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Biomedical subjects

T Sakashita

Publications and source records attributed to T Sakashita.

At least 19 recordsLinked to original sources

A case study of radon-222 transport from continental North-East Asia to the Japanese islands in winter by numerical analysis.

A case study of the regional transport ( approximately 3000 km) of radon-222 ((222)Rn) from continental North-East Asia to the Japanese islands was performed by numerical analysis using five separate source areas (South, Middle and North China, Russia and Korea), while a seasonal northwest wind blew over the Japan Sea. The results for three periods (Term I: 16-18, Term II: 22-25 and Term III: 27-28 in December 1990) were compared with concentrations measured at the Kanazawa site (near the coast of the Japan Sea facing the seasonal wind) and the Nagoya site (overland and downwind on the shores of the Pacific Ocean). Most of the (222)Rn at the Kanazawa site was calculated to come from North China and Korea in Term I, Middle China, North China, and Korea in Term II, and Russia and Korea in Term III. The considerable differences in the origins of (222)Rn emanated from the continent were estimated between Terms I, II and III, even though the similar northwest wind was dominant over the Japan Sea. A contour line analysis indicated movement of (222)Rn emanated from Middle China in a northerly direction first and then a southeasterly direction, resulting from low pressure. The results suggest that the low-pressure systems play an important role in the transport of (222)Rn in North-East Asia.

Air Movements↗

Effects of gamma-ray and high energy carbon ion irradiation on swimming velocity of Euglena gracilis.

The effects of gamma-ray and high energy carbon ion irradiation on the swimming velocity of the photosynthetic flagellate Euglena gracilis strain Z were studied, focusing on a dose-effect relationship. Cells were exposed to 60Co gamma-rays at 6 doses of 10, 15, 20, 40, 100 and 200 Gy for water, and also to 290 MeV/amu carbon ions from the Heavy Ion Medical Accelerator in Chiba at 7 doses (5, 10, 15, 20, 50, 100 and 200 Gy for water). The swimming velocity was measured by a biomonitoring system, called ECOTOX. The swimming velocities of Euglena gracilis cells were significantly decreased by >40 Gy gamma-rays and >5 Gy carbon ions, respectively. The 50% effective doses for inhibition, 34 +/- 4 Gy (gamma-rays) and 13 +/- 1 Gy (290 MeV/amu carbon ions), were estimated from the best fit to data of the logistic model. The relative biological effectiveness (2.6 +/- 0.4) was calculated by the ratio of 50% effective doses. The inhibition of the swimming velocity of the cells irradiated with gamma-rays was still present after 3 days, while recovery of the swimming velocity was shown in the cells exposed to 290 MeV/amu carbon ions. It is suggested that ionizing radiation inhibits ATP production and/or increases frictional drag on beating of the flagellum, thus decreasing swimming velocity.

Adenosine Triphosphate↗

High-energy carbon ion irradiation and the inhibition of negative gravitaxis in Euglena gracilis Z.

PURPOSE: To study the effects of high-energy carbon ion irradiation on negative gravitaxis in the photosynthetic flagellate Euglena gracilis strain Z in a dose-response-dependent manner. MATERIALS AND METHODS: Cells were exposed to 290 MeV amu(-1) carbon ion from the Heavy Ion Medical Accelerator in Chiba (HIMAC) at 12 doses (0, 1, 5, 7.5, 10, 15, 20, 50, 75, 100, 150, 200 Gy for water). r was used to quantify negative gravitaxis observed in a recently developed biomonitoring system. RESULTS: Negative gravitaxis of Euglena was significantly affected by irradiation at a dose >7.5 Gy, 28 h after irradiation. Negative gravitaxis recovered after a few days. The rising phase of r during the first 30 s of orientation was independent of irradiation dose. The recovery mechanism itself was damaged by 290 MeV amu(-1) carbon ions at a dose >50 Gy. CONCLUSIONS: The results indicate that negative gravitaxis in Euglena may be affected by the radiation experienced during a space experiment especially during the occurrence of solar flares. The analyses of time needed to reorient to the gravitational vector suggest that the steering control of the flagellar apparatus is affected by exposure to the 290 MeV amu(-1) carbon ion irradiation, resulting in an altered beating pattern of a flagellum and/or changes of the cell form during reorientation.

