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Biomedical subjects

T Oki

Publications and source records attributed to T Oki.

At least 55 records · Page 3Linked to original sources

Arisostatins A and B, new members of tetrocarcin class of antibiotics from Micromonospora sp. TP-A0316. I. Taxonomy, fermentation, isolation and biological properties.

Arisostatins A and B, new members of tetrocarcin class of antibiotics were isolated from the culture broth of an actinomycete strain. The producing strain, TP-A0316, was identified as Micromonospora sp. Arisostatins were obtained from the culture fluid by solvent extraction and chromatographic purification. They showed antibiotic activity against Gram-positive bacteria and antitumor activity.

Aminoglycosides↗

Arisostatins A and B, new members of tetrocarcin class of antibiotics from Micromonospora sp. TP-A0316. II. Structure determination.

Structures of arisostatins A and B were determined by spectroscopic analyses. Arisostatins were found to be new analogs of tetrocarcin A and possess an iso-butanoyldigitoxose unit instead of the acetyldigitoxose one. NMR analyses of arisostatins and tetrocarcin A led to the revision of the anomeric configurations in the tetrasaccharide moiety of tetrocarcin A.

Aminoglycosides↗

New Cdc25B tyrosine phosphatase inhibitors, nocardiones A and B, produced by Nocardia sp. TP-A0248: taxonomy, fermentation, isolation, structural elucidation and biological properties.

Strain TP-A0248 which produces two new Cdc25B tyrosine phosphatase inhibitors and also possessing antifungal activity, designated nocardiones A (1) and B (2), was considered to belong to the genus Nocardia on the basis of literature comparison of chemotaxonomic properties. The nocardiones were isolated by solvent extraction of fermentation broth of Nocardia sp. TP-A0248 and purified by the conventional column chromatography. Spectroscopic studies led to determination that 1 and 2 belong to a class compound of naphtho[1,2-b]furan-4,5-diones. Compound 1 inhibited the activity of Cdc25B, PTP1B and FAP-1 protein tyrosine phosphatases at a concentration of 10 microM. It also showed moderate in vitro antifungal and cytotoxic activity.

Antifungal Agents↗

Xanthoepocin, a new antibiotic from Penicillium simplicissimum IFO5762.

A new antifungal antibiotic xanthoepocin was isolated from the culture broth of Penicillium simplicissimum IFO5762. Xanthoepocin was obtained from the culture fluid by solvent extraction and chromatographic purification. It showed antibiotic activity against Gram-positive bacteria and yeasts.

Anti-Bacterial Agents↗

Neuron-specific expression of reporter gene in transgenic mice carrying the 5'-upstream region of mouse P/Q-type Ca2+ channel alpha 1A subunit gene fused to E. coli lacZ reporter gene.

To dissect the molecular mechanisms underlying the neuron-specific expression of the P/Q type calcium channel alpha 1A subunit gene, transgenic mice carrying a 0.5-kb, 1.5-kb, 3.0-kb or 6.3-kb 5'-upstream region of the gene fused to Escherichia coli lacZ reporter gene were produced. In transgenic mice carrying the 1.5-kb, 3.0-kb or 6.3-kb 5'-upstream region, the reporter gene was exclusively expressed in the nervous system, although those with the 0.5-kb 5'-upstream region failed to show reporter expression. Histological examinations showed that the three 5'-upstream regions induced distinct expression patterns of the reporter gene in the CNS and adrenal medulla. The 1.5-kb 5'-upstream region drove reporter gene expression in the olfactory bulb, dorsal cortex and hippocampus, while the regulatory element for the expression in the amygdaloid nucleus, septum, habenula medial nucleus, choroid plexus, substantia nigra, inferior colliculus, pontine nucleus and cerebellum was located in the 5'-upstream sequence between 1.5 kb and 6.3 kb. In the cerebellum, the expression of the reporter gene was induced by the 3.0-kb region in granule cells, whereas it was induced by the 6.3-kb region in Purkinje cells. The expression of the reporter gene in chromaffin cells in the adrenal medulla was induced only by the 6.3-kb 5'-upstream region. These results suggest that the expression of the mouse P/Q-type Ca2+ channel alpha 1A subunit gene is regulated in a complex fashion by both positive and negative cis-regulatory elements.

