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F Tashiro

Publications and source records attributed to F Tashiro.

At least 55 records · Page 3Linked to original sources
PubMed1995

Autoepitopes of the 52-kd SS-A/Ro molecule.

OBJECTIVE: This study was undertaken to clarify the mechanisms responsible for the generation of anti-52-kd SS-A/Ro autoantibodies and to elucidate why, as has recently been reported, anti-52-kd autoantibodies preferentially recognize the denatured form rather than the native 52-kd molecule. METHODS: Using a series of truncated 52-kd autoantigens, produced as beta-galactosidase fusion proteins in Escherichia coli, the B cell epitope distribution was probed with 18 anti-Ro-positive sera by immunoblotting and by enzyme-linked immunosorbent assay. RESULTS: Nearly all the antigenicity of the molecule was found to be linked to its leucine zipper region. In a further study using 9 of the 18 sera, the antigenicity of the molecule was found to be mainly formed by multiple conformational epitopes, and one of these epitopes appeared to be universally recognized by all the sera tested. CONCLUSION: The recognition of multiple epitopes indicates that the Ro 52-kd antigen itself drives the autoimmunity to this molecule. Further, the concentration of the antigenicity at the leucine zipper region may explain why anti-52-kd antibodies preferentially recognize the denatured protein rather than its native form.

Autoantibodies↗
PubMed1995

Function of RNH-1/14-3-3 beta gene in cellular differentiation and proliferation.

It has recently been reported that the members of 14-3-3 protein family participate in cell cycle control and associate with Raf, Bcr, Bcr-Abl, and polyomavirus middle tumor antigen (MT) as modulators of signal transduction. During cDNA cloning for the 17-kDa neuronal differentiation factor (K2 factor) secreted from rat hepatoma Kagura-2 (K2) cells from a K2 cDNA library using rat prepronerve growth factor (prepro NGF) cDNA as a probe, we obtained RNH-1 (rat NGF homologue) clone, which was identified as 14-3-3 beta cDNA, but not K2 factor, although no significant homology is present between 14-3-3 beta and prepro NGF cDNAs. RNH-1/14-3-3 beta gene was markedly expressed as a 2.9-kb mRNA in K2 cells and in newborn rat brain tissue. In PC12 cells the expression of this gene was down-regulated during the neuronal differentiation primed by NGF. The enforced expression of RNH-1/14-3-3 beta in PC12 and K2 cells conferred on them a higher sensitivity to NGF for neuronal differentiation and an intense growth ability in low serum medium, respectively. These results provide additional evidence that RNH-1/14-3-3 beta protein participates in cellular differentiation, proliferation and transformation through the signal transduction pathways of various growth factors.

14-3-3 Proteins↗
PubMed1995

A 6-kb upstream region of the human transthyretin gene can direct developmental, tissue-specific, and quantitatively normal expression in transgenic mouse.

To ascertain whether a 6-kb upstream region of the human transthyretin (TTR) gene contains the cis-element(s) required for proper specificity and level of expression, transgenic mice carrying the human mutant TTR gene containing either 6-kb (6.0-hMet30) or 0.6-kb (0.6-hMet30) of the upstream region were produced and studied. The 6.0-hMet30 gene was expressed in the yolk sac, liver, and choroid plexus, where the mouse endogenous TTR gene is also expressed. In contrast, expression of the 0.6-hMet30 gene was restricted to the yolk sac and liver. The expression levels of the 6.0-hMet30 gene in the liver and serum were similar to those of the mouse TTR gene, and about 10-fold those of the 0.6-hMet30 gene. Before birth, the developmental profiles of the expression of both transgenes in each tissue were similar to those of the mouse TTR gene. However, the expression levels of the 6.0-hMet30 gene in the liver and serum increased after birth to reach adult levels at an age of 4 weeks, while expression of the 0.6-hMet30 gene remained at a low level after birth. These results suggest that the 6-kb upstream sequence contains the cis-elements required for developmental, tissue-specific, and quantitatively normal expression.

Animals↗
PubMed1994

Mutation of low affinity nerve growth factor receptor gene in spontaneously hypertensive and stroke-prone spontaneously hypertensive rats: one of the promising candidate genes for hypertension.

