Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 181 records · Page 10Linked to original sources

PubMed1997

Spinal trabecular bone loss and fracture in American and Japanese women.

This study examined trabecular bone mineral density (BMD) in Japanese women with and without spinal fracture, and compared the results to American women with and without fracture. The quantitative computed tomography (QCT) systems used at the University of California, San Francisco (UCSF) and at Nagasaki University were cross-calibrated. Normative BMD was assessed with the K2HPO4 liquid phantom in 538 Americans aged 20-85 years, and with the B-MAS200 phantom in 577 Japanese aged 20-83 years. These BMD were adjusted for use with the Image Analysis solid phantom using the result of cross-calibration. The trabecular BMD in 111 postmenopausal American women (55 with fracture), and in 185 postmenopausal Japanese women (67 with fracture) were compared for investigation of the difference in BMD values relative to fracture status. The absolute BMD values in Japanese were lower than those in Americans, and the differences were greater with advancing age. The magnitude of the BMD difference was 8.6, 20.5, 38.1 mg/cm3 in women aged 20-24 years, 40-44 years, 60-64 years, respectively. In premenopausal women, BMD began to decrease at the age of 20 in Japanese, whereas the peak bone mass was maintained until the age of 35 in the American women. In immediate postmenopausal women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age in the Japanese women but decreased less rapidly in the American women. The aging decrease of BMD was 1.4% and 2.2% per year in the later postmenopausal American and Japanese women, respectively. The fracture threshold is considered to be lower in Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without fracture. The Z-scores of fracture subjects versus controls were 2.9 in American and 1.8 in Japanese women. In conclusion, Japanese women were found to have a lower BMD and lower fracture threshold than American women. The significant decrease of spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese women.

Adult↗

PubMed1997

Cisplatin-based combination chemotherapy for elderly patients with non-small-cell lung cancer.

PURPOSE: To compare the response rates, toxicities and survival durations of elderly patients (70 years of age or more) with those of younger patients (less than 70 years of age) with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. PATIENTS AND METHODS: We analyzed retrospectively the data of 203 assessable patients entered on a prospective randomized trial of cisplatin-based combination chemotherapy. Chemotherapy consisted of three dosage regimens: (1) vindesine and cisplatin (VP); (2) mitomycin, vindesine and cisplatin (MVP); or (3) etoposide and cisplatin alternating with vindesine and mitomycin (EP/VM). RESULTS: A greater proportion of elderly patients had localized disease and more squamous cell carcinoma than non-elderly patients. The overall response rates were 44% in the elderly group and 28% in the non-elderly group. In the EP/VM arm, the response rate was significantly better in the elderly group than in the non-elderly group. The frequency of grade 4 leukocytopenia in the MVP and EP/VM arms in the elderly group was significantly greater than in the non-elderly group (P < 0.05). No differences were found in nonhematological toxicities between the two groups. There was no difference in overall survival between the groups. CONCLUSION: Elderly patients treated with mitomycin-containing regimens have higher hematologic toxicities than younger patients. The results of this study are consistent with the previously reported pharmacologic data on mitomycin suggesting altered pharmacokinetics in elderly patients. The improved response rate in the elderly patients was probably because more elderly patients had earlier disease, squamous cell carcinoma and better performance status. Cisplatin-based chemotherapy was tolerable for most elderly NSCLC patients with good performance status.

Age Factors↗

PubMed1997

Differential expressions of cyclin A and the retinoblastoma gene product in histological subtypes of lung cancer cell lines.

