The radiological features of adult T-cell leukaemia/lymphoma

Adult T-cell leukaemia/lymphoma (ATLL) results from a monoclonal expansion of T-cells infected with the human T-cell lymphotropic virus type 1 (HTLV-1). Six cases of ATLL, three males and three females all from the Caribbean and with a mean age of 55 years, have been reviewed retrospectively, illustrating the wide spectrum of radiological changes. One patient had extensive mediastinal adenopathy, hitherto an unrecorded finding in ATLL.     

Tumor suppressor gene alteration in adult acute lymphoblastic leukemia (ALL). Analysis of retinoblastoma (Rb) and p53 gene expression in lymphoblasts of patients with de novo, relapsed, or refractory ALL treated in Southwest Oncology Group studies

To examine the impact of inactivation of tumor suppressor genes on outcome in adult ALL, we compared two groups of patients registered to SWOG treatment protocols for loss of the Rb gene product and p53 overexpression: (1) 89 patients with de novo ALL, and (2) 26 patients with relapsed/refractory ALL. The groups were comparable with respect to age, sex, and race. Cell lysates (> or = 80% blasts) were analyzed by immunoblotting which enabled detection of Rb or p53 proteins in as little as 1 microg of lysate. Loss of Rb expression (pRbneg) was found in 54/85 (64%) de novo and 11/19 (58%) relapsed patients (P = 0.79). Overexpression of p53 (p53abn), indicative of p53 point mutations, was found in 16/75 (21%) de novo and 8/19 (42%) relapsed patients (P = 0.08). Using a nonisotopic RNase cleavage assay, p53 point mutations in exons 5-9 were confirmed in 14/23 (61%) p53abn specimens. For the de novo ALL group, patients with normal Rb protein had higher WBC and higher peripheral blast and lymphocyte counts. Otherwise neither abnormal Rb or p53 expression correlated with any of a large panel of clinical and laboratory variables including FAB class, blast lineage, expression of myeloid antigens or CD34, and presence of the Ph1 chromosome or BCR-ABL. Analyses of treatment outcomes demonstrated no significant impact of Rb or p53 status alone on CR rates, relapse-free or overall survival. An identical percentage (11%) of both de novo and relapsed/refractory patients had concurrent abnormalities of both Rb and p53 expression (pRbneg/p53abn). The survival curve of these patients suggests an increased rate of early death, but the number of patients in this group was small. Summarizing, (1) loss of Rb expression is common in adult ALL; (2) overexpression of p53 may be more frequent in relapsed/refractory than de novo adult ALL; and (3) although Rb or p53 alterations alone are not strong independent predictors of outcome, their concurrent expression may predict a poor response to therapy.     

Paternally inherited chromosomal structural aberrations detected in mouse first-cleavage zygote metaphases by multicolour fluorescence in situ hybridization painting

We describe a fluorescence in situ hybridization (FISH) procedure for assessing zygotic risk of paternal exposure to endogenous or exogenous agents. The procedure employs multicolour FISH with chromosome-specific DNA painting probes plus DAPI staining for detecting both balanced and unbalanced chromosomal aberrations in mouse first-cleavage (1-Cl) zygote metaphases. Four composite probes specific for chromosomes 1, 2, 3 or X, each labelled with biotin, plus a composite probe specific for chromosome Y labelled with digoxigenin, were used. We applied this method to evaluate the effects of paternal exposure to acrylamide, a model germ cell clastogen. First-cleavage zygote metaphases, collected from untreated females mated to males whose sperm or late spermatids were treated with acrylamide, were scored for the induction of structural aberrations using both chromosome painting (PAINT analysis) and DAPI analysis. Structural chromosomal aberrations were observed in the sperm-derived, but not in the egg-derived, pronuclei. While 59.4% of the zygotes had structural aberrations by DAPI analysis, 94.1% of the same zygotes had structural aberrations by PAINT analysis (P < 0.001), illustrating the increased sensitivity for detecting translocations and insertions obtained by adding chromosome painting. These findings show that FISH painting of mouse 1-Cl zygotes when used in conjunction with DAPI analysis is a powerful model for investigating the cytogenetic defects transmitted from father to offspring.     

Unilateral multilayered musculocutaneous V-Y advancement flap for the treatment of pressure sore

We have devised a modified technique using the gluteus maximus musculocutaneous flap as multilayered sliding V-Y advancement to cover pressure sores on the sacral area. Nine patients with relatively large (average 7 x 7 cm) sacral grade IV pressure sores underwent unilateral multilayered V-Y advancement flap. All patients were followed for a minimum of 8 weeks. The mean postoperative follow-up was 32.3 months, with a range of 24 to 39 months. Using this technique, the success of surgery, i.e., the percentage of sores that healed, was 100 percent in our patients. The advantages of this technique include sufficient advancement of the flap, coverage of large ulcer defects using only a unilateral musculocutaneous flap, and preservation of the contralateral gluteus maximus muscle for future use.     

