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S Koizumi

Publications and source records attributed to S Koizumi.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Experience of direct hemoperfusion using polymyxin B-immobilized fiber on patients with endotoxin shock from urosepsis].

We report the effects of direct hemoperfusion using polymyxin B-immobilized fiber (PMX treatment) on two patients with endotoxin shock from urosepsis. In both cases, urosepsis caused by pyelonephritis from a ureteral stone progressed to endotoxin shock and disseminating intravascular coagulation (DIC). Single J catheter was indwelt in the ureter for the purpose of drainage before PMX treatment. Drainage of the origin of infection, using effective antibiotics and PMX treatment improved shock state and DIC earlier than we expected.

Anti-Bacterial Agents↗
PubMed2001

A novel single-nucleotide polymorphism in the 3'-untranslated region of the human dihydrofolate reductase gene with enhanced expression.

A novel single-nucleotide polymorphism (SNP), 829C-->T in the 3'-untranslated region of the human dihydrofolate reductase (DHFR) gene transcript, was identified in the study population of 37 patients with childhood leukemias/lymphomas and 83 healthy Japanese children. Frequencies of the DHFR 829C/C, 829C/T, and 829T/T genotypes were 83.8, 10.8, and 5.4%, respectively, in the cases and 74.7, 19.3, and 6.0% in the controls, showing no significant difference in genotype frequencies between the cases and controls. When determined by real-time quantitative reverse transcription-PCR analysis, the highest expression of the DHFR transcript was demonstrated in the samples with a DHFR 829T/T polymorphism (P < 0.001). Direct association of the presence of the SNP with methotrexate-related adverse events in each patient was not demonstrated in this limited analysis. These data suggest that the novel DHFR 829 polymorphism is associated with a positive role in gene expression and provide evidence of a functional SNP in the 3' regulatory region of the gene.

3' Untranslated Regions↗
PubMed2000

Identification and characterization of three novel beta 1,3-N-acetylglucosaminyltransferases structurally related to the beta 1,3-galactosyltransferase family.

We have isolated three types of cDNAs encoding novel beta1,3-N-acetylglucosaminyltransferases (designated beta3Gn-T2, -T3, and -T4) from human gastric mucosa and the neuroblastoma cell line SK-N-MC. These enzymes are predicted to be type 2 transmembrane proteins of 397, 372, and 378 amino acids, respectively. They share motifs conserved among members of the beta1,3-galactosyltransferase family and a beta1,3-N-acetylglucosaminyltransferase (designated beta3Gn-T1), but show no structural similarity to another type of beta1,3-N-acetylglucosaminyltransferase (iGnT). Each of the enzymes expressed by insect cells as a secreted protein fused to the FLAG peptide showed beta1,3-N-acetylglucosaminyltransferase activity for type 2 oligosaccharides but not beta1,3-galactosyltransferase activity. These enzymes exhibited different substrate specificity. Transfection of Namalwa KJM-1 cells with beta3Gn-T2, -T3, or -T4 cDNA led to an increase in poly-N-acetyllactosamines recognized by an anti-i-antigen antibody or specific lectins. The expression profiles of these beta3Gn-Ts were different among 35 human tissues. beta3Gn-T2 was ubiquitously expressed, whereas expression of beta3Gn-T3 and -T4 was relatively restricted. beta3Gn-T3 was expressed in colon, jejunum, stomach, esophagus, placenta, and trachea. beta3Gn-T4 was mainly expressed in brain. These results have revealed that several beta1,3-N-acetylglucosaminyltransferases form a family with structural similarity to the beta1,3-galactosyltransferase family. Considering the differences in substrate specificity and distribution, each beta1,3-N-acetylglucosaminyltransferase may play different roles.

Amino Acid Sequence↗
PubMed2000

Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats: involvement of heteromeric P2X2/3 receptor signaling in capsaicin-insensitive primary afferent neurons.

