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Biomedical subjects

T Taniguchi

Publications and source records attributed to T Taniguchi.

At least 343 records · Page 19Linked to original sources
PubMed1996

Identification of the lysyl oxidase gene as target of the antioncogenic transcription factor, IRF-1, and its possible role in tumor suppression.

The transcriptional activator IFN regulatory factor 1 (IRF-1) and its antagonistic repressor IRF-2 are regulators of the IFN system. IRF-1 also manifests tumor suppressive activity, and its inactivation could contribute to the development of human hematopoietic malignancies. Here, we report the identification of the lysyl oxidase gene as a target gene of IRF-1. An IRF response element was identified in the lysyl oxidase gene promoter. We also demonstrate that the transformed phenotype of ras-expressing embryonic fibroblasts with a null mutation in the IRF-1 allele could be suppressed by the expression of the lysyl oxidase cDNA, implicating its potential role in tumor suppression. Thus, the regulation of the lysyl oxidase gene by IRF-1 could contribute to the multistep process of malignant transformation.

3T3 Cells↗
PubMed1996

Changes of neurocalcin, a calcium-binding protein, in the brain of patients with Alzheimer's disease.

We assessed the amount of neurocalcin, a calcium-binding protein, in samples from the postmortem normal human and Alzheimer's disease (AD) brains using a specific antibody. In the AD brains, the amount of neurocalcin in the temporal cortical tissues was significantly lower than that in the controls. Neurocalcin was detected immunohistochemically mainly in the neuropil in the temporal cortex, and its localization was very similar to that of synaptophysin. These findings suggest that reduced levels of neurocalcin reflect a biochemical deficit related to the synaptic degeneration in AD.

Aged↗
PubMed1996

Cholecystokinin-B/gastrin receptors mediate rapid formation of actin stress fibers.

Specific receptors for brain-gut peptide hormones, cholecystokinin (CCK) and gastrin, are expressed in a variety of human tumor cells. CCK and gastrin promote the growth of NIH3T3 cells into which the CCK-B/gastrin receptor had been introduced via a eukaryotic expression vector. In this study, we have examined the effect of CCK-8 on the actin cytoskeleton by using two mouse fibroblast cell lines expressing human CCK-B/gastrin receptors. Treatment with very low concentration of CCK-8 (10(-10) M) induced the formation of actin stress fibers within one minute. Stress fiber formation increased for 30 min. In contrast, a potent mitogen for fibroblasts, platelet-derived growth factor (PDGF), initially induced membrane ruffling and, later, a weak formation of stress fibers. Microinjection of rho GDP dissociation inhibitor or Clostridium botulinum ADP-ribosyltransferase C3 which is known to impair the function of a small GTP-binding protein, rho p21, inhibited the stress fiber formation by CCK-8 as well as by PDGF. These results indicate that CCK-B/gastrin receptor could regulate stress fiber formation in a rho p21-dependent manner. The signals from CCK-B/gastrin receptor might affect cell growth as well as cell motility or adhesion by regulating the actin cytoskeleton.

3T3 Cells↗
PubMed1996

Quantitative analysis of vascular endothelial growth factor in primary breast cancer.

BACKGROUND: Recent clinical studies have demonstrated that tumor angiogenesis is a potent prognostic indicator for breast cancer patients. The quantitation of endothelial growth factors is thought to be useful to assess angiogenic phenotype in the tumor. Among the many new endothelial growth factors, vascular endothelial growth factor (VEGF) is known to be particularly responsible for promoting the neovascularization in human breast cancer. METHODS: Intratumoral protein levels of VEGF were measured by enzymatic immunoassay in 135 primary breast cancer tissues. The VEGF levels were compared with the microvessel density evaluated by immunostaining the endothelial antigen and also were compared with intratumoral protein levels of other endothelial growth factors, including basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF). RESULTS: Intratumoral VEGF concentrations varied from 3.3 pg/mg protein to 2032 pg/mg protein (average 148 pg/mg protein). An immunocytochemical analysis using anti-VEGF antibody confirmed that VEGF was located mainly in the cytoplasm of the tumor cells. The VEGF concentrations were significantly higher in vascularly rich tumors than in vascularly poor tumors. No significant association was found between VEGF concentrations and the two other endothelial growth factor concentrations. CONCLUSIONS: The quantitation of intratumoral VFGF levels seems to be useful for assessing the activity of tumor angiogenesis.

