scholarly journals Performance of Diagnostic Tests for Plasma Cell Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5570-5570
Author(s):  
Gilda Zagoya ◽  
Alejandro Ruiz-Argüelles ◽  
Guillermo J. Ruiz-Arguelles
Keyword(s):  
Plasma Cell ◽  
Diagnostic Tests ◽  
Laboratory Tests ◽  
Light Chains ◽  
Plasma Cell Myeloma ◽  
Immunoglobulin Light Chains ◽  
Predictive Values ◽  
Sensitivity Specificity ◽  
Total Immunoglobulin

Abstract Introduction. In vitro laboratory tests to diagnose of plasma cell myeloma vary considerably in sensitivity, specificity and positive and negative predictive values. We compared the performance of quantification of free immunoglobulin light chains with other methods used to detect a monoclonal protein in serum and/or urine. Objective. Compare sensitivity, specificity and positive and negative predictive values of several in vitro laboratory tests to detect monoclonal proteins in serum and urine in persons with plasma cell myeloma. Methods. 70 subjects with plasma cell myeloma and 50 controls were studied. Diagnostic tests included: (1) quantification of free and total immunoglobulin light-chains by immune assays; (2) immune fixation of heavy-and light-chains in serum and urine after gel electrophoresis; and (3) serum protein capillary electrophoresis. Diagnosis of plasma cell myeloma was based on clinical and radiological criteria, bone marrow examination and flow cytometric immune phenotyping with monoclonal antibodies to CD56, CD19, CD138 (CD38) and CD45. Sensitivity, specificity and positive and negative predictive values for each tests were estimated from contingency tables. Results. Quantification of free immmunoglobulin light-chains had the highest sensitivity and specificity and best positive and negative predictive values. Immune fixation of serum immunoglobulins was next best. Quantification of total immunoglobulin light-chains was the least sensitive and specific with the worst positive and negative predictive values. Quantitation of free light-chains had the additional advantage of objectivity (independence from observer bias). The immune fixation test was the most subject to observer bias. Conclusion. Quantification of free immunoglobulin light-chains had the best sensitivity, specificity and positive and negative predictive values for diagnosing plasma cell myeloma. (Table 1) Disclosures No relevant conflicts of interest to declare.

Biclonal plasma cell myeloma with the simultaneous appearance of both secretory lambda and nonsecretory kappa monoclonal light chains

2017 ◽  
Vol 55 (1) ◽  
pp. e21-e24
Author(s):  
Hyun Jung Gu ◽  
Sun Young Cho ◽  
Juhie Lee ◽  
Ji-Youn Sung ◽  
Tae Sung Park
Keyword(s):  
Plasma Cell ◽  
Light Chains ◽  
Plasma Cell Myeloma

scholarly journals A plaque assay to enumerate circulating Ig-secreting cells of each type of the different Ig classes

Blood ◽  
1980 ◽  
Vol 56 (2) ◽  
pp. 199-202
Author(s):  
K Shimizu ◽  
A Hirano ◽  
A Kunii
Keyword(s):  
Plasma Cell ◽  
Plaque Assay ◽  
Assay System ◽  
New Method ◽  
Light Chains ◽  
Plasma Cell Myeloma ◽  
Circulating Cells ◽  
Normal Individuals

A new method to quantitate circulating cells secreting immunoglobulin (Ig) of each type of the different classes by hemolytic plaque technique is reported. The ratio of kappa (k)-secreting cells and lambda(lambda)-secreting cells of the different lg classes in normal individuals is almost equal to that of kappa:lambda light chains in corresponding serum lg class, whereas the ratio in plasma cell myeloma patients is extraordinarily high or low, indicative of the type and class specificity of this assay system as well as the monoclonal nature of circulating Ig-secreting cells in such patients.

