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Biomedical subjects

T Satoh

Publications and source records attributed to T Satoh.

At least 127 records · Page 7Linked to original sources

Detection of hypermethylation of the p16(INK4A) gene promoter in chronic hepatitis and cirrhosis associated with hepatitis B or C virus.

BACKGROUND/AIM: Inactivation of the p16(INK4A) (p16) tumour suppressor gene by promoter region hypermethylation has been demonstrated not only in many types of tumours, including hepatocellular carcinoma (HCC), but also in early preneoplastic lesions in the lung, colon, oesophagus, and pancreas. The aim of this study was to examine the methylation status of the p16 promoter in pre- and/or non-neoplastic liver diseases. PATIENTS/SUBJECTS/METHODS: The methylation status of p16 was evaluated in 22 HCC, 17 cirrhosis, 17 chronic hepatitis, nine primary biliary cirrhosis (PBC), eight autoimmune hepatitis, seven drug induced liver disease, six fatty liver, and three normal liver tissues using methylation specific polymerase chain reaction (MSP). p16 protein expression was also examined by immunohistochemical staining. RESULTS: Methylation of the p16 promoter was detected in HCC (72.7%, 16/22) and also in cirrhosis (29.4%, 5/17) and chronic hepatitis (23.5%, 4/17), all of which were positive for hepatitis B or C virus infections. Methylation was not detected in any of the other samples. All methylation positive HCC, cirrhosis, and chronic hepatitis samples showed loss of p16 expression, and a significant correlation was found between methylation and loss of expression. Analysis of serial samples from individual patients with methylation positive HCC revealed that loss of p16 expression with promoter methylation occurred in 18 of 20 patients at the stage of chronic hepatitis without clinically detectable carcinoma. CONCLUSIONS: Our results suggest that methylation of the p16 promoter and the resulting loss of p16 protein expression are early events in a subset of hepatocarcinogenesis and that their detection is useful in the follow up of patients with a high risk of developing HCC, such as those with hepatitis B or C viral infections.

Adult↗

Acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension.

OBJECTIVE: To assess acute and chronic effects of surgical thromboendarterectomy on exercise capacity and ventilatory efficiency in patients with chronic thromboembolic pulmonary hypertension (CTEPH). DESIGN: Cardiopulmonary exercise testing was performed in 20 patients with CTEPH before thromboendarterectomy (baseline), one month after (early phase), and four months after (late phase). Peak oxygen uptake (peak VO(2)) and the ventilatory response to carbon dioxide production (VE-VCO(2) slope) were measured for assessment of exercise capacity and ventilatory efficiency. Right heart catheterisation was performed in all patients before and one month after surgery. RESULTS: Baseline peak VO(2) decreased and VE-VCO(2) slope increased along with the increase in pulmonary vascular resistance in patients with CTEPH. After thromboendarterectomy, the VE-VCO(2) slope decreased greatly from baseline to the early phase (mean (SD), 50 (9) to 37 (7), p < 0.05) and reached a steady level thereafter. In contrast, a continued increase in peak VO(2) was noted from the early to the late phase (16.9 (4.1) to 21.1 (5.0) ml/kg/min, p < 0.05). The decrease in the VE-VCO(2) slope from baseline to the early phase, but not the increase in peak VO(2), correlated strongly with the decrease in pulmonary vascular resistance after surgery (r = 0.75, p < 0.01). CONCLUSIONS: Thromboendarterectomy may cause an immediate improvement in ventilatory efficiency, possibly through its beneficial haemodynamic effects. In contrast, exercise capacity may continue to improve towards the late phase, reflecting peripheral adaptation to exercise.

Acute Disease↗

Human immunodeficiency virus type 1 Tat binding protein-1 is a transcriptional coactivator specific for TR.

