Fifty-three Japanese patients with the lymphoma-type adult T-cell leukemia (ATL) were analyzed to study the prognostic value of various clinical findings recorded at the time of diagnosis. All patients were positive for human T-cell leukemia virus type I (HTLV-I) antibody and demonstrated monoclonal integration of HTLV-I proviral DNA in their malignant cells. The important individual variables detected in a previous univariate analysis were placed in a multiple regression model to identify the major prognostic factors for survival. This analysis showed that serum lactate dehydrogenase (LDH), calcium, and total protein levels had a strong predictive relationship with the length of survival (in descending order of importance). Among the 53 patients, 46 were dead at the time of analysis. The cause of death in relation to the duration of survival is also reviewed in this article.
The antigen-driven clonal proliferation of B cells within target tissue has been reported in some autoimmune diseases. The purpose of this study was to examine the clonal characteristics of B cells in the liver portal area of primary biliary cirrhosis (PBC).The liver portal area was microdissected from liver biopsy sections from two PBC patients. Genomic DNA was extracted and rearranged immunoglobulin heavy chain variable region (VH) genes were amplified and sequence analyzed.Sixteen VH sequences from portal area 1A of patient 1 had three different rearrangements. Nineteen VH sequences from portal area 1B of this patient had three different rearrangements. In three sequences from the portal area 1B, a stepwise accumulation of somatic mutations was observed. Between the sequences from the two portal areas, no common VH sequence was observed. In patient 2, 15 VH sequences from portal area 2A had three different rearrangements. Fourteen VH sequences from portal area 2B had two different rearrangements. One rearrangement was present both in the portal area 2A and portal area 2B.The oligoclonal B cell proliferation and stepwise accumulation of somatic mutations suggested that an antigen-driven B cell response had occurred in the portal area of PBC.
AbstractTelomeres, G-rich structures at the ends of chromosomes are essential for maintaining chromosomal integrity. Most tumor cells contain telomerase, a ribonucleoprotein that elongates telomeric repeats, and it plays an essential role in indefinite proliferation. To better understand regulatory mechanisms of telomerase, in relationship with apoptosis and the cell cycle, we examined telomerase activity in PCM6, an interleukin-6 (IL-6)-responsive, interferoncl (IFN-α)-sensitive multiple myeloma cell line, using a PCR-based assay. When PCM6 cells were cultured in serum-free media, the addition of IFNα resulted in apoptosis of the cells, but with no influence on telomerase activity. When IFNα was added to the culture with serum plus rIL-6 after serum deprivation, G1-S transition was inhibited and telomerase activity was lower compare to findings in culture with no IFN-α. Dose response experiments of rIL-6 and IFN-α, and the measurement of telomerase activity of sorted cells in S-phase using CD71, demonstrated a higher activity of telomerase in the samples which contained a larger proportion of cells in S-phase. These data indicate that regulation of telomerase activity is closely related to cell cycle status, in particular cells in S-phase have an high telomerase activity. While telomeres play an important role in cellular senescence, the regulation of telomerase is independent from apoptotic signals induced by IFN-α in myeloma cells.Key Words: multiple myelomatelomeraseapoptosiscell cycle
The effect of preload on myofilament Ca 2+ sensitivity was examined using α-toxin permeabilization and fura-2 fluorometry in rabbit cerebral arteries. The [Ca 2+ ]i-force curves shifted leftward at a high preload, with a decrease in median effective concentration of Ca 2+ in the permeabilized artery. In the fura-2-loaded artery, the preload modulated the force without affecting [Ca 2+ ]i levels during K + depolarization, and a high preload moved the [Ca 2+ ]i-force curve upward and to the left. It is thus concluded that the preload regulates the Ca 2+ sensitivity of the myofilament and, therefore, may play a role in the regulation of cerebral arterial tonus and blood flow.
