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Biomedical subjects

A Ido

Publications and source records attributed to A Ido.

At least 37 records · Page 2Linked to original sources
PubMed1998

Retrovirus-mediated gene therapy for human hepatocellular carcinoma transplanted in athymic mice.

Gene therapy using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of the 0.3-kb human alpha-fetoprotein (AFP) gene promoter (LNAF0.3TK virus) in combination with ganciclovir (GCV) treatment was performed in athymic mice harboring AFP-producing HuH-7 human hepatoma cells. GCV treatment resulted in pronounced growth inhibition of the virus-infected HuH-7 xenograft in mice, but did not affect growth of the parental xenograft. These results indicate that the AFP gene promoter sequence allows enough therapeutic gene expression to induce the GCV-mediated cytotoxicity in vivo in AFP-producing human hepatoma cells.

Animals↗
PubMed1998

[Significance of coronary risk factors and coronary arteriosclerosis for coronary vasospasm].

The clinical significance of coronary arteriosclerosis and coronary risk factors was investigated in patients with coronary spasm. Coronary spasm induction test with acetylcholine was performed in 140 consecutive patients (85 males and 55 females) with chest pain in our hospital. The patients were divided into positive, borderline, and negative groups according to the results of the test. The positive and borderline groups were categorized as the coronary contractive group. The coronary sclerosis index was used to evaluate the degree of coronary arteriosclerosis. Coronary risk factors were evaluated in terms of hypertension, diabetes mellitus, hyperlipidemia, obesity, history of smoking and drinking, and family history of cardiovascular events. Patients could be divided into 34.3% in the positive group and 23.6% in the borderline group, i.e. 57.9% in the coronary contractive group, and 42.1% in the negative group. There were more males than females in both positive and coronary contractive groups. The proportion of males in the coronary contractive group was higher in patients over 60 years of age than in patients under 60. In contrast, the proportion of females was higher in patients under 60 than in patients over 60. In male patients, the coronary sclerosis indices in the positive, borderline, and coronary contractive groups were higher than those in the negative group. The indices in female patients in the positive and coronary contractive groups were higher than the index in the negative group. There were no differences in terms of the presence or absence, or the degree of organic stenosis between spastic sites and nonspastic branches in the positive group. The history of smoking in male patients was significantly more common in the positive group than in the negative group. The family history was more relevant in female patients in the positive or coronary contractive group compared to the negative group. Moreover, the history of smoking in the coronary contractive group was significantly more common than that in the negative group. The development of coronary spasm may be determined, at least in part, by the degree of coronary sclerosis as well as by gender and age. Smoking habits in both sexes and family history in females are proposed as the most important risk factors for coronary spasm.

Acetylcholine↗
PubMed1997

[Clinical significance of 123I-MIBG myocardial scintigraphy in patients with hypertrophic cardiomyopathy].

We studied the abnormality of myocardial sympathetic nervous system in patients with hypertrophic cardiomyopathy using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in comparison with the parameters of other clinical examinations. In 50 patients with HCM, the heart to mediastinum 123I-MIBG uptake ratio (H/M) was significantly low and washout rate (WR) of 123I-MIBG was significantly high respectively compared with normal subjects (n = 8). H/M was negatively correlated with serum norepinephrine level, wall thickness of left ventricle, left ventricular mass index, left ventricular end diastolic pressure respectively, and WR was positively correlated with those parameters respectively. On the other hand, LF/HF calculated by spectral analysis in holter electrocardiogram was positively correlated with H/M, and negatively correlated with WR. In HCM, H/M in patients with subjective symptoms was significantly lower than that without subjective symptoms, and WR in patients with paroxysmal atrial fibrillation was significantly higher than that without paroxysmal atrial fibrillation. This study revealed that H/M and WR reflected the severity and the difference of disease type in HCM. In conclusion, 123I-MIBG contributes to evaluating more details in diagnosis and pathophysiology of HCM.

3-Iodobenzylguanidine↗
PubMed1996

Cloning of the cDNA encoding the mouse ATBF1 transcription factor.

