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T Nishi

Publications and source records attributed to T Nishi.

At least 145 records · Page 8Linked to original sources
PubMed1997

An adenosine deaminase inhibitor prevents puromycin aminonucleoside nephrotoxicity.

Puromycin aminonucleoside (PAN) toxicity was totally inhibited in the rat in vivo and in cultured glomerular epithelial cells (GECs) in vitro using the adenosine deaminase (ADA) inhibitor, 2'-deoxycoformycin (DCF). DCF completely inhibited ADA activity in glomeruli and protected against the development of PAN nephrosis; the 24-h urinary protein excretion of treated rats compared with controls (PAN rats) 9 days after PAN injection was 16 +/- 2 mg and 524 +/- 55 mg, respectively (p < .01). Morphological examination also demonstrated that the glomerular epithelial cells were protected against PAN-induced damage. Furthermore, when DCF was added to the first passage of GECs simultaneously with PAN, the adenosine triphosphate contents of remnant GECs on culture substrata increased in a dose-dependent manner, and PA toxicity was completely inhibited by 10(-4) M DCF. The order of ADA activity in glomeruli from various species was as follows: rat > monkey > guinea pig > dog > rabbit > mouse. High activity of ADA in the glomerulus was limited to species in which PAN induced nephrosis. Additionally, DCF increased glomerular cyclic AMP contents, resulting from enhanced adenosine accumulation in the pericellular space. These results indicate that the pathogenesis of PAN toxicity is closely related to adenosine metabolism and that ADA plays a key role in this model. Furthermore, we speculate that DCF contributes to the inhibition of reactive oxygen metabolites by decreasing the substrate of xanthine oxidase and/or increasing pericellular adenosine accumulation.

Adenosine↗
PubMed1997

Switch from conventional to high-flux membrane reduces the risk of carpal tunnel syndrome and mortality of hemodialysis patients.

The use of a high-flux membrane, which eliminates larger molecular weight solutes with better biocompatibility, has steadily increased since the discovery of beta-2 microglobulin (beta 2m) amyloidosis in 1985. The long-term effects of a dialyzer membrane on morbidity and mortality are not completely understood. To examine the membrane effect as a factor of carpal tunnel syndrome onset and mortality, multivariate Cox regression analysis with time-dependent covariate was conducted on 819 patients from March 1968 to November 1994 at a single center. Two hundred and forty-eight of the patients were either switched from the conventional to high-flux membrane or treated only with a high-flux membrane. Fifty-one patients underwent a CTS operation and 206 died. Membrane status (on high-flux or on conventional) was considered as time-dependent covariate and risk was adjusted for age, gender, type of renal disease and calendar year of dialysis initiation. The relative risk of CTS was reduced to 0.503 (P < 0.05) and mortality 0.613 (P < 0.05) by dialysis on the high-flux membrane, compared to the conventional membrane. Serial measurements of beta 2m indicated significantly lower beta 2m to persist in patients on the high-flux membrane. The high-flux membrane decreased the risk of morbidity and mortality substantially. Larger molecule elimination was shown important not only for preventing beta 2m amyloidosis, but for prolonging survival of dialysis patients as well.

Adult↗
PubMed1997

Functional expression of a GLT-1 type Na+-dependent glutamate transporter in rat pinealocytes.