Induction of Apoptosis and Paradoxical Activation of NF-κB by Trichostatin A in Plasma Cell Myeloma Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4851-4851
Author(s):  
Keiko Asakura ◽  
Hideo Uchida ◽  
Akihiro Muto ◽  
Yoshitaka Miyakawa ◽  
Yasuo Ikeda ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Cell Lines ◽  
Plasma Cell ◽  
Hdac Inhibitor ◽  
Antitumor Effect ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Plasma Cell Myeloma ◽  
Induced Apoptosis

Abstract Plasma cell myeloma (PCM) is a mature B cell malignancy characterized by monoclonal gammopathy and destructive bone lesions. Although recent development of therapeutic drugs including thalidomide or proteasome inhibitor may prolong survival time, PCM is still an incurable disease. To improve the treatment outcome of PCM, the development of novel, pathophysiology-based therapies are needed. Histone acetylation plays a role in transcriptional regulation by altering the chromatin structure, which allows the transcription factors to access the DNA. Histone acetyltransferases (HATs) are involved in tumor suppression and inhibition of histone deacetylases (HDACs) results in antitumor effect. HDAC inhibitors have also reported to induce apoptosis or differentiation of tumor cells. Trichostatin A (TSA) is one of the HDAC inhibitors, and it has shown to be effective in vitro against leukemic cells with characteristic chromosomal translocations. Although none of the disease-specific genetic alterations involving aberrant transcription factors in PCM have been reported, previous studies have demonstrated the antitumor effect of HDAC inhibitors on PCM. Accordingly, to address the detailed molecular mechanisms of HDAC inhibitor-induced apoptosis, we examined the in vitro effects of TSA on PCM cell lines. By using flow cytometric analyses, we found that cell cycle arrest at G1 phase and apoptosis were induced in various PCM cell lines, RPMI8226, IM9, and U266 treated with 100nM of TSA for 24 hours. Especially, the viability of TSA-treated RPMI8226 cells was strongly suppressed to approximately 30% compared to the cells without TSA. Nuclear factor (NF) -κB is thought to be a key molecule of cellular growth in PCM; therefore, we studied the functional alterations of NF-κB in PCM cell lines stimulated with TSA. Immunoblot and electrophoretic mobility shift assays demonstrated that TSA augmented the nuclear localization of NF-κB, which resulted in the increased DNA binding activity and upregulation of downstream target gene expression such as ICAM-1. Increased phosphorylation of Iκ-Bα by TSA was observed simultaneously. Transient transfection assays showed that the transcriptional activity of NF-κB was upregulated more than 4-fold by TSA, and the synergistic effects of TSA with TNF-α or PMA were observed. Interestingly, an NF-κB-specific inhibitor, SN50, induced apoptosis of PCM cell lines, and TSA showed a synergism with SN50. These data may provide a notion that increased activity of NF-κB by TSA could be a compensatory response against proapoptotic signals induced by TSA. Additionally, we investigated other molecules responsible for TSA-stimulated apoptosis, and found the downregulation of Mcl-1, Bcl-XL, XIAP proteins, as well as dephosphorylation of Akt and cleavage of Bid proteins in a time-dependent manner. These results suggest that either PI 3-K/Akt pathway or JNK-dependent pathway could be involved in the TSA-induced apoptosis. In conclusion, HDAC inhibitors will be promising agents to improve survival of patients with PCM, and the combination of HDAC inhibitor and NF-κB inhibitor may provide a novel therapeutic strategy against PCM.

Immunodiagnostic potency of homologous antigens for natural Haemonchus contortus infection in small ruminants in plate and paperenzyme linked immunosorbent assay

2016 ◽  
Author(s):  
Niranjan Kumar ◽  
Bhupamani Das ◽  
Mehul M. Jadav ◽  
Jayesh B. Solanki
Keyword(s):  
Molecular Weight ◽  
Haemonchus Contortus ◽  
Cysteine Proteinase ◽  
Cathepsin L ◽  
Small Ruminants ◽  
Somatic Antigen ◽  
Predictive Values ◽  
Dot Elisa ◽  
Sensitivity Specificity

