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Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 217 records · Page 12Linked to original sources

Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors.

PURPOSE: To investigate the histologic bases of rim enhancement of breast masses demonstrated on dynamic contrast material-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: Dynamic MR images of breast lesions (invasive carcinoma, n = 29; other, n = 6) in 35 women were reviewed. In each patient, subtraction images of the dynamic contrast-enhanced study were obtained, and early and delayed rim enhancement and delayed internal enhancement were evaluated. The MR findings were correlated with the ratio of microvessel density of the peripheral to the central portion of the lesion, fibrosis, and other histologic features, including expression of vascular endothelial growth factor (VEGF) and transforming growth factor ss1. RESULTS: Early rim enhancement was observed in 29% and delayed rim enhancement was noted in 60% of all patients. Small cancer nests, a high ratio of peripheral-to-central microvessel density, peripheral VEGF expression, and a low ratio of peripheral-to-central fibrosis were correlated with early rim enhancement. Delayed rim enhancement was correlated with a high degree of fibrosis and inflammatory changes. Delayed internal enhancement was correlated with a high degree of fibrosis. CONCLUSION: Rim enhancement of breast lesions at MR imaging is due to a combination of angiogenesis, distribution and degree of fibrosis, expression pattern of VEGF, and various histologic features.

Adenocarcinoma, Mucinous↗

Differential effect of antiallergic drugs on IgE-mediated cutaneous reaction in passively sensitized mice.

We investigated the effect of several antiallergic agents on murine IgE-mediated biphasic cutaneous reaction. Mice were passively sensitized by an intravenous injection of monoclonal anti-dinitrophenol (anti-DNP) IgE antibody. Skin reaction was elicited by an epicutaneous challenge of dinitrofluorobenzene (DNFB) and occurred biphasically with immediate-phase response (IPR) and late-phase response (LPR) at 1 and 24 h, respectively. Classical histamine H1 receptor antagonists and some chemical mediator-release inhibitors, such as diphenhydramine and terfenadine, inhibited IPR, but not LPR. In contrast, leukotriene B(4) (LTB(4)) receptor antagonist (ONO-4057) inhibited LPR only. Antagonists for LTC(4), D(4), E(4) receptor (ONO-1078) and platelet-activating factor (PAF) receptor (Y-24180) significantly inhibited both IPR and LPR, similarly to prednisolone. We recently found that a third-phase inflammatory reaction with marked infiltration of eosinophils (named very-late-phase response; vLPR), which is supposed to be a more important reaction in allergic diseases, was induced, peaking at day 8 following IPR and LPR in this model. The effect of these drugs on the triphasic skin reaction can be scored based on efficacy against IPR / LPR / vLPR; +/+/+ (prednisolone, a PAF receptor antagonist Y-24180, cyclosporin A and FK-506), +/-/- (diphenhydramine), +/+/- (azelastine and LT receptor antagonist ONO-1078), and -/+/+ (an LTB(4) receptor antagonist ONO-4057). Thus the inhibitory effect on vLPR as well as LPR may relate to the inhibition of eosinophil function mediated by LTB(4) and PAF and/or T cells. These findings may provide the basis for a treatment modality using various antiallergic agents in allergic disease.

Animals↗

Clinical correlates and prognostic significance of six-minute walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing.

The six-minute walk test is a submaximal exercise test that can be performed even by a patient with heart failure not tolerating maximal exercise testing. To elucidate the clinical significance and prognostic value of the six-minute walk test in patients with primary pulmonary hypertension (PPH), we sought (1) to assess the relation between distance walked during the six-minute walk test and exercise capacity determined by maximal cardiopulmonary exercise testing, and (2) to investigate the prognostic value of the six-minute walk test in comparison with other noninvasive parameters. The six-minute walk test was performed in 43 patients with PPH, together with echocardiography, right heart catheterization, and measurement of plasma epinephrine and norepinephrine. Symptom-limited cardiopulmonary exercise testing was performed in a subsample of patients (n = 27). Distance walked in 6 min was significantly shorter in patients with PPH than in age- and sex-matched healthy subjects (297 +/- 188 versus 655 +/- 91 m, p < 0. 001). The distance significantly decreased in proportion to the severity of New York Heart Association functional class. The distance walked correlated modestly with baseline cardiac output (r = 0.48, p < 0.05) and total pulmonary resistance (r = -0.49, p < 0. 05), but not significantly with mean pulmonary arterial pressure. In contrast, the distance walked correlated strongly with peak V O(2) (r = 0.70, p < 0.001), oxygen pulse (r = 0.57, p < 0.01), and V E-VCO(2) slope (r = -0.66, p < 0.001) determined by cardiopulmonary exercise testing. During a mean follow-up period of 21 +/- 16 mo, 12 patients died of cardiopulmonary causes. Among noninvasive parameters including clinical, echocardiographic, and neurohumoral parameters, only the distance walked in 6 min was independently related to mortality in PPH by multivariate analysis. Patients walking < 332 m had a significantly lower survival rate than those walking farther, assessed by Kaplan-Meier survival curves (log-rank test, p < 0.01). These results suggest that the six-minute walk test, a submaximal exercise test, reflects exercise capacity determined by maximal cardiopulmonary exercise testing in patients with PPH, and it is the distance walked in 6 min that has a strong, independent association with mortality.

