Search PubMed⌕ Search

Biomedical subjects

T Miki

Publications and source records attributed to T Miki.

At least 433 records · Page 24Linked to original sources

Growth phenotypes of Escherichia coli carrying a mutation of acidic phospholipid synthesis.

We identified novel phenotypes of a pgsA3 mutant lacking the potential to synthesize phosphatidylglycerophosphate, a precursor of phosphatidylglycerol. The first phenotype is limited cell growth at a high temperature, under the condition of low salt. The phenotype was co-transduced with a phenotype lacking the potential to synthesize phosphatidylglycerol in a P1 transduction experiment, and was restored by transformation with a plasmid containing a wild type pgsA gene. The second phenotype of the pgsA3 mutant was resistant to growth in the presence of a low concentration of kanamycin (4 micrograms/ml). P1 transduction and transformation with the plasmid containing the wild-type pgsA gene revealed that the pgsA3 mutation was also responsible for the second phenotype.

Escherichia coli↗

Influence of the linking number of template DNA on sigma 32-dependent transcription initiation in vitro of the Escherichia coli groE gene.

Plasmids carrying the groE promoter with a superhelical density of 0 to -0.091 were used for in vitro transcription with RNA polymerase holoenzyme containing sigma 32. The promoter activity of the groE gene in vitro on the plasmid DNA was decreased to 100-fold when the superhelical density of the template DNA decreased from -0.059 to 0. As the superhelical density of DNA inside the cells was estimated to be approximately -0.025, it seems likely that the increase in the linking number of template DNA caused by stress which induces heat shock response may not stimulate the groE promoter activity in vivo on the chromosomal DNA. At higher concentrations of salt, the dependence of the groE promoter activity on negative supercoiling was even more apparent. Since melting of the DNA duplex is inhibited by high salt concentrations, DNA supercoiling may facilitate melting of the groE promoter by an RNA polymerase holoenzyme containing sigma 32.

DNA Topoisomerases, Type II↗

Oxidative stress response in yeast: purification and characterization of glutathione reductase from Hansenula mrakii.

Glutathione reductase was purified from a yeast. Hansenula mrakii IFO 0895, to approximately 3500-fold with 59% activity yield. The enzyme was homogeneous on polyacrylamide gel electrophoresis. The molecular weight of the enzyme was estimated to be 56 kDa by SDS-polyacrylamide gel electrophoresis, and 123 kDa by gel filtration using a calibrated Sephadex G-150 column. The Km values for glutathione disulfide and NADPH were 21.3 microM and 14.3 microM, respectively. The enzyme was most active at pH 7.5, 55 degrees C. The enzyme was stable up to 40 degrees C, and between pHs 4 and 10. The enzyme was inhibited by p-chloromercuribenzoate and metal ions such as Fe3+, Cd2+, Cu2+, and Zn2+.

Chloromercuribenzoates↗

Analysis and comparison of new candidate loci for hypertension between genetic hypertensive rat strains.

To search for the genes that determine the level of blood pressure, we performed linkage analyses using rat microsatellite markers in two sets of F2 rats derived from two hypertensive rat strains and one normotensive rat strain. In the first F2 progeny obtained from spontaneously hypertensive rats and Wistar-Kyoto rats, it was found that two different loci cosegregated with blood pressure. One was gamma-crystallin locus on rat chromosome 9, which has a hypertensive effect, and the other was peroxisomal 3-keto acyl-CoA thiolase locus on rat chromosome 8, which has a hypotensive effect. Then, we studied the same loci in second F2 progeny obtained from Dahl/Iwai salt-sensitive rats and Wistar-Kyoto rats. It was found that the locus located on rat chromosome 8 also had a hypotensive effect, although the others were not cosegregated with blood pressure in this cross. We suggest that a new locus for hypertension is located on rat chromosome 9 and that a locus on rat chromosome 8 has a common effect that makes blood pressure decrease in different hypertensive strains.

Animals↗

Effect of mazindol on body weight and insulin sensitivity in severely obese patients after a very-low-calorie diet therapy.

