Expression of matrix metalloproteinase-2 (MMP-2) and of membrane-type-1-matrix metalloproteinase (MT1-MMP) in transitional cell carcinoma of the upper urinary tract

Tumor cell invasion and metastasis are biologically dependent on the proteolytic destruction of surrounding matrix components. Matrix metalloproteinase-2 (MMP-2) is able to cleave type IV collagen, and membrane-type-1-matrix metalloproteinase (MT1-MMP) induces activation of proMMP-2. We investigated the expression of MMP-2 and MT1-MMP using in situ hybridization and immunohistochemistry in 102 cases of transitional cell carcinoma of the upper urinary tract (TCC-UUT). A positive expression of each metalloproteinase was recognized in all samples and was apparent within the cytoplasm of tumor epithelial cells and/or stromal cells situated at the interface between tumor and stroma. Our analysis of clinicopathologic findings showed a relationship between MMP-2 and MT1-MMP expression and stage. The correlation between the MMP-2 protein staining score for tumor epithelial cells and overall survival rate reached significance in the univariate analysis. However, only stage was associated with disease-free and overall survivals in the multivariate analysis. In conclusion, the detection of MMP-2 and MT1-MMP would appear to be of limited value in informing the prognosis of TCC-UUT.     

Inhibition of chlamydia trachomatis growth by human interferon-alpha: mechanisms and synergistic effect with interferon-gamma and tumor necrosis factor-alpha

We have evaluated the effect of natural human interferon (IFN)-alpha on the growth of chlamydia trachomatis in human epithelial cells in vitro and revealed that IFN-alpha has reduced both growth and infectivity of C. trachomatis. The effect of IFN-alpha was reversed by the addition of exogenous L-tryptophan and iron to the culture medium, suggesting that antichlamydial effect of IFN-alpha was caused by depletion of intracellular tryptophan and iron, both of which are essential for chlamydial growth. When IFN-alpha was combined with another antichlamydial cytokines, IFN-gamma and tumor necrosis factor (TNF)-alpha, the effect was synergistically enhanced. Therefore, IFN-alpha would act coordinately with other cytokines such as IFN-gamma and TNF-alpha, and play an important role in host defense against infection and in the establishment of persistent chlamydial infection of host, in which the organism remains viable, but in a culture-negative state.     

No association of GSK3beta gene (GSK3B) with Japanese schizophrenia.

Several lines of evidence indicate that glycogen synthase kinase-3beta (GSK3beta) is one of the candidates for schizophrenia-susceptibility factor. However, it has not been reported the association analysis between GSK3beta gene (GSK3B) and Japanese schizophrenia based on linkage disequilibrium (LD). We provide an association analysis using relatively large samples (381 schizophrenia, and 352 controls) after determination of "tag single nucleotide polymorphisms (SNPs)." In this LD mapping, we selected and genotyped for eight polymorphisms (seven SNPs and one diallelic (CAA)(n) repeat), which covered the entire region of GSK3B, and determined two "tag SNPs." In the following association analysis using these two "tag SNPs," we could not find association with Japanese schizophrenia. Furthermore, we also include subgroup analysis considering age-at-onset and subtypes, neither could we find associations. Because our samples provided quite high power, these results indicate that GSK3B may not play a major role in Japanese schizophrenia.     

Simple method for the identification of oxidative fibers in skeletal muscle

Skeletal muscle is composed of several different types of myofiber: slow oxidative (SO), fast glycolytic oxidative and fast glycolytic. However, the classification is usually determined by myosin heavy chain typing rather than by metabolic index. In this study, the oxidative metabolic index was investigated as a possible method of myofiber typing. Myoglobin, which is involved in oxygen transport and storage in myofibers, and mitochondria, which are the central organelles for oxidative metabolism, were studied. High levels of myoglobin and mitochondria are believed to exist in SO fibers, but the current study showed that they are considerably richer in some fast type fibers. As myofiber typing using the oxidative metabolic index is important physiologically, an attempt was made to find a simple method for this purpose. Some mitochondrial proteins have been observed to auto-fluoresce but until now this effect was too faint to detect easily. Owing to the recent advances in cooling charge-coupled device technology, such auto-fluorescence can now be used for myofiber typing, and the simple and rapid method for doing so is reported here.     

Expression of tocopherol-associated protein in mast cells

Tocopherol-associated protein (TAP) was expressed in mouse mast cells. TAP was predominantly localized in the cytoplasm, and the subcellular localization was not changed by alpha-tocopherol. The results suggest that the physiological role of TAP in mast cells is not regulation of tocopherol function but an as-yet-unidentified activity.     

