Elimination of clonogenic stem cells from human multiple myeloma cell lines by a plasma cell-reactive monoclonal antibody and complement

The monoclonal antibody (MoAb) MM4 reacts with human multiple myeloma (MM) cell lines and bone marrow from patients with plasma cell dyscrasias but not with normal peripheral blood or bone marrow cells. Treatment with MM4 and rabbit complement (C') was cytotoxic to the plasma cell-derived cell lines GM 1312, RPMI 8226, and ARH-77, as demonstrated by chromium release microcytotoxicity and trypan blue exclusion assays. The same treatment eliminated greater than 99% of clonogenic myeloma stem cell colony formation of these cell lines, with less than 20% inhibition of normal human bone marrow pleuripotent progenitor colony formation in vitro. As an experimental model to explore the efficacy of MM4 + C' in purging MM-involved bone marrow, normal marrow cells were mixed with RPMI 8226 or GM 1312 cells in the ratio of 90:10 or 50:50 (marrow:myeloma cells). Colony growth assays indicated that MM4 + C' eliminated at least 2 logs of clonogenic myeloma stem cells in both 90:10 and 50:50 preparations, while sparing the majority of normal marrow progenitors (inhibition of CFU-C:10% to 13%; BFU-E:0%). The selectivity of MM4-mediated cytotoxicity may be useful for eliminating myeloma clonogenic stem cells from bone marrow of patients with multiple myeloma.     

The economic burden of chronic obstructive pulmonary disease (COPD) in a U.S. Medicare population

RATIONALE: Although the economic burden of COPD has gained attention in recent years, data on the costs of COPD among U.S. Medicare beneficiaries are lacking. METHODS: This study used administrative claims and eligibility records from a large U.S. multi-state Medicare managed care database. Study patients were 65+ years of age with paid claims during 2004. The COPD cohort comprised patients with 1+ inpatient/ER claims or 2+ outpatient claims (>30 days apart) for COPD (ICD-9-CM codes 491.xx, 492.x, 496). The comparison cohort included patients without COPD matched 3:1 to the COPD cohort on age, sex, enrollment months, and Medicare plan. Excess costs of COPD were estimated as the difference in overall health plan payments between the two cohorts during 2004. Attributable costs were calculated using medical claims with listed diagnoses of COPD or other respiratory-related conditions and pharmacy claims for respiratory medications. RESULTS: A total of 8370 patients were included in the COPD cohort and were matched to 25,110 comparison cohort patients. For both groups, mean (SD) age was 78 (8) years, 54% were female, and duration of eligibility was 11 (2) months. COPD patients were more likely to utilize healthcare services and had excess total healthcare costs about $20,500 higher (P<0.0001) than the comparison cohort. Comorbidities were high in the COPD cohort, accounting for 46% of the observed excess cost. The attributable cost of COPD averaged about $6,300; other respiratory-related costs averaged about $4,400. CONCLUSION: In this U.S. Medicare managed care population, COPD posed a substantial burden in terms of both respiratory-related and total healthcare costs. A comparison of these cost-of-illness estimates to those for elderly COPD patients in other countries would be of great interest, given the increasing age of populations in most Western countries.     

Limitations of flow cytometry in the analysis of CDIalHLADR+ human oral mucosal Langerhans cells

Suspensions of human oral epithetial cells were stained with antibodies to CD la and HLADR conjugated with fluorochromes and analysed by flow cytometry with the aim of purifying double-labetled Langerhans cells, a population comprising approximatety 2% of the cell total. Whole suspensions had high levets of autofluorescence and a wide range of forward and right angle scatter properties. The mean percentage of CDIalHLADR+ cells was 2.I%, though the double-labetled cells did not form a discrete group and the percentages of positive cells using control antibodies were similar. Density gradient centrifugation prior to flow cytometry did not facilitate Langerhanr cell identification within the suspension. The results indicate flow cytometric analysis of minority cell populations (such as Langerhans cells) within oral epithetium is limited by the autofluorescence of physically heterogeneous keratinocytes, and emphasise the importance of controls in studies of oral epithetium which use this method.