Biomedical subjects

S Koizumi

Publications and source records attributed to S Koizumi.

At least 91 records · Page 5Linked to original sources

PubMed1999

[A case of spontaneous hemopneumothorax associated with uncontrolled massive bleeding after inserting thorathic drain].

A 31-year-old man admitted to our hospital complaining of right chest pain. Chest X-ray on admission revealed a collapsed lung and an air fluid line in the right thorax. A chest tube drainage was carried out, but hemorrhagic pleural fluid was drainaged. Forty minutes later, an anemia developed and chest X-ray showed increased massive right pleural collection. Therefore, emergent surgery was performed. An operation under thoracoscopic guidance was converted into thoracotomy because of massive blood clots and fresh bleeding. A bleeding originating from the branch of 1st intercostal artery and a bulla on upper lobes were noted. The artery was coagulated with electrocoutary and ligated using Endo-loop. This artery is not congenital abnormal one but collateral expanded one of which the elastic lamina is thickened. Spontaneous hemopneumothorax is life-threatening, emergent operation should be undergone.

Adult↗

PubMed1999

[Three cases of gastric cancer (Borrmann type IV) presenting with right back pain caused by right hydronephrosis as the first symptom].

We experienced three cases of right hydronephrosis, which were later diagnosed to have been caused by gastric cancer (Borrmann type IV). The patients were 25-, 38-, and 50-year-old women who complained of right back pain. Ultrasound sonography revealed right hydronephrosis in all three cases. We conducted drip infusion pyelography, computed tomographic scan and retrograde pyelography, but there were no signs of urinary stones or tumors, except for the presence of right ureteral stenosis. Since the patients had upper abdominal discomfort, they underwent gastrofiberscopy, which revealed scirrhous gastric cancer. We suspected that the right ureteral stenosis was caused by metastasis of gastric cancer. After a double J catheter was indwelt at the right ureter, combination chemotherapy of methetrexate + 5-fluorouracil was conducted. The right hydronephrosis diminished and all three patients became catheter-free.

Adult↗

PubMed1999

Second opinion behaviour among Japanese primary care patients.

BACKGROUND: Second opinion behaviour is often observed among Japanese primary care patients. These patients secretly visit university-affiliated hospitals without informing their doctors. Research to elucidate the psychosocial determinants of this behaviour in the Japanese primary care setting is needed. AIM: To describe the sociodemographic characteristics of second opinion patients (SOPs), and to determine the factors related to this behaviour. METHOD: Patients from the general medicine clinic answered our original questionnaire and a 30-item General Health Questionnaire (GHQ-30). A random sample of patients was questioned using the Diagnostic Interview Schedule. SOPs were defined as those patients who had visited another medical facility with the same complaint, and 'doctor-shopping' patients (DSPs) were defined as those patients who had visited two or more medical facilities with the same complaint. RESULTS: There were 420 SOPs among 1033 patients (41.0%). The multivariate analysis showed that residence and GHQ-30 were the significant differences between the SOPs and the first-visit patients (FVP) (P < 0.0005 for both factors). Also, the SOPs were anxious and sought advice from anybody, unlike the FVPs. Compared with the DSPs, they had a short duration of illness and they did not feel a worsening of their symptoms (P = 0.0001 for duration of illness; P = 0.006 for condition of illness). CONCLUSION: Our results showed that the SOPs who lived far from the medical school hospital felt anxiety and went to a university-affiliated hospital on the advice of anybody. Determining the reasons for this behaviour will require empirical studies regarding the nature of the patient's anxiety for illness.

Adolescent↗

PubMed1998

Frequent aberration of FHIT gene expression in acute leukemias.

