Patterns of cytokine expression in AIDS-related non-Hodgkin's lymphoma

The pathogenesis of AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) involves accumulation of genetic lesions, stimulation and selection by antigen, as well as infection by viruses. Deregulation of cytokine loops has also been proposed to contribute to AIDS-NHL development, although data are available only for a limited number of cytokines. In this study we have utilized a panel of AIDS-NHL cell lines to investigate in detail the pattern of tumour expression and production of a wide spectrum of cytokines. The cytokines investigated included interleukin (IL)-1α, IL-1β, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, TNFα, TNFβ, IFNγ, TGFβ₂, G-CSF, GM-CSF and SCF. The AIDS-NHL cell lines utilized were representative of both AIDS-related Burkitt lymphoma (AIDS-BL) and AIDS-related body cavity-based lymphoma (AIDS-BCBL). Overall, AIDS-NHL were found to produce IL-6, IL-10 and TNFβ, although with different patterns depending upon the biological features of the tumour. Production of high levels of IL10 preferentially associated with Epstein-Barr virus (EBV) positive AIDS-BL and AIDS-BCBL, although lower levels of the cytokine were also detectable among EBV-negative AIDS-BL. Production of IL-6 was restricted to EBV-positive AIDS-BL and AIDS-BCBL, whereas it was absent among EBV-negative AIDS-BL. Production of TNFβ clustered with AIDS-BL, whereas this was absent among AIDS-BCBL. These results define that the pattern of cytokine expression of AIDS-NHL depends upon the biological features of the tumour and may have implications for the pathogenesis of these disorders.     

Screening a coastal population in Southern Italy: iodine deficiency and prevalence of goitre, nutritional aspects and cardiovascular risk factors

BACKGROUND AND AIM: To evaluate the prevalence of goitre by means of urinary iodine excretion, palpatory and ultrasonographic thyroid examinations in a heterogeneous population living by the sea. METHODS AND RESULTS: We used a special self-administered questionnaire to evaluate thyroid size, iodine intake, eating habits and cardiovascular risk factors in 600 subjects with a mean age of 45 +/- 17 years: 253 men (42.3%) and 347 women (57.7%). Urinary iodine excretion was low (72.1 +/- 15.7 microg/L; median 71.2) and associated with ultrasonographic evidence of an enlarged thyroid (16%) or structural thyroid abnormalities (30%), thus allowing us to define the Salerno Gulf as a mild-moderate area of endemic goitre. All of the subjects ate a Mediterranean diet, with a mean of two portions of fish/week. The cardiovascular risk factors considered were obesity, cigarette smoking, hypertension, hypercholesterolemia, hypertriglyceridemia and diabetes, the prevalences of which were in line with those reported in other studies of similar age-matched populations. CONCLUSIONS: The moderate intake of fish and the consumption of a Mediterranean diet did not prevent goitre. Iodine deficiency and subsequent goitre endemia are also present at sea level, probably because of a diet based on local products grown on soil with a low iodine content or possible seawater, soil and air environmental pollution that may interfere with the availability of iodine. The assessment of iodine deficiency should therefore involve the entire population and not only subjects living far from the sea.     

Course and prognosis of human immunodeficiency virus-associated nephropathy

PURPOSE: Patients infected with the human immunodeficiency virus (HIV) have been described to have an unusual form of renal disease known as HIV-associated nephropathy. This condition is characterized by severe proteinuria, rapid progression to renal insufficiency, and a morphologic pattern of focal segmental glomerulosclerosis (FSGS) on renal biopsy. Despite increasing awareness of this entity, the epidemiology and clinical course of HIV-associated nephropathy are not yet well defined. We therefore decided to study HIV-infected patients with this biopsy-proven pattern of focal sclerosis. PATIENTS AND METHODS: Using life-table analysis, we evaluated the clinical features and course of 26 patients with HIV infection and biopsy-proven FSGS and compared them with those in 24 subjects with HIV infection who had no glomerular disease at autopsy. RESULTS: The group with FSGS had a higher percentage of blacks (96% versus 46%) and intravenous drug abusers (42% versus 17%), and had a higher mean serum creatinine level (5.4 mg/dL versus 1.0 mg/dL) than the group of HIV-infected subjects without glomerular disease. At the time of diagnosis of FSGS, six patients had clinical acquired immunodeficiency syndrome (AIDS), eight had AIDS-related complex (ARC), and 12 patients had no evidence of AIDS or ARC. The progression to end-stage renal disease for all patients was rapid, with a median time to dialysis of 10.9 weeks. Duration of patient survival was dependent upon the stage of HIV infection at the time of diagnosis of renal disease. Patients who presented with AIDS had a median survival of 1.9 months, compared to a median survival of 3.6 months for those with ARC and 9.7 months for initially asymptomatic HIV carriers (p less than 0.05). Fifteen patients either presented with or developed AIDS during the course of the study, and all died as a consequence of their immunodeficiency. Survival curves from the diagnosis of AIDS to death were similar in the group with HIV-associated nephropathy (7.3 weeks) compared to the control AIDS group without renal disease (6.9 weeks). CONCLUSION: Our data indicate that FSGS associated with HIV infection can occur before other manifestations of AIDS, is more common in blacks and in intravenous drug abusers, and is rapidly progressive to uremia. Patient survival is dependent upon the stage of HIV infection. These findings may prove useful in devising more effective strategies for the care of this growing patient population.     

