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Biomedical subjects

S Osaki

Publications and source records attributed to S Osaki.

At least 19 recordsLinked to original sources

Orientational distribution of collagen fibers in cobra skin.

The orientation and distribution of collagen fibers were studied in leather prepared from cobra skin using both the mechanical method and Osaki's microwave method. The degree of preferred collagen-fiber orientation was largest at the centre of the dorsum and decreased gradually from the dorsum to the abdomen. The collagen fibers were, on average, aligned parallel to the spinal column in the dorsum, and tended to be aligned equally in all directions in the abdomen. The skin expanded easily in the direction perpendicular to the direction of collagen-fiber orientation. These results indicate that it is difficult for the skin to expand or shrink in the cranial to caudal direction, whereas it is relatively easy for the skin to expand around the circumference of the body of the cobra. Collagen-fiber orientation therefore seems to be closely related to the functional motions of cobra skin during locomotion and when swallowing prey.

Animals↗

Multiple superconducting phases in new heavy fermion superconductor PrOs4Sb12.

The superconducting gap structure of recently discovered heavy fermion superconductor PrOs4Sb12 was investigated by using thermal transport measurements in magnetic field rotated relative to the crystal axes. We demonstrate that a novel change in the symmetry of the superconducting gap function occurs deep inside the superconducting state, giving a clear indication of the presence of two distinct superconducting phases with twofold and fourfold symmetries. We infer that the gap functions in both phases have a point node singularity, in contrast to the familiar line node singularity observed in almost all unconventional superconductors.

Journal Article↗

Transfer of IkappaBalpha gene increase the sensitivity of paclitaxel mediated with caspase 3 activation in human lung cancer cell.

In oncogenic therapies, apoptosis seems to be the important mechanism of deciding chemotherapy effect. NF-kappaB transcription factors are implicated in the control of cell proliferation and apoptosis. NF-kappaB is activated by chemotherapy and by irradiation, and this pathway has been shown to protect cells potently from their stimuli-induced apoptosis. Furthermore, inhibition of NF-kappaB leads to enhanced apoptosis in response to various stimuli. However, because the role of NF-kappaB as a modifier of the intrinsic chemosensitivity of cancer cells is less clear, we have studied the impact of IkappaBalpha (an inhibitor of NF-kappaB) on the chemosensitivity of human lung cancer cells. We used adenoviral vectors expressing human IkappaBalpha (AdIkappaBalpha) and investigated the effects of IkappaBalpha gene transfer in combination with 6 anticancer agents on a human pulmonary adenocarcinoma cell line, A549. Solutions containing anticancer agents at various concentrations were added followed by the addition of recombinant adenovirus solutions, and each IC50 was calculated based on the dose-response curves. The gene transfer of AdIkappaBalpha decreased IC50 from 12.0 to 2.2 nM on paclitaxel and increased IC50 from 0.27 to 16.0 microM on SM5887 compared with the transfer of control gene, AdLacZ. The IC50 did not change clearly on the other anticancer drugs. To investigate this molecular mechanism, we measured caspase 3 activity by the transfer of IkappaBalpha gene. On result, paclitaxel increased caspase 3 activity and SM5887 decreased the activity. These results indicate that the cell killing effect of anticancer drug is influenced by the inhibition of NF-kappaB activity and may, at least in part, depend on the regulation of caspase 3 activation. Adenovirus mediated IkappaBalpha gene transfer improve the anti-cancer effect of paclitaxel to lung cancer cells through the regulation of caspase 3 activation.

Adenocarcinoma↗

Orientation and distribution of collagen fibers in the sagittal plane of the human adult calcaneus.