The present investigations were performed in order to clarify the effects of mazindol on body weight and insulin sensitivity in patients with morbid obesity who had already been treated with a very-low-calorie diet containing 480 kcal food (VLCD) with various amino acids. We attempted to study whether a further decrease in body weight would be achieved by the administration of mazindol, because it is difficult to obtain sufficient and continuous reduction of body weight after VLCD therapy. Thirteen female severely obese subjects were 51.0 +/- 13.9 years old (25-73 years old), with a mean height of 154.7 +/- 5.6 cm (146.0-160.5 cm), mean weight of 84.5 +/- 9.4 kg (69-98 kg) and a mean body mass index (BMI) of 35.3 +/- 3.6 kg/m2 (29.2-41.0 kg/m2). Their mean body weight decreased to 76.7 +/- 2.2 kg (net decrease: 6.3 +/- 0.9 kg) after VLCD therapy for 2-4 weeks. Then they were treated by the administration of mazindol with diet restriction (1000-1200 kal/day). Mazindol administration resulted in a further weight reduction of 2.9 +/- 0.5 kg after 4 weeks, 4.9 +/- 0.5 kg after 8 weeks and 6.9 +/- 0.9 kg after 12 weeks. Their blood pressure was not changed after mazindol treatment. The responses of blood glucose and insulin levels in a 75 g oral glucose tolerance test (OGTT) were not significantly different before and after mazindol administration. The blood glucose area calculated from the data obtained during OGTT for 120 min did not significantly differ before and after mazindol administration, while the insulin area significantly decreased after mazindol treatment (from 98.0 +/- 12.1 before administration to 70.1 +/- 7.8). The mean M value reflecting insulin sensitivity in the whole body determined by euglycemic glucose clamping was increased significantly after mazindol treatment (from 4.92 +/- 0.30 mg/kg/min to 6.36 +/- 0.43 mg/kg/min). The results demonstrated that mazindol administration with diet restriction further reduced body weight in the morbidly obese subjects after treatment with VLCD, with an increase in the M value and a decrease in insulin release. The results suggest that mazindol is useful for reducing body weight as well as improving insulin sensitivity.

Adult↗

Mass screening for complete deficiency of thyroxine-binding globulin in adult Japanese by comprehensive health examination.

The incidence of complete thyroxine-binding globulin (TBG) deficiency (TBG-CD) was determined for a Japanese population from a comprehensive health examination, in which a T3 resin uptake test of the upper 5% (78 subjects from among 1,589 men) was the screening line for TBG-CD. Further analysis of the known mutation in TBG-CD gene of the Japanese population (reported as TBG-CDJ with codon 352 deletion) was performed on 72 subjects, and three were found to have TBG-CDJ, two of whom were siblings. Only those three subjects had a serum TBG concentration of less than 5 mg/l. The six subjects for whom the DNA analysis was not performed, did not have a serum TBG level of less than 5 mg/l. From these findings, the gene frequency of TBG-CDJ was calculated to be 0.13%. The incidence of TBG-CDJ in the total Japanese population is suggested to be 0.09%.

Adult↗

Renovascular hypertension with massive proteinuria.

A 65-year-old woman with renovascular hypertension and massive proteinuria is reported. Her urinary protein ranged from 3 to 5 g/day. Serum potassium was 2.9 mEq/l. Plasma renin activity and plasma aldosterone concentration were very high. A CT scan disclosed atrophy of the left kidney. Renogram showed a non-functioning pattern of the left kidney. An abdominal aortogram showed complete occlusion of the left renal artery at its ostium. After left nephrectomy, her high blood pressure and urinary protein were normalized. It seemed that the massive proteinuria was mainly due to some endocrinological effect of the left kidney.

Aged↗

[Primary biliary cirrhosis with polymyositis successfully treated with prednisolone and ursodeoxycholic acid].

A 65-year-old woman was given a diagnosis of polymyositis in April 1991. She was treated with prednisolone until December 1993, at which time muscle strength had increased and high blood pressure had developed. In May 1994 she was hospitalized for muscle weakness and mild liver dysfunction. Prednisolone was given and the levels of hepatobiliary enzymes decreased. Immunological examination revealed strongly positive results for anti-mitochondria antibody and M-2 antibody, which lead to the diagnosis of primary biliary cirrhosis. administration of ursodeoxycholic acid in addition to prednisolone was followed by normalization of liver function and a decrease in the production of the autoantibodies. Although polymyositis can be complicated by autoimmune diseases, reports of complication by primary biliary cirrhosis are rare, here we report that treatment with the combination of ursodeoxycholic acid and prednisolone was successful in a patient with liver dysfunction and primary biliary cirrhosis.

Aged↗

Internal DNA deletion within the BCL-6 gene on untranslocated chromosome in non-Hodgkin's lymphoma with 3q27 abnormality.

Chromosomal translocations involving the band 3q27 are recognized as common specific cytogenetic abnormalities in B cell non-Hodgkin's lymphoma (NHL), and the BCL-6 gene, identified on 3q27 was shown to be disrupted by these translocations. Previously, we have reported biallelic BCL-6 rearrangements occurring in some patients with B cell NHL. In the present study, we describe a NHL patient with t(3;22)(q27;q11) translocation. In this patient, biallelic BCL-6 abnormalities were indicated by Southern blot analysis. Further studies revealed that one of the two independent abnormalities was a juxtaposition to the immunoglobulin (Ig) lambda gene associated with chromosomal translocation, whereas the other was an internal DNA deletion of 1.5 kb area on untranslocated chromosome 3. Deletion junctions were located within the first exon and the 5' region of the first intron. The result provides the evidence that, besides chromosomal translocation, submicroscopic local DNA recombination can cause structural alteration of the BCL-6 gene.

