Soluble IL-6R in plasma cell dyscrasias

The understanding of the biology of multiple myeloma has advanced significantly in the past few years. The identification of the pivotal role of Interleukin-6 (IL-6), the soluble IL-6 receptor (sIL-6R), and how the ligand receptor complex interacts with the signal transducer gp130 has provided new biological insights into plasma cell disorders. Some studies have suggested that sIL-6R levels may have prognostic significance in MM, however this is not a consistent finding. Here the biology and function of IL-6 and sIL-6R are reviewed and the clinical significance of sIL-6R discussed.     

Increased serum CA125 levels in plasma cell dyscrasias

We describe two cases of malignant lymphoma presenting as inflammatory nodules of the leg and mimicking panniculitis clinically. In both cases the skin biopsies showed prominent involvement of the subcutaneous tissue by lymphoma cells. In addition, lymphoma cells invaded blood vessels in the dermis or the subcutaneous tissue. One case was characterized by predominantly extravascular and intravascular location of the lymphoma cells, and the other case by the predominantly extravascular and intramural location of lymphoma cells. These histological findings were compatible with those of angiocentric T-cell lymphoma but with some unusual features. Angiocentric T-cell lymphoma of the skin should be listed in the group of diseases which present as inflammatory nodules of the leg.     

Mutational activation of N- and K-ras oncogenes in plasma cell dyscrasias

The frequency of N- and K-ras oncogene mutations was investigated in plasma cell dyscrasias. Genomic DNAs from 128 patients were selected for this study: 30 monoclonal gammopathies of undetermined significance, 8 solitary plasmacytomas, 77 multiple myelomas (MM), and 13 plasma cell leukemias (PCL). A two-step experimental approach was devised. All samples were screened for mutations by single-strand conformation polymorphism analysis. DNA fragments displaying an altered electrophoretic mobility were further studied by direct sequencing to confirm and characterize the nature of the mutations. Ras mutations are not randomly distributed because they are detectable only in MM (9%) and PCL (30.7%). N-ras codons 12, 13, and 61 and K-ras codon 12 were found to be mutated, but N-ras codon 61 mutation was the most frequent finding (63.6%). In conclusion, ras mutations were found in PCL, and in a subset of MM characterized by advanced-stage disease and adverse prognostic parameters. Furthermore, based on our findings, it is possible to speculate that ras mutations represent a late molecular lesion in the process of multistep carcinogenesis.     

Clinical significance of determining serum soluble IL-6 receptor concentration in plasma cell dyscrasias

The authors analyze results of treatment of 778 children with malignant and benign tumors of the bones, pseudoarthroses, amputations of lower extremities and fingers, injuries of the tendons, vessels and contused-lacerated wounds of distal phalanges of fingers. The possibility to use a precision technique for the reconstructive operations of the vessels in children is shown.     

Concomitant rash and blood dyscrasias in geriatric psychiatry patients treated with carbamazepine

PURPOSE: To present two successful cases of labour analgesia in patients who had been treated with radiation to the lumbar spine for neuroblastomas and to discuss the considerations when planning the anaesthetic management of these patients. CLINICAL FEATURES: We recently encountered two primigravidas requesting labour analgesia, both of whom were noted to have very thin backs with prominent spinous processes and obvious scoliosis. In both patients, the epidural space was easily identified and very shallow. Successful labour analgesia was achieved in both patients, one with a combined spinal epidural technique and the other with an epidural catheter. CONCLUSION: Craniospinal irradiation is known to have long-term effects on exposed nervous tissue, bone, and blood vessels. While a larger experience is necessary to demonstrate safety of regional anaesthesia in parturients following previous spinal irradiation, we provide reports of two successful cases.     

Head and neck manifestations of plasma cell neoplasms

Absorbance changes were monitored from 250 to 650 nm during the first microsecond after photolysis of detergent suspensions of bovine rhodopsin at 20 degrees C. Global analysis of the resulting data produced difference spectra for bathorhodopsin, BSI and lumirhodopsin which give the change in absorbance of the aromatic amino acid side chains in these photointermediates relative to rhodopsin. These spectra show that the significant bleaching of absorbance near 280 nm, which has been seen previously for the lumirhodopsin, metarhodopsin I and metarhodopsin II intermediates, extends to times as early as bathorhodopsin. Because no corresponding absorbance increase is observed in the 250-275 nm region, the earliest bleaching of the 280 nm absorbance in rhodopsin is attributed to disruption of a hyperchromic interaction affecting Trp265. Partial decay of this 280 nm bleaching as bathorhodopsin converts to BSI takes place maximally near 290 nm, where Trp265 has been shown to absorb, and could be due to the ring of the retinylidene chromophore resuming a position at the BSI stage that reestablishes the hyperchromic interaction with Trp265. A subsequent change in the 250-300 nm region, which has no counterpart in the visible chromophore bands, indicates the possible presence of a protein-localized process as lumirhodopsin is formed.     

