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T Inada

Publications and source records attributed to T Inada.

At least 91 records · Page 5Linked to original sources

Down regulation of cAMP production by cAMP receptor protein in Escherichia coli: an assessment of the contributions of transcriptional and posttranscriptional control of adenylate cyclase.

Escherichia coli cells that are deficient in the cAMP receptor protein (CRP) overproduce cAMP. We and others have previously found that transcription of the adenylate cyclase gene (cya) is negatively regulated by the CRP-cAMP complex. Here, we have investigated the contribution of this transcriptional regulation to the control of cAMP levels. Several variants of the cya gene have been constructed and characterized with respect to their expression and their ability to produce cAMP. Overproduction of cAMP in a crp- background was reduced from 200-fold to 50-fold when transcriptional regulation by CRP-cAMP was eliminated by replacing the cya promoter with the constitutive bla promoter. When the C-terminal 48 amino acids of adenylate cyclase were deleted without changing the promoter, the degree of overproduction of cAMP was reduced to 4-fold. Finally, the increase in cAMP level observed in crp- cells was almost completely abolished when the truncated cyclase was expressed from the bla promoter. We conclude that transcriptional regulation of cya does indeed play a role in the down-regulation of cAMP production by CRP, although the major regulation is exerted at the posttranscriptional level. The C-terminal region comprising the last 48 amino acids of cyclase is responsible for the posttranscriptional regulation. A simple new method for the determination of cAMP is also described.

Adenylyl Cyclases↗

Prevention of methamphetamine-induced behavioral sensitization in rats by a cyclic AMP phosphodiesterase inhibitor, rolipram.

Effects of an interaction between rolipram, a cyclic adenosine 3', 5'-monophosphate (cyclic AMP) phosphodiesterase inhibitor, and methamphetamine on the development of behavioral sensitization were observed in rats. In vivo microdialysis showed that a single dose of 4 mg/kg methamphetamine (i.p.) significantly increased striatal dopamine levels while coadministration with 4 mg/kg rolipram (i.p.) did not affect these levels. Also, methamphetamine alone did not alter striatal cyclic AMP levels but coadministration with rolipram and rolipram alone significantly increased these levels. The administration of 4 mg/kg methamphetamine (i.p.) once a day for 5 days significantly enhanced hyperlocomotion and rearing induced by a 2-mg/kg methamphetamine challenge (i.p.) after a 1-week withdrawal period, compared with controls or coadministration with 4 mg/kg rolipram (i.p.). Striatal dopamine levels, detected by in vivo microdialysis, were increased following the challenge but were comparable between the groups. These findings suggest that rolipram prevents methamphetamine-induced behavioral sensitization by increasing cyclic AMP levels while not affecting dopamine-releasing processes.

3',5'-Cyclic-AMP Phosphodiesterases↗

Characterization of a ligand for receptor protein-tyrosine kinase HTK expressed in immature hematopoietic cells.

HTK is a receptor tyrosine kinase that belongs to the Eph subfamily. An extensive screening using BIAcore system revealed that a colon cancer cell line, C-1, expressed the ligand for HTK. From the conditioned medium of C-1 cells, a soluble form of ligand was purified by receptor affinity chromatography, and the isolation of full-length cDNA revealed that this ligand is identical to the human HTK ligand (HTKL) previously reported. HTK receptor tyrosine phosphorylation was induced by membrane-bound or clustered soluble HTKL but not by unclustered soluble HTKL, indicating that HTKL requires cell-to-cell interaction for receptor activation. Binding analysis demonstrated that HTKL binds to HTK with a much higher affinity (Kd: 1.23 nM) than the other transmembrane-type ligand for Eph family, LERK-2/ELKL (Kd: 135 nM). The expression of HTK in cord blood cells was upregulated after the culture in the presence of stem cell factor. Clustered soluble HTKL stimulated the proliferation of sorted HTK+ cord blood cells and a hematopoietic cell line, UT-7/EPO from which HTK was isolated. These findings suggest the involvement of HTK-HTKL system in the proliferation of HTK+ hematopoietic progenitor cells in the hematopoietic environment.

Amino Acid Sequence↗

Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode.

To investigate the possible role of the dopamine transporter (DAT) gene in determining the phenotype in human subjects, allele frequencies for the 40-bp variable number of tandem repeats (VNTR) polymorphism at this site were compared between 117 Japanese normal controls and 118 schizophrenic patients, including six subgroups: early-onset, those with a family history, and those suffering from one of the following psychiatric symptoms at their first episode: delusion and hallucination; disorganization; bizarre behavior; and negative symptoms. No significant differences were observed between the group as a whole or any subgroup of schizophrenic patients and controls. The results indicate that VNTR polymorphism in the DAT gene is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects.

