[Endocrine disrupting substances (continued)--characteristic actions and test methods].
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Animals↗
Biomedical subjects
T Inoue
Publications and source records attributed to T Inoue.
[An adjustment procedure for comparing migration data based on different definitions in Japanese censuses].
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Age Factors↗
Semi-automated renal region of interest selection method using the double-threshold technique: inter-operator variability in quantitating 99mTc-MAG3 renal uptake.
In calculating the relative and absolute renal uptake of technetium-99m mercaptoacetyltriglycine (MAG3), inter-operator variability in the assignment of the renal region of interest (ROI) is a critical factor. Our goal was to develop a semi-automated method of assigning the renal ROI and then to compare the inter-operator variability in calculating the percent injected dose (%ID) in the kidney at 1-2 min, using semi-automated versus manual ROIs. The manual ROIs were drawn independently by three operators (A, B and C). Operator A had about 20 years, experience in nuclear medicine, while operators B and C respectively had 3 years and 1 year of experience. In the semi-automated renal ROI selection method using the double-threshold technique, the operators only click around the centre of each kidney. The same three operators processed the ROIs using this double-threshold method on 1-2 min images. The semi-automated method failed in three kidneys with very markedly reduced function owing to superimposition by liver or spleen. Inter-operator reproducibility in the remaining 59 kidneys was estimated using manual and semi-automated ROIs. With manual ROIs, the %ID (mean+/-standard error of mean) was 4.32+/-0.167 for A, 4. 14+/-0.165 for B and 3.28+/-0.139 for C. Although there was good correlation among them, these values were significantly different (P<0.0001). Using semi-automated ROIs, the %ID was 4.38+/-0.160 for three operators. No significant difference was observed. Complete reproducibility was shown in 58 of 59 kidneys; the %ID difference of the remaining kidney was only 1.2%. The lowest %ID of all the kidneys successfully detected using the semi-automated method was 0. 77%. The semi-automated renal ROI selection method using the double-threshold technique displays good detectability of the renal contour. The renal uptake calculated using this method is reproducible and acceptable in routine clinical practice.
Adolescent↗
Clinical significance of neutrophil adhesion molecules expression after coronary angioplasty on the development of restenosis.
To investigate the neutrophil activation process following percutaneous transluminal coronary angioplasty (PTCA), we examined the expressions of Mac-1 (CD11b/CD18), L-selectin (CD62L), and sialyl-LewisX (SLX) on the surface of neutrophils after the PTCA procedure, by flow cytometric analysis. Twenty-nine patients with single vessel coronary artery disease of the left anterior descending artery who underwent elective PTCA were enrolled. In the 17 patients without restenosis at the follow-up angiography, the mean channel fluorescence intensity (MFI) for CD18, CD62L and SLX did not change after PTCA. Only the CD11b level was increased at 48 h after the PTCA. In the remaining 12 patients who developed restenosis, the MFI values for CD18 and CD11b were increased at 24 h and 48 h after the PTCA. The MFI value for CD62L was decreased and that for SLX was increased at 48 h after the PTCA. These changes were more prominent in the coronary sinus blood samples than in those of the peripheral blood samples. Our data indicate the down-regulation of L-selectin, probably by shedding, as well as the up-regulations of Mac-1 and sialyl-LewisX, especially in patients with restenosis. It is suggested that neutrophil activation by an interaction between the selectin family and carbohydrate ligands after PTCA may play a role in the development of restenosis, as does the integrin family.
Angioplasty, Balloon, Coronary↗
[Selection of clinical evaluation criterion and method of measurement].