We have isolated a mouse ATBF1 cDNA which is 12-kb long and capable of encoding a 406-kDa protein containing four homeodomains and 23 zinc-finger motifs. Mouse ATBF1 is 94% homologous to the human ATBF1-A transcription factor. Northern blot and RNase protection analysis showed that levels of ATBF1 transcripts were low in adult mouse tissues, but high in developing brain, consistent with a role for ATBF1 in neuronal differentiation.

Amino Acid Sequence↗
PubMed1996

Developmental changes in expression of the ATBF1 transcription factor gene.

The expression of the ATBF1 gene in developing brain was analyzed in mice from 13 days of gestation to 28 days after birth using RNase protection and in situ hybridization methods. The level of ATBF1 transcripts was the highest on embryonic day 13-15 and then progressively decreased to a hardly detectable level on postnatal day 28. Throughout the period examined, ATBF1 mRNA was expressed consistently in the basal telencephalon, diencephalon, and mesencephalon, with the highest levels in the inferior colliculus and thalamus. On the other hand, no significant expression was observed in cerebellum, neocortex, hippocampus, and olfactory bulb. These results illustrate significant regional differences in the ATBF1 expression and suggest a role of the ATBF1 gene in the formation of some specific cell populations in developing central nervous system.

Animals↗
PubMed1995

Cloning and characterization of an ATBF1 isoform that expresses in a neuronal differentiation-dependent manner.

The human ATBF1 cDNA reported previously, now termed ATBF1-B, encodes a 306-kDa protein containing 4 homeodomains and 18 zinc fingers including one pseudo zinc finger motif. Here, we report the isolation of a second ATBF1 cDNA, 12 kilobase pairs long, termed ATBF1-A. The deduced ATBF1-A protein is 404 kDa in size and differs from ATBF1-B by a 920-amino acid extention at the N terminus. Analysis of 5'-genomic sequences showed that the 5'-noncoding sequences specific to ATBF1-A and ATBF1-B transcripts were contained in distinct exons that could splice to a downstream exon common to the ATBF1-A and ATBF1-B mRNAs. The expression of ATBF1-A transcripts increased to high levels when P19 and NT2/D1 cells were treated with retinoic acid to induce neuronal differentiation. Preferential expression of ATBF1-A transcripts was also observed in developing mouse brain. Transient transfection assays showed that the 5.5-kilobase pair sequence upstream of the ATBF1-A-specific exon (exon 2) supported expression of the linked chloramphenicol acetyltransferase gene in neuronal cells derived from P19 cells but not in undifferentiated P19 or in F9 cells, which do not differentiate into neurons. These results showed that ATBF1-A and ATBF1-B transcripts are generated by alternative promoter usage combined with alternative splicing and that the ATBF1-A-specific promoter is activated during neuronal differentiation.

Alternative Splicing↗
PubMed1995

Gene therapy for hepatoma cells using a retrovirus vector carrying herpes simplex virus thymidine kinase gene under the control of human alpha-fetoprotein gene promoter.

The alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but is reactivated in hepatocellular carcinoma. It has been shown that the positive and negative transcriptionally regulatory elements of the human AFP gene, which play an important role in its developmental regulation, exist over the quite extended region (4 kb). We constructed a hybrid gene consisting of herpes simplex virus thymidine kinase (HSV-tk) gene under the control of the 0.3-kb human AFP gene promoter and inserted it into a retroviral vector. When AFP-producing hepatoma cells were infected with this recombinant retrovirus (LNAF0.3TK virus), the cells expressed HSV-tk gene and exhibited increased sensitivity to ganciclovir parallel with the ability of AFP production. On the other hand, the retroviral infection had little effect on ganciclovir-mediated cytotoxicity in AFP-nonproducing hepatoma or non-hepatoma cells. Moreover, the addition of dexamethasone increased the cytotoxicity of aciclovir to the virus-infected, AFP-producing cells through a glucocorticoid-responsive element in the AFP promoter, although aciclovir, by itself, had little cytotoxicity. These results demonstrate that the AFP promoter sequence alone can provide enough tumor-specific activity for therapeutic gene expression and induce selective growth inhibition by ganciclovir in the virus-infected, AFP-producing human hepatoma cells. In addition, it is possible that expression of the therapeutic gene is modulated by administration of dexamethasone or other agents that alter AFP promoter activity after gene transduction.