Breast Neoplasms↗
PubMed1996

In vivo induction of inducible nitric oxide synthase by microinjection with interferon-gamma and lipopolysaccharide in rat hippocampus.

To clarify whether the inducible nitric oxide synthase (iNOS) protein can be induced in in vivo brain, we examined the influence of direct intrahippocampal injection with interferon-gamma (IFN-gamma) plus lipopolysaccharide (LPS) in the rat. In the area surrounding the microinjection site, NOS activity (NO2- accumulation) was enhanced 24 h after injection with IFN-gamma plus LPS. Although the level of 160-kDa nNOS protein was not changed, the 130-kDa iNOS protein was induced 12 h after the injection. On the other hand, iNOS mRNA could be detected at 6 and 12 h but not at 24 h. iNOS immunoreactivity was observed in CD11b-immunopositive microglia in close proximity to the injection site, but the immunoreactivity was not colocalized with glial fibrillary acidic protein-immunopositive astrocytes. Although CD11b-immunopositive microglia were of the ramified type even after injection with vehicle after 24 h, injection with IFN-gamma plus LPS caused numerous microglia to change to the ameboid type and to express major histocompatibility complex (MHC) class II antigens. In some of these ameboidal microglia, iNOS immunoreactivity was observed. These results suggest that intrahippocampal injection with IFN-gamma plus LPS induced iNOS mRNA after 6 h and iNOS protein after 12 h in some of the ameboidal microglia that expressed MHC class II antigens in in vivo rat brain.

Animals↗
PubMed1996

Ampullary somatostatinoma in a patient with von Recklinghausen's disease.

We report a case of somatostatinoma of the ampulla of Vater associated with von Recklinghausen's disease in a 44-year-old woman. On admission the patient was jaundiced, and percutaneous Cholangio-drainage was performed. Cholangiography revealed stenosis of the common bile duct at the lower end Duodenoscopy showed a yellowish tumor of the ampulla of Vater, and the biopsy specimens showed no malignant cells. Pylorus-preserving pancreaticoduo-denectomy was performed. Histologically, the tumor was composed of small round cells with a solid or trabecular pattern and with multiple psammoma bodies. Immunohistochemical examination showed that the tumor cells stained for somatostatin. Genomic examination showed neither K-ras nor p53 gene mutations of the resected specimen.

Adult↗
PubMed1996

The precipitate formed by thiopentone and vecuronium.

PURPOSE: To determine the composition and solubility of the precipitate formed by thiopentone and vecuronium in vitro. METHODS: The precipitate formed by mixing thiopentone 2.5% and vecuronium 0.1% at room temperature was analyzed by ultraviolet spectrophotometry and high performance liquid chromatography (HPLC). The solubility of the precipitate in human plasma was measured by HPLC. RESULTS: The UV absorption spectrum of the precipitate resembled that of thiopentone. HPLC analysis produced a single peak with the same retention time as thiopentone (4.6 min). In human plasma the solubility of the precipitate was not different from that of thiopentone acid. The solubility of thiopentone was greater than that of the precipitate. CONCLUSION: The precipitate formed by thiopentone and vecuronium in vitro consisted of thiopentone acid, which was insoluble in human plasma.

Chemical Precipitation↗
PubMed1996

Effects of lipoprotein(a) and low density lipoprotein on growth of mitogen-stimulated human umbilical vein endothelial cells.

We investigated the effects of lipoprotein(a) (Lp(a)) and low density lipoprotein (LDL) on proliferation of human umbilical vein endothelial cells (HUVECs). Both Lp(a) and LDL stimulated the growth of HUVECs synergistically with basic fibroblast growth factor and insulin in a dose-dependent manner. The potency of Lp(a) to promote the cell proliferation was 40% less than that of LDL. Addition of anti-transforming growth factor-beta 1 neutralizing antibody into the medium could not diminish the difference of HUVECs proliferation by Lp(a) and LDL. However, addition of anti-LDL receptor antibody suppressed HUVECs proliferation to the same level and sequestered the difference by the two lipoproteins. Moreover, cholesteryl ester content incubated with Lp(a) was 50% less than that with LDL. These results suggest that Lp(a) has less effect on HUVECs proliferation and cholesterol delivery to the cells than LDL. Therefore, Lp(a) may play a role as an atherogenic lipoprotein by delaying the repair of endothelium after injury.