The criterion for clinical evaluation of radiotherapy is defined by the authors as follows: Cost-effectiveness = Quality adjusted life year of a patient divided by the expenditure for the patient. Here, quality adjusted life year is calculated by estimating transition probabilities employing the Malkov process model. An expression model for estimation of radiotherapy effectiveness of the patient was proposed and applied. The actual cost of radiotherapy for the patient was calculated by carrying out a Care Map Study in a radiotherapy facility. The time study measures, the hours spent treating the patient by the kind of medical staff. Then, cost-effectiveness was calculated using these two variables in 2,926 patients from 147 radiotherapy facilities collected from a multi-institutional radiation oncology database developed and operated for the five years. A worksheet composed of 55 items of radiotherapy record for one site of a patient. Another worksheet for patient follow-up was composed of 14 items. Six retrospective and prospective data collections and three follow-up investigations were carried out. This study intended to determine the cost-effectiveness of radiotherapy in terms of cancer sites, diseases and treatment modalities. A further target is to expand this method to evaluate new technologies of health care at large as well as radiation oncology.
Cost-Benefit Analysis↗
[Clinical evaluation based on cost-effectiveness].
We carried out two Phase III clinical trials using high dose rate (HDR) remote afterloading brachytherapy unit. We evaluated the clinical results based not only on the medical but also the economical standpoint. The first trial is the Phase III trial for cervical cancer treated with HDR or medium dose rate (MDR) intracavitary radiotherapy. The second one is the Phase III trial for tongue cancer treated with HDR or low dose rate (LDR) interstitial radiation. For cervical cancer, the survival rate of patients treated with HDR brachytherapy is the same as for LDR brachytherapy. The average total cost of treatment for the HDR group was 1.47 million yen, while that for the MDR group was 1.58 million yen. The average total admission days was 63. For tongue cancer, the local control rate of the HDR group is almost the same as that of the LDR groups. The average total cost for the HDR group was 780 thousand yen, and that for the LDR group was 830 thousand yen. The average total admission days was 34. According to the cost-effectiveness, HDR brachytherapy for cervical cancer has the same result as MDR, and HDR brachytherapy for tongue cancer has the same result as LDR. However, HDR can be treated without admission for patients who live near the hospital. HDR can be applied for these patients with less expense. We must be aware of not only the medical results but also the cost-effectiveness.
Adult↗
[Orbito-facial reconstruction after extensive anterior skull base, head and neck resection using a rectus abdominis musculocutaneous flap].
In response to the recent advances in aggressive excision of skull base and head and neck malignancies, a more sophisticated method primary reconstruction has been developed using a craniofacial techniques for preservation of postoperative quality of life. We have developed an inferior pedicled rectus abdominis musculocutaneous flap with rib cartilages for reconstruction of the orbito-facial region. The advantages of this flap are as follows; 1) Simultaneous flap elevation in a supine position is possible, 2) Easy, versatile and reliable flap adjustment can be made for complicated space defect, 3) Curvature of the ipsilateral rib cartilages is suitable for inferior orbital rim, 4) Lower risk of pleura laceration as compared with a superior pedicled flap. In the past 5 years, the composite free flaps have been applied for 3 cases of hemi orbito-facial defect, with better results than in previous cases. Our technique for the flap application in a representative case is illustrated.
Head and Neck Neoplasms↗
Cytochrome P450 2C9 catalyzes indomethacin O-demethylation in human liver microsomes.
Indomethacin is a widely used nonsteroidal anti-inflammatory drug. We studied the human cytochrome P450 (CYP) isoform responsible for indomethacin O-demethylation, the major metabolic pathway for indomethacin. For indomethacin O-demethylase activities, the KM value was 34.6 +/- 5.4 muM and the Vmax value was 14.1 +/- 3.9 pmol/mg/min in human liver microsomes (N = 4). Indomethacin O-demethylase activity in human liver microsomes was competitively inhibited by sulfaphenazole, (S)-warfarin, and tolbutamide and was not affected by alpha-naphthoflavone, (S)-mephenytoin, or erythromycin. Indomethacin O-demethylase activities in microsomes from nine human livers were significantly correlated with tolbutamide hydroxylase activities (r = 0.750, p < 0.05) and not with (S)-mephenytoin 4'-hydroxylase activities. When the capacity for indomethacin O-demethylation in microsomes of B lymphoblastoid cells expressing human CYPs was investigated at an indomethacin concentration of 5 microM, cDNA-expressed CYP2C9 exhibited 6-fold greater activity than did CYP2C19. At an indomethacin concentration of 50 microM, cDNA-expressed CYP1A2 and CYP2D6 also exhibited slight activities. The KM values were 9.9 +/- 1.2 and 117.1 +/- 13.8 microM and the Vmax values were 0.33 +/- 0.05 and 0.24 +/- 0.04 pmol/min/pmol CYP in microsomes with cDNA-expressed CYP2C9 and CYP2C19, respectively (N = 4). Considering the 16-fold higher intrinsic clearance of CYP2C9, compared with that of CYP2C19, and these expression levels in human livers, the contribution of CYP2C19 to indomethacin O-demethylation was considered to be negligible. Indomethacin appears to be O-demethylated exclusively by CYP2C9 in humans.
