The temperature-sensitive BHK21 hamster cell line tsBN67 ceases to proliferate at the nonpermissive temperature after a lag of one to a few cell divisions, and the arrested cells display a gene expression pattern similar to that of serum-starved cells. The temperature-sensitive phenotype is reversible and results from a single missense mutation-proline to serine at position 134-in HCF, a cellular protein that, together with the viral protein VP16, activates transcription of herpes simplex virus (HSV) immediate-early genes. The tsBN67 HCF mutation also prevents VP16 activation of transcription at the nonpermissive temperature. The finding that the same point mutation in HCF disrupts both VP16 function and the cell cycle suggests that HCF plays a role in cell-cycle progression in addition to VP16-dependent transcription.[Key Words: tsBN67; HCF protein,-VP16 function,-GQ/GI cell cycle arrest; transcription] Received November 14, 1996; accepted in revised form February 7, 1997.Conditional mutations, particularly temperature-sensitive mutations, have been valuable tools for clarifying cell-cycle regulation in yeast as well as mammalian cells (for review, see Marcus et al. 1985). Previously, we have isolated a series of temperature-sensitive cell-proliferation mutants from the hamster BHK21 cell line (Nishimoto and Basilico 1978;Nishimoto et al. 1982). Following mutagenesis with N-methyl-N'-nitro-JV-nitrosoguanidine, mutants that proliferate at the permissive temperature of 33.5°C but not at the nonpermissive temperature of 39.5°C were concentrated through multiple rounds of negative selection with the cytotoxic base analog 5-fluoro-2-deoxyuridine to eliminate proliferating cells at the elevated temperature. Based on the ability of hybrid cells created by the fusion of different mutant lines to grow at the nonpermissive temperature, these temperature-sensitive lines have been classified into 25 complementation groups (Nishimoto and Basilico 1978;Nishimoto et al. 1982).To identify the genes affected by these mutations, human DNA has been used to complement the hamsterPresent address:

A proliferation-inducing ligand (APRIL or TNFSF13) shares receptors with B-cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen-induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL À/À mice exhibited increased T-cell proliferation, enhanced Th2 cytokine production under non-polarizing conditions, and augmented IL-13 and IL-17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL À/À mice responded with an increased antigen-specific IgG1 response. We also show that in APRIL À/À mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen-specific IgG2a autoantibody and IL-17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL-triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis.

Reportedly, ossification of the posterior longitudinal ligament (OPLL) usually involves the cervical spine and often accompanies other ligamentous ossification such as diffuse idiopathic skeletal hyperostosis (DISH). It is considered serious because it sometimes causes severe radiculomyelopathy; however, the present study, based on a fixed population sample, revealed that OPLL of the thoracic spine is nearly always asymptomatic. The prevalence of thoracic OPLL was 0.6%, with three times as many women as men being affected, compared with cervical OPLL which occurs predominantly among men. No marked radiculomyelopathy was observed, nor definite evidence of neurological involvement due to thoracic OPLL. DISH was rare, especially among women.

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BACKGROUND The clinical course of patients with multiple myeloma varies, and therefore it is important to evaluate the disease state. We studied the telomerase activity of myeloma cells as a possible prognostic factor in such patients. METHODS Twenty five samples from patients with multiple myeloma were studied. We purified myeloma cells in bone marrow samples according to the expression of surface antigens, CD38 and CD45. CD38+/CD45− or dim cells had morphologic characteristics of myeloma cells, with a purity exceeding 95%. The telomerase activity of myeloma cells was determined by a polymerase chain reaction‐based telomeric repeat amplification protocol assay. Ki‐67 positivity of the purified cells was determined by flow cytometry using anti‐Ki‐67 antibody. The relationship between telomerase activity and prognostic factors was also examined. RESULTS A significantly high degree of telomerase activity was detected in subjects with a serum β2‐microglobulin level ≥ 6mg/dL or at Stage III (P = 0.002). The serum C‐reactive protein, lactate dehydrogenase, and creatinine levels did not correlate with the telomerase activity, but this activity did significantly correlate with Ki‐67 positivity and the percentage of plasma cells in the bone marrow (r = 0.561, P = 0.004, and r = 0.397, P = 0.049, respectively). The patients with high levels of telomerase activity were thus found to have a significantly short survival time after sampling (P = 0.035). CONCLUSIONS The measurement of the telomerase activity in myeloma cells was found to be a reliable marker for the proliferating capacity and tumor mass in myeloma patients. The telomerase activity of myeloma cells may therefore be useful as a prognostic factor. Cancer 2002;94:2232–8. © 2002 American Cancer Society. DOI 10.1002/cncr.10472