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Biomedical subjects

M Mori

Publications and source records attributed to M Mori.

At least 109 records · Page 6Linked to original sources

A ligand for peroxisome proliferator activated receptor gamma inhibits cell growth and induces apoptosis in human liver cancer cells.

BACKGROUND AND AIMS: Induction of apoptosis of cancer cells through ligands of nuclear hormone receptors (NHRs) is a new approach in cancer therapy. Recently, one of the NHRs, peroxisome proliferator activated receptor gamma (PPARgamma), has been shown to influence cell growth in certain cancer cells although its effect on hepatocellular carcinoma (HCC) has not been analysed. METHODS: Experiments were conducted using three human liver cancer cell lines, PLC/PRF/5, Hep G2 and HuH-7, in vitro. These cells were exposed to troglitazone, a synthetic ligand for PPARgamma, and the effects on cell growth were analysed. RESULTS: Expression of PPARgamma mRNA was detected in all three liver cancer cell lines. Activation of PPARgamma by troglitazone caused a marked growth inhibition in a dose dependent manner in three hepatoma cell lines. The DNA fragmentation ELISA assay and Hoechst 33258 staining revealed that the growth inhibitory effect by adding troglitazone was due to apoptosis of PLC/PRF/5, which strongly expressed PPARgamma. Troglitazone also induced activation of the cell death protease, caspase 3, but not caspase 8, in PLC/PRF/5 cells. However, expression levels of antiapoptotic factor bcl-2 and apoptosis inducing factor bax were not affected. CONCLUSION: Our study showed that PPARgamma was expressed in human liver cancer cells and that the ligand for PPARgamma, troglitazone, inhibited the growth of these cells by inducing apoptosis through caspase 3 activation, indicating that troglitazone could be potentially useful as an apoptosis inducer for the treatment of HCC.

Antineoplastic Agents↗

Distribution patterns of demyelination correlate with clinical profiles in chronic inflammatory demyelinating polyneuropathy.

BACKGROUND: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder having a wide clinical range, and is characterised by multifocal demyelination that can involve the distal nerve terminals, intermediate nerve segments, and nerve roots. OBJECTIVE: To investigate whether the distribution patterns of demyelination along the course of the nerve correlate with clinical profiles in patients with CIDP. METHODS: Motor nerve conduction studies were carried out on 42 consecutive patients. According to the physiological criteria for demyelination, the presence of a demyelinative lesion was determined in the distal nerve segments (distal pattern) or intermediate nerve segments (intermediate pattern), or in both (diffuse pattern). The serum concentration of tumour necrosis factor (TNF)-alpha was measured by immunoassay. RESULTS: Patients were classified as having a distal (n=10), intermediate (n=13), or diffuse (n=15) pattern, or were unclassified (n=4). Patients with the distal or diffuse pattern had common clinical features such as subacute onset, symmetric symptoms, and weakness involving proximal as well as distal muscles. Patients with the distal pattern had a good response to treatment and a monophasic remitting course, but the diffuse pattern was associated with a treatment dependent relapsing course, reflecting longer disease activity. The serum TNF-alpha concentrations increased only in the "diffuse" subgroup of patients, and this might be associated with breakdown of the blood-nerve barrier and therefore, involvement of the intermediate segments. The intermediate pattern was characterised by a chronic course, asymmetric symptoms, less severe disability, and refractoriness to treatments. CONCLUSIONS: CIDP consists of subtypes with varying predilections for lesions along the course of the nerve. The distribution patterns of conduction abnormalities may be useful in the prediction of outcome of patients with CIDP.

Adolescent↗

Spinal reconstruction for symptomatic thoracic haemangioma using a titanium cage.

