An increased systemic production of oxygen-free radicals by activated inflammatory cells is thought to be involved in the pathophysiology of asthma. The aim of this study is to evaluate the clinical effects of radon and thermal therapy on asthma in relation to antioxidant enzymes and lipid peroxide. Radon and thermal therapy were performed once a week. All subjects went to a hot bathroom with a high concentration of radon, and nasal inhalation of vapor from a hot spring was performed for 40 min once a day under conditions of high humidity. The room temperature was 48 degrees C; the room radon concentration was 2,080 Bq/m3. Blood samples were collected at 2 h, 14, and 28 days after the first therapy. A blood sample also was collected before the first therapy (at body temperature and background radon level) to be used as the control. The forced expiratory volume in one second (%FEV1) was significantly increased 28 days after the first therapy. On day 28, the catalase (CAT) activity was significantly increased in comparison with the control. The superoxide dismutase (SOD) activity was significantly increased compared to the control after first inhalation. On days 14 and 28, the lipid peroxide level was significantly decreased in comparison with the control. In conclusion, the present pilot study has shown that radon and thermal therapy improved the pulmonary function of asthmatics by increasing the reduced activities of antioxidant enzymes.

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The helix-loop-helix (HLH) family of transcriptional regulatory proteins are key regulators in numerous developmental processes. The class I HLH proteins, such as E12 are ubiquitously expressed. Class II HLH proteins, such as MyoD, are expressed in a tissue-specific manner. Class I and II heterodimers can bind to E-boxes (CANNTG) and regulate lineage commitments of embryonic cells. In an attempt to identify partners for the E12 protein that may exert control during liver development, we performed the yeast 2-hybrid screen using an expression complementary DNA library from human fetal liver. A novel dominant inhibitory HLH factor, designated HHM (human homologue of maid), was isolated and characterized. HHM is structurally related to the Id family and was highly expressed in brain, pituitary gland, lung, heart, placenta, fetal liver, and bone marrow. The helix-loop-helix (HLH) family of transcriptional regulation proteins are key regulators for various kinds of organ developmental processes. 1 Classification of the HLH proteins into 7 groups based on tissue distribution, dimerization capability, and DNA-binding specificities has been devised. 2 Briefly, class I HLH proteins, such as E12, E47, HEB, E2-2, and Daughterless, are also called E proteins. These proteins are ubiquitously expressed in many tissues and make either homodimers or heterodimers. 3 The specific DNA-binding site of class I proteins is known as an E-box, having the consensus sequence CANNTG. 4 Class II HLH proteins, such as MyoD, myogenin, Atonal, and NeuroD/BETA2, show a tissue-specific expression pattern. [5][6][7][8][9][10][11][12] With few exceptions, they are incapable of forming homodimers and preferentially heterodimerize with the E proteins. The heterodimer of class I and II HLH proteins bind to the E-boxes that are found in a number of cell type-specific promoters and enhancers and regulate different developmental pathways, such as myogenesis, neurogenesis, lymphopoiesis, and sex determination. [13][14][15] Class III HLH proteins include the Myc family of transcription factors, TFE3, SREBP-1, and the Microphthalmia-associated transcription factor, Mi. Proteins of this class contain a leucine zipper (LZ) adjacent with the HLH motif. 16,17 Class IV HLH proteins included Mad, Max, and Mxi, that are capable of dimerizing with the Myc proteins or with one another. [18][19][20] Class V HLH proteins lack the basic domain and consequently do not bind to DNA. These include Id and emc. [21][22][23][24][25][26] Class VI HLH proteins have a specific feature that includes a proline in their basic region. Drosophila proteins Hairy and Enhancer of split are included in this class. 27,28 The class VII HLH proteins are characterized by the presence of the bHLH-PAS domain and include the aromatic hydrocarbon receptor and its nucleartranslocator. 29 It has been clearly shown that the basic HLH (bHLH) factor can directly or indirectly regulate a network of gene expressions. 1 This regulation can be either "enabling," i.e., promoting an execution of a differ...

