Cartilage intermediate layer protein promotes lumbar disc degeneration.

Lumbar disc disease (LDD) is one of the most common musculoskeletal disorders, and accompanies intervertebral disc degeneration. CILP encodes cartilage intermediate layer protein, which is highly associated with LDD. Moreover, CILP inhibits transcriptional activation of cartilage matrix genes in nucleus pulposus (NP) cells in vitro by binding to TGF-β1 and inhibiting the phosphorylation of Smads.

Preventive effects of metallothionein against DNA and lipid metabolic damages in dyslipidemic mice under repeated mild stress.

The effects of repeated mild stress on DNA and lipid metabolic damages in multiple organs of dyslipidemic mice, and the preventive role of metallothionein (MT) were investigated. Female adult wild-type and MT-null mice fed high-fat diet (HFD) or standard diet (STD) were repeatedly subjected to fasting or restraint for three weeks. The liver, pancreas, spleen, bone marrow and serum samples were taken for evaluating DNA damage, MT, glutathione (GSH), corticosterone, carnitine and adiponectin.

Adipose tissue derived stromal stem cell therapy in murine ConA-derived hepatitis is dependent on myeloid-lineage and CD4+ T-cell suppression.

Mesenchymal stromal stem cells (MSCs) are an attractive therapeutic model for regenerative medicine due to their pluripotency. MSCs are used as a treatment for several inflammatory diseases, including hepatitis. However, the detailed immunopathological impact of MSC treatment on liver disease, particularly for adipose tissue derived stromal stem cells (ADSCs), has not been described.

Adipose tissue-derived stem cells as a regenerative therapy for a mouse steatohepatitis-induced cirrhosis model.

Unlabelled: Cirrhosis is a chronic liver disease that impairs hepatic function and causes advanced fibrosis. Mesenchymal stem cells have gained recent popularity as a regenerative therapy since they possess immunomodulatory functions. We found that injected adipose tissue-derived stem cells (ADSCs) reside in the liver.

Association of changes in the gene expression profile of blood cells with the local tumor inflammatory response in a murine tumor model.

Cancer tissue is frequently associated with the host inflammatory response, which involves blood cells. Using DNA microarrays, we examined the gene expression profiles of blood and tumors in a murine subcutaneous hepatocellular carcinoma model, in which tumors develop during the initial 10 days and then diminish and disappear by day 25 after implantation. Immunohistochemical and gene expression analysis indicated that tumor tissues were associated with an active immune response, particularly the CD4+ T cell-mediated immune response, on day 10.

Myxoid liposarcoma-associated EWSR1-DDIT3 selectively represses osteoblastic and chondrocytic transcription in multipotent mesenchymal cells.

Background: Liposarcomas are the most common class of soft tissue sarcomas, and myxoid liposarcoma is the second most common liposarcoma. EWSR1-DDIT3 is a chimeric fusion protein generated by the myxoid liposarcoma-specific chromosomal translocation t(12;22)(q13;q12). Current studies indicate that multipotent mesenchymal cells are the origin of sarcomas.

Early changes induced by environmental stresses in insulin sensitivity-related genes.

Although adipocytes have been shown to secrete various adipocytokines, the factors that influence them are not clearly understood. We investigated whether repeated exposure to mild stresses affects the expression of adipocytokines in white adipose tissue (WAT). Male ICR mice were exposed to repeated restraint and tail-pinch (10 min/day) for 2 weeks.

Tissue-dependent preventive effect of metallothionein against DNA damage in dyslipidemic mice under repeated stresses of fasting or restraint.

Aims: To investigate the effect of repeated stress on DNA damage in seven organs of dyslipidemic mice, and the preventive role of metallothionein (MT).

Main Methods: Female adult 129/Sv wild-type and MT-null mice fed high-fat diet (HFD) were repeatedly subjected to mild stress of fasting or restraint in weeks 2 to 4 of 4-week study period. Serum cholesterol level, DNA damage in the liver, pancreas, spleen, bone marrow, kidney, lung and gastric mucosa, and other parameters were determined.