Most vertebral haemangiomas are asymptomatic. A case of spinal reconstruction for symptomatic extraosseous thoracic haemangioma using a titanium cage is reported. Radiographs of the T11 vertebra demonstrated characteristic vertical striations. Magnetic resonance imaging and computed tomography showed spinal cord compression by extraosseous tumour extension. Several tumour feeding vessels were shown by angiography. Through a transpedicular biopsy, a histological diagnosis of cavernous haemangioma was made. Embolisation of feeding vessels was performed using coils before surgery. Laminectomy and subtotal vertebrectomy were performed by a single posterior approach. Rigid stabilisation of the spine was achieved with pedicle screw systems and a cage filled with an autogenous bone graft. Five months postoperatively, stabilisation of the spine was established without loosening of the cage or pedicle screws. Clinical symptoms were improved.

Aged↗

Surface expression of toll-like receptor 4 on THP-1 cells is modulated by Bu-Zhong-Yi-Qi-Tang and Shi-Quan-Da-Bu-Tang.

Human Toll-like receptor 4 (TLR4) has recently been identified and has been shown to be the main protein involved in recognizing Gram-negative bacteria. We examined the regulation of TLR4 surface expression in a human monocytic cell line (THP-1 cells) by two traditional Chinese herbal medicines. Bu-Zhong-Yi-Qi-Tang (TJ-41) and Shi-Quan-Da-Bu-Tang (TJ-48). TJ-41 and TJ-48 upregulated TLR4 surface expression in THP-1 cells, as well as enhanced TLR4 surface expression in these cells both dose- and time-dependently. These findings suggest that TJ-41 and TJ-48 increase the receptor involved in the response to Gram-negative bacteria and may enhance defenses against these pathogens.

Animals↗

Allelic imbalance and microsatellite instability in plasma DNA released from polyclonal pancreatic adenocarcinoma.

Evidence of circulating soluble DNA in blood-stream of cancer patients has emerged. Because the plasma DNA is largely derived from cancer cells, genetic analysis of plasma DNA is important to understand the molecular events occurred in cancer patient. Seven microsatellite markers in the soluble plasma DNA from patients with pancreatic adenocarcinoma and other pancreato-biliary malignant tumors were examined for microsatellite instability (MSI) and allelic imbalance (AI). A variety of genetic alterations including MSI and AI were detected in the plasma DNA. Some alterations were detected before recurrence of the tumor was verified. Analysis of five primary pancreatic adenocarcinomas by microdissection revealed that the heterogeneous nature of pancreatic tumors is associated with both MSI and AI in the same tumor. The presence of altered plasma DNA including MSI and/or AI from the same pancreatic cancer patient may be important evidence for the presence of these alterations in heterogeneous primary tumors. Analysis of plasma DNA could become one of the diagnostic or therapeutic measures for this type of pancreatic adenocarcinoma.

Aged↗

Association of parvovirus B19 infection with acute glomerulonephritis in healthy adults: case report and review of the literature.

An otherwise healthy 20-year-old woman presented with an erythematous rash on her face as well as arthralgia and anemia. She also had systemic edema, proteinuria and hypertension. Laboratory data on admission showed hypocomplementemia, human parvovirus B 19 (HPV) DNA and both immunoglobulin (Ig) M and IgG antibodies to HPV in her serum. Renal biopsy specimens showed features of endocapillary glomerulonephritis under light microscopy. Electron microscopy showed massive subendothelial electron-dense deposits. No cause was probable other than immune complex-mediated glomerulonephritis associated with HPV infection. In a review of this and similar cases reported in the literature, several characteristic features come to light: female dominance, onset in the second or third decade of life, hypocomplementemia, histologic renal endocapillary and/or mesangioproliferative glomerulonephritis with subendothelial deposits and spontaneous recovery.

Adult↗

Increased levels of platelet-associated immunoglobulin G in a patient with mixed connective tissue disease.

We report the case of a 71-year-old Japanese woman with mixed connective tissue disease and increased levels of platelet-associated immunoglobulin G. After administration of oral prednisolone, platelet-associated immunoglobulin G levels decreased with a simultaneous increase in the number of platelets, suggesting that the thrombocytopenia observed in this patient was mediated by immune mechanisms. This is the first reported case of increased platelet-associated immunoglobulin G levels in a patient with mixed connective tissue disease.