5' Untranslated Regions↗

Isolation and functional characterization of the 5'-upstream region of mouse P/Q-type Ca2+ channel alpha1A subunit gene.

The omega-agatoxin-IVA-sensitive P/Q-type Ca2+ channel is predominantly expressed in the nervous system. To dissect the molecular mechanisms underlying the neuron-specific expression of the P/Q-type channel, we have isolated and characterized the 5'-upstream region of the mouse alpha1A subunit gene. A transcription start site appeared to exist at -269 bp upstream from the start codon as found by 5' RACE analysis. The proximal promoter of the alpha1A subunit gene lacks a typical TATA box, but contains several transcription factor binding sequences, including two Sp1 sites. When linked to a placental alkaline phosphatase (PLAP) reporter gene to examine the promoter activity, the 6.3-kb (-6,273 to +269) 5'-upstream region, but not a smaller 3.0-kb construct (-3, 021 to +269), was able to drive the reporter gene in neuron-like PC12 cells. In contrast, neither of these constructs enhanced the PLAP expression in fibroblast NIH3T3 cells. The sequence between 6.3 and 3.0 kb of the 5'-upstream region did not show promoter activity in either of the cell lines, but enhanced TK promoter activity in PC12 cells, though not in NIH3T3 cells. These results suggest that neuron-specific elements of the alpha1A subunit gene are likely to be located in the distal upstream regions (-6,273 to -3,021) of the 5'-upstream sequence.

3T3 Cells↗

cDNA cloning and mapping of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT2) in human and mouse.

We subcloned human and mouse full-length cDNAs of a novel subtype of glutamine:fructose-6-phosphate amidotransferase (GFAT), which was designated GFAT2 (the previously reported GFAT was named GFAT1). Both the human and the mouse GFAT2 proteins deduced from their open reading frame sequences are composed of 682 amino acids of approximately 77.0 kDa. At the amino acid level, homologies between the human GFAT1 and GFAT2, between the mouse GFAT1 and GFAT2, and between the human GFAT2 and the mouse GFAT2 were 75.6, 74.7, and 97. 2%, respectively. Northern blot analysis using probe specific to human GFAT1 or GFAT2 showed that major transcripts were approximately 3.0 kb in both the human GFAT subtypes. The analysis also revealed different tissue distribution between GFAT1 and GFAT2: GFAT1 was more highly expressed in the placenta, pancreas, and testis than GFAT2; GFAT2 was expressed throughout the central nervous system, especially in the spinal cord, but GFAT1 expression was weak. The locus was mapped to human chromosome 5q and mouse chromosome 11, where a synteny between the two species has been known. GFAT2 can provide insights into understanding the roles of the hexosamine pathway in various tissues, particularly with the development of glucose toxicity and diabetes complications.

Amino Acid Sequence↗

Bone mineral density in postmenopausal women with endometrial cancer.