Alkylation↗
[The effect of matrix metalloproteinase inhibitor on pseudomonal proteinases].
We examined the effect of CS-610, a newly developed matrix metalloproteinase (MMP) inhibitor, on pseudomonal proteinase in vitro. Alkaline proteinase (1143-4977 unit/ml Type I collagenase equivalent) and elastase (13.6-22.6 unit/ml Type I collagenase equivalent) were obtained from strains of P. aeruginosa of IID-1117, IID-1030 and IID-1130. Zymographic analysis of cultured broth of P. aeruginosa demonstrated that CS-610 inhibited alkaline proteinase with an IC50 (50% inhibition concentration) of 1.06-29.0 (x 10(-8)M) and elastase with an IC50 of 1.0-33.3 (x 10(-8)M). CS-610 is a potent inhibitor of pseudomonal proteinases.
Dose-Response Relationship, Drug↗
Pentavalent technetium-99m-dimercaptosuccinic acid scintigraphy in renal osteodystrophy.
Pentavalent 99mTc-dimercaptosuccinic acid (DMSA) scintigraphy and 99mTc-hydroxymethylene diphosphonate (HMDP) bone scan were performed in one patient with renal osteodystrophy (ROD) before and after vitamin D3 pulse therapy. The bone scan showed diffusely increased tracer uptake in the whole skeleton, and no change of tracer distribution was noted before or after vitamin D3 pulse therapy. However, 99mTc(V)-DMSA scintigraphy revealed diffusely increased tracer uptake in the whole skeleton before therapy, and markedly decreased tracer uptake in the bones was seen at 5 mo after therapy. Increased uptake of 99mTc(V)-DMSA was observed at 7 mo after therapy, which reflected the laboratory findings. Technetium-99m-(V)-DMSA scintigraphy appeared to be more sensitive than the conventional 99mTc-HMDP bone scan in assessing the characteristics and therapeutic effect of bone disease in ROD.
Adult↗
Enhancement of fibrinolysis by plactins: structure-activity relationship and effects in human U937 cells and in mice.
Plactin D, a cyclic pentapeptide [cyclo(-D-Val-L-Leu-D-Leu-L-Phe-D-Arg-)] produced by a fungal strain, enhances fibrinolytic activity (6). The present study deals with the structure-activity relationship of plactins and their effects in U937 cells and mice. The results obtained from 50 plactin D analogues with a single amino acid substitution demonstrated that the following substitutions were detrimental: the enantiomer for each of the five residues; a polar, an acidic or a basic residue for D-Val, L-Leu, D-Leu or L-Phe; a polar, a hydrophobic or an acidic residue for D-Arg. On the other hand, a compound with L-Leu or L-Val in place of L-Phe was seven times as active as plactin D. These results suggest an essential role of a sterically restricted arrangement of four hydrophobic residues and the adjacent basic residue. The enhancement of fibrinolysis was dependent on plasma, ranging from 2- to 3-fold when U937 cells were incubated with 15-30 microM plactin D in the presence of 6-50% plasma, while no elevation was observed when cells were incubated in the absence of plasma. Plasminogen alone could not substitute for plasma. The plactin D effect was totally abolished by anti-urokinase IgG but not by anti-tissue plasminogen activator IgG. Plactin D caused a plasma-dependent, transient increase in the cellular urokinase activity. This urokinase activation may have accounted for the increased fibrinolytic activity of plactin D-treated U937 cells. Homogenates of the lung obtained from mice 0.5 to 2 h after intravenous plactin D (5 mg/kg) showed 2- to 3-fold increased levels of fibrinolytic activity, while activities of the brain, heart, liver, spleen, kidney and aorta were not significantly affected. In conclusion, plactin D enhances fibrinolysis both in cultured mammalian cells and in experimental animals.