Aged↗

Analysis of DNA fragmentation in bovine somatic nuclear transfer embryos using TUNEL.

The production of cloned animals is an inefficient process because of early or late embryonic losses. This study focused on the DNA fragmentation that occurs during embryonic development. The occurrence of DNA fragmentation was examined in bovine embryos produced by in vitro fertilization (IVF) and somatic cell nuclear transfer (NT) using the terminal deoxynucleotidyl transferase (TdT) nick-end labelling (TUNEL). IVF and NT embryos at the two-cell to blastocyst stage were stained by TUNEL for the analysis of DNA-fragmented nuclei and with propidium iodide for determination of the total number of cells. DNA fragmentation was first detected in NT embryos at the four-cell stage, but in IVF embryos at the six- to eight-cell stage. The percentage of embryos with at least one DNA-fragmented nucleus increased with the advance of the developmental stage of embryos in both IVF and NT groups. The DNA-fragmented nucleus index in NT embryos that developed beyond the four-cell stage was significantly higher (P<0.01) than that of IVF embryos at the same stage. In the both IVF and NT groups, TUNEL-labelled cells were detected in almost all blastocysts and were mainly observed in presumptive inner cell mass (ICM) cells of embryos. The DNA-fragmented nucleus index was negatively correlated with the total number of cells in NT blastocysts, but this relationship was not observed in IVF blastocysts. These results suggest that the high occurrence of DNA fragmentation observed in NT embryos may be related to early embryonic loss after transfer.

Animals↗

Molecular characterization of ionizing radiation-hypersensitive mutant M10 cells.

An ionizing radiation-sensitive mutant derivative of mouse lymphoma L5178Y cell, M10, is defective in rejoining DNA double-strand breaks (DSBs). The complementation test and the results of chromosome transfer suggested that M10 may belong to X-ray cross-complementation (XRCC) group 4. In the present study, sequence analysis of Xrcc4 cDNA in M10 cells disclosed a transversion of A (370) to T, which results in a change of arginine (124) to a termination codon. Interestingly, the mutation occurred in one allele and the transcripts of the Xrcc4 gene were expressed exclusively from the mutant allele. Transfection of M10 cells with the murine Xrcc4 cDNA completely rescued X-ray sensitivity of the mutant cells. M10 is a novel Xrcc4-deficient cell line.

Alleles↗

Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo.

The effect of hepatocyte growth factor/scatter factor (HGF/SF) during wound healing in the skin was investigated, using HGF/SF-overexpressing transgenic mouse model. Histological analysis of HGF/SF transgenic mouse excisional wound sites revealed increased granulation tissue with marked vascularization. Northern blot analysis demonstrated that, relative to control, vascular endothelial growth factor (VEGF) expression in transgenic skin was significantly higher at baseline and was robustly up-regulated during wound healing. Elevated levels of VEGF protein were detected immunohistochemically, predominantly in endothelial cells and fibroblasts within the granulation tissue of HGF/SF transgenic skin. Serum levels of VEGF were also elevated in HGF/SF transgenic mice. Thus, results from our study suggest that HGF/SF has a significant effect on vascularization and granulation tissue formation during wound healing in vivo, involving with induction of VEGF.

Animals↗

Nickel-promoted alkylative or arylative carboxylation of alkynes.

[reaction: see text]. Nickel-promoted alkylative or arylative carboxylation of terminal alkynes via a carbon dioxide fixation process was investigated. In the presence of a stoichiometric amount of a zero-valent nickel complex, the reaction of alkynes with CO2 gave a nickelacycle, which was reacted with various organozinc reagents under very mild conditions to provide beta,beta'-disubstituted, alpha,beta-unsaturated carboxylic acids in a highly regio- and stereoselective manner.

