DNA aneuploidy in adult acute leukemia

Using flow cytometric techniques, we determined DNA ploidy levels in the bone marrow of 318 successive adult patients with newly diagnosed acute leukemia. Overall, 26% exhibited DNA stem line abnormalities, usually with a 10%-15% DNA excess, regardless of morphologic diagnosis. DNA aneuploidy was seen most frequently in patients with a hyperdiploid chromosome number and karyotype instability (50%), but was also present in a third of patients with chromosomal translocations and in 20% of patients with a normal diploid karyotype. Thus, among 73 patients with DNA aneuploidy, quantitatively concordant karyotype abnormalities were observed in almost 40% of patients; the discrepancy between DNA content and chromosome number in the remaining patients may reflect differences in the cell cycle position of target cells in G1/0 phase or mitosis, respectively. Cytogenetics affected treatment outcome in acute myelogenous leukemia (AML) with more favorable short- and long-term prognosis among patients with translocations compared with those with numeric abnormalities. The presence of an abnormal DNA stem line, among AML patients with translocations, identified a favorable subgroup with significantly longer remission duration and survival (25 and 26 months versus 18 and 13 months, respectively). In addition, the prognostic implications of DNA aneuploidy in AML were age-dependent, in that favorable effects among patients with translocations and unfavorable effects among those with numeric abnormalities or diploid karyotypes were most obvious in young and not in older patients (greater than or equal to 40 years). In adults with ALL, DNA aneuploidy was associated with shorter survival (15 versus 39 months in the diploid group), an observation that is distinctly at variance with recent findings in childhood ALL. Our results indicated that DNA flow cytometry was complementary to standard cytogenetics for the detection of genomic abnormalities; and DNA aneuploidy emerged, like in children but not in adults with ALL, as a new favorable prognostic feature in a subgroup of adults with AML, the biologic basis of which remains to be determined.     

Acoustic radiation force in vivo: a mechanism to assist targeting of microbubbles

The goal of targeted imaging is to produce an enhanced view of physiological processes or pathological tissue components. Contrast agents may improve the specificity of imaging modalities through selective targeting, and this may be particularly significant when using ultrasound (US) to image inflammatory processes or thrombi. One means of selective targeting involves the attachment of contrast agents to the desired site with the use of a specific binding mechanism. Because molecular binding mechanisms are effective over distances on the order of nanometers, targeting effectiveness would be greatly increased if the agent is initially concentrated in a particular region, and if the velocity of the agent is decreased as it passes the potential binding site. Ultrasonic transmission produces a primary radiation force that can manipulate microbubbles with each acoustic pulse. Observations demonstrate that primary radiation force can displace US contrast agents from the center of the streamline to the wall of a 200-microm cellulose vessel in vitro. Here, the effects of radiation force on contrast agents in vivo are presented for the first time. Experimental results demonstrate that radiation force can displace a contrast agent to the wall of a 50-microm blood vessel in the mouse cremaster muscle, can significantly reduce the velocity of flowing contrast agents, and can produce a reversible aggregation. Acoustic radiation force presents a means to localize and concentrate contrast agents near a vessel wall, which may assist the delivery of targeted agents.     

‘Hints’ in the horn: diagnostic clues in the stratum corneum

The stratum corneum or horny layer is the uppermost layer of the epidermis, and is mainly responsible for the skin's barrier function. In spite of its complexity at the ultrastructural and molecular level, the features accessible to visualization on conventional histology are relatively limited. Nevertheless, knowledge of subtle clues that one may observe in the stratum corneum can prove useful in a wide range of situations in dermatopathology. We herein review a selection of common and rare entities in which the horny layer may reveal significantly important hints for the diagnosis. These clues include parakeratosis and its different patterns (focal, confluent, alternating, associated with spongiosis, epidermal hyperplasia or lichenoid changes), subcorneal acantholysis, infectious organisms in the stratum corneum (including fungal, bacterial and parasitic), thickening or thinning of the stratum corneum and the presence of different kinds of pigment. Even when normal, the horny layer may prove to be useful when seen in association with severe epidermal damage, a combination of features testifying to the acute nature of the underlying pathological process.     

Levels of Aflatoxin M1 in Breast Milk of Lactating Mothers in Monterrey,Mexico: Exposure and Health Risk Assessment of Newborns

The present study aimed to determine the presence of the aflatoxin M1 (AFM1) in breast milk samples from 123 nursing women and the degree of exposure of infants to this toxin, in the metropolitan area of Monterrey, Nuevo Leon state (northeast Mexico). Upon analysis, 100% of the samples were found to be contaminated with the toxin at an average concentration of 17.04 ng/L, with a range of 5.00 to 66.23 ng/L. A total of 13.01% of the breast milk samples exceeded the regulatory limit of 25 ng/L for AFM1 concentration, set by the European Union. The estimated daily intake for AFM1 and the carcinogenic risk index were also determined in the 0- to 6-, 7- to 12-, 13- to 24-, and 25- to 36-month-old age groups. The AFM1 intake through breast milk ranged from 1.09 to 20.17 ng/kg weight/day, and was higher than the tolerable daily intake, indicating a carcinogenic risk for infants in the age groups of 0- to 24-months old. This evidence demonstrates a susceptibility of breast milk to AFM1 contamination that may suggest a carcinogenic risk for the breastfed infants in Monterrey city, Nuevo Leon state, and the need to control the presence of aflatoxins in foods eaten by nursing mothers.     

Sezary syndrome cells unlike normal circulating T lymphocytes fail to migrate following engagement of NT1 receptor

Circulating malignant Sezary cells are a clonal proliferation of CD4+CD45RO+ T lymphocytes primarily involving the skin. To study the biology of these malignant T lymphocytes, we tested their ability to migrate in chemotaxis assays. Previously, we had shown that the neuropeptide neurotensin (NT) binds to freshly isolated Sezary malignant cells and induces through NT1 receptors the cell migration of the cutaneous T cell lymphoma cell line Cou-L. Here, we report that peripheral blood Sezary cells as well as the Sezary cell line Pno fail to migrate in response to neurotensin although they are capable of migrating to the chemokine stromal-cell-derived factor 1 alpha. This is in contrast with normal circulating CD4+ or CD8+ lymphocytes, which respond to both types of chemoattractants except after ex vivo short-time anti-CD3 monoclonal antibody activation, which abrogates the neurotensin-induced lymphocyte migration. Furthermore, we demonstrate that neurotensin-responsive T lymphocytes express the functional NT1 receptor responsible for chemotaxis. In these cells, but not in Sezary cells, neurotensin induces recruitment of phosphatidylinositol-3 kinase, and redistribution of phosphorylated cytoplasmic tyrosine kinase focal adhesion kinase and filamentous actin. Taken together, these results, which show functional distinctions between normal circulating lymphocytes and Sezary syndrome cells, contribute to further understanding of the physiopathology of these atypical cells.