OBJECTIVE: The aim of the study was to investigate the relationship between endometrial cancer and bone mineral density (BMD). MATERIALS AND METHODS: A total of 55 postmenopausal Japanese women with well-differentiated adenocarcinoma and 284 age-matched healthy women were studied. Baseline characteristics including age, age at menopause, years since menopause (YSM), weight, height, body mass index (BMI), prior menstrual history, parity, and fertility were recorded for each subject. Lumbar spine BMD (L2-4), and body fat indices including body fat mass amount and percent body fat were measured by dual-energy X-ray absorptiometry. These variables were compared between the two groups. In all subjects (n = 339), correlations of BMD with the presence of endometrial cancer, baseline characteristics, and body fat indices were investigated, using univariate and multiple regression analyses. RESULTS: BMD, weight, BMI, body fat mass amount, and percent body fat were significantly higher in women with endometrial cancer. Other baseline characteristics did not differ between the two groups. Age at menopause, height, weight, BMI, percent body fat, and body fat mass amount were positively correlated with BMD, while age and YSM were inversely correlated with BMD. After adjusting for age, YSM, and height, the presence of endometrial cancer was still correlated with BMD (P < 0.05). However, after adding body fat mass amount to these three adjusted variables, there was no correlation between the presence of endometrial cancer and BMD. CONCLUSION: Women with endometrial cancer have a high BMD. This is attributable to high body fat mass amount in this disease.

Adenocarcinoma↗

Serum androgen levels and muscle mass in women with polycystic ovary syndrome.

OBJECTIVE: To relate serum androgen levels and muscle size in women with polycystic ovary syndrome (PCOS). METHODS: Forty-eight women with PCOS were studied. Baseline characteristics included age, height, weight, and hirsutism. Total-body lean mass was measured by wholebody scanning with dual-energy x-ray absorptiometry, and the lean mass index (total-body lean mass/height2, kg/m2) was calculated. Trunk-leg fat mass ratio (trunk-leg fat ratio) was assessed by dual-energy x-ray absorptiometry. Serum testosterone, dehydroepiandrosterone sulfate, and androstenedione levels were measured by radioimmunoassay. Subjects were arbitrarily divided into two groups according to lean mass index (lean mass index at least 14 kg/m2, n = 24; or less than 14 kg/m2, n = 24). Baseline characteristics and serum androgen levels were compared between the groups. In all subjects, lean mass index was correlated with age, height, trunk-leg fat ratio, and serum androgen levels. RESULTS: Although trunk-leg fat ratio, serum testosterone and androstenedione levels, and the prevalence of hirsutism were significantly higher in women with a lean mass index at least 14 kg/m2, age and height did not differ significantly between the groups. Trunk-leg fat ratio and serum testosterone and androstenedione levels correlated significantly with lean mass index (r = .68, .75, and .54, respectively). Hirsutism also correlated with lean mass index (standardized regression coefficient = .49; P<.05). CONCLUSION: Muscle size in women with PCOS correlated positively with serum androgen levels and upper body-fat distribution, independent of height.

Adult↗

Effect of aging on diastolic left ventricular myocardial velocities measured by pulsed tissue Doppler imaging in healthy subjects.

We evaluated the effect of aging on diastolic left ventricular (LV) wall motion velocity in 80 healthy persons with the use of pulsed tissue Doppler imaging. The wall motion velocity patterns were recorded at the middle regions of the LV posterior wall and ventricular septum in the parasternal (along the short axis) and apical (along the long axis) LV long-axis views. In the posterior wall, the peak early diastolic wall motion velocities (Ews) along both axes correlated inversely with age (long axis: r = -0.61, P <. 0001; short axis: r = -0.55, P <.0001), and the peak atrial systolic wall motion velocities(Aws) along both axes correlated directly with age (long axis: r = 0.59, P <.0001; short axis: r = 0.65, P <.0001). In the ventricular septum, the Ew along the long axis correlated inversely with age (r = -0.51, P <.0001), and the Aws along both axes correlated directly with age (long axis: r = 0.57, P <.0001; short axis: r = 0.53, P <.0001). The Ews along both axes at the posterior wall correlated directly with the peak early diastolic transmitral flow velocity. The Aws along both axes at the ventricular septum and posterior wall correlated directly with the peak atrial systolic transmitral flow velocity. The times from the second heart sound to the peak of the early diastolic waves of the ventricular septum and posterior wall along both axes significantly increased with age. The times from the aortic component of the second heart sound to the peak of the early diastolic motion velocities along both axes were significantly longer at the ventricular septum than at the posterior wall. Pulsed tissue Doppler imaging may be useful for evaluating the effect of aging on diastolic LV function in healthy persons.

