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Biomedical subjects

H Satoh

Publications and source records attributed to H Satoh.

At least 289 records · Page 16Linked to original sources

Organochlorine compounds from a terrestrial higher plant: structures and origin of chlorinated orcinol derivatives from diseased bulbs of Lilium maximowiczii.

Seven chlorine-containing orcinol derivatives (2-8) and orcinol (9) have been isolated from diseased bulbs of the edible lily Lilium maximowiczii, and their structures have been elucidated. Six of the chlorinated orcinol derivatives (2, 4-8) showed antifungal activity. Because organochlorine compounds are rare in terrestrial higher plants, their biosynthetic origin was examined. These compounds were shown to be induced in intact bulb scales by UV irradiation or by inoculation with the pathogenic fungus Fusarium oxysporum f. sp. lilii. Biosynthetic studies suggested that these "natural organochlorine pesticides" are produced by enzymatic chlorination of orcinol (9) with chloroperoxidase and hydrogen peroxide, which are both induced in the plant tissue under stress conditions.

Antifungal Agents↗

Severe growth defect in mouse cells lacking the telomerase RNA component.

The ribonucleoprotein enzyme telomerase synthesizes telomeric DNA onto chromosome ends. Telomere length is maintained, by the presence of telomerase activity, in the vast majority of primary tumours and stem cells, suggesting that telomere maintenance is essential for cellular immortalization. Recently, the telomerase RNA component in human and mouse (TERC and Terc, respectively), a telomerase-associated protein TEP1/TLP1 (refs 6,7) and the human catalytic subunit protein TERT (refs 8,9) have been identified. To examine the role of telomerase in telomere maintenance and cellular viability, we established Terc-deficient embryonic stem (ES) cells. It is known that telomerase activity is absent in cells from Terc-knockout mice. Although the study showed that telomere shortening was observed in the Terc-deficient cells from first to six generation animals, whether telomerase-dependent telomere maintenance was essential for cellular viability remained to be elucidated. To address this issue, we examined Terc-deficient ES cells under long-term culture conditions. Accompanying the continual telomere shortening, the growth rate of Terc-deficient ES cells was gradually reduced after more than 300 divisions. An impaired growth rate was maintained to approximately 450 divisions, and then cell growth virtually stopped. These data clearly show that telomerase-dependent telomere maintenance is critical for the growth of mammalian cells.

Animals↗

Heterogeneity and underlying mechanism for inotropic action of endothelin-1 in rat ventricular myocytes.

1. To clarify the mechanisms underlying the positive inotropic action of endothelin-1 (ET-1), we investigated the effect of ET-1 on twitch cell shortening and the Ca2+ transient in rat isolated ventricular myocytes loaded with a fluorescent Ca2+ indicator indo-1. 2. There was a cell-to-cell heterogeneity in response to ET-1. ET-1 (100 nM) increased twitch cell shortening in only 6 of 14 cells (44%) and the increase in twitch cell shortening was always accompanied by an increase in the amplitude of the Ca2+ transient. 3. The ET(A)- and ET(B)-receptors antagonist TAK-044 (100 nM) almost reversed both the ET-1-induced increases in twitch cell shortening and in the Ca2+ transient. In the ET-1 non-responding cells, the amplitude of the Ca2+ transient never increased. 4. Intracellular pH slightly increased (approximately 0.08 unit) after 30 min perfusion of ET-1 in rat ventricular myocytes. However, ET-1 did not change the myofilament responsiveness to Ca2+, which was assessed by (1) the relationship between the Ca2+ transient amplitude and twitch cell shortening, and by (2) the Ca2+ transient-cell shortening phase plane diagram during negative staircase. 5. We concluded that there was a cell-to-cell heterogeneity in the positive inotropic effect of ET-1, and that the ET-receptor-mediated positive inotropic effect was mainly due to an increase in the Ca2+ transient amplitude rather than to an increase in myofilament responsiveness to Ca2+.

Animals↗

Angiocytotoxic therapy in human non-small cell lung cancer cell lines--advantage of combined effects of TNP-470 and SN-38.

The combined effects of TNP-470, a promising antiangiogenic agent, and SN-38, a camptothecin derivative, were evaluated in four human cultured cell lines derived from non-small cell lung cancer (NSCLC). Cytotoxicity experiments were determined by using a tetrazolium salt (MTT) assay. The inhibitory effects of TNP-470 on cell proliferation were dose related and the 50% inhibitory concentrations on these cell lines were 47.3-139.8 microM. Evaluation of drug interactions with isobologram and the combination index values showed that sequential exposure to SN-38 followed by TNP-470 produced synergistic effects in the four cell lines tested. Our findings suggest that such an angiocytotoxic chemotherapy might be promising for the treatment of NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Pharmacokinetics of recombinant human interferon-alpha 2a combined with 5-fluorouracil in patients with advanced colorectal carcinoma.