Extracellular ATP has been known to activate sensory neurons via the ATP-gated ion channels P2X receptors, indicating that the P2X receptors may play a role in signal transduction of pain from the periphery to the spinal cord in vivo. Here, we found a novel nociceptive response induced by ATP, mechanical allodynia (hypersensitivity to innocuous mechanical stimulus). Injection of alpha,beta-methylene ATP (alpha(beta)meATP), an agonist to P2X receptor, into plantar surface in rats produced the mechanical allodynia along with previously described nocifensive behavior and thermal hyperalgesia. This allodynic response was blocked by pretreatment with the P2 receptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulfonate. Interestingly, only the mechanical allodynia evoked by alpha(beta)meATP selectively remained in neonatal capsaicin-treated adult rats that had selectively lost the capsaicin-sensitive neurons. ATP has been shown to produce two distinguishable electrophysiological responses (inward currents with rapid and slow desensitization) in dorsal root ganglion (DRG) neurons. In the present electrophysiological experiment, the percentage of DRG neurons that responded to alpha(beta)meATP with slow desensitizing inward current remained constant in capsaicin-treated rats, whereas the percentage that responded with rapid desensitizing current dramatically decreased. Taken together with our previous finding that the alpha(beta)meATP-activated slow desensitizing current in DRG neurons is mediated by heteromeric P2X2/3 (P2X2 and P2X3) receptors, it is hypothesized that activation of heteromeric P2X2/3 receptors in peripheral terminals of capsaicin-insensitive primary afferent fibers leads to the induction of mechanical allodynia.

Adenosine Triphosphate↗
PubMed2000

Novel responses of ZRF, a variant of human MTF-1, to in vivo treatment with heavy metals.

Heavy metal-dependent transcriptional activation of metallothionein (MT) genes is mediated by multiple enhancer sequences, metal responsive element (MRE), located in the upstream region of the genes. Previously, we have reported purification of a zinc-dependent MRE-binding protein, zinc regulatory factor (ZRF), from HeLa cells, and have pointed to the close relationship between ZRF and mouse MRE-binding transcription factor-1 (MTF-1) according to the analysis of partial amino acid sequences. By means of cDNA cloning and the product analyses, we show that ZRF is a variant of human MTF-1 (hMTF-1), which carries a single amino acid exchange in the zinc finger domain. Accordingly, ZRF is renamed hMTF-1b. Expression of hMTF-1b in HeLa cells is constitutive at both mRNA and protein levels, and is unaffected by treatment with cadmium (Cd). On the other hand, when cells were fractionated into nuclear extract and cytosol, a large part of the hMTF-1b was recovered in the cytosol fraction. A significant increase in the amount of nuclear hMTF-1b occurs when cells are treated with various heavy metals, including Cd, Zn, Cu and Ag, which is associated with concomitant decrease in the amount recovered in the cytosol fraction. Since immunocytochemical analysis revealed that intracellular distribution of hMTF-1b is restricted to the nucleus irrespective of the heavy metal treatment, such an increment in the nuclear extracts apparently results from promotion of nuclear retention of hMTF-1b by the heavy metal treatment. Analysis by native gel electrophoresis shows that the mobility of hMTF-1b significantly changes in association with Cd treatment, raising the possibility that a conformational change of hMTF-1b occurs in response to treatment with heavy metals in vivo.

Amino Acid Sequence↗
PubMed2000

Fournier's gangrene caused by Candida species as the primary organism.

Fournier's gangrene is a rare entity caused by polymicrobial aerobic and anaerobic bacteria. We report a case of Fournier's gangrene caused by Candida as the primary organism. A 65-year-old man presented with perineal soft-tissue infections. He underwent surgical debridement and suprapubic cystostomy with both antifungal and antimicrobial therapy. The histopathologic examination revealed necrotizing fasciitis with Candida species as the sole initial pathogen. The case suggests that primary fungal pathogens should be considered as a causative organism of Fournier's gangrene.

Aged↗
PubMed2000

Roles of zinc fingers and other regions of the transcription factor human MTF-1 in zinc-regulated DNA binding.

