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M Kawamoto

Publications and source records attributed to M Kawamoto.

At least 19 recordsLinked to original sources
PubMed2005

Functional analysis of genetic variants in the human concentrative nucleoside transporter 3 (CNT3; SLC28A3).

The human concentrative nucleoside transporter, CNT3 (SLC28A3), plays an important role in mediating the cellular entry of a broad array of physiological nucleosides and synthetic anticancer nucleoside analog drugs. As a first step toward understanding the genetic basis for interindividual differences in the disposition and response to antileukemic nucleoside analogs, we examined the genetic and functional diversity of CNT3. In all, 56 variable sites in the exons and flanking intronic region of SLC28A3 were identified in a collection of 270 DNA samples from US populations (80 African-Americans, 80 European-Americans, 60 Asian-Americans, and 50 Mexican-Americans). Of the 16 coding region variants, 12 had not been previously reported. Also, 10 resulted in amino-acid changes and three of these had total allele frequencies of >/=1%. Nucleotide diversity (pi) at nonsynonymous and synonymous sites was estimated to be 1.81 x 10(4) and 18.13 x 10(4), respectively, suggesting that SLC28A3 is under negative selection. All nonsynonymous variants, constructed by site-directed mutagenesis and expressed in Xenopus laevis oocytes, transported purine and pyrimidine model substrates, except for c. 1099G>A (p. Gly367Arg). This rare variant alters an evolutionarily conserved site in the putative substrate recognition domain of CNT3. The presence of three additional evolutionarily conserved glycine residues in the vicinity of p. Gly367Arg that are also conserved in human paralogs suggest that these glycine residues are critical in the function of the concentrative nucleoside transporter family. The genetic analysis and functional characterization of CNT3 variants suggest that this transporter does not tolerate nonsynonymous changes and is important for human fitness.

Adenosine↗
PubMed2005

Genetic polymorphisms and haplotypes of the human cardiac sodium channel alpha subunit gene (SCN5A) in Japanese and their association with arrhythmia.

Genetic variations in cardiac ion channels have been implicated not only as the causes of inherited arrhythmic syndromes, but also as genetic risk factors for some acquired arrhythmias. To elucidate the potential roles of genetic polymorphisms of the alpha subunit of the voltage-gated sodium channel type V (SCN5A) in cardiac rhythm disturbance, the entire SCN5A coding exons and their flanking introns were sequenced in 166 Japanese arrhythmic patients and 232 healthy controls. We detected 69 genetic variations, including 54 novel ones. Out of the 12 novel nonsynonymous single nucleotide polymorphisms (SNPs), p.Leu1988Arg was found at a frequency of 0.015. The other 11 SNPs were rare (0.001), with 6 found in arrhythmic patients and 5 in healthy controls. The frequency of a novel intronic SNP, c.703+130G>A, was significantly higher in the patients than in the controls, suggesting this SNP is associated with an unknown risk factor for arrhythmia. Following linkage disequilibrium analysis, the haplotype structure of SCN5A was inferred using high-frequency SNPs. The frequency of the haplotype harbouring both p.Leu1988Arg and the common SNP p.His558Arg (haplotype GG) was significantly lower in the patients than in the controls. This finding suggests that this haplotype (GG) might have been positively selected in the controls because of its protective effect against arrhythmias. This study provides fundamental information necessary to elucidate the effect of genetic variations in SCN5A on channel function and cardiac rhythm in Japanese, and probably in the Asian population.

Arrhythmias, Cardiac↗
PubMed2005

Single nucleotide polymorphisms in the gene encoding the major histocompatibility complex class II transactivator (CIITA) in systemic lupus erythematosus.