Pinealocytes, the neuroendocrine cells that produce melatonin, accumulate glutamate in microvesicles through a specific vesicular transporter energetically coupled with vacuolar-type proton ATPase. The glutamate is secreted into the extracellular space through microvesicle-mediated exocytosis and then stimulates neighboring pinealocytes, resulting in inhibition of norepinephrine-dependent melatonin synthesis. In this study, we identified and characterized the plasma membrane-type glutamate transporter in rat pinealocytes. The [3H]glutamate uptake by cultured pinealocytes was driven by extracellular Na+, saturated with the [3H]glutamate concentration used, and significantly inhibited by L-glutamate, L-aspartate, beta-threo-hydroxyaspartate, pyrrolidine dicarboxylate, and L-cysteine sulfinate, substrates or inhibitors of the plasma membrane glutamate transporter. Consistently, the clearance of extracellular glutamate, as measured by HPLC, was also dependent on Na+ and inhibited by beta-threo-hydroxyaspartate and L-cysteine sulfinate. Immunological studies with site-specific antibodies against three isoforms of the Na+-dependent glutamate transporter (GLT-1, GLAST, and EAAC1) revealed the expression of only the GLT-1 type transporter in pineal glands. Expression of the GLT-1 type transporter in pineal glands was further demonstrated by means of reverse transcription-polymerase chain reaction with specific DNA probes. Immunohistochemical analysis indicated that the immunological counterpart(s) of the GLT-1 is localized in pinealocytes. These results suggested that the GLT-1-type Na+-dependent transporter is expressed and functions as a reuptake system for glutamate in rat pinealocytes. The physiological role of the transporter in the termination of the glutamate signal in the pineal gland is discussed.

ATP-Binding Cassette Transporters↗
PubMed1997

Transcriptional activation of H+/K+-ATPase genes by gastric GATA binding proteins.

H+/K+-ATPase (composed of alpha and beta subunits) and histamine H2 receptor are specifically expressed in gastric parietal cells. The GATA binding proteins (GATA-GT1 and GATA-GT2, also called GATA-6 and GATA-4, respectively) originally found in the gastric mucosa recognized a sequence motif [gastric motif, (G/C)PuPu(G/C)NGAT(A/T)PuPy] in the upstream regions of the ATPase genes [Tamura, S., Wang, X.-H., Maeda, M., and Futai, M. (1993) Proc. Natl. Acad. Sci. USA 90, 10876-10880]. These proteins activated the transcription of the reporter gene ligated downstream of the control region of the rat ATPase alpha or beta subunit gene but had no effect on the same reporter ligated downstream of the H2 receptor gene. Deletion analyses suggested that the upstream 249 (alpha gene) and 323 (beta gene) base pair sequences from the first letter of the initiation codon are sufficient for activation by the GATA proteins. Interestingly, two and three gastric motifs are located near the TATA-boxes of the alpha and beta genes, respectively. Mutagenesis studies demonstrated that the two motifs proximal to the TATA-box sequences of the ATPase alpha and beta subunit genes were essential for the activation. These results suggest that both the alpha and beta subunit genes are regulated similarly by the GATA binding proteins. The expression system established in this study is a useful system for analyzing the roles of GATA proteins in transcriptional regulation of the H+/K+-ATPase gene.

Animals↗
PubMed1997

Ultrasonographic diagnosis of fetal cholelithiasis.

A case of opacity in the fetal gallbladder was diagnosed by ultrasound. The lesion resolved spontaneously in the postnatal period. Careful follow-up ultrasound examinations are necessary for fetal cholelithiasis in the pre- and postnatal periods, and conservative management is mandatory.

Adult↗
PubMed1997

Antimicrobial activity of DU-6681a, a parent compound of novel oral carbapenem DZ-2640.

The in vitro antibacterial activity of DU-6681a, a parent compound of DZ-2640, against gram-positive and -negative bacteria was compared with those of penems and cephalosporins currently available. MICs at which 90% of the isolates are inhibited (MIC90s) of the compound for clinical isolates of methicillin-susceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis, including methicillin-susceptible and -resistant strains, were 0.10, 25, and 12.5 microg/ml, respectively. DU-6681a inhibited the growth of all strains of Streptococcus pyogenes and of penicillin-susceptible and -insusceptible Streptococcus pneumoniae at 0.006, 0.025, and 0.20 microg/ml, respectively, and MIC90s of the compound were 6.25 and >100 microg/ml for Enterococcus faecalis and Enterococcus faecium, respectively. MIC90s of DU-6681a were 0.20, 0.10, and 0.025 microg/ml for Haemophilus influenzae, Moraxella catarrhalis, and Neisseria gonorrhoeae, respectively. For Pseudomonas aeruginosa, the MIC50 and MIC90 of DU-6681a were 25 and 50 microg/ml, respectively. DU-6681a activity was not affected by different media, varied inoculum size (10(4) to 10(7) CFU), or the addition of human serum but was decreased under acidic conditions against gram-negative bacteria, under alkaline conditions against gram-positive bacteria, and in human urine, as was the activity of the other antibiotics tested. The frequency of spontaneous resistance to DU-6681a was less than or equal to those of the reference compounds. Time-kill curve studies demonstrated the bactericidal action of DU-6681a against S. aureus, S. pneumoniae, Escherichia coli, and H. influenzae.