The formation of fibrous capsule around the cancer nodule and of the septum in the tumor is frequently observed with the development of hepatocellular carcinoma (HCC). We aimed to clarify how the capsule and septum were formed during the growth of HCC. Liver samples surgically resected from 25 patients with HCC were studied with in situ hybridization for type-I, -III, and -IV procollagen. Type-I and -III procollagen-expressing cells, mostly alpha-smooth muscle actin (SMA)-positive, were increased in the fibrous capsule and in the septum between HCC nodules. These cells were also found at the invasion front of HCC and around the necrotic cancer tissues. Type-IV procollagen gene expression was mainly observed in mesenchymal cells localized in both HCCs and non-cancerous liver. Cancer cells or hepatocytes did not express any of these procollagen genes. The present study reveals that the capsule and septum are mainly formed by alpha-SMA-positive mesenchymal cells at the interface between two different tissues (e.g., cancer nodule vs non-cancerous liver or another cancer nodule). The wound healing occurs even in HCC. The capsule formation may result from interaction between tumor and host liver and interfere the growth and invasion of HCC.

Objective The effects of perilla seed oil (n-3 fatty acids) on bronchial asthma were compared with the effects of corn oil (n-6 fatty acids) in relation to the pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes.Methods and Subjects 14 asthmatic subjects were divided randomly into two groups: one group (7 subjects) consumedperilla seed oil-rich supplementation and the other group (7 subjects) consumed corn oil-rich supplementation for 4 weeks. Generation of LTsby leucocytes and respiratory function were comparedbetween the two groups.Results The generation of LTB4 and LTC4 by leucocytes tended to increase in subjects (N=7) with corn oil-rich supplementation, and decrease in subjects (N=7) with perilla seed oil-rich supplementation. Significant differences between the two groups were observed in the generation of LTB4 at 2 weeks (p<0.05) and LTC4 at 2 weeks (p<0.05) after dietary supplementation. Significant increases in the value of PEF (p<0.05), FVC (p<0.01), FEV1 0 (p<0.05) and V25 (p<0.05) were found in subjects who received perilla seed oil supplementation for 4 weeks. And significant differences in the value of FVC (p<0.05) and FEV1 0 (p<0.05) were observed between the two groups after 4 weeks of dietary supplementation.Conclusion These results suggest that perilla seed oilrich supplementation is useful for the treatment of asthma in terms of suppression of LTB4and LTC4generation by leucocytes, and improvement of pulmonary function.

Background-Low attenuation areas (LAA) on computed tomographic (CT) scans have been shown to represent emphysematous changes in patients with chronic obstructive pulmonary disease (COPD). However, the significance of LAA is still controversial in patients with asthma. This study was undertaken to assess the usefulness of lung CT densitometry in the detection of airspace enlargement in association with asthma severity. Methods-Forty five asthmatic subjects and 15 non-smoking controls were studied to determine the influence of age, pulmonary function, and asthma severity on mean lung density ( Conclusions-Decreased CT lung density in non-smoking asthmatics is related to airflow limitation, hyperinflation and aging, but not with lung transfer factor. (Thorax 2001;56:851-856) Keywords: high resolution computed tomography; asthma severity; lung function; age Asthma is a disease characterised by airflow limitation that reverses spontaneously or in response to treatment.1 The nature of asthma as a chronic inflammatory disease of the airways is well recognised.2 This inflammation process leads to irreversible changes in the airway.3-5 Frequent airway and lung parenchymal changes associated with asthma are considered to be responsible for the irreversibility of airway obstruction, an outcome that is observed in many severe asthmatics. Emphysema, on the other hand, is defined pathologically as a process that results in the increase of distal airspaces with destruction of their walls without obvious fibrosis. 6 The evidence for the presence of emphysema in asthmatic patients is controversial.Numerous studies have demonstrated the usefulness of computed tomographic (CT) scanning and high resolution CT (HRCT) scanning to detect and quantify pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD), [7][8][9][10][11][12][13][14][15][16][17][18][19] and a quantitative method using digital data as well as visual assessment of the scan are used to analyse the CT images. Low attenuation areas (LAA) on CT scans in vivo have been shown to represent macroscopic and/or microscopic emphysematous changes in the lungs of patients with COPD.7-12 However, one report has suggested that mean lung density (MLD) gives a good indication of hyperinflation rather than of emphysema. 20Some studies have investigated the use of CT lung densitometry in non-smoking asthmatic patients. [21][22][23][24] One study suggested that the percentage of pixels below -900 Hounsfield Units (HU) at full expiration reflects air trapping in asthmatic patients and correlates with pulmonary function. 21 Gevenois et al showed that acute expiratory airflow limitation and chronic hyperinflation did not influence the MLD or the relative area of the lungs showing attenuation values less than -950 HU (RA 950 ) in nonsmoking asthmatic patients. 22 They also found that CT lung densitometry was influenced by the total lung capacity (TLC) and age in healthy subjects. Biernacki et al observed that some patients with chronic stable asthma devel...