Base Sequence↗

Toward localization of the Werner syndrome gene by linkage disequilibrium and ancestral haplotyping: lessons learned from analysis of 35 chromosome 8p11.1-21.1 markers.

Werner syndrome (WS) is an autosomal recessive disorder characterized by premature onset of a number of age-related diseases. The gene for WS, WRN, has been mapped to the 8p 11.1-21.1 region with further localization through linkage disequilibrium mapping. Here we present the results of linkage disequilibrium and ancestral haplotype analyses of 35 markers to further refine the location of WRN. We identified an interval in this region in which 14 of 18 markers tested show significant evidence of linkage disequilibrium in at least one of the two populations tested. Analysis of extended and partial haplotypes covering 21 of the markers studied supports the existence of both obligate and probable ancestral recombinant events which localize WRN almost certainly to the interval between D8S2196 and D8S2186, and most likely to the narrower interval between D8S2168 and D8S2186. These haplotype analyses also suggest that there are multiple WRN mutations in each of the two populations under study. We also present a comparison of approaches to performing disequilibrium tests with multiallelic markers, and show that some commonly used approximations for such tests perform poorly in comparison to exact probability tests. Finally, we discuss some of the difficulties introduced by the high mutation rate at microsatellite markers which influence our ability to use ancestral haplotype analysis to localize disease genes.

Age of Onset↗

[Biochemical markers of bone formation in osteoporosis].

We measured circulating bone Gla-protein(BGP) changes following short-term(2 weeks) active vitamin D treatment in elderly men with osteoporosis (73.0 +/- 9.4 years, n = 9) to evaluate osteoblastic function. We also measured serum levels of BGP(n = 245) and bone specific ALP(B-ALP) in women (n = 113) with normal lumbar bone mineral density, and evaluated the difference in clinical significance between these markers of bone formation. Serum BGP was significantly increased at the end of the first and 2nd week of daily oral 2 micrograms of 1 alpha(OH)D3 administration. BGP measurement is a clinically useful method to detect osteoblastic function after active vitamin D3 treatment. Significant positive correlations were found between age and BGP (r = 0.402, p < 0.01) or B-ALP (r = 0.494, p < 0.01). These markers were significantly higher in postmenopausal women compared with age-matched premenopausal women. The z-score of the difference in B-ALP was 1.47 and that of BGP was 0.7. Although B-ALP and P1CP in sera remained stable even at room temperature for at least 4 hours, the BGP level was significantly lower when the blood sample was kept at room temperature for more than 1 hour. These findings suggest that B-ALP is a more sensitive and stable marker than BGP in evaluating bone formation, although both markers have significant correlations with each other, and BGP is useful to detect the active vitamin D3 effect on osteoblastic function.

Aged↗

[Relationship between postoperative prognosis and preoperative immunological factors in aortitis syndrome].

Valve detachment or pseudoaneurysm is a well known complication of surgical treatment for cardiovascular disease due to aortitis syndrome. Although the preoperative management of inflammation by steroid therapy is very important, occasionally, the operation in active phase might be recommended because of progressive heart failure or impending rupture of aortic aneurysm. The pathology of aortitis syndrome is related to immunological abnormality, but there has been little information concerning the immunological factors. In order to evaluate the relationship between immunological factors and surgical results in patients with aortitis syndrome, immunological examination was obtained before surgery in 12 patients. Cardiovascular lesions due to aortitis syndrome were aortic regurgitation in 6 patients, annuloaortic ectasia in 1 patient, aortic arch aneurysm in 1 patient, mitral regurgitation in 2 patients, and coronary artery disease in 2 patients. Hospital mortality including initial operative death was not found. However, 6 late death (50%) occurred at late time with the mean of 23.8 months because of severe complications such as valve detachement or pseudoaneurysm after operation. In a comparison of the preoperative immunological values between survival group and late death group, immunoglobulins such as IgG, IgA, C3 and C4 were significantly higher in late death group. According to the recurrence of inflammation, the patients were divided into three groups. Group A included 3 patients who remains in active phase after initial operation in active phase. Group B included 3 patients who changed to active phase after initial operation in inactive phase. Group C included 6 patients who remains in inactive phase after initial operation. In a comparison among 3 groups, IgG and C4 showed no significant difference. However, IgA and C3 of group C were significantly lowest among three groups. This outcome is considered to be related to existence of latent inflammation. At operation, insertion of rigid prosthesis to fragile position due to latent inflammation may stimulate immunological reactions. We conclude that the preoperative values of the immunological factors, especially IgA and C3, are reliable predictors in postoperative prognosis.

Adult↗