[Epidemiology of hepatitis delta virus infection].
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Hepatitis D↗
Biomedical subjects
T Tsuda
Publications and source records attributed to T Tsuda.
Cellular physiology of epileptogenic phenomena. A hint for future therapy by a herbal mixture.
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Animals↗
[Expression of CD44 alternative splicing variants in lung cancer].
Expression of isoforms of the CD44 is generated by alternative splicing of CD44 gene; CD44H: lacks all 10 alternative exons, CD44R: the alternative exons v8 to v10, CD44V: other group of variants which contains the alternative exon v6. In some tumors such as colorectal cancer, breast cancer, non-Hodgkin lymphoma, and melanoma, over-expressed CD44 isoform which contains such alternative-spliced variant exons may play a causative role in tumor metastasis. In lung cancer, however, the role of CD44 variants in tumor progression and metastasis is uncertain. In our study and reported literature, no definite correlation was observed between the expression of specific CD44 isoform and tumor progression or metastasis of lung cancer.
Alternative Splicing↗
[Family intervention for schizophrenia based on expressed emotion (EE) research: a review of the technique and evaluation].
The present study reviews eight series of trials on psycho-social family intervention for schizophrenia based on Expressed Emotion (EE). All studies used randomized controlled trials (RCT) except one which was non-randomized controlled trial. The relapse risk ratios (intervention/control) for 9-12 months after discharge were 0 to .73 and for 24 months were .20 to .57. Taking into account the shortcomings of the studies, the authors conclude that psycho-social family intervention based on EE is effective in preventing schizophrenic relapse, and discuss four important issues: 1) For effective family intervention, methods for Japanese patients should be established from a trans-cultural view point; 2) The interaction of two or more therapeutic measures should be evaluated quantitatively; 3) The mechanisms of schizophrenic relapse prevention through family psycho-social intervention should be explored. A psycho-physiological study including skin conductance measurement is promising; 4) The authors point out the ethical aspect of family intervention, and discuss the importance of informed consent and the need to place emphasis on family's needs.
Emotions↗
Detection of c-ras gene mutation and expression of p21 protein in dysplasias and carcinomas complicating ulcerative colitis.
Point mutations of c-ras genes and the expression of p21 protein were analyzed in 13 patients with colorectal carcinoma complicating ulcerative colitis; in 12 of the 13, there were dysplastic lesions close to the carcinomas. Point mutations of c-ras genes were studied by polymerase chain reaction and dot blot hybridization with 32p-labeled oligonucleotide probes. Findings indicated mutations of c-Ki-ras at condons 12, 13, and 61 and c-Ha-ras and c-N-ras at condons 12 and 61. The expression of p21 protein was analyzed by immunohistochemical staining using a monoclonal antibody. Only 1 of the 13 patients with carcinoma showed a point mutation, this being from G to A transition at the second position of codon 12 of c-Ki-ras. No point mutations of c-Ki-ras, c-Ha-ras, or c-N-ras were found in other carcinomatous lesions and dysplasias. In the dysplastic or carcinomatous lesions of 11 patients, the increased expression of p21 protein was observed. These results suggest that point mutations of c-ras genes are rare in dysplasias and carcinomas complicating ulcerative colitis and that the increased expression of p21 protein is not always correlated with point mutations of c-ras genes.
Colitis, Ulcerative↗
[Metachromatic leukodystrophy (MLD) and Multiple sulphatase deficiency (MSD)].
MLD is caused by a deficiency of arylsulfatase A and hence sulfolipids are accumulated in various patient's tissues. Various clinical phenotypes including activator deficiency, pseudodeficiency and MSD. Recently, molecular basis of these disorders have been identified. Clinical phenotype in MLD is well correlated with their genotype. Most common mutation in Caucasian MLD is caused by 609A mutation which produces late infantile MLD. In Japanese, most common mutation is 445A mutation. Essential treatment of MLD is recently carried out by bone marrow transplantation. On the hand, MSD is caused by multiple deficiencies of various sulfatases and hence accumulated various sulfated compounds such as sulfatide and acid mucopolysaccharides. The clinical features have combined characteristics of MLD and mucopolysaccharidosis. The cause of this disorder is recently identified as abnormal modification of various sulfatase.