The treatment of plasma cell myeloma

In a previous publication the ultrastructure of pleural effusions in cases of pleural mesothelioma was reported. The same method has now been applied to a study of effusions produced by pleural metastases. The findings are considered sufficiently conclusive to justify the use of electron microscopic cytology in determining the nature and sometimes the origin of such effusions.     

Auer-rod-like bodies in plasma cells in patient with plasma cell dyscrasia

Auer-rod-like bodies were found in plasma cells from a 74-year-old man with plasma cell dyscrasia. These bodies exhibited red purple staining by May-Giemsa staining and were indistinguishable from Auer bodies often found in acute myeloid leukemia. These bodies, however, failed to stain with peroxidase and showed acid phosphatase positivity. Bone marrow examinations were performed three times at the sternum or iliac crest. The proportions of plasma cells were 4.4%, 3.4% and 3.8%. The Auer-rod-like bodies were found in 0.05% (2/3824), 0.07% (4/6883) and 0.08% (2/2656) of the plasma cells.     

Intermittent melphalan and prednisolone therapy in plasma cell myeloma

Thirty-two consecutive, previously untreated patients with plasma cell myeloma were treated with 4-day courses of melphalan (0.25 mg/kg/day) and prednisolone (2 mg/kg/day) every sixth week. The observation period ranged from 26 to 75 months and the total median survival time was 29 months. 75% of the patients responded to therapy and their median survival time was 42 months. Sex did not influence either the response rate or the survival time. Most patients were treated in an out-patient clinic and required a minimum of check-ups.     

Binding of plasma selenoprotein P to cell membranes

Competitive binding assays were performed to determine the amount of binding of 75Se-labeled plasma selenoprotein P (PSP) to membranes from different rat tissues at physiologic pH. 75Se PSP for use as a ligand in the binding assays was labeled in vivo by injecting rats with 75Se selenious acid. PSP was obtained from plasma by salt precipitation and affinity and ion-exchange chromatography. Membranes for receptor assays were prepared from liver, kidney, testes, and brain of rats fed diets with either 0.01, 0.1, or 2 ppm selenium. At pH 7.4 PSP was bound differentially to tissues in the following order: brain > kidney > testes > liver. Specific binding of PSP to tissue membranes from rats fed the different levels of selenium increased with increasing amounts of dietary selenium. Saturation assays indicated apparent saturation of membrane receptors by the 75Se-labeled PSP. Another significant new finding was a 134-kDa complex of PSP and membrane receptor, identified by gel-filtration chromatography of cross-linked samples from binding assays. This provides evidence for a membrane receptor for PSP in rat tissues.     

Optimizing plasma cell content in bone marrow aspirates

Bone marrow samples used for flow cytometric analysis of plasma cells frequently provide a low plasma cell content. Regularly, samples used for flow cytometry are provided by second step aspiration while the first aspirate is used for cytologic examination. We investigated whether the use of secondary aspirates leads to a systematic underestimation of the bone marrow plasma cell content as a consequence of an increased blood contaminant. To test the hypothesis, plasma cell (CD38bright) percentages were established by flow cytometry in 13 pairs of primary/secondary aspirates. In all cases we found lower plasma cell contents in secondary as compared to primary aspirates (p = 0.0015). Median plasma cell counts in secondary aspirates were 57% lower compared to primary aspirates. We conclude that the use of secondary aspirates leads to systematic underestimation of the bone marrow plasma cell content.     

