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Biomedical subjects

T Ohtsuki

Publications and source records attributed to T Ohtsuki.

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

An "elongated" translation elongation factor Tu for truncated tRNAs in nematode mitochondria.

We have found the gene for a translation elongation factor Tu (EF-Tu) homologue in the genome of the nematode Caenorhabditis elegans. Because the corresponding protein was detected immunologically in a nematode mitochondrial (mt) extract, it could be regarded as a nematode mt EF-Tu. The protein possesses an extension of about 57 amino acids (we call this domain 3') at the C terminus, which is not found in any other known EF-Tu. Because most nematode mt tRNAs lack a T stem, domain 3' may be related to this feature. The nematode EF-Tu bound to nematode T stem-lacking tRNA, but bacterial EF-Tu was unable to do so. A series of domain exchange experiments strongly suggested that domains 3 and 3' are essential for binding to T stem-lacking tRNAs. This finding may constitute a novel example of the co-evolution of a structurally simplified RNA and the cognate RNA-binding protein, the latter having apparently acquired an additional domain to compensate for the lack of a binding site(s) on the RNA.

Amino Acid Sequence↗
PubMed2001

Association analysis of the pituitary adenyl cyclase activating peptide gene (PACAP) on chromosome 18p11 with schizophrenia and bipolar disorders.

In neurons, pituitary adenyl cyclase activating peptide (PACAP) stimulates signaling cascades, involving cAMP and calcium. PACAP appears to play a role in up-regulation of tyrosine hydroxylase and dopamine beta-hydroxylase via protein kinase C and/or protein kinase A. Furthermore, the PACAP gene (ADCYAP1) is located in chromosome 18p11, where linkage of bipolar disorders and schizophrenia has been reported. In this study, we scanned the coding region of the PACAP gene for mutations in 24 Japanese patients with schizophrenia and 24 Japanese patients with bipolar disorders. No variant in the coding region was found. One polymorphism, INV3-37A/T, in the third intron was detected. Case-control comparisons revealed no significant association between this polymorphism and schizophrenia or bipolar disorders. This study did not provide evidence for the contribution of the PACAP gene to the etiology of schizophrenia or bipolar disorders in the Japanese population.

Adolescent↗
PubMed2001

Mutation analysis of the NMDAR2B (GRIN2B) gene in schizophrenia.

NMDA receptor dysfunction may be involved in the pathophysiology of schizophrenia. Based on this hypothesis, we screened 48 Japanese patients with schizophrenia for mutations in the coding region of the NMDAR2B subunit gene (GRIN2B). An association study between the identified DNA sequence variants and schizophrenia was performed in 268 Japanese patients with schizophrenia and 337 Japanese control subjects. Eight single nucleotide polymorphisms were detected, all of which were synonymous. The association sample showed statistically significant excesses of homozygosity for the polymorphisms in the 3' region of the last exon in the patients with schizophrenia (P = 0.004) and higher frequency of the G allele of the 366C/G polymorphism (corrected P = 0.04) in the patients than in the controls. Although we did not detect NMDAR2B protein variants, our findings support the possibility that the GRIN2B gene or a locus in linkage disequilibrium with it may confer susceptibility to schizophrenia. Replication studies in independent samples are warranted.

Adult↗
PubMed2001

Neural control: novel evaluation of stretch reflex sensitivity.

We evaluated the stretch reflex activities of the elbow flexor and extensor muscles considering the relationship between the reflex electromyographic (EMG) responses and their corresponding standardized muscle stretch velocities. Specifically, muscular stretch velocity was estimated by using ultrasonograms. Stretch reflex EMG responses were elicited in the biceps brachii, brachioradialis and triceps brachii with a ramp-and-hold rotation at the elbow joint, which consisted of various angular velocities for the extension- or flexion-direction. The whole muscle stretch velocity induced by each ramp-and-hold rotation was calculated on the basis of fibre length changes associated with the elbow joint angle. A linear regression equation was fitted to the relation between the whole muscle stretch velocity and the reflex EMG responses, and the variables from the equation were used to quantify sensitivity of each reflex EMG component. The reflex EMG responses were increased as the ramp-and-hold rotational velocity increased. There were no significant differences in the recorded magnitudes of reflex EMG responses with equivalent joint rotational velocity between the brachioradialis and the triceps brachii medial head. These muscles showed the highest reflex responses in the flexor and extensor muscles, respectively. To the contrary, the reflex EMG response elicited by the standardized muscle stretches was significantly greater in the extensor muscles, indicating a higher reflex sensitivity. This was because of the lower muscle stretch velocity of the triceps brachii with an equivalent elbow joint rotation. The stretch reflex sensitivity in both the elbow flexor and extensor muscles might be regulated so as to make the reflex responses the same when the equivalent joint rotational velocity is applied to these muscles.