Animals↗

Gamma-irradiation effect: variation of photosynthetic activity of Euglena.

OBJECTIVE: To study the effects of gamma-ray irradiation on carbon fixation (Specific production rate: SPR), CO2 utilization efficiency (CUE) and electron transfer rate (ETR) in the photosynthetic flagellate Euglena gracilis strain Z in a dose-response dependent manner. METHODS: Euglena cells were cultured in an inorganic nutrient medium containing ammonium chloride or proteose peptone. Cells were exposed to gamma-ray at 5 doses (0, 100, 250, 350, 500 Gy for water). Five days after irradiation, three photosynthetic activities were measured. SPR, which is a carbon uptake rate per unit carbon mass, was determined by 13C tracer methodology. CUE was evaluated using a relation of carbon isotope fractionation in Calvin cycle. ETR in photosystem II (PS II) was measured by a chlorophyll fluorescence analysis. RESULTS: Even at a dose of 500 Gy, 80% of ETR of the non-irradiated control (0 Gy) was sustained, while SPR and CUE were about half the level in the non-irradiated control at 500 Gy. Furthermore, the dose response of ETR was considerably different from the others. CONCLUSION: Our findings suggest that not only PS II but also the Calvin cycle in the photosynthetic system is affected by gamma ray irradiation.

Animals↗

Low density lipoprotein receptor-related protein is required for macrophage-mediated oxidation of low density lipoprotein by 12/15-lipoxygenase.

The oxidative modification of low density lipoprotein (LDL) has been implicated in the early stage of atherosclerosis through multiple potential pathways, and 12/15-lipoxygenase is suggested to be involved in this oxidation process. We demonstrated previously that the 12/15-lipoxygenase overexpressed in mouse macrophage-like J774A.1 cells was required for the cell-mediated LDL oxidation. However, the mechanism of the oxidation of extracellular LDL by the intracellular 12/15-lipoxygenase has not yet been elucidated. In the present study, we found that not only the LDL receptor but also LDL receptor-related protein (LRP), both of which are cell surface native LDL-binding receptors, were down-regulated by the preincubation of the cells with cholesterol or LDL and up-regulated by lipoprotein-deficient serum. Moreover, 12/15-lipoxygenase-expressing cell-mediated LDL oxidation was decreased by the preincubation of the cells with LDL or cholesterol and increased by the preincubation with lipoprotein-deficient serum. Heparin-binding protein 44, an antagonist of the LDL receptor family, also suppressed the cell-mediated LDL oxidation in a dose-dependent manner. The cell-mediated LDL oxidation was dose-dependently blocked by an anti-LRP antibody but not by an anti-LDL receptor antibody. Furthermore, antisense oligodeoxyribonucleotides against LRP reduced the cell-mediated LDL oxidation under the conditions in which the expression of LRP was decreased. The results taken together indicate that LRP was involved essentially for the cell-mediated LDL oxidation by 12/15-lipoxygenase expressed in J774A.1 cells, suggesting an important pathophysiological role of this receptor-enzyme system as the initial trigger of the progression of atherosclerosis.

Animals↗

Phenotype of apolipoprotein E influences the lipid metabolic response of postmenopausal women to hormone replacement therapy.

OBJECTIVES: We investigated whether the phenotype of apolipoprotein E (apo E) would influence the response of postmenopausal Japanese women to hormone replacement therapy (HRT). METHODS: We measured the plasma levels of lipoprotein and apolipoprotein in 242 postmenopausal women at baseline and again after 12 months of HRT. Patients were divided into three groups according to apo E phenotype: E2+ (E2/2 and E2/3, n=21), E3/3 (n=176), E4+ (E3/4 and E4/4, n=45). RESULTS: We found that the E4+ group had the highest levels of total and low density lipoprotein (LDL) cholesterol and apolipoprotein B, being significantly higher than in the E2+ group at baseline. The plasma levels of total and LDL cholesterol showed a significant decrease only in the E2+ and E3/3 groups after 12 months of HRT (E2+ group, total cholesterol -8.9% and LDL cholesterol -21.5%; E3/3 group, total cholesterol -2.9% and LDL cholesterol -9.5%). No significant difference in the reduction of total and LDL cholesterol was found in the E4+ group. Other lipid parameters did not differ in the three groups. CONCLUSIONS: These data show that the apo E phenotype influenced the response of lipid metabolism in postmenopausal women to HRT, especially in the reduction of LDL cholesterol. Therefore, apo E phenotyping may be important in predicting the cholesterol-lowering effect of HRT.