BACKGROUND: The major histocompatibility complex (MHC) class II transactivator (CIITA) is a master switch of antigen presentation and activates expression of the MHC II gene. Insufficient up regulation of MHC class II molecules is reported to be one of the major immunological mechanisms in systemic lupus erythematosus (SLE). OBJECTIVE: To examine the association between single nucleotide polymorphisms (SNPs) in the human CIITA gene (MHC2TA) and SLE. METHODS: Promoters and coding regions of MHC2TA were evaluated for polymorphisms in 100 patients with SLE and 100 healthy donors. Eight oligonucleotide primer sets that covered the coding region and each promoter region were used for genomic analysis of SNPs. RESULTS: Allele frequencies of previously reported SNPs did not differ between healthy donors and patients with SLE. Additionally, a new polymorphism in an intronic region at nt 485 (A-->A/G) was identified, which is close to the polymorphism at nt 474 that has been associated with one of the disease causing CIITA cDNA mutations in bare lymphocyte syndrome. This SNP was found in 11% of patients with SLE and in 3% of healthy donors, suggesting it may have a role in the pathogenesis of SLE. CONCLUSIONS: A newly identified polymorphism in an intronic region at nt 485 (A-->A/G) may have an important role in the pathogenesis of SLE.

Adolescent↗
PubMed2004

A comparison of the effects of prolonged (>10 hour) low-flow sevoflurane, high-flow sevoflurane, and low-flow isoflurane anaesthesia on hepatorenal function in orthopaedic patients.

This study compared the effects of low-flow sevoflurane, high-flow sevoflurane and low-flow isoflurane on hepatorenal function during and after more than 10 hours of anaesthesia. Twenty-five patients scheduled for elective orthopaedic surgery were categorized into three groups; low-flow sevoflurane (fresh gas flow at 1 litre/min, n = 9), high-flow sevoflurane (5 l/rmin, n = 7), or low-flow isoflurane (1 l/min, n=9). Inspiratory compoundA concentrations were measured. The groups had similar duration of anaesthesia and exposure to anaesthetic agents. The area under the curve of concentration (mean, SD) of compound A in the low-flow sevoflurane group (359.8, 106.1 ppm.h) was greater than that in the high-flow sevoflurane group (61.1, 29.3 ppm.h; P<0.01). All groups showed normal plasma creatinine and creatinine clearance, and transient postoperative increases in plasma alanine aminotransferase and alpha glutathione-S-transferase, as well as urinary glucose and alpha glutathione-S-transferase, with no significant differences between groups. There were no significant relationships between the area under the curve of concentration of compound A and the biomarkers. These findings suggest that prolonged anaesthesia with low-flow sevoflurane has similar effects on hepatorenal function to prolonged anaesthesia with high-flow sevoflurane and low-flow isoflurane.

Adult↗
PubMed2004

Factors affecting clinical outcome of patients who undergo transcatheter arterial embolisation in splenic injury.

Transcatheter arterial embolisation (TAE) offers a less invasive approach to traditional laparotomy for the management of bleeding in the context of blunt splenic injury. This is a retrospective review study to identify clinical factors associated with clinical outcome of the patients who underwent this procedure. Of 65 patients with splenic injuries at our institution, 26 patients underwent TAE for management of bleeding. The following factors were assessed to determine their relationship to procedure outcomes: American Association for the Surgery of Trauma (AAST) grade, complications, age, shock index, injury severity score (ISS), haemoglobin (Hb), haematocrit (Ht), prothrombin time (PT), activated partial thromboplastin time (APTT), systolic blood pressure (BP), BP changes during TAE, blood transfused before TAE and timing of TAE. The overall good clinical outcome rate was 73.1% (19/26). Of the factors we assessed, absence of concomitant pelvic injury, higher Hb, higher Ht, higher BP, greater increases in BP during TAE and a decreased requirement for blood transfusions before TAE were associated with good clinical outcome of the patients who underwent TAE in splenic injury.

Adolescent↗
PubMed2002

Heart rate to arterial pressure impulse response during one lung ventilation.

