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Excessive bone resorption in human plasmacytomas: direct induction by tumour cells in vivo.

We studied the bone resorption (BR) in 82 patients with overt plasmacytomas (PCT) by histomorphometry. All the solitary PCT and 90% of overt PCT in complete remission lacked excessive BR. In contrast, 73% of the 68 patients with active overt PCT had an excessive BR. This excessive BR was highly related to the presence of tumour cells within the bone sample. Indeed, 92% of patients with active PCT and tumour cells within the biopsy had an excessive BR. On the other hand, 70% of patients with active PCT but lacking tumour cells within the biopsy had normal BR.

Aged↗

Studies with murine LPC-1 plasmacytoma using [6-14C]arginine.

[16-14C]Arginine ([6-14C]Arg) was used as an in vivo pulse label to study BALB/c murine LPC-1 plasmacytoma synthesis and secretion of its tumour-associated M component (IgG2a, kappa). With this isotope, an eight- to ten-fold enhancement in the labelling of the gamma globulin region and ten-fold reduction in the albumin labelling were observed. Production and secretion of the M component was detected (within 30 min) after cell transfer. Only mice which received tumour cells showed significant labelling in the gamma globulin region 24 hr after isotope injection. The labelling behaviour of the tumour M component correlated with the administered cell dose. The peak heights of radioactivity in the gamma region increased with increments in cell number. When the percentage radioactivity diverted into M component was plotted as a function of cell dose, a linear relationship was noted. This study demonstrates the feasibility of using [6-14C]Arg as a tool to follow the newly synthesized tumour-associated protein, and provides a means of estimating tumour cell number.

Animals↗

Analysis of MOPC-315 plasmacytoma by elutriation and flow cytometry.

Intravenously transplanted murine plasmacytoma MOPC-315 cells were separated from normal spleen cells from a tumour-bearing mouse by elutriation and characterized according to morphology, immunologic properties and clonogenicity. Morphologically, both lymphocytoid and plasmacytoid cells were separable by elutriation. Flow cytometry correlated DNA content and intracytoplasmic IgA content and demonstrated two distinct populations, both in cell cycle, but with markedly different cellular IgA levels. Density gradient separation characterized the lower-density cells with lower IgA content and higher clonogenicity. From these studies a model of cellular differentiation is proposed.

Animals↗

Huge cutaneous plasmacytomas complicating multiple myeloma.

The case of a 46-year-old woman with multiple myeloma and extramedullary dissemination to the urinary bladder and skin is described. Cutaneous plasmacytomas were scattered as firm, violaceous-red, lesions of variable diameter (2-13 cm) which were extremely tender. Despite combined chemotherapy and half-body irradiation, the lesions progressed until the patient died 8 months following diagnosis.

Arm↗

The potential value of immuno-isoelectric focusing in the diagnosis and management of solitary plasmacytoma.

Immuno-isoelectric focusing is a highly sensitive method of detecting small quantities of monoclonal protein. We have previously reported the first demonstration of serum paraprotein in non-secretory myeloma using this technique (Sheehan et al. 1985). We now report a case of solitary plasmacytoma where this technique revealed a small concentration of serum paraprotein when conventional techniques failed, and discuss the potential value of focusing in plasma cell dyscrasia, with limited tumor cell mass. focusing in plasma cell dyscrasia, with limited tumour cell mass.

Aged↗

Pseudoepithelial pattern in smears prepared from fine needle aspirates of plasmacytomas.

A pseudoepithelial pattern was observed in smears prepared from fine needle aspirates (FNA) from three plasmacytomas. In one case cells displayed a markedly granular, 'oncocytic' cytoplasm. Granularity of the cytoplasm was due to a large number of mitochondria as shown by electron microscopy. B-lymphocytic origin of the neoplasms was confirmed by immunocytochemistry.

Aged↗

Immunoreactive cytokeratins in plasmacytomas.

Fourteen plasma cell tumours, including examples of solitary plasmacytoma and multiple myeloma, were studied with a panel of antibodies reactive in formalin-fixed, paraffin wax-embedded tissue. Each case showed immunoglobulin light chain restriction. Five tumours were reactive with antibodies to cytokeratin. Of these five cases, four were negative with antibodies to leucocyte common antigen and only one was weakly positive. Anti-cytokeratin reactivity by plasma cell tumours is more common than was originally anticipated and represents an important diagnostic pitfall.

Humans↗

Multicentric Castleman's disease in association with a solitary plasmacytoma: a case report.

