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T Inada

Publications and source records attributed to T Inada.

At least 127 records · Page 7Linked to original sources

Novel proteins of the phosphotransferase system encoded within the rpoN operon of Escherichia coli. Enzyme IIANtr affects growth on organic nitrogen and the conditional lethality of an erats mutant.

Two rpoN-linked delta Tn10-kan insertions suppress the conditionally lethal erats allele. One truncates rpoN while the second disrupts another gene (ptsN) in the rpoN operon and does not affect classical nitrogen regulation. Neither alter expression of era indicating that suppression is post-translational. Plasmid clones of ptsN prevent suppression by either disruption mutation indicating that this gene is important for lethality caused by erats. rpoN and six neighboring genes were sequenced and compared with sequences in the database. Two of these genes encode proteins homologous to Enzyme IIAFru and HPr of the phosphoenolpyruvate:sugar phosphotransferase system. We designate these proteins IIANtr (ptsN) and NPr (npr). Purified IIANtr and NPr exchange phosphate appropriately with Enzyme I, HPr, and Enzyme IIA proteins of the phosphoenolpyruvate: sugar phosphotransferase system. Several sugars and tricarboxylic acid cycle intermediates inhibited growth of the ptsN disruption mutant on medium containing an amino acid or nucleoside base as a combined source of nitrogen, carbon, and energy. This growth inhibition was relieved by supplying the ptsN gene or ammonium salts but was not aleviated by altering levels of exogenously supplied cAMP. These results support our previous proposal of a novel mechanism linking carbon and nitrogen assimilation and relates IIANtr to the unknown process regulated by the essential GTPase Era.

Amino Acid Sequence↗

Rolipram, a selective c-AMP phosphodiesterase inhibitor suppresses oro-facial dyskinetic movements in rats.

Since striatal dopamine D2 receptor supersensitivity in the etiology of tardive dyskinesia has been suggested and dopamine D2 receptors are known to inhibit adenylate cyclase activity resulting in a decrease of cyclic adenosine 3',5'-monophosphate (cAMP) levels, we hypothesized that an increase in cAMP levels ameliorates the condition. In the present study, 21-day haloperidol treatment (1.5 mg/kg I.P.) in rats resulted in an increase in striatal [3H]-spiperone (D2) binding whereas [3H] SCH23390 (D1) binding was unaltered. This haloperidol treatment also induced a significantly increase in the frequency of involuntary chewing movements and tongue protrusions, which are considered as a model of tardive dyskinesia. These dyskinetic movements were suppressed by administration of rolipram (0.5 and 1.0 mg/kg I.P.), an inhibitor of the cAMP phosphodiesterase type IV. The present results suggest that selective cAMP phosphodiesterase type IV inhibitors could be putative therapeutic drugs for tardive dyskinesia.

3',5'-Cyclic-AMP Phosphodiesterases↗

Lethal double-stranded RNA processing activity of ribonuclease III in the absence of suhB protein of Escherichia coli.

The suhB gene of Escherichia coli has been defined by its mutant allele that suppresses other mutants in secY, rpoH, dnaB, and era. The suhB mutant by itself is cold sensitive, and is shown to have defects in protein synthesis. Starting with the suhB cold-sensitive mutant, cold-resistant suppressors were isolated. These suppressors mapped to the gene rnc encoding RNase III (a double-strand RNA-processing enzyme), and restored normal protein synthesis to the suhB mutants. Two known rnc mutations, rnc70 or rnc105, both defective in RNA cleavage activity, similarly restored growth of suhB. These rnc mutations did not alter the level of suhB expression. These results suggest that wild-type RNase III exerts a lethal effect on E coli upon depletion of SuhB at low temperatures. One explanation is to assume that the double-strand RNA-processing activity of RNase III itself is potentially lethal to E coli and the normal function of SuhB modulates the lethal action of RNase III.

Amino Acid Sequence↗

The effects of a selective cAMP phosphodiesterase inhibitor, rolipram, on methamphetamine-induced behavior.

The effects of rolipram, a selective cAMP phosphodiesterase inhibitor, on locomotor activity, rearing, and stereotyped behavior (sniffing, repetitive head movements) induced by methamphetamine (MAP) over 1 hour were investigated in rats. Coadministration of rolipram (4 mg/kg IP) significantly attenuated the responses of locomotor activity, rearing and repetitive head movements to MAP (2,4 or 8 mg/kg IP). Rolipram (0.5, 1, 2, or 4 mg/kg IP) dose-dependently inhibited locomotor hyperactivity and rearing induced by 4 mg/kg of MAP. The rearing was completely inhibited by 4 mg/kg of rolipram, whereas the maximal inhibition of the locomotor hyperactivity was about 50%. However, rolipram did not alter MAP-induced sniffing and repetitive head movements. These results indicate that there is heterogeneity in the response of MAP-induced behavior to rolipram, suggesting that MAP-induced behavioral alteration may be partly regulated by cAMP levels in the brain.

Animals↗

Tracheal tube cuff pressure during cardiac surgery using cardiopulmonary bypass.