BACKGROUND: Although one lung ventilation (OLV) is commonly used, little is known about the modulation of the autonomic nervous system with OLV while under general anesthesia. As the frequency domain and time domain analyses are powerful analytic tools, we investigated their modulation during OLV. METHODS: Patients undergoing thoracic surgery were classified into two groups: those who did (group A, n=8) and those who did not (group N, n=8) receive atropine. After a double lumen tube was placed endotracheally, mechanical ventilation of both lungs (BLV) was established at 18 min(-1) while under isoflurane anesthesia. Electrocardiogram, systolic arterial pressure (SAP), and inspiratory flow (Finsp) were digitally recorded as follows: awake before anesthesia; BLV after anesthesia; BLV after intravenous 10 microg kg(-1) of atropine (group A) or not (group N); left OLV; and right OLV. Power spectral analyses of heart rate (HR) and SAP were computed by determining low-(LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0.40 Hz) components, and impulse response analysis was executed among HR, SAP, and Finsp. Impulse responses were assessed by the maximum values in the time domain. RESULTS: In frequency domain analysis, atropine depressed LF and LF/HF but not HF in HR variability, while no difference was observed between right OLV and left OLV. The heart rate to SAP impulse response was maintained at a significantly higher level in group A than in group N (905+/-360 vs. 425+/-375 mmHg beats(-1)min(-1)) at right OLV. A significant difference was also observed between left and right OLV within group N. CONCLUSION: Impulse response analysis demonstrated that there is a greater effect on autonomic nervous system modulation during right OLV than in left OLV, which mainly results from a parasympathetic neural linkage origin.

Adult↗
PubMed2001

Developmental changes in GABA transporter (GAT1 and GAT3) mRNA expressions in the rat olfactory bulb.

Developmental expressions of GABA transporters 1 and 3 (GAT1 and GAT3) were investigated in the rat olfactory bulb by using in situ hybridization histochemistry. We found that the expression of GAT1 and GAT3 mRNAs was dramatically changed in the granule cell layer (GCL), external plexiform layer (EPL) and glomerular layer (GL) during postnatal development. Among bulbar neurons, granule cells and periglomerular cells are GABAergic and they are localized in the GCL and GL, respectively. In the EPL, granule cells make GABAergic synapses with mitral cell dendrites. Thus, the changes seen in the GCL, EPL and GL seemed related to the development of the GABAergic system in the olfactory bulb. On the whole, our results demonstrated that expression patterns of GAT1 and GAT3 mRNAs have become similar to adult patterns on postnatal day 14 (P14), suggesting that GABA transporters may play a pivotal role in GABAergic neurotransmission after P14. However, expression patterns of GAT1 and GAT3 mRNAs in early postnatal days were quite distinct from those in adulthood. For example, in the GCL, immature granule cells already exhibited strong levels of GAT1 mRNA on P1 and the expression level was higher than that of granule cells in adulthood. GAT3 mRNA was strongly expressed in presumable radial glial cells surrounding the subependymal layer. In the EPL, few signals for the two transcripts were detected on P1 but they were markedly increased by P14. Our results indicate that GAT1 and GAT3 may play important roles in the development of the GABAergic system in the olfactory bulb.

Animals↗
PubMed2001

Detection of Epstein-Barr virus DNA and expression of CD30 antigen in primary anaplastic diffuse large B-cell lymphoma of the brain.

We describe a case of primary anaplastic diffuse large-cell lymphoma arising in the central nervous system (CNS). Primary CD30-positive anaplastic diffuse large B-cell lymphoma of the brain is very rarely reported. Given that this tumor is immunohistochemically heterogeneous, polymerase chain reaction (PCR) and Epstein-Barr virus (EBV) analysis of tumor DNA are essential techniques for early and accurate histological diagnosis in these CD30-positive cerebral lymphoma cases. We report an early CD30- and EBV-positive anaplastic diffuse large B-cell lymphoma in the CNS that was diagnosed not only from the immunohistochemical study and MRI findings, but also from the genotype confirmations. This tumor was documented to have EBV episomes of monoclonal origin by PCR analysis of immunoglobulin gene rearrangement.

B-Lymphocytes↗
PubMed2001

Distribution and molecular forms of adrenomedullin and proadrenomedullin N-terminal 20 peptide in the porcine gastrointestinal tract.

Adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP) are potent hypotensive peptides that are generated from the same precursor and expressed in a variety of mammalian tissues. The purpose of this study was to elucidate the distribution and endogenous molecular forms of AM and PAMP. To this end, we used new radioimmunoassays that recognize the ring structure of AM and the C-terminal region of PAMP to compare the distribution of AM and PAMP in porcine gastrointestinal tissues. Immunoreactive AM was abundant in the duodenum (0.334+/-0.132 fmol/mg) and ileum (0.439+/-0.235 fmol/mg), and ubiquitous in other gastrointestinal tissues. The duodenal and ileal concentrations of AM were about 4 to 14 times higher than those in other gastrointestinal tissues. Similarly, immunoreactive PAMP was abundant in the duodenum (0.577+/-0.417 fmol/mg) and ileum (1.575+/-1.445 fmol/mg) and ubiquitous in other gastrointestinal tissues. The concentrations of immunoreactive AM and PAMP were highest in the ileum. Characterization of these peptides in the ileum, using high-performance liquid chromatography, showed that they were authentic. Furthermore, the concentrations of immunoreactive AM and PAMP in the mucosa and submucosa of the ileum were significantly higher than those in whole ileum. These results suggest that AM and PAMP play physiological roles in the porcine small intestine.

Adrenomedullin↗
PubMed2001

Small dose of prostaglandin E(1) increases cardiac output without altering blood volume.

STUDY OBJECTIVE: To investigate the effect of small dose of intravenous (IV) prostaglandin E(1) (PGE(1)) on blood volume (BV) and cardiac output (CO) by pulse dye-densitometry (PDD) in patients administered isoflurane anesthesia. DESIGN: Prospective, randomized study. SETTING: University hospital. PATIENTS: 14 ASA physical status I and II adult patients undergoing elective neurosurgery. INTERVENTIONS: Patients were randomly assigned to either the PGE(1) group (n = 7) or the control group (n = 7). Anesthesia was induced with thiamylal, fentanyl, and vecuronium, and maintained with isoflurane and nitrous oxide. When the cardiovascular system stabilized after craniotomy and incision of the dura mater, we administered a small dose of PGE(1) at a rate of 0.02 microg/kg/min (PGE(1) group) or saline at a rate of 2 mL/min (control group). MEASUREMENTS AND MAIN RESULTS: Blood volume, CO, and mean transit time (MTT) were measured by PDD before and 60 minutes after the start of administration. At the same timing, mean arterial pressure (MAP), heart rate (HR), and central venous pressure (CVP) were measured, and systemic vascular resistance (SVR), cardiac index (CI), and CO/BV were computed. As for MAP, there was no significant difference within a group and between groups. In the PGE(1) group, significant increases were noted in CI from 2.54 +/- 0.46 to 3.24 +/- 0.83 (mean +/- SD) L/min/m(2) (p < 0.05), in CO/BV from 0.90 +/- 0.24 to 1.19 +/- 0.33 (p < 0.05), and in HR from 65.7 +/- 10.1 to 74.9 +/- 12.1 bpm (p < 0.05), and a significant decrease was observed in MTT from 22.3 +/- 6.5 to 18.2 +/- 5.1 seconds (p < 0.05 ). Cardiac index and CO/BV in the PGE(1) group increased higher than in the control group, while BV, CVP and SVR remained consistent in both groups. CONCLUSIONS: A small dose of PGE(1), low enough not to provoke hypotension, increased CO without alterations in BV. The increase in CO seemed to be mainly due to an increase in HR.

Alprostadil↗
PubMed2001

Prostaglandin E(2) inhibits fibroblast chemotaxis.