Human right calcaneus bone, consisting of hydroxyapatite and collagen fibers, was cut in the sagittal plane which was parallel to the long axes of the calcaneus bone and the human lower limb, into samples approximately 1.5 mm thick. The angular dependence of transmitted microwave intensity at 12 GHz was measured for each sample, using Osaki's microwave method. The direction and the degree of collagen-fiber orientation for the cut specimens changed with changing position from the heel end to the anterior, along to the long axis of the calcaneus bone. The direction of orientation deviated by about -60 degrees from the direction of the long axis of the human lower limb, in the region between the heel end and the middle, and by about 60 degrees near the anterior. The position at which the orientation angle changed drastically from negative to positive corresponded to the neck defined as the position where a posterior face of the talus contacts the calcaneus. The results suggest that the mechanical stress applied to the neck of the calcaneus bone from the lower limb may effectively disperse, on average, in two different directions where the collagen fibers are oriented at the neck.

Aged↗

Biologically induced Po emission from fresh water.

Behavior of Po in fresh waters was examined in laboratory culture experiments using fresh water collected from a small pool, Xi river and Xiqing lake, showing formation of volatile Po compounds followed by emission to air. Addition of tryptone to the fresh water cultures increased the emission of Po considerably along with a growth of microorganisms, suggesting a connection of chemoheterotrophs to Po emission. Participation of photoautotrophs was also considered because Po emission was increased when NaHCO3 was added to the fresh water cultures. The emission behavior of Po and S in these experiments appeared in different ways. The quantity of Po emitted was comparable to the previous culture experiments (Momoshima, Song, Osaki & Maeda, Environ. Sci. Technol., 35, 2956-2960, 2001) in which artificial culture medium containing 3% NaCl was used and inoculated with sea sediment extract. The biological support for Po emission, thus, would be a general phenomenon in fresh water as well as a seawater environment and is possibly a source for atmospheric Po.

Culture Media↗

Effects of acute and chronic alacepril treatment on exercise capacity and hemodynamics in patients with heart failure: a preliminary study.

OBJECTIVE: This study determined whether alacepril treatment improves exercise hemodynamics in patients with heart failure. METHODS: Supine bicycle ergometer exercise was performed after administration of placebo and after acute and chronic (12 weeks) alacepril treatment in 4 patients with heart failure. Oxygen uptake (VO2), arterial oxygen saturation (SaO2), and mixed venous oxygen saturation (SvO2) were measured continuously using a pulse oxymeter and a fiber optic catheter. Cardiac index was calculated with Fick's equation. RESULTS: Acute alacepril treatment did not significantly alter the VO2 or hemodynamics. After chronic alacepril treatment, peak VO2 increased (placebo vs chronic alacepril treatment: 17.7 +/- 2.8 vs 21.7 +/- 2.8 ml/min/kg, p < 0.05). Arteriovenous oxygen difference (SaO2 - SvO2) at peak exercise was not altered, however, cardiac index at peak exercise (5.07 0.67 vs 6.35 +/- 0.48 I/min/m2, p = 0.02) increased and stroke volume index at peak exercise (37.3 +/- 3.4 vs 46.5 +/- 1.1 ml/m2, p = 0.07) tended to increase. CONCLUSIONS: Chronic treatment with alacepril improved maximal exercise capacity in patients with heart failure. The increased peak VO2 was primarily due to the increased cardiac index, but not due to the widening of arteriovenous oxygen difference. Therapy-induced increase in stroke volume index may contribute to the increased cardiac index at peak exercise in our patients with heart failure.

Adult↗

Formation and emission of volatile polonium compound by microbial activity and polonium methylation with methylcobalamin.

We observed biologically mediated emission of Po from culture solution inoculated sea sediment extract and incubated under natural light/dark cycle condition or dark condition the emitted Po compound would be lipophilic because of effective collection in organic solvent. Sterilization of the culture medium with antibiotics or CuSO4 completely suppressed growth of microorganisms and resulted in no emission of Po, indicating biological activity of microorganisms is responsible for formation and emission of volatile Po compound. Po emission also occurred when seawater was used as a culture medium. Our finding indicates a possibility of biotic source for atmospheric Po in the environment, which has been believed to be originated from abiotic sources. We compared emission behavior of Po and S in the culture experiments, the elements belong to XVI group in the Periodical Table, and consider that their emission mechanisms involved would be different though the emission of both elements is supported by biological activity of microorganisms. One of the chemical forms of S emitted was confirmed to be dimethyl sulfide (DMS) but that of Po is not known. Methylation experiments of Po with methylcobalamin demonstrated a formation and emission of volatile Po compound. The methylation of Po with methylcobalamin might be related to the observed Po emission in the culture experiments.

