[Hepatocyte nuclear factor 6: a novel class of liver-enriched transcription factor].
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Animals↗
Biomedical subjects
H Oda
Publications and source records attributed to H Oda.
Tenascin expression may reflect the activity and chronicity of human IgA nephropathy.
BACKGROUND: Tenascin is a large oligomeric glycoprotein component of the extracellular matrix that increases rapidly after inflammation or injury, suggesting that it may be an indicator of renal disease activity. Histological activity and chronicity indices are currently used to evaluate the activity and chronicity of IgA nephrophathy. PATIENTS AND METHODS: We investigated whether tenascin staining could be an indicator of activity or chronicity in patients with IgA nephropathy using immunohistochemical and in situ polymerase chain reaction methods. Immunostaining for tenascin was done on 58 renal specimens, (51 from IgA nephropathy patients and 7 from normal kidneys), and the in situ polymerase chain reaction was performed on 24 renal specimens (21 from IgA nephropathy patients and 3 from normal kidneys). RESULTS: Tenascin expression in the glomeruli was correlated with tenascin expression in the tubulointerstitium (protein; r = 0.386, p = 0.0063, mRNA; r = 0.510, p = 0.0225). Tenascin protein staining in the glomeruli was correlated with the chronicity index (r = 0.506, p = 0.0003), and glomerular tenascin mRNA positivity was correlated with the activity index (r = 0.449, p = 0.0448). CONCLUSION: Tenascin expression was similar in the glomeruli and tubulointerstitium, but glomerular staining more closely reflected the pathological state. Tenascin protein expression may be an indicator of chronicity and tenascin mRNA expression may be an indicator of disease activity in IgA nephropathy.
Adolescent↗
Vancomycin therapy for treatment of peritonitis in outpatients on peritoneal dialysis.
Vancomycin therapy is frequently used for peritonitis in patients on peritoneal dialysis, but the emergence of resistance has been reported. We evaluated the efficacy of a single intraperitoneal dose of vancomycin for peritonitis in peritoneal dialysis patients. We assessed 24 episodes of peritonitis in 16 patients, and compared clinical parameters between responders and nonresponders. Vancomycin was effective for 12 patients (18 out of 24 episodes, 75.0%). Nonresponders had a significantly higher initial C-reactive protein level and dialysis fluid leukocyte count, and the mean serum albumin over three months before onset was significantly lower than in responders. Patients with a serum albumin level 3.0 g/dl or more were significantly more likely to respond than those with a level less than 3.0 g/dl. In conclusion, it seems reasonable for peritonitis patients with a mild inflammatory response and a serum albumin 3.0 g/dl or more to receive intraperitoneal vancomycin on an outpatient basis.
Adult↗
[Polymyositis-induced respiratory failure in the presence of antecedent pleural effusion].
Pulmonary involvement is generally recognized to be an important determinant of the clinical course in cases of polymyositis. A patient with bilateral pleural effusion as an initial symptom developed respiratory failure due to muscle weakness. Polymyositis was diagnosed on the basis of a muscle biopsy. A chemotherapy regimen consisting of methyl prednisolone (1 g/day for 3 days) followed by prednisolone (60 mg/day) alleviated, the pleural effusion and respiratory failure. Though pleural complications in polymyositis have been described mostly in association with concomitant interstitial lung disease, our patient exhibited only bilateral pleural effusion. Given that pleural effusion can be an initial symptom of polymyositis, it seems necessary that polymyositis be taken into consideration by differential diagnoses of pleural effusion of unknown etiology.
Aged↗
[Treatment outcome on 52 patients with 53 testicular germ cell tumors].
