Activation of Nesfatin‐1‐Containing Neurones in the Hypothalamus and Brainstem by Peripheral Administration of Anorectic Hormones and Suppression of Feeding via Central Nesfatin‐1 in Rats

Peripheral anorectic hormones, such as glucagon‐like peptide (GLP)‐1, cholecystokinin (CCK)‐8 and leptin, suppress food intake. The newly‐identified anorectic neuropeptide, nesfatin‐1, is synthesised in both peripheral tissues and the central nervous system, particularly by various nuclei in the hypothalamus and brainstem. In the present study, we examined the effects of i.p. administration of GLP‐1 and CCK‐8 and co‐administrations of GLP‐1 and leptin at subthreshold doses as confirmed by measurement of food intake, on nesfatin‐1‐immunoreactive (‐IR) neurones in the hypothalamus and brainstem of rats by Fos immunohistochemistry. Intraperitoneal administration of GLP‐1 (100 μg/kg) caused significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the supraoptic nucleus (SON), the area postrema (AP) and the nucleus tractus solitarii (NTS) but not in the paraventricular nucleus (PVN), the arcuate nucleus (ARC) or the lateral hypothalamic area (LHA). On the other hand, i.p. administration of CCK‐8 (50 μg/kg) resulted in marked increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the SON, PVN, AP and NTS but not in the ARC or LHA. No differences in the percentage of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the nuclei of the hypothalamus and brainstem were observed between rats treated with saline, GLP‐1 (33 μg/kg) or leptin. However, co‐administration of GLP‐1 (33 μg/kg) and leptin resulted in significant increases in the number of nesfatin‐1‐IR neurones expressing Fos‐immunoreactivity in the AP and the NTS. Furthermore, decreased food intake induced by GLP‐1, CCK‐8 and leptin was attenuated significantly by pretreatment with i.c.v. administration of antisense nesfatin‐1. These results indicate that nesfatin‐1‐expressing neurones in the brainstem may play an important role in sensing peripheral levels of GLP‐1 and leptin in addition to CCK‐8, and also suppress food intake in rats.     

Three sisters of pulmonary Mycobacterium avium complex disease

We reported three sisters of pulmonary Mycobacterium avium complex (MAC) disease. The oldest sister was complaining of bloody sputum, and cultures were positive for M. avium. By monotherapy with clarithromycin, symptom and imaging findings had shown no progression for six years. The second sister was complaining of productive cough, and cultures were positive for M. intracellulare. Her symptom and imaging findings had shown no progression for seven years without any treatment. The third sister had rheumatoid arthritis and diabetes mellitus, and cultures were positive for M. intracellulare. Although she received chemotherapy with rifampicin, clarithromycin, ethambutol, and kanamycin, symptom and imaging findings had progressed gradually. She died of respiratory failure four years later. Autopsy findings revealed no disseminated MAC disease. The results which three cases showed different isolate patterns and clinical courses suggest the importance of underlying anti-mycobacterial immunological impairment and defects of local host defense rather than virulence of infected strains as the pathogenesis of pulmonary MAC disease.     

Evaluation of video-assisted thoracoscopic surgery lobectomy requiring emergency conversion to thoracotomy

Objective: Video-assisted thoracoscopic surgery (VATS) lobectomy has been employed for the treatment of lung cancer. Many investigators have reported that the outcomes of VATS lobectomy for lung cancer are comparable to those of thoracotomy; however, several controversial issues remain. One of the critical concerns is the safety. VATS lobectomy often requires an emergency conversion to thoracotomy, for example, in the event of massive bleeding. In this study, cases in which VATS lobectomy for lung cancer was converted to thoracotomy intra-operatively (converted VATS lobectomy) were identified. The safety of the converted VATS lobectomy was evaluated. Methods: Between 2003 and 2007, VATS lobectomy was converted to thoracotomy in 24 out of 492 cases. Information regarding the patients’ characteristics, reasons for the conversion and perioperative complications as well as the recurrence and survival data were carefully reviewed. The reasons for the conversion were classified into two groups: (1) problems related to the VATS procedure (VATS-related problems) and (2) problems not related to the VATS procedure (non-VATS-related problems). Results: Of the 24 converted cases, 19 (79%) had a history of smoking. Nine patients (38%) had a history of lung disease. Left upper lobectomy was the most frequently associated with conversion (11/24, 46%), followed by right lower lobectomy and right upper lobectomy. The most frequent reasons for the conversion were hilar lymphadenopathy and bleeding (seven patients each), followed by fused fissure. Eight of the conversions were considered to be attributable to VATS-related problems. Perioperative complications were observed in four patients, consisting of prolonged air leak in three patients and transient recurrent laryngeal nerve palsy in one patient. However, there were no life-threatening complications. The median follow-up period was 26 months. Recurrence occurred in two patients: pleural dissemination in one and bone metastasis in the other. Two deaths were observed during the follow-up period: one related to lung cancer and another related to other type of cancer. Conclusions: The safety of the conversion was acceptable. Our findings suggest that VATS lobectomy for lung cancer is feasible from the viewpoint of safety, even after taking into account the potential need for conversion to thoracotomy in some patients.     