Base Sequence↗
[Clinical evaluation of kinetic model for the quantification of liver function with Tc-99m PMT and dynamic scintigraphy].
The purpose of this study was to quantify the uptake and excretion of Tc-99m-N-pyridoxyl-5-methyltryptophan (PMT) by hepatocytes using a tracer kinetic modeling approach, and to clarify the pathophysiological changes of diffuse parenchymal liver diseases. Fifty-two patients with liver diseases and seven normal subjects were studied. Studies were performed using an intravenous bolus injection of 185 MBq of PMT. Our compartment model consisted of three compartments. These parameters were calculated using the non-linear least-square method. The fitting curves agreed well with the measured ones. K1 correlated with blood tests of liver function better than parameters from the two-compartment model such as ku. K1 correlated especially closely with K-ICG (r = 0.898). K1 reflected hepatic blood flow, and the decrease of K1 was associated with hepatic dysfunction. Although K3 correlated poorly with serum bilirubin (r = -0.447), it correlated well with MTT (deconvolutional analysis) (r = -0.833). K3 reflected excretory function, and did not decrease until liver function was moderately damaged. By using three-compartment analysis, we were better able to explain the pathophysiological status of the liver. Our model is more useful for the assessment of liver function than the simple model.
Adult↗
Molecular cloning of the amino-terminal region of a rat MUC 2 mucin gene homologue. Evidence for expression in both intestine and airway.
To obtain cDNAs for analysis of mucin gene transcription in rat models of human disease, we screened a rat intestinal cDNA library in lambda ZAPII using an upstream non-tandem repeat cDNA fragment of the human MUC 2 gene (Gum, J., Hicks, J., Toribara, N., Rothe, E., Lagace, R., and Y., K. (1992) J. Biol. Chem. 267, 21375-21383). Three cDNAs, 1-1, 8-1, and 21-1, were isolated. A translation start site was found in cDNA 21-1. Combined nucleotide sequence for the three cDNAs contained an open reading frame spanning 4546 base pairs. This amino-terminal sequence contains a non-tandem repeat domain enriched in cysteine (1391 residues) followed by an irregular tandem repeat domain (122 residues). Identity with the human gene is about 80% in the non-tandem repeat domain and about 38% in the irregular tandem repeat domain. Primer extension and S1 nuclease protection analysis indicate a transcription start site at 28 base pairs upstream of translation initiation. Northern analysis showed expression of cognate RNA in the intestine and airway but not heart and spleen. The cDNAs have been used to isolate the gene promoter, the structure of which should yield clues to the regulation of mucin expression in rat models of human disease.
Amino Acid Sequence↗
[Clinical study of eosinophilic pneumonia].
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Humans↗
Angiotensin II inhibits cytokine-stimulated inducible nitric oxide synthase expression in vascular smooth muscle cells.
In cultured vascular smooth muscle cells (VSMC), inflammatory cytokines such as interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha stimulated nitric oxide (NO) production via the expression of an inducible type of NO synthase (iNOS). A potent vasoconstrictor, angiotensin II (Ang II), which causes a rapid phospholipase C-mediated phosphoinositide hydrolysis via the Ang II type 1 (AT1) receptor in VSMC, by itself did not stimulate the production of nitrite, a stable metabolite of NO, but dose dependently inhibited the IL-1 beta-induced nitrite production. This inhibitory effect of Ang II was blocked by an AT1 receptor antagonist, CV-11974, but not by an Ang II type 2 receptor antagonist, PD 123319. The presence of Ang II during the early induction phase of iNOS was required for this inhibition. Consistently, Ang II suppressed IL-1 beta-induced increases in iNOS mRNA and protein levels. Ang II also inhibited increases in nitrite production and iNOS mRNA and protein levels caused by tumor necrosis factor alpha. A protein kinase C-activating phorbol ester, phorbol 12-myristate 13-acetate, and a membrane-permeable diacylglycerol, 1,2-dioctanoyl-glycerol, similarly inhibited the IL-1 beta-induced nitrite production and iNOS mRNA and protein expression, although repetitive additions were needed in the case of diacylglycerol. These results indicate that Ang II negatively modulates cytokine-induced NO production by blocking iNOS expression via the AT1 receptor in VSMC and suggest that protein kinase C could be involved in this process.