Air Pollutants↗

Use of hair pores to determine the orientation of collagen fibers in skin.

Most people are interested in recovery of skin defects caused by burn, scald or trauma from the aesthetic and functional point of view. It will occupy an important role for successful skin graft for patients with such skin defects that the orientation of collagen fibers in the grafted skin matches to the fiber orientation in surrounding skin. There have been, to my best knowledge, no methods for determining the orientation of collagen fibers in the skin from the clinical point of view. Recently, the author has found a new method for directly determining the collagen-fiber orientation without cutting samples from a calf leather by analyzing the anisotropic shape of hair pore. Its principle is based on the quantitative evaluation of collagen-fiber orientation by approximating a hair pore to an ellipse. The results obtained by the new method using hair pores were supported by the microwave method, mechanical measurements and scanning electron microscopy. Such a method will be applicable for determining the orientational distribution of collagen fibers in skins of animals and humans and give a valuable probe for performing skin grafting based on the scientific data of hair pores.

Animals↗

Altered purine nucleotide degradation during exercise in patients with essential hypertension.

Purine degradation occurs during strenuous muscle exercise and plasma levels of hypoxanthine (HX), purine degradation intermediate, increase. Purine nucleotide degradation has not been investigated in patients with essential hypertension (HTN). The present study determined whether purine nucleotide degradation is altered in patients with HTN. Cardiopulmonary exercise test was performed with serial measurements in blood lactate and plasma HX in 24 patients (14 men and 10 women) with essential HTN (World Health Organization [WHO] class I to II; mean age, 57.7 +/- 2.1 years) and 24 age-, sex-matched normal subjects. Exercise was terminated either by severe fatigue or excess blood pressure increase. Peak work rate (WR) (normal v HTN, 151 +/- 10 v 135 +/- 8 W, not significant [NS]) was not different, but peak oxygen uptake (peak Vo(2), 26.3 +/- 1.5 v 22.2 +/- 0.9 mL/min/kg, P <.05) and anaerobic threshold were lower in patients with HTN. Resting levels of blood lactate and plasma HX were similar, but the increment from rest to peak exercise (Delta) for lactate (Delta lactate: 4.4 +/- 0.4 v 3.4 +/- 0.4 mmol/L, P <.05) and for HX (Delta HX, 15.9 +/- 2.2 v 9.1 +/- 1.1 micromol/L, P <.05) were significantly smaller in patients with HTN. When normalized by the peak WR, Delta HX/peak WR (0.105 +/- 0.013 v 0.069 +/- 0.007 micromol/L/W, P <.05) was significantly lower in patients with HTN. Patients with HTN exhibited reduced HX response to exercise with impaired exercise capacity. The exercise-induced changes in plasma HX were smaller in patients with HT when normalized with peak WR. These results suggest that the purine nucleotide degradation is reduced in patients with HTN.

Exercise Test↗

L-arabinose feeding prevents increases due to dietary sucrose in lipogenic enzymes and triacylglycerol levels in rats.

L-Arabinose is a natural, poorly absorbed pentose that selectively inhibits intestinal sucrase activity. To investigate the effects of L-arabinose feeding on lipogenesis due to its inhibition of sucrase, rats were fed 0-30 g sucrose/100 g diets containing 0-1 g L-arabinose/100 g for 10 d. Lipogenic enzyme activities and triacylglycerol concentrations in the liver were significantly increased by dietary sucrose, and arabinose significantly prevented these increases. Arabinose feeding reduced the weights of epididymal adipose tissue. Moreover, plasma insulin and triacylglycerol concentrations were significantly reduced by dietary L-arabinose. These findings suggest that L-arabinose inhibits intestinal sucrase activity, thereby reducing sucrose utilization, and consequently decreasing lipogenesis.

ATP Citrate (pro-S)-Lyase↗

Crystal structure of glucose dehydrogenase from Bacillus megaterium IWG3 at 1.7 A resolution.