Adult↗

A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 12.7-28.0 min region on the linkage map.

The 718,122 base pair sequence of the Escherichia coli K-12 genome corresponding to the region from 12.7 to 28.0 minutes on the genetic map is described. This region contains at least 681 potential open reading frames, of which 277 (41%) have been previously identified, 147 (22%) are homologous to other known genes, 139 (20%) are identical or similar to the hypothetical genes registered in databases, and the remaining 118 (17%) do not show a significant similarity to any other gene. In this region, we assigned a cluster of cit genes encoding multienzyme citrate lyase, two clusters of fimbrial genes and a set of lysogenic phage genes encoding integrase, excisionase and repressor in the e14 genetic element. In addition, a new valine tRNA gene, designated valZ, and a family of long directly repeated sequences, LDR-A, -B and -C, were found.

DNA, Bacterial↗

The modulating effect of interferon alpha-2a on the antitumor activity of UFT against a human gastric carcinoma xenograft, SC-1-NU, in nude mice.

The modulating effect of recombinant human interferon alpha-2a (IFN) on the antitumor activity of UFT, a mixed compound of tegafur and uracil at a molar ratio of 1:4, was investigated against SC-1-NU, a human gastric cancer xenograft serially transplanted in nude mice. IFN was administered subcutaneously at a dose of 60,000 IU/mouse daily for 14 days, and UFT was given at a dose of 15 mg/kg as tegafur daily, except on Sundays, for 3 weeks. The agents were administered either alone or simultaneously. Synergistic antitumor activity on SC-1-NU was produced by the combination of IFN and UFT without any increment of side effects, and the combination therapy also increased intratumoral thymidylate synthetase (TS) inhibition and the amount of 5-fluorouracil (5-FU) in the intratumoral RNA. Thus, IFN seems to modulate the antitumor activity of UFT against SC-1-NU through an inhibition of DNA synthesis and RNA distortion, and therefore this combination could be useful for clinical application.

Adenocarcinoma↗

Changes in the cerebral arteriovenous oxygen content difference by surgical incision are similar during sevoflurane and isoflurane anaesthesia.

PURPOSE: To investigate changes of cerebral arteriovenous oxygen content difference (AVDO2) induced by surgical incision and to determine carbon dioxide (CO2) reactivity of the cerebral circulation during sevoflurane and isoflurane anaesthesia. METHODS: Twenty-one ASA 1-2 patients undergoing elective surgery for supratentorial tumours were randomly allocated to receive either 1.3 MAC sevoflurane/N2O anaesthesia (n = 10) or equi-MAC isoflurane/N2O anaesthesia (n = 11). Before and after incision, haemodynamic measurements and AVDO2 determinations were performed. After opening the dura, AVDO2 was determined before and after the respiration rate was increased by 50%. RESULTS: Incision produced an increase in mean arterial pressure from 69 +/- 11 to 97 +/- 22 mmHg (mean +/- SD) (P < 0.0005) and from 71 +/- 6 to 89 +/- 12 mmHg (P < 0.0001) in the sevoflurane and isoflurane groups, respectively, whereas the heart rate increased from 60 +/- 9 to 72 +/- 8 bpm (P < 0.001) and from 65 +/- 6 to 70 +/- 7 bpm (P < 0.001), respectively. Arterial carbon dioxide tension (PaCO2) was increased from 33.6 +/- 2.3 to 34.6 +/- 1.8 mmHg (P < 0.05) with incision in the sevoflurane group. The AVDO2 was decreased from 6.5 +/- 1.6 to 5.3 +/- 1.6 vol% (P < 0.0005) in the sevoflurane group and from 6.7 +/- 1.1 to 6.0 +/- 1.1 vol% (P < 0.01) in the isoflurane group. The % change of AVDO2 was larger in the sevoflurane group than in the isoflurane group (-18.3 +/- 8.4% vs -9.1 +/- 9.0%; P < 0.05) but no difference remained after the post-incisional AVDO2 value of the sevoflurane group was corrected for pre-incisional PaCO2. Carbon dioxide reactivity, calculated as the percent change in AVDO2 per mmHg change in PaCO2, was 6.1 +/- 3.0%.mmHg-1 in the sevoflurane group and 5.9 +/- 2.4%.mmHg-1 in the isoflurane group (P = NS). CONCLUSIONS: Sevoflurane and isoflurane are associated with similar impairment of cerebral flow-metabolism coupling at incision, while CO2 reactivity is maintained during both anaesthetics.