Multicentric Castleman's disease with aggressive systemic symptomatology is usually associated with the plasma cell variant. We report a case in which the clinical presentation was typical of multicentric Castleman's disease but which was associated with the hyaline vascular subtype histologically. Plasma cells were absent from all biopsies until, at autopsy, a solitary plasmacytoma was found in the vertebral column. This case supports the view that plasma cells are of primary importance in the clinical and pathological manifestations of multicentric Castleman's disease.

Adult↗

Ligand-induced redistribution and augmentation of surface-bound myeloma protein on MOPC 315 plasmacytoma cells.

The dinitrophenyl (DNP)- and trinitrophenyl (TNP)-binding IgA(lambda2) myeloma protein M315, bound on the surface of MOPC315 mouse plasmacytoma cells, was redistributed into spots, patches, and, more rarely, into caps by TNP14-BSA and by divalent but not monovalent anti-M315 antibodies. Antiserum to the L-chain of M315 (L315) induced similar redistribution of L315 bound on the surface of variant cells that only produced L315. The spots were much larger and more brilliant when the cells were incubated with the ligands at 37 degrees C than at 4 degrees C. Redistribution of M315 also occurred on M315-producing cells in peritoneal diffusion chambers incubated in BALB/c mice producing antibodies against the M315 idiotype. The clearance of immune aggregates and the regeneration of new surface-bound M315 in diffusion chambers were much slower for MOPC315 cells than that reported for B lymphocytes. The total pool of M315 was 1.9 pg per cell (about 8 x 10(6) 7S molecules), but only an average of 6 x 10(3) [125I]TNP-BSA molecules were bound on the surface of each MOPC cell at 4 degrees C. The amount of surface-bound TNP-BSA increased eightfold when the cells were preincubated at 37 degrees C with rabbit anti-mouse IgA; at 4 degrees C the increase was only twofold. The data indicate that multivalent ligands specific for M315 induce an accumulation of M315 on the cell surface that correlates with secretion; the immediate precursors of secreted myeloma protein may be arrested in their transit through the membrane by the ligands.

Animals↗

Purification and characterization of a specific histone H1 protein kinase from mouse plasmacytoma.

A protein kinase with high specificity for histone H1 was purified from a plasmacytoma microsomal fraction by a high-salt wash, ammonium sulfate precipitation, chromatography on DEAE-cellulose, hydroxyapatite and Sephadex G-200 columns, and the main properties of this kinase were studied. A sulfhydryl compound, such as 2-mercaptoethanol or dithiothreitol, was necessary for full activity. The optimum pH was 7.4-7.8. After purification, the histone H1 kinase was not stimulated by cAMP or cGMP. It was not inhibited by the heat-stable cAMP-dependent protein kinase inhibitor from beef heart. It utilized preferentially GTP over ATP as phosphate donor. Km values for ATP and GTP were 58 microM and 1.4 microM respectively; the Km for histone H1 was 14 microgram ml-1. The molecular weight was approximately 90 000 by gel-exclusion chromatography. Analysis of the purified H1-specific protein kinase by polyacrylamide gel electrophoresis in dodecylsulfate showed two bands having molecular weights of approximately 64 000 and 54 000. Many characteristics of this kinase were similar to those of the chromatin-bound protein kinase reported by other workers in rapidly proliferating cells.

Animals↗

Stimulation by tubulin of an adenylate cyclase from murine plasmacytoma.

Different brain tubulin preparations were shown to stimulate membrane-bound adenylate cyclase from the murine plasmacytoma MOPC 173. Purified tubulin devoid of microtubule-associated proteins and of nucleoside-diphosphate kinase activity was responsible for this stimulation. Activation of the basal adenylate cyclase activity occurred in less than 2 min at 32 degrees C and was amplified by a 4 degree C preincubation of tubulin with plasma membranes. Tubulin affected the Km and the V of the enzyme and was shown to be associated with the membrane during the activation phenomenon. Tubulin was more active on the basal adenylate cyclase activity than that stimulated by fluoride or guanosine 5'-[beta, gamma-imido]triphosphate. GTP has no effect on the tubulin-stimulated enzyme.

Adenylyl Cyclases↗

Protein kinases and their protein substrates in free messenger ribonucleoprotein particles and polysomes from mouse plasmacytoma cells.