Administration, Oral↗
PubMed1997

High level expression of XMP aminase in Escherichia coli and its application for the industrial production of 5'-guanylic acid.

To improve the efficiency of the enzymatic conversion of 5'-xanthylic acid (XMP) to 5'-guanylic acid (GMP), we attempted to increase the activity of the conversion enzyme, XMP aminase (GMP synthetase) encoded by the guaA gene in Escherichia coli. By connecting the PL promoter of lambda phage, the SD sequence of trpL of E. coli, and ATG, at a suitable position upstream of the guaA gene, we obtained plasmid pPLA66. Sequencing of the nucleotides of the upstream region of the guaA gene on pPLA66 showed that the C-terminal region of the guaB gene, which encodes IMP dehydrogenase, was conserved and a short peptide consisted of 14 amino acids was coded. E. coli MP347/pPLA66 showed an increase in the activity of approximately 370 times when compared with that of the strain MM294, and the amount of the enzyme protein represented approx. 34% of the total cellular protein. Strain MP347/pPLA66 was cultivated in a 5-liter jar fermentor using a medium which contained mainly corn steep liquor. The culture broth had high XMP aminase activity. In the conversion reaction using mixed broths consisted of 600 ml of XMP-fermentation broth of Corynebacterium ummoniagenes KY13203 and 30 ml of cultured broth of E. coli MP347/pPLA66, a surfactant, Nymeen S-215 and xylene were added to the reaction mixture to make the cell membrane permeable to nucleotides. After 23 h of the reaction, 70 mg/ml (131 mM) of GMP.Na2.7H2O was accumulated from 83 mg/ml (155 mM) of XMP.Na3.7H2O, without addition of ATP. The molar conversion yield was approx. 85%. The facts that the cell membrane was treated to allow nucleotides to permeate and that the conversion reaction proceeded well enough in spite of a small amount of E. coli cells indicate ATP was regenerated from AMP by C. ammoniagenes cells and supplied to E. coli cells. Therefore, it was considered that the coupling reaction between these two kind of strains was established.

Bacteriophage lambda↗
PubMed1997

Prenatal diagnosis of urinary tract abnormalities.

BACKGROUND: To compare magnetic resonance imaging with ultrasonography for the diagnosis of urinary tract abnormalities. METHODS: Two cases of multicystic dysplastic kidney, six cases of ureteropelvic junction obstruction, and one case of autosomal recessive polycystic kidney disease were diagnosed on antenatal ultrasonography and/or magnetic resonance imaging. RESULTS: In case of multicystic dysplastic kidney and ureteropelvic junction obstruction, ultrasonography showed characteristic features of their diseases. Magnetic resonance imaging was insufficient to diagnose these diseases. In a case of autosomal recessive polycystic kidney disease, ultrasonography and magnetic resonance imaging were both useful to show characteristic features of this disease, and thus made it possible to make a correct diagnosis of the disease. CONCLUSIONS: For a prenatal fetal diagnosis, it is necessary to observe both fetal anatomy and an evolution of the fetal abnormality. The above mentioned three types of urinary tract abnormalities changed their anatomic configurations and/or texture of urinary tracts as the pregnancies progressed. To observe these changes, the usefulness of ultrasonography is superior to that of magnetic resonance imaging for the present. Although ultrasonography and magnetic resonance imaging show fetal urinary tract abnormalities, these instruments should be used properly during the period of the pregnancy on case-by-case bases.

