Cytogenetic studies on human myeloma cell lines

Cell lines (U-266, U-1957, U-1996 and U-2030) established from 4 patients with multiple myeloma (MM) were analyzed cytogenetically. The cell lines represent different stages in B-cell differentiation as evidenced by ultrastructural and functional characteristics. The karyotypic pattern in 3 newly established myeloma lines was studied after a few months in culture and compared to the old myeloma cell line U-266, which was examined after 6, 7 and 8 years of continuous cultivation. Frequency of progressive numerical and structural aberrations during long-term cultivation and their correlation with alterations in growth properties were addressed. We describe the presence of a high frequency of both numerical and structural chromosomal abnormalities in the cells of all 4 myeloma lines studied. Chromosomes often associated with structural abnormalities were 1, 3, 6, 12 and 14. A 14q + marker chromosome was detected in 2 of the 4 cell lines. The breakpoints on the chromosomes participating in structural aberrations in myeloma exhibit some correlation to chromosome sites at or close to locations of mapped oncogenes. No translocations of c-myc were found. These data were further supported by Southern blot analysis (unpublished data). The extent of numerical, but not structural, aberrations correlates with the differentiation stage of the myeloma lines in that the 2 mature lines U-266 and U-1957 were both near-diploid. Multiple progressive chromosomal changes have emerged in U-266 during a period of 8 years with development of independence of feeder cells and increased growth rate. However, capacity for production of complete Ig molecules has remained stable.     

Natriuretic peptides in unstable coronary artery disease.

Patients with unstable coronary artery disease (CAD), i.e., unstable angina or non-ST-elevation myocardial infarction, vary widely in clinical presentation, prognosis and response to treatment. To select appropriate therapy, early risk stratification has become increasingly important. This review focuses on the emerging role of natriuretic peptides in the early assessment of patients with unstable CAD. We conclude that levels of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are strongly associated to mortality and the risk of future congestive heart failure, and carry important prognostic information independent from previously known risk factors in unstable CAD. There are some data indicating that these markers can also be helpful in the selection of appropriate therapy in these patients but further studies are needed. Before a routine use of BNP or NT-proBNP in unstable CAD can be recommended, the cost-effectiveness of adding these new markers to the currently routine markers and their impact on selection of treatment needs further evaluation.     

Relation between renal function,presentation, use of therapies and in‐hospital complications in acute coronary syndrome: data from the SWEDEHEART register

Abstract. Szummer K, Lundman P, Jacobson SH, Schön S, Lindbäck J, Stenestrand U, Wallentin L, Jernberg T, for SWEDEHEART. (Karolinska Institute, Karolinska University Hospital, Stockholm; Karolinska Institute, Danderyd Hospital, Danderyd; Ryhov County Hospital, Jönköping; University Hospital, Uppsala and University Hospital, Linköping; Sweden) Relation between renal function, presentation, use of therapies and in‐hospital complications in acute coronary syndrome: data from the SWEDEHEART register. J Intern Med 2010; 268 :40–49. Objective. To examine clinical characteristics, presenting symptoms, use of therapy and in‐hospital complications in relation to renal function in patients with myocardial infarction (MI). Design. Observational study. Setting. Nationwide coronary care unit registry between 2003–2006 in Sweden. Subjects. Consecutive MI patients with available creatinine (n = 57 477). Results. Glomerular filtration rate was estimated with the Modification of Diet in Renal Disease Study formula. With declining renal function patients were older, had more co‐morbidities and more often used cardio‐protective medication on admission. Compared to patients with normal renal function, fewer with renal failure presented with chest pain (90% vs. 67%, P < 0.001), Killip I (89% vs. 58%, P < 0.001) and ST‐elevation myocardial infarction (STEMI) (41% vs. 22%, P < 0.001). In a logistic regression model lower renal function was independently associated with a less frequent use of anticoagulant and revascularization in non‐ST‐elevation MI. The likelihood of receiving reperfusion therapy for STEMI was similar in patients with normal‐to‐moderate renal dysfunction, but decreased in severe renal dysfunction or renal failure. Reperfusion therapy shifted from primary percutaneous coronary intervention in 71% of patients with normal renal function to fibrinolysis in 58% of those with renal failure. Renal function was associated with a higher rate of complications and an exponential increase in in‐hospital mortality from 2.5% to 24.2% across the renal function groups. Conclusion. Renal insufficiency influences the presentation and reduces the likelihood of receiving treatment according to current guidelines. Short‐term prognosis remains poor.     