Fibroblasts are the major source of extracellular connective tissue matrix, and the recruitment, accumulation, and stimulation of these cells are thought to play important roles in both normal healing and the development of fibrosis. Prostaglandin E(2) (PGE(2)) can inhibit this process by blocking fibroblast proliferation and collagen production. The aim of this study was to investigate the inhibitory effect of PGE(2) on human plasma fibronectin (hFN)- and bovine bronchial epithelial cell-conditioned medium (BBEC-CM)-induced chemotaxis of human fetal lung fibroblasts (HFL1). Using the Boyden blind well chamber technique, PGE(2) (10(-7) M) inhibited chemotaxis to hFN 40.8 +/- 5.3% (P < 0.05) and to BBEC-CM 49.7 +/- 11.7% (P < 0.05). Checkerboard analysis demonstrated inhibition of both chemotaxis and chemokinesis. The effect of PGE(2) was concentration dependent, and the inhibitory effect diminished with time. Other agents that increased fibroblast cAMP levels, including isoproterenol (10(-5) M), dibutyryl cAMP (10(-5) M), and forskolin (3 x 10(-5) M) had similar effects and inhibited chemotaxis 54.1, 95.3, and 87.0%, respectively. The inhibitory effect of PGE(2) on HFL1 cell chemotaxis was inhibited by the cAMP-dependent protein kinase (PKA) inhibitor KT-5720, which suggests a cAMP-dependent effect mediated by PKA. In summary, PGE(2) appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response after injury.

Adrenergic beta-Agonists↗
PubMed2001

High survival rate of 6 cases of pulmonary large cell neuroendocrine carcinoma formerly classified as small cell carcinoma.

UNLABELLED: In the revised WHO classification of lung cancer, published in 1999, large cell neuroendocrine carcinoma (LCNEC) was employed as a new histological entity. LCNEC is generally considered a high-grade malignant lung cancer, and appropriate treatment remains to be determined. Before its new classification, LCNEC had long been classified into several entities. Advancing the review of previous cases in Nippon Medical School Hospital, we noticed that some LCNEC patients were formally diagnosed as having small cell lung cancer (SCLC), and they showed long-term survival. MATERIAL AND METHODS: All histological specimens of surgically resected SCLC in Nippon Medical School Hospital were reclassified according to the 1999 WHO classification manual. Their neuroendocrine differentiations were confirmed by the use of immunostainings with chromogranin A and synaptophysin. RESULTS: Fourteen cases satisfied the qualifications for both histological and clinical reevaluation. Among them, 6 patients were reclassified as LCNEC, and their stage distribution was as follow: IA; 1, IB; 2, IIIA; 2, and IIIB; 1. Their survival term ranged from 33.8 to 78.0 months; 5 were still alive, and 1 (IIIB) died 57.6 months after surgery. DISCUSSION: According to this study, all the LCNEC patients who were treated as SCLC patients showed more favorable prognoses than patients described in published studies, even overall lung cancer. Therefore, it is suggested that multimodality therapy for SCLC may improve the prognoses of patients with LCNEC.

Aged↗
PubMed2001

[Assessment of general movements at routine medical examination of one-month-old infants].

On routine medical examination of one-month-old infants, general movements (GMs) were video-recorded for about 5 minutes of 252 infants born at Kyoto City Hospital or other hospitals, including the infants discharged from the NICU. Their ages ranged from 39 postmenstrual to 8 post-term weeks. One of the experimenters assessed 181 infants among 252 available for assessment of their GMs twice at intervals of more than one month without being informed about their clinical histories. The subjects included 19 low-birthweight infants, and their average age was 3.5 post-term weeks. The assessment was carried out in comparison to the "gold standard" GMs depicted in a demonstration video produced by the GMs Trust. The Kappa value for intra-observer concordance was 0.85. Twenty (11.0%) out of the 181 infants were judged abnormal because of their poor repertoire of GMs in both the first and second assessment. Neither cramped synchronized GMs nor chaotic ones were observed. Meanwhile, 155 (85.6%) out of the 181 infants were found to be normal. The incidence of abnormal GMs was significantly higher among infants with history of asphyxia and/or respiratory distress than among low-risk infants. There of the experimenters independently assessed GMs of 50 infants among 181 which had been video-recorded between June and September 1998. The inter-observer concordance was higher among the low-birth weight infants than among full-term ones. In conclusion, qualitative assessment of GMs by an experienced observer at routine medical examination of one-month old infants is a useful method for the follow-up of high-risk infants.

