The novel finding is that OSA may inhibit the recovery of LV function in patients with AMI.

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.

Summary Membrane cofactor protein (MCP, CD46) is one of the complement regulatory proteins, and is widely distributed in human organs and protects cells from complement-mediated cytotoxicity. We analysed the distribution and the intensities of MCP in liver diseases and evaluated the role of MCP during hepatocarcinogenesis. Western blot analysis revealed that relative densities (density of the sample/density of the standard sample) of MCP in 27 HCC, 18 liver cirrhosis, nine chronic hepatitis and 12 normal liver were 0.63 ± 0.23, 0.21 ± 0.07, 0.25 ± 0.10 and 0.11 ± 0.03 (mean ± s.d.) respectively. MCP expression in hepatocellular carcinoma (HCC) was significantly higher than that in both liver cirrhosis and chronic hepatitis (P < 0.01). The difference in the tumour sizes, the grades of differentiation and viral marker status did not affect the expression. Immunohistological analysis revealed that MCP was distributed mainly in the basolateral membrane of the hepatic cord in non-cancerous liver, along with endothelial cells and bile duct cells. In HCC, the protein was observed on the membrane in a non-polarized fashion. These data suggest that HCC cells acquire the increased MCP expression in a development of HCC and may escape from tumour-specific complement-mediated cytotoxicity.

No abstract

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%...

E LECTROCARDIOGRAPHIC findings in acute myocarditis show widespread ST deviations, conduction disturbances, and abnormal Q waves which sometimes imitate acute myocardial infarction.1-4) The incidence of abnormal Q waves ranges widely from 14 to 63% in myocarditis.1,5-7) A transient appearance of Q waves during an acute illness1,7) may indicate gross, but reversible myocardial damage. To our knowledge, previous studies give little attention to the differences in clinical characteristics between patients with Q wave myocarditis and non-Q wave myocarditis. This study was designed on the hy-From the

MAGE gene family encodes peptides recognized by autologous cytotoxic T lymphocytes in a major histocompatibility complex (MHC) class-I restricted fashion. In the present study, we have performed reverse-transcription polymerase chain reaction (RT-PCR) for the genes, as well as immunohistochemical analysis and Western blotting of MAGE-1 and -3 proteins in 33 surgically resected hepatocellular carcinomas (HCCs). MAGE-1 and -3 mRNAs were constitutively expressed exclusively in 78 and 42% of HCCs respectively. On immunohistochemistry with monoclonal antibodies, 77B for MAGE-1 and 57B for MAGE-3, MAGE-1 and -3 proteins were recognized in cytoplasm of only six among 33 (18%) and two of 29 HCCs (7%) respectively. The distribution pattern was mostly focal in HCC nodules. By contrast, the Western blot analysis revealed that the MAGE-1 (46 kDa) and -3 proteins (48 kDa) were expressed in 80 and 60% of 15 HCCs examined respectively. The proteins of MAGE-1 and -3 were also expressed exclusively in HCCs regardless of the histological grading and clinical staging. Our results indicate that the detection of the genes by RT-PCR or the proteins by Western blotting is useful for differentiating early HCCs from non-cancerous lesions, and that the peptides derived from MAGE-1 and -3 proteins might be suitable targets for immunotherapy of human HCC. © 1999 Cancer Research Campaign

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies, and the treatment has been extremely difficult, although several treatment modalities are available, including liver transplantation. 1 An approach involving retrovirus-2,3 or adenovirus-4,5 mediated gene therapy for the treatment of HCCs has recently been described, attempting differential expression of particular genes (e.g., suicide genes such as herpes simplex virus/thymidine kinase gene) controlled by transcriptional regulatory sequence (TRS) of liverspecific genes such as ␣-fetoprotein (AFP) or albumin. These ideas are based on the fact that AFP, normally expressed only in the fetus, is frequently reactivated in many cases of HCC, and that, in the case of albumin, retrovirus is only integrated into the host genome of the cells that are in cell cycle.Of particular importance in the genetic treatment of malignancies is that transduced genes must be expressed tumor-specifically in response to particular transcriptional signals. For targeting genes being expressed in HCC cells, the choice of the TRS is the first key step, and either AFP-or albumin-TRS has been frequently chosen for this purpose. [2][3][4][5][6][7][8] In this regard, it is necessary to have the knowledge as to how and up to what differentiation stages of HCC the AFP and/or albumin genes are expressed.AFP is a plasma protein produced by fetal liver, yolk sac, and mostly by HCCs in adults. 9 The expression of the AFP gene has been studied in three HCC samples by in situ hybridization, and it has shown even hybridization signals in the majority of HCC cells. 10 Albumin is one of the major plasma proteins and is synthesized mostly in hepatocytes. Albumin gene expression can be used as a diagnostic tool in the differential diagnosis of HCC from cholangiocellular carcinomas or other metastatic liver cancers. 11,12 Thus, the expressions of AFP and albumin have been used as specific markers of HCC cells and the cells of hepatocellular lineage, respectively.Although the needs of specific TRSs for gene therapy are expanding, the lack of knowledge on cellular distribution of transcripts for AFP or albumin genes in human HCCs makes the accurate targeting difficult, and the validity of using these Abbreviations: AFP, ␣-fetoprotein; DIG, digoxigenin; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HCC, hepatocellular carcinoma; SSC, standard saline citrate; TRS, transcriptional regulatory sequence.