Elbow Joint↗
PubMed2001

Stereochemical applications of the expression of the L-2,3-butanediol dehydrogenase gene in Escherichia coli.

The L-2,3-butanediol dehydrogenase (L-BDH) gene of Brevibacterium saccharolyticum was strongly expressed in Escherichia coli using the tac promoter. However, the stereospecificity of the resulting L-BDH was reduced. The region upstream of the meso-BDH gene of Klebsiella pneumoniae was also involved in the expression of the B. saccharolyticum gene. However, in this case, the resulting L-BDH exhibited more stable stereospecificity. A stereospecificity recognition region was located within the rear sequence (Hpa I site, carboxy terminal) of the BDH open reading frame. Using a transformed strain of E. coli, the conversion of L-acetoin (L-AC), in the commercially available racemic mixture of AC, to L-2,3-butanediol (L-BD) was attempted. As a result, 0.37% L-BD was formed from 1% AC added to the culture.

Acetoin↗
PubMed2001

Colon cancer with meningeal carcinomatosis and myelodysplastic syndrome in a patient who underwent intensive chemotherapy for acute myelogenous leukemia: a case report.

A 59-year-old man was admitted to our hospital because of disturbance of consciousness and hyponatremia. The patient had suffered from acute myelogenous leukemia (AML) with 46,XY and received chemotherapy for 5 years. Meningeal carcinomatosis was diagnosed due to the detection of carcinoma cells in the cerebrospinal fluid (CSF). Hyponatremia was caused by syndrome of inappropriate secretion of anti-diuretic hormone (SIADH). Bone marrow examination revealed myelodysplastic syndrome (MDS) with deletion of the long arm of chromosome 7. Emergence of a new abnormal clone was suggested. The patient died from brain herniation. Post mortem examination showed adenocarcinoma in the colon. An association between chemotherapy and both colon cancer and MDS was suggested.

Adenocarcinoma↗
PubMed2001

Requirement of modified residue m1A9 for EF-Tu binding to nematode mitochondrial tRNA lacking the T arm.

Most of nematode mitochondrial (mt) tRNAs lacking the T arm have 1-methyladenosine (m1A) at position 9. To investigate the effect of m1A, we constructed a nematode Ascaris suum mt tRNA(Met) containing only m1A9 as the modified nucleoside by means of molecular surgery. Although the unmodified A. suum mt Met-tRNA(Met) did not bind to nematode mt EF-Tu, the m1A9-containing tRNA bound to the EF-Tu, suggesting that m1A at position 9 is necessary for binding of nematode mt tRNAs lacking the T arm to the EF-Tu, probably because of maintenance of the L-shape-like structure or interaction with the C-terminal amino acid residues of the EF-Tu.

Adenosine↗
PubMed2001

Induction of the HSP110/105 family in the rat hippocampus in cerebral ischemia and ischemic tolerance.

Recently, the authors isolated a novel gene of the HSP110 family, ischemia responsive protein 94 kDa (irp94), and demonstrated the expression of this gene after transient forebrain ischemia. In the current study, the authors investigated the expression profiles of all HSP110 family members including hsp110/105 and osp94/apg-1, after transient forebrain ischemia using rat four-vessel occlusion model. Among three members of the HSP110 family, induction of hsp110/105 was the most prominent after ischemia. hsp110/105 mRNA expression was clearly enhanced from 4 to 24 hours after a 6-minute or longer ischemic period. First, hsp110/105 mRNA expression was induced in the dentate gyrus, and later in the pyramidal layer. HSP110/105 protein expression also was enhanced by a 6-minute or longer period of ischemia. Profiles of HSP110/105 expression after ischemia were similar to those of inducible HSP70. After transient forebrain ischemia for 10 minutes, HSP110/105 protein was induced in the dentate gyrus and the CA3 pyramidal layer, but not in the CA1 pyramidal neurons. However, 6 minutes of ischemia induced the HSP110/105 protein, as well as the HSP70 protein, in the CA1 region. CA1 pyramidal neurons expressing HSP110/105 acquired tolerance against subsequent severe ischemia. In conclusion, HSP110/105 showed the most prominent induction after ischemia among the three HSP110 gene family members. Colocalization of HSP110/105 and HSP70 in the CA1 neurons that acquired tolerance suggested that induced HSP110/105 might contribute to ischemic tolerance together with HSP70.