The DNA-binding domain of nuclear hormone receptors functions as an interaction interface for other transcription factors. Using the DNA-binding domain of TRbeta1 as bait in the yeast two-hybrid system, we cloned the Tat binding protein-1 that was originally isolated as a protein binding to the human immunodeficiency virus type 1 Tat transactivator. Tat binding protein-1 has subsequently been identified as a member of the ATPase family and a component of the 26S proteasome. Tat binding protein-1 interacted with the DNA-binding domain but not with the ligand binding domain of TR in vivo and in vitro. TR bound to the amino-terminal portion of Tat binding protein-1 that contains a leucine zipper-like structure. In mammalian cells, Tat binding protein-1 potentiated the ligand-dependent transactivation by TRbeta1 and TRalpha1 via thyroid hormone response elements. Both the intact DNA-binding domain and activation function-2 of the TR were required for the transcriptional enhancement in the presence of Tat binding protein-1. Tat binding protein-1 did not augment the transactivation function of the RAR, RXR, PPARgamma, or ER. The intrinsic activation domain in Tat binding protein-1 resided within the carboxyl-terminal conserved ATPase domain, and a mutation of a putative ATP binding motif but not a helicase motif in the carboxyl-terminal conserved ATPase domain abolished the activation function. Tat binding protein-1 synergistically activated the TR-mediated transcription with the steroid receptor coactivator 1, p120, and cAMP response element-binding protein, although Tat binding protein-1 did not directly interact with these coactivators in vitro. In contrast, the N-terminal portion of Tat binding protein-1 directly interacted in vitro and in vivo with the TR-interacting protein 1 possessing an ATPase activity that interacts with the activation function-2 of liganded TR. Collectively, Tat binding protein-1 might function as a novel DNA-binding domain-binding transcriptional coactivator specific for the TR probably in cooperation with other activation function-2-interacting cofactors such as TR-interacting protein 1.

ATPases Associated with Diverse Cellular Activitie↗

Wistar strain rats as the model for IgE antibody experiments.

The amount of plasma IgE antibody formed and its change over time were investigated by enzyme-linked immunosorbent assay (ELISA) in male and female Sprague-Dawley (SD), Donryu, and Wistar strain rats. IgE antibody formation was initiated by injecting a mixture of 2,4-dinitrophenylated ascaris extract (DNP-As) as antigen and killed Bordetella pertussis as adjuvant into the paws of the animals. The amount of IgE antibody formed was low on day 10 in both male and female SD (40-80 ng/ml) and Donryu (20-40 ng/ml) strain rats, and an increase in the amount was observed on day 20. The peak value of IgE antibody was observed day 10 in Wistar strain rats and was 130 and 200 ng/ml in the male and female rats, respectively. These results suggest that Wistar strain rats produce the most IgE antibody when DNP-As is used as antigen and they can serve as a model for allergic diseases.

2,4-Dinitrophenol↗

Antioxidative and 5-lipoxygenase inhibiting activities of novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives.

Novel bis(4-hydroxy-2,3,5-trimethylphenoxy)alkyl derivatives were synthesized and evaluations were made of their inhibiting action on Fe3+-ADP induced lipid peroxidation in rat liver microsome and reducing action on alpha,alpha-diphenyl-beta-picrilhydrazyl (DPPH), a stable radical, in addition to their inhibiting action on 5-lipoxygenase (5-LO), an enzyme that synthesizes leukotrienes. We performed a structure-activity correlation study on these derivatives. A strong Fe3+-ADP induced lipid peroxidation preventing activity was observed for the derivatives with an odd number of methylene groups including 1,3-bis(4-hydroxy-2,3,5-trimethylphenoxy)propane (3b) and 3a. No change in the DPPH reducing activity was found with change in the number of methylene groups. 5-LO inhibiting activity among the derivatives was the highest for 1,6-bis(4-hydroxy-2,3,5-trimethylphenoxy)hexane (3e). MM2 calculations were performed to find a stable steric structure for the derivatives, and 1,5-bis(4-hydroxy-2,3,5-trimethylphenoxy)pentane (3d) showed a strong activity in both antioxidative action and 5-LO inhibiting action.