Mammalian metallothionein genes are transcriptionally regulated by heavy metals through cis-acting metal responsive elements (MREs). The MRE-binding transcription factor-1 (MTF-1), a protein containing six C(2)H(2)-type Zn fingers, is essential for MRE-mediated transcriptional activation. DNA binding of MTF-1 is known to be stimulated by Zn in vitro, but the binding was also largely influenced by redox conditions, suggesting that redox signals could modulate MTF-1 activity. To locate the functional domain required for Zn regulation, several deletion mutants of human MTF-1b, a newly cloned transcriptionally active MTF-1 variant, were characterized. This analysis showed that the N-terminal region and Zn-finger domain play roles in metal response. Functional roles of individual Zn fingers were estimated by co-transfection assays by using an MRE-driven reporter gene and vectors that express MTF-1b mutants each carrying one defective finger. Mutations in the N-terminal four fingers dramatically reduced the transcriptional activity, and at least for three of them the transcriptional defect was due to reduced DNA binding. These results indicate that the six Zn fingers are not functionally equivalent, probably sharing distinct roles such as direct DNA recognition and regulatory functions.

Binding Sites↗
PubMed2000

Structural evidence of genomic exon-deletion mediated by Alu-Alu recombination in a human case with heme oxygenase-1 deficiency.

We previously reported a family affected by heme oxygenase-1 (HO-1) deficiency [Yachie et al., 1999]. The proband was a compound heterozygote for a complete loss of exon 2 (the maternal allele) and a two-nucleotide deletion within exon 3 (the paternal allele). In this report, we describe a large genomic deletion (1730 bp) including entire exon 2 in this family as a specific mechanism generating exon-2 absence observed in the HO-1 mRNA. Analysis of the deletion junction demonstrated fusion of a 5' portion of Alu-Sx element with a 3' portion of Alu-Sq element. The junction contained sequences with high homology to the recombinogenic Alu "core" sequence. These structural features of the HO-1 gene suggest homologous recombination associated with Alu element. This study presents the initial characterization of the HO-1 gene defect causing a human case of HO-1 deficiency and provides the molecular basis for understanding this genetic disease.

Alleles↗
PubMed2000

Large-scale production of CMP-NeuAc and sialylated oligosaccharides through bacterial coupling.

A large-scale production system of cytidine 5'monophospho-N-acetylneuraminic acid (CMP-NeuAc) and sialyloligosaccharides was established by a whole-cell reaction through the combination of recombinant Escherichia coli strains and Corynebacterium ammonia-genes. For the production of CMP-NeuAc, two recombinant E. coli strains were generated that overexpressed the genes of CMP-NeuAc synthetase and CTP synthetase, respectively. C. ammoniagenes contributed to the formation of UTP from orotic acid. CMP-NeuAc was accumulated at 27 mM (17 g/l) after a 27-h reaction starting with orotic acid and N-acetylneuraminic acid. When E. coli cells that overexpressed the alpha-(2-->3)-sialyltransferase gene of Neisseria gonorrhoeae were put into the CMP-NeuAc production system, 3'-sialyllactose was accumulated at 52 mM (33 g/l) after an 11-h reaction starting with orotic acid, N-acetylneuraminic acid, and lactose. Almost no oligosaccharide byproducts other than 3'-sialyllactose were observed after the reaction. The production of 3'-sialyllactose at a 5-l jar fermenter scale was almost the same as that at a beaker scale, which indicated the high potential of the 3'-sialyllactose production on an industrial scale.

Biotechnology↗
PubMed2000

Production of riboflavin by metabolically engineered Corynebacterium ammoniagenes.

Improved strains for the production of riboflavin (vitamin B2) were constructed through metabolic engineering using recombinant DNA techniques in Corynebacterium ammoniagenes. A C. ammoniagenes strain harboring a plasmid containing its riboflavin biosynthetic genes accumulated 17-fold as much riboflavin as the host strain. In order to increase the expression of the biosynthetic genes, we isolated DNA fragments that had promoter activities in C. ammoniagenes. When the DNA fragment (P54-6) showing the strongest promoter activity in minimum medium was introduced into the upstream region of the riboflavin biosynthetic genes, the accumulation of riboflavin was 3-fold elevated. In that strain, the activity of guanosine 5'-triphosphate (GTP) cyclohydrolase II, the first enzyme in riboflavin biosynthesis, was 2.4-fold elevated whereas that of riboflavin synthase, the last enzyme in the biosynthesis, was 44.1-fold elevated. Changing the sequence containing the putative ribosome-binding sequence of 3,4-dihydroxy-2-butanone 4-phosphate synthase/GTP cyclohydrolase II gene led to higher GTP cyclohydrolase II activity and strong enhancement of riboflavin production. Throughout the strain improvement, the activity of GTP cyclohydrolase II correlated with the productivity of riboflavin. In the highest producer strain, riboflavin was produced at the level of 15.3 g l(-1) for 72 h in a 5-l jar fermentor without any end product inhibition.