Animals↗
PubMed2001

Delayed, but marked, expression of apolipoprotein E is involved in tissue clearance after cerebral infarction.

Clearance of infarct tissue would be an important process for tissue repair after a stroke. Delayed clearance may hamper reconstitution of the blood-brain barrier and glial boundary formation. Recent growing evidence has indicated that apolipoprotein E (APOE), a major apoprotein, plays an important role in lipid transport and homeostasis in the brain. The tissue in the infarction contains abundant lipids must be removed for tissue clearance. In the current study, the authors investigated APOE expression after focal ischemia and the functional role of APOE in tissue clearance using APOE-knockout mice. Expression of APOE was delayed, but marked, in immunohistochemistry and immunoblotting 7 days after permanent focal ischemia. Macrophages were found to express APOE in the infarct center. Infarct size was similar after focal ischemia between wild-type and APOE-knockout mice, although there was no APOE protein expression in knockout mice. However, clearance of infarct tissue 2 weeks after ischemia was significantly delayed in APOE-knockout mice compared with wild-type mice. The current study supports current thinking that APOE is a key molecule for tissue remodeling in the brain. Clearance of damaged tissue may be one of the important functions of APOE in the brain.

Animals↗
PubMed2001

Mutation screening of the metabotropic glutamate receptor mGluR4 (GRM4) gene in patients with schizophrenia.

Disturbances in glutamate function have been implicated in the pathophysiology of schizophrenia. We searched for mutations in the exons of the metabotropic glutamate receptor mGluR4 (GRM4) gene on human chromosome 6p21.3 and evaluated associations between these polymorphisms with schizophrenia in Japanese patients. Nine nuclear variants of 450G > T, 1455T > C, 2202A > G, 2389G > A (Val797 > Ile797), 2890A > G, 3601C > T, 3639C > T, IVS4-36G > A, and IVS5 + 29(CCGGG)1-2, were found. The Val797Ile variant, although found in both the patient and control groups, was rare and the only variant that causes a non-synonymous amino acid change. There was no statistically significant association between any mGluR4 gene polymorphism and schizophrenia. Thus, this study did not provide evidence for the contribution of the mGluR4 gene to schizophrenia in the Japanese.

Adult↗
PubMed2001

Transient crossed cerebellar diaschisis following thalamic hemorrhage.

This report concerns a 65-year-old right-handed woman with cerebral hemorrhage who presented with mild right-sided hemiparesis. Computed tomography (CT) revealed hematoma in the left thalamus and compression of the posterior limb of the internal capsule by a brain edema surrounding the lesion. 99mTc-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) images obtained 4 days after onset showed hypoperfusion in the left thalamus containing a hematoma as well as contralateral cerebellar hypoperfusion to the supratentorial lesion, which is well recognized as crossed cerebellar diaschisis (CCD) after stroke. CT 14 days after the onset revealed reduction of the brain edema of the posterior limb of the internal capsule accompanied by gradual neurological improvement. SPECT obtained 14 and 28 days later showed that CCD had disappeared. In this case report, the authors discuss the disappearance of CCD due to transient edematous compression of the internal capsule following thalamic hemorrhage on serial 99mTc-HMPAO SPECT scans. CCD was possibly caused by the lesion confined to the posterior limb of the internal capsule, which anatomically constitutes the cerebropontocerebellar pathway.

Aged↗
PubMed2001

Significance of earlier carotid atherosclerosis for stroke subtypes.