Amino Acid Oxidoreductases↗
Pyridoxal 5'-phosphate probes at Lys-480 can sense the binding of ATP and the formation of phosphoenzymes in Na+,K(+)-ATPase.
The Lys-480 in the alpha-subunits of Na+,K(+)-ATPase from pig kidneys was specifically modified with pyridoxal 5'-phosphate (PLP) or pyridoxal 5'-diphospho-5'-adenosine (AP2PL) probes in the presence of NaCl. The site was shown to be the same as the ATP-protectable binding of these probes (Hinz, H.R., and Kirley, T.L. (1990) J. Biol. Chem. 265, 10260-10265). Modifications strongly reduced both Na+,K(+)-ATPase activity and the amount of Na(+)-dependent phosphoenzyme from [32P]ATP but not from [32P]acetyl-phosphate (AcP). Addition of AcP to the enzyme induced a slight decrease in the fluorescence of the PLP probe in the presence of 2 M NaCl and 4 mM MgCl2 but a single exponential increase in the presence of 16 mM NaCl and 4 mM MgCl2. The addition of ATP induced single exponential fluorescence increases at both Na+ concentrations. The data show that these probes can sense molecular events related to the formation of phosphoenzymes induced by AcP and presumably to the formation of Mg-Na-ATP-enzyme complex. The data also suggest that PLP or AP2PL probes at Lys-480 in the presence of Na+ and Mg2+ do not affect the transphosphorylation from AcP to Asp-369 to form phosphoenzymes but that they inhibit the transphosphorylation from the gamma-phosphoryl group of ATP and also ATP binding in the absence of Mg2+.
Adenosine Triphosphate↗
Alzheimer's disease and possible gene interaction.
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Alzheimer Disease↗
Are the associations between Alzheimer's disease and polymorphisms in the apolipoprotein E and the apolipoprotein CII genes due to linkage disequilibrium?
Allele frequencies for polymorphisms in the apolipoprotein E and the apolipoprotein CII genes were determined in subjects of Ashkenazi Jewish origin with late-onset Alzheimer's disease and in unaffected control subjects from the same ethnic group. A significant association was observed between late-onset Alzheimer's disease and the epsilon 4 (112Cys-->Arg) allele of apolipoprotein E; however, no association was detected with apolipoprotein CII. These results suggest that the association with epsilon 4 is probably not due to linkage disequilibrium.
Aged↗
Homozygous inheritance of the Machado-Joseph disease gene.
We report a patient presenting at age 16 years with postural instability and falls who developed severe generalized dystonia by the age of 20 years. He was the product of a consanguineous marriage. Maternal grandfather and paternal grandmother (brother and sister) living in the Azores were both affected by Machado-Joseph disease (MJD) beginning late in life. To date neither of the patient's parents are clinically affected. Linkage studies in this family and others of Azorean descent have confirmed the recent mapping of the MJD gene to chromosome 14q. Genotyping of the members of this pedigree provides strong genetic evidence that our patient is homozygous for the MJD gene. Our results combined with experience in 2 putative homozygotes previously reported in the literature suggest that gene dosage is an important determinant of age of onset and clinical phenotype in MJD. Other possible influencing factors are discussed.
Adult↗
Autoradiographic analysis of [14C]deoxy-D-glucose in thyroid cancer xenografts: a comparative study with pathologic correlation.
An experimental model of thyroid cancer was prepared for evaluating the accumulation of [14C]deoxy-D-glucose ([14C]DG) in thyroid cancer xenografts (AC2). A continuous cell line established from a biopsy specimen of a metastatic thyroid carcinoma possessed the ability to synthesize the cellular protein without increase in cell division after adding bovine TSH in vitro. The histological sections of the xenografts resected from the 131I treated nude mice mainly consisted of structures showing follicular and trabecular growth. Immunohistochemically the cytoplasm of the tumor cells was positive for human thyroglobulin(hTg). These observations provide strong evidence that the AC2 cell originates in the thyroid follicular epithelium. By comparing autoradiographic accumulation patterns of [14C]DG and histopathological examinations, it was found that the uptake of [14C]DG was higher in the granulation tissues surrounding necrosis than in viable tumor cells of trabeculary growing and follicle forming tissues. It is suggested that the degree of [14C]DG content reflects not only tumor cell viability and proliferation but also the inflammatory and degenerative reaction accompanying tumor cell growth.