Animals↗

Synthesis and physiological activity of novel tocopheryl glycosides.

Vitamin E glycosides were synthesized and enzymatic hydrolysis was examined for use as potential pro-drugs, however, the glycoside bond was found to be stable. On the other hand, among the glycosides synthesized, dl-alpha-tocopherylglucoside (6b) and dl-alpha-tocopherylmannoside (6c) showed strong inhibitory action on histamine release from mast cells. In addition, 6c also showed a suppressive action on IgE antibody formation. Thus, tocopheryl glycoside showed new properties compared to tocopherol (vitamin E). In particular, 6c was shown to be a novel lead compound with excellent manifold anti-allergic activity and anti-inflammatory activity.

Animals↗

Excessive ventilation after acute myocardial infarction and its improvement in 4 months.

The relationship between ventilation (VE) and CO2 output (VCO2) is fitted linearly. The steeper gradient implies excessive ventilation. Through an evaluation of the VE-VCO2 slopes, this study investigated whether patients with acute myocardial infarction (AMI) have excessive ventilation and whether it improved in 4 months. The VE-VCO2 slopes were determined in exercise tests at 1 and 4 months in 131 patients with AMI. Patients were divided into 3 groups according to the 1 month VE-VCO2 slope value: (i) normal (<30); (ii) intermediate (30-32); and (iii) excessive (>32). In the normal group (n=76), at 4 months, the slope decreased in 10, increased in 5 and remained unchanged in 61 patients; in the intermediate (n=31) group, 9, 2 and 20; and in the excessive (n=24) group, 15, 3 and 6, respectively, showing that the slope reduction was greater in the excessive group (p<0.01). The slope correlated with age and acute phase heart failure. The percent reduction of the slope did not correlate with these parameters. In conclusion, a substantial fraction of patients with AMI have excessive ventilation that improves in 4 months. The improvement is greater in patients with greater excessive ventilation but is not associated with an improvement in exercise capacity nor hemodynamics.

Acute Disease↗

Coronary heart disease mortality among men aged 35-44 years by prefecture in Japan in 1995-1999 compared with that among white men aged 35-44 by state in the United States in 1995-1998: vital statistics data in recent birth cohort.

The levels of risk factors for coronary heart disease (CHD) in men in the post World War II (WWII) birth cohort are almost similar between Japan and the USA, except for the considerably higher prevalence of cigarette smoking in Japan and the much higher prevalence of obesity in the USA. The present study evaluated the CHD mortality among men in the post WWII birth cohort by prefecture in Japan in 1995-1999 and then compared the data with those for white men in different states in the USA. There was a greater than 2-fold difference in CHD mortality among men aged 35-44 by prefecture in Japan: 5.3/100,000 in Kumamoto vs 12.6/100,000 in Tochigi. CHD mortality among men aged 35-44 in the top 3 prefectures in Japan is about half that of white men in the USA and is similar to that of white men in the lowest 3 states. The much lower CHD mortality in Japan does not appear to be caused by differences in the classification of causes of death and the results suggest that there may be strong and important protective factors that reduce the risk of CHD in Japan.

Adult↗

Effects of beta-casomorphins on neuronal survival in culture of embryonic chick dorsal root ganglion neurons.

We studied the effects of beta-casomorphins (beta-CMs, mu-acting opioid peptides from milk protein beta-casein) on survival of primary-cultured chick dorsal root ganglion neurons in the presence of nerve growth factor. Beta-CM-5 and beta-CM-7 had potent neuronal survival-promoting activities. Beta-CM-4 amide (morphiceptin) and des-Tyr'-beta-CM-7 also exhibited the similar promoting effects, although their effects were very weak. The promoting effect of beta-CM-5 was prevented by co-administration of naloxone, or pretreatment with pertussis toxin. These results suggest that the neuronal survival-promoting effects of beta-CMs might be mediated through opioid receptors coupled to G proteins.

