VR1, but not P2X(3), increases in the spared L4 DRG in rats with L5 spinal nerve ligation

We investigated the expression of two candidate transducers of noxious stimuli in peripheral tissues, the vanilloid receptor subtype 1 (VR1) and the P2X(3), a subunit of the ionotropic P2X receptor for ATP, in spared L4 DRG neurons following L5 spinal nerve ligation, a neuropathic pain model. VR1 mRNA expression increased in the small- and medium-sized DRG neurons from the first to 28th day after injury, and this up-regulation corresponded well with the development and maintenance of thermal hyperalgesia of the hind paw. The increase in VR1-immunoreactive (ir) neurons was confirmed at the third day after surgery. In contrast, there was no change in expression of P2X(3) mRNA over 4 weeks after ligation, or in the percentage of P2X(3)-ir neurons observed 3 days after surgery. Our data suggests that increased VR1 in the spared L4 DRG may contribute to the exaggerated heat response observed in this neuropathic pain model. Taken together with the previous reports that P2X(3) expression increases in the spared DRG neurons in other neuropathic pain models, there appears to be differences in the phenotypic changes and pathomechanisms of the various neuropathic pain models.     

Effects of gonadotropin-releasing hormone agonist and dopamine antagonist on hypothalamus-pituitary-gonadal axis of pre-pubertal female red seabream (Pagrus major)

The effects of GnRH agonist (GnRHa) on the hypothalamus-pituitary-gonadal axis were studied in female pre-pubertal red seabream. Sexually immature 16-month-old fish were implanted intramuscularly with cholesterol pellets containing GnRHa or GnRHa in combination with domperidone, putative dopamine antagonist, and reared for 10-20 days. In both GnRHa and GnRHa+domperidone implanted groups, vitellogenesis was observed on Day 10 and ovulation was observed on Day 20, while ovarian development was not observed in the control fish throughout the experimental period. The levels of GnRH receptor mRNA were significantly higher in both GnRHa implanted groups than in the control. The expressions of all three gonadotropin subunit genes were up-regulated and serum luteinizing hormone levels were increased by the GnRHa implantation. Serum testosterone and estradiol-17beta levels were also increased on Day 10 and maintained high levels on Day 20. On the other hand, seabream (sb) GnRH mRNA levels in the brain were relatively low and unchanged in all experiment groups. The present study first shows that GnRH alone can induce precocious puberty in red seabream. These results indicate that the system of pituitary-gonadal axis has already been developed in 16-month-old fish and the commencement of sbGnRH secretion may be an important physiological event for the onset of puberty in the red seabream.     

Combined hepatocellular and cholangiocarcinoma with marked squamous cell carcinoma components arising in non-cirrhotic liver

We report a surgical case of liver tumor, 40 x 35 mm in size, with squamous cell carcinoma (SCC) and hepatocellular carcinoma (HCC) components in a 60-year-old Japanese man with steatohepatitis. Most of the SCC component showed typical intercellular bridge and keratinization, while most of the HCC components showed a thick trabecular pattern with mild to moderate nuclear atypia. Both components transit each other without undifferentiated foci; however, a small foci showing glandular structure was intermediated. No cyst formation was found in the liver. The primary site of the squamous cell carcinoma was not detected in general clinical and radiological examination. Immunohistochemical analysis revealed that part of the HCC components neighboring the SCC showed patchy and weak expression of cytokeratin 7. There are several possibilities for the origin of squamous cell carcinoma in this case: marked squamous metaplastic change of cholangiocarcinoma and/or HCC, and carcinoma originating from pleuripotential stem cells. Irregular fatty changes, scattered giant mitochondria and acellular fibrosis with bridging were seen in the liver; however, this patient had no episode of hepatitis-associated viral infection. This is an interesting case of combined hepatocellular and cholangiocarcinoma with marked SCC components arising in a non-cirrhotic fibrotic liver.     

Familial inclusion body myositis: a report on two Japanese sisters

Familial occurrence of inclusion body myositis is extremely rare, and only a few cases in Western countries have been reported. In these reports, a strong association of this disease with DR3 (DRB1*0301/0302) and the efficacy of immunosuppressants suggested that an immune pathomechanism is involved in the disease. We, for the first time, report two Japanese sisters who suffered myopathy clinicopathologically similar to inclusion body myositis. One sister received corticosteroid and azathioprine and the therapy relieved dysphagia. Both of our patients had DR15(2)/4 (DRB1*1502/0405), suggesting a distinct genetic association with the disease in the Japanese population.     

Corticosteroids for treatment of patients with chronic obstructive pulmonary disease

There is scientific evidence that corticosteroids should be given in exacerbation of COPD. It is still controversial if patients with stable COPD could receive benefits by long-term administration with inhaled corticosteroids. However, many investigators recently consider favorable opinions for inhaled corticosteroids, since inhaled corticosteroids could decrease the frequency of exacerbation especially in severe to moderate COPD.