Diagnosis, Differential↗
PubMed1997

[Esophageal cancer and multiple primary cancer].

Two hundred eleven cases, 27.1%, of multiple primary cancers of esophagus and other organs were found in 778 cases of esophageal cancers which were treated in our institution. Among them, double cancer accounted for 92.9%, triple cancer accounted for 6.6% and quadruple cancer for 0.5%. As for the other organ of esophageal double cancer. 59.9% of them were head and neck, 25.1% were stomach, 4.9% were colon and rectum, and remaining included liver, breast, lymphoma lung kidney etc. Head and neck cancers consisted with hypopharynx, tongue, larynx, oral floor and gingiva regarding incidence in its order. For discovering of double cancer in esophagus and other organs, 1. head and neck, stomach, colon and rectum, lung, liver etc. should be investigated preoperatively in the patients of esophageal cancer, 2. Esophagus should be examined preoperatively in the patients of these cancers, 3. Screening of esophageal cancer should be performed in the patients of high risks of esophageal cancer. As for the multiple primary cancer of esophagus and other organs, the balance of treatment should be considered to take the priority of the cancer limiting the prognosis.

Adult↗
PubMed1997

Treatment of cancer using pulsed electric field in combination with chemotherapeutic agents or genes.

Electroporation is a standard laboratory technique originally developed for in vitro transfer of molecules into cells. It involves application of electrical pulses ranging from micro- to milliseconds that create transient pores in the cell membrane allowing intracellular access of exogenous molecules. This technique has been successfully applied to regress tumors in animal models by combining electroporation with chemotherapeutic agents--a process known as electrochemotherapy (ECT) which substantially enhance cytotoxicity of some antineoplastic agents. Recently ECT has moved into clinical arena and patients with cutaneous tumors and head and neck cancers have been treated very effectively with ECT. Parallel to ECT, a technique has also been developed which makes it possible to inject plasmid DNA and combine it with in vivo electroporation--electro--genetherapy (EGT)--to deliver in a highly efficient manner both marker and functional genes into target tissue and achieve gene expression. Thus, in vivo electroporation is contributing to the development of a new strategy for cancer treatment with both drugs and genes.

Animals↗
PubMed1997

[Endoscopic classification of reflux esophagitis and its new developments].

Endoscopic diagnosis and classification of reflux esophagitis were described, which is gradually increasing in number in Japan. It is important to diagnosefor a type, grade, and degree, hearing stage and others (stenosis, Barrett's esophagus etc), when we perform endoscopic examination for reflux esophagitis patients. Iodine staining should be applied as far as possible. Los Angeles system for classification of reflux esophagitis was proposed at the 10th World Congress of Gastroenterology in October 1994. As for LA classification, reflux esophagitis is classified to 4 grade, from A to D, predicated on the grade of mucosal break. For any doctors, this is easy to apply to the classification of reflux esophagitis and the diagnosis of classification will be equal. The Japanese Society of Disease of Esophagus also proposed the new classification of reflux esophagitis, that is JSED '96 Classification. This classification contains grade 0, which indicate no reflux esophagitis and grade 1, which indicate the discoloring type of esophagitis. Another 3 grades are based on the length of esophagitis and also occupation on circumference of esophagus. This will be suitable for the Japanese reflux esophagitis and can be changed to LA classification easily. The International Society of Disease of Esophagus proposed AFP classification which is useful to decide the application to surgical treatment. The detail of these classifications and the important points on the endoscopic diagnosis of reflux esophagitis were mentioned in this paper.

Esophagitis, Peptic↗
PubMed1996

Tight-binding inhibitory sequences against pp60(c-src) identified using a random 15-amino-acid peptide library.