Adult↗

Tumour necrosis factor is expressed in cardiac tissues of patients with heart failure.

Tumour necrosis factor (TNF), a cytokine produced mainly by macrophages, has also been found in vascular smooth muscle cells. Elevated serum levels of TNF have been reported in various cardiac diseases, especially congestive heart failure (CHF). Although the myocardium produces several cytokines, the expression of TNF in human cardiac tissue has not yet been demonstrated. We examined TNF expression in right atrial (RA) specimens obtained from 15 patients during cardiac surgery with immunohistochemistry using an anti-human TNF monoclonal antibody, enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR). TNF immunoreactivity was found only in cardiac myocytes and some vascular smooth muscle cells of small vessels of specimens from patients with severe CHF (3/5), and not in those from patients without severe CHF (0/10). ELISA of four RA specimens revealed that RA tissues from two patients with severe CHF contained more TNF than did those from two patients without severe CHF (3.1 and 4.7 pg/mg vs. 0.1 and 0.3 pg/mg). RT-PCR revealed TNF mRNA in all seven cases we examined. It was concluded that TNF mRNA is expressed by atrial tissue. The production of immunoreactive TNF-like peptides by myocytes and vascular smooth muscle cells is augmented in patients with severe CHF.

Aged↗

Autogenous control of the suhB gene expression of Escherichia coli.

The suhB gene encodes a 29-kDa protein that possesses inositol monophosphate activity and its mutations suppress several temperature-sensitive mutations in Escherichia coli. We found that the suhB gene is autoregulated; suhB- mutant strains oversynthesized the suhB mRNA and suhB-lacZ gene/operon fusion products. Since the half-life of the suhB transcript in the suhB mutant was much greater than the half-life in the wildtype strain, the suhB protein is implicated in the control of gene expression by modulating mRNA turnover.

Escherichia coli↗

Mechanism responsible for glucose-lactose diauxie in Escherichia coli: challenge to the cAMP model.

BACKGROUND: The inhibition of beta-galactosidase expression in glucose-lactose diauxie is a typical example of the glucose effect in Escherichia coli. It is generally believed that glucose exerts its effect at least partly by reducing the intracellular cAMP level. However, there is no direct evidence that the inhibitory effect of glucose on the expression of the lac operon is mediated by a reduction of the cAMP level in the glucose-lactose system. RESULTS: To examine the roles of cAMP and the cAMP receptor protein (CRP) in the glucose effect, the intracellular levels of these factors were determined during diauxic growth in a glucose-lactose medium. We found that the levels of cAMP and CRP in a lactose-grown phase were not higher than those in a glucose-grown phase, although the cAMP levels increased transiently during the lag phase. The addition of exogenous cAMP eliminated diauxic growth but did not eliminate glucose repression. Glucose repression and diauxie were observed in cells which lack cAMP but produce a cAMP-independent CRP. In addition, inactivation of the lac repressor by the disruption of the lacI gene or the addition of IPTG, eliminated glucose repression. CONCLUSION: We conclude that the repression of beta-galactosidase expression by glucose is not due to the reduction of the cAMP-CRP level but due to an inducer exclusion mechanism which is mediated by the phosphoenolpyruvate-dependent sugar phosphotransferase system.

Cyclic AMP↗

Changes in tracheal tube position during laparoscopic cholecystectomy.

The distance from the carina to the tip of the tracheal tube was measured with a fibreoptic bronchoscope in 21 consecutive patients undergoing elective laparoscopic cholecystectomy. After placement of an Eschmann tracheal tube with a printed intubation guide mark at the vocal cords, the distance was 28 (15) [5-54] mm (mean (SD) [range]). The tube was then repositioned so that the distance was 34 (3) [30-40] mm from tip of the tube to the carina. After creation of pneumoperitoneum, the distance was significantly decreased to 26 (5) [17-35] mm (p < 0.005), which was not significantly altered by subsequent moving of the patient to the reverse Trendelenburg and left lateral tilt position. The maximum distance of tube migration was 8 (4) [0-15] mm. Four out of 21 patients would have been at risk of bronchial intubation after pneumoperitoneum if the tube had not been repositioned. Placement of the tube according to the guide mark is not recommended for laparoscopic cholecystectomy.