Amino Acid Sequence↗

Mechanism of sodium load-induced hypertension in non-insulin dependent diabetes mellitus model rats: defective dopaminergic system to inhibit Na-K-ATPase activity in renal epithelial cells.

Obesity-related non-insulin dependent diabetes mellitus (NIDDM) is frequently accompanied by hypertension. The present study was designed to clarify this mechanism. We first determined the blood pressure in male Wistar fatty rats (WFR), one of the NIDDM model rats, and in Wistar lean rats (WLR) as the control, with a normal (0.7% NaCl) or high (7% NaCl) salt diet. We observed no difference in systolic and mean blood pressures between WFR and WLR. WFR, however, became extremely hypertensive as a result of ingesting the high salt diet. We next investigated the mechanism for sodium sensitivity in WFR. Although the urinary excretion of dopamine (DA), a potent natriuretic factor, which reflects the ability for renal DA production, was preserved in WFR, the sodium balance with the high salt diet was positive. Moreover, Na-K-ATPase activity in isolated proximal convoluted tubules (PCT) from WFR with a normal salt diet was significantly (p<0.05) higher than that from WLR. A high salt load produced a significant (p<0.05) decrease in Na-K-ATPase activity in WLR but not in WFR. Similarly, Na-K-ATPase activity in WLR with a normal salt diet was significantly (p<0.05) inhibited by DA (10(-5) M), but this was not true in WFR. Furthermore, urinary excretion of norepinephrine in WFR with a high salt diet was the highest among all the groups. These results indicate that WFR tend to develop salt-sensitive hypertension that could be caused by the excessive sodium retention occurring as the results of a defective dopaminergic system in the kidney that fails to inhibit Na-K-ATPase activity. Augmentation of the renal sympathetic nervous system may play some role in this setting.

Animals↗

In situ gene therapy for prostate cancer: immunomodulatory approaches.

The development of effective treatments for prostate cancer is thwarted by the natural history of the disease. The biological and clinical potential of most individual cancers is uncertain. In many cases the disease will not progress to clinical significance but experimental and clinical studies indicate that prostate cancer can and may metastasis early in the course of the disease from relatively small foci (i.e., not necessarily the largest or index cancer). Localised prostate cancer is potentially curable with localised therapies (radical prostatectomy or irradiation therapy). However, there are no curative therapies for metastatic prostate cancer. Gene therapy, especially those approaches with an immunomodulatory component, may provide additional therapeutic options with the potential to affect both localised and systemic disease. We have pioneered the development and application of in situ gene therapy protocols using adenoviral vectors to transduce specific genes that generate cytotoxic activity and/or a systemic antitumour immune response. In addition we have completed initial studies that demonstrate the therapeutic potential of adenoviral vector-mediated gene modified cell-based vaccines. Our review discusses preclinical studies focused on the development of immunostimulatory in situ gene therapy approaches that hopefully will provide novel and effective treatments for localised and metastatic prostate cancer.

Animals↗

Alcohol consumption as a major risk factor in the development of early esophageal cancer in patients with head and neck cancer.