Cell-cycle-dependent phosphorylation of the tumor-suppressor protein product of the retinoblastoma gene (RB) is mediated by a family of cyclin-dependent kinases and cyclins. We examined the expressions of RB protein and cyclin A protein in 13 small-cell lung cancer (SCLC) lines and 14 non-small-cell lung cancer (NSCLC) lines by immunoblotting. RB protein was not present or was of a mutant type in 77% of the SCLC lines (10/13) but was present in all the NSCLC lines. Cyclin A was expressed in 38% of the SCLC lines (5/13) and in 86% of the NSCLC lines (12/14). A positive correlation (P = 0.0034) between expression of cyclin A and wild-type RB protein was found by Fisher's exact probability test. Densitometric analysis of the expression of RB protein in RB(+) lung cancer lines showed that the phosphorylated form was predominant in 2/3 of the SCLC and 8/14 of the NSCLC lines. The positive correlation between the expressions of RB protein and cyclin A suggests that RB protein in most RB(+) lung cancer cell lines is a target of cyclin-A-dependent kinase and that the tumor-suppressor function may be inactivated by phosphorylation.

Adenovirus E1A Proteins↗

PubMed1997

Topographic distribution and collateral projections of the two major populations of nigrothalamic neurons. A retrograde labeling study in the rat.

The principal target nuclei of nigrothalamic projections in the rat are the mediodorsal (MD) and ventromedial (VM) nuclei. The present study examined the patterns of distribution and collateral projections of the two major groups of nigrothalamic neurons, i.e., nigro-MD and nigro-VM neurons. Retrograde fluorescent labeling with Fluoro-Gold was used to examine whether the distribution areas of nigro-MD and nigro-VM neurons might be overlapped with or segregated from each other in the substantia nigra pars reticulata. A clear tendency was observed that nigro-MD neurons were distributed more ventrally than nigro-VM neurons. It was further examined by retrograde fluorescent double labeling with Fluoro-Gold and Fluoro-Ruby whether or not these nigrothalamic neurons might provide axon collaterals to the superior colliculus or the pontine reticular formation. The nigro-MD neurons were found to send axon collaterals to the superior colliculus more frequently than the nigro-VM neurons. Additionally, a small number of nigrothalamic neurons were found to send axon collaterals to the pontine reticular formation. The functional significance of the two major populations of nigrothalamic neurons was discussed on the basis of their collateral projections to the superior colliculus or the pontine reticular formation.

Animals↗

PubMed1997

High plasma immunoreactive leptin level in essential hypertension.

Insulin resistance, the most important factor in metabolic syndrome X, has been considered to raise blood pressure. Recently it was reported that insulin resistance was related to an elevated plasma level of leptin, which is an adipocyte-specific ob gene product and which plays a role in food intake suppression, thermogenesis, and energy expenditure through the activation of the hypothalamus. However there are no reports that deal with the relationship of insulin resistance to plasma leptin and blood pressure. To evaluate the role of leptin in essential hypertensives, two groups of subjects who were carefully matched for body mass index (BMI) were studied; 22 normotensives (NT, age: 46.5 +/- 2.6 years, BMI: 23.9 +/- 0.4 kg/m2, male/female: 14/8) and 45 mild-to-moderate essential hypertensives (EHT, age: 51.9 +/- 2.0 years, BMI: 24.5 +/- 0.4 kg/m2, male/female: 21/24). We applied the euglycemic hyperinsulinemic glucose clamp technique to all subjects and insulin sensitivity was evaluated as the M value. EHT showed a significantly lower M value (160.2 +/- 7.4 v 184.3 +/- 7.3 mg/m2/min, P < .05) and higher basal plasma immunoreactive leptin level (7.6 +/- 0.8 v 5.0 +/- 0.8 ng/mL, P < .05) than NT, despite the fact that there was no significant difference between NT and EHT in age, gender, or BMI. The relationship between mean blood pressure and leptin showed a significant positive correlation in all of the subjects (r = 0.31, P < .05), suggesting that leptin may be related to a pathophysiology of essential hypertension.

Adult↗

PubMed1997

CODE chemotherapy with and without granulocyte colony-stimulating factor in small-cell lung cancer.

Sixty-three patients with extensive-stage small-cell lung cancer were randomized to receive either cyclophosphamide, vincristine, doxorubicin and etoposide (CODE) alone or CODE plus recombinant human granulocyte colony-stimulating factor (rhG-CSF). rhG-CSF administration in support of CODE chemotherapy resulted in increased mean total received dose intensity for all drugs (P = 0.03) with a significant improvement in survival (P = 0.004).