Adult↗

Endothelin-1 and its receptor in hypertrophic cardiomyopathy.

Endothelin-1, a potent vasoconstrictor produced by vascular endothelial cells, activates the hypertrophic program in cultured heart muscle cells. However, the role of endothelin-1 in cardiac hypertrophy in humans is unknown. Therefore, we studied hypertrophic cardiomyopathy patients with normal pulmonary arterial pressure, in whom cardiac hypertrophy is a specific feature of the disease. Radioimmunoassay with a monoclonal antibody to human endothelin-1 showed that the plasma level of immunoreactive endothelin was more than twofold higher in hypertrophic cardiomyopathy patients than in control subjects (P < .005). In situ hybridization analysis of endomyocardial biopsy specimens showed positive signals of endothelin-1 type A receptor mRNA in ventricular myocytes of all specimens. The receptor expression in ventricular myocytes was similar between hypertrophic cardiomyopathy patients and control subjects. We propose that endothelin-1 might represent an important factor involved in hypertrophic cardiomyopathy. Whether endothelin-1 plays a causal role in cardiac hypertrophy or is a marker of its occurrence needs to be clarified.

Analysis of Variance↗

Current topics in neuroleptic-induced extrapyramidal symptoms in Japan.

This article reviews current topics in neuroleptic-induced extrapyramidal symptoms in Japan, focusing especially on the clinical features of akathisia and dystonia. Akathisia is a common side effect associated with antipsychotic drugs. It is most commonly characterized by subjective inner restlessness and objective motor signs, especially in the lower extremities. The mechanisms underlying akathisia remain unclear and controversial; however, an increase in the activity of beta-adrenergic systems relative to dopaminergic systems has been hypothesized, based on clinical therapeutic observations that beta-blocking agents are effective in this condition. A Japanese version of the Barnes Akathisia Scale has recently been established and uses a standardized videotape method for its precise evaluation. Various acute and chronic manifestations of neuroleptic-induced dystonia have been reported in Japan, including blepharospasm, difficulty in opening the eye lids, torticollis, retrocollis, oculogyric crisis, and Pisa syndrome. This review also introduces several other topics related to drug-induced extrapyramidal symptoms in Japan. These include; 1) the Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), which has recently been established, 2) studies on the discontinuation of anticholinergic drugs, and 3) a summary of extrapyramidal symptoms induced by drugs other than neuroleptics.

Akathisia, Drug-Induced↗

[Multiple myeloma associated with phenytoin (diphenylhydantoin) therapy].

The occurrence of multiple myeloma is described in a patient receiving phenytoin (diphenylhydantoin) for 43 years. In this article, five cases of multiple myeloma and one of immunoblastic lymphadenopathy associated with diclonal gammopathy diagnosed after longterm phenytoin therapy are reviewed. These cases are characterized by lymphadenopathy, hepatosplenomegaly, and no or equivocal bone lesions, which are quite unusual in multiple myeloma. Because of the association of lymphomas with phenytoin, the role of the drug in the etiology of multiple myeloma or plasma cell dyscrasias is still in controversy, but highly suspected. It is suggested that a periodic examination of patients receiving phenytoin may be useful in an early detection of M-component. The possibility of reversing multiple myeloma by removal of phenytoin early in the course of the disease should be investigated.

Aged↗

[Recent research trends in diagnosis, treatment, and prevention of drug-induced extrapyramidal symptoms seen in psychiatric patients].

Extrapyramidal symptoms (EPS) induced by neuroleptics (NLP) are still one of the major clinical problems in treating psychiatric patients. The reliability of the drug-induced extrapyramidal symptoms scale (DIEPSS) and the Japanese version of Barnes Akathisia Scale has recently been established, and these scales are used in the clinical psychopharmacological studies performed in Japan. One of the recent research trends of the epidemiological studies on tardive dyskinesia (TD) is characterized by the prospective longitudinal design with older subjects. Although no effective treatment for TD has yet been established, the efficacy of vitamin E for TD has been tested in the USA, while an open clinical trial of rolipram was recently performed in Japan. One of the preventive studies for TD, searching for genetic variations that could act as a marker to identify especially vulnerable patients to TD, is now being conducted by our research group. It is believed that the use of clozapine, an atypical antipsychotic drug, or a serotonin-dopamine antagonist such as risperidone will leave patients free of EPS, however, the real value of these drugs in terms of the effect of reducing EPS, including TD, in Japanese patients requires further evaluation.

Aged↗