OBJECTIVE: To clarify the incidence of concomitant esophageal cancers in patients with head and neck cancer (HNC), and to investigate which risk factors are responsible for this association. PATIENTS AND METHODS: From 1994 to 2000, 134 patients with HNC underwent upper gastrointestinal endoscopy using the 0.8% Lugol stain method to detect esophageal cancer. A case-control study was designed to compare HNC patients with and without esophageal cancer. Logistic-regression analysis was used to obtain odds ratios of risk factors. RESULTS: Out of 134 patients with HNC, Lugol unstained area was detected in 42 patients. Biopsy specimens revealed squamous cell carcinoma in 17 (12.7%), dysplasia in 9 patients (6.6%), and normal in the others. Gastric carcinoma was also detected in 7 patients (5.2%). The estimated depth of cancer invasion was mucosa in 9 patients, submucosa in 5 patients, and proper muscle or deeper in 3 patients. In the results of statistical analysis, high alcohol consumption of more than 75 g per day increased the risk of esophageal cancer (odds ratio: 20.2, p<0.01). Intake of hard liquor showed a high odds ratio (whisky: 28.7, p<0.05, shochu: 12.7, p<0.05). The amount of cigarette smoking was not related to this association. CONCLUSION: High incidence of esophageal cancer was found in the patients with HNC. A high alcohol consumption level, and in particular hard liquor, participated in the development of esophageal cancer in the patients with HNC. But cigarette smoking was not related to this association.

Adult↗

Idiopathic giant cell granulomatous hypophysitis with hypopituitarism, right abducens nerve paresis and masked diabetes insipidus.

A 38-year-old man presented with headache, fever, and double vision associated with right abducens nerve paresis. He had neither nuchal rigidity nor visual field defect. Laboratory data revealed elevated erythrocyte sedimentation rate (ESR), eosinophilia, and lymphocytic pleocytosis in the cerebrospinal fluid (CSF). Provocation tests of pituitary hormones showed partial hypopituitarism. Magnetic resonance imaging (MRI) revealed swelling of the hypophysis and a mass lesion expanding into the right cavernous sinus. The supplement dose of dexamethasone for hypothalamic hypocortisolism manifested diabetes insipidus. Biopsy, carried out through the transsphenoidal approach, revealed giant cell granuloma. Systemic granulomatous diseases were ruled out, and the lesion was considered to be idiopathic giant cell granulomatous hypophysitis. Right abducens nerve paresis, diabetes insipidus and dysfunction of the anterior lobe were amended by the treatment with prednisolone for 4 months, and findings of the pituitary gland and stalk were normalized. The present case shows that glucocorticoid has an effect on amendment of idiopathic giant cell granulomatous hypophysitis.

Abducens Nerve Diseases↗

Transluminal imaging with perspective volume rendering of computed tomographic angiography for the delineation of cerebral aneurysms.

Transluminal imaging with perspective volume rendering of computed tomographic angiography was used to investigate three patients with unruptured cerebral aneurysms. Selective changes in the opacity chart of computed tomography values, based on a spiked peak curve, represented the contour of the vessel and aneurysmal walls as a series of rings, and allowed a transluminal view from outside or inside the vessel lumen through the spaces between the rings. This imaging technique provided direct visualization of the underlying structures and an extensive perspective view of the cerebral aneurysms, including the parent arteries and surrounding bony structures, through the overlying vessel and aneurysmal walls. Transluminal imaging may be a useful method for the extra- and intraluminal diagnosis of a cerebral aneurysm, and for simulation of the interventional and surgical procedures considered for cerebral aneurysms.

Adult↗

The trend in airborne asbestos concentrations at plants manufacturing asbestos-containing products in Japan.

In Japan, chrysotile is still permitted to use under the Ordinance on Prevention of Hazards due to Specified Chemical Substances. In recent years many countries have introduced a policy of prohibiting the use of asbestos, based on clinical and epidemiological studies. In light of this, it is important to evaluate the airborne asbestos concentrations in workplaces and also estimate the number of related disease cases in order to discuss the ban of asbestos use. The survey covered 528 workplaces in 145 plants and included 2795 asbestos handling workers from 1985 to 1998. These plants were belonging to the Japan Asbestos Association (JAA) as member companies. In Japan, nearly all of the asbestos using manufacturing companies are members of JAA. In our study, all of the workplaces were divided under each separate manufacturing process and classified into 3 categories of Control Classes. Of the 454/528 (86.0%) workplaces classified as Control Class 1 are improved to 376/378 (99.5%). Though in the cases of small enterprises, other factors such as a shift in product lines, and the economic recession, as well as efforts, contributed to improvements in working conditions. JAA recommended self-administered concentrations of 1.0 f/ml (compatible to <0.3 f/ml in personal exposure level) in 1991 to promote further improvements of the work environment. From this point of view, exposure limits can almost be technically achieved in Japan, and it is expected that asbestos related disease could be expected to decrease in 20 to 30 years later. This survey will become basic material for verifications whether we could control asbestos related diseases enough in such well-controlled work environment.