Adolescent↗

Requirement of thyrotropin-releasing hormone for the postnatal functions of pituitary thyrotrophs: ontogeny study of congenital tertiary hypothyroidism in mice.

We recently reported that TRH-deficient mice showed characteristic tertiary hypothyroidism. In the present study, we investigated how this tertiary hypothyroidism occurred particularly in pre- and postnatal stages. Immunohistochemical analysis revealed a number of TSH-immunopositive cells in the TRH-/- pituitary on embryonic day 17.5 and at birth. The mutant pituitary at birth in pups born from TRH-deficient dams also showed no apparent morphological changes, indicating no requirement of either maternal or embryonic TRH for the development of pituitary thyrotrophs. In contrast, apparent decreases in number and level of staining of TSH-immunopositive cells were observed after postnatal day 10 in mutant pituitary. Similar decreases were observed in the 8-week-old mutant pituitary, while no apparent changes were observed in other pituitary hormone-producing cells, and prolonged TRH administration completely reversed this effect. Consistent with these morphological results, TRH-/- mice showed normal thyroid hormone levels at birth, but the subsequent postnatal increase was depressed, resulting in hypothyroidism. As expected, TSH content in the TRH-/- pituitary showed a marked reduction to only 40% of that in the wild type. Despite hypothyroidism in the mutant mice, both the pituitary TSHbeta and alpha mRNA levels were lower than those of the wild-type pituitary. These phenotypic changes were specific to the pituitary thyrotrophs. These findings indicated that 1) TRH is essential only for the postnatal maintenance of the normal function of pituitary thyrotrophs, including the normal feedback regulation of the TSH gene by thyroid hormone; 2) neither maternal nor embryonic TRH is required for normal development of the fetal pituitary thyrotroph; and 3) TRH-deficient mice do not exhibit hypothyroidism at birth. Moreover, reflecting its name, TRH has more critical effects on the pituitary thyrotrophs than on other pituitary hormone-producing cells.

Animals↗

Sulfotransferases in a human colon carcinoma cell line, Caco-2.

We investigated the expression of sulfotransferases (STs) in the human colon carcinoma cell line, Caco-2, which is widely used as a human intestine model for orally administered drugs. By reverse transcription-polymerase chain reaction (RT-PCR), we could detect mRNA expressions of phenol STs (P-ST), hydroxysteroid ST (HS-ST) and estrogen ST (E-ST). Treatment with 1,25-dihydroxyvitamine D3, which induces CYP3A4 expression in Caco-2 cells, did not affect the ST expression of the cells. We detected significant P-ST activity toward 2-naphthol and dopamine in the cell extract. We also observed detectable HS-ST activity toward dehydroepiandrosterone (DHEA), but no E-ST activity toward beta-estradiol was observed in the extract. Analyses by RT-PCR and separation of P-ST activities on ion-exchange column chromatography showed that the thermolabile monoamine phenol sulfotransferase (M-PST) is dominant in Caco-2 cells.

Arylsulfotransferase↗

[The public health significance of the measurement of cytokines in serum].