BACKGROUND AND PURPOSE: In addition to advanced stenosis, earlier stages of carotid atherosclerosis are associated with the risk for stroke. However, the significance has not been established for specific stroke subtypes. This study examines the association of earlier carotid atherosclerosis with stroke subtypes. METHODS: The subjects comprised 1059 patients (mean+/-SD age, 62+/-11 years) with <60% carotid stenosis. With the use of ultrasound, carotid atherosclerosis was evaluated by the plaque score, as defined by the sum of all plaque heights in bilateral carotid arteries. On the basis of neurological signs and symptoms, medical history, and brain MRI, we diagnosed stroke and its subtypes as follows: no stroke (n=738), atherothrombotic infarction (AI) (n=56), lacunar infarction (LI) (n=117), cardioembolic infarction (n=65), cerebral hemorrhage (n=26), and other or unclassified stroke (n=57). RESULTS: The plaque score was higher in AI (10.5+/-5.9) and LI (6.0+/-5.1) groups than in the no-stroke group (4.3+/-4.9) (both P<0.05), although it was similar between other stroke groups and the no-stroke group. Each 1 SD greater plaque score was associated with 2.5-fold (95% CI, 2.0 to 3.2) higher risk for AI and 1.4-fold (95% CI, 1.2 to 1.7) higher risk for LI compared with the no-stroke group. When we adjusted for cardiovascular risk factors, plaque score remained significantly associated with AI but not with LI. By receiver operating characteristic curve analyses, the receiver operating characteristic area for AI (0.81 to 0.86) was greater than that for LI (0.62 to 0.67) when we used plaque score either alone or in combination with cardiovascular risk factors. CONCLUSIONS: Although evaluation of carotid atherosclerosis may aid in the risk assessment for AI and LI, the benefit appears to be greater for AI.

Aged↗
PubMed2001

Neurogenesis by progenitor cells in the ischemic adult rat hippocampus.

BACKGROUND AND PURPOSE: Recently, there has been great interest in adult neurogenesis. We investigated whether transient forebrain ischemia could influence the proliferation of neuronal progenitor in the subgranular zone (SGZ) of the rat hippocampus and whether aging could influence the neurogenesis after ischemia. METHODS: Male Wistar rats were subjected to 4-vessel occlusion model. We used a bromodeoxyuridine (BrdU) labeling method to identify the postproliferation cells and double-immunostaining with confocal microscopy to determine the cell phenotype. RESULTS: The number of BrdU-positive cells in the SGZ increased approximately 5.7-fold 8 days after ischemia, compared with the control. BrdU-positive cells formed clusters, which suggested that these cells had divided from an original progenitor cell, and expressed Musashi1 (Msi1), a marker of neural stem/progenitor cells. Although astrocytes also expressed Msi1 in the adult brain, Msi1-positive cells that formed clusters in the SGZ did not express glial fibrillary acidic protein, an astrocyte marker. About 70% of all BrdU-positive cells in the SGZ represented the neuronal phenotype 4 weeks after the BrdU injection. Although proliferation of progenitor cells was stimulated in both young and older animals, aging accelerated the reduction in newborn cells after ischemia. CONCLUSIONS: Our results indicate that ischemic stress stimulated the proliferation of neuronal progenitor cells in the SGZ of both young and old rats but resulted in increased neurogenesis only in young animals. Our findings will be important in developing therapeutic intervention to enhance endogenous neurogenesis after brain injury.

Aging↗
PubMed2001

Characterization of the NADH-linked acetylacetoin reductase/2,3-butanediol dehydrogenase gene from Bacillus cereus YUF-4.

A 1.4-kbp DNA fragment, including the NADH-linked acetylacetoin reductase/2,3-butanediol dehydrogenase (AACRII/BDH) gene from the chromosomal DNA of Bacillus cereus YUF-4, was cloned in Escherichia coli DH5alpha after its insertion into pUC119, and the resulting plasmid was named pAACRII119. The AACRII/BDH gene had an open reading frame consisting of 1047 bp encoding 349 amino acids. The enzyme exhibited not only AACR activity, but also BDH activity. However, the gene was not located in a 2,3-butanediol (BD) operon, as is the case in the BDH gene of Klebsiella pneumoniae and that of K. terrigena. In addition, there was no BD-cycle-related enzyme gene in the region surrounding the AACRII/BDH gene. The AACR and BDH activities in E. coli DH5alpha/pAACRII119 were 200-fold higher than those in the original B. cereus YUF-4. The characteristics of the AACRII/BDH from E. coli DH 5alpha/pAACRII119 are similar to those of the AACRII/BDH from B. cereus YUF-4. The AACRII/BDH was considered to belong to the NAD(P)- and zinc-dependent long-chain alcohol dehydrogenase (group I ADH) family on the basis of the following distinctive characteristics: it possessed 14 strictly conserved residues of microbial group I ADH and consisted of about 350 amino acids. The enzymatic and genetic characteristics of AACRII/BDH were completely different from those of BDHs belonging to the short-chain dehydrogenase/reductase family. These findings indicated that the AACRII/BDH could be considered a new type of BDH.

