The Effects of Volcanic Disaster on the Prevalence and Severity of Bronchial Asthma

Objectives: To evaluate the impact of volcanic disaster on bronchial asthma, the prevalence and the extent of deterioration of asthma were studied among primary school children aged 6 to 11 years who experienced the volcanic eruption of Mt. Unzen Fugen, Nagasaki, Japan. Methods: Questionnaire data were collected from the parents or guardians of primary school children. Asthma was classified into four categories: diagnosed asthma, current asthma, remitted asthma, and deteriorated asthma, and the prevalence of each category was compared according to sex and grade. We also analyzed the relation between asthma and past illness and family history including experience of volcanic disaster. Results: Multiple logistic regression analysis showed that past illnesses of allergic diseases, such as allergic rhinitis, dermatitis and conjunctivitis were associated with either current asthma or deteriorated asthma. On the effects of volcanic disaster, a change of family member after volcanic disaster was significantly associated with deteriorated asthma (odds ratio=3.20, 95% confidence interval=1.79-5.70). Location of school seemed to somewhat influence the prevalence of deteriorated asthma, which might relate to the distance from the volcanic crater. Conclusion: Our findings suggest that not only gases and ash but also changes in psychosocial conditions by refuge or related anxiety may influence the prevalence of asthma among primary school children

Identification of hepta-histidine as a candidate drug for Huntington's disease by in silico-in vitro- in vivo-integrated screens of chemical libraries.

We identified drug seeds for treating Huntington's disease (HD) by combining in vitro single molecule fluorescence spectroscopy, in silico molecular docking simulations, and in vivo fly and mouse HD models to screen for inhibitors of abnormal interactions between mutant Htt and physiological Ku70, an essential DNA damage repair protein in neurons whose function is known to be impaired by mutant Htt. From 19,468 and 3,010,321 chemicals in actual and virtual libraries, fifty-six chemicals were selected from combined in vitro-in silico screens; six of these were further confirmed to have an in vivo effect on lifespan in a fly HD model, and two chemicals exerted an in vivo effect on the lifespan, body weight and motor function in a mouse HD model. Two oligopeptides, hepta-histidine (7H) and Angiotensin III, rescued the morphological abnormalities of primary neurons differentiated from iPS cells of human HD patients. For these selected drug seeds, we proposed a possible common structure. Unexpectedly, the selected chemicals enhanced rather than inhibited Htt aggregation, as indicated by dynamic light scattering analysis. Taken together, these integrated screens revealed a new pathway for the molecular targeted therapy of HD

Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73

Transcriptional disturbance is implicated in the pathology of polyglutamine diseases, including Huntington's disease (HD). However, it is unknown whether transcriptional repression leads to neuronal death or what forms that death might take. We found transcriptional repression-induced atypical death (TRIAD) of neurons to be distinct from apoptosis, necrosis, or autophagy. The progression of TRIAD was extremely slow in comparison with other types of cell death. Gene expression profiling revealed the reduction of full-length yes-associated protein (YAP), a p73 cofactor to promote apoptosis, as specific to TRIAD. Furthermore, novel neuron-specific YAP isoforms (YAPΔCs) were sustained during TRIAD to suppress neuronal death in a dominant-negative fashion. YAPΔCs and activated p73 were colocalized in the striatal neurons of HD patients and mutant huntingtin (htt) transgenic mice. YAPΔCs also markedly attenuated Htt-induced neuronal death in primary neuron and Drosophila melanogaster models. Collectively, transcriptional repression induces a novel prototype of neuronal death associated with the changes of YAP isoforms and p73, which might be relevant to the HD pathology

Esophagectomy in Combination with a Resection of Involved Lung for Esophageal Cancer

The combined resection with involved lung for esophageal carcinoma was evaluated in terms of surgical indication and outcome in the 6 patients who underwent subtotal esophagectomy with pulmonary resection. It was confirmed that the operation was technically feasible but the surgical results were unsatisfactory. It was reasoned that grave surgical insult and adjuvant therapy to prevent recurrence result in immunodepressive status of the host and tends to accompany postoperative complications related to operative death. In conclusion, prevention of immunosuppression for the host is required by meticulous cares of nutrition and elimination of surgical stress by staged operation in order to obtain satisfactory result after surgery