We analyzed the mRNA expression of the FHIT gene by reverse transcription-PCR (RT-PCR) in 54 cases of acute lymphoblastic leukemia (ALL; 11 cases of T-cell ALL [T-ALL] and 43 cases of non-T-ALL) and 40 cases of acute myeloid leukemia (AML). In 46% of the ALL cases and 55% of the AML cases, FHIT expression was absent or markedly decreased. Only abnormal short bands were detected in 30% of the ALL cases and 5% of the AML cases. Eighteen of 19 abnormal transcripts had the same fusion of exons 2-7, and all lacked the starting codon in exon 5. No obvious normal-sized PCR products were detected in cases exhibiting abnormal transcripts. These findings suggest that the expression of functional FHIT protein was lost in the majority of ALL (76%) and AML (60%) cases. Differential quantitative PCR of exons 3-9 of the FHIT gene and RT-PCR of the PTPRG gene, which is centromeric to the FHIT gene, showed the presence of the target sequences. Fluorescence in situ hybridization analysis using probes covering exons 5 and 8 revealed no difference in the signal patterns between leukemia and normal cells, showing one or two signal doublets in more than 90% of nuclei, and indicated that gross segments of the FHIT gene were not homozygously deleted in these cases. A small number of transcripts with an aberrant fusion between exons 2 and 7 were detected by RT-PCR in the bone marrow cells from four healthy individuals. Granulocytes, lymphocytes, and monocytes in the bone marrow cells of a healthy individual contained transcripts with the same fusion. This unique fusion of exons 2 and 7 might be preferentially seen in either neoplastic or normal hematopoietic cells, regardless of their lineage. The finding that FHIT expression was abolished in the majority of leukemia cases might support the hypothesis that the FHIT gene acts as a tumor suppressor, at least in leukemia.

Acid Anhydride Hydrolases↗

PubMed1998

Developmental changes and functional properties of human memory T cell subpopulations defined by CD60 expression.

The present study was undertaken to examine developmental changes of T cells expressing CD60 and their functional properties. Three-color immunofluorescence analysis revealed that the CD60 antigen was preferentially expressed on a proportion of memory (CD45RO+) CD4+ T cells, but less on memory CD8+ T cells, while this antigen is undetectable in naive (CD45RO-) T cells. A frequency of memory CD4+ T cells expressing CD60 in the peripheral blood was negligible in newborns and gradually increased with advancing age. CD60+ memory CD4+ T cells showed stronger proliferative responses to PPD and produced higher levels of IL-4 and IL-10 than CD60- ones, whereas production of IL-2 and IFN-gamma was similarly found in both cell subpopulations. In addition, it was shown that efficient helper activity for Ig production by B cells was predominated in CD60+ memory CD4+ T cells. These results suggest that CD60 may be primarily expressed on the functionally differentiated memory effector cells among circulating CD45RO+ CD4+ T cells.

Adolescent↗

PubMed1998

Acetylcholine triggers L-glutamate exocytosis via nicotinic receptors and inhibits melatonin synthesis in rat pinealocytes.

Rat pinealocytes, melatonin-secreting endocrine cells, contain peripheral glutaminergic systems. L-Glutamate is a negative regulator of melatonin synthesis through a metabotropic receptor-mediated inhibitory cAMP cascade. Previously, we reported that depolarization of pinealocytes by externally added KCl and activation of L-type Ca2+ channels resulted in secretion of L-glutamate by microvesicle exocytosis. What is unknown is how and what kinds of stimuli trigger glutamate exocytosis under physiological conditions. Here, we report that the nicotinic acetylcholine receptor can trigger glutamate exocytosis from cultured rat pinealocytes. Moreover, acetylcholine or nicotine inhibited norepinephrine-dependent serotonin N-acetyltransferase activity, which results in decreased melatonin synthesis. These activities were blocked by (2S,3S, 4S)-2-methyl-2-(carboxycyclopropyl)glycine, an antagonist of the metabotropic glutamate receptor. These results suggest that cholinergic stimulation initiates the glutaminergic signaling cascade in pineal glands and that parasympathetic neurons innervating the gland exert negative control over melatonin synthesis by way of the glutaminergic systems.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1998

Functional coupling of secretion and capacitative calcium entry in PC12 cells.