Adult↗

PubMed1997

CD28-b7 blockade in organ dysfunction secondary to cold ischemia/reperfusion injury.

Ischemic injury to cadaver organs is a major risk factor for development of chronic organ dysfunction. We have recently shown that the B7 costimulatory pathway plays a critical role in early organ dysfunction developing after renal cold ischemia/reperfusion injury. We extended these observations to investigate the role of this pathway in the development and progression of chronic organ dysfunction following such injury. Uninephrectomized rats which underwent cold ischemia/reperfusion injury developed progressive proteinuria as compared to uninephrectomized controls. Animals treated with CTLA4Ig, which blocks B7 costimulation, starting on the day of injury had significantly better long-term survival and developed significantly less proteinuria than control animals treated with control Ig. RT-PCR analysis of kidney tissue showed significant reduction in expression of activation and inflammatory cytokines, chemoattractants, and growth factors, as compared to controls. Delaying administration of CTLA4Ig for one week, but not four weeks, after injury was still effective in ameliorating development of progressive proteinuria. Interestingly, selective blockade of B7-1 by a mutant form of CTLA4Ig had no effect on early or chronic organ dysfunction. These findings indicate the long-term functional and molecular consequences of experimental cold ischemia/reperfusion injury, and suggest that B7-2 is critical in the development of organ dysfunction following ischemic injury, even in the absence of alloantigen.

Abatacept↗

PubMed1997

Transcutaneous needle biopsy of the lung.

PURPOSE: To evaluate the usefulness of transcutaneous needle biopsy (TCNB). MATERIAL AND METHODS: From May 1988 to December 1994, we performed TCNB under fluoroscopic control in 408 patients with mass lesions of the peripheral lung. The Surecut needle (1.5 mm) was selected mainly because of its ability to obtain specimens large enough for histological examination. Of the 408 patients, 286 had had previous bronchofiberscopic examinations but no definite diagnosis had been reached. RESULTS: A definite diagnosis was obtained by TCNB in 305 (74.7%) of 408 cases (251 malignant neoplasms, 54 benign lesions). In malignant neoplasms, the pathological diagnosis based on cytology and histology together was more reliable than that based on cytology alone. Although the complications of this procedure (such as pneumothorax) were within the range of acceptability, care should be taken to avoid air embolism and the seeding of cancer cells along the needle tract. CONCLUSION: TCNB with the Surecut needle is a useful procedure with relatively low risk.

Biopsy, Needle↗

PubMed1997

Enhancement of tumor radio-response by irinotecan in human lung tumor xenografts.

We investigated the ability of 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin (CPT-11) to increase tumor radio-response in vivo using human lung tumor xenografts. The xenografts were treated with (1) CPT-11 (10 mg/kg) intraperitoneally on days 1, 5 and 9, (2) single dose radiation (10 Gy/leg) on day 1, or (3) a combination regimen of both treatments in which radiation was given 1 h after the first dose of CPT-11. DNA flow cytometry studies were performed to define the cell cycle changes following treatment for 1 to 12 h with 0, 0.5, 2.0 or 8.0 ng/ml SN-38, the major active metabolite of CPT-11. In both small cell lung cancer (MS-1) and small cell/large cell carcinoma (LX-1) xenografts, combination treatment resulted in significant tumor regression compared with the use of CPT-11 (P = 0.0005, 0.0053) or radiation treatment (P = 0.00221, 0.0035) alone. Neither severe body weight loss nor enhanced skin reaction was observed following the combined treatment. In flow cytometry studies, the proportion of cells in G2/M-phase, the most radio-sensitive phase, increased after 1 h exposure to the lowest dose of SN-38 (0.5 ng/ml). These findings suggest that CPT-11 is a potent radiosensitizing agent, and that its activity is related to the cell cycle. This is the first report to indicate that CPT-11 serves as a radiosensitizer in vivo.