Between August 1983 and April 1996, 53 testicular germ cell tumors in 52 patients were treated at Toranomon Hospital. The average age of the patients was 36.1 years (range 21-89). The affected side was the right side in 24, left in 27 and bilateral in 1 case. Of the 53 tumors 34 (64.2%) were seminoma and 19 (35.8%) were non-seminomatous germ cell tumor (NSGCT). High ligation orchiectomy was performed in all cases. Of 29 stage I seminomas, post-operative adjuvant radiotherapy was performed in 6 cases prior to 1991. None of these tumors recurred. Two cases of relapses (8.7%) were found among the 23 stage I seminomas followed by surveillance. Of 8 stage I NSGCTs followed by surveillance, 4 (50.0%) tumors which contained embryonal carcinoma element and vascular invasion relapsed within 12 months after orchiectomy. A case of stage IIA seminoma was treated successfully by irradiation. Seven cases of stage II (3 seminomas and 4 NSGCTs) and 8 cases of stage III (1 seminoma and 7 NSGCTs) as well as cases of 6 stage I patients who developed relapse during surveillance were treated by VAB-6 chemotherapy. Of these 21 cases, 11 (52.4%) achieved complete response (CR) and 10 (47.6%) partial response (PR). Salvage surgery and/or additional chemotherapy was successful to bring the 10 PR cases into CR condition. One NSGCT patient, however, died of electrolyte imbalance during the maintenance chemotherapy for disease progression after achieving CR. All 34 patients with seminomas and 18 of the 19 with NSGCTs were alive without evidence of disease after a mean follow up period of 61.1 months (range 4-150 months).
Adult↗
Expression of lipocalin-type prostaglandin D synthase (beta-trace) in human heart and its accumulation in the coronary circulation of angina patients.
Lipocalin-type prostaglandin D synthase (L-PGDS) is localized in the central nervous system and male genital organs of various mammals and is secreted as beta-trace into the closed compartment of these tissues separated from the systemic circulation. In this study, we found that the mRNA for the human enzyme was expressed most intensely in the heart among various tissues examined. In human autopsy specimens, the enzyme was localized immunocytochemically in myocardial cells, atrial endocardial cells, and a synthetic phenotype of smooth muscle cells in the arteriosclerotic intima, and accumulated in the atherosclerotic plaque of coronary arteries with severe stenosis. In patients with stable angina (75-99% stenosis), the plasma level of L-PGDS was significantly (P < 0.05) higher in the great cardiac vein (0.694 +/- 0.054 microg/ml, n = 7) than in the coronary artery (0.545 +/- 0.034 microg/ml), as determined by a sandwich enzyme immunoassay. However, the veno-arterial difference in the plasma L-PGDS concentration was not observed in normal subjects without stenosis. After a percutaneous transluminal coronary angioplasty was performed to compress the stenotic atherosclerotic plaques, the L-PGDS concentration in the cardiac vein decreased significantly (P < 0.05) to 0.610 +/- 0.051 microg/ml at 20 min and reached the arterial level within 1 h. These findings suggest that L-PGDS is present in both endocardium and myocardium of normal subjects and the stenotic site of patients with stable angina and is secreted into the coronary circulation.
Angina Pectoris↗
HNF-6 is expressed in endoderm derivatives and nervous system of the mouse embryo and participates to the cross-regulatory network of liver-enriched transcription factors.
Hepatocyte nuclear factor-6 (HNF-6) is a liver-enriched transcription factor that contains a single cut domain and a novel type of homeodomain. Here we have studied the developmental expression pattern of HNF-6 in the mouse. In situ hybridization experiments showed that HNF-6 mRNA is detected in the liver at embryonic day (E) 9, at the onset of liver differentiation. HNF-6 mRNA disappeared transiently from the liver between E12.5 and E15. In transfection experiments HNF-6 stimulated the expression of HNF-4 and of HNF-3 beta, two transcription factors known to be involved in liver development and differentiation. HNF-6 was detected in the pancreas from E10.5 onward, where it was restricted to the exocrine cells. HNF-6 was also detected in the developing nervous system. Both the brain and the spinal cord started to express HNF-6 at E9-9.5 in postmitotic neuroblasts. Later on, HNF-6 was restricted to brain nuclei, to the retina, to the ventral horn of the spinal cord, and to dorsal root ganglia. Our observations that HNF-6 contributes to the control of the expression of transcription factors and is expressed at early stages of liver, pancreas, and neuronal differentiation suggest that HNF-6 regulates several developmental programs.