The caffeine-evoked effects on the intracellular Ca2+ concentration ([Ca2+]i) and on the release of dopamine by PC12 cells were investigated. Stimulation by caffeine resulted in a transient Ca2+ release which was followed by a sustained phase of Ca2+ entry through a non-voltage dependent pathway. Treatment with cyclopiazonic acid (CPA) or thapsigargin, inhibitors of the Ca2+ATPase pump of the endoplasmic reticulum, resulted in only a sustained rise in [Ca2+]i in the presence of extracellular Ca2+. Pretreatment of cells with CPA or thapsigargin abolished the subsequent Ca2+ responses to caffeine. Caffeine also evoked the release of dopamine from the cells only in the presence of extracellular Ca2+, which was mimicked by CPA. These results suggest that store-dependent Ca2+ entry evoked by caffeine has an indispensable role in the secretory response in an excitable cell line, PC12 cells.

Animals↗

PubMed1998

Inhibition by imipramine of ATP-evoked responses in rat pheochromocytoma cells.

The effect of imipramine on the ATP-evoked release of dopamine was analyzed in parallel with its effects on the rise in the intracellular Ca2+ concentration ([Ca2+]i) and current induced by ATP in rat pheochromocytoma PC12 cells. Imipramine (10-300 microM) inhibited the ATP-evoked release of dopamine and rise in [Ca2+]i in a concentration-dependent fashion though the effect of imipramine on the release was slightly more obvious. Imipramine also inhibited the ATP-activated inward current at a similar concentration range. These results show a new pharmacological profile of imipramine, namely the inhibition of P2X2 receptors.

Adenosine Triphosphate↗

PubMed1998

Functional coupling of secretion and capacitative calcium entry in PC12 cells.

The caffeine-evoked effects on the intracellular Ca2+ concentration ([Ca2+]i) and on the release of dopamine by PC12 cells were investigated. Stimulation by caffeine resulted in a transient Ca2+ release which was followed by a sustained phase of Ca2+ entry through a non-voltage dependent pathway. Treatment with cyclopiazonic acid (CPA) or thapsigargin, inhibitors of the Ca2+ ATPase pump of the endoplasmic reticulum, resulted in only a sustained rise in [Ca2+]i in the presence of extracellular Ca2+. Pretreatment of cells with CPA or thapsigargin abolished the subsequent Ca2+ responses to caffeine. Caffeine also evoked the release of dopamine from the cells only in the presence of extracellular Ca2+, which was mimicked by CPA. These results suggest that store-dependent Ca2+ entry evoked by caffeine has an indispensable role in the secretory response in an excitable cell line, PC12 cells.

Animals↗

PubMed1998

A prospective analysis of the factors influencing pancreaticojejunostomy performed using a single method, in 100 consecutive pancreaticoduodenectomies.

The factors influencing the healing process of pancreaticojejunostomy (P-J) following pancreaticoduodenectomy (PD) are still ill defined, allowing the recommendation of various anastomotic methods. We conducted a prospective study to determine the risk factors influencing the protracted healing of P-J, examining 100 consecutive patients who underwent PD followed by P-J, performed as an end-to-side "mucosa-to-mucosa" anastomosis using vertical mattress sutures (VMS method). Protracted healing of P-J was classified as either peripancreatic sepsis (PPS), defined as prolonged suppurative discharge of less than 50 ml a day from the drain beneath the P-J for more than 1 week; or a pancreatic fistula (PF), defined as prolonged discharge of more than 50 ml a day with a high amylase content (> 1000 IU) for more than 1 week. There were 80 patients with a malignant neoplasm, and 20 with benign disease. The overall incidence of healing problems following P-J was 9%, which included 6 patients (6%) with PPS and 3 (3%) with PF. Apart from an advanced age of more than 70 years, none of the patients' characteristics or postoperative complications influenced the healing of P-J. The type of reconstruction, an anastomotic stent, the duct size, and a "soft" pancreas were not risk factors either. In conclusion, no factors, apart from the age or any special problem of an individual patient, influenced the dehiscence of P-J when the VMS method was used after PD.

