Trisomy 3 in marginal zone B-cell lymphoma: a study based on cytogenetic analysis and fluorescence in situ hybridization

Trisomy 3 represents the most frequent and consistent chromosomal abnormality characterizing the recently defined entity marginal zone B-cell lymphoma (MZBCL). By cytogenetic analysis and/or fluorescence in situ hybridization (FISH) on interphase nuclei we found an increased copy number of chromosome 3 in 22/36 (61%) successfully analysed cases, including 8/12 cases with extranodal MZBCL, 8/13 cases with nodal MZBCL, and 6/11 patients with splenic MZBCL. Sensitivity of interphase cytogenetics was somewhat higher than that of conventional cytogenetic investigation. Structural chromosomal changes involving at least one chromosome 3 were seen in 11/20 cases with an increased copy number of chromosome 3: +del(3)(p13) was demonstrated in three cases, and was the sole chromosomal abnormality in one of them; +i(3)(q10) was seen in two other patients; and rearrangements involving various breakpoints on the long arm of chromosome 3 were found in the remaining cases. FISH on metaphase spreads confirmed these structural abnormalities and additionally showed two unexpected translocations involving chromosome 3. We conclude that: (1) trisomy 3 occurs in a high proportion of extranodal, nodal and splenic MZBCL; (2) FISH on interphase nuclei is an additional and sensitive tool in detecting an increased copy number of chromosome 3 in MZBCL; (3) additional structural abnormalities involving the long arm of chromosome 3 are frequent but non-recurrent and are perhaps secondary changes; and (4) abnormalities such as +del(3)(p13) and +i(3)(q10) suggest that genes located on the long arm of chromosome 3 are of particular importance in the pathogenesis of MZBCL.     

NUTRITIONAL STATUS IN CHRONICALLY ALCOHOLIC MEN FROM THE MIDDLE SOCIOECONOMIC CLASS AND ITS RELATION TO ETHANOL INTAKE

Two-hundred and fifty chronically alcoholic men (mean age, 41± 11 years) entering an alcoholism treatment programwere studied. Detailed clinical history, nutritional assessmentand measurement of muscle strength by electronic myometer wereperformed in each case. In addition, hepatic ultrasonographyand liver biopsy, echocardiography and radionuclide cardiacscanning, and electrophysiological testing of peripheral nerveswere performed when there was clinical evidence of liver disease,cardiomyopathy or neuropathy, respectively. Alcoholic cirrhosiswas diagnosed in 20 cases, skeletal myopathy in 117, dilatedcardiomyopathy in 20 and peripheral neuropathy in 41 cases.No patients with chronic myopathy or cardiomyopathy showed eitherclinical or laboratory evidence of malnutrition. Patients withcirrhosis showed a significantly lower lean body mass than controls(P = 0.03) and significantly lower nutritional protein levelsthan those alcoholics without cirrhosis. Alcoholics with peripheralneuropathy had significantly lower anthropometric parametersand nutrition protein levels than their counter parts (P <0.001). However, in the multivariate analysis, the only independentfactor for developing these complications of alcoholism wasthe total lifetime dose of ethanol (P < 0.001). We concludethat alcohol-related diseases are common in asymptomatic alcoholicmen and these diseases appear to be due to an accumulative toxiceffect of ethanol. Age and nutritional status do not seem toplay a part in the development of such diseases     

Ostium Primum Atrial Septal Defect Associated with Obstructive Hypertrophic Cardiomyopathy

A 48-year-old white male was referred for cardiac catheterization following a bout of near syncope and severe angina. He was diagnosed to have obstructive hypertrophic cardiomyopathy by transthoracic echocardiography (TTE). Right bundle branch block and plethoric chest X ray suggested shunt physiology, which was confirmed on transesophageal echocardiography and angiocardiography to be a primum type of atrial septal defect (primum ASD) with cleft mitral leaflet. He underwent septal myomectomy and patching of the ASD. Surgical pathological specimen revealed enlarged nuclei and myocardial disarray consistent with congenital hypertrophic cardiomyopathy. (ECHOCARDIOGRAPHY, Volume 8, May 1991)     

Dissociation of Autoaggression and Self-Superantigen Reactivity

Self-superantigens have been described as products of endogenous retroviruses of the mouse ('minor lymphocyte stimulating loci') that are capable of interacting without prior processing with conserved domains of TCR Vβ chains, causing the activation and deletion of most T cells expressing products of determined Vβ gene families [1–4], The fact that superanti-gens activate a far higher percentage of T cells (1–20%) than conventional, peptidic antigens (< 0.1 %) provides the methodological advantage that the degree of clonal deletion may be measured by the analysis of the TCR repertoire using appropriate anti-Vβ antibodies. Although much information on the spatio-temporal organization of repertoire-purging has been gathered by virtue of self-superantigens, serious doubts exist as to the possibility that such structures serve as pathogenetically relevant autoantigens. Thus, certain inbred mice spontaneously develop autoimmune diseases, although they bear T-cell repertoires that appear to be purged from self-superantigen-reactive Vβ products. In addition, therapeutic interventions targeted to Vβ gene products that are not specific for self-superantigens are successful in preventing disease development. The lack of correlation between superantigen-related Vβ deletions and autoimmune disease development is substantiated in further models of murine autoimmunity. Based on these observations, we formulate the hypothesis that self-superantigen-reactive T cells are not involved in the development of autoimmune diseases.     

CHLORACNE IN THE 1990s

Background. Chloracne is a disease associated with toxicity of halogenated compounds used in some industrial processes. A patient affected by chloracne led us to study a total of nine cases from a single factory. Methods. We studied the clinical features of nine patients exposed chronically to chlorobenzenes. On all of them blood samples were drawn and biopsies of affected skin and liver were taken. Their work environment was visited and studied. Results. All nine patients were men and had polymorphic skin lesions, characterized mainly by comedones and cysts. They had chronic conjunctivitis and seven had cysts in the Meibomian glands. All of them had polyneuropathy and liver damage and seven had hypertriglyceridemia. Compounds known to cause chloracne were found in exceedingly high concentrations in the water used in the workplace. Conclusions. Every patient exposed to halogenated compounds with the cutaneous manifestations of chloracne should be carefully investigated for systemic complications (such as ophthalmic, neuropathic, hepatic, and lipoprotein abnormalities).