Coamplification of 12p11 and 12q13 approximately q22 in multiple ring chromosomes in a spindle cell sarcoma resolved by novel multicolor fluorescence in situ hybridization analysis

An 80-year-old male presented with a lobulated mass in the lower abdominal wall. A diagnosis of an intermediate grade myofibroblastic spindle cell sarcoma was made. Cytogenetic analysis demonstrated a complex karyotype with a der(6), a small marker and five, different in size, ring chromosomes. Fluorescence in situ hybridization (FISH), multiplex FISH, and multicolor banding analysis was used to further delineate this complex karyotype. The der(6) was shown to be a der(18)t(6;18;9;12;18), the marker chromosome was identified as del(17), and the ring chromosomes as r(9) and r(12;18)x4. Amplification of 18 and coamplification of 12p and 12q was detected in the ring and marker chromosomes. No intercellular heterogeneity was observed although a few micronuclei containing chromosome 18 and anaphase bridges, containing chromosome 12 material, the result of bridge-fusion-bridge (BFB) cycles, were observed. Our findings combined with results from others indicate that amplification of chromosomes 12 and 18 as well as BFB phenomena characterize this type of sarcoma.     

Enrollment of women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute

BACKGROUND: With the recognition that certain aspects of cardiovascular disease are specific to sex, the government has sought to ensure that federally funded clinical research yields adequate high-quality information about heart disease in women. METHODS: We tabulated the numbers of men and women in cardiovascular clinical trials funded by the National Heart, Lung, and Blood Institute (NHLBI) between 1965 and 1998, recording both total numbers and the numbers for each type of cardiovascular disease. We analyzed the data according to the sex-specific prevalence of disease and assessed changes in enrollment over time. We performed a similar analysis after excluding all single-sex trials. RESULTS: A total of 398,801 subjects (215,796 women and 183,005 men) were enrolled in NHLBI-funded studies of cardiovascular disease. The overall enrollment rate for women (54 percent) exceeded the prevalence of cardiovascular disease in women in the general population (49 percent) and increased over time (P=0.002). With single-sex trials excluded, the enrollment rate for women was 38 percent, which did not change significantly over time. In studies of coronary artery disease and hypertension the rates of enrollment of women were similar to or exceeded the prevalence of these disorders in women. The enrollment rate increased significantly over time in studies of coronary artery disease (P<0.001) but not in studies of hypertension or arrhythmia. Women were under-enrolled in studies of heart failure, and the rate of enrollment did not change significantly over time. When single-sex trials were excluded from the analysis of enrollment rates according to the prevalence of disease, the results were similar. There was no change in enrollment rates overtime for any category of disease. CONCLUSIONS: Federal efforts to increase the representation of women in clinical trials have been moderately successful primarily because of the institution of a small number of large, single-sex trials involving coronary artery disease. There has been no change in the sex composition of cohorts in the majority of studies of cardiovascular disease.     

Cryopreservation of human mononuclear cells for quality control in clinical immunology. I. Correlations in recovery of K- and NK-cell functions,surface markers,and morphology

Cryopreserved human peripheral blood mononuclear cells (PBMC) were tested for natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) and for high-affinity (29°C) and total (4°C) rosette formation with sheep erythrocytes. PBMC produced variable NK activity following freezing and thawing, but consistently reacted well in ADCC. A significant correlation was found between low NK activity and a decreased percentage of low-affinity rosette-forming cells. On the contrary, the number of large granular lymphocytes (LGL), among which NK cells are restricted, and the reactivity with the monoclonal antibody OKT10, which recognizes the majority of LGL in the peripheral blood, were not significantly altered by cryopreservation. Cryopreserved cells proved to be excellent controls for determining the day-to-day variability of the NK assay and for selecting optimum conditions for this test in the clinical immunology laboratory.     