Animals↗
Loss of imprinting of the IGF2 gene in a Wilms' tumor in an adult.
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Adult↗
Endothelin enhances lipopolysaccharide-induced expression of inducible nitric oxide synthase in rat glial cells.
Lipopolysaccharide is known to stimulate production of nitrite via expression of inducible nitric oxide (NO) synthase in not only macrophages but also glial cells. We found that in glial cell cultures lipopolysaccharide-stimulated inducible NO synthase expression and nitrite accumulation were synergistically enhanced by pretreatment with endothelin, whereas endothelin itself did not induce these responses. Pretreatment with endothelin-1, endothelin-3, and the selective endothelin type B (ETB) receptor agonist IRL 1620 caused the same effect with similar potencies, suggesting that the synergism was mediated via the endothelin ETB receptor. A protein kinase C inhibitor, calphostin C, suppressed endothelin-3-enhanced inducible NO synthase expression. Pretreatment with either endothelin-3 or phorbol ester enhanced lipopolysaccharide-induced production of tumor necrosis factor-alpha (TNF-alpha). Simultaneous addition of TNF-alpha increased lipopolysaccharide-stimulated inducible NO synthase expression. These results suggest that the increase in inducible NO synthase expression by endothelin was due to the elevated TNF-alpha production via protein kinase C. Our findings present the possibility that endothelin is implicated in neurotoxicity via enhancement of inducible NO synthase expression.
Animals↗
A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis.
Bone-resorbing multinucleated cells were efficiently formed in primary culture of cells isolated from synovial tissues of patients with rheumatoid arthritis in 2-3 weeks in the presence of 1,25(OH)2vitaminD3 without any additional stromal cells, and that formation was further facilitated by macrophage-colony stimulating factor. Furthermore, we show that osteoclast-like cells are formed in co-culture of peripheral blood mononuclear cells and rheumatoid synovial fibroblasts obtained by continued sub-cultures. The multinucleated cells showed all the phenotypical and functional characteristics of osteoclasts including the expression of tartrate resistant acid phosphatase, vitronectin receptors, receptors for human calcitonin and the ability to resorb bone. These results indicate that synovial macrophages are capable of differentiating into osteoclasts in the presence of rheumatoid synovial fibroblasts which can support differentiation of monocytes/ macrophages, implicating that osteoclasts generated within the synovial membrane are probably involved in bone destruction in rheumatoid arthritis.
Acid Phosphatase↗
Accumulation of Armadillo induced by Wingless, Dishevelled, and dominant-negative Zeste-White 3 leads to elevated DE-cadherin in Drosophila clone 8 wing disc cells.
Drosophila genetic studies suggest that in the Wingless (Wg) signaling pathway, the segment polarity gene products, Dishevelled (Dsh), Zeste-white 3 (ZW-3), and Armadillo (Arm), work sequentially; wg and dsh negatively regulate zw-3, which in turn down-regulates arm. To biochemically analyze interactions between the Wg pathway and Drosophila E-cadherin (DE-cadherin) which bind to Arm, we overexpressed Dsh, ZW-3, and Arm, in the Drosophila wing disc cell line, clone 8, which responds to Wg signal. Dsh overexpression led to accumulation of Arm primarily in the cytosol and elevation of DE-cadherin at cell junctions. Overexpression of wild-type and dominant-negative forms of ZW-3 decreased and increased Arm levels, respectively, indicating that modulation in zw-3 activity negatively regulates Arm levels. Overexpression of an Arm mutant with an amino-terminal deletion elevated DE-cadherin levels, suggesting that Dsh-induced DE-cadherin elevation is caused by the Arm accumulation induced by Dsh. Moreover, the Dsh-, dominant-negative ZW-3-, and truncated Arm-induced accumulation of DE-cadherin protein was accompanied by a marked increase in the steady-state levels of DE-cadherin mRNA, suggesting that transcription of DE-cadherin is activated by Wg signaling. In addition, overexpression of DE-cadherin elevated Arm levels by stabilizing Arm at cell-cell junctions.