3T3 Cells↗
PubMed1995

Analysis of wild-type and e antigen-defective hepatitis B viruses during the course of a short-term corticosteroid therapy in chronic hepatitis B.

Hepatitis B virus (HBV), with a G-to-a point mutation at nucleotide 83 in the precore region (mutant HBV83), accounts for most cases of hepatitis B e antigen (HBeAg)-defective HBV. However, it is still not clear how mutant HBV83 is associated with HBe seroconversion. Twenty-six HBeAg-positive patients with chronic hepatitis B who received oral prednisolone (30 mg/day) for 3 weeks were studied to clarify the prevalence of mutant HBV83 during the treatment using polymerase chain reaction with a restriction fragment length polymorphism assay. Twelve (46%) patients seroconverted to anti-HBe 1 year after treatment, whereas 14 (54%) did not. The proportion of mutant HBV83 to whole HBV remained unchanged in both groups during an acute exacerbation induced by withdrawal of corticosteroids. Among 12 anti-HBe-seroconverted patients, five (56%) of nine patients with only wild-type HBV at baseline developed detectable levels of mutant HBV83 while all three patients with a mixed viral population of wild-type HBV and mutant HBV83 at baseline developed a higher proportion of mutant HBV83 one year after treatment. In contrast, these changes were observed in only one (14%) of seven who failed to seroconvert. The results indicate that a flare-up of hepatitis precedes emergence or selection of mutant HBV83, followed by HBe seroconversion in patients with chronic hepatitis B.

Adrenal Cortex Hormones↗
PubMed1995

[Systemic and regional myocardial distribution of 123I-BMIPP in normal subjects].

We estimated the systemic and left ventricular (LV) regional myocardial distribution of 123I-BMIPP (beta-methyl-p-iodophenyl-pentadecanoic-acid) in normal subjects (n = 13, mean age 43.9). In planar studies, the count ratios of heart, lung and liver to mediastinum were 2.63, 1.28 and 3.80 in the early images, and 2.23, 1.20 and 2.26 in the delayed images, respectively. The uptake in liver was almost identical with that in heart in the delayed images. In SPECT studies, the regional relative counts in anterior, septal, posterior and lateral LV walls were 100, 98, 96 and 108 (%) in the initial images, and 100, 98, 99 and 107 (%) in the delayed images, respectively. The regional relative uptake was significantly higher in the lateral wall than those in the other parts of LV walls in both images. The relative counts in the basal, mid- and apical portions were 100, 111 and 87 (%) in the initial images, and 100, 113, 92 (%) in the delayed images, respectively. These results suggest that the myocardial regional distribution of BMIPP is not always uniform even in normal subjects. Thus, it is necessary to interpret with caution in the light of these findings, especially for detect in a myocardial lesion in an early phase of cardiomyopathy or a mild myocardial ischemia.

Adult↗
PubMed1994

Activation of ATBF1, a multiple-homeodomain zinc-finger gene, during neuronal differentiation of murine embryonal carcinoma cells.

ATBF1 is a transcription factor containing four homeodomains and 17 zinc fingers. Since the Drosophila homolog, ZFH-2, is implicated in neurogenesis, we examined ATBF1 expression in developing mouse brain and in P19 mouse embryonal carcinoma cells during differentiation. We found that pre- and postnatal mouse brains expressed high levels of ATBF1 mRNA, but the adult brain contained only a small amount of ATBF1 transcripts. In P19 cells, ATBF1 transcripts were undetectable before differentiation; however, 1 day after induction of neuronal differentiation with retinoic acid, ATBF1 mRNA was expressed at a high level. This increased level reached a maximum on the 4th day and then declined. No comparable level of ATBF1 mRNA was expressed when P19 cells were treated with dimethyl sulfoxide to induce muscle cells. These temporal patterns of ATBF1 expression in vivo and in vitro suggest that ATBF1 may play a role in neuronal differentiation.

Animals↗
PubMed1994

Reciprocal regulation of alpha-fetoprotein and albumin gene expression by butyrate in human hepatoma cells.