There is evidence that abnormal formation of the sympathetic nervous system might be important for pathogenesis of hypertension. In the present study we analyzed nucleotide sequences of low affinity nerve growth factor receptor (LNGFR) genes in the spontaneously hypertensive rat and its stroke-prone substrain. There was a point mutation generating an amino acid substitution in signal peptide of these LNGFRs. This result suggested that the mutated LNGFR gene is one of the promising candidate genes for hypertension.

Amino Acid Sequence↗
PubMed1994

Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice.

To study the paracrine effect of IL-10 on autoimmune insulitis and diabetes, we produced IL-10 transgenic non-obese diabetic (NOD) mice (NOD-IL-10) in which murine IL-10 was expressed in pancreatic islet A cells under the control of a rat glucagon promoter without directly manipulating pancreatic islet B cells. Among 11 founder mice, four of four males and three of seven females developed diabetes by 10 weeks of age. Histological analysis of six NOD-IL-10 revealed severe insulitis and prominent ductal proliferation. NOD-IL-10 also showed spotty lymphocytic infiltration in the lung and liver in four of six founder mice. The onset of diabetes in NOD-IL-10 was remarkably earlier than that of 14 weeks of age at the earliest in female non-transgenic NOD mice. When the NOD-IL-10 mouse was backcrossed to C57BL/6 mice, none of the resulting F1, B-N2 or B-N3 generation toward C57BL/6 mice showed diabetes even at 39 weeks of age, in spite of the presence of peri-insulitis and prominent ductal proliferation, while two of four mice of the N-N2 generation toward NOD mice showed early-onset diabetes. Thus, transgenic paracrine expression of IL-10 in situ in the NOD genetic background enhances autoimmune insulitis and diabetes in their onset and severity, ignoring gender difference. Because expression of IL-10 was detected by polymerase chain reaction in pancreatic islets of non-transgenic NOD mice after 5 weeks of age, IL-10 secreted in situ is regarded to enhance cell-mediated autoimmune diabetes, in spite of established in vitro anti-Th1 activity of IL-10.

Animals↗
PubMed1994

Resistance to cyclophosphamide-induced diabetes in transgenic NOD mice expressing I-Ak.

Transgenic expression of the MHC (major histocompatibility complex) class II I-Ak molecule was previously shown to effectively reduce the incidence of insulitis in non-obese diabetic (NOD) mice at the age of 20 weeks. We have further characterized the expression and function of the I-Ak molecule and examined its effects on the incidence of diabetes in NOD mice. The newly expressed I-Ak molecule was recognized as an alloantigen by the T lymphocytes of normal NOD mice as shown by mixed lymphocyte reaction (MLR). The levels of endogenous I-Ag7 expression on peripheral blood lymphocytes were not affected by the transgene expression. Transgenic NOD mice were completely resistant to spontaneous diabetes, but the treatment by cyclophosphamide, which effectively induces diabetes in normal NOD mice, caused diabetes, although at a much lower incidence than that of normal NOD mice. On the basis of these findings, we discuss the role of I-Ak in the prevention of diabetes in NOD mice.

Animals↗
PubMed1994

[Current studies on the identification of susceptibility genes for IDDM in NOD mice].

Until recently, localization of genes involved in multifactorial diseases, such as diabetes, was thought to be impracticable. The recent development of microsatellite genetic markers detected by PCR has facilitated detailed genetic analysis of complex traits. Microsatellite markers have been utilized for genetic analysis of NOD mice which spontaneously develop autoimmune IDDM similar to the human disease. There is evidence for ten distinct loci that affect the development of insulitis and diabetes in NOD mice. One of these loci, designated Idd-1, has been linked to the MHC on chromosome 17. Transgenic mouse experiments have shown that Idd-1 is composed of MHC class II genes I-A beta and I-E alpha.

Animals↗
PubMed1993

Effects of nivalenol on hepatic drug-metabolizing activity in rats.