The crystal structure of glucose dehydrogenase (GlcDH) from Bacillus megaterium IWG3 has been determined to an R-factor of 17.9% at 1.7 A resolution. The enzyme consists of four identical subunits, which are similar to those of other short-chain reductases/dehydrogenases (SDRs) in their overall folding and subunit architecture, although cofactor binding sites and subunit interactions differ. Whereas a pair of basic residues is well conserved among NADP(+)-preferring SDRs, only Arg39 was found around the adenine ribose moiety of GlcDH. This suggests that one basic amino acid is enough to determine the coenzyme specificity. The four subunits are interrelated by three mutually perpendicular diad axes (P, Q, and R). While subunit interactions through the P-axis for GlcDH are not so different from those of the other SDRs, those through the Q-axis differ significantly. GlcDH was found to have weaker hydrophobic interactions in the Q-interface. Moreover, GlcDH lacks the salt bridge that stabilizes the subunit interaction in the Q-interface in the other SDRs. Hydrogen bonds between Q-axis related subunits are also less common than in the other SDRs. The GlcDH tetramer dissociates into inactive monomers at pH 9.0, which can be attributed mainly to the weakness of the Q-axis interface.

Amino Acid Sequence↗

Comparison of cedar pollen-induced allergic rhinitis in passively and actively sensitized guinea pigs.

We have developed an allergic rhinitis model in guinea pigs using Japanese cedar pollen as antigen. In the present study, we examined whether provocation by pollen induces similar magnitudes of rhinitis symptoms in passively and actively sensitized guinea pigs. One group of animals was actively sensitized by intranasal application of pollen extract, and another was passively sensitized by intraperitoneal injection with anti-pollen serum. Actively and passively sensitized groups were then challenged by repeated and a single pollen inhalation, respectively. In both groups, sneeze was induced immediately after the challenge. The actively sensitized animals developed not only early but also late nasal blockage, whereas the passively sensitized animals showed only early nasal blockage. In both groups, an H1 antagonist, mepyramine, inhibited the occurrence of sneezing but did not inhibit nasal blockage. Nasal hyperresponsiveness to intranasal instillation of leukotriene D4 was obvious only in the actively sensitized animals. We thus conclude that although early nasal blockage is induced by a single antigen-antibody reaction, repetitive anaphylactic reaction is required for occurrence of late nasal blockage and hyperresponsiveness to stimuli. Furthermore, histamine plays a central role in induction of sneezing but not in nasal blockage, irrespective of whether animals are actively or passively sensitized.

Airway Resistance↗

Radiolabeling brachytherapy sources with Re-188 through chelating microfilms: stents.

Rhenium-188 (Re-188, T(1/2) = 17 h) emits beta particles (E(max) = 2. 12 MeV) having an ideal range for intravascular brachytherapy and certain cancer brachytherapies. Re-188 was attached to metal wafers and stents via a chelating microfilm, and these brachytherapy sources characterized in vitro and in vivo. To prepare the sources, a siloxane film containing reactive amines was plasma deposited on the metal, a chelating microfilm conjugated to the amines, and the chelating microfilm used to attach Re-188. Re-188 was selectively bound to materials coated with the chelating microfilm. Binding correlated with the amount of radionuclide used. Wafers (1 cm(2)) bound up to 62.9 MBq (1.7 mCi) of Re-188 with yields generally near 30%. Stents bound up to 26.6 MBq (720 microCi). Typically, stents were labeled to bind 4-12 MBq and deposit 10-30 Gy at 2 mm in the arterial wall. In phantom studies, the longer nitinol stents deposited doses of 2.3 Gy/MBq (0.085 Gy/microCi), while shorter stainless steel stents deposited 4.62 Gy/MBq (0.171 Gy/microCi). After placement in arteries of pigs, only the Re-188-stents were detected by scintigraphy at times up to 24 h. Scintigraphy did not detect activity in other organs. Blood sampling (0.1-24 h) detected maximum radioactivity (up to 388 cpm/mL/100micro Ci) at 6 h. We conclude that on-demand radiolabeling of stents and other brachytherapy sources with Re-188 can be performed routinely.