Journal Article↗
PubMed2001

Purification and characterization of L-2,3-butanediol dehydrogenase of Brevibacterium saccharolyticum C-1012 expressed in Escherichia coli.

The L-2,3-butanediol dehydrogenase produced in E. coli JM109/pLBD2-CTC was purified by 5 steps. The molecular mass of this enzyme was estimated at 110 kDa and the subunit was measured to be 30 kDa. The L-BDH had some differences from the BDHs from other sources in substrate specificity, pI value, pH stability, effects of divalent cations, and organic acids.

Alcohol Oxidoreductases↗
PubMed2001

[Outcome of acute myelogenous leukemia in 41 patients treated with idarubicin: the prognosis of t(8;21) cases].

Idarubicin (IDR) has been used as the main drug in induction chemotherapy for acute myelogenous leukemia (AML) in the USA and Europe. Between May 1995 and October 1998, we treated 41 cases of fresh AML using IDR induction chemotherapy and analyzed the clinical course, remission rate, relapse rate and prognosis. The results obtained in these cases were similar to those in 26 cases treated with daunorubicin (DNR) in our hospital according to JALSG-AML92. The outcome in cases with abnormal chromosomes and cases showing relapse was very poor. In particular, all 5 t(8;21) cases in our series relapsed, suggesting that t(8;21) cannot be considered a favorable prognostic factor in cases treated with IDR-containing regimens. However, 3 of the 5 t(8;21) cases were positive for CD56, which itself is an unfavorable prognostic factor. Thus it is possible that CD56 was related to the poor outcome. Intensive post-remission induction chemotherapies will be required in order to obtain prolonged disease-free survival.

Adult↗
PubMed2001

Natural history of hypertrophic cardiomyopathy: Japanese experience.

BACKGROUND AND OBJECTIVES: Most patients with hypertrophic cardiomyopathy (HCM) remain clinically stable for long periods of time, whereas some patients progress to severe systolic dysfunction. Therefore, the natural history of HCM is largely unknown. METHODS: The present study followed up 59 patients with HCM (32 males, 27 females, mean age 38.6 +/- 13.6 years) for 10 years or more (mean 16.0 +/- 4.7 years) after the initial diagnosis. RESULTS: Eight of 17 patients who showed abnormal Q-waves at the initial examination had lost Q-waves, suggesting remodeling from asymmetric to generalized hypertrophy. The thickness of the interventricular septum showed remarkable changes, increasing by > or = 5 mm in 7 patients and decreasing by > or = 5 mm in 21. These observations indicate that ventricular remodeling occurs in patients with HCM. Follow-up electrocardiography demonstrated new Q-waves in 10 patients and bundle branch blocks or intraventricular conduction disturbances in 13. Left ventricular end-diastolic diameter increased from 41.6 to 48.1 mm, associated with a decrease in fractional shortening from 40.6% to 34.0%. Left ventricular systolic dysfunction, defined as left ventricular end-diastolic diameter > 55 mm or fractional shortening < 25%, developed in 13 patients. These observations indicate that myocardial disease including the conduction system is progressive in patients with HCM and finally deteriorates to systolic dysfunction. Left ventricular outflow obstruction also presented evolutional changes. At the initial study, 23 patients showed systolic anterior motion of the mitral valves. Systolic anterior motion disappeared in 13 patients, reduced in 2, increased in 2, and remained stable in only 6. One patient without systolic anterior motion at the initial study developed new systolic anterior motion. Impaired left ventricular filling increased left atrial diameter from 35.5 to 46.9 mm and atrial fibrillation frequently developed (24 patients). CONCLUSIONS: These findings suggest that HCM is a slowly progressive disease which develops evolutional remodeling of left ventricular hypertrophy and outflow obstruction, eventually progressing to systolic dysfunction with cavity dilation and wall thinning.

Adult↗