Adaptor Proteins, Signal Transducing↗
Analysis of low-molecular-mass proteins in cerebrospinal fluid by sodium dodecyl sulfate capillary gel electrophoresis.
Proteins of low molecular (M(r)) in human cerebrospinal fluid (CSF) were analyzed by capillary electrophoresis in a sodium dodecyl sulfate-containing polymer solution. Under the conditions employed, peaks of beta 2-microglobulin (beta MG) (M(r): 11,700), gamma-trace protein (12,300), myelin basic protein (18,000), beta-trace protein (beta TP) (23,000 to 30,000) and alpha 1-acid glycoprotein (42,000) were detected on the electropherograms. The concentrations of beta MG and beta TP were determined based on the peak area relative to that of an internal standard, Orange G, which was added at a constant amount as the front marker. It was demonstrated that their levels in CSF change under various pathological conditions in the central nervous system.
Adolescent↗
Future prognostic factors for renal cell carcinoma: Workgroup No. 5. Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC).
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Biomarkers, Tumor↗
Regulation of expression of the human MTH1 gene encoding 8-oxo-dGTPase. Alternative splicing of transcription products.
The enzyme 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase (8-oxo-dGTPase) hydrolyzes 8-oxo-dGTP to 8-oxo-dGMP, thereby preventing misincorporation of 8-oxo-dGTP into DNA. We investigated expression of MTH1 gene encoding 8-oxo-dGTPase. Large amounts of MTH1 mRNA were present in thymus and testis, embryonic tissues, and certain cell lines. In peripheral blood lymphocytes, the level of MTH1 mRNA was significantly increased after concomitant treatment with phytohemagglutinin and interleukin-2. Analyses of the 5' regions of the MTH1 transcripts revealed that 7 types of MTH1 mRNAs, which may be produced by transcription initiation at different sites and/or alternative splicing. The MTH1 gene consists of 5 major exons, some of which are composed of differentially processed segments. All types of MTH1 mRNAs carry the entire coding region, and may be functional. Three ATG initiation codons in-frame were found in the 5' regions of some of the MTH1 mRNAs. There is a polymorphic alteration at the 5' splicing site (GT to GC) located in exon 2, an event which affects splicing patterns of the MTH1 transcript. Allele frequency of this polymorphism is about 20% among healthy volunteers.
Alternative Splicing↗
Prevalence of p53 mutations and protein expression in esophageal cancers in southern Thailand.
To investigate p53 alterations in esophageal squamous-cell carcinomas of patients in the high-risk area of southern Thailand, 72 paraffin-embedded samples were analyzed immunohistochemically for p53 protein expression and 16 frozen samples for p53 mutational status. Forty-two of the 72 tumors (58.3%) showed p53 protein accumulation in the nuclei of tumor cells. Expression of p53 in tumors was not significantly correlated with gender, histological grading, depth of invasion, node involvement, smoking or alcohol consumption. Analysis of the p53 gene in a sub-set of 16 tumors showed mis-sense mutations in 7 out of 11 p53-positive and 1 out of 5 p53-negative tumors. The p53 mutational spectrum was 50% transitions (3 C-to-T and 1 G-to-A, all occurring at CpG dinucleotide sites) and 50% transversions (one each, C-to-G, G-to-T, T-to-G, and T-to-A). Our findings support the hypothesis that alterations of p53 are involved in the carcinogenesis of most squamous-cell carcinomas of the esophagus, irrespective of the population and the factors responsible for carcinogenesis. The mutation profile of the p53 gene might indicate etiologic contributions of different mutagen exposures in patients from high-risk areas of southern Thailand.