Adult↗

Estrogen replacement therapy in postmenopausal women augments reactive hyperemia in the forearm by reducing angiotensin converting enzyme activity.

The precise mechanism of the vasoprotective effect of estrogen replacement therapy in postmenopausal women is not fully understood. The present study sought to determine the role of nitric oxide (NO) and angiotensin-converting enzyme (ACE) in the vasodilator response of the forearm vessels induced by estrogen administration to postmenopausal women. Subjects were divided into two groups. One group received conjugated equine estrogen (0.625 mg daily) orally for 3 months (n=26), while the other received no treatment (control group, n=10). Forearm blood flow was measured by strain-gauge plethysmography. The concentrations of nitrite/nitrate (metabolites of NO), ACE activity, and lipid parameters were measured. Basal forearm blood flow, body weight, blood pressure, and heart rate were similar at baseline in both groups. After 3 months of estrogen administration, the maximal forearm blood flow response during reactive hyperemia and the serum level of nitrite/nitrate each showed a significant increase over baseline values: from 23.6+/-2.0 to 36.5+/-3.1 ml/min per 100 ml tissue (P<0.01), and from 24.8+/-2.3 to 38.6+/-3.6 micromol/l (P<0.01), respectively. Plasma levels of ACE activity were significantly reduced from baseline after 3 months of estrogen treatment (from 12.2+/-0.6 to 10.9+/-0.6 IU/l, P<0.01). No changes were seen in controls. The change in forearm blood flow after sublingual nitroglycerin was similar at baseline versus after 3 months of estrogen administration. The increase in the serum level of nitrite/nitrate after 3 months of estrogen therapy showed a significant inverse correlation (r=0.52, P<0.01) with the reduction in the plasma level of ACE activity. There was no significant correlation between the increase in serum nitrite/nitrate and any change in serum lipids, blood pressure, or other parameters. The administration of oral estrogen to postmenopausal women for 3 months increased the NO-mediated forearm endothelium-dependent vasodilatation. This was likely due, at least in part, to ACE inhibition. The latter may be one mechanism by which ERT provides its well-known cardiovascular benefit.

Blood Flow Velocity↗

Lifetime risk of lung cancer due to radon exposure projected to Japanese and Swedish populations.

Lifetime risk projections depend greatly on both background lung cancer rates and the selection of the risk model. Since background lung cancer rates differ from subject populations and the time, etiological risk of lifetime lung cancer mortality per unit radon exposure in WLM should be estimated for each subject population and the time of interest. To answer quantitatively how much are the differences among the projected risks for different populations, the Swedish case-control-study-based risk projection model was applied to the Japanese and Swedish populations from 1962 to 1997 as subject populations because of their distinct trends of lung cancer rates. To compare the results with the reference population and authorized risk projection models, U.S. population 1997 and the two risk projection models in BEIR VI report were applied, respectively. Lifetime risk of lung cancer mortality projected for Japanese, Swedish, and U.S. populations in 1997 per radon progeny exposure were estimated to range from 1.50 (0.40-3.19) x 10(-4) WLM(-1) to 9.86 (2.62-20.9) x 10(-4) WLM(-1), which could be compared to the detriment associated with a unit effective dose. Conclusive dose conversion coefficients in this study ranged from 2.05 (0.55-4.37) to 13.5 (3.59-28.6) mSv WLM(-1), and within this range the discrepancy between dosimetric and epidemiological approaches was included.

Environmental Exposure↗

[Changes in otoacoustic emission during the glycerol test in the ears of patients with Meniere's disease].