As variable functions of cytokines have been proved in recent years, cytokine levels in biological fluids such as serum, plasma, and synovial fluid of patients with every kind of disease have been enthusiastically measured. As a result, many studies have shown an increase or decrease in the production of cytokines or abnormal cytokine levels in biological fluids. However, the relationship between the abnormal levels of cytokines and the intensity of the clinical symptoms or the prognosis remains unclear. The significance for the measurement of cytokines depends on whether it should be valid for detecting a preclinical status such as AST or ALT used for health checks or for disease screening such as some tumor markers. The purpose of this study is to know whether or not some cytokine levels in serum could be biomarkers for preventive purposes. Serum cytokine levels (IL-4, 6, 8, 12, and IFN-gamma) were measured in three different types of cohorts (nursery school infants, manufacturing workers and middle and old aged women) with chemiluminescence ELISA. The results showed no differences with atopic status in infants, pulmonary fibrosis in workers or with the decrease in bone stiffness, these results are mainly due to a great inter-individual variability of serum cytokine levels. This study concludes that serum cytokine levels are inappropriate as biomarkers for preventive purposes. However, a further detailed evaluation in healthy people with high serum cytokine levels may be necessary.

Adolescent↗

Ocular fundus abnormalities detected by fluorescein and indocyanine green angiography in the Royal College of Surgeons dystrophic rat.

The ocular fundi of the Royal College of Surgeons (RCS) dystrophic rats were examined by conventional fundus photography, fluorescein angiography (FA) and indocyanine green angiography (IA). In the fundus, a reddish colored background was observed in the RCS dystrophic rats at 3 weeks of age. At 9 weeks of age, the background had changed to pale in color. In FA, the RCS dystrophic rats at 3 week of age demonstrated background fluorescence with homogeneous brightness. Fluorescent dye leakage was observed in the late phase of the postinjection period at 9 weeks of age. In IA, the RCS dystrophic rats at 3 weeks of age had background fluorescence with homogeneous brightness, and at 5 weeks of age, spots of hyperfluorescence were scattered over the dark background. At 7 weeks of age, numerous delimited, irregular round spots of hyperfluorescence appeared over the dark background. Such hyperfluorescent lesions had further increased in number and size in the RCS dystrophic rats at 9 weeks of age. In this way, ocular findings related to abnormalities in the retinal pigment epithelium and choroid in the RCS dystrophic rat were demonstrated by fundus photography, fluorescein angiography and indocyanine green angiography.

Aging↗

Relationship between p53 gene mutation and protein expression: clinical significance in transitional cell carcinoma of the bladder.

Although the mutated p53 gene has been postulated to induce immunohistochemically-detectable p53 protein, reports regarding the relationship between p53 mutation and p53 protein expression have been contradictory. This study investigated the relationship between p53 mutations and p53 expression and their clinical significance for patients with transitional cell carcinoma of the bladder. Eighty-seven transitional cell carcinoma of the bladder were analyzed by immunohistochemistry (IHC) for p53 nuclear accumulation, and the results compared to mutations detected in the p53 gene evaluated by polymerase chain reaction single-strand conformation polymorphism (SSCP) and DNA sequence analysis. By p53 IHC analysis, positive p53 staining was observed in 50 (57.5%) of the 87 tumors. The specificity of IHC, defined as a percentage of IHC negative (<20%) tumors among tumors without mutation, was 94.6%. Despite the good concordance between p53 mutation and p53 protein expression (p<0.0001), 48.0% (24/50) of the tumors showed p53 overexpression without mutation, and 2 (5.4%) tumors with mutation showed no p53 immunoreactivity. Patients with higher grade (grade 3), stage (stages pT2-4), and p53 mutations had a poorer prognosis by Kaplan-Meier survival analysis. A Cox univariate analysis found that grading (hazard ratio 3.139; p=0.002), staging (hazard ratio 3.832; p=0.0005) and p53 mutation (hazard ratio 2.498; p=0.013) were significant variables in these patients, but no variable was independently associated with an increased survival of bladder carcinoma by multivariate analysis. We found that a 20% cut-off level of p53 overexpression showed the highest correlation with prognosis and p53 mutation, however, p53 overexpression and mutation were not superior to staging as prognostic markers. These data suggest that careful assessment of the TNM staging system remains the most reliable predictive indicator of survival for patients with transitional cell carcinoma of the bladder.

Adult↗

Infrequent widespread microsatellite instability in hepatocellular carcinomas.