Acquired cutis laxa associated with a plasma cell dyscrasia

Cardiovascular disease is the major cause of death in chronic renal failure (CRF) patients managed by dialysis or kidney transplantation. Whilst the use of human growth hormone (hGH) is of established benefit in CRF children particularly in those with short stature, in the present study we assessed in CRF children the effect of hGH treatment on circulating lipoprotein(a) [Lp(a)], a genetically determined cardiovascular risk factor. We studied 15 CRF children treated by dialysis or conventional therapy and after kidney transplantation. Overnight fasting blood samples were collected immediately before and after 6 months hGH treatment. In all but one of the children there was a significant increase in serum Lp(a) over the 6 month treatment period -(+)66.7% over the basal levels (range 14 to 180%). After the hGH treatment, in six children Lp(a) levels were elevated to above 300 mg/l, the cut-off level for increased coronary artery disease (CAD) risk. Concomitantly/children also had an increase in serum levels of IGF-I (+96.4%) and insulin (+85.8%). All children had an accelerated growth velocity during the treatment; there was no effect on serum creatinine. Our study shows that hGH treatment in CRF children, though beneficial in its growth promoting effects, increases the already characteristically high levels of serum Lp(a), a risk factor for CAD, and that serum Lp(a) monitoring during treatment with hGH may be useful in evaluating future cardiovascular risk.     

Laminin and fibronectin promote the chemotaxis of human malignant plasma cell lines

We examined chemotaxis of human plasma cells (PCs) in response to extracellular matrix proteins (ECMs) in the human PC cell lines FR4ds and OPM-1ds. The FR4ds cells expressed beta 1+, beta 3-, alpha 2-, alpha 3-, alpha 4+, alpha 5+, alpha 6+, and alpha v+ integrins, whereas the OPM-1ds cells expressed beta 1+, beta 3-, alpha 2-, alpha 3+, alpha 4+, alpha 5-, alpha 6+, and alpha v+. Fibronectin (FN) and laminin (LN) promoted the chemotaxis of the PCs. An inhibitory assay with anti-integrin monoclonal antibodies (MoAbs) showed that anti-alpha 4 MoAb partially inhibited the chemotaxis of FR4ds and completely inhibited the chemotaxis of OPM-1ds. Anti-alpha 5 MoAb alone had no effect on either of these two lines. Nevertheless, anti-alpha 5 MoAb completely inhibited chemotaxis when it was added with anti-alpha 4 in FR4ds, demonstrating a novel complementary role of VLA-5 toward VLA-4 in the chemotaxis induced by FN. LN facilitated chemotaxis both in OPM-1ds expressing alpha 3 and alpha 6 integrins and in FR4ds expressing alpha 6 integrin alone. Anti-alpha 6 MoAb completely inhibited FR4ds chemotaxis, whereas anti-alpha 3 and -alpha 6 MoAb had synergistic inhibitory effects on the chemotaxis of OPM-1ds. These results indicated that the distribution of PCs in human tissue are determined by at least two factors: the concentration of the ECM proteins FN and LN and the expression of integrins.     

Relationship between cell size, plasma cholesterol and rat adipocyte cholesterol storage

Organotypic cultures of newborn hamster choroid plexus were inoculated with equal titre doses of newly isolated or hamster adapted strains of mumps virus. The ultrastructure of virus replication in choroid epithelial cells of the cultures was compared. No qualitative differences were observed; however, the adapted strain produced significantly greater numbers of virions and earlier destruction of the cultures. These findings are consistent with previous in vivo observations of the ultrastructure of the replication of these strains in the newborn hamster central nervous system. This in vitro study leads further support to the hypothesis that differences in the in vivo biological effects of the virus strains are primarily the result of virus-cell rather than virus-host interactions.     

Stimulation of tumor-specific immunity using tumor cell plasma membrane antigen

An improved methodology is described for the separation of yolk IgG into subpopulations using immobilized metal ion (Fe3+) affinity chromatography. The yolk IgG was first extracted using a prechilled, pre-acidified method. After extraction, the yolk IgG was then fractionated using an Fe3+ column. Using an ascending pH gradient, four IgG containing peaks were well resolved based upon the elution pH, specific activity and the relative avidity index.     

Atypical monoclonal plasma cell hyperplasia: its identity and treatment. Case report

Atypical monoclonal plasma cell hyperplasia, like plasma cell granuloma, is an inflammatory pseudotumor. Both are extremely rare in the central nervous system. Atypical monoclonal plasma cell hyperplasia is a recently identified neuropathological entity described by Weidenheim, et al., in 1989. A second case of this disease entity is now reported. The histological findings that differentiate this lesion from plasma cell granuloma, plasmacytoma, and meningioma are discussed. The present case clearly demonstrates the complete resolution of the disease after a course of fractionated radiotherapy.