We evaluated the pharmacokinetics of 5-fluorouracil (5-FU) combined with recombinant human interferon (IFN)-alpha 2a in 10 previously untreated patients with advanced colorectal carcinoma. 5-FU was administered as a continuous i.v. infusion, 750 mg/m2/day for 5 days during week 1. One s.c. injection of IFN-alpha 2a, 9 x 10(6) IU, was administered during week 2. Beginning with week 3, a continuous i.v. infusion of 5-FU 750 mg/m2/day for 5 days was administered in combination with IFN-alpha 2a, 9 x 10(6) IU s.c. three times per week. The combination of 5-FU and IFN-alpha 2a was continued every other week until either 3 months after complete remission or tumor progression. No grade 4 toxicity was observed. Granulocytopenia (two patients), leukopenia (one patient), thrombocytopenia (one patient), stomatitis (two patients), fatigue (one patient) and hand-foot syndrome (one patient) were the major (grade 3) toxic reactions encountered. Overall, one complete and six partial responses were noted. The results of the paired t-test showed no statistically significant differences between the means of the two treatments, 5-FU and 5-FU plus IFN-alpha 2a, with respect to the steady-state plasma concentration, area under the concentration-time curve, total body clearance, or steady-state volume of distribution of 5-FU, or the serum concentration of IFN. We conclude that 5-FU and IFN-alpha 2a do not interact pharmacokinetically at the doses and schedules in the regimen studied.

Adult↗

Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan.

OBJECTIVE: To compare the predictive powers of self-measurement of blood pressure at home (home blood pressure measurement) and casual (screening) blood pressure measurement for mortality. DESIGN: A prospective cohort study. SUBJECTS AND METHODS: We obtained home and screening blood pressure measurements for 1789 subjects aged > or = 40 years who were followed up for a mean of 6.6 years. The prognostic significance of blood pressure for mortality was determined by the Cox proportional hazards regression model adjusted for age, sex, smoking status, past history of cardiovascular disease, and the use of antihypertensive medication. RESULTS: When the home blood pressure values and the screening blood pressure values were simultaneously incorporated into the Cox model as continuous variables, only the average of multiple (taken more than three times) home systolic blood pressure values was significantly and strongly related to the cardiovascular mortality risk. The average of the two initial home blood pressure values was also better related to the mortality risk than were the screening blood pressure values. CONCLUSIONS: Home blood pressure measurement had a stronger predictive power for mortality than did screening blood pressure measurement for a general population. This appears to be the first study in which the prognostic significances of home and screening blood pressure measurements have been compared.

Adult↗

Cross-correlation between 1/f-like fluctuations in heartbeat and diurnal changes in the sleep-waking stage.

The cross-correlation function between diurnal changes in 1/f-like fluctuations of the R-R interval and those of the sleep-waking stage was calculated based on the data from six normal subjects in order to investigate the interactions among circadian components. Sleep stage was scored according to the standard criteria and waking stage was scored with criteria developed for the present study. Polysomnography was performed for 11 h during the daytime. The equation for 1/f was approximated using the power spectra of the R-R interval every 10 min. Cross-correlation analysis between sleep-waking stage and 1/f fluctuation of the R-R interval suggested that the neural network for 1/f fluctuation in heartbeat is influenced by the sleep-wake cycle with a time lag in the order of tens of minutes.

Adult↗

Elevated serum sialyl Lewis X-i antigen levels in non-small cell lung cancer with lung metastasis.

To evaluate the relationship between serum levels of sialyl Lewis X-i antigen and lung metastasis in patients with non-small cell lung cancer (NSCLC), we measured the serum level of the antigen in 299 patients with untreated locally advanced or metastatic NSCLC. Before treatment, serum levels of sialyl Lewis X-i antigen were significantly higher in patients with lung metastasis than in those without lung metastatis (p = 0.0001). Of 201 patients without lung metastasis at the time of primary diagnosis, 121 patients died between July 1987 and December 1995. Serum levels of sialyl Lewis X-i antigen in 21 patients who developed lung metastasis during the period were significantly higher than those in 100 patients who did not develop lung metastasis (p = 0.0171). Our results suggested that sialyl Lewis X-i antigen might be a good indicator for the presence or development of lung metastasis, and it might provide clinical information about the management of patients with NSCLC.

Aged↗

Reference values for 24-hour ambulatory blood pressure monitoring based on a prognostic criterion: the Ohasama Study.