Monitoring of cochlear function is one proposed clinical application of otoacoustic emission (OAE). To determine the clinical utility of OAE in monitoring, we studied changes in OAE during the glycerol test used to diagnose endolymphatic hydrops. Transiently evoked OAE (TEOAE) and distortion product OAE (DPOAE) were measured before and 3 hours after oral administration of glycerol in 22 ears of patients with Meniere's disease. The positive result in the glycerol test was observed in 11 of 22 ears. TEOAE was recorded using a nonlinear click stimulus, and total echo power (TEP) of the whole response and filtered echo power (FEP) of its mid-frequency (1000-2000 Hz) component were used as TEOAE parameters. The growth functions of DPOAE were recorded at 3 F2 frequencies--1000, 1500, and 2000 Hz. Changes in the growth function were determined based on changes in 2 parameters--maximum level and detection threshold of DPOAE. When changes in these 4 parameters exceeded 2 standard deviations above mean test-retest variability determined from OAE data for 17 normal ears, they were considered significant. Significant changes indicating improved cochlear function in 4 OAE parameters or the appearance of OAE during the glycerol test were judged positive for OAE. Regardless of glycerol test results, positive findings were observed in both OAEs whenever a pure-tone threshold at 1000 or 2000 Hz improved. However, even in ears for which pure-tone thresholds at these frequencies did not improve, both OAEs frequently exhibited positive findings. In all ears with a positive result in the glycerol test, positive findings were observed in DPOAE, but not in TEOAE. Of the 2 parameters of TEOAE, FEP always exhibited a positive finding in ears with a positive TEP finding and FEP positivity was higher than that of TEP. In DPOAE, no cases showed a positive finding only at F2 = 2000 Hz, and DPOAE at F2 = 1000 Hz could not be detected in 4 ears due to high noise floor. Overall, positive findings were obtained in 14 ears (63.9%) for TEOAE and 20 ears (90.9%) for DPOAE. In only 1 ear were no positive findings observed in either OAE. The sensitivity of OAE measurement as a diagnostic test for endolymphatic hydrops was higher than that of pure-tone audiometry. Of the 2 OAEs, test sensitivity was much higher for DPOAE than for TEOAE. These results show that OAE measurement detects changes in cochlear function during the glycerol test more sensitively than pure-tone audiometry. They also suggest that FEP is a better indicator than TEP as a parameter of TEOAE, and that DPOAE measurement at F2 = 1000 and 1500 Hz is sufficient for practical clinical use. However, of the 2 OAEs, DPOAE was considered more appropriate than TEOAE for monitoring during the glycerol test because of its high sensitivity in detection of changes in cochlear function. In conclusion, clinical use of OAE, especially DPOAE, as a test complementary to pure-tone audiometry during the glycerol test is very useful and will improve the diagnosis of endolymphatic hydrops.

Adult↗

Oral estrogen replacement therapy increases forearm reactive hyperemia accompanied by increases in serum levels of nitric oxide in postmenopausal women.

The present study sought to determine the correlation between the vasodilator response of forearm resistance vessels and the circulating levels of nitric oxide (NO) after the administration of oral estrogen for 12 weeks to postmenopausal women. We classified postmenopausal women into two groups: those treated with conjugated equine estrogen (0.625 mg daily) orally for 12 weeks (n = 24) or those who received no treatment (control group, n = 8). Forearm blood flow was measured using strain-gauge plethysmography during hyperemia to evaluate endothelium-dependent vasodilation, and after sublingual nitroglycerin administration to evaluate endothelium-independent vasodilation. Serum levels of nitrite/nitrate (metabolites of NO) and lipid parameters were measured. Basal forearm blood flow, body weight and heart rate were similar in each group. After 12 weeks of estrogen administration, the maximal forearm blood flow response during reactive hyperemia and the serum level of nitrite/nitrate each showed a significant increase from 26.9 +/- 1.9 to 37.9 +/- 3.5 ml/min per 100 ml tissue (p < 0.01), and from 25.2 +/- 2.2 to 37.5 +/- 3.7 mumol/l (p < 0.05), respectively. No increases were seen in controls. The changes in forearm blood flow after sublingual nitroglycerin were similar before and after 12 weeks of estrogen administration. The increase in maximal forearm blood flow with reactive hyperemia was significantly correlated with the increase in nitrite/nitrate in the group administered estrogen (r = 0.48, p < 0.05). There was no significant correlation between maximal forearm blood flow with reactive hyperemia, nor any change in serum lipids, blood pressure or other parameters. In conclusion, the 12-week administration of oral estrogen increased forearm reactive hyperemia in postmenopausal women, probably via an increase in the production of NO.

