Establishment and characterization of a new human Bence Jones-type myeloma cell line, NOP-2.

A new human myeloma cell line NOP-2, producing immunoglobulin (Ig)-lambda-light chain was established from a patient with Bence Jones-type multiple myeloma. Morphologically, the cell line had plasmacytoid characteristics by light- and electron-microscopic examination. Phenotypic studies of NOP-2 cells revealed no surface Ig, but they were positive for cytoplasmic Ig-lambda, OKT10 (CD 38), and PCA-1. Epstein-Barr nuclear antigen was not detected. Chromosomal abnormalities of t(11;14) and t(8;22) were found in both NOP-2 cells and the original myeloma cells obtained from the patient. NOP-2 cells produced and secreted Ig-lambda light chain, but lacked immunoglobulins of any heavy chains. Rearrangements of both immunoglobulin heavy- and light-chain genes were observed in NOP-2 cells, though the cells expressed detectable mRNA only for Ig-lambda light chain. This cell line may serve as a useful model for understanding the hierarchy of human immunoglobulins and the pathophysiology of Bence Jones-type multiple myeloma.     

Cytokine enhancement of monocyte/synovial cell attachment to the surface of cartilage: a possible trigger of pannus formation in arthritis

Summary When rheumatoid articular cartilage samples were incubated with normal peripheral blood monocytes and cultured synovial cells in the presence of recombinant human interleukin-1 (IL-1) in vitro, large numbers of monocytes were seen to be attached to the articular surface. Significant numbers of monocytes invaded the cartilage tissue when the rheumatoid cartilage samples were pre-incubated with 10 U/ml of IL-1. Considerable numbers of monocytes were also attached to normal cartilage when these were pre-incubated with IL-1. It is of interest that recombinant human gamma interferon (-IFN) did not enhance monocyte attachment. However, there was a significantly greater attachment of monocytes to rheumatoid than to normal cartilage. When normal cartilage was exposed to collagenase and then incubated with monocytes or synovial cells in the presence of 10 U/ml of IL-1, large numbers of cells were attached to the natural cartilage surface but not to the cut surface. These phenomena were much more intense when the rheumatoid cartilage was pre-incubated with collagenase. These results indicate that increased levels of IL-1 in the rheumatoid joint may play an important role in joint destruction by stimulation of pannus formation by inducing synovial cell attachment to the articular surface.     

Mouse immunoglobulin coding sequences for the heavy-chain variable region arose as repeats of the two short building blocks.

The coding sequence for the 97-amino-acid-residue-long immunoglobulin heavy-chain variable (VH) regions of the mouse apparently arose as repeats of the two short building blocks. Three of the recognizable copies of the one 21-base-long prototype sequence A-C-T-G-G-A-T-A-T-G-A-C-C-T-G-G-A-G-T-G-G are invariably found to occupy the fixed positions within the 5' half of each VH coding sequence. Interestingly, the first and third copies specify the relatively invariant regions represented by the 7th to 13th and 41st to 47th amino acid residues (the first and second framework regions), whereas the second copy specifies the first hypervariable region (31st to 35th amino acid residues). These copies maintain at least 57.2% (12 out of 21) base sequence homology to the above-noted prototype building block. Base sequences of the other 14- to 15-base-long prototype building block differ from each other by as much as 60% between individual VHS. Yet one of its copies invariably occupies the terminal region of each VH coding sequence, thus specifying the very invariant third framework region. Other copies occupy unfixed positions in the VH and its attendant hydrophobic leader coding sequence as well as in adjacent noncoding sequences. The homology thus revealed between the VH coding sequence and its adjacent noncoding sequences suggests their concordant evolution.     

Clinical Benefit of the Change of Dialysate Calcium Concentration From 3.0 to 2.75 mEq/L