A bacteriophage peptide library containing a random 15-amino-acid insert was screened for identification of peptide sequence(s) that bind pp60(c-src). Sequencing the random insert from more than 100 virions indicated that more than 60% of the phage virions that bound to this enzyme contained a GXXG sequence motif in which X was frequently a hydrophobic residue. The GXXG sequence was often repeated as GXXGXXG. Two nonameric peptides were synthesized to determine whether or not the peptide inhibits pp60(c-src) tyrosine kinase activity and the importance of the glycine residues within this sequence. The peptide containing glycine had a Ki of 24 microM, whereas replacing the glycines with proline increased the Ki value to 3.1 mM.

Amino Acid Sequence↗
PubMed1996

Expression of tissue factor correlates with grade of malignancy in human glioma.

BACKGROUND: Tissue factor (TF), a cell surface receptor of factor VII/VIIa, was initially recognized as an initiator of the extrinsic coagulation pathway. TF has recently been found to be expressed highly in certain types of malignant tumors. In addition, TF belongs to the interferon receptor family and is one of the immediate early genes, suggesting that TF may participate in the regulation of cell growth. However, the correlation between the expression of TF and cell growth is still unclear. METHODS: Expression of TF in 6 glioma cell lines and 44 glioma surgical specimens was studied by Northern blot analysis, Western blot analysis, immunohistochemistry, and in situ hybridization. RESULTS: Northern blot analysis showed that glioma cells expressed minor novel transcripts of 3.3 kb and 1.6 kb, in addition to the transcripts of 2.2 kb and 3.1 kb that were previously reported. Western blot analysis revealed that the level of TF protein did not correlate with that of TF transcripts. Although immunohistochemical analysis of surgical specimens showed that all gliomas were positive for TF, it was interesting that 1 of 10 benign gliomas (10%) was positive for TF (malignancy Grade I-II), 13 of 14 anaplastic astrocytomas (86%) (malignancy grade III) and 19 of 20 glioblastomas (95%) (malignancy grade IV) were moderately or strongly positive for TF. In situ hybridization showed the expression of TF mRNA in glioma cells. CONCLUSIONS: TF is expressed in glioma and the level of expression correlates with the histologic grade of malignancy.

Astrocytoma↗
PubMed1996

High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation.

A novel method for high-efficiency and region- controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cell 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoattractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in tumor tissue. This method, electrogene therapy, which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy.

Animals↗
PubMed1996

Expression cloning of a human GT3 synthase. GD3 AND GT3 are synthesized by a single enzyme.

Gangliosides of the C series such as GT3 are polysialylated glycosphingolipids whose synthesis is developmentally regulated. Here we report the expression cDNA cloning and characterization of GT3 synthase that adds the second alpha-2,8-sialic acid to GD3, NeuNAcalpha2-->8NeuNAcalpha2-->3Galbeta1-->4Glc-->Cer, thus forming GT3, NeuNAcalpha2-->8NeuNAcalpha2-->8NeuNAc alpha2-->3Galbeta1--> 4Glc-->Cer. Unexpectedly, the cloned cDNA was found to be identical to the cDNA that encodes GD3 synthase. The newly identified enzyme was therefore named GD3/GT3 synthase (GD3/GT3ST). GD3/GT3ST synthesized GT3 most efficiently when GM3, NeuNAcalpha2-->3Galbeta1-->4Glc-->Cer, was incubated as an acceptor, indicating that GD3/GT3ST is a polysialyltransferase that can transfer more than one sialic acid residue via alpha-2,8 linkage to gangliosides. Moreover, a longer period of incubation of GD3 with GD3/GT3ST produced a significant amount of GT3 and higher polysialogangliosides. Among various cell lines expressing GD3/GT3ST, higher polysialogangliosides including GT3 were detected only in cell lines where the amount of GD3/GT3 mRNA is sufficiently high. The expression of GD3/GT3ST mRNA among human tissues is highly restricted to fetal and adult brains. The GD3/GT3ST gene was found to be located at chromosome 12, region p12. Taken together, these results indicate that C series polysialogangliosides are synthesized by a ganglioside-specific polysialyltransferase, GD3/GT3ST, that is specifically expressed in neural tissues.

Adult↗