Hepatitis C virus within a malignant lymphoma lesion in the course of type II mixed cryoglobulinemia

Hepatitis C virus (HCV) has been implicated as the major etiologic factor sustaining B-cell clonal expansion in type II mixed cryoglobulinemia (MC). A putative pathogenetic role of HCV in the development of MC-associated B-cell malignancies has also been speculated. We report for the first time the localization of HCV within a parotid non-Hodgkin's lymphoma (NHL) lesion in the course of HCV- related type II essential MC, an important step to implicate any infectious agent in the lymphomagenesis. Plus and minus strand HCV RNA was first demonstrated by polymerase chain reaction on the whole RNA from the lesion. Further immunohistochemical studies localized HCV c22 proteins in the residual ductal or acinar parotid structures, which also abnormally expressed HLA-DR antigens. Weak c22 signals were inconstantly detected in cells strictly confined around the residual epithelium, while all the remaining infiltrating cells in the parotid lesion stained c-22-negative. Staining for c33 and c100 HCV antigens was negative. In situ hybridization (ISH) studies again identified the residual parotid epithelial cells as the site of HCV infection and replication in the NHL lesion. Sialotropic viruses previously involved in lymphoproliferation, ie, Epstein-Barr virus and human herpesvirus-6, were absent in the same tissue lesion. According to the current models of B-cell lymphomagenesis, a role of HCV as an exogenous antigenic stimulus should be considered for NHL development in the present case, whereas malignant B cells do not appear permissive of active HCV replication. Further efforts would be worthwhile to clarify a role of HCV infection in the development of some B-cell malignancies.     

An oligonucleotide microchip for genome-wide microRNA profiling in human and mouse tissues

MicroRNAs (miRNAs) are a class of small noncoding RNA genes recently found to be abnormally expressed in several types of cancer. Here, we describe a recently developed methodology for miRNA gene expression profiling based on the development of a microchip containing oligonucleotides corresponding to 245 miRNAs from human and mouse genomes. We used these microarrays to obtain highly reproducible results that revealed tissue-specific miRNA expression signatures, data that were confirmed by assessment of expression by Northern blots, real-time RT-PCR, and literature search. The microchip oligolibrary can be expanded to include an increasing number of miRNAs discovered in various species and is useful for the analysis of normal and disease states.     

IgG monitoring to identify the risk for development of infection in heart transplant recipients

Infectious complication represents a significant source of morbidity and mortality in heart transplant recipients. To assess humoral immunity markers that can predict the development of infection, 38 consecutive recipients of heart transplants performed at a single center were prospectively studied. Induction therapy included daclizumab. Immunoglobulin (IgG, IgA, IgM) and complement factors (C3, C4, and factor B) were performed by nephelometry in peripheral blood samples obtained before transplantation, and 7 days and 1 month after transplantation. During a mean follow-up of 16.9 months, 13 patients had at least one episode of infection (34.2%). Eight of these were cytomegalovirus (CMV) infections treated with intravenous ganciclovir, 2 were bacterial pneumonia, 1 patient had bacterial septicemia, 1 patient had urinary tract infection, and 1 patient had pulmonary nocardiosis. No significant association was found between infection and age, sex, immunosuppression, CMV serostatus of donor and recipient, or treated rejection episodes. Pre-transplant IgG (below median value=1140 mg/dL; relative risk [RR] 3.69; 95% confidence interval [CI] 1.01-13.54; P=0.04) and post-transplant IgG levels at day 7 (below median value=679 mg/dL; RR 11.21; CI 1.04-89.48; P=0.022) were associated with an increase in the risk for developing infections. Early monitoring of immunoglobulin levels might help to identify the risk for developing infection in heart transplantation.     

Phase Delay of the Rhythm of 6-Sulphatoxy Melatonin Excretion by Artificial Light

The purpose of this study was to investigate the effect of bright artificial light exposure on the rhythms of 6-sulphatoxy melatonin cortisol excretion in urine. Six healthy males were exposed to light (> 3,000 lux) from 1900 to 0200 h (sunset 1928 h) on one occasion. The artificial light delayed the onset of 6-sulphatoxy melatonin excretion. On the next evening the onset of 6-sulphatoxy melatonin excretion in normal light/darkness was delayed by 1 h. The timing of the peak excretion of cortisol was not affected by the light treatment; however, cortisol excretion rate was maintained at a signficantly higher rate in the morning afternoon after the treatment. These results demonstrate the inhibitory action of high intensity light in humans suggest that one 6-h period of extra light in the evening can phase delay the melatonin onset.