Aging↗

Pulsed tissue Doppler imaging of left ventricular systolic and diastolic wall motion velocities to evaluate differences between long and short axes in healthy subjects.

Our objective was to evaluate in healthy subjects the left ventricular (LV) wall motion velocities along the long and short axes by means of pulsed tissue Doppler imaging (TDI) to clarify the differences in the LV systolic and diastolic function between both axes. Wall motion velocities were recorded at the mid-wall portion of the middle site of the LV posterior wall in the parasternal long-axis view, and at the subendocardial portion of the middle site of the LV posterior wall in the apical long-axis view by pulsed TDI in 35 healthy subjects (mean age 26 +/- 10 years, mean heart rate 72 +/- 7 bpm). In all subjects, the LV pressure curve, its first derivative (dP/dt), the LV wall motion velocity, the phonocardiogram, and the electrocardiogram were simultaneously recorded. The systolic wave of the LV posterior wall motion velocity exhibited 2 peaks: the first and second systolic waves (Swl and Sw2, respectively). The diastolic wave also exhibited 2 peaks, the early diastolic and atrial systolic waves. The Swl along the long axis was greater than either the Sw1 and Sw2 along the short axis or the Sw2 along the long axis. The peak Sw1 along the long axis coincided with the peak dP/dt and was slightly earlier than the peak Swl along the short axis. The onset of Sw1 along the long axis coincided with the onset of the first heart sound. The Sw2 along the short axis was greater than that along the long axis. The early diastolic wave along the short axis was greater than that along the long axis, whereas the atrial systolic wave along the long axis was greater than that along the short axis. Thus, in healthy subjects, shortening of the longitudinal fibers predominated over that of the circumferential fibers during early systole, whereas shortening of the circumferential fibers predominated over the longitudinal fibers during the ejection phase. During diastole, the circumferential fibers predominated in the LV wall expansion at early diastole, whereas the longitudinal fibers predominated at atrial systole. In conclusion, pulsed TDI provided information that is useful in understanding the characteristics of LV wall motion along the long and short axes.

Adult↗

Effect of an acute increase in afterload on left ventricular regional wall motion velocity in healthy subjects.

We recorded left ventricular (LV) wall motion velocities before and after angiotensin II infusion by pulsed tissue Doppler imaging in 20 healthy subjects, and evaluated the responses of systolic and diastolic LV function along the long and short axes during an acute increase in afterload. Angiotensin II was administered intravenously to obtain a 30% increase in mean blood pressure. After angiotensin II infusion, LV end-systolic dimension and end-systolic circumferential wall stress increased significantly, and the percentage of LV fractional shortening decreased significantly. Peak first systolic LV wall motion velocity (Sw1 ) along the long axis decreased markedly compared with that along the short axis, and peak second systolic LV wall motion velocity (Sw2 ) along the short axis decreased significantly compared with that along the long axis. Early diastolic LV wall motion velocities along both the long and short axes decreased significantly, whereas atrial systolic LV wall motion velocity did not change. In conclusion, an acute increase in afterload caused a significant decrease in longitudinal fiber shortening during the isovolumic contraction phase (Sw1 along the long axis), circumferential fiber shortening during the ejection phase (Sw2 along the short axis), and LV relaxation during early diastole (early diastolic LV wall motion velocities along both axes) in healthy subjects. Pulsed tissue Doppler imaging may be useful for detecting the effect of various loading conditions on LV wall motion velocities along the long and short axes.

Adult↗

Left ventricular systolic wall motion velocities along the long and short axes measured by pulsed tissue Doppler imaging in patients with atrial fibrillation.