Apoptosis-inducing protein derived from hepatocyte selectively induces apoptosis in lymphocytes

The liver is where lymphocytes undergo activation-induced cell death (AICD) at the resolution phase of an immune response, which is crucial for homeostasis of the immune system and prevention of autoimmunity. Exploring the machinery of AICD in the liver, we found that a primary culture supernatant of murine hepatocytes had an antiproliferative effect on antigen-stimulated T clone and T lymphoma cells. Biological study showed that the antiproliferation was due to induction of apoptosis in a caspase-dependent manner. The apoptosis-inducing potential was sensitive to trypsin, heat (> 70 degrees ) and acid (< pH 5) treatment but could not be neutralized by anti-tumour necrosis factor-alpha, anti-Fas ligand, or anti-transforming growth factor-beta antibodies. Biochemical study of the isolated and purified apoptosis-inducing component from the supernatant showed that it was a protein with a molecular mass of about 68,000-70,000. It induced apoptotic change in murine T and B cells, and to a lesser degree, in human lymphoid cells, but not in macrophages. Biochemical and biological characteristics distinguish this protein from others that have been reported to induce apoptosis of lymphocytes. The identification of an apoptosis-inducing protein derived from murine hepatocytes, which selectively induces apoptosis in lymphocytes, suggests one possible mechanism for immune suppression in the liver.     

Effects of body position on snoring in apneic and nonapneic snorers

STUDY OBJECTIVES: The positional dependency of obstructive sleep apnea (OSA) is well known, but objective evidence for the positional effect on snoring is lacking. The aim of this study is to elucidate the effect of body position on snoring, and that of sleep stage as well. DESIGN: Retrospective analysis of the effects of body position and sleep stage on snoring in nonapneic snorers (snorer group) and OSA patients (apneic group). SETTING: A sleep laboratory in a national hospital in Japan. PATIENTS: Seventy-two patients who complained of habitual snoring and underwent overnight polysomnography. INTERVENTIONS: N/A MEASUREMENTS AND RESULTS: In the lateral position, most subjects in the snorer group showed decreased snoring both in time (p = 0.0004) and intensity (p = 0.0003), but subjects in the apneic group showed variable changes. In the apneic group, the positional dependency of snoring (the ratio of lateral value to supine value) was correlated with supine apnea-hypopnea index (AHI), that is, OSA patients with higher supine AHI tended to show increased snoring in the lateral position. AS to the effect of sleep stage, snoring was increased in deeper non-rapid eye movement sleep and decreased in rapid eye movement sleep in a given position. CONCLUSIONS: This study demonstrated that the positional dependency is different between nonapneic snorers and OSA patients. Most of the nonapneic snorers snore less in the lateral position than in the supine position in contrast to OSA patients who often fail to decrease snoring even in the lateral position.     

Electro-acupuncture stimulation effects on duodenal motility in anesthetized rats

The effect of electro-acupuncture stimulation (EAS) on duodenal motility was examined in anesthetized, artificially ventilated rats. EAS was applied to the abdominal area or to a hindpaw for 30 s at stimulus intensities of 0.1-10.0 mA with a stimulus frequency of 20 Hz. The duodenal motility was measured using the balloon method at a position about 1.5 cm caudal from the pylorus. Duodenal motility was inhibited by EAS at intensities of more than 5.0 mA (suprathreshold of group IV afferent excitation) when applied to the abdominal area. The duodenal inhibitory response existed after bilateral vagotomy or spinal transection, but was abolished by sectioning bilateral splanchnic nerves. Duodenal motility was facilitated by EAS at intensities of more than 2.0 mA (subthreshold of group IV, and suprathreshold for groups II+III afferent excitation) when applied to a hindpaw. The duodenal facilitatory response by EAS to a hindpaw existed after sectioning the splanchnic nerves, but disappeared after bilateral vagotomy or spinal transection. Furthermore, repetitive electrical stimulation of vagal efferent nerves enhanced duodenal motility, while repetitive electrical stimulation of the splanchnic efferent nerves inhibited the motility. It was concluded that the inhibitory response of duodenal motility elicited by EAS to the abdominal area is a spinal reflex response involving splanchnic inhibitory efferent nerves, and the enhanced response of duodenal motility by EAS to a hindpaw is a supraspinal reflex response involving vagal excitatory nerves.