Journal Article↗

Absence of Msh2 protein expression is associated with alteration in the FHIT locus and Fhit protein expression in colorectal carcinoma.

Frequent loss of Fhit expression has been reported in human gastrointestinal tract carcinomas; opinions remain divergent regarding Fhit expression in colorectal carcinoma (CRC) cases. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins, particularly Msh2. Immunohistochemical analysis of Msh2 and Fhit protein expression in 62 CRC cases was performed. The same CRCs were examined for allelic loss at three loci within or near FHIT and for FHIT mRNA expression by reverse transcription-PCR amplification. Half of the 62 CRC cases were positive for Fhit protein. Fhit protein loss correlated significantly with the progression of carcinoma (P < 0.01) as well as lymph node metastasis (P < 0.05). Loss of Msh2 protein correlated significantly with loss of Fhit protein (P < 0.05) and FHIT locus alteration (P < 0.05). Loss of Fhit protein expression was observed in 50% of sporadic CRCs and was significantly more frequent in more advanced cancers. Interestingly, alteration of the fragile FHIT locus and loss of Fhit protein expression were significantly more frequent in sporadic CRCs lacking Msh2 protein, suggesting that this mismatch repair protein may be important in maintaining the integrity of the common fragile locus within the FHIT gene.

Acid Anhydride Hydrolases↗

Induction of CHOP and apoptosis by nitric oxide in p53-deficient microglial cells.

Excessive nitric oxide (NO) has been implicated in neurotoxicity after stresses such as ischemia. NO toxicity is generally thought to be mediated by the DNA damage-p53 pathway or mitochondrial dysfunction. We investigated the mechanism of NO toxicity by using murine microglial MG5 cells established from p53-deficient mice. When MG5 cells were exposed to bacterial lipopolysaccharide plus interferon-gamma, mRNA and protein for inducible NO synthase (iNOS) were markedly induced, and apoptosis occurred. Under these conditions, we found that mRNA and protein for CHOP/GADD153, a C/EBP family transcription factor which is involved in endoplasmic reticulum (ER) stress-induced apoptosis, are induced. iNOS mRNA was induced 2 h after treatment, whereas CHOP mRNA began to increase at 6 h with a time lag. CHOP mRNA was also induced by NO donors S-nitroso-N-acetyl-DL-penicillamine (SNAP) or NOC18, or a peroxynitrite generator 3-(4-morpholinyl)-sydnonimine hydrochloride (SIN-1). Bip/GRP78, an ER chaperone which is known to be induced by ER stress, was also induced by SNAP or SIN-1, indicating that NO causes ER stress. These results suggest that NO-induced apoptosis in MG5 cells occurs through the ER stress pathway involving CHOP, but is independent of p53.

Animals↗

Nitric oxide inhibits the proliferation of murine microglial MG5 cells by a mechanism involving p21 but independent of p53 and cyclic guanosine monophosphate.

We investigated the effect of nitric oxide (NO) on the proliferation of microglial MG5 cells established from p53-deficient mice. Cells were treated with bacterial lipopolysaccharide and interferon-gamma, and expression of inducible NO synthase (iNOS) and p21/waf1, a cyclin-dependent kinase inhibitor protein which is a critical downstream effector of p53, was investigated by RNA blot and immunoblot analyses. iNOS mRNA was induced 2 h after treatment and increased with time up to 24 h. p21 mRNA was expressed at a low level in untreated cells and increased with a kinetics similar to that for iNOS mRNA. iNOS and p21 proteins were also induced. An NO donor SNAP induced p21 mRNA and protein. SNAP inhibited incorporation of [(3)H]thymidine in MG5 cells in a dose-dependent manner. 8-Bromo-cGMP neither induced p21 mRNA nor inhibited [(3)H]thymidine incorporation. These results suggest that NO inhibits the proliferation of MG5 cells by induction of p21, which occurs independent of p53 and cGMP.

Animals↗