Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow limitation in the lungs. Smoking is one of the amongst major risk factors for the development of COPD. Environmental pollution, age, and airway hyperreactivity are also the risk factors. The protease-antiprotease imbalance and the oxidant-antioxidant imbalance cause airway inflammation and destruction. The genes related to these balances may contribute to development of COPD pathology. Candidate gene-association studies and linkage analyses have been reported for COPD patients. The alpha-1 antitrypsin, glutathione S-transferase, microsomal epoxide hydrolase, and matrix metalloproteinase, are candidate genes. In acquired factors for COPD pathology, the adenoviral latent infection may enhance airway inflammation, leading to airflow obstruction. The current progress and future visions of genetic predisposition of COPD are discussed.

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Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world (1). In 1999, COPD ranked sixth among the most common causes of death and twelfth as a worldwide burden of disease. It has been estimated that by the year 2020 COPD will be the third leading cause of death and fifth as a worldwide burden of disease (1). Thus, COPD is a major medical problem and there is evidence that it is increasing throughout the world (1-3). Despite recognition of COPD as an important international health problem, COPD has been neglected among common diseases, with little investment in research on its underlying cellular and molecular mechanisms.
Recently, global and Japanese guidelines for COPD have been published (3, 4). These guidelines seem to be useful to improve the underdiagnosis and undertreatment of COPD. In this review, I describe briefly the current recommendation for pharmacological therapy of stable COPD according to the global and Japanese guidelines for COPD (3, 4).

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Cancer is caused by genetic abnormalities: activation of oncogenes and functional inactivation of tumor-suppressor genes. Direct correction of these abnormalities should be the essential treatment for cancer; however, we have not developed any techniques to effectively fix the genome to date. Molecular biological analyses have demonstrated the cancer function of abnormal gene products, activated signal transduction pathways, and cancer-specific cell surface antigens. Molecular target drugs have been designed to suppress these molecules, important for maintaining cancer status, at stages of mRNA and protein. Some targets contributing to cancer progression are even within host cells such as angiogenic factor receptors. Differing from conventional chemotherapeutic agents screened and developed with cytotoxicity to tumor cells, molecular target drugs show higher specificity for cancer and sometimes simply stabilize the tumor. The effect of such drugs depends on the expression and functional importance of the target in cancer, and prediction of the effect using molecular techniques such as DNA microarray may be necessary for appropriate use.

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Rituximab, a genetically engineered, chimeric anti-CD20 monoclonal antibody, induces the apoptosis of B-lymphoma cells, in addition to the lyses by complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC), as shown in Fig. 1 (1). A Japanese phase I study of rituximab in relapsed or refractory patients with B-cell non-Hodgkin's lymphoma (B-NHL) showed an overall response rate (ORR) of 64% (7/11) with minimal toxicities. Elimination half-life (T_1/2) of serum rituximab was 445±361 hours, and the serum rituximab was detectable at three months. In the subsequent phase II study, 90 relapsed or refractory patients with indolent B-NHL or mantle cell lymphoma (MCL) were treated with rituximab at 375 mg/m²×4 weekly infusions. ORRs in indolent B-NHL and MCL were 61% (37/61) and 46% (6/13), respectively. In this presentation, the results of clinical trials of antibody therapy of malignant lymphoma are summarized, focusing on the two recent Japanese multicenter trials of rituximab and a Japanese feasibility study of anti-CD20 radioimmunotherapy with yttrium-90-lableled ibritumomab tiuxetan (2).

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Although steatohepatitis can be induced by an excessive intake of alcohol, it can also arise through various other causes, in which case it is known as non-alcoholic fatty liver disease (NAFLD). NAFLD is classified into two categories:simple fatty liver with a favorable clinical outcome, and non-alcoholic steatohepatitis (NASH), which is intractable and progressive. Recently in Japan, there has been an increase in the number of individuals at risk of lifestyle-related diseases, due to increased insulin resistance and visceral fat obesity. The metabolic syndrome (MS) is associated with several risk factors for atherosclerosis, including diabetes mellitus (DM), hypertension, and hyperlipidemia. Visceral fat obesity is the prime cause of NASH in the liver, and is therefore considered to be one of the phenotypic features of MS. Furthermore, most chronic liver diseases are associated with hepatitis C virus (HCV) infection. Fatty degeneration of hepatocytes is often observed in the liver of HCV-infected individuals, and results from viral suppression of mitochondrial beta-oxidation of fatty acid. The natural outcome of HCV infection is worse in patients with lifestyle-related high insulin resistance and visceral fat obesity. In this review, we describe the recent advances in research on progressive liver diseases that are the result of fat accumulation in the liver, with special reference to MS.

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In Japan, the number of patients with both chronic pancreatitis (CP) and pancreatic cancer (PC) is increasing. A nationwide survey on CP revealed that the total number of patients treated for CP in Japan in 2002 was estimated as 45,200 (95% confidence interval, 35,600-54,700), and 20,137 patients died of PC in 2002. Alcoholic pancreatitis was the most common type of pancreatitis (67.5 %). Cigarette smoking was an independent and significant risk factor for CP. The risks of pancreatic and nonpancreatic cancers increased in the course of CP. While alcohol consumption may increase the risk of PC via CP, smoking was important as a risk factor for both CP and PC. The increasing incidence of PC was closely related to the increasing intake of animal fat. Lifestyle in patients with CP appeared to be the same as that in patients with PC. Environmental factors such as lifestyle in combination with genetic factors may increase the risk for both CP and PC. Therefore, changing and improving lifestyle habits such as drinking, smoking and nutrition may reduce the risks for both CP and PC.

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Wrong:Ffailure
Right:Failure

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Wrong:C. albican
Right:C. albicans

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