Adult↗

PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗

PubMed1998

Large-scale production of UDP-galactose and globotriose by coupling metabolically engineered bacteria.

A large-scale production system of uridine 5'-diphospho-galactose (UDP-Gal) has been established by the combination of recombinant Escherichia coli and Corynebacterium ammoniagenes. Recombinant E. coli that overexpress the UDP-Gal biosynthetic genes galT, galK, and galU were generated. C. ammoniagenes contribute the production of uridine triphosphate (UTP), a substrate for UDP-Gal biosynthesis, from orotic acid, an inexpensive precursor of UTP. UDP-Gal accumulated to 72 mM (44 g/L) after a 21 h reaction starting with orotic acid and galactose. When E. coli cells that expressed the alpha1,4-galactosyltransferase gene of Neisseria gonorrhoeae were coupled with this UDP-Gal production system, 372 mM (188 g/L) globotriose (Galalpha1-4Galbeta1-4Glc), a trisaccharide portion of verotoxin receptor, was produced after a 36 h reaction starting with orotic acid, galactose, and lactose. No oligosaccharide by-products were observed in the reaction mixture. The production of globotriose was several times higher than that of UDP-Gal. The strategy of producing sugar nucleotides by combining metabolically engineered recombinant E. coli with a nucleoside 5'-triphosphate producing microorganism, and the concept of producing oligosaccharides by coupling sugar nucleotide production systems with glycosyltransferases, can be applied to the manufacture of other sugar nucleotides and oligosaccharides.

Base Sequence↗

PubMed1998

The effect of a secreted form of beta-amyloid-precursor protein on intracellular Ca2+ increase in rat cultured hippocampal neurones.

1. The effects of secreted forms of beta-amyloid-precursor proteins (APP(S)s) on the intracellular Ca2+ concentration ([Ca2+]i) were investigated in rat cultured hippocampal neurones. APP695S, a secretory form of APP695, attenuated the increase in [Ca2+]i evoked by glutamate. In addition, APP695S itself evoked an increase in [Ca2+]i in 1 or 2 day-cultured hippocampal cells, but not in 7 to 13 day-cultured cells. 2. Eighty-one percent of neurones which were immunocytochemically positive for microtubule-associated protein 2 responded to APP695S with an increase in [Ca2+]i. 3. APP695S induced a transient rise in [Ca2+]i even in the absence of extracellular Ca2+ and produced an elevation in inositol-1,4,5-trisphosphate (IP3) in a concentration-dependent manner from 100 to 500 ng ml(-1). In the presence of extracellular Ca2+, APP695S caused a transient rise in [Ca2+]i followed by a sustained phase at high [Ca2+]i, suggesting Ca2+ entry from the extracellular space. 4. The [Ca2+]i elevation was mimicked by amino terminal peptides of APPs, but not by carboxy terminal peptides. 5. These results taken together suggest that APP695S induces an increase in [Ca2+]i in hippocampal neurones through an IP3-dependent mechanism that changes according to the stage of development.

Amyloid beta-Protein Precursor↗

PubMed1998

ATP stimulation of Ca2+ -dependent plasminogen release from cultured microglia.

