Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Lipoma of the left ventricle

A 36-year-old female was admitted with dyspnea on exertion of one year's duration. Echocardiography revealed a tumor arising from interventricular septum with dynamic left ventricular outflow tract obstruction. On cardiopulmonary bypass with cardioplegic arrest, the tumor was approached through a transverse aortotomy, and excised from the interventricular septum through the aortic valve. Postoperative recovery was uneventful and the patient was asymptomatic with no recurrence at follow-up after one year.     

Regulation of stimulated integrin surface expression in human neutrophils by tyrosine phosphorylation

The control of the adhesive properties of human neutrophils is an essential element of their defense function. One level at which this control is exerted involves the upregulation of the surface expression of beta 2-integrins. In this study, we have examined the potential involvement of tyrosine phosphorylation in the latter process. Two inhibitors of tyrosine kinases with differing modes of action, erbstatin and herbimycin A, were found to inhibit the expression of CD11b and CD18 stimulated by chemotactic factors (fMet-Leu-Phe or leukotriene B4) or growth factors (tumor necrosis factor alpha). This inhibition was not shared by an inactive analog of erbstatin or by the protein kinase C inhibitor Ro 31-8330. Erbstatin also inhibited the unveiling of activation-specific neoepitopes detected by antibody CBRM1/5. Pretreatment of neutrophils (but not of endothelial cells) with erbstatin inhibited the stimulation of neutrophils' adherence to endothelial cells induced by fMet-Leu-Phe. Augmentation of tyrosine phosphorylation by inhibiting tyrosine phosphatases using hydroperoxyvanadate led to an increased surface expression of CD11b and CD18 and enhanced the adhesion of neutrophils to endothelial cells. Finally, the leumedin NPC 15669, which had previously been shown to inhibit stimulated CD11b expression and neutrophil adherence to endothelial cells and to exhibit anti-inflammatory properties in various in vivo models of inflammation, inhibited the stimulation of tyrosine, phosphorylation induced by fMet-Leu-Phe. Taken together, these data establish a strong correlation between tyrosine phosphorylation and integrin upregulation in stimulated human neutrophils.     

Impact of coronary collaterals on outcome following percutaneous coronary intervention (from the National Heart, Lung, and Blood Institute Dynamic Registry)

Coronary collateral circulation is beneficial in patients with coronary artery disease, but controversy still exists regarding the association between angiographic collaterals and outcome after percutaneous coronary intervention (PCI). We compared the baseline characteristics and cumulative 1-year event rates of consecutive patients undergoing PCI by target vessel collateral status-no angiographic evidence of collateral circulation (NC; n = 5051), treated artery supplied collaterals (SC; n = 239), and treated artery received collaterals (RC; n = 893)-using the National Heart, Lung, and Blood Institute Dynamic Registry. Patients in the SC group were older and had more previous coronary bypass surgery, myocardial infarction, co-morbid illness, and heart failure than the NC and RC groups and had less often undergone revascularization for acute myocardial infarction (p <0.01 for all). The total angiographic PCI success was comparable for the SC and NC groups but higher than for the RC group (94.1% vs 94.4% vs 83.9%, respectively; p <0.001). Overall stent use was 77.5% and was highest in the SC group (82.4%, p <0.001). At 1 year, significant differences in outcome were observed by collateral status. Compared with the NC group, patients with PCI of a SC artery had higher adjusted mortality (relative risk [RR] 1.95, 95% confidence interval [CI] 1.27 to 3.01, p = 0.002) and death/myocardial infarction (RR 1.75, 95% CI 1.26 to 2.45, p <0.001) rates. Patients with PCI of a RC vessel, conversely, had lower adjusted death/myocardial infarction (RR 0.72, 95% CI 0.54 to 0.96, p = 0.02) and repeat revascularization (RR 0.73, 95% CI 0.59 to 0.91, p = 0.005) rates. In conclusion, our results suggest that PCI on collateralized vessels is warranted, but that patients with PCI in arteries that supply collaterals are a high-risk group that may benefit from closer follow-up and complete revascularization.     

Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors

Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.     

Synthesis and Characterization of Impurities in the Production Process of Lopinavir

Lopinavir is an antiretroviral drug used for the inhibition of HIV protease. Four related substances of lopinavir were observed during the manufacturing process of lopinavir in the laboratory and they were identified. The present work describes the origin, synthesis, characterization, and control of these related substances.