Animals↗

PubMed1997

Endothelium-derived relaxing and contracting factors during the early neonatal period.

The interaction and relative potency of nitric oxide, an endothelium-derived relaxing factor, and endothelin-1, an endothelium-derived contracting factor, may be important in the transition from fetal to extrauterine life. The change in level of nitric oxide during the early neonatal period has not been measured. Accordingly, the serum levels of nitric oxide metabolites (the sum of nitrite and nitrate) and plasma endothelin-1 were determined in 20 healthy neonates at birth, at 12 and 24 h postnatally, and at the age of 5 d. The lowest serum concentration of nitric oxide metabolites was observed at birth (26.2 +/- 9.1 micromol l(-1), mean +/- SD) and increased with age, whereas the highest plasma concentration of endothelin-1 was observed at birth (14.0 +/- 6.7 pg ml(-1)) and decreased with age. These changes suggest that nitric oxide and endothelin-1 play roles in the circulatory adaptation of the neonate to extrauterine life.

Adaptation, Physiological↗

PubMed1997

Assessment of osteoporosis: comparison of radiographic absorptiometry of the phalanges and dual X-ray absorptiometry of the radius and lumbar spine.

PURPOSE: To evaluate radiographic absorptiometry (RA) of the phalanges in healthy women and in women with osteoporosis and to compare the results of RA with those of dual x-ray absorptiometry (DXA) of the radius and spine. MATERIALS AND METHODS: Thirty-two healthy premenopausal women, 39 healthy postmenopausal women, and 35 postmenopausal women with osteoporosis underwent RA of the phalanges and DXA of the radius and lumbar spine. Pairwise comparisons, age-related bone losses, and percentage decrements and Student t values for intergroup discrimination were calculated. The ability to identify patients with osteoporotic fractures was evaluated by using receiver operating characteristic and age-adjusted logistic regression analyses. The diagnostic agreement for osteoporosis was assessed with kappa statistics. RESULTS: Findings from RA were correlated with those from spinal DXA (r = .56). The annual bone losses in healthy women, as measured with RA, radial DXA, and spinal DXA, were 0.47%, 0.47%, and 0.32%, respectively. Intergroup percentage decrements and t values obtained with RA were comparable to those obtained with radial and with spinal DXA. Receiver operating characteristic analysis showed no statistically significant differences. The odds ratios for RA, radial DXA, and spinal DXA were 2.1, 1.9, and 2.4, respectively. The kappa scores were 0.44 for both RA versus radial DXA and RA versus spinal DXA, and the score was 0.22 for radial DXA versus spinal DXA. CONCLUSION: RA appears to be a useful technique for assessing age- and menopause-related bone loss and for identifying women with osteoporosis.

Absorptiometry, Photon↗

PubMed1997

Effect of magnesium sulfate treatment on neonatal bone abnormalities.

OBJECTIVE: It has been reported that neonatal bone abnormalities occur as a result of long-term intravenous magnesium administration (MgSO4) to pregnant women. The purpose of this retrospective study was to evaluate the frequency of such abnormalities and the clinical background of both mothers and neonates. PATIENTS AND METHODS: We reviewed maternal (114 cases) and neonatal (139 cases) charts from all pregnant women who received intravenous MgSO4 administration for preterm labor and preeclampsia between June 1, 1992, and May 31, 1994. All chest X-ray films were obtained within 48 h after birth and reviewed by a doctor who was unaware of the clinical data. Radiolucent transverse metaphyseal bands of the proximal humerus were considered as abnormal. The subjects were divided into affected (group 1 and 1a) and unaffected (group 2 and 2a) groups. Neonates born to pregnant women given no MgSO4 at the same period, were considered as control. RESULTS: The total number of bone abnormalities in the offspring of mothers receiving MgSO4 amounted to 13 (11.4%). Group 1 consisted of 13 cases and group 2 of 101 cases. In the control group bone abnormalities were not observed (p < 0.05). Significant differences were found between groups 1 and 2 in the gestational ages at the start of MgSO4 administration and at delivery, and in the total duration of administration and doses of MgSO4. Also, cases of multiple pregnancy and pregnancy complicated with impaired glucose tolerance were more prevalent in group 1. According to the results obtained from 139 neonates, cases showing low Apgar and high magnesium score and those receiving respiratory support were more noticeable in group 1a (15 cases). CONCLUSIONS: The gestational ages and the total doses of MgSO4 in pregnant women were the main factors related to the onset of neonatal bone abnormalities, but other factors also have a possible bearing on the condition. In addition, the cases with onset of bone abnormality seemed to be associated with symptoms attributable to hypermagnesemia of neonates.