Base Sequence↗
PubMed2000

Tubular injury as a cardinal pathologic feature in human heme oxygenase-1 deficiency.

Heme oxygenase (HO) catalyzes degradation of heme to biliverdin, iron, and carbon monoxide. It consists of three isoforms: an inducible form (HO-1), a constitutive form (HO-2), and the third isoform (HO-3), with properties similar to HO-2. There is limited evidence to suggest that the induction of HO-1 may have anti-inflammatory effects in an in vivo model of oxidative stress-mediated renal injury. We experienced the first human case of HO-1 deficiency. The patient had persistent proteinuria and hematuria, with biochemical evidence of renal tubular injury. We obtained three consecutive renal specimens: two from renal biopsies at 2 and 5 years of age and the third from autopsy at 6 years of age. The patient had systemic vascular endothelial-cell injury with massive intravascular hemolysis. The serum was loaded with heme and a large amount of heme-conjugated haptoglobin. A high concentration of haptoglobin was also detectable in urine. Mesangial proliferation or change in glomerular capillary-wall thickness was relatively mild to moderate in all specimens. Electron microscopic examination showed widespread endothelial detachment and subendothelial deposits of an unidentifiable material. It was striking that tubulointerstitial injury, with tubular dilatation and/or atrophy, interstitial fibrosis, and inflammatory cell infiltration, advanced progressively. Tubular epithelial cells were injured, and massive deposition of iron and haptoglobin was detectable. Bowman's capsules were dilated significantly, probably secondary to the collapse of atrophic tubuli. This is the first report to show that HO-1 has critical roles in vivo in protecting renal tubuli, in addition to vascular endothelium, from oxidative injury.

Child, Preschool↗
PubMed2000

Large-scale production of oligosaccharides using engineered bacteria.

Rapid advances in the cloning and expression of glycosyltransferase genes, especially from bacteria, could open the way to overcoming difficulties in the mass production of oligosaccharides. The large-scale production of oligosaccharides using either glycosyltransferases isolated from engineered microorganisms or whole cells as an enzyme source could promote a new era in the field of carbohydrate synthesis.

Bacteria↗
PubMed2000

Proliferation-associated expression of the MEN1 gene as revealed by in situ hybridization: possible role of the menin as a negative regulator of cell proliferation under DNA damage.

The gene responsible for multiple endocrine neoplasia type 1 (MEN1) has recently been identified. Wide expression of the MEN1 gene in endocrine and non-endocrine organs examined by northern blotting has been reported, but the detailed cellular distribution of the MEN1 transcript in each tissue has not yet been examined in any species. In this report, expression of the MEN1 gene in adult human tissues was studied by in situ hybridization. The MEN1 transcript was widely observed in all tissues examined, and an enhanced expression in relation to cell proliferation was seen in some organs. Cell cycle arrest at the G1-S border reduced the MEN1 mRNA level to less than 50% of that in exponentially growing asynchronous cells. The expression increased as cells entered into S phase, indicating cell cycle-associated transcriptional regulation of the MEN1 gene. Increase or decrease of the amount of menin did not affect proliferation of CHO cells under normal conditions. However, when cells were exposed to the DNA-cross-linking agent, diepoxybutane, overexpression of wild-type menin inhibited DNA synthesis. This effect was not observed when cells were exposed to ultraviolet light. These results suggest that menin may negatively regulate cell cycle under certain DNA damage.

Adult↗
PubMed2000

Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients.