Barriers to Dissemination: Exploring the Criticisms of Behavior Therapy for Tics

The review by Cook and Blacher (2007 ) suggests that behavior therapy for tic disorders is indeed efficacious. Given the empirical support for these treatments, researchers should begin to place effort on examining various strategies for treatment dissemination. The current article addresses possible barriers to dissemination, focusing specifically on various concerns that have been raised by many medical and psychological care providers. The validity of these concerns is examined in the context of existing data. In addition, limitations of the current literature and future directions for research are discussed.     

Ectopic expression of a cecropin transgene in the human malaria vector mosquito Anopheles gambiae (Diptera: Culicidae): effects on susceptibility to Plasmodium

Genetically altering the disease vector status of insects using recombinant DNA technologies is being considered as an alternative to eradication efforts. Manipulating the endogenous immune response of mosquitoes such as the temporal and special expression of antimicrobial peptides like cecropin may result in a refractory phenotype. Using transgenic technology a unique pattern of expression of cecropin A (cecA) in Anopheles gambiae was created such that cecA was expressed beginning 24 h after a blood meal in the posterior midgut. Two independent lines of transgenic An. gambiae were created using a piggyBac gene vector containing the An. gambiae cecA cDNA under the regulatory control of the Aedes aegypti carboxypeptidase promoter. Infection with Plasmodium berghei resulted in a 60% reduction in the number of oocysts in transgenic mosquitoes compared with nontransgenic mosquitoes. Manipulating the innate immune system of mosquitoes can negatively affect their capacity to serve as hosts for the development of disease-causing microbes.     

Depletion of peripheral blood T lymphocytes and NK cells during the course of ebola hemorrhagic Fever in cynomolgus macaques

During the course of an experimentally induced Ebola virus (EBOVA) infection of cynomolgus macaques, peripheral blood mononuclear cells were isolated and characterized by multi-color flow cytometry. Both CD4+ and CD8+ lymphocyte counts decreased 60-70% during the first 4 days after infection. Among CD8+ lymphocytes, this decline was greatest among the CD8(lo) population, which was composed mostly of CD3- CD16+ NK cells. In contrast, the number of CD20+ B lymphocytes in the blood did not significantly change during the course of the infection. Phenotypic analysis of T lymphocyte subsets by flow cytometry failed to show evidence of a robust immune response to the infection. Apoptosis could be detected as early as day 2 postinfection among the CD8+ and CD16+ subsets of lymphocytes. Increased expression of CD95 (Fas) suggests that apoptosis may be induced via signaling through the Fas/Fas-L cascade. In contrast, the number of HLA-DR+ cells increased tenfold in the blood during the course of infection. These data suggest that EBOV may block dendritic cell maturation after infection, thereby inhibiting activation of lymphocytes and eliminating those subsets that are most likely to be capable of mounting an effective response to the virus.     

Trends in HIV prevalence among public sexually transmitted disease clinic attendees in the Western region of the United States (1989-1999)

OBJECTIVES: Using data from anonymous unlinked testing of routinely collected sera, trends in HIV are compared among sexually transmitted disease patients in 4 Western urban centers. METHODS: Between 1989 and 1999, remnant sera obtained for routine syphilis testing from 256,819 patient visits to Denver, Los Angeles, San Francisco, and Seattle clinics were tested for HIV antibodies in an unlinked survey. HIV antibody test results were linked to anonymous demographic and risk information abstracted from the medical record. RESULTS: Overall cumulative HIV seroprevalences among women and among men who had sex exclusively with women were < or = 2%, declined over time, and did not exceed 8% among those who injected drugs. In contrast, cumulative HIV seroprevalences among men who have sex with men ranged from 13% in Seattle to 30% in San Francisco and declined a mean of 2.1% (95% CI, 1.6, 2.6) to 2.8% (CI 2.6, 3.1) per year, after adjustment. CONCLUSIONS: HIV infection declined over time across counties. Relative levels of HIV differed little by demographic and behavioral risk group despite differences in the severity of each county's epidemic. Because of the unique contribution of unlinked serosurveillance studies in monitoring these trends, their reinstitution in high-risk settings should be considered.