Biocompatible Materials↗

Alteration of drug chemosensitivity caused by the adenovirus-mediated transfer of the wild-type p53 gene in human lung cancer cells.

The aim of the present study is to identify the optimal anticancer agents for use in combination with gene therapy using wild-type (wt) p53 gene transfer. We used adenoviral vectors expressing human wt p53 (AdCAp53) and investigated the effects of wt p53 gene transfer in combination with 12 anticancer agents on a human pulmonary squamous cell carcinoma cell line, NCI-H157, and a human pulmonary large cell carcinoma cell line, NCI-H1299. Solutions containing anticancer agents at various concentrations were added followed by the addition of recombinant adenovirus solutions; after a 5-day incubation period, the anticancer activity was then evaluated by a 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carbo xanilide assay. Each 50% inhibitory concentration was calculated based on the dose-response curves. The agents showing a high degree of effectiveness on NCI-H157 cells were cisplatin (CDDP), 5-fluorouracil (5-FU), bleomycin, and 7-ethyl-10-hydroxy-camptothecin (SN-38), an active metabolite of irinotecan (CPT-11); conversely, cyclophosphamide and paclitaxel showed a low degree of effectiveness. Based on these data, an isobologram was performed to investigate the interaction between AdCAp53 and some anticancer agents. A supra-additive effect was thus observed for 5-FU and SN-38 on NCI-H157 cells. An additive effect was also observed for CDDP, paclitaxel, bleomycin, and cyclophosphamide on NCI-H157 cells. CDDP, paclitaxel, 5-FU, and SN-38 had an additive effect on NCI-H1299 cells. No drug showed any subadditive or protective effects. These findings suggest that CPT-11 and 5-FU may thus be useful as possible anticancer agents for use in a combination therapy regimen using wt p53 gene transfer. CDDP and CPT-11 had a significant antitumoral effect on H157 cell xenografts of nude mice in vivo. These results indicate that CPT-11 as well as CDDP would be a candidate for the combination of chemotherapy and gene therapy for non-small cell lung cancer.

Adenoviridae↗

Augmented response in plasma brain natriuretic peptide to dynamic exercise in patients with left ventricular dysfunction and congestive heart failure.

OBJECTIVES: We have previously demonstrated that patients with symptomatic congestive heart failure (CHF), but not with asymptomatic left ventricular dysfunction (LVD), have augmented plasma atrial natriuretic peptide (ANP) response to exercise. Plasma brain natriuretic peptide (BNP) response to exercise is less extensively studied. The aim of this study was to determine whether responses of plasma BNP during exercise normalized for exercise workload are altered in patients with LVD and CHF. SUBJECTS AND METHODS: Twenty-nine patients with LVD, 32 patients with CHF (NYHA classes II-III) and 27 age-matched control subjects were studied. Ventilatory, plasma ANP and BNP responses were assessed during symptom-limited cardiopulmonary exercise testing. Plasma natriuretic peptide levels were measured at rest and immediately after peak exercise. The increment in plasma BNP was divided by the increment in oxygen uptake (VO2) from rest to peak exercise, and this ratio [BNP exercise ratio: (peak BNP - rest BNP)/(peak VO2 - rest VO2)] was compared amongst the three groups. RESULTS: Peak VO2 (Control, LVD and CHF: 28.2 +/- 1.7, 21.1 +/- 1.8, 16.2 +/- 0.6 ml, min(-1) kg(-1), respectively), anaerobic threshold and peak workload became smaller as heart failure worsened. Resting and peak plasma ANP levels were significantly higher only in CHF, whilst resting and peak plasma BNP levels displayed a significant and continuous increase from normal subjects to LVD and CHF. The ANP exercise ratio (1.25 +/- 0.36, 2.61 +/- 0.57, 7.72 +/- 1.65, ANOVA P = 0.0002) was significantly higher only in patients with CHF, whilst the BNP exercise ratio (0.35 +/- 0.10, 2.60 +/- 0.69, 4.98 +/- 0.97, ANOVA P = 0.0001) was significantly higher in patients with LVD and became progressively higher in patients with CHF. CONCLUSIONS: These data showed that the BNP exercise ratio, an exercise plasma BNP response normalized with exercise workload, was augmented in patients with LVD, and became progressively higher in CHF, suggesting that an augmented exercise BNP ratio exists early in the course of developing CHF.