Bone Development↗

PubMed1997

High ratios of free to total insulin-like growth factor-I in early infancy.

Insulin-like growth factor-I (IGF-I) is a major effector of somatic growth and metabolism. In normal, nonpregnant plasma, most of the IGF-I is complexed to specific IGF-binding proteins (IGFBPs), particularly IGFBP-3; only a minor fraction of plasma IGF-I exists in a free form. Recently, we have reported that free IGF-I levels, as measured using a new immunoradiometric assay, are relatively high in maternal plasma during pregnancy because of increased IGFBP-3 proteolytic activity. These high free IGF-I levels are physiologically important for the growth of maternal tissues such as uterus and placenta, which are related to the fetal growth. Growth during early infancy may be a continuation of fetal growth. In the present study, we have analyzed free and total plasma IGF-I and IGFBP-3 proteolytic activity in early infancy. Although the levels of free and total IGF-I were not significantly different in early infancy as compared with prepubertal periods, the ratio of free to total IGF-I (mean = 2.04%) was relatively increased and was similar to the ratio in pregnancy plasma (1.86%). However, unlike in maternal plasma, the high ratios were not totally caused by increased IGFBP-3 proteolytic activity. Our results suggest that there may be an increased conversion of plasma IGF-I to a free form in early infancy. The resultant increase in IGF-I bioavailability could contribute to the rapid somatic growth in early infancy.

Adult↗

PubMed1997

Effect of pulsed output ultrasound on the transdermal absorption of indomethacin from an ointment in rats.

The effect of pulsed output ultrasound (1 MHz) with on/off ratios of 1:2, 1:4 and 1:9 on transdermal absorption of indomethacin from an ointment was studied in rats. Ultrasound energy was supplied for between 10 and 19 min at a range of intensities (1.0-2.5 W.cm-2), energy levels commonly used for therapeutic purposes. The on/off pulsed ratio, intensity and the time of application were found to play an important role in the transdermal phonophoretic delivery system of indomethacin; 1:2 pulsed output ultrasound appeared to be the most effective in improving the transdermal absorption. The highest penetration was observed at an intensity of 1.0 W.cm-2 and application time of 15 min. With pulsed output it was possible to use higher intensities of ultrasound without increasing skin temperature or damaging skin.

Administration, Cutaneous↗

PubMed1997

Aconitine induces bradycardia through a transmission pathway including the anterior hypothalamus in conscious mice.

Aconitine administered intraperitoneally (i.p.) produces bradycardia mainly by a central muscarinic action. The involvement of hypothalamic regions in the occurrence of aconitine-induced bradycardia was investigated in hypothalamus-lesioned mice. The lesions were made by passing a direct current (1.5 mA, 13 s) through a monopolar electrode. The aconitine (30 micrograms/kg, i.p.)-induced bradycardia was prevented by bilateral lesions of either the whole hypothalamus, except for the lateral hypothalamus area, or the anterior hypothalamus (AH). The bradycardia was not prevented by bilateral lesions of the ventromedial, the paraventricular, the posterior or the lateral hypothalamus regions. Bupivacaine, but not atropine (1 microgram, administered into the intact AH) prevented aconitine-induced bradycardia in mice with a contralaterally lesioned AH. Aconitine (0.8 microgram) directly administered into the unilateral AH in intact mice caused a late phase and lesser extent of bradycardia. These results suggest that a transmission pathway including the AH contributes to the aconitine-induced bradycardia but does not involve the activation of muscarinic receptors in the AH.