To determine the effects of cardiopulmonary bypass (CPB) on tracheal cuff pressure, we have measured intracuff pressure (ICP) in 29 consecutive patients undergoing cardiac surgery with CPB. Premedication comprised hyoscine and, after induction of anaesthesia with diazepam and fentanyl, followed by vecuronium, the trachea was intubated using a Portex Profile tracheal tube. Anaesthesia was maintained with high-dose fentanyl and 100% oxygen. ICP was measured with a transducer and the ICP was adjusted to 20 mm Hg. CPB was used with mild to deep hypothermia and blood-gas tensions were regulated according to alpha-stat (temperature uncorrected) pH management. Before CPB, ICP was significantly reduced from the mean baseline value of 20 (SEM 0.2) to 16.7 (0.6) mm Hg (P < 0.01). ICP changed significantly during CPB, decreasing to 8.0 (1.0) mm Hg before rewarming (P < 0.01 vs immediately before CPB) and increasing to 17.0 (0.6) mm Hg after the start of rewarming (P < 0.01 vs before rewarming). After CPB, ICP did not differ significantly from that immediately before CPB. We conclude that the decrease in ICP during the hypothermic phase of CPB may protect the tracheal mucosa against hypotensive ischaemic injury.

Adult↗

Dopamine D3 receptor gene polymorphism and the psychiatric symptoms seen in first-break schizophrenic patients.

To investigate the possible effect of polymorphism at the BalI site of the dopamine D3 receptor gene (DRD3) on the phenotype in human subjects, allele and genotype frequencies for this polymorphic site were examined in 113 schizophrenic patients, including six subgroups, and 48 normal controls. The schizophrenic subgroups included patients with early onset, those with a family history, and those who suffered from one of the following psychiatric symptoms at their first episode: (1) delusion and hallucination; (2) disorganization; (3) bizarre behavior; and (4) negative symptoms. No significant differences were observed in genotype, allele and homozygosity frequencies between the whole group or any subgroup of schizophrenic patients and the controls. The present results indicate that polymorphism at the BalI site of the DRD3 is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects.

Adult↗

Glucose lowers CRP* levels resulting in repression of the lac operon in cells lacking cAMP.

CRP-cAMP-dependent operons of Escherichia coli can be expressed in cells lacking functional adenylate cyclase when they carry a second-site mutation in the crp gene (crp*). It is known that the expression of these operons is repressed by glucose, but the molecular mechanism underlying this cAMP-independent catabolite repression has been a long-standing mystery. Here we address the question of how glucose inhibits the expression of beta-galactosidase in the absence of cAMP. We have isolated several mutations in the crp gene that confer a CRP* phenotype. The expression of beta-galactosidase is reduced by glucose in cells carrying these mutations. Using Western blotting and/or SDS-PAGE analysis, we demonstrate that glucose lowers the cellular concentration of CRP* through a reduction in crp* mRNA levels. The level of CRP* protein correlates with beta-galactosidase activity. When the crp promoter is replaced with the bla promoter, the inhibitory effect of glucose on crp* expression is virtually abolished. These data strongly suggest that the lowered level of CRP* caused by glucose mediates catabolite repression in cya- crp* cells and that the autoregulatory circuit of the crp gene is involved in the down-regulation of CRP* expression by glucose.

Adenylyl Cyclases↗

Current topics in tardive dyskinesia in Japan.

This article reviews current topics in tardive dyskinesia (TD), a movement disorder associated with the prolonged use of neuroleptic agents, especially therapeutic and preventive strategies which have been or are now being studied in Japan. Tardive dyskinesia has become a major problem in the clinical psychiatric field since the early 1970s in Japan, lagging behind Western countries by more than 10 years. The average prevalence rate of TD has been estimated as 7.7% in Japan, while it has been reported in the English literature at around 15 to 20%. Clinical trials of treatments for TD have been or are now being performed in Japan with a number of novel compounds, such as ceruletide, meclofenoxate, and rolipram; however, no effective treatment has yet been established and measures to prevent TD have therefore been emphasized. These include (i) the development of new antipsychotic drugs which are free from TD, (ii) the identification of risk factors from prospective longitudinal studies, and (iii) the investigation of genetic variations that could act as a marker to identify especially vulnerable patients within the whole population of patients who need neuroleptic therapy.

Antipsychotic Agents↗

Orotracheal intubation through the laryngeal mask airway in paediatric patients with Treacher-Collins syndrome.

The laryngeal mask airway (LMA) is useful as an airway intubator (conduit) for an intubating tracheal bougie or fibreoptic bronchoscope, over which a tracheal tube is passed. However, in our paediatric patients with Treacher-Collins syndrome, only the latter technique was successful. This was attributed to the fact that a posteriorly protruded tongue displaced the LMA, made the glottis move considerably anterior and interfered with the attempts to enter the trachea with a bougie. Downward displacement of the epiglottis, which can sometimes impair the intubation technique through the LMA, was not observed in our patients. Partial obstruction of a tracheal tube within the LMA occurred in one of the patients.