Relative biological effectiveness of boron ions on human melanoma cells

PURPOSE: To compare the difference in relative biological effectiveness (RBE) between (10)B ions and a (60)Co gamma-ray beam for human melanoma cells using in vitro cell survival based on a clonogenic assay. MATERIALS AND METHODS: Cells were irradiated in vitro under aerobic conditions with (60)Co and (10)B ions with different linear energy transfer (LET) (40, 80 and 160 eV nm(-1)). The dose to the cells was determined using ferrous sulphate dosimetry and an ionisation chamber. The standard linear-quadratic model and the newly proposed repairable conditionally repairable damage (RCR) model were used to calculate the RBE. RESULTS: The RBE at 10% cell survival for 40, 80 and 160 eV nm(-1) boron ions compared with (60)Co were 1.98 (1.83-2.22), 2.85 (2.64-3.11) and 3.37 (3.17-3.58), respectively, of almost independence of the model used in the calculation. CONCLUSIONS: Different cell survival models may generate different RBE, especially at low doses and high cell survival levels.     

A comparison of wind noise in four hearing instruments

Wind noise was measured in four behind-the-ear hearing instruments with different microphone openings. A silent airflow of 7 m/s was directed toward the ear of a Kemar head and the resulting wind noise was measured. The amplification was set to an insertion gain of 35 dB at 1.6 kHz. The wind noise amplitude at the position of the drum ranged from 84 to 97 dB(A). The hearing instrument with a partially covered microphone entrance proved best, whereas one with an open microphone entrance had the poorest performance. A reduction in wind noise of 6-17 dB could be achieved in all hearing instruments by using a simple windscreen made of Styrofoam. The windscreen affected the frequency response by less than 2 dB. By subtracting the insertion gain from the wind noise, an equivalent wind noise could be presented as a function of frequency. A considerable difference was found between the wind noise sensitivity in different hearing instruments. All could be improved by a windscreen without adversely affecting the frequency response.     

The effect of α and γ-interferon on proliferation and production of IgE and β2-microglobulin in the human myeloma cell line U-266 and in an α-interferon resistant U-266 subline

An IFN-resistant subline (U-266^r_α) was established from the IFN-α-sensitive myeloma cell line U-266 by subculturing U-266 cells with increasing doses of INF-α. The U-266^r_α secreted IgE at a higher rate than the U-266 (7.2 × 10^?13 g/c/8 h as compared to 3.3 × 10^?13 g/c/8 h). The 2 cell lines were found to be equally high producers of β₂m (9.2 and 9.6 × 10^?13 g/c/8 h). The U-266 produced 2.9 times less IgE and 5 times more β₂m compared to the initial production rates at establishment. INF-α and recombinant IFN-αM₂ (rIFN-α₂) inhibited proliferation and concomitantly decreased the rate of IgE and β₂m secretion in U-266 but not in U-266 IFN^r_α, which in contrast was slightly stimulated by IFN-α with respect to growth, IgE and β₂m secretion. In addition, IFN-α at a concentration of 100 U/ml was shown to decrease the IgE and β₂m production without exerting more than minimal cytotoxicity on U-266 cells. No antiproliferative effect was found for IFN-γ or recombinant IFN-γ (rIFN-γ) on either of the 2 cell lines. IFN-γ and rIFN-γ were, however, found to stimulate the production of β₂m. Our results show that the U-266 and the derived IFN-α-resistant subline can be used as models for studying some of the biological effects of IFN-α and -γ in vitro. The clinical implications of these in vitro results, in particular the usefulness of serum determinations of immunoglobulin and β₂m concentrations for monitoring the tumor cell mass, are discussed.     

Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study

Objectives

Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients.

Design

The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study.

Setting

Coronary care units in the Stockholm metropolitan area.

Subjects

Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded.

Results

In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 6–28) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified.

Conclusion

In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.     

Reinfarction in Patients with Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA): Coronary Findings and Prognosis

Background

Myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is common. There are limited data on the mechanisms and prognosis for reinfarction in MINOCA patients.