Animals↗
Dispensability of p53 degradation for tumorigenicity and decreased serum requirement of human papillomavirus type 16 E6.
Certain types of human papillomavirus (HPV), such as types 16 and 18, are etiological agents for carcinogenesis of the uterine cervix. These HPVs have two oncogenes, E6 and E7, that have transforming activities in established murine cells. Tumorigenicity and decreased serum requirement for cell growth are conferred by the E6 gene, whereas anchorage-independent growth is mainly governed by the E7 gene. To understand the mechanism of cellular transformation by the HPV16 E6 gene, we examined three mutant E6 proteins defective for p53 binding, p53 degradation, or transactivation of the adenovirus E2 promoter for the ability to induce tumorigenicity and decreased serum requirement. The results showed that tumorigenicity and decreased serum requirement were associated with the ability of E6 to bind to p53, although the subsequent degradation of p53 was not required for these functions.
Animals↗
Sacral perineurial cyst with ossification of the arachnoid membrane.
A case of sacral perineurial cyst with ossification of the arachnoid membrane discovered intraoperatively is reported. We are not aware of any similar cases in the literature.
Arachnoid↗
Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent.
UNLABELLED: Iodine-123-alpha-methyl tyrosine has proven to be a promising SPECT agent for imaging amino acid uptake in tumors. We developed L-[3-(18)F]-alpha-methyl tyrosine (FMT) for PET studies. The aim of this study was to investigate its potential use as a tumor-detecting agent by using tumor-bearing mice. METHODS: We investigated the biodistribution in normal BALB/C mice and BALB/cA nude mice bearing human rectal cancer cell line (LS180) until 120 min postinjection. FMT tumor uptake at 60 min postinjection in mice with LS180 rectal cancer, RPM11788 B-cell lymphoma and MCF7 mammary cell carcinoma was assessed, and the results were compared with 18F-fluoro-2-deoxy-D-glucose (FDG) tumor uptake. The effect of competitive inhibition of large neutral amino acid transport system using unlabeled L-alanine was also investigated. RESULTS: The amount of FMT in blood fell to 1.05%ID/20 g at 60 min postinjection, whereas that in the pancreas was 15.2%ID/20 g, resulting in a high pancreas-to-blood ratio of 14.5. In other organs, initial uptake peaked at 5 min postinjection and then declined with time. In LS180 tumor-bearing mice, peak FMT uptake in tumor was observed at 60 min postinjection. Tumor-to-blood and tumor-to-muscle ratios ranged from 1.60 to 2.94 and from 2.79 to 3.25 over the 120-min observation period. Tumor uptake of FMT was clearly reduced by inhibition of the amino acid transport system. In mice with LS180 and MCF7 tumors, FMT tumor uptake at 60 min postinjection was significantly higher than FDG tumor uptake, whereas in RPM11788 lymphoma, uptake of FDG was significantly higher than FMT tumor uptake. Tumor-to-blood ratios of FMT in mice with LS180, RPMI1788 and MCF7 tumor at 60 min postinjection were 1.82, 5.88 and 3.56, respectively. CONCLUSION: FMT, like other fluorinated amino acids, may become a promising tumor-detecting agent for PET, assuming that efficient methods of radiosynthesis are developed.