Body Weight↗

[A case of pulmonary Nocardia farcinica infection in a patient with non-tuberculous mycobacteriosis].

A 64 years old woman without systemic immunological disorders was admitted to our hospital because of a productive cough, low grade fever and bloody sputum. Chest X-ray revealed multiple nodules with calcification, infiltrates and bronchiectasis. Laboratory findings showed mild hypoproteinemia and elevated sedimentation rate. Both Nocardia farcinica and Mycobacterium intracellulare were isolated from the bronchial lavage fluid. Administration of sulfamethoxazole-trimethoprim improved her symptoms. In a recurrent study of bronchial lavage N. farcinica was not isolated, but M. intracellurale was still isolated. We believe that N. farcinica may cause infectious exacerbation of chronic lung disease: non-tuberculous mycobacteriosis and bronchiectasis.

Female↗

Evaluation of radiological examination for sensorineural hearing loss.

The accuracy of radiological examinations has improved and their diagnostic ability has markedly increased. However, the cost of such examinations has also recently become an issue. In this study, the clinical significance of radiological examinations for sensorineural hearing loss (SNHL) was evaluated and the value of their utilization was reconsidered. A total of 1,276 ears of 724 patients who demonstrated unilateral or bilateral SNHL was studied retrospectively. Findings of radiological examinations such as plain X-ray (X-p), computed tomography (CT) and magnetic resonance imaging (MRI) of the brain or the temporal bone were investigated. Temporal bone X-p was usually performed to rule out acoustic tumors (AT). CT was further performed in 119 patients (16.4%) and MRI in 84 patients (11.6%) in total. The reasons or symptoms for further examination such as CT or MRI were X-p findings or auditory symptoms suspicious for AT or vertigo/dizziness suspicious for intracranial disease. Of five causes with AT, two with a small tumor exhibited normal findings for the internal auditory canal on temporal bone X-p. These small ATs were finally confirmed by MRI. MRI could also detect lacunar infarctions, cerebral atrophy and high jugular bulb which might be related to SNHL. These findings confirmed that MRI is very useful for detecting small ATs and suggested that MRI also reveals cerebral vascular insufficiency in patients with SNHL.

Adolescent↗

Growth stimulation and induction of epidermal growth factor receptor by overexpression of cyclooxygenases 1 and 2 in human colon carcinoma cells.

There are two isoforms of cyclooxygenase (COX), COX-1 and COX-2. Recent epidemiological and experimental studies indicated a close relationship between COXs and the pathogenesis of colorectal cancer. The purpose of this study was to investigate the possible roles of both isoforms in the proliferation of colon carcinoma cells. A human colon carcinoma cell line, COLO 320DM, was transfected with an eukaryotic expression vector carrying cDNA of either COX-1 or COX-2, the expression of which was driven by a powerful elongation factor-1alpha promoter in pEF-BOS. Both COX-1- and COX-2-expressing cells possessed a similar enzyme activity, 8-10 nmol/10 min per mg protein. Growth rates of both cell lines were stimulated by about 2-fold during a course of culture for 7 days as compared with mock-transfected cells. Although COX-1 and COX-2 are believed to have fundamentally different biological roles, essentially no differences in growth stimulation were observed between the COX-1 and COX-2 overexpressions in our experiments. The reason may be explained by high levels of COX expression, and subtle differences between the both cell lines would be possibly apparent by lower expression levels. The stimulated growth of the COX-transfected cells was accompanied by increased DNA synthesis as assessed by [3H]thymidine incorporation. Furthermore, expression of epidermal growth factor receptor was markedly increased in these cells as examined by reverse transcription-polymerase chain reaction. A COX inhibitor, indomethacin, suppressed the stimulated growth, increased DNA synthesis and induction of epidermal growth factor receptor in COX-1- and COX-2-transfected cells.

Cell Division↗

Essential involvement of 12-lipoxygenase in regiospecific andstereospecific oxidation of low density lipoprotein by macrophages.