Previous neuropathological studies have revealed that the corticolimbic system of schizophrenic patients expresses abnormal levels of various synaptic molecules, which are known to be influenced by the neuronal differentiation factors, neurotrophins. Therefore, we determined levels of neurotrophins and their receptors in the postmortem brains of schizophrenic patients and control subjects in relation to molecular impairments in schizophrenia. Among the neurotrophins examined, levels of brain-derived neurotrophic factor (BDNF) were elevated specifically in the anterior cingulate cortex and hippocampus of schizophrenic patients, but levels of nerve growth factors and neurotrophin-3 showed no change in any of the regions examined. In parallel, the expressions of TrkB receptor and calbindin-D, which are both influenced by BDNF, were reduced significantly in the hippocampus or the prefrontal cortex. However, neuroleptic treatment did not appear to mimic the neurotrophic change. Neither withdrawal of drug treatment in patients nor chronic administration of haloperidol to rats altered levels of BDNF. These findings suggest that neurotrophic abnormality is associated with the corticolimbic structures of schizophrenic patients and might provide the molecular substrate for pathological manifestations of the illness.

Adult↗
PubMed2000

Characterization of immune function and analysis of RAG gene mutations in Omenn syndrome and related disorders.

Omenn syndrome was recently found to be caused by missense mutations in RAG1 or RAG2 gene that result in partial V(D)J recombination activity. Although the clinical hallmarks of the disease are well defined, there have been several cases with clinical findings similar to, but distinct from Omenn syndrome. The data on immune functions and RAG gene mutations of such cases are limited. We described five Japanese infants from four unrelated families, including two cases of Omenn syndrome and three cases of related disorders. Sibling cases with typical Omenn phenotype were found to be compound heterozygotes of R396C and L885R mutations in RAG1. The former has been reported in European cases and may constitute a hot spot. The latter is a novel missense mutation. Infants with related disorders exhibited erythroderma, eosinophilia, hypogammaglobulinaemia, decreased number of B cells and skewing to Th2, and their lymph node specimens showed architectural effacement, lymphocyte depletion and histiocytic hyperplasia, each of which is seen characteristically in Omenn syndrome. However, in these cases serum IgE levels were low or undetectable. We found no mutation in RAG genes except for a K820R substitution in RAG1, which was regarded to be a functional polymorphism, in two of these cases. Our study suggests that RAG missense mutation may be a genetic abnormality unique to Omenn syndrome with characteristic clinical and laboratory findings. Variations of Omenn syndrome, or related disorders, may represent a different type of immunodeficiency, distinct from abnormalities in lymphoid-specific recombinase activity.

Apoptosis↗
PubMed2000

Abnormal illness behavior and psychiatric disorders: a study in an outpatient clinic in Japan.

Abnormal illness behavior, such as hypochondriacal attitude and inappropriate treatment-seeking, has been associated with various psychiatric disorders in which patients tend to abuse medical services and seek inappropriate treatment in general practice clinics rather than psychiatric clinics. However, the relationship between illness behavior and psychiatric disorders in Japan is yet to be elucidated. We examined the abnormal illness behavior of 243 patients who visited the outpatient department of psychiatry at Saga Medical School Hospital, Saga, Japan, using a Japanese version of the Illness Behavior Questionnaire (IBQ). Multivariate analysis indicated significant association between some of the IBQ scale scores and age, sex and employment status. Patients with anxiety disorder scored higher on five of the seven IBQ scales compared with patients with another major disorder (mood disorder, schizophrenia or somatoform disorder). When compared with the IBQ scale scores reported in Australian patients in a psychiatric hospital, most of the IBQ scale scores differed significantly in our patients; a higher score among Japanese patients on the general hypochondriasis scale was most prominent. A similar trend in IBQ scale scores was also noted among Japanese patients visiting the hospital's general medicine clinic in comparison with Australian patients visiting a general practice clinic. Japanese patients with anxiety disorder may display the most salient abnormal illness behaviors among patients with psychiatric disorders. Sociocultural background may contribute to the characteristic abnormal illness behaviors of Japanese patients.

Adolescent↗