1. ATP (10-100 microM), but not glutamate (100 microM), stimulated the release of plasminogen from microglia in a concentration-dependent manner during a 10 min stimulation. However, neither ATP (100 microM) nor glutamate (100 microM) stimulated the release of NO. A one hour pretreatment with BAPTA-AM (200 microM), which is metabolized in the cytosol to BAPTA (an intracellular Ca2+ chelator), completely inhibited the plasminogen release evoked by ATP (100 microM). The Ca2+ ionophore A23187 induced plasminogen release in a concentration-dependent manner (0.3 microM to 10 microM). 2. ATP induced a transient increase in the intracellular calcium concentration ([Ca2+]i) in a concentration-dependent manner which was very similar to the ATP-evoked plasminogen release, whereas glutamate (100 microM) had no effect on [Ca2+]i (70 out of 70 cells) in microglial cells. A second application of ATP (100 microM) stimulated an increase in [Ca2+]i similar to that of the first application (21 out of 21 cells). 3. The ATP-evoked increase in [Ca2+]i was totally dependent on extracellular Ca2+, 2-Methylthio ATP was active (7 out of 7 cells), but alpha,beta-methylene ATP was inactive (7 out of 7 cells) at inducing an increase in [Ca2+]i. Suramin (100 microM) was shown not to inhibit the ATP-evoked increase in [Ca2+]i (20 out of 20 cells). 2'- and 3'-O-(4-Benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP), a selective agonist of P2X7 receptors, evoked a long-lasting increase in [Ca2+]i even at 1 microM, a concentration at which ATP did not evoke the increase. One hour pretreatment with adenosine 5'-triphosphate-2', 3'-dialdehyde (oxidized ATP, 100 microM), a selective antagonist of P2X7 receptors, blocked the increase in [Ca2+]i induced by ATP (10 and 100 microM). 4. These data suggest that ATP may transit information from neurones to microglia, resulting in an increase in [Ca2+]i via the ionotropic P2X7 receptor which stimulates the release of plasminogen from the microglia.

Adenosine Triphosphate↗

PubMed1998

Characterization of Ca2+ influx through recombinant P2X receptor in C6BU-1 cells.

1. The effects of exogenous adenosine 5'-triphosphate (ATP) and alpha,beta-methylene ATP (alpha,beta meATP) on C6BU-1 cells transfected with P2X2 and P2X3 subtypes, separately or together (P2X2+3), were investigated using fura-2 fluorescence recording and whole-cell patch clamp recording methods. 2. Untransfected C6BU-1 cells showed no intracellular Ca2+ ([Ca2+]i) increase in response to depolarizing stimulation with high K+ or stimulation with ATP. There was no current induced by ATP under voltage clamp conditions in untransfected C6BU-1 cells. ATP caused Ca2+ influx only from extracellular sources in C6BU-1 cells transfected with the P2X subtypes, suggesting that the C6BU-1 cell line is suitable for the characterization of Ca2+ influx through the P2X subtypes. 3. In C6BU-1 cells transfected with the P2X2 subtype, ATP (more than 10 microM) but not alpha,beta meATP (up to 100 microM) evoked a rise in [Ca2+]i. 4. In the cells transfected with the P2X3 subtype, current responses under voltage clamp conditions were observed at ATP concentrations higher than 0.1 microM of alpha,beta meATP were required. This discrepancy in the concentration dependence of the agonist responses with respect to the [Ca2+]i rise and the current response was seen only with the P2X3 subtype. In addition, the agonist-induced rise in [Ca2+]i was observed only after the first application because of desensitization of this subtype. 5. In C6BU-1 cells co-transfected with P2X2 and P2X3, ATP at 1 microM evoked a [Ca2+]i rise. This responsiveness was higher than that of the other subtype combinations tested. The efficiency of expression was improved by co-transfection with P2X2 and P2X3, when compared to transfection with the P2X3 subtype alone. The desensitization of the P2X2+3 was apparently slower than that of the P2X3 subtype alone. Therefore, this combination could respond to the repeated application of agonists each time with a [Ca2+]i rise. 6. These results suggest that the P2X2 and P2X3 subtypes assemble a heteromultimer and that this heterogeneous expression acquires more effective Ca2+ dynamics than that by homogeneously expressed P2X2 or P2X3.

Adenosine Triphosphate↗

PubMed1998

Peripheral blood stem cell autografts for the treatment of children over 1 year old with stage IV neuroblastoma: a long-term follow-up.