The objective of this study was to characterize Haemonchus contortus antigens, and to standardize and evaluate indirect plate and dot-ELISA using homologous antigens in the small ruminants. Electrophoretic separation of somatic antigen in reducing condition on 15% polyacrylamide gel resolved into 16 proteins of molecular weight ranging from 14-100 kDa. Two step ethanolic extraction of the supernatant of in-vitro culture of H. contortus yielded excretory-secretory (E-S) antigen/ cathepsin L cysteine proteinase of molecular weight 28 kDa. The animals (Goats=103; Sheep=91) were broadly kept into post-mortem (PM) and faecal examined groups and further sub-grouped based on mono or multiply helminths infection. At many occasion, the somatic antigen found to cross reacts with other helminths parasites thus minimizing the specificity of the selected tests and antigens. There was no any direct correlation between the parasites load and ELISA reactivity pattern. The prevalence rate of haemonchosis was 55.7 (34/61) in goats/ 47.6 (40/84) % in sheep as per PM examination while it was 45.63 (47/103) in goats/ 41.76% (38/91) in sheep and 36.89 (38/103) in goats/ 35.16% (32/91) in sheep using E-S antigen based plate and dot-ELISA, respectively. With E-S antigen, the overall % sensitivity, specificity, positive and negative predictive values of plate-ELISA was 89.74 (goats)/ 80.95 (sheep), 81.25 (goats)/ 91.84 (sheep), 74.47 (goats)/ 89.47 (sheep), 92.86 (goats)/ 84.91 (sheep), respectively while for dot-ELISA it was 66.67 (goats)/ 61.9 (sheep), 81.25 (goats)/ 87.76 (sheep), 68.42 (goats)/ 81.25 (sheep), 80 (goats)/ 72.88 (sheep), respectively, so the tests and E-S antigen can be recommended for the detection haemonchosis in the small ruminants.

Clinical Epidemiology

2016 ◽  
pp. 285-290
Author(s):  
Scott C. Litin ◽  
John B. Bundrick
Keyword(s):  
Diagnostic Test ◽  
Diagnostic Tests ◽  
Clinical Decision Making ◽  
Clinical Epidemiology ◽  
Clinical Decision ◽  
Test Results ◽  
Specific Patient ◽  
Predictive Values ◽  
Test Sensitivity ◽  
Sensitivity Specificity

Diagnostic tests are tools that either increase or decrease the likelihood of disease. The sensitivity, specificity, and predictive values of normal and abnormal test results can be calculated with even a limited amount of information. Some physicians prefer interpreting diagnostic test results by using the likelihood ratio. This ratio takes properties of a diagnostic test (sensitivity and specificity) and makes them more helpful in clinical decision making. It helps the clinician determine the probability of disease in a specific patient after a diagnostic test has been performed.

Evaluation of the EYTEX® System as a Screening Method for the Ocular Irritancy of Chemical Products

1994 ◽  
Vol 22 (1) ◽  
pp. 32-50
Author(s):  
Jean-François Régnier ◽  
Christophe Imbert ◽  
Jean-Charles Boutonnet
Keyword(s):  
False Negative ◽  
Screening Method ◽  
In Vitro Test ◽  
Predictive Values ◽  
Ocular Irritation ◽  
Wide Range ◽  
Dangerous Substances ◽  
Sensitivity Specificity ◽  
Interlaboratory Reproducibility

The EYTEX® method is an in vitro test used to predict ocular irritation, based on alterations in a protein matrix. We have evaluated this method with the aim of using it to screen chemicals. One hundred and forty-two products (commodities and specialities), having a wide range of chemical properties and ocular irritation potential in the rabbit, were tested with either the standard, MPA, AMA, KMA or UMA protocols. The results were compared with in vivo data obtained previously for each chemical and with the EEC labelling of eye irritation for dangerous substances. Intralaboratory repeatability and interlaboratory reproducibility were evaluated with seven other laboratories. Ninety-three per cent of the chemicals tested were qualified with the EYTEX method. The coefficients of the linear correlation between the EYTEX score and the maximal Draize score on the one hand and the maximal corneal score on the other hand, were 0.69 and 0.65, respectively. Compared to the EEC classification, the labelling of dangerous substances and for the prediction of severe irritants, sensitivity, specificity and equivalence were 94%, 89% and 78%, respectively. We observed nine false positives (22%) and two false negatives (2%) for the identification of R41-, R34- and R35-labelled products. The predictive values, for identifying R41, R34 and R35 products and non-irritants or R36 products were 78% and 97%, respectively. Repeatability (6.3) and reproducibility (8.9) were quite satisfactory. The EYTEX system exhibits the characteristics of a good screening method: compatibility with a large range of chemicals; a simple and rapid procedure; good intralaboratory and interlaboratory reproducibility; cost effectiveness; high sensitivity, specificity and predictive value; and a low incidence of false negative and false positive results. Based on these results, we consider the EYTEX method to be a valuable tool for the screening of eye irritancy.

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