Pulsed tissue Doppler imaging was performed to measure systolic left ventricular (LV) posterior wall motion velocity along the long and short axes and to evaluate the relationships between the systolic variables and the maximum first derivative (peak dP/dt) of the LV pressure curve and the 2 preceding R-R intervals in 39 patients with atrial fibrillation (AF). The study group consisted of 22 patients with AF only, 17 patients with dilated or ischemic cardiomyopathy and AF, and 25 healthy control subjects in sinus rhythm. The systolic component of the LV posterior wall motion velocity was divided into the first (Sw1) and second (Sw2 ) systolic waves. The peak Sw1 along the long axis was greater than either that along the short axis or the peak Sw2s along the long and short axes in the control and AF-only groups. The peak Sw1 along the long axis was lower in the AF-only group than in the control group, and those along the short and long axes were lower in the dilated AF group than in the other groups. The peak Sw1 almost coincided with the peak dP/dt. The peak Sw1 along the long axis correlated closely with the peak dP/dt, and the ratio of the preceding R-R interval to the interval before the preceding ("prepreceding") R-R interval in both AF groups, particularly in the dilated AF group, and the slopes of their relationships were steeper in the dilated AF group than in the AF-only group. The peak Sw2 along the short axis was greater than that along the long axis in the control and AF-only groups. The peak Sw2 along the long axis was lower in the AF-only group than in the control group, and those along the short and long axes were lower in the dilated AF group than in the other groups. The peak dP/dt was lower and the LV end-diastolic pressure was higher in the dilated AF group than in the other groups. In conclusion, peak Sw1 along the long axis is useful for the evaluation of isovolumic myocardial LV contractility, and the interval-force relation and the Frank-Starling mechanism are important factors of beat-to-beat variability in systolic LV function in patients with AF.

Atrial Fibrillation↗

Evaluation of left ventricular contraction abnormalities in patients with dilated cardiomyopathy with the use of pulsed tissue Doppler imaging.

The left ventricular (LV) systolic wave, as recorded by pulsed tissue Doppler imaging, usually consists of 2 components (Sw(1) and Sw(2)). However, the clinical significance of these waves has not been studied in patients with dilated cardiomyopathy (DCM) and sinus rhythm. We studied 25 patients with DCM (DCM group) and 22 age-matched normal subjects (control group). The LV posterior wall motion velocities along the short and long axes were recorded by pulsed tissue Doppler imaging, and the peak velocities of the Sw(1) and Sw(2) and the times from the electrocardiographic Q wave to the peak Sw(1) and Sw(2) (Q-Sw(1) and Q-Sw(2), respectively) were determined. In all patients cardiac catheterization was performed immediately after the noninvasive examination, and the LV end-diastolic pressure and peak dP/dt were determined. The LV end-diastolic pressure and peak dP/dt were significantly greater and lower, respectively, in the DCM group. The peak Sw(1) along the long axis was significantly greater than Sw(1) and Sw(2) along the short axis and Sw(2) along the long axis in the control group. The peak Sw(1) and Sw(2) along the long and short axes were all significantly lower in the DCM group than in the control group. The Q-Sw(1) along the long axis was significantly shorter than that along the short axis, whereas no significant difference was seen in the Q-Sw(2) in either axis in any patient. The Q-Sw(1) and Q-Sw(2) along both axes were significantly longer in the DCM group than in the control group. All systolic pulsed tissue Doppler imaging variables, particularly the peak Sw(1) along the long axis, correlated well with the peak dP/dt in all patients. LV contractility along both the short and long axes is commonly impaired in patients with DCM. In particular, peak Sw(1) along the long axis is a useful parameter for evaluating LV myocardial contractility during isovolumic contraction.

Blood Flow Velocity↗

Influence of aging on systolic left ventricular wall motion velocities along the long and short axes in clinically normal patients determined by pulsed tissue doppler imaging.