Cell Division↗
PubMed1996

Relationship of acid phosphatase activity to ultrastructural features in mice inoculated with Mycobacterium paratuberculosis.

Macrophage activation, measured as increased acid phosphatase (AcPase)-positive areas by image analysis, and ultrastructural features were examined in granulomatous mycobacterial lesions of mice innately susceptible (BALB/c mice; Bcg) and innately resistant (C3H/HeJ mice; Bcg) to Mycobacterium paratuberculosis strain ATCC 19698. In the liver and spleen of BALB/c mice 3 weeks after intraperitoneal inoculation with M. paratuberculosis, AcPase activity detected in epithelioid cell nodules was high; it had decreased, however, in the liver and spleen after a further 3 and 6 weeks, respectively. In C3H/HeJ mice, the size of epithelioid cell nodules in the liver and spleen was smaller than in BALB/c mice, and infiltrating macrophages, which had increased by week 9 after inoculation, showed high AcPase activity. Ultrastructurally, by week 32 in BALB/c mice, small phagolysosomes (SPLs) had greatly increased in number in the epithelioid cells. These SPLs contained a few AcPase-positive areas and a small number of bacteria, most of which were surrounded by an electron-translucent space (or electron-transparent zone [ETZ]). In contrast, only a few SPLs were observed in C3H/HeJ mice at week 32; in the liver and spleen, large phagolysosomes (LPLs) showed high AcPase activity and contained many degenerated bacteria, which also had an ETZ. These results suggest that the enzymatic and ultrastructural differences in phagolysosomes between BALB/c mice and C3H/HeJ mice reflect the susceptibility of these mouse strains to M. paratuberculosis.

Acid Phosphatase↗
PubMed1996

Trabeculotomy ab externo, cataract extraction, and intraocular lens implantation: preliminary report.

PURPOSE: To compare the results of a triple procedure using either extracapsular cataract extraction (ECCE) or one of two phacoemulsification techniques combined with trabeculotomy ab externo and intraocular lens (IOL) implantation. SETTING: Kyoto University Hospital, Kyoto, Japan, and Nagata Eye Hospital, Nara, Japan. METHODS: In this comparative study, 25 eyes with primary open-angle glaucoma had ECCE combined with trabeculotomy ab externo and IOL implantation and 22 had the same procedure using phacoemulsification instead of ECCE. Of the eyes that had phacoemulsification, 10 had a single-flap and 12 had a double-flap procedure. RESULTS: All 22 eyes that had phacoemulsification had a postoperative IOP of 21 mm Hg or less, as did all ECCE eyes except 2. Although the self-sealing incision might have caused the higher incidence of IOP spikes in the immediate postoperative period, IOPs in the phacoemulsification groups were lower after 3 months. Results were similar in the single-flap and double-flap phacoemulsification groups. There were no significant complications. CONCLUSION: Cataract extraction by phacoemulsification or ECCE combined with IOL implantation and trabeculotomy ab externo is a safe, effective treatment for patients with coexisting glaucoma and cataract.

Aged↗
PubMed1996

Somatic overgrowth associated with overexpression of insulin-like growth factor II.

Overexpression of the normally imprinted fetal insulin-like growth factor II (IGF2) has been implicated in the pathogenesis of the cancer-predisposing Beckwith-Wiedemann syndrome (BWS). We have detected constitutional relaxation of imprinting of IGF2 in four children with somatic overgrowth who do not show diagnostic features of BWS. Three children showed constitutional abnormalities of H19 methylation. All four children showed nephromegaly and two developed Wilms' tumors. Gene methylation is known to be associated with gene silencing, and three children showed constitutional abnormalities of H19 gene methylation. Disruption of H19 methylation, and concomitant relaxation of IGF2 imprinting, provides another mechanism that can increase IGF2 expression in children with overgrowth. The accumulated data on normal and pathologic IGF2 expression are now sufficient to define an entity, "IGF2 overgrowth disorder," of which BWS may be one extreme manifestation. These findings have broad implications for the characterization of idiopathic overgrowth.