BACKGROUND/AIMS: Butyrate, a product of colonic bacterial flora, functions as an antiproliferative agent and induces cell differentiation in a variety of cell types. In the present study, the effects of butyrate on cell growth and expression of alpha-fetoprotein (AFP) and albumin genes in HuH-7 human hepatoma cells were investigated. METHODS: The HuH-7 cells were treated with sodium butyrate (0-1 mmol/L), and numbers of viable cells were counted at 24, 48, and 72 hours after treatment. To elucidate the effects of sodium butyrate on AFP and albumin gene expression, Northern blotting and transient chloramphenicol acetyltransferase plasmid transfection experiments were performed. RESULTS: Cell growth was dose dependently inhibited by sodium butyrate. By Northern blot analysis, the level of AFP messenger RNA was reduced by treatment with sodium butyrate, whereas the level of albumin messenger RNA was elevated by this treatment. In transient chloramphenicol acetyltransferase plasmid transfection experiments, sodium butyrate repressed the AFP promoter activity but did not change the AFP enhancer or silencer activities. In contrast, the albumin promoter activity was stimulated by sodium butyrate. CONCLUSIONS: These results suggest that butyrate leads to the reciprocal differentiating regulation of AFP and albumin gene expression at the transcriptional level in human hepatoma cells.

Albumins↗
PubMed1992

A possible mechanism of inverse developmental regulation of alpha-fetoprotein and albumin genes. Studies with epidermal growth factor and phorbol ester.

Epidermal growth factor (EGF) and 12-O-tetradecanoylphorbol-13-acetate (TPA) synergistically suppress activities of the promoter and enhancer of the human alpha-fetoprotein (AFP) gene in HuH-7 human hepatoma cells as analyzed by transient transfection assays using the chloramphenicol acetyltransferase gene as a reporter. In contrast to the AFP gene, albumin promoter and enhancer activities were not affected by EGF and TPA. Unexpectedly, however, Northern blot analysis revealed that the albumin mRNA level as well as the AFP mRNA level were reduced by treatment with EGF and TPA. We propose that in HuH-7 cells, the AFP enhancer stimulates the albumin promoter as well as the AFP promoter; and consequently, inhibition of the AFP enhancer by EGF and TPA results in reduction of both AFP and albumin mRNA levels. The significance of the involvement of the AFP enhancer in albumin transcription is discussed in relation to the inverse pattern of expression of the AFP and albumin genes in neonatal growth.

Albumins↗
PubMed1992

[Left ventricular aneurysm with normal coronary arteriogram after myocardial infarction].

Left ventricular aneurysms after myocardial infarction are generally considered one of the complications of severe coronary artery disease. Postinfarction ventricular aneurysms with normal coronary arteriogram are rare. Only a few cases have been reported previously in Japan. We examined the incidence and the clinical characteristics of postinfarction ventricular aneurysms without coronary obstruction. Among the consecutive 1800 patients studied in our laboratory with selective coronary cineangiography and left ventriography, we found 5 (4 male, 1 female) patients with left ventricular aneurysms with no or minimal coronary arterial obstruction. The patient's ages ranged from 34 to 83 with a mean of 59. Interestingly, no patient had prior anginal history, and every case occurred with a first sudden attack of chest pain. The likely mechanisms causing the development of myocardial infarction were coronary spasm and/or thromboembolic accident. One patient, in whom a coronary induction test was performed, showed positive findings. It is possible that poor collateral circulation and well preserved contraction of viable myocardium in these patients bring about the formation of left ventricular aneurysm after myocardial infarction with normal coronary arteriogram.

Adult↗
PubMed1992

[Case report of angiomyolipoma of the posterior upper mediastinum].

A case of posterior upper mediastinal angiomyolipoma is reported. The patient was an asymptomatic 63-year-old female, in whom an abnormal shadow was detected on chest x-ray at medical examination. On computed tomogram, the mass was located in the right paravertebral upper mediastinum, and its density had a CT-number of 12. It had high MRI intensity. Since there remained a possibility of malignancy, thoracotomy was carried out. The resected tumor was soft in consistency and the size was 20 x 23 x 37 mm. Histological examination showed that the mass was composed of fatty tissue, smooth muscle, and vascular tissue. Therefore, the tumor was diagnosed as angiomyolipoma. Although angiomyolipomas are often found in the kidney, those in the mediastinum are very rare and there have been only 2 cases reported in the literature. We consider that angiomyolipoma is rare, but important in the differential diagnosis of mediastinal tumors.

Aged↗