Airway Obstruction↗

Hemolytic anemia in a patient with subacute bacterial endocarditis due to Streptococcus sanguis.

We describe a case of hemolytic anemia with subacute bacterial endocarditis due to Streptococcus sanguis. The major hematological features of the patient were a normocytic anemia with reticulocytosis, an elevation of serum lactate dehydrogenase, and a marked reduction of serum haptoglobin. All these signs of hemolytic anemia fluctuated in parallel with changes in inflammatory activity and were dramatically improved by the administration of benzylpenicillin, suggesting that the infection with S. sanguis itself was the cause of hemolytic anemia in this case.

Acute Disease↗

Transient regression in lymphocyte count in B-cell chronic lymphocytic leukemia after viral infection.

Transient regression in the lymphocyte count of a patient with B-cell chronic lymphocytic leukemia (B-CLL) after viral infection is reported. A similar event occurred under natural interferon-alpha (IFN-alpha) treatment. It was confirmed that the event was not caused by a direct cytotoxic effect of IFN-alpha by analyzing the DNA fragmentation to estimate apoptotic and necrotic cell death before and after the administration of IFN-alpha. The study also suggested that the event was not caused by a cytostatic effect of IFN-alpha.

Adult↗

Mechanism of the down-regulation of cAMP receptor protein by glucose in Escherichia coli: role of autoregulation of the crp gene.

Glucose causes catabolite repression by lowering the intracellular levels of both cAMP and cAMP receptor protein (CRP) in Escherichia coli. The molecular mechanism underlying the down-regulation of CRP by glucose has been investigated. We show that glucose lowers the level of crp mRNA without affecting its stability. Replacement of the crp promoter with the bla promoter almost completely abolishes the glucose-mediated regulation of crp expression. Only a slight reduction in the crp expression by glucose is observed in cya- or crp- strains, suggesting that a CRP-cAMP complex is needed for this regulation. We previously showed that transcription of the crp gene is regulated both negatively and positively. Positive autoregulation of crp is caused by the binding of CRP-cAMP to the CRP binding site II located upstream of the crp promoter. Here we show that disrupting the CRP binding site II essentially eliminates the down-regulation of crp expression by glucose. We conclude that the autoregulatory circuit of the crp gene plays a key role in the down-regulation of CRP by glucose.

Base Sequence↗

Endothelin-1-selective receptor in the arterial intima of patients with hypertension.

Endothelin-1 is a potent vasoconstrictor produced by vascular endothelial cells. A recently cloned endothelin-1-selective receptor, the endothelin-A receptor, mediates the vasoconstrictive action of endothelin-1. Because endothelin-1 also possesses mitogenic properties, it may play a role in regulating the proliferation of intimal smooth muscle cells. In this study, we analyzed the expression of endothelin-A receptor gene in the thickened arterial intima of patients with hypertension. Internal mammary artery specimens obtained from 12 patients undergoing cardiovascular surgery were subjected to in situ hybridization using a digoxigenin-labeled cRNA probe. High, homogeneous signals of endothelin-A receptor mRNA were observed in the medial smooth muscle cells of all vessels examined but not in the endothelial cells. Patients with hypertension displayed more severe intimal thickening than those without hypertension. Immunohistochemical analysis suggested that almost all of the intimal proliferative cells originated from smooth muscle cells. In contrast to media, endothelin-A receptor mRNA signals in intimal smooth muscle cells were low and heterogeneous. In the thickened arterial intima of hypertensive patients, the signals were detected just beneath the luminal endothelium but not deep in the intimal smooth muscle cell layer. By contrast, staining with anti-alpha-smooth muscle actin antibody was more intense in the deep layer than in the subendothelium. These findings suggest that the modulation of endothelin-A receptor gene expression in smooth muscle cells differs between the intima and media. Its regulated expression in intimal smooth muscle cells might affect the proliferative activity of these cells in patients with hypertension.

Aged↗

[Influence of age on cardiac pump function during laparoscopic cholecystectomy--measurements by ear densitography].

Using ear densitography, consisting of photoelectric plethysomography and Holter electrocardiography, we measured systolic time intervals (STI) in 21 patients, ASA class 1 and 2, undergoing laparoscopic cholecystectomy using CO2 insufflation under general anesthesia (neuroleptanesthesia with isoflurane in air, FIO2 0.5). The patients were divided into two groups: Y-group (10 patients under 59 years of age) and O-group (11 patients over 60 years of age). We investigated the influence of age on cardiac pump function during pneumoperitoneum non-invasively. Y-group showed improvement of cardiac pump function (reduction of PEP/LVET) from 30 minutes after the beginning of insufflation and quick recovery of cardiac function immediately after deflation. O-group showed a tendency of increasing PaCO2 and arterial diastolic pressure, and delayed recovery of cardiac function (elongation of PEP at 60 minutes, and increase of PEP/LVET at 60 and 90 minutes, respectively, after insufflation). Hypertension and tachycardia were apparent immediately after pneumoperitoneum in the O-group. We conclude that special care and monitoring are mandatory for the aged patients with impaired cardiac or respiratory function during laparoscopic surgery.

Aged↗