Our objective was to evaluate the influence of aging on left ventricular (LV) regional systolic function along the long and short axes in clinically normal patients. We recorded LV wall motion velocity patterns at the mid-wall portion of the middle of the LV posterior wall in the parasternal long-axis view (short-axis direction) and at the endocardial portion of the middle of the LV posterior wall in the apical long-axis view (long-axis direction) with pulsed tissue Doppler imaging in 80 normal patients (age range 15 to 78 years). In all patients the LV pressure curve and its first derivative (dP/dt) were recorded. The systolic wave of the LV posterior wall motion velocity pattern exhibited 2 peaks, the first (Sw(1)) and second (Sw(2)) systolic waves. No significant changes were seen with aging in the percent LV fractional shortening determined by M-mode echocardiography, LV ejection fraction determined by left ventriculography, the peak Sw(1) and Sw(2) along the short axis, the peak Sw(2) along the long axis, and the peak dP/dt. The peak Sw(1) along the long axis correlated inversely with age (P <.0001) but did not correlate significantly with the peak dP/dt. These results suggest that shortening of the longitudinal fibers in early systole is impaired with increased age in healthy individuals. This impairment results in insufficient spherical change in the LV cavity, although global LV pump function and myocardial contractility are maintained.

Adolescent↗

Difference in the diastolic left ventricular wall motion velocities between aortic and mitral regurgitation by pulsed tissue Doppler imaging.

We evaluated the difference in the diastolic left ventricular (LV) wall motion velocity between chronic isolated aortic and mitral regurgitation (AR and MR, respectively) by recording subendocardial motion velocity patterns at the middle site of the LV posterior wall in the parasternal (along the short axis) and apical (along the long axis) long-axis views of the left ventricle with pulsed tissue Doppler imaging. We studied 33 patients with AR and 35 with MR, showing moderate to severe regurgitation, and 34 healthy controls (C). The end-diastolic LV dimension along the short axis was greater in the AR and MR groups than in the C group, and that along the long axis was greater in the AR group than in the MR and C groups. There were no significant differences in percent LV fractional shortening along the short axis among the 3 groups, whereas that along the long axis was significantly smaller in the AR group than in the MR and C groups. The peak early diastolic wall motion velocity (Ew) and the time to Ew from the aortic component of the second heart sound (S2 -Ew) along the long axis were significantly lower and longer, respectively, in patients with AR than in the 2 other groups. The Ew and S2 -Ew along both the short and long axes were significantly higher and shorter, respectively, in patients with MR than in the 2 other groups. The peak early diastolic velocity of the transmitral flow correlated positively with Ew along the short axis in all patients with AR and correlated positively with Ews along the long and short axes in all patients with MR. In conclusion, early diastolic LV filling was associated with expansion of the LV wall along the short axis but with decreased excursion along the long axis in patients with AR, whereas that in patients with MR was associated with expansion of the LV wall along both the long and short axes. Pulsed tissue Doppler imaging was useful for evaluation of diastolic LV function along the long and short axes in patients with diastolic LV volume overload.

Adult↗

NMR study of pradimicin derivative BMY-28864 and its interaction with calcium ions in D2O.

The dynamic structure of the antifungal antibiotic pradimicin BMY-28864 in D2O and its interaction with calcium ions were analyzed using one- and two-dimensional 1H nuclear magnetic resonance (NMR). Spectra indicate extensive self-association of molecules in the solution. Two-component spectra were observed simultaneously in a very dilute solution, suggesting equilibrium of two aggregative states. The addition of CaCl2 caused a number of changes in NMR spectra. Therefore we concluded that pradimicin BMY-28864 could form a complex with the Ca2+ ion, causing a movement of the equilibrium. The position of the bound calcium ion is determined indirectly by observing how the NMR shift affects protons that are close to the binding site. The stoichiometry of Ca2+ ion to the Pradimicin molecule for the Ca(2+)-saturated complex is verified to be 1:2. Signal broadening and changes in chemical shift in the 1H NMR spectroscopy of BMY-28864 are assumed to be related to changes in the molecular aggregate conformation.

Anthracyclines↗