HARUSHIGE NAKATSUKASA, KOUZOU ASHIDA, TOSHIHIRO HIGASHI, SOUHEI OHGUCHI, SO TSUBOI, NAOKI HINO, KAZUHIRO NOUSO, YOSHIAKI URABE, NOBUYUKI KINUGASA, KEIGO YOSHIDA, SHUJI UEMATSU, MASAHIKO ISHIZAKI, YOSHIYUKI KOBAYASHI, AND TAKAO TSUJI Hepatocellular carcinoma (HCC) is one of the most prevaThe cellular distribution of tissue inhibitor of melent malignancies in Japan and China, and frequently occurs talloproteinases (TIMP)-1, and TIMP-2 was studied by in hepatitis B or C virus-related chronic hepatitis or cirrhousing in situ hybridization in surgically removed husis. In particular, cirrhosis has been regarded as a high-risk man hepatocellular carcinomas (HCCs) and cholandisease state for developing HCCs. A unique feature of HCC giocellular carcinomas (CCCs). The purpose of this development is the occurrence of the tumor in fibrotic or cirstudy was to characterize the potential involvement rhotic liver that contains abundant extracellular matrices of TIMPs in the development of HCCs and CCCs. All (ECMs). Therefore, the capacity of HCC to degrade the surHCCs and CCCs expressed TIMPs. The distribution rounding ECMs may be an important trait for growth, invaof transcripts for TIMPs in the tumors was mostly sion, and metastasis. homogeneous. Expression of TIMPs in cancer cellsThe characteristic features of malignant tumors are the was more intense than that in the surrounding noninvasion to cross tissue boundaries and the metastasis to cancerous liver (either, cirrhosis, chronic hepatitis, distant organs. Many steps that occur during cancer invasion or normal), and expression of TIMP-1 was stronger and metastasis require specific interactions between maligthan that of TIMP-2. Expression of TIMPs varied nant cells and the ECMs, 1 particularly in regard to HCC and among HCC nodules, but there was no obvious associcirrhotic liver. Multiple humoral factors are involved in this ation between the expression level of TIMPs and difprocess: matrix metalloproteinases (MMPs), tissue inhibitor ferentiation stages or invasiveness of the HCCs. Tranof metalloproteinases (TIMPs), and various cytokines. An imscripts for TIMPs were clearly demonstrated in the balance between TIMPs and MMPs may be an important metastatic HCC nodules in the lung. Expression of factor in tumor invasion and metastasis. TIMP-1 in CCC was strong, and small nodules of CCC Three members of the TIMP family have been described. 2 were recognized in the liver. ImmunohistochemicalEach TIMP is the product of a separate gene. TIMP-1 is a 28-study for TIMP-1 revealed a consistent staining of the kd glycoprotein, whereas TIMP-2 is a 21-kd nonglycosylated TIMP-1 protein with the transcripts. In the perituprotein. Between TIMP-1 and TIMP-2, there is 37% amino moral histologically normal liver, which was not inacid identity and 65.6% overall homology. 3 TIMP-3 has been fected with either hepatitis B or C virus, expression identified as a 21-kd protein and shares an amino acid seof TIMP-1 was found in various cell types, but that of quence homology of 40% with TIMP-1 and 45%...

Recently, it was shown that both mean lung density (MLD) and the relative lung area with an attenuation of v-950 HU (RA950) are related to severity of asthma in nonsmoking asthmatics. The aim of the present study was to examine whether reduced computed tomography (CT) lung density during exacerbation could change after treatment.A cross-sectional study was performed to compare CT lung density in 30 stable asthmatics, 30 unstable asthmatics and 25 control subjects. In order to investigate longitudinally the effect of treatment on decreased CT lung density, 17 asthmatics with an exacerbation were followed at the initiation of treatment and 2 months after relief.The MLD was significantly lower and the RA950 significantly higher in unstable asthmatics than in controls and stable asthmatics. Both MLD and RA950 changed significantly with administration of systemic glucocorticoid therapy. The changes in forced expiratory volume in one second correlated significantly with those in both MLD and RA950. The changes in residual volume also correlated significantly with those in both MLD and RA950.It was concluded that decreased computed tomographic lung density during an asthma exacerbation is at least partially reversible, and changes in mean lung density and the relative lung area with a radiation attenuation of v-950 HU are related to the change in forced expiratory volume in one second and residual volume.