Widespread or high-frequency microsatellite instability (MSI) due to the defective DNA mismatch repair (MMR) occurs in the majority of hereditary non-polyposis colorectal cancer and a subset of sporadic malignant tumors. The incidence of MSI and underlying DNA MMR defects have been well characterized in gastrointestinal carcinogenesis, but not in hepatocarcinogenesis. To address the issue, we analyzed 55 Japanese hepatocellular carcinomas using several indicators of DNA MMR defects, such as microsatellite analysis, loss of heterozygosity (LOH) and mutation analysis of MMR genes, methylation of hMLH1 promoter, and frameshift mutations of mononucleotide repeat sequences within possible target genes. Mutation of beta2-microglobulin gene, which is presumably involved in MSI-positive tumor cell escape from immune surveillance was also examined. Some of these analyses were also carried out in 9 human liver cancer cell lines. None of the 3 quasi-monomorphic mononucleotide markers sensitive for MSI, BAT26, BAT25, and BAT34C4 presented shortened unstable alleles in any of the carcinoma, cirrhosis, chronic hepatitis tissues, or cell lines. LOH at MMR genes was infrequent (4.4 approximately 7.1%), and no mutations were detected. Neither hMLH1 hypermethylation nor frameshift mutation in the target genes was detected. No mutations were found in beta2-microglobulin. Widespread MSI due to the defective DNA MMR appears to play little if any part in Japanese hepatocarcinogenesis.

Adult↗

[Propofol potentiates the neuromuscular blocking effects of vecuronium in man].

The possible interaction between vecuronium and propofol has been investigated in 40 healthy (ASA I-II) patients. They were randomly allocated to two groups according to the method of anesthesia; continuous propofol infusion group (propofol) and droperidol and fentanyl group (control). The electromyographic response of abductor digiti minimi was monitored at 20-s interval after train-of-four stimulations of the ulnar nerve. The ED50 and ED95 (dose required to produce a 50% and 95% depression of twitch tension, respectively,) of vecuronium in the propofol group (n = 20) were 29.4 +/- 0.5 and 56.6 +/- 2.1 micrograms.kg-1 (mean +/- SEM), and in the control group (n = 20), 36.7 +/- 1.8 and 73.6 +/- 5.2 micrograms.kg-1, respectively. Under propofol anesthesia, the cumulative dose-response curves of vecuronium were shifted to the left when compared with control ED50 and the slope showed that propofol had potentiated the action of vecuronium.

Adult↗

[Halothane anesthesia decreases the level of interstitial striatal dopamine of awake freely moving rats in an in vivo microdialysis study].

We investigated the effect of halothane on the level of interstitial dopamine of in vivo awake, free moving rats brain striatum using microdialysis techniques. Rats were implanted a microdialysis probe to right striatum of the brain and administered 1.5% of halothane (approximately 1.2 MAC) for 1 or 2 hours, and dialysates from the probe were determined every 20 minutes. Halothane anesthesia reduced the amount of dopamine derived from dialysate, and after discontinuation of halothane and at emergence from anesthesia, the level of dopamine was increased. The levels of metabolites of dopamine during anesthesia were increased lineally in a time dependent manner. We hypothesized that halothane might increase the rate of re-uptake of dopamine at nerve endings and decreased level of interstitial dopamine is compensated by dopamine releases during anesthesia.

Anesthesia, Inhalation↗

[Investigations on the position and safety of Swan-Ganz catheters].

Swan-Ganz catheters (S-G catheter) may cause many complications. We measured floating distance (FD) of catheter tip with balloon inflation or deflation, and distal movement (DM) before and after the operation. FD and DM were significantly altered with 7 Fr. S-G catheters. These results suggest that careful observation is required in order to prevent unpredictable pulmonary artery perforation and infarction during the use of 7 Fr. S-G catheters.

Catheterization, Swan-Ganz↗

[The new law concerning the prevention of infectious diseases and medical care for patients of infections].

A new law concerning the prevention of infectious diseases and medical care for patients with infectious diseases was enacted on Oct 2, 1998 and became effective on April 1, 1999. In the new infection control law, all infectious diseases are included as the targets of national epidemiological surveillance and are classified into new categories 1 through 4, depending on their contagiousness and severity. Under this new law, the national epidemiological surveillance of infectious diseases is defined as one of the main objects. This new law also specified the provision of a medical care supply system including assigned hospitals and medical fees.

Communicable Disease Control↗

Photodynamic therapy with the phthalocyanine photosensitizer Pc 4 of SW480 human colon cancer xenografts in athymic mice.

