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.     

Increased serum granulocyte colony-stimulating factor correlates with coronary artery dilatation in Kawasaki disease

In acute-phase Kawasaki disease, neutrophils cause injury to the coronary arterial endothelium through the production of elastase. Previous research has demonstrated the modulation of neutrophil function and kinetics, such as development and maturation, by granulocyte colony-stimulating factor (G-CSF). To examine the correlation between G-CSF and cardiac complications in Kawasaki disease, functional activity of serum G-CSF and cytokines was measured by enzyme-linked immunosorbent assay in 30 patients with acute-phase Kawasaki disease aged 2 months to 5 years. The mean serum G-CSF was higher in the 1st week of Kawasaki disease than during weeks 2 to 4, and G-CSF was significantly higher in patients with coronary artery dilatation (CAL) than in those without. There was no significant difference in the activity of other cytokines studied or white blood cell counts between the patients with CAL. Conclusion: granulocyte colony-stimulating factor is correlated with coronary artery dilatation in acute-phase Kawasaki disease and increased neutrophil function may contribute to the pathogenesis of coronary arterial endothelial injury in these patients.     

Pharmacokinetics and metabolism of radiolabelled SNI-2011, a novel muscarinic receptor agonist,in healthy volunteers. Comprehensive understanding of absorption,metabolism and excretion using radiolabelled SNI-2011

The pharmacokinetics and metabolism of SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine]monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), a novel muscarinic acetylcholine receptor agonist developed for the treatment of Sj?gen's syndrome, were investigated in six healthy volunteers after a single oral administration of 14C-SNI-2011. After administration, plasma concentrations of the radioactivity and SNI-2011 reached to Cmax at approximately 2 h, and then decreased with t 1/2 of 9 and 4 h, respectively. Cmax and AUC0-infinity of the radioactivity in plasma were 2.2 and 5.0 times higher than those of SNI-2011, respectively. The main excretion route of the radioactivity was urine, and 97.3% of the dose excreted in urine within 168 h, indicating that 14C-SNI-2011 was completely absorbed. The mean recoveries of the metabolites in urine at 24 h after administration were 16.0% for SNI-2011, 35.8% for SNI-2011 trans-sulfoxide (SNI-t-SO), 8.7% for SNI-2011 cis-sulfoxide, 4.1% for SNI-2011 N-oxide, furthermore, two unknown metabolites, UK-1 and UK-2, were detected 14.6% and 7.7%, respectively. LC/MS analysis and hydrolysis studies revealed that UK-1 and UK-2 were glucuronic acid conjugates of SNI-2011 and SNI-t-SO, respectively.     

Radiographic pulmonary and pleural changes after carbon ion irradiation

PURPOSE: For the treatment of Stage I non-small-cell lung cancers, a Phase I/II study of carbon ion irradiation was undertaken. In the present study, we focus on posttreatment radiographic lung damage: specifically, its timing, features, and relation to dose-volume factors. MATERIALS AND METHODS: Forty-three patients with 44 Stage I non-small-cell lung cancers were treated with carbon ion irradiation ranging from 59.4 to 95.4 photon Gy equivalent dose (GyE) in 18 fractions over 6 weeks, according to our dose escalation protocols. Primary lesions were irradiated by 2-4 portals. Follow-up evaluation with computed tomography (CT) was sequentially performed to assess changes in the lung. CT findings were classified into two categories: pulmonary reaction and pleural reaction. A dose-volume histogram for each patient was calculated, using a three-dimensional CT planning system. Statistical analysis was conducted using Spearman's rank test. RESULTS: The median appearance period of pulmonary reactions was 3 months after the start of carbon ion irradiation, whereas the maximum period was 6 months. The severity of pulmonary reactions statistically correlated with lung volumes irradiated no less than 20 GyE (vol. 20) and 40 GyE (vol. 40) (p = 0.017 and p = 0.0089). Geometrically unique findings in the irradiated fields were observed in 7 patients (16%). The median appearance period of pleural reactions was 4 months after the start of carbon ion irradiation. The occurrence of pleural reactions significantly correlated with planning target volume (p = 0.000098), vol. 20 (p = 0.00011), and vol. 40 (p = 0.00097). CONCLUSIONS: Lung damage after carbon ion irradiation was observed in the parenchyma and in the pleura. The severity of pulmonary reactions was correlated with dose-volume factors. These findings might provide useful information in the planning and management of carbon ion irradiation.     