Although reference values for ambulatory blood pressure (ABP) monitoring have been investigated in several population studies, these values were derived from cross-sectional observations and were based merely on the statistical distribution of blood pressure values. Therefore, we conducted a prospective cohort study to identify reference values for 24-hour ABP in relation to prognosis. We obtained measurements of 24-hour ABP for 1542 subjects (565 men) aged 40 years and over in a general population of a rural Japanese community and then followed-up their survival status. There were 117 deaths during the follow-up period (mean, 6.2 years). The association between baseline 24-hour ABP values and mortality, examined by the Cox proportional hazards regression model adjusted for possible confounding factors, showed a better fit with a second-degree equation than with a first-degree equation. On the basis of the results of this analysis, we identified the following reference values as the optimal blood pressure ranges that predict the best prognosis: 120 to 133 mm Hg for systolic blood pressure and 65 to 78 mm Hg for diastolic blood pressure. 24-Hour ABP values >134/79 mm Hg and <119/64 mm Hg were related to increased risks for cardiovascular and noncardiovascular mortality, respectively. This is the first report to propose reference values for 24-hour ABP based on a prognostic criterion.

Adult↗

Discrepancy between screening blood pressure and ambulatory blood pressure: a community-based study in Ohasama.

We investigated factors underlying discrepancy between screening blood pressure and daytime ambulatory blood pressure (the difference) in a community-based population in northeastern Japan. Screening and ambulatory pressures were measured in 706 untreated subjects aged 20 yr or older. We analyzed the effects of age and blood pressure on the difference and then performed multivariate stepwise linear regression analysis using the difference as the dependent variable. The systolic difference positively correlated with age in men. Women in their 40s exhibited a large difference, disturbing the linear relationship between the difference and age. The difference positively correlated with the screening pressure in men and women. A positive difference (screening pressure > ambulatory pressure) was observed at screening pressures above 130/75 mmHg. The difference inversely correlated with the ambulatory pressure. Multivariate analysis demonstrated that body mass index and male sex were positively associated with the systolic and diastolic blood pressure differences. The daytime pulse rate was negatively associated with the systolic difference, and the standard deviation of daytime diastolic ambulatory blood pressure was positively associated with the diastolic difference. The diastolic difference in subjects with isolated systolic hypertension based on the screening pressure was significantly smaller than that in subjects with systolic/diastolic hypertension. The difference in subjects with isolated systolic hypertension based on ambulatory pressure was significantly higher than that in systolic/diastolic hypertension. When white-coal (isolated screening) hypertension was defined as a screening systolic pressure > or = 140 mmHg, a diastolic pressure > or = 90 mmHg, or both, and a 24-h ambulatory pressure < 136/87 mmHg in men and < 131/86 mmHg in women, white-coat (isolated screening) hypertension was present in 79 (56.8%) of 139 subjects with screening hypertension. The results confirm that the discrepancy between screening and ambulatory blood pressure is due to a variety of factors, including age, sex, blood pressure levels, and baroreflex function. Our results indicate that screening blood pressure in elderly hypertensive patients should be evaluated carefully.

Adult↗

Growth reacceleration of school children in the city of Sendai, Japan.

Height and weight of 6th year-grade children in primary schools and the 3rd year-grade children in junior high schools have been recorded in Sendai in every October since pre-World War II days, and the secular trends of the annual gains in the measures were compared among the latest three decades of 1965-74, 1975-84 and 1985-94. Acceleration and then reduction in acceleration in growth were observed in the first and the second decade, respectively, and such were followed by reacceleration in the latest 10 year-period. The three-phased changes were most evident in height and weight of primary school children of both sexes, whereas less clear or unclear among children in junior high schools.

Adolescent↗

Effects of mild chronic heat exposure on the concentrations of thiobarbituric acid reactive substances, glutathione, and selenium, and glutathione peroxidase activity in the mouse liver.

To determine whether mild and chronic heat stress leads to oxidative stress and to differentiate such effects of different exposure periods, we kept male ICR-mice at an ambient temperature of either 35 degrees C or 25 degrees C for 6 hours, 3 days, or 7 days and measured the concentrations of thiobarbituric acid reactive substances (TBARS), glutathione (GSH), selenium (Se), and glutathione peroxidase (GSH-Px) activities in the liver. Since the food consumption of the heat-exposed group was only half that of the control, we prepared pair-fed groups, which were kept at 25 degrees C and whose food consumption were limited to those of the heat-exposed group for the 3-day and the 7-day exposure. TBARS concentrations of the liver was significantly higher in the heat group than the control after the 3-day exposure, while there was no significant difference among the groups after the 7-day exposure. There was no significant difference in GSH concentrations between the heat-exposed group and the control after the 7-day exposure, when the GSH concentration of the pair-fed group was significantly lower than that of the control. Hepatic cytosolic Se GSH-Px activity in the heat group was significantly less than that in the control group after the 6-hour exposure and it tended to be lower in the heat group than that of the control group after the 7-day exposure, while there was no difference in the total GSH-Px activity among the three groups. Our results showed that mild and chronic heat exposure may cause oxidative damage to organisms and that GSH-related anti-oxidative systems would play an important role to defensive reaction.

