbon↗
PubMed2001

Giant intrasacral cellular schwannoma treated with high sacral amputation.

STUDY DESIGN: A case report of a man with a gigantic cellular schwannoma in the sacrum treated with high sacral amputation accompanied by careful nerve root-sparing dissection. OBJECTIVES: To describe the atypical clinical course of an intrasacral cellular schwannoma and the surgical procedure of high sacral amputation performed in a way to prevent needless sacrifice of functionally essential nerve roots. SUMMARY OF BACKGROUND DATA: Fundamentally, a cellular schwannoma is a benign tumor, but the clinical course is atypical. The symptoms are mild and the clinicopathologic features often mislead us to make a diagnosis of malignancy. The occurrence rate of intraosseous cellular schwannoma was reported to be 0.2% of all bony tumors, and the main location was the retroperitoneal space in the pelvis. Forty-one cases of giant intrasacral schwannomas have been reported so far. Among them, large sacral schwannoma with anterior cortex erosion and associated intrapelvic extension was extremely rare. METHODS: The patient presented with a 5-year history of right leg and buttock pain, which did not disturb his daily activities. After a histopathologic diagnosis and a complete set of image studies, high sacral amputation with preservation of uninvolved nerve roots was performed at S1-S2 through a combined anterior and posterior approach. Both S1 nerve roots and the right S2-S3 nerve roots were saved using a threaded saw. The lumbar spine was stabilized to the pelvic girdle using spinal instrumentation with posterolateral fusion. RESULTS: Eighteen months after the tumor was resected the patient had a very good clinical outcome, and there were no radiologic signs of instability or recurrence of the tumor. Locomotor function of both lower extremities and bowel and urinary functions were well maintained. The patient returned to his previous work. CONCLUSIONS: High sacral amputation following a combined anteroposterior approach provided good results without causing any disability. A detailed preoperative planning and careful dissection of uninvolved nerve roots prevented unnecessary neurologic impairment in locomotion and the detrusor and anorectal function.

Dissection↗
PubMed2001

Inhibition of adenylyl cyclase activity in brain membrane fractions by arachidonic acid and related unsaturated fatty acids.

Pretreatment of mouse brain membranes with arachidonic acid (AA) and related unsaturated fatty acids at 30 degrees C for 10 min decreased basal activity and isoproterenol/guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S)- and forskolin-stimulated activities of adenylyl cyclase to a level less than 5% of control. The presence of the carboxyl group on the fatty acids was essential for the inhibition, because no such inhibition was found with ethyl arachidonate or AA attached to diacylglycerols and phospholipids. The AA-mediated inhibition was observed when the activity was measured in the presence of Mn2+ or forskolin and was insensitive to pertussis toxin or guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), indicating a mechanism independent of GTP-binding proteins. In addition, the fact that stimulators of the adenylyl cyclase catalytic unit, ATP, GTP gamma S and forskolin, when present during pretreatment, attenuate the inhibitory effect of AA may suggest that the catalytic unit is a target of AA. Bovine serum albumin suppressed the inhibition when present in the mixtures for pretreatment, but could not restore the adenylyl cyclase activity that had been reduced by AA, indicating an irreversible inhibition by AA. The effect of AA was found to be additive to P-site-mediated inhibition. The present study suggests the existence of another mechanism of regulation of adenylyl cyclase by unsaturated fatty acids.

Adenosine Triphosphate↗