Aconitine↗

PubMed1997

The transport of ciprofloxacin in cultured kidney epithelial cells LLC-PK1.

In this study, the transport characteristics of ciprofloxacin (CPFX) were investigated in a LLC-PK1 kidney epithelial cell line. CPFX uptake from the apical medium into LLC-PK1 cells on plastic dishes was shown to be temperature-dependent. Guanidine and cimetidine inhibited the uptake of CPFX, whereas tetraethylammonium chloride (TEA) and N1-methylnicotinamide (NMN) did not. CPFX transport across LLC-PK1 cell monolayers cultured on permeable supports was about 1.8 times larger in the basolateral-to-apical direction than in the apical-to-basolateral direction. Both the basolateral-to-apical and apical-to-basolateral transport of CPFX were inhibited by guanidine, whereas CPFX transport in both directions was not inhibited by TEA, NMN, or cimetidine. The basolateral-to-apical transport of CPFX was sensitive to the pH of the apical medium, and increased in an acidic pH. Enoxacin (ENX) as well as guanidine, inhibited the basolateral-to-apical transport of CPFX, and the inhibitory effect of ENX was sensitive to the pH of the apical side of the monolayers.

Animals↗

PubMed1997

[Preparation and evaluation of solid dispersions of pilocarpine hydrochloride for alleviation of xerostomia].

This investigation was carried out to try the application of pilocarpine hydrochloride (PC) solid dispersion as sustained release dosage form. Four preparations of PC with ethylcellulose and/or hydroxypropylmethylcellulose phthalate were prepared by the organic solvent method. The preparation D including PC: ethylcellulose: hydroxypropylmethylcellulose phthalate (1:9:10 at weight ratio) showed the best sustained release behavior in dissolution test among four preparations. The preparation D was examined by powder X-ray diffractometry and differential scanning calorimetry, and confirmed to be solid dispersion. Saliva secretory effect of preparation D was examined in healthy male volunteers, and its effect for Xerostomia was showed.

Cellulose↗

PubMed1997

A preliminary evaluation of the lunar expert-XL for bone densitometry and vertebral morphometry.

We have evaluated the Lunar Expert-XL for standard bone mineral densitometry (BMD) and for morphometric imaging of the spine in the lateral projection. The short-term precision in vitro of the Expert-XL for BMD measurements was 0.7% for the Hologic and European spine phantoms, and the long-term stability (15-month) measurements had a 1.1% coefficient of variation. The precision in vivo for three operators examining a group of 10 premenopausal women was 0.9-1.5% for lumbar spine (L2-L4), 1.7-2.2% for the femoral neck, and 0.9% for the total hip region of interest. For a group of nine postmenopausal women, the lumbar spine, femoral neck, and total femur precision ranges were 2.0-2.4, 1.2-2.9, and 1.6-1.7% respectively. For L2-L4, BMD comparison between the Expert-XL and DPX-L yielded a correlation coefficient of r = 0.98, a slope of 0.86, and an intercept of 0.139 g/cm2. The femoral neck results were r = 0.92, slope = 1.00, and intercept = 0.03 g/cm2. In an evaluation of the Expert-XL for lateral morphometry, we employed a group of 16 postmenopausal women. Comparison of vertebral dimensions between the Expert-XL and radiographic morphometry showed strong agreement (r = 0.97), but the interobserver variability for vertebral height was higher for the Expert-XL than for radiographs (3-5% vs. 1-2%). In a subset of four women who had repeat scans, the interscan precision for measuring vertebral dimensions was 1.9, 4.1, and 43% for the L1-L4, T12-T8, and T7-T5 levels respectively. In the Expert-XL images, it was possible to identify clearly L4-T4 in 10 of 16 patients and L4-T6 in 15 of 16, indicating potential utility for vertebral fracture prescreening.

Absorptiometry, Photon↗