This is the first report of the long-term therapeutic results in 22 children more than 1 year old with stage IV neuroblastoma who were treated with autologous peripheral blood stem cell transplantation (PBSCT). The median age of the patients at PBSCT was 4 years (1 to 10 years) and seven of the 17 patients who were evaluated for N-myc amplification were positive. PBSC were collected by a median of four aphereses per patient. The patients underwent PBSCT from 6 to 21 months after the start of therapy (median 10.5 months) at which time 13 patients were in CR, seven were in PR, and two had refractory disease. Multi-drug therapy using the 'high-MEC' regimen consisting of carboplatinum (400 mg/m2) and VP-16 (200 mg/m2) on days -7 to -4, and melphalan (90 mg/m2) on days -3 and -2, was the primary cytoreductive regimen. The median number of infused MNC and CFU-GM was, respectively, 4.3 x 10(8)/kg and 2.4 x 10(5)/kg. After PBSCT, three patients died of regimen-related toxicities and one patient who was transplanted with refractory disease died of disease progression without any benefit from transplantation. Hematological recovery was evaluated in 21 patients, excluding one early death. The median number of days required to achieve an AGC of >0.5 x 10(9)/l and platelet count of >50 x 10(9)/l were, respectively, 11 and 46. Eleven patients relapsed 3 to 50 months after PBSCT, and currently seven patients (5/13 who were transplanted in CR and 2/7 in PR) are surviving disease-free at 52 to 84 months. Although the retrospective nature of this study and several variables prevent a meaningful analysis, the overall results still support the feasibility of developing a prospective study of PBSCT with a larger number of children with high-risk neuroblastoma.

Child↗

PubMed1998

Association of the Src family tyrosine kinase Fyn with TrkB.

Fyn tyrosine kinase, a member of the Src family, was recently reported to be present in neurons and glia cells. We investigated whether Fyn is involved in the Trk-dependent signal transduction pathways of neurotrophin. The Fyn-Src homology domain 2 (SH2) was observed to associate in vitro with the intracellular domain of TrkB (ICD-TrkB). This association was dependent on the autophosphorylation of ICD-TrkB. The Fyn-SH2 domains bound to phosphorylated ICD-TrkB (pICD-TrkB) with an affinity similar to the binding of phospholipase Cgamma (PLCgamma)-SH2 domains to its autophosphorylation site in TrkB. The Src-SH2 domains showed substantially lower affinity with pICD-TrkB, suggesting that the association between Fyn-SH2 and pICD-TrkB is not due to nonspecific interactions of SH2 domains with phosphorylated tyrosine residues. This is further supported by the observation that Fyn-SH2 was able to trap phosphorylated TrkB in cell lysate prepared from primary rat cortical neurons stimulated with brain-derived neurotrophic factor (BDNF). In contrast, endogenous Fyn was coprecipitated with TrkB from cortical neurons without BDNF stimulation. This basal association showed a threefold increase on BDNF stimulation, probably due to the SH2/phosphotyrosine interaction that was observed in the cell-free system. All these data suggest the involvement of Fyn in the neurotrophin signal transduction pathways downstream of TrkB.

Animals↗

PubMed1998

Novel Fas (CD95/APO-1) mutations in infants with a lymphoproliferative disorder.

Fas is an apoptosis-signaling receptor important for homeostasis of the immune system. In this study, Fas-mediated apoptosis and Fas mutations were analyzed in three Japanese children from two families with a lymphoproliferative disorder characterized by lymphadenopathy, hepatosplenomegaly, pancytopenia, hypergammaglobulinemia and an increase in TCR alphabeta+ CD4- CD8- T cells. Apoptosis induced by anti-Fas mAb was defective in both activated T cells and B cells, and granulocytes from these patients. Truncated Fas receptor lacking the cytoplasmic death domain caused by a point mutation in the splice region of intron 7 were demonstrated in two siblings. A homozygous point mutation in the splice acceptor of intron 3 was found in the Fas gene of the third patient, which resulted in the skipping of exon 4 and complete loss of Fas expression. Corresponding to these mutations, soluble Fas concentrations were decreased and reciprocally soluble Fas ligands were increased in patients' sera. Interestingly, co-stimulation by immobilized anti-Fas mAb in T cells from the two siblings was comparable to that seen in normal T cells. These results suggest that Fas-mediated apoptosis plays a pivotal role in immunological homeostasis in vivo, especially regarding clonal deletion of immune cells in humans.

Apoptosis↗