To establish a role of the 12-lipoxygenase on the generation of oxidized low density lipoprotein (LDL) in macrophages that leads to foam cell formation in atherosclerosis, we overexpressed 12-lipoxygenases in a macrophage-like cell line, J774A.1, that does not show intrinsic enzyme activity. When the 12-lipoxygenase-expressing cells were incubated with 400 microg.mL-1 LDL in Dulbecco's modified Eagle's medium at 37 degrees C for 12 h, LDL oxidation, as determined by thiobarbituric acid reactive substance, was markedly increased compared with the mock-transfected cells. Oxygenated products in the modified LDL were examined by HPLC before and after alkaline hydrolysis. Most of the oxygenated derivatives were of an esterified form, and the major product was identified as 13S-hydroxyoctadeca-9Z,11E-dienoic acid. These results clearly demonstrate that esterified fatty acids in LDL are oxygenated by the 12-lipoxygenases expressed in the J774A.1 cells. Furthermore, the oxidized LDL generated by intracellular 12-lipoxygenases was recognized by a scavenger receptor as assessed by macrophage degradation assay.

Animals↗

Anisakidosis: a cause of intestinal obstruction from eating sushi.

We report a case of strangulating small bowel obstruction in a 60-yr-old Japanese woman caused by anisakidosis (previously known as anisakiasis). With the increasing popularity of Japanese cuisine such as sushi in the United States, the incidence of anisakidosis is expected to increase. Intestinal anisakidosis can now be treated temporarily, but this condition may cause a serious obstruction afterwards, as evidenced by this particular case. Over 13,500 cases were reviewed in both the Japanese and English literature, and we discuss the prevention of anisakidosis without negatively altering the taste of the raw fish.

Animals↗

Sound lateralization and speech discrimination in patients with sensorineural hearing loss.

Sound lateralization and speech discrimination abilities are both closely related to central auditory system function. In this study, we investigated the relationship between sound lateralization and speech discrimination in patients with sensorineural hearing loss (SNHL) of unknown aetiology or presbycusis. Interaural intensity difference (IID) and interaural time difference (ITD) discriminations were measured using a self-recording apparatus for dichotic sound presentation, and the means of bilateral maximum scores in speech discrimination tests were calculated. Subjects with normal sound lateralization had good speech discrimination scores above 70%, while those with abnormal sound lateralization had poor scores below 70%. Some patients, however, had good speech discrimination but abnormal sound lateralization. These findings were obtained in both IID and ITD discrimination tests. Furthermore, some subjects could not discriminate ITD, although all could discriminate IID. These findings suggest that sound lateralization ability may be affected more than speech discrimination in SNHL of unknown aetiology or in presbycusis.

Adult↗

Patterns of change in growth function of distortion product otoacoustic emissions in Menière's disease.

The patterns of change in the growth function of distortion product otoacoustic emissions (DPOAEs) associated with hearing improvement in six patients with Menière's disease were investigated. The growth functions of 2F1-F2 DPOAEs at F2 frequencies of 1001, 2002 and 4004 Hz (DP-1, DP-2 and DP-4, respectively) were measured with F2 intensities ranging from 70 to 37 dBSPL in 3-dB steps. The F1 intensity was maintained 10 dB higher than the F2 intensity. The growth function was paired with the hearing threshold at the corresponding F2 frequency, and the relationships between changes in DP-1, DP-2 and DP-4 and those in hearing thresholds at 1, 2 and 4 kHz, respectively, were also investigated. The patterns of change in the growth function associated with hearing improvement could be classified into five types. In the first type, the DPOAE growth function became detectable, while the remaining four types were distinguished by combinations of changes in DPOAE amplitudes for lower and higher primary intensities. Multiple parameters, such as maximum amplitude and detection threshold of the growth function, appeared to be required for simple detection and discrimination of these patterns of change. It was also found that the DPOAE growth functions clearly changed in some cases even though the hearing thresholds did not change significantly at the corresponding F2 frequencies. This finding suggests that DPOAE growth function measurement can detect small changes in cochlear function which do not lead to changes in hearing threshold, and has higher sensitivity than pure tone audiometry in monitoring of cochlear function. In conclusion, our findings suggest that measurement of the DPOAE growth function is useful for monitoring cochlear function, and that information on its patterns of change is clinically important and useful.

Adult↗