Anaerobic Threshold↗

Ammonia response to constant exercise: differences to the lactate response.

1. We evaluated the plasma ammonia response to constant exercise at different intensities. Ten healthy male volunteers were asked to perform constant exercise for 15 min at five different intensities: 80, 90, 100, 110 and 120% of their ventilatory threshold (VT). Blood concentrations of lactate, ammonia and hypoxanthine were measured during and after exercise. 2. The concentration of lactate increased continuously during exercise intensities equivalent to 100, 110 and 120% VT. Plasma ammonia began to increase at 6 min exercise and continued increasing during exercise at all five exercise intensities. Plasma hypoxanthine levels also increased continuously during exercise at all exercise intensities; however, they peaked at 5-10 min after exercise. The response of plasma ammonia and hypoxanthine increased with increasing intensities of exercise. 3. While the extent of the increase in lactate levels during exercise at 100, 110 and 120% VT was significantly higher than that at 80% VT, only the increase in ammonia and hypoxanthine levels at 120% VT were significantly higher than those at 80% VT. 4. In conclusion, the plasma ammonia response to constant exercise differed to the lactate and ammonia responses to short-term exhaustive exercise.

Adult↗

Cardiac and plasma catecholamine responses to exercise in patients with type 2 diabetes: prognostic implications for cardiac-cerebrovascular events.

BACKGROUND: Patients with diabetes mellitus have an altered exercise plasma catecholamine response, which may be related to the abnormal sympathoadrenal function and autonomic neuropathy. Presence of autonomic neuropathy is associated with poor prognosis, but relationship between exercise plasma catecholamine and prognosis has not been investigated. This study determined if altered plasma catecholamine response to exercise was associated with cardiac-cerebrovascular events. METHODS: Forty patients with type 2 diabetes without apparent macrovascular complications and 30 control subjects performed treadmill exercise with serial measurements of plasma norepinephrine and epinephrine. Clinical, exercise, and catecholaminergic variables considered relevant to the cardiac-cerebrovascular events were examined by Cox regression model. Analysis of 24-hour heart rate variability was performed in a subgroup of patients. RESULTS: During 7.2 years, 8 patients, but no control subjects, had events (3 myocardial and 5 cerebral infarctions). Compared with Event(-) patients, Event(+) patients had: (1) orthostatic hypotension; (2) lower peak exercise heart rate; (3) lower plasma norepinephrine immediately after exercise; and (4) lower plasma epinephrine at peak exercise. High frequency components in heart rate variability analysis were diminished in Event(+) patients. Multivariate analysis showed that peak heart rate (P = 0.04) and plasma epinephrine at peak exercise (P = 0.03) were independent predictors of subsequent events. CONCLUSIONS: These data suggest that chronotropic incompetence and lower plasma epinephrine response to exercise are associated with high risk of cardiac-cerebrovascular events in patients with type 2 diabetes.

Catecholamines↗

Crystallization and preliminary X-ray analysis of glucose dehydrogenase from Bacillus megaterium IWG3.

Glucose dehydrogenase from Bacillus megaterium IWG3 has been crystallized in the presence of NAD(+) using the hanging-drop vapour-diffusion method with PEG 2000 as the precipitant. Crystals belong to space group C2 and have unit-cell parameters a = 120.8 (1), b = 66.7 (1), c = 119.6 (1) A, beta = 93.25 (3) degrees with standard deviations in parentheses. Assumption of four subunits in the asymmetric unit gave the most probable Matthews coefficient V(M) of 2.1 A(3) Da(-1) (solvent content 41.7% by volume). X-ray diffraction data were collected to 1.7 A on a synchrotron-radiation source.

Bacillus megaterium↗