Air Pollutants, Occupational↗

Angiogenesis and mast cells in non-Hodgkin's lymphoma: a strong correlation in angioimmunoblastic T-cell lymphoma.

Mast cells are likely to play a role in angiogenesis under pathological conditions. Solid tumor growth is dependent on angiogenesis, but the influence of mast cells on angiogenesis in non-Hodgkin's lymphoma, (NHL) is not clear. We investigated mast cell number and vessel count in 61 cases of NHL. We also evaluated expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), both important cytokines for angiogenesis. The number of mast cells was greater in T-cell lymphomas than in B-cell lymphomas. Of the T-cell lymphomas, the greatest number of mast cells was observed in the angioimmunoblastic T-cell lymphoma (AIL). In all NHLs, significant correlation was found between vessel count and the number of mast cells (p < 0.0001) and between vessel count and the number of VEGF-expressing cells (p < 0.05) but not between vessel count and bFGF-expressing cells. Strong correlation was detected between the number of mast cells and the number of VEGF-expressing cells (p < 0.0001) in all NHLs. Double fluorescence staining of VEGF mRNA and mast cell tryptase revealed that mast cells expressed VEGF mRNA. Our data suggest that mast cells play a very important role in angiogenesis by expressing VEGF in NHL, especially in AIL.

Cell Count↗

Experience with the high occipital transcortical approach in the treatment of intraventricular hemorrhage. Report of two cases.

Two patients with intraventricular hemorrhage (IVH) were treated by direct removal of their intraventricular hematomas via a high occipital transcortical approach with successful results. This approach lies between the parietooccipital transcortical approach and the occipital transcortical approach. The patients were a 90-year-old woman with idiopathic IVH and a 60-year-old man with hemorrhage caused by bleeding in the thalamus. In both cases, the hematoma was tightly packed in the lateral ventricle. In the former case, the inferior horn of the lateral ventricle was extremely swollen, and the patient was at risk for development of uncal herniation. With the goals of complete elimination of the hematoma in the inferior horn and identification of the source of bleeding, a high occipital transcortical approach was applied, and the hematoma was removed under direct vision. With the patient in the lateral position, a minor craniotomy of approximately 3 cm was performed around the puncture site of the posterior horn (8 cm craniad from the inion and 3 cm lateral from the midline). A 1-cm cortical incision was made and the posterior horn was reached. First, the portion of hematoma at this site was removed, and then the remainder was completely removed from the interior horn and corpus. Using this method, the entire region of the lateral ventricle, including the inferior horn, corpus, and posterior horn, can be covered in a single operative field, and it is also possible to have sufficient working space for the operation.

Aged↗

[Usefulness of new triple therapy containing PPI].

The guideline on the management of H. pylori was developed by the Japanese Society for Helicobacter Research in 2000, and new triple therapy with lansoprazole, amoxicillin and clarithromycin is recommended. At first, we determined the eradication ratio and the frequency of adverse effects, considering difference of genetic polymorphism in metabolizing enzyme of PPI, CYP2C19. No significant difference was shown among the groups of different metabolizing activity in the two points of view. Next, resistance to antibiotics of H. pylori were determined in the eradication-failure cases and compared before and after the therapy. The result did not showed that strains newly acquired the resistance during the therapy. We emphasis that the new triple therapy can be performed without considering the genetic difference or antibacterial resistance until now and that we should examine how eradication is completely performed.

2-Pyridinylmethylsulfinylbenzimidazoles↗