Clinical Analysis of Perforated Intestinal Behcet Disease

Clinical pattern of perforated intestinal Behcet disease was analyzed in the five patients who underwent surgery in terms of preoperative symptoms, the condition of perforation, the extent of resection and recurrence. In the experienced patients, recurrences were included in four of the five patients in spite of treatment. Perforation was based on deep multiple ulcers, characteristic of the punchedout type. It is emphasized that intestinal Behcet disease is more likely to occur as a catastrophic event of perforation which requires an urgent operation, and more extensive resection is mandatory for prevention of recurrence

Esophageal Carcinomas with Synchronous and Metachronous Primary Malignant Carcinomas in Other Organs

Seventeen patients with 10 synchronous and 7 metachronous double cancers with carcinomas of the esophagus were surgically treated in the First Department of Surgery, Nagasaki University School of Medicine. All patients were men with an average of age 68.5. The incidence of double cancers with carcinoma of the esophagus accounted for 12.7% in a total of 134 of this series. The three triple cancers were included. Of the three, one was synchronous triple cancers in the esophagus, the stomach and the colon. The outcome was not necessarily satisfactory. Two had recurrence 3 and 5 months after surgery, but one is still alive for 33 months, free from carcinoma

Significance of Needle Aspiration Biopsy for Breast Cancer

The results of aspiration biopsy cytology were clinically evaluated on the basis of clinical experience with 608 patients with breast cancer at the First Department of Surgery, Nagasaki University School of Medicine. Aspiration biopsy is of clinical value in making a diagnosis of small-sized tumors. There was no detrimental outcome to promote tumor-cell spread locally as well as to give rise to distant metastasis into the other organ. One should be aware of a no cell finding in relation to scirrhous carcinoma and intraductal papillomatosis. Emphasis is placed on recommendation of open biopsy without repeated aspiration maneuver

Mutant huntingtin impairs Ku70-mediated DNA repair

Mutant huntingtin prevents interaction of the DNA damage repair complex component Ku70 with damaged DNA, blocking repair of double-strand breaks

Dynamic changes of the phosphoproteome in postmortem mouse brains.

Protein phosphorylation is deeply involved in the pathological mechanism of various neurodegenerative disorders. However, in human pathological samples, phosphorylation can be modified during preservation by postmortem factors such as time and temperature. Postmortem changes may also differ among proteins. Unfortunately, there is no comprehensive database that could support the analysis of protein phosphorylation in human brain samples from the standpoint of postmortem changes. As a first step toward addressing the issue, we performed phosphoproteome analysis with brain tissue dissected from mouse bodies preserved under different conditions. Quantitative whole proteome mass analysis showed surprisingly diverse postmortem changes in phosphoproteins that were dependent on temperature, time and protein species. Twelve hrs postmortem was a critical time point for preservation at room temperature. At 4°C, after the body was cooled down, most phosphoproteins were stable for 72 hrs. At either temperature, increase greater than 2-fold was exceptional during this interval. We found several standard proteins by which we can calculate the postmortem time at room temperature. The information obtained in this study will be indispensable for evaluating experimental data with human as well as mouse brain samples

Dynamic Changes of the Phosphoproteome in Postmortem Mouse Brains

Protein phosphorylation is deeply involved in the pathological mechanism of various neurodegenerative disorders. However, in human pathological samples, phosphorylation can be modified during preservation by postmortem factors such as time and temperature. Postmortem changes may also differ among proteins. Unfortunately, there is no comprehensive database that could support the analysis of protein phosphorylation in human brain samples from the standpoint of postmortem changes. As a first step toward addressing the issue, we performed phosphoproteome analysis with brain tissue dissected from mouse bodies preserved under different conditions. Quantitative whole proteome mass analysis showed surprisingly diverse postmortem changes in phosphoproteins that were dependent on temperature, time and protein species. Twelve hrs postmortem was a critical time point for preservation at room temperature. At 4uC, after the body was cooled down, most phosphoproteins were stable for 72 hrs. At either temperature, increase greater than 2-fold was exceptional during this interval. We found several standard proteins by which we can calculate the postmortem time at room temperature. The information obtained in this study will be indispensable for evaluating experimental data with human as well as mouse brain samples