Effects of nivalenol (NIV), a trichothecene mycotoxin, on hepatic drug-metabolizing activity and aflatoxin B1 (AFB1) metabolism were investigated in male rats. In rats fed the diets containing 6-12 ppm NIV for 2 or 4 wk, decreases in initial feed uptake, terminal weight gain and organ weights were evident. An increase in cytochrome P-450 activity was observed in the hepatic microsomes, and Western blot analysis revealed a transient increase in P4502B1/2, together with a slight induction of P4501A2. The activity of cytosolic glutathione S-transferase (GST) enzymes was also enhanced in the rats, and Western blot analysis demonstrated an elevation of GST 1-2. The formation of aflatoxin B1-DNA adducts (AFB1-DNA) was increased in experiments using hepatic microsomal preparations from rats fed the NIV diet, whereas supplementation with cytosol prepared from NIV-treated rats reduced the microsomal potential for adduct formation. In in vivo experiments, the AFB1-DNA concentration in NIV-treated rats was lower than that in the controls. These results suggest that activities of cytochrome P-450 and GST enzymes were increased in rats fed NIV for several weeks. Alteration of these phase I and phase 2 enzyme levels resulted in the modulation of AFB1 adduction to DNA in vitro and in vivo.

Administration, Oral↗
PubMed1992

[Transgenic mouse and gene targeting].

Transgenic mouse technology has proved to be a powerful tool for medical research. So far, a large number of transgenic mice have been generated expressing, e.g. oncogenes, viral genes, immunoglobulins, lymphokines and MHC antigens, and have provided much valuable information. Furthermore, gene targeting technology (homologous recombination between specific chromosomal DNA sequences and exogenously introduced DNA sequences) has been improved and applied to pluripotent, mouse embryonic stem (ES) cells, providing the means to create mice of specifically altered genotype. In this review, some of the background and recent advances of transgenic mouse technology and gene targeting in mouse ES cells are described.

Animals↗
PubMed1992

Effect of serum amyloid P component level on transthyretin-derived amyloid deposition in a transgenic mouse model of familial amyloidotic polyneuropathy.

To elucidate the pathogenesis of amyloid deposition associated with familial amyloidotic polyneuropathy (FAP), we developed several transgenic mouse lines carrying the human mutant transthyretin (TTR) gene. We found that human TTR and mouse serum amyloid P component (SAP) are deposited as amyloid in tissues of these mouse lines. Because SAP is a major acute-phase reactant in mice, we asked whether repeated injections of Escherichia coli lipopolysaccharide (LPS) would enhance the amyloid deposition in one of these transgenic mouse lines. During the course of repeated LPS injections, serum levels of SAP in the transgenic mice remained between severalfold to about 50-fold higher than seen in the absence of stimulation. As no significant difference was detected in the onset, progression, and tissue distribution of TTR-derived amyloid (ATTR) deposition between the LPS-stimulated and unstimulated transgenic mice, the induction of SAP synthesis by acute inflammation probably does not affect the onset and extent of ATTR deposition.

Amyloid↗
PubMed1991

Elevation of nerve growth factor synthesis by constitutive expression of v-src oncogene in cultured rat fibroblasts.

Rat fibroblast 3Y1 cells transformed by Rous sarcoma virus (RSV) or transfected with the v-src gene showed a highly constitutive v-src gene expression. Simultaneously, marked increases in the cellular level of nerve growth factor (NGF) mRNA and NGF content in the culture medium were observed. The levels of NGF mRNA and NGF secreted into the medium were correlated with the expression level of v-src mRNA gene in both transformants and control 3Y1 cells. These results suggest that v-src gene expression is relevant to regulation of NGF synthesis in rat 3Y1 fibroblasts.

Animals↗
PubMed1991

Transformation of mammalian cells by luteoskyrin.

The transforming activity of luteoskyrin (LS), a bis-anthraquinoid mycotoxin produced by Penicillium islandicum Sopp., and a hepatocarcinogen in rodents, was examined by an in vitro transformation assay using mouse embryonal Balb/3T3 A31-1-1 cells. The results revealed that LS induced type III foci at 0.5 micrograms/ml, and that the cells selected from these foci by soft-agar cloning grew with a high saturation density. Thus, it was confirmed that LS not only induces hepatic tumours in laboratory animals, but also transforms in vitro cultured mammalian cells. The tumorigenicity of the transformants obtained was confirmed by transplantation into nude mice and by image analysis with IIIIn. A transfection assay, using calcium phosphate co-precipitation, demonstrated that the DNA of the cloned cells transformed NIH3T3 cells. Northern blot also revealed transcriptional activation of c-myc and c-Ha-ras oncogenes. The possible participation of LS-derived hydroxy radicals in the formation of genetic lesions was discussed.