Female↗
PubMed2001

[Development of the chromatography analysis of liquid trapping 99mTc-Technegas using Jikei impinger].

We developed the equipment which collected 99mTc-Technegas into liquid (saline) and named this equipment an impinger of Jikei University Style. We further developed a technique using this impinger to evaluate its formation qualitatively by paper chromatography. Utilizing this technique we investigated various factors that caused environmental contamination by 99mTc-Technegas, including changes over time in a Technegas generator. It was demonstrated that upon getting mixed with oxygen gas to the argon gas, the Technegas generator induced contamination of 99mTc-Pertechnegas easily, leading to changes in its formation. The change of formation quality of the Technegas generator with the lapse of time was also revealed. These findings indicated that the maintenance and inspection of the equipment were important. This method is a simple and easy technique for the evaluation of 99mTc-Technegas formation, making it possible to perform the quality control of examination agent and the Technegas generator.

Chromatography, Paper↗
PubMed2001

A prospective multicenter trial to determine the incidence of transient neurologic symptoms after spinal anesthesia with phenylephrine added to 0.5% tetracaine.

The addition of vasoconstrictors for spinal anesthesia is controversial, since an increase in the incidence of transient neurologic symptoms (TNS) has been reported. A multicenter, randomized, double-blind study was conducted to assess the effectiveness of spinal anesthesia with phenylephrine in addition to tetracaine as well as the incidence of neurological complications. We studied 64 patients with comparable demographic characteristics who were scheduled for elective surgery for a lower limb, or a gynecological or urological procedure. The patients were allocated randomly into 2 groups. Group P (n = 34) received 0.5% tetracaine in 10% glucose with 0.025% phenylephrine, while group C (n = 30) received 0.5% tetracaine in 10% glucose. Our results showed that only 2 patients (6.7%) in group C experienced TNS, and their symptoms disappeared within 72 hr after anesthesia, while none of the patients (0%) in group P complained of symptoms. The incidence of TNS was thus not significantly different between the two groups. Six hours after the sensory block, group P patients demonstrated sensory disturbance, with the median spinal dermatome corresponding to the L1 segment. Moreover, systolic blood pressure in group P was significantly higher than that in group C, 5 min, 15 min, and 20 min after injection. The incidence of TNS in the present study does not seem to be greater after surgery with spinal anesthesia using 0.5% hyperbaric tetracaine and 0.5 mg phenylephrine than without phenylephrine. Randomized, double-blind, cross-over trials with a larger sample size would be required in the future to obtain more reliable results.

Anesthesia, Spinal↗
PubMed2001

[Patient-controlled epidural analgesia with bupivacaine and fentanyl suppresses postoperative delirium following hepatectomy].

Postoperative delirium occurs frequently following major surgery, especially after hepatectomy. We hypothesized that better methods of postoperative pain control would decrease postoperative delirium. To clarify the magnitude of postoperative pain and incidence of postoperative delirium in hepatectomy patients, subjects received patient-controlled epidural analgesia (PCEA) using bupivacaine and fentanyl (Group P), or continuous epidural mepivacaine (Group E) following intraoperative epidural administration of morphine. The magnitude of postoperative pain was estimated by use of an analgesic adjuvant and delirium was classified as mild (insomnia, disturbance of sleepwake cycle), moderate (disorientation, hallucination), or severe (restlessness, confusion, agitation), based on the medical records. Analgesic adjuvant usage was less in Group P than in Group E, while the incidences of moderate and severe delirium were significantly less frequent in Group P than in Group E (35.7% versus 75.0%, and 14.3% versus 50.0% respectively). Moreover, less amount of antipsychotic drugs was given in Group P than in Group E. These results suggest that the better pain relief and patient satisfaction provided by PCEA contributed to a decrease in the incidence of delirium, because of continuous opioid administration and patient-control analgesia. We concluded that PCEA with bupivacaine and fentanyl can limit postoperative delirium following hepatectomy.

Aged↗