Animals↗
Localization of mucin (MUC2 and MUC3) messenger RNA and peptide expression in human normal intestine and colon cancer.
BACKGROUND/AIMS: Several studies have reported Northern blot data showing that mucin is expressed in a tissue-specific manner. To determine whether expression is limited to specific cell types within these tissues requires histological analysis. METHODS: Both immunocytochemistry and in situ hybridization were used to identify cell types expressing the MUC2 and MUC3 mucins in the human small intestine, colon, and colon carcinoma. RESULTS: In the normal small intestine and colon, an antibody recognizing the MUC2 apomucin stained goblet cells. In contrast, an antibody recognizing the MUC3 apomucin stained both goblet and absorptive cells. Consistent with this, in situ hybridization showed MUC2 messenger RNA (mRNA) only in goblet cells and MUC3 mRNA in both goblet and absorptive cells. In several samples of moderately well-differentiated colon cancer, MUC2 and MUC3 showed distinct patterns of expression, but the expression level of each was reduced compared with levels in normal tissue; there was considerable tumor-to-tumor and cell-to-cell variability using both mucin antibodies and complementary DNA probes. CONCLUSIONS: Individual mucin genes have distinct patterns of expression within mucin-producing tissues, suggesting that the various mucin gene products play distinct functional roles.
Colon↗
Primary health care in Japan and the United States.
Japan has universal health insurance and its total health expenditure as a percentage of the gross domestic product is almost 50% less than that of the United States where 15% of persons under age 65 are uninsured. The health of the Japanese population as judged by neonatal, postnatal, and total infant mortality, percent of infants born with birth weights below 2500 g, and life expectancy at birth and ages 20 and 65 is superior to the health of Americans. Primary care, however, as an academic discipline and primary care training programs are absent in Japan. Physician training, incongruent with need, combined with government controlled low professional medical fees contribute to an extraordinarily high annual ambulatory patient contact rate (14 compared with 2.8 for Americans) and excessive use of diagnostic testing. Although primary care training is better developed in the U.S.A., interest in receiving, such training among medical school graduates is declining. Several factors that contribute to quality of care are examined. Comparisons between countries, however, must be viewed with caution because of the multitude of demographic, genetic, historical, economic and cultural variables that influence how health care is delivered and received. Both countries face major challenges. The projected rapid increase in the relative ratio of the elderly to total population in Japan will severely strain its ability to contain health care costs. Interest in primary care training in Japan dates back to 1978 but its implementation has been largely unsuccessful. The challenges in the U.S.A. are far more formidable.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Postprandial increase in the duodenal pH and the effect of intravenous secretin injection on ionic compositions of duodenal fluid and plasma in sheep.
Testing five castrated male sheep with a pH-electrode inserted into the duodenal digesta through a T-shaped cannula, we found that the pH of the duodenal digesta was significantly increased from 3.11 +/- 0.11 to 3.47 +/- 0.09 after a meal. Secretin (2.5 CHR U/kg) was intravenously injected to mimic the duodenal pH increase. The administration significantly increased the duodenal digesta pH from 3.32 +/- 0.18 to 4.85 +/- 0.61, which was accompanied by an increase in sodium concentration, but by a decrease in potassium and chloride concentrations. It also significantly decreased the arterial blood pH from 7.543 +/- 0.002 to 7.515 +/- 0.008, which was accompanied by a reduced plasma HCO3- concentration. From these results, we conclude that in sheep, feeding increases the duodenal digesta pH, and the postprandial pH increase in the duodenal fluid would be due to the raised HCO3- secretion from the gastrointestinal tract.
Acid-Base Equilibrium↗