Glypican-3, overexpressed in hepatocellular carcinoma,modulates FGF2 and BMP-7 signaling

The Glypican (GPC) family is a prototypical member of the cell-surface heparan sulfate proteoglycans (HSPGs). The HSPGs have been demonstrated to interact with growth factors, act as coreceptors and modulate growth factor activity. Here we show that based on oligonucleotide array analysis, GPC3 was upregulated in hepatocellular carcinoma (HCC). By northern blot analysis, GPC3 mRNA was found to be upregulated in 29 of 52 cases of HCC (55.7%). By Western blot analysis carried out with a monoclonal anti-GPC3 antibody we generated, the GPC3 protein was found to be overexpressed in 6 hepatoma cell lines, HepG2, Hep3B, HT17, HuH6, HuH7 and PLC/PRF/5, as well as 22 tumors (42.3%). To investigate the role of overexpressed GPC3 in liver cancer, we analyzed its effects on cell growth of hepatoblastoma-derived cells. Overexpression of GPC3 modulated cell proliferation by inhibiting fibroblast growth factor 2 (FGF2) and bone morphogenetic protein 7 (BMP-7) activity. An interaction of GPC3 and FGF2 was revealed by co-immunoprecipitation, while GPC3 was found to inhibit BMP-7 signaling through the Smad pathway by reporter gene assay. The modulation of growth factors by GPC3 may help explain its role in liver carcinogenesis. In addition, the ability of HCC cells to express GPC3 at high levels may serve as a new tumor marker for HCC.     

Allelic loss on chromosomes 2q, 3p and 21q: possibly a poor prognostic factor in oral squamous cell carcinoma

Loss of heterozygosity (LOH) correlates with inactivate tumor suppressor gene. The aim of this study was to see if LOH on chromosomes 2q, 3p and 21q correlated with a poor prognostic factor in oral squamous cell carcinoma (SCC). We analyzed chromosomes 2q, 3p and 21q for LOH in 40 primary oral SCCs using 30 markers and constructed a deletion map for these chromosome arms. Significant LOH (>20%) occurred at alleles in chromosome bands 2q14–21 (21.7%), 2q32–35 (31.6%), 2q35 (21.1%), 2q36 (36.7%), 3p25 (32.4%), 3p21.3 (23.8%), 21q11.1 (52.4%), 21q21 (21.6%) and 21q22.1 (22.2%). A significant correlation was observed between the number of regions showing LOH at 2q and TNM clinical stage (P=0.0063), consistent with the progressive accumulation of genetic errors during the development oral SCC. The number at more than two LOH loci was significant with a poor prognosis at 2q (P=0.0208). These findings demonstrate that oral SCC exhibits genetic alterations at multiple loci and that allelic loss at more than two locations is indicative of a poor prognosis. This is the first study to demonstrate the prognostic significance of LOH at 2q, 3p and 21q for oral cancer and may help to identify patient who should receive more aggressive treatment.     

Primary sebaceous carcinoma of the lacrimal gland treated by carbon ion radiotherapy

Sebaceous carcinoma is a rare primary neoplasm of the lacrimal gland and, to the best of our knowledge, only six cases have been reported previously. Sebaceous carcinoma of the orbit more commonly occurs as secondary invasion from the eyelid, but may occur by way of metastatic spread from elsewhere in the body. We describe a patient who presented with a rapidly growing neoplasm of the lacrimal gland which, histologically, was a sebaceous carcinoma. The eyelid was entirely normal on examination. In this patient we found a single tumor cell line within the normal lacrimal gland. In this article we describe the diagnosis and treatment with carbon ion radiotherapy of primary sebaceous carcinoma of the lacrimal gland, a condition not previously reported in Japan.     

CT imaging of the patulous eustachian tube--comparison between sitting and recumbent positions

OBJECTIVE: The objective was to evaluate the three-dimensional anatomy of the eustachian tube (ET) and its surrounding tissues of patulous ET patients in the sitting positions by the horizontal computed tomography (CT) system with the multiplanar reconstruction (MPR) technique, and to compare the findings with those obtained in the recumbent position. METHODS: Two patients with severe bilateral patulous ET were investigated. After performing temporal bone CT examination both in the sitting and recumbent position, MPR images of the ET were reconstructed and measurement was made on a workstation. RESULTS: The ET lumen was identified at most of the portion from the pharyngeal orifice to the tympanic orifice in both positions. At the cartilaginous portion, the air space in the ET lumen was larger in the sitting position than in the recumbent position. At the bony portion of the ET, there did not seem to be any significant difference in the results of measurement in both cases. CONCLUSION: For the first time, we were able to obtain reconstructed images of patulous ET patients in the sitting position and to compare the findings with those of the recumbent position. We suggest that this method is useful for better understanding of the ET and ET-related diseases such as patulous ET.     

A comparison of heart rate during rest and work in shift workers with different work styles

To determine if the type of work performed should be considered in research on shift work and cardiovascular disease, we compared the heart rates, total number of steps walked, and blood pressures of 12 shift workers on the same rotating 3-shift schedule in a pulp and paper mill. Six workers were selected from the paper manufacturing section (group 1) and six workers from the chemical products section (group 2). Average heart rate (in beats per min) monitored during duty time was 84.3 in group 1 and 87.4 in group 2. Average heart rate during work was not significantly higher than that during rest in both groups 1 (work 85.8, rest 75.3) and 2 (work 87.9, rest 83.1). There was no significant difference in the total number of steps walked. A non-significant decrease in systolic blood pressure value was found in group 1 compared with that in group 2. Although future studies will be needed to explain the relation between different work styles and their effects on the health of shift workers, our results suggest no significant difference in heart rates among workers engaged in different kinds of work on the same shift work schedule.