Animals↗
PubMed1991

Role of serum amyloid P component for systemic amyloidosis in transgenic mice carrying human mutant transthyretin gene.

The role of serum amyloid P component (SAP) for systemic amyloidosis in a transgenic mouse model for an autosomal dominant disease, familial amyloidotic polyneuropathy (FAP), was examined. For this purpose, two lines of transgenic mouse were produced by introducing the human mutant transthyretin (TTR) gene and the human SAP gene, respectively. Two lines of transgenic mice were mated to produce double transgenic mice carrying both human mutant TTR gene and human SAP gene. The serum concentration of human SAP in these transgenic mice was about 42 micrograms/ml and was about equal to that in human control serum. In case of single transgenic mice carrying human mutant TTR gene, amyloid deposition starts at around 6 months of age, and the amount of amyloid deposition increases gradually with age. Amyloid deposition is observed in many tissues including heart, kidney and thyroid gland, where amyloid deposition is commonly observed in FAP patients. In double transgenic mice, onset, progression and tissue distribution of amyloid deposition were the same as those in single transgenic mouse. These results clearly suggest that SAP is not important for the initiation and progression of amyloid deposition.

Age Factors↗
PubMed1991

Effect of long-term feeding of nivalenol on aflatoxin B1-initiated hepatocarcinogenesis in mice.

Nivalenol, a trichothecene, occurs widely in cereals and foods; our current two-year feeding trial has revealed no tumorigenic activity in female mice. To investigate whether dietary nivalenol modulates the development of aflatoxin B1 (AFB1)-initiated hepatocarcinogenesis, one-week old C57Bl/6 x C3H F1 mice were injected intraperitoneally with 6 mg/kg bw AFB1 and six weeks later fed diets containing 0, 6 or 12 ppm nivalenol for one year. Male mice in all three groups developed hepatocellular carcinomas and adenomas, while the incidences in females were 31% in those given AFB1 alone and 20% and 0 in those given AFB1 with 6 and 12 ppm nivalenol, respectively. These findings indicate that dietary nivalenol suppresses AFB1-initiated hepatocarcinogenesis in female mice, presumably by acting on the promotion step.

Aflatoxin B1↗
PubMed1991

Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met30) gene. Pathologic similarity to human familial amyloidotic polyneuropathy, type I.

To analyze the pathologic processes of amyloid deposition in type I familial amyloidotic polyneuropathy (FAP), mice were made transgenic by introducing the human mutant transthyretin (TTR) gene. In these transgenic mice, amyloid deposition started in the gastrointestinal tract, cardiovascular system, and kidneys 6 months after birth and extended to various other organs and tissues with advancing age. At age 24 months, the pattern of amyloid deposition was similar to that observed in human autopsy cases of FAP, except for its absence in the choroid plexus and in the peripheral and autonomic nervous systems. Amyloid deposition was shown to be composed of human mutant TTR and, in addition, mouse serum amyloid P component. These results clearly indicate that human variant TTR produced in transgenic mice deposits is a major component of amyloid fibrils in various organs and tissues. Thus this animal model is useful for analyzing how amyloid deposition initiates and proceeds in FAP.

Amyloid↗
PubMed1990

Establishment and characterization of cell lines (Kagura-1 and Kagura-2) from aflatoxin B1-induced rat hepatoma.

Two hepatoma cell lines designated Kagura-1 and Kagura-2 were established from rat hepatocellular carcinomas induced by aflatoxin B1, and have been propagated for over two years. Both cell lines grew as monolayered sheets with a population doubling time of about 20 h. Chromosome counts of Kagura-1 cells ranged from 34 to 45 with a modal number of 40, while that of Kagura-2 cells ranged widely from 40 to 130 with a modal number of 65. Subcutaneous inoculation of cultured cells of both these lines into nude mice resulted in tumor formation. The histopathological appearances of the induced tumors were similar to those of the original tumors. Kagura-1 and Kagura-2 cell lines express at least two tumor markers, glutathione-S-transferase P and gamma-glutamyl transpeptidase; the level of c-myc messenger ribonucleic acid was also highly elevated.

Aflatoxin B1↗