No abstract

Adult T-cell leukemia (ATL) is associated with prior infection with human T-cell leukemia virus type 1 (HTLV-1); however, the mechanism by which HTLV-1 causes adult T-cell leukemia has not been fully elucidated. Recently, a functional basic leucine zipper (bZIP) protein coded in the minus strand of HTLV-1 genome (HBZ) was identified. We report here a novel isoform of the HTLV-1 bZIP factor (HBZ), HBZ-SI, identified by means of reverse transcription-PCR (RT-PCR) in conjunction with 5 and 3 rapid amplification of cDNA ends (RACE). HBZ-SI is a 206-amino-acid-long protein and is generated by alternative splicing between part of the HBZ gene and a novel exon located in the 3 long terminal repeat of the HTLV-1 genome. Consequently, these isoforms share >95% amino acid sequence identity, and differ only at their N termini, indicating that HBZ-SI is also a functional protein. Duplex RT-PCR and real-time quantitative RT-PCR analyses showed that the mRNAs of these isoforms were expressed at equivalent levels in all ATL cell samples examined. Nonetheless, we found by Western blotting that the HBZ-SI protein was preferentially expressed in some ATL cell lines examined. A key finding was obtained from the subcellular localization analyses of these isoforms. Despite their high sequence similarity, each isoform was targeted to distinguishable subnuclear structures. These data show the presence of a novel isoform of HBZ in ATL cells, and in addition, shed new light on the possibility that each isoform may play a unique role in distinct regions in the cell nucleus. Adult T-cell leukemia (ATL) is an aggressive and lethal CD4ϩ T-cell malignancy with characteristic nuclear irregularity. Human T-cell leukemia virus type 1 (HTLV-1) is a singlestranded RNA virus belonging to the subfamily Deltaretrovinae and containing reverse transcriptase. The RNA of the retrovirus is transcribed into DNA by reverse transcriptase, and is then inserted into the host genome by an integrase, forming the provirus. Since ATL is associated with prior infection with HTLV-1 (11, 27), although the mechanisms by which tumorigenesis occurs are not fully defined, the viral proteins from HTLV-1 genome have been thought to be essential for the process of leukemogenesis in ATL.The HTLV-1 genome encodes common structural and enzymatic proteins (Gag, Pol and Env) and regulatory and accessory proteins (Tax, Rex, p12 I , p13 II and p30 II ) (13). Among these HTLV-1 viral proteins, Tax protein is considered to play a central role in the early stage of leukemogenesis (8,14,21,24,25,29). However, leukemic cells frequently lack the expression of Tax due to genetic and epigenetic changes of the HTLV-1 provirus (5,23,26), suggesting that while Tax may be a necessary prerequisite for the malignant transformation of infected cells, it is not essential for the maintenance of ATL cells in vivo. In the final stage of leukemogenesis, other continuously expressed viral proteins from the HTLV-1 genome are likely to be involved in the maintenance of ATL cells, because ATL is a uniqu...

Blastic natural killer (NK) cell lymphoma corresponding to CD4+CD56+ malignancies is a novel disease entity, according to the results of clinical, morphologic, and immunologic studies. It is especially noteworthy that this disease likely arises from plasmacytoid dendritic cells (pDCs), described previously as plasmacytoid T-cells, which have an important role in innate and adaptive immunity. However, the exact relationship between the tumor cells and pDCs remains to be elucidated. We encountered a patient with typical blastic NK cell lymphoma, which later converted to leukemic manifestations, and tried to establish a cell line using the leukemic cells. We succeeded in establishment of a novel cell line, CAL-1, which originated from the primary malignant cells. The genetic and phenotypic features of CAL-1 cells bear a similarity to those of pDCs, namely, plasmacytoid morphology at light and electron microscopy; negative results for CD11c and lineage-associated markers of CD3, CD14, CD19, and CD16; positive results for HLA-DR, CD4, CD56, CD45RA, and CD123; and negative results for TCR and IgH gene rearrangements. An interesting finding was that CAL-1 cells change morphologically into the mature DC appearance with many long dendrites after short-term culture in the presence of granulocyte-macrophage colony-stimulating factor and interleukin 3. CAL-1 cells can secrete tumor necrosis factor alpha but not interferon alpha. Thus although they do not share in part phenotypic and functional features with their normal counterparts, CAL-1 cells mostly exhibit a striking pDC phenotype. We describe the first novel pDC cell line of CAL-1. This cell line should open the opportunity for study not only of CD4+CD56+ tumor cells but also of pDCs in vitro.

This is the first comprehensive study to evaluate the mutual expression profile of HBZ and Tax in provirus-positive cells, revealing that there are quantitative and relative characteristic features among infected cells, primary ATL cells, and cell lines.

We evaluated the effect of diabetes mellitus on the prognosis of hepatocellular carcinoma after an elective hepatic resection. Of the 342 patients who underwent a hepatic resection between April 1985 and March 1995, 87 (25.4%) were diabetic. Postoperative morbidity was more common among diabetics than among nondiabetics (36.0% vs. 22.5%, P ‫؍‬ .0239). The postoperative survival rate and the cancer-free survival rate were also better in patients without diabetes than in those with diabetes (P ‫؍‬ .0333, P ‫؍‬ .0149). The results of a multivariate analysis show diabetes mellitus to be an independent and prognostic indicator after a hepatic resection with hepatocellular carcinoma. According to the above findings, diabetes mellitus is thus considered to be a risk factor for prognosis after hepatic resection in patients with hepatocellular carcinoma. (HEPATOLOGY 1998;27:1567-1571.)The influence of diabetes mellitus on the outcome of elective surgical procedures remains controversial. [1][2][3][4] We previously reported that diabetic patients who underwent elective hepatic resections developed a higher incidence of postoperative morbidity, but not a shorter long-term survival. 5,6 Recently, Adami et al. 7 reported diabetes mellitus to be a risk factor for carcinogenesis in primary liver cancer based on a cohort study. However, little proof has been found regarding the effect of diabetes mellitus on the long-term outcome of patients with hepatcellular carcinoma after a hepatic resection. Therefore, the purpose of this study is to clarify the effect of diabetes mellitus on the long-term survival after a hepatic resection for hepatocellular carcinoma. PATIENTS AND METHODSBetween April 1985 and March 1995, 342 patients with hepatocellular carcinoma underwent a curative hepatic resection in the department of Surgery II, Kyushu University Hospital and affiliated hospitals. They ranged in age from 33 to 79 years (mean Ϯ SD, 59.7 Ϯ 8.3 years), and 275 (80.4%) were males. Liver cirrhosis was identified in 183 patients (53.5%). The methods of resection used included a trisegmentectomy in eight patients, a lobectomy in 84, a segmentectomy in 52, a subsegmentectomy in 64, and a partial hepatectomy consisting of less than a subsegmentectomy in 134. The follow-up period ranged from 34 to 4,036 days (median, 1,278 days; 25th percentile, 724 days; 75th percentile, 2,012 days).Of these patients, 87 (25.4%) were diagnosed with diabetes. The definition of diabetes mellitus was a fasting serum glucose above 7.8 mmol/L (140 mg/dL), abnormal results for a 75-g oral glucose tolerant test, or the need for insulin or an oral antihyperglycemic drug to control glucose levels. The preoperative control of diabetes mellitus was done either by diet alone or in combination with subcutaneous injections of insulin to maintain the fasting glucose below 8.3 mmol/L (150 mg/dL) and the 24-hour urinary glucose excretion below 10 g.The preoperative, intraoperative, and postoperative variables in the patients who underwent a hepatic resection with (HCC) were...