Adolescent↗
Prostaglandin D synthase (beta-trace) in human arachnoid and meningioma cells: roles as a cell marker or in cerebrospinal fluid absorption, tumorigenesis, and calcification process.
Glutathione-independent prostaglandin D synthase (PGDS) is an enzyme responsible for biosynthesis of prostaglandin D2 in the CNS and is identical to a major cerebrospinal fluid protein, beta-trace. Although PGDS has been identified recently in rat leptomeninges, little information is available about human meninges or meningiomas. Here, we report PGDS to be expressed consistently in 10 human arachnoid and arachnoid villi and in 21 meningiomas by immunohistochemistry, Western blot, and reverse transcription (RT)-PCR analyses. In arachnoid, PGDS immunoreactivity was seen in arachnoid barrier cells but was negligible in arachnoid trabecula and pia mater. In contrast, in arachnoid villi, PGDS was seen in core arachnoid cells rather than in the cap cell cluster or arachnoid cell layer. Meningioma cells also showed intense immunoreactivity in the perinuclear region, and it was often concentrated within meningocytic whorls and around calcifying psammoma bodies. Immunoelectron microscopic data, when compared with the ultrastructure, showed that PGDS was localized at rough endoplasmatic reticulum of arachnoid and meningioma cells. Western blot showed a 29 kDa immunoreactive band indicating PGDS, but the extent of expression was variable from case to case, which was compatible with immunohistochemical data. RT-PCR revealed PGDS gene expression in all meningiomas studied, regardless of histological subtypes, and also in human arachnoid villi. Because human arachnoid and meningioma cells exclusively express PGDS, it can be considered their specific cell marker. These results show functional differences in various types of meningeal cells attributable to differences in PGDS expression.
Animals↗
Biochemical and functional characterization of DNA complexes capable of targeting genes to hepatocytes via the asialoglycoprotein receptor.
Electrostatic binding of polycations or basic polypeptides to the DNA phosphate backbone has been previously described as a one-step process which results in uncontrolled aggregation and precipitation of the DNA in solution. We describe here a multistep process in which the condensation of DNA in the presence of poly-L-lysine can be controlled to produce particles of discrete size and shape suitable for receptor-mediated gene transfer in vivo and in vitro. The first step in this process involves the gradual accretion of poly-L-lysine onto the DNA phosphate backbone, until charges are neutralized. The addition of poly-L-lysine to a concentrated solution of DNA in this fashion prevents intermolecular aggregation of the DNA, presumably by promoting the formation of a nucleus of condensation along the length of each DNA molecule. The second stage of the process involves adjusting the ionic strength of the solvent to facilitate the solubilization of compact DNA.poly-L-lysine complexes. Several physical and biochemical parameters have been studied and correlated with the efficacy of DNA/ligand-poly-L-lysine particles in transferring genes to the liver of adult animals by receptor-mediated endocytosis.
Asialoglycoprotein Receptor↗
Loss of p53 is an early event in induction of brain tumors in mice by transplacental carcinogen exposure.
Experimental carcinogenesis studies using p53-deficient mice have suggested that loss of function of this tumor suppressor gene is generally not an early event but is rather related to tumor progression. However, the biological functions of p53 and the accumulating evidence of alteration in human tumors imply a possible role for loss of p53 in the initial stages of tumorigenesis. Ethylnitrosourea administration to p53-heterozygous pregnant mice resulted in rapid development of primary brain tumors, which are extremely rare in mice, in 70% of the p53-null offspring. Brain tumors also developed later in 4% of heterozygous mice, but they had lost the wild-type allele. Thus, loss of normal p53 gene expression is of direct significance to early events in brain tumorigenesis, and this tumor suppressor gene may protect embryos from DNA damage in the brain induced by transplacental carcinogen exposure.
Animals↗