Total body irradiation followed by bone marrow transplantation: comparison of once-daily and twice-daily fractionation regimens

Purpose The purpose of this study was to evaluate the results of two sequential total body irradiation (TBI) regimens, especially focusing on pulmonary complications. Materials and methods Patients with malignant disease who underwent TBI followed by bone marrow transplantation were retrospectively reviewed. There were 86 patients (51 males, 35 females). Altogether, 36 patients were treated on twice-daily fractions of 2 Gy for 3 days to a total 12 Gy (group A). Another 50 patients were treated on once-daily fractions of 2.4 or 3.0 Gy for 4 or 5 days to a total 12 Gy (group B). Results The 5-year overall survival rate was 49.2%, and relapse-free survival was 44.3%. There were no significant differences between the two groups regarding overall survival (P = 0.1237) or relapse-free survival (P = 0.1548). Two patients in group A had interstitial pneumonitis of grade 3 or higher severity compared with three patients in group B. There was no significant difference between patients in group A (5-year probability rate was 7.6%) and patients in group B (5-year probability rate was 13.9%) (P = 0.9519). Conclusion We concluded that our once-daily TBI regimen is feasible and had the benefit of reducing the complexity of TBI. We believe that further investigation of the TBI regimen is needed.     

Identification of a novel HLA-B allele, HLA-B*5904

The new human leukocyte antigen (HLA) class I allele, HLA-B*5904 was identified in Japanese individual. HLA-B*5904 differs from HLA-B*5901 by two non-synonymous nucleotide exchanges at codon 163 (ACG to CTG).     

A case of gastric neuroendocrine cell carcinoma successfully treated by neoadjuvant chemotherapy

A 74-year-old man, whose chief complaint was epigastralgia, was referred to our hospital and diagnosed gastric cancer with liver metastasis. Gastrointestinal endoscopy showed a tumor on the lesser curvature of cardia of stomach. He was diagnosed as neuroendocrine cell carcinoma by biopsy specimens. He was treated by combined chemotherapy of CPT-11 and CDDP. After 11 courses, endoscopic examination revealed a complete disappearance of the primary tumor. CT-scan and MRI showed that the liver metastasis had been disappeared. We diagnosed as clinical CR and performed total gastrectomy with lymph node dissection and partial hepatectomy. Histological findings revealed a few cells in stomach and no cancer cells in the liver. He was treated with adjuvant chemotherapy of S-1. After 3-course, he suffered from anemia of grade 3, thus we interrupted chemotherapy. The patient remains alive for 28 months without recurrence. We conclude that chemotherapy was effective for neuroendocrine cell carcinoma of the stomach, which was to be considered of poor prognosis, and that liver resectomy was often effective.     

A new molecular targeted therapeutic approach for renal cell carcinoma with a p16 functional peptide using a novel transporter system

Molecular targeting agents have become formidable anticancer weapons showing much promise against refractory tumors and functional peptides and are among the more desirable of these nanobio-tools. Intracellular delivery of multiple functional peptides forms the basis for a potent, non-invasive mode of delivery, providing distinctive therapeutic advantages. We examine the growth suppression efficiency of human renal cell carcinoma (RCC) by single-peptide targeting. We simultaneously introduced p16INK4a tumor suppressor peptides by Wr-T-mediated peptide delivery. Wr-T-mediated transport of p16INK4a functional peptide into 10 RCC lines, lacking expression of the p16INK4a molecule, reversed the specific loss of p16 function, thereby drastically inhibiting tumor growth in all but 3 lines by >95% within the first 96?h. In?vivo analysis using SK-RC-7 RCC xenografts in nude mice demonstrated tumor growth inhibition by the p16INK4a peptide alone, however, inoculation of Wr-T and the p16INK4a functional peptide mixture, via the heart resulted in complete tumor regression. Thus, restoration of tumor suppressor function with Wr-T peptide delivery represents a powerful approach, with mechanistic implications for the development of efficacious molecular targeting therapeutics against intractable RCC.     

Attenuation of natural killer cell activity during 2-h exercise in individuals with spinal cord injuries

DESIGN: Non-randomized study. OBJECTIVE: To determine natural killer cell cytotoxic activity (NKCA) to 2-h arm ergometer exercise in persons with spinal cord injuries (SCI) and the underlying mechanism of such response. SETTING: University of Occupational and Environmental Health, Japan. METHODS: We examined NKCA response to 2-h arm crank ergometer exercise at 60% of maximum oxygen consumption (VO(2max)) in SCI and able-bodied persons. NKCA and plasma concentrations of prostaglandin E(2) (PGE(2)), adrenaline and cortisol were measured before, during and immediately after the exercise. The study included seven subjects with SCI between Th11 and L4 and six able-bodied persons. RESULTS: NKCA in able-bodied subjects increased (P<0.05) at 60 min of exercise and immediately after the exercise, and remained elevated up to 2 h after exercise. However, NKCA in SCI decreased (P<0.05) immediately after exercise but recovered at 2 h after exercise. Plasma adrenaline in both groups increased significantly (P<0.05) immediately after exercise and returned to baseline level 2 h after the exercise. Plasma cortisol in both groups remained constant throughout the study. In SCI, PGE(2) significantly increased immediately after 2 h exercise and returned to the baseline level 2 h after exercise; however, it remained unchanged during the test in able-bodied subjects. CONCLUSION: Our results suggested that increase of PGE(2) in SCI partially contributes to NKCA.