Base Sequence↗
PubMed1996

Essential and non-redundant roles of p48 (ISGF3 gamma) and IRF-1 in both type I and type II interferon responses, as revealed by gene targeting studies.

BACKGROUND: Interferons (IFNs) are a class of cytokines which confer cellular resistance against viral infections. Type I (IFN-alpha and -beta) and type II (IFN-gamma) IFNs utilize distinct receptors, the stimulation of which results in the induction of downstream target genes. These target genes usually contain within their promoter region an IFN responsive element, termed ISRE (IFN stimulated response element) which binds a heterotrimeric transcription factor, ISGF3 (IFN-stimulated gene factor 3) consisting of p48 (ISGF3 gamma), Stat1 (Signal transducers and activators of transcription-1; alpha or beta), and Stat2. The ISRE sequence overlaps with that of IRF-E which binds another IFN-inducible factor, IRF-1 (IFN regulatory factor-1). RESULTS: We generated mice lacking p48 by gene targeting. We show that p48 plays an essential role in both type I and type II IFN responses; activation of IFN-inducible genes and establishment of the antiviral state by IFN-alpha or -gamma are both severely impaired, and ISRE-binding activities induced by both IFNs are absent in the p48-negative embryonic fibroblasts (EFs). Furthermore, we generated mice deficient for both p48 and IRF-1 and found that at least one IFN-inducible gene is dependent on both factors. CONCLUSIONS: p48 and IRF-1 do not perform redundant functions in the cell, but rather complement one another in both type I and II IFN responses.

Animals↗
PubMed1996

Regulation of IFN-alpha/beta genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN-alpha/beta.

BACKGROUND: Efficient production of interferons (IFNs) in virally infected cells is an essential aspect of the host defence. The transcription factor complex ISGF3 (IFN-stimulated gene factor 3) was originally identified as a critical mediator of the IFN signal; it is formed upon IFN receptor (IFNR) stimulation and binds to ISREs (IFN-stimulated response elements) to activate IFN-inducible genes. It has recently been shown that the DNA binding component of ISGF3, p48 (ISGF3gamma) also binds to virus-inducible elements in the IFN-alpha/beta genes, suggesting a potential new role of p48 in IFN production. RESULTS: Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus-induced IFN-alpha/beta gene expression. A similar defect was also observed in cells lacking type I IFNR or Stat1, further demonstrating the role of IFN signalling in the induction of these IFN genes. ISGF3 in fact binds to the virus-inducible elements within the IFN-alpha/beta promoters. We also provide evidence showing that these elements are additionally controlled by an unidentified factor(s) which presumably triggers the primary phase of IFN gene induction. CONCLUSIONS: Our results demonstrate that the IFN signal transducing complex ISGF3 plays a crucial role in IFN production and suggest that ISGF3 may participate directly in the activation of IFN-alpha/beta promoters. This dual function of ISGF3 may insure the efficient operation of this cytokine system in the host defence.

Animals↗
PubMed1996

Ca2+-dependent and Ca2+-independent protein kinase C changes in the brain of patients with Alzheimer's disease.

We examined protein kinase C (PKC) activity in Ca2+-dependent PKC (Ca2+-dependent PKC activities) and Ca2+-independent PKC (Ca2+-independent PKC activities) assay conditions in brains from Alzheimer's disease (AD) patients and age-matched controls. In cytosolic and membranous fractions, Ca2+-dependent and Ca2+-independent PKC activities were significantly lower in AD brain than in control brain. In particular, reduction of Ca2+-independent PKC activity in the membranous fraction of AD brain was most enhanced when cardiolipin, the optimal stimulator of PKC-epsilon, was used in the assay; whereas Ca2+-independent PKC activity stimulated by phosphatidylinositol, the optimal stimulator of PKC-delta, was not significantly reduced in AD. Further studies on the protein levels of Ca2+-independent PKC-delta, PKC-epsilon and PKC-zeta in AD brain revealed reduction of the PKC-epsilon level in both cytosolic and membranous fractions, although PKC-delta and PKC-zeta levels were not changed. These findings indicated that Ca2+-dependent and Ca2+-independent PKC are changed in AD, and that among Ca2+-independent PKC isozymes, the alteration of PKC-epsilon is a specific event in AD brain, suggesting its crucial role in AD pathophysiology.

Alzheimer Disease↗