In free messenger ribonucleoprotein particles (mRNP) and polysomes from plasmacytoma cells, a phosphorylated protein/protein kinase system has been characterized by a combination of oligo(dT)-cellulose chromatography and CsCl isopycnic gradient centrifugation. The presence phosphorylated in vivo has been detected in both types of particles. Endogenous protein phosphorylation occurs in vitro by particle-associated cAMP-independent protein kinase(s) using [gamma-32P]ATP and [gamma-32P]GTP. These kinases are sensitive to hemin action. Analysis of mRNP proteins by gel electrophoresis and autoradiography showed strong analogies between the phosphorylation patterns obtained in vivo and in vitro, suggesting a substrate specificity for the associated enzymes. The phosphorylated proteins have been compared to initiation factors and ribosomal proteins. We have partially purified the cAMP-independent protein kinase activities responsible for the endogenous phosphorylation in free mRNP and polysomes; two activities were identified in free mRNP whereas three activities were found to be associated with polysomes.

Adenosine Triphosphate↗

Properties of a DNA repair endonuclease from mouse plasmacytoma cells.

The properties of a DNA-repair endonuclease isolated from mouse plasmacytoma cells have been further studied. It acted on ultraviolet-light-irradiated supercoiled DNA, and the requirement for a supercoiled substrate was absolute at ultraviolet light doses below 1.5 kJ m-2. At higher doses relaxed DNA could also serve as a substrate, but the activity on this DNA was due mostly to hydrolysis of ultraviolet-light-induced apurinic/apyrimidinic (AP) sites by the AP-endonuclease activity associated with the enzyme. The latter enzyme activity did not require a supercoiled form of the DNA. The enzyme also introduced nicks in unirradiated d(A-T)n. The nicked ultraviolet-light-irradiated DNA served as a substrate for DNA polymerase I, showing that the nicks contained free 3'-OH ends. Treatment of the nicked ultraviolet-light-irradiated DNA with bacterial alkaline phosphatase followed by T4 polynucleotide kinase, resulted in the phosphorylation of the 5' ends of the nicks, indicating that the nicks possessed a 5'-phosphate group; 5'- and 3'-mononucleotide analyses of the labelled DNA suggested that the enzyme introduced breaks primarily between G and T residues. The enzyme did not act on any specific region on the supercoiled DNA molecule; it produced random nicks in ultraviolet-light-modified phi X 174 replicative form I DNA. Antibodies raised against ultraviolet-light-irradiated DNA inhibited the activity. DNA adducts such as N-acetoxy-2-acetylaminofluorene and psoralen were not recognized by the enzyme. It is suggested that the enzyme has a specificity directed toward helical distortions.

Animals↗

Solitary plasmacytoma of the submandibular lymph node with stromal amyloid deposits.

This report concerns a case of solitary extramedullary plasmacytoma of the left submandibular lymph node in a 56-year-old man. The tumor showed monoclonal proliferation of abnormal plasma cells which revealed highly positive stainings of both methylgreen pyronin and kappa light chain using the immunoperoxidase technique in the cytoplasms, and further revealed massive amyloid deposits in the stroma, which suggested the possibility of sequential amyloid formation upon the secretion of paraprotein by tumor cells.

Amyloid↗

Plasmacytoma of lymph node. Recurrent lymphadenopathy terminating in plasma cell dyscrasia with polyneuropathy and endocrine disturbances.

A case with lymphadenopathy of the left side of the neck in a 38-year-old male is described. He had a history of several relapses of about 10 years duration. Swollen lymph nodes were histologically similar to those of the hyaline-vascular type of Castleman's disease, but contained clear-cut lymph sinus and a sheet-like proliferation of plasma cells. Lymph follicles showed proliferation and atrophic germinal centers, in which cellular hypertrophy in the wall of ramifying small blood vessels, called angiosclerosis, was frequently encountered. During its progress, the patient developed plasmacytoma of the lymph nodes with varied clinical manifestations such as polyneuropathy, disturbance of gait, unusual perspiration, hirsutism, gynecomastia, bilateral papilledema, and albumino-cytologic dissociation in cerebrospinal fluid.

Adult↗

Interleukin-2 receptor antigen, leukocyte common antigen, and Ki-1 antigen-expressing gastric plasmacytoma. A case report with an immunohistochemical study.

A case of primary gastric plasmacytoma expressing various surface and cytoplasmic antigens is reported. With the use of formalin-fixed and deparaffinized sections, 13 different antibodies were applied. Neoplastic plasma cells revealed monoclonal IgG and kappa light chain in the cytoplasm, and expressed epithelial membrane antigen, Ki 67 antigen, cytokeratin, CD 22 antigen, interleukin-2 receptor antigen, leukocyte common antigen and Ki-1 (CD 30) antigen. However, tumor cells were devoid of HLA-DR antigen. These data suggest that the neoplastic plasma cells are at the plasmoblastic stage of maturation and express various surface and cytoplasmic phenotypes.

Aged↗