Because active vitamin D preparations and calcimimetics have been widely used to treat secondary hyperparathyroidism, maintenance of acceptable serum calcium and phosphate levels is important. A 2.75 mEq/L dialysate calcium product, which may bring the calcium balance closer to 0, has recently been launched, and we had an opportunity to examine its possible benefits. We performed a 6‐month retrospective review after switching from 3.0 mEq/L to 2.75 mEq/L calcium dialysate in 85 outpatients undergoing chronic hemodialysis. We evaluated blood biochemical parameters, including predialysis and postdialysis serum calcium and phosphate levels, predialysis intact parathyroid hormone (iPTH) levels; dialysis dose (Kt/V); and doses of concomitant active vitamin D preparations, calcimimetics, phosphate binder, and erythropoiesis‐stimulating agents. Postdialysis calcium levels were significantly lower and predialysis corrected calcium levels significantly decreased. The change in calcium levels before and after dialysis was smaller after switching of the dialysate than before. iPTH levels significantly increased 1 month after switching of the dialysate. No remarkable changes were observed in phosphate levels or Kt/V. The dose of alfacalcidol, one of the concomitant drugs, somewhat increased, and no remarkable changes in dosage were observed for other concomitant drugs. These results were favorable in terms of calcium balance. However, there may be limitations in interpreting the results, but the resultant calcium levels suggest that switching to 2.75 mEq/L calcium dialysate may improve the control of calcium levels. In addition, it is hoped that the treatment choice of secondary hyperparathyroidism is extended.     

Phenotypic conversion of T lymphoblastic lymphoma to acute biphenotypic leukemia composed of lymphoblasts and myeloblasts. Molecular genetic evidence of the same clonal origin.

Acute biphenotypic leukemia composed of lymphoblasts and myeloblasts developed in a patient with T lymphoblastic lymphoma (T-LBL) who had an anterior mediastinal mass. A novel myeloid cell line, termed TK-1, has been established from his peripheral blood after the leukemic conversion. The identical rearranged pattern of T cell receptor gamma-chain gene was observed among the DNAs derived from lymph node cells in the lymphoma phase, the myeloid cell line TK-1, and the subclones with different karyotypes (TK-1B and TK-1D), which showed that myeloid cells had been derived from the T-LBL of the same patient. This finding demonstrates that phenotypic conversion occurs in the clonally propagating tumor cells and suggests that some hematopoietic cells retain the capacity to adopt either lineage.     

Inhibitory effects of antithyroid drugs on oxygen radical formation in human neutrophils

The effects of antithyroid drugs and related agents on human neutrophil function were studied. Neutrophil function was mainly assessed through oxygen radical formation as determined by chemiluminescence (CL) response, superoxide anion (O-2) generation and hydrogen peroxide production. Propylthiouracil (PTU) at a therapeutic concentration (10 micrograms/ml) inhibited CL response evoked by phorbol myristate acetate (PMA) and other stimulators. The inhibitory effect was not enhanced by pre-incubation of neutrophils with PTU and not exerted through a direct cytotoxic effect of the drug. It was not related to the kind of stimulators to evoke CL response in neutrophils either. However, the inhibitory effect disappeared when PTU was removed from the reaction mixture for CL response. PTU did not inhibit O-2 generation but markedly inhibited hydrogen peroxide production in neutrophils or activity of hydrogen peroxide in vitro. Morphologically, the unique change of cellular configuration of chemotactic neutrophils caused by N-formyl-methionyl-leucyl-phenylalanine (FMLP) was not influenced with PTU. Since hydrogen peroxide is mainly derived from O-2, these observations suggest that PTU may have a scavenger effect on hydrogen peroxide activity. Inhibition of CL response in neutrophils was also demonstrated with methimazole (MMI), thiouracil and thiourea, but not with imidazole and uracil, which suggests that their inhibitory effect on CL response in neutrophils may be closely related to the antithyroid activity.     

Electromyographic evaluation of masticatory function in denture wearers in related to existing occlusal support

The aim of this study was to clarify the relationship between partially edentulous pattern and the masticatory function in removable partial denture wearers. Eighty eight removable partial denture wearers and 7 subjects with intact dentition volunteered for this study. Using the Eichner's index, all subjects were divided into 6 groups. Electromyographic (EMG) activities of the masticatory muscle were recorded during chewing a piece of raw carrot. The masticatory function was analyzed by using the variation coefficient (VC) of the time parameter of EMG interval recorded during mastication. The association of the VC with group classification based on Eichner's index was analyzed using analysis of covariance with gender and age as the covariates. The result of the analysis revealed that the VC was significantly associated with group classification and the patients in groups without posterior occlusal supports exhibited significantly higher VC values than those in groups with posterior occlusal supports. These findings suggested that the reduced function in patients without the posterior occlusal contacts was difficult to attain improved and satisfactory outcome with removable partial dentures and that there is a significant need for posterior occlusal support for the preservation of masticatory function.