Frequent loss of heterozygosity in two distinct regions,8p23.1 and 8p22, in hepatocellular carcinoma

AIM: To identify the precise location of putative tumor suppressor genes (TSGs) on the short arm of chromo- some 8 in patients with hepatocellular carcinoma (HCC). METHODS: We used 16 microsatellite markers informative in Japanese patients, which were selected from 61 pub- lished markers, on 8p, to analyze the frequency of loss of heterozygosity (LOH) in each region in 33 cases (56 lesions) of HCC. RESULTS: The frequency of LOH at 8p23.2-21 with at least one marker was 63% (20/32) in the informative cases. More specifically, the frequency of LOH at 8p23.2, 8p23.1, 8p22, and 8p21 was 6%, 52%, 47%, and 13% in HCC cases. The LOH was significantly more frequent at 8p23.1 and 8p22 than the average (52% vs 22%, P = 0.0008; and 47% vs 22%, P = 0.004, respectively) or others sites, such as 8p23.2 (52% vs 6%, P = 0.003; 47% vs 22%, P = 0.004) and 8p21 (52% vs 13%, P = 0.001; 47% vs 13%, P = 0.005) in liver cancer on the basis of cases. Notably, LOH frequency was significantly higher at D8S277, D8S503, D8S1130, D8S552, D8S254 and D8S258 than at the other sites. However, no allelic loss was detected at any marker on 8p in the lesions of nontumor liver tissues. CONCLUSION: Deletion of 8p, especially the loss of 8p23.1-22, is an important event in the initiation or promotion of HCC. Our results should be useful in identi- fying critical genes that might lie at 8p23.1-22.     

Impending epidemic: future projection of heart failure in Japan to the year 2055.

BACKGROUND: The future burden of heart failure in Japan was projected to 2055 in order to prospectively estimate of the number of these patients. METHODS AND RESULTS: The statistics are based on prevalence data of left ventricular dysfunction (LVD) in Sado City using the Sado Heart Failure Study (2003) and population estimates from the Japanese National Institute of Population and Social Security Research Report (2006). The number of Japanese outpatients with LVD was 979,000 in 2005, and is predicted to increase gradually as the population ages, reaching 1.3 million by 2030. CONCLUSION: LVD is expected to precipitate a future epidemic of heart failure in Japan.     

Caspase activation and neuroprotection in caspase-3- deficient mice after in vivo cerebral ischemia and in vitro oxygen glucose deprivation

Caspase-3 is a major cell death effector protease in the adult and neonatal nervous system. We found a greater number and higher density of cells in the cortex of caspase-3(-/-) adult mice, consistent with a defect in developmental cell death. Caspase-3(-/-) mice were also more resistant to ischemic stress both in vivo and in vitro. After 2 h of ischemia and 48 h of reperfusion, cortical infarct volume was reduced by 55%, and the density of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling-positive cells was decreased by 36% compared with wild type. When subjected to oxygen-glucose deprivation (2 h), cortical neurons cultured from mice deficient in caspase-3 expression were also more resistant to cell death by 59%. Mutant brains showed caspase-specific poly(ADP-ribose) polymerase cleavage product (85-kDa fragment) in vivo and in vitro, suggesting redundant mechanisms and persistence of caspase-mediated cell death. In the present study, we found that caspase-8 mediated poly(ADP-ribose) polymerase cleavage in caspase-3(-/-) neurons in vivo and in vitro. In addition, mutant neurons showed no evidence of compensatory activation by caspase-6 or caspase-7 after ischemia. Taken together, these data extend the pharmacological evidence supporting an important role for caspase-3 and caspase-8 as cell death mediators in mammalian cortex and indicate the potential advantages of targeting more than a single caspase family member to treat ischemic cell injury.     

Hyperthyroid Graves' disease after hemithyroidectomy for papillary carcinoma: report of three cases

Here we report three cases of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary carcinoma. In Case 1, the patient first developed hyperthyroidism 2 years after resection of left thyroid lobe, was treated for 2 years with antithyroid drug which was then discontinued, and relapsed with periodic paralysis after 8 years of remission. In Case 2, a hyperfunctioning remnant thyroid was noted 22 years after right hemithyroidectomy. In Case 3, where thyrotoxic symptoms became evident 7 weeks after right hemithyroidectomy, autoantibodies to thyroglobulin and thyroid microsome were positive in preoperative serum, in line with a report by others detecting these antibodies in 2 out of 3 such cases examined. Later bioassay revealed activity of thyroid stimulating antibodies in that serum, with further increase in titer in the sample taken at the clinical manifestation. Hence in Case 3, surgical stress may have altered immunological homeostasis, promoting a preclinical Graves' disease to full-blown hyperthyroidism.     

Islet cell-activating protein reverses anti-fucosyl GM1 ganglioside antibody-induced inhibition of adenosine 3',5'-monophosphate production in FRTL-5 rat thyroid cells

Our previous study revealed that a specific antibody against fucosyl GM1 ganglioside (fGM1) inhibits basal and ligand-stimulated cAMP production in FRTL-5 rat thyroid cells. To further elucidate the mechanism of this inhibitory action of the antibody, the involvement of guanine nucleotide-binding proteins was studied using islet cell-activating protein (IAP) and cholera toxin. When FRTL-5 cells were pretreated with IAP and incubated with the antibody, the inhibitory activity of the antibody on cAMP production was completely abolished. Furthermore, the inhibitory activity of the antibody on TSH- or forskolin-stimulated cAMP production was also abolished by IAP preincubation. The inhibitory activity of the antibody by pretreatment of the cells was also reversed by the addition of IAP. Coincubation of FRTL-5 cells with the antibody and cholera toxin reduced the cAMP inhibitory action of the antibody. Similar results were obtained with anti-fGM1 pretreatment before cholera toxin stimulation. These results provide evidence that anti-fGM1 antibody acts via guanine nucleotide-binding proteins in inhibiting cAMP production in FRTL-5 cells.     

An esophageal cancer case unresectable due to tuberculous fibrosing mediastinitis: report of a case

We present a case of esophageal carcinoma in which esophagectomy was not possible because of tuberculous fibrosing mediastinitis. A 77-year-old man was diagnosed with carcinoma of the thoracic esophagus and admitted to our hospital. Chest radiography on admission revealed no abnormality except pleural thickening of the pulmonary apices, suggesting a history of subclinical infection of tuberculous pleurisy. The patient underwent surgery with a curative intent. Thoracotomy revealed that the mediastinum had been replaced with dense fibrous tissues and was widely encased with laminar calcification. Esophagectomy was not performed because it was considered impossible to do so safely. Although diagnosis of fibrous mediastinitis was not made preoperatively, review of the preoperative computed tomographic scans revealed proliferation of mediastinal soft tissues that were associated with patchy and laminar calcifications. Tuberculous fibrosing mediastinitis is an uncommon but clinically important disease for physicians who are involved in the diagnosis and treatment of esophageal cancer.     

H5N1 highly pathogenic avian influenza virus isolated from conjunctiva of a whooper swan with neurological signs

An H5N1 highly pathogenic avian influenza virus was isolated from conjunctiva of a whooper swan with neurological signs, which was captured during the latest H5N1 HPAI outbreak in Japan. The conjunctival swab contained a larger amount of the virus in comparison with the tracheal swab. This is the first report on H5N1 virus isolation from the conjunctiva of a wild bird, and the result may suggest the conjunctival swab to be a critical sample for H5N1 HPAIV detection in waterfowl. Phylogenetic analysis of the HA gene indicated that the virus falls into H5N1 clade 2.3.2.1.