Amino Acids↗
[Estimation of integral value of input function for the quantification of cerebral blood flow with 123I-IMP using one-point arterial blood sampling].
Cerebral blood flow (CBF) has been measured using a microsphere model with octanol-extracted radioactivity counts (integral value of input function). We developed a new method estimating the integral value of input function. First, we fitted the whole brain time-activity curves early after intravenous injection of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) by the least-squares method. Second, we differentiated this equation. Third, we calibrated it using octanol-extracted radioactivity counts of the arterial blood sampled at 5 min. Finally, we integrated it. A significant correlation was found between the integral values obtained using a new method and those obtained using the continuous arterial blood sampling data (y = 1.048x-1206, r = 0.984). The errors between the CBF values obtained using a new method and those obtained using the 5-min continuous arterial blood sampling was 6.88 +/- 4.78%. Measurement of integral values of the input function using a new method with one-point arterial blood sampling is less invasive and convenient, and is not influenced by cardiopulmonary disease or smoking. Therefore, it would be useful for the routine measurement of CBF.
Amphetamines↗
[Simplified method to quantitate regional cerebral blood flow by 123I-IMP microsphere model: validity of input counts by using the whole brain time-activity curve and one point arterial blood sampling].
We developed a new microsphere method using 123I-IMP in which arterial blood is collected at one time point early after 123I-IMP injection instead of conventional continuous arterial blood sampling, and the input count is estimated using a whole brain time-activity curve until that time point. The differential curve dCb(t)/dt of the brain time-activity curve Cb(t) early after 123I-IMP injection (when the microsphere model is established) approximates the arterial time-activity curve Ca(t) as an input function. The input count as the integral value of Ca(t) at 0-5 min was estimated using the 50 min whole brain activity Cb(5 min) and the differential value dCb(5 min/dt and the 5-min octanol-extracted count of arterial samples obtained at one time point Ca(5 min). The input counts calculated by this method were very closely correlated with measurement values obtained by continuous arterial sampling. This method is more convenient and less invasive than the continuous arterial sampling method.
Amphetamines↗
[Abnormal hemoglobinopathy (HbE) diagnosed from microcytic hypochromic red blood cells in a 31 year-old Bangladeshian male].
Microcytic hypochromic red blood cells (RBC) were discovered in a 31 year-old Bangladeshi man. Additional laboratory data revealed only slight elevations of LDH and transaminase activities. The patient was clinically asymptomatic and showed no signs of anemia. On this basis, along with biochemical genetic analysis of hemoglobin, a diagnosis of hemoglobinopathy (HbE) was made. HbE is common in southeast Asia with over 30% of the population affected. Most people are asymptomatic. In northern Asia, including Japan, HbE is found in only 0.001% of the population. With ther recent influx of southeast Asians to Japan, care must be taken not to overlook the diagnosis of hemoglobinopathies.
Adult↗
Loss of heterozygosity on chromosome 18q in cohesive-type gastric cancer is associated with tumor progression and poor prognosis.
Although loss of heterozygosity (LOH) on chromosome 18q is frequently found in gastric cancer, the clinical significance of this abnormality has not been well documented. We examined LOH on chromosome 18q22-23 in DNA extracted from the tissues of gastric cancer patients using the PCR-based dinucleotide repeat assay with two microsatellite markers, D18S61 and D18S58. We investigated LOH in 100 samples of DNA extracted from formalin-fixed, paraffin-embedded tissues of cohesive-type gastric cancer patients operated on between 1984 and 1993. Thirty-two of 83 informative cases (39%) showed LOH on chromosome 18q22-23 at one or two loci. The LOH correlated significantly with serosal invasion of the tumor (P = 0.004) and hematogenous recurrence (P = 0.035). In 60 cases who were cured, the 5-year survival rate in patients with LOH (54%) was lower than that in patients without LOH (81%; P = 0.019). These results suggest that 18q22-23 LOH in cohesive gastric cancer is associated with tumor progression and a patient's poor prognosis.
Aged↗