Animals↗

Regenerative process after experimental injury of hypoglossal nerves in guinea pigs.

The nerve regenerative process has been investigated by many studies. However, the quantification of the degree of crush of peripheral nerves has not yet been performed. The aim of this study was to determine and standardize the ligature intensity and crush level of the hypoglossal nerve of guinea pigs. The compound action potentials evoked by electric stimulation were used as an index of the degree of nerve crush. To demonstrate nerve regeneration after ligating and crushing of the right hypoglossal nerve, fluorescein isothiocynate conjugated cholera toxin-B subunit (CTb-FITC) was injected into the intact fiber of the left hypoglossal nerve, and the central side from the crushed region of the right hypoglossal nerve fiber. The total cross sectional area of the retrograde-labeled hypoglossal motoneurons was investigated under a confocal laser scanning microscope. The results of the evaluation using CTb-FITC indicated that the nerve regeneration occurred from two weeks after crush and recovered in six weeks.

Action Potentials↗

A new reduction technique for a patellar fracture.

We report 4 cases of patellar fracture with skin injury over the patella which were treated operatively immediately after onset with a new reduction technique using Ilizarov pins. This technique made it possible to perform early operative treatment even in the cases with skin injury over the patella which prevents conventional surgical approach.

Adult↗

[Functional hearing loss in children who were not aware of their hearing loss].

We investigated one hundred and fourteen ears of 60 children (8 males, 52 females, aged from 6 to 13 years) with diagnoses of functional hearing loss (FHL), and were not aware of their own hearing loss. Forty nine (81.7%) of 60 cases examined were detected by school screening tests, 6 (10.0%) were referred to our hospital because their families noticed poor hearing responses, and 5 (8.3%) were enrolled because they complained of otalgia or discomfort in the ear. Forty (66.7%) showed only pure tone threshold loss without complications, and the remaining 20 associated nonorganic disorders. In addition, our investigation found 11 cases (18.3%) with nonorganic otalgia, 5 (8.3%) with functional visual disturbance, 1 (1.7%) with enuresis nocturna who refused to attend school, 1 with tinnitus, 1 with vertigo, and 1 with tic. Moreover, 11 (18.3%) of the 60 cases were suspected of being in conflict with school and/or home. The Type V Békésy pattern, which is frequently observed in FHL and it has clinical utility to distinguish FHL from other types of organic hearing loss, was detected in 44 ears (38.6%). Fifty two (45.6%) of 114 ears showed normal pure-tone thresholds during the clinical course. Sixteen (14.0%) ears needed more than 1 year for thresholds to normalize. These findings suggest that some FHL cases without awareness of their hearing loss resemble psychogenic hearing loss. In such cases, otolaryngologists should carefully check the patient's individual circumstances, and when appropriate, refer patients for psychiatric consultation.

Adolescent↗

[A case of so-called carcinosarcoma of peripheral lung].

A 67-year-old man was admitted to our hospital with blood sputum. Adenocarcinoma was diagnosed by sputum cytological examination. A chest X-ray film showed a tumor shadow in the lower field of the right lung. The middle and lower lobes were resected and lymph node dissection was performed. Tumor was composed of well differentiated adenocarcinoma and spindle cell sarcomatous element, and diagnosed as so-called carcinosarcoma. Pathological staging was IIIA by pT1N2M0. Postoperative chemotherapy was not performed for side effect, so radiotherapy only was done. He died of recurrence and metastasis after about 1 postoperative year.

Aged↗

[Telomerase activity in colorectal cancer--a semi-quantitative procedure].

Telomerase maintains telomere at the end of chromosome and stabilizes chromosome. It is thought to have important roles in cancer progression and cell immortality. We evaluated the role of telomerase expression in colorectal carcinogenesis. Materials included 13 colonic adenomas, 9 early colorectal cancers, 32 advanced colorectal cancers, 5 metastatic tumors, and 30 non-cancerous colon mucosas. The telomerase activity was analyzed using TRAP-eze (Oncor Inc.) for a semi-quantitative method. The positive rate of telomerase activity was 13.3% in non-cancerous colonic mucosa, 15.4% in colonic adenomas, 77.8% in early colorectal cancers, 93.8% in advanced colorectal cancers, and 100% in metastatic tumors; the mean value was 18.0, 29.9, 65.8, 97.0 and 161.3. The correlation between telomerase activity and tumor size, histologic type, or depth of invasion was noted. Sensitivity, specificity and accuracy were on the order of 89%, 98% and 93% at the cut-off level as two times the mean value of non-cancerous mucosa. Telomerase had an important role in carcinogenesis, and progression of colorectal cancer, and it was suggested to be useful for a tumor marker.

Adenocarcinoma↗