Tissue-dependent preventive effect of metallothionein against DNA damage in dyslipidemic mice under repeated stresses of fasting or restraint.

Aims: To investigate the effect of repeated stress on DNA damage in seven organs of dyslipidemic mice, and the preventive role of metallothionein (MT).

Main Methods: Female adult 129/Sv wild-type and MT-null mice fed high-fat diet (HFD) were repeatedly subjected to mild stress of fasting or restraint in weeks 2 to 4 of 4-week study period. Serum cholesterol level, DNA damage in the liver, pancreas, spleen, bone marrow, kidney, lung and gastric mucosa, and other parameters were determined.

Clinicopathological significance of circadian rhythm-related gene expression levels in patients with epithelial ovarian cancer.

Objective: Recent studies implicate circadian genes in the regulation of cell cycle, apoptosis, and cell proliferation at a molecular level. These genesey affect cancer incidence, prognosis, and chemosensitivity. In this study, we measured the expression levels of clock genes and correlated their expression levels with clinicopathological parameters in epithelial ovarian cancer.

[Improvement of sensitivity in the second generation HCV core antigen assay by a novel concentration method using polyethylene glycol (PEG)].

A HCV core antigen (Ag) detection assay system, Lumipulse Ortho HCV Ag has been developed and is commercially available in Japan with a lower detection level limit of 50 fmol/l, which is equivalent to 20 KIU/ml in PCR quantitative assay. HCV core Ag assay has an advantage of broader dynamic range compared with PCR assay, however the sensitivity is lower than PCR. We developed a novel HCV core Ag concentration method using polyethylene glycol (PEG), which can improve the sensitivity five times better than the original assay.

Expression of phospholipase D2 in human colorectal carcinoma.

Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline. PA acts as a second messenger in cell proliferation; therefore PLD is believed to play an important role in carcinogenesis. PLD activity has been reported to be elevated in human breast, gastric, renal cell and colorectal carcinomas, compared with adjacent non-neoplastic tissues.

Circadian rhythm of apoprotein H (beta2-glycoprotein-1) in human plasma.

Many physiological, biochemical, and behavioral processes are under circadian regulation, which is generated by an internal time-keeping mechanism referred to as biological clock. The regulators of circadian rhythm in human plasma have not been completely elucidated. Here we demonstrated that the isolated protein from human plasma, which down-regulated expression level of cry1 in Jurkat cells, was apoprotein H (ApoH).

Possible inhibitory effect of oral zinc supplementation on hepatic fibrosis through downregulation of TIMP-1: A pilot study.

Aim: To investigate the effect of oral zinc supplementation (polaprezinc) for 24 weeks (34 mg/day zinc) on liver fibrosis in patients with advanced chronic liver disease.

Methods: Various markers of liver fibrosis, and fibrogenic and fibrolytic enzyme activities were measured before and after zinc supplementation in 17 patients with early cirrhosis.

Results: Serum zinc levels were decreased in the patients as compared with healthy controls.

Involvement of oxidative stress in the synthesis of metallothionein induced by mitochondrial inhibitors.

We previously reported that synthesis of metallothionein (MT) was induced by mitochondrial inhibitors such as 2,4-dinitrophenol (DNP) or antimycin A (Kondoh et al., 2001), which are potent inhibitors of mitochondrial respiration. Although the inhibitors are known to be radical generators in mitochondria, the involvement of oxidative stress in the synthesis of MT induced by mitochondrial inhibitors and the biological functions of MT remain obscure.

[A case of malignant peritoneal mesothelioma successfully treated with carboplatin and paclitaxel].

A 71-year-old woman was seen at our hospital because of abdominal fullness and dyspnea. Examinations revealed a tumor in the pelvis with fluid collection and dissemination was seen in the abdomen and chest. Moreover, hyaluronate in ascites rose to 20,000 mg/dl.

[Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype.

Activation of caspase-3 in HL-60 cells treated with pyrithione and zinc.

The transition metal zinc (Zn) is an endogenous regulator of apoptosis. The ability of Zn to modulate apoptosis is believed to be mediated by the regulation of caspase activity. Previously, we reported that an acute influx of labile Zn induced apoptosis via activation of caspase in human leukemia HL-60 cells treated with a Zn ionophore (Py, pyrithione) and Zn at 1 and 25 microM, respectively.

Benefit of hepatitis C virus core antigen assay in prediction of therapeutic response to interferon and ribavirin combination therapy.

A highly sensitive second-generation hepatitis C virus (HCV) core antigen assay has recently been developed. We compared viral disappearance and first-phase kinetics between commercially available core antigen (Ag) assays, Lumipulse Ortho HCV Ag (Lumipulse-Ag), and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor test, version 2 (Amplicor M), to estimate the predictive benefit of a sustained viral response (SVR) and non-SVR in 44 genotype 1b patients treated with interferon (IFN) and ribavirin. HCV core Ag negativity could predict SVR on day 1 (sensitivity = 100%, specificity = 85.

Expression of copper-transporting P-type adenosine triphosphatase (ATP7B) in human hepatocellular carcinoma.

One of the major obstacles in the treatment of hepatocellular carcinoma (HCC) is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphate (ATP7B) has been reported to be associated with cisplatin resistance in vitro. However, the expression of ATP7B has not previously been addressed in human liver and HCC.

Induction of hepatic metallothionein synthesis by endoplasmic reticulum stress in mice.

Metallothionein (MT) is a small sulfhydryl-rich protein whose levels are elevated by various inducers of organelle stresses, such as nuclear stress (cisplatin), mitochondrial stress (antimycin A, 2,4-dinitrophenol) and lysosomal stress (paraquat). Although abnormal folding of protein in the endoplasmic reticulum (ER) causes ER stress, induction of MT synthesis by ER stress has never been investigated. In this study, we examined the induction of MT by an inducer of ER stress, tunicamycin (Tun), which induces ER stress by inhibiting N-linked glycosylation of protein in the ER.

Thymidine phosphorylase expression in gastric carcinoma as a marker for metastasis.

Background: Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECCF) and has a function of angiogenesis in vitro and in several types of human carcinoma tissues. We have reported that expression of dThdPase was an independent prognostic factor in 116 gastric carcinomas by immunohistochemical analysis.

Materials And Methods: In the present study, we updated the analysis of recurrence in 116 patients with gastric carcinomas to find how dThdPase plays an important role in progression of gastric carcinoma.

Total synthesis of mappicine ketone (nothapodytine B) by means of sulfur-directed 5-exo-selective aryl radical cyclization onto enamides.

Enamides 5, on treatment with Bu(3)SnH-AIBN, underwent aryl radical cyclization in a 5-exo manner to give 1-[bis(phenylthio)methyl]dihydroisoindoles 6, which were partially desulfurized with Bu(3)SnH-AIBN to give 1-mono(phenylthio)methyl congeners 7. Formation of 6 from 5 may be explained by the presence of two phenylthio groups at the terminus of the N-vinylic bond of 5, since enamide 8a having no phenylthio group underwent aryl radical cyclization in a 6-endo manner. Compound 7d (R = CF(3)) was transformed into sulfoxide 16, which was treated with (CF(3)CO)(2)O and then with 10% NaOH to give a model compound 20 of mappicine ketone (MPK) (1) through aldol condensation of aldehyde 18.

Antioxidant property of metallothionein in fasted mice.

Metallothionein (MT) is a low-molecular-weight and sulfur-rich protein that is induced by not only heavy metals but also physiological stresses such as fasting and restraint stresses. Although MT plays a role as a radical scavenger and a regulator of metabolism of metals, the biological function of MT induced by fasting stress has not been elucidated. In this study, we investigated the antioxidative role of MT in fasted mice.