Photodynamic therapy (PDT) using the silicon phthalocyanine photosensitizer Pc 4 [HOSiPcOSi(CH3)2(CH2)3N-(CH3)2] is an oxidative stress associated with induction of apoptosis in various cell types. We assessed the effectiveness of Pc 4-PDT on SW480 colon cancer xenografts grown in athymic nude mice. Animals bearing xenografts were treated with 1 mg/kg body weight Pc 4 and 48 h later were irradiated with 150 J/cm2 672-nm light from a diode laser delivered at 150 mW/cm2. Biochemical studies were performed in xenografts resected at various time points up to 26 h after Pc 4-PDT treatment, whereas tumor size was evaluated over a 4-week period in parallel experiments. In the tumors resected for biochemical studies, apoptosis was visualized by activation of caspase-9 and caspase-3 and a gradual increase in the cleavage of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) to a maximum of approximately 60% of the total PARP present at approximately 26 h. At that time all Pc 4-PDT-treated tumors had regressed significantly. Two signaling responses that have previously been shown to be associated with Pc 4-PDT-induced apoptosis in cultured cells, p38 mitogen-activated protein kinase and p21/WAF1/Cip1, were examined. A marked increase in phosphorylation of p38 was observed within 1 h after Pc 4-PDT without changes in levels of the p38 protein. Levels of p21 were not altered in the xenografts in correspondence with the presence of mutant p53 in SW480 cells. Evaluation of tumor size showed that tumor growth resumed after a delay of 9-15 days. Our results suggest that: (a) Pc 4-PDT is effective in the treatment of SW480 human colon cancer xenografts independent of p53 status; (b) PARP cleavage may be mediated by caspase-9 and caspase-3 activation in the Pc 4-PDT-treated tumors; and (c) p38 phosphorylation may be a trigger of apoptosis in response to PDT in vivo in this tumor model.

Animals↗

[Changes of latency and amplitude of short latency somatosensory evoked potentials during slow induction of anesthesia with sevoflurane].

In the present study, changes of latency and amplitude of short latency somatosensory evoked potentials (SSEPs) were evaluated continuously during slow induction of anesthesia from sevoflurane awake to deep levels of anesthesia in eight scheduled surgical patients. Not consistent with other previous investigations, the latency of N20 was significantly shortened with sevoflurane after 25 minutes from the beginning of inhalation compared with the awake control levels. No increase of latency was observed. The amplitudes of N20 were decreased with sevoflurane anesthesia in relation to duration of anesthesia. These results suggest that sevoflurane alone might have no marked pharmacological properties to change the latency of SSEPs even in the deep level of anesthesia.

Anesthesia, Inhalation↗

Phenacetin deacetylase activity in human liver microsomes: distribution, kinetics, and chemical inhibition and stimulation.

Microsomal and cytosolic phenacetin deacetylase activities were examined in human liver and kidneys. Kinetic properties of the activities were also studied in human liver microsomes. Phenacetin deacetylase activity was predominantly localized in the liver microsomal fraction. The specific activities of phenacetin deacetylation in liver cytosol and in kidney microsomes and cytosol were all less than 5% of that in liver microsomes. In human liver microsomes, Eadie-Hofstee plots for phenacetin deacetylation were monophasic, indicating a single-enzyme catalytic reaction. The Michaelis-Menten parameters, K(m) and V(max), for the deacetylation were 4.7 mM and 5.54 nmol/min/mg of protein, respectively. The intrinsic clearance, calculated as V(max)/K(m), was 1.18 microl/min/mg of protein. Although the organophosphate bis(4-nitrophenyl)phosphoric acid markedly inhibited the reaction in human liver microsomes, the activity has a tolerance to the treatment of phenylmethylsulfonyl fluoride, a serine hydrolase inhibitor. Prazosin, a peripheral alpha(1)-adrenergic antagonist, noncompetitively inhibited the phenacetin deacetylation with a K(i) value of 19.0 microM. Flutamide, a nonsteroidal androgen receptor antagonist, stimulated the activity by up to 349%. This increase was accompanied by a decrease in the K(m) value and no change in the V(max) value, resulting in an increase in the intrinsic clearance by up to 700% of the control. These results suggest that the phenacetin deacetylase localized in human liver microsomes has not only a catalytic site but also a negative and/or positive modulation site or sites.

Carboxylic Ester Hydrolases↗