The prototypic Th2 autoimmunity induced by mercury is dependent on IFN-gamma and not Th1/Th2 imbalance

Chromosomal translocations leading to deregulation of specific oncogenes characterize approximately 50% of cases of diffuse large B-cell lymphomas (DLBL). To characterize additional genetic features that may be of value in delineating the clinical characteristics of DLBL, we studied a panel of 96 cases at diagnosis consecutively ascertained at the Memorial Sloan-Kettering Cancer Center (MSKCC) for incidence of gene amplification, a genetic abnormality previously shown to be associated with tumor progression and clinical outcome. A subset of 20 cases was subjected to comparative genomic hybridization (CGH) analysis, which identified nine sites of chromosomal amplification (1q21-23, 2p12-16, 8q24, 9q34, 12q12-14, 13q32, 16p12, 18q21-22, and 22q12). Candidate amplified genes mapped to these sites were selected for further analysis based on their known roles in lymphoid cell and lymphoma development, and/or history of amplification in tumors. Probes for six genes, which fulfilled these criteria, REL (2p12-16), MYC (8q24), BCL2 (18q21), GLI, CDK4, and MDM2 (12q13-14), were used in a quantitative Southern blotting analysis of the 96 DLBL DNAs. Each of these genes was amplified (four or more copies) with incidence ranging from 11% to 23%. This analysis is consistent with our previous finding that REL amplification is associated with extranodal presentation. In addition, BCL2 rearrangement and/or REL, MYC, BCL2, GLI, CDK4, and MDM2 amplification was associated with advanced stage disease. These data show, for the first time, that amplification of chromosomal regions and genes is a frequent phenomenon in DLBL and demonstrates their potential significance in lymphomagenesis.     

Comparison of total DNA adduct levels induced in mouse tissues and human skin by mainstream and sidestream cigarette smoke condensates

Cigarette smoke condensates (CSCs) of both mainstream (MS) and sidestream (SS) smoke were used to treat mice topically in equivalent amounts. Human skin maintained in short-term culture was also treated with the condensates. DNA adducts, induced by the CSCs and detected by the nuclease P1 method of 32P-postlabelling, were quantified in a number of murine tissues and in the human skin DNA. In the five mouse tissues studied both MS-CSC and SS-CSC produced characteristic diagonal radioactive zones on TLC, indicative of the formation of multiple DNA adducts. In three tissues (skin, lung and kidney), SS-CSC induced greater total adduct levels than MS-CSC (statistically significant in skin and kidney, p < 0.05). However, greater adduct levels induced by MS-CSC were recorded for heart and bladder DNA (not statistically significant). Similar results to those found in mouse skin were obtained with human skin; SS-CSC induced a approximately 2-fold greater level of DNA adducts than MS-CSC (p < 0.05). Incubation of DNA directly with condensates in vitro demonstrated that DNA adducts could be formed without an exogenous metabolizing system. This direct interaction of condensates with DNA occurred at similar levels for both MS- and SS-CSC, although inclusion of an oxygen radical-generating system enhanced the SS-CSC binding to a greater extent than that of the MS-CSC.     

A comparison of cause-specific melanoma mortality and all-cause mortality in survival analyses after radiation treatment for uveal melanoma

OBJECTIVE: To determine the causes and patterns of mortality after uveal melanoma radiation. DESIGN: A cohort study from a single institution was performed. Mortality was modeled using semiparametric survival techniques. All cause and cause-specific mortality analyses were performed. Mortality was compared with expected mortality from the U.S. census data. PARTICIPANTS: A total of 731 patients were studied, and 710 (97%) of these had medium or large melanomas. The mean tumor diameter was 11.3 mm, and the mean tumor thickness was 5.8 mm. Ciliary body was involved in 122 (17%) of patients. Complete follow-up was available on 99.6% (728 of 731) of patients. MAIN OUTCOME MEASURES: The authors analyzed the distribution and causes of post-treatment mortality. RESULTS: The 5- and 10-year all-cause Kaplan-Meier survival rates were 75.6% and 62.3%, respectively. Both melanoma risk factors (older age, ciliary body involvement, and larger tumor diameter) and nonmelanoma risk factors (older age and medical condition) were significant prognostic factors of all-cause mortality. Deaths from nonmelanoma causes accounted for 91 (42.3%) of 215 deaths. The 5-year and 10-year estimates of nonmelanoma deaths were 8.3% and 15.9%, respectively. Nonmelanoma mortality was similar to that observed in the general U.S. population (91 observed, 98.1 expected). Melanoma metastases accounted for 124 (57.7%) of 215 deaths. The 5- and 10-year estimates for probability of metastatic death were 16.1% and 21.8%, respectively. The largest tumor diameter was the best predictor for melanoma mortality; ciliary body involvement, older age, and distance from the fovea also were significant in multivariate analyses. CONCLUSION: A significant proportion of patients with uveal melanoma die of nonmelanoma causes after radiation. In analyzing prognostic factors, considerable information may be lost if analyses are based on all-cause mortality rather than cause-specific mortality.