Spheroids in radiobiology and photodynamic therapy

Spheroids are tridimensional aggregates of tumor cells coming from one or several cell clones. This model, which mimics the micro-tumors structure and some of their properties, shows oxygen, pH and nutrient gradients inducing a necrotic area in the center of the spheroid. Analysis of spheroids, cultured under static or stirred conditions, can be performed on whole spheroids or dissociated spheroids. The spheroids sensitivity to ionizing radiation and photodynamic therapy can be altered by oxygen status, damage repair, intercellular commmunications and apoptosis induction, as in experimental tumor models. In radiobiology, the similarity of radiation response between spheroids and tumor xenograft bearing mice makes the spheroids to be a good alternative model to in vivo irradiation studies. In photodynamic therapy, spheroids lead to a better understanding of the own tumor response without interactions with vascular system. Finally, despite the quality of spheroid model, only the use of new technology for analysis of spheroid populations will help to increase their experimental use, particularly in preclinical oncology.     

Elevated NAD(P) glycohydrolase activity: a possible enzymatic marker for malignancy in Burkitt's lymphoma cells

A comparative analysis of enzymatic activities has been performed on 47 human continuous lymphoid lines: 22 tumors derived from Burkitt's lymphoma lines, 6 other lymphomatous long-term cultures, and 19 nonmalignant ties determined on the cell extracts. 4 showed no significant differences between the various lines. They included adenosine diphosphoribose incorporation, glucose-6-phosphate dehydrogenase, cyclic-AMP phosphodiesterase, and glutathione reductase. However, striking differences of activity were found for the enzyme, NAD(P) glycohydrolase (EC 3.2.2.6). Activity levels were, as a mean, four times higher in Burkitt's lymphoma-derived cell lines than in nonmalignant control lines, and the difference was highly significant (p less than 0.02). All Burkitt cell lines containing translocations of chromosome 8 with either chromosomes 2, 14 or 22 showed an increased activity. The specificity and significance of this possible enzymatic marker of Burkitt's lymphoma cells is discussed.     

The response of red cell hexose monophosphate shunt after sulfhydryl inhibition

In this investigation, we studied the importance of cellular glutathione (GSH) in the hexose monophosphate shunt (HMPS) activity of unstimulated human erythrocytes and the mechanism by which pyruvate stimulates the HMPS. The rate of HMPS activity was measured by the production of radioactive CO2 from 14C-1-glucose or 14C-1-ribose using a vibrating reed electrometer and ionization chamber. HMPS activity was not significantly impaired by N-ethylmaleimide (NEM) in concentrations which bound all red cell GSH. Red cells incubated under carbon monoxide (CO), an experimental condition which eliminates peroxide production, still had HMPS activity which was 44% of the value under air. Pyruvate stimulation of the HMPS was unaffected by doses of NEM which bound all cellular GSH or by incubation under CO. These data indicated that pyruvate stimulation of the HMPS occurs by pathways which do not involve peroxide formation, GSH, or oxygen. This study indicates that sulfhydryl blockade of GSH does not necessarily inhibit HMPS activity and that HMPS activity in red cells may respond to reactions not linked directly to glutathione reduction.     

Interstitial lung fibrosis and rheumatic disorders in patients with hepatitis C virus infection

A possible aetiopathogenetic role of hepatitis C virus (HCV) has been reported in various immune-mediated disorders, such as mixed cryoglobulinaemia, which may be complicated by interstitial lung involvement; moreover, different viruses, including HCV, have been correlated with idiopathic pulmonary fibrosis. Here, a cohort of eight HCV-positive patients (M/F = 4/4, mean age 61 +/- 8 S.D. yr) with interstitial lung fibrosis and a variable number of rheumatic disorders are described. Interstitial lung involvement appeared medially 4.5 +/- 3.2 S.D. yr after the clinical onset of chronic hepatitis. During the clinical follow-up, some rheumatic symptoms were also recorded: articular involvement (four patients): mild sicca syndrome (one patient); severe polymyositis and cranial neuropathy (one patient); serum cryoglobulins and/or autoantibodies (eight patients). In all patients, a moderate (four patients) or severe (four patients) lung fibrosis was evaluated by means of high-resolution computed tomography. The presence of parenchymal radiotracer uptake on 67Ga scan (7/7 patients) and increased percentages of neutrophils (4/4 patients) and lymphocytes (2/4) at bronchoalveolar lavage suggested an active lung involvement. Different degrees of reduction of single breath diffusing capacity for carbon monoxide (DLco) (mean value 57.6 +/- 15%, range 37- 80) were observed in all cases, while spirometric abnormalities, consistent with a global restrictive pattern, were less frequently found. In all cases, anti-HCV antibodies and HCV viraemia were demonstrated: viral genome was also detected in peripheral lymphocytes from 4/4 subjects and in one case in lung biopsy specimens. A desquamative interstitial pneumonia pattern was demonstrated in two cases by lung biopsy. The present work supports the hypothesis that HCV chronic infection could represent a trigger factor for interstitial lung fibrosis and various rheumatic disorders.      

Prevalence and predictors of Toxoplasma seropositivity in women with and at risk for human immunodeficiency virus infection

We assessed the prevalence and predictors of latent Toxoplasma infection in a large group of human immunodeficiency virus (HIV)-infected and HIV-uninfected at-risk US women. The prevalence of latent Toxoplasma infection was 15% (380 of 2525 persons) and did not differ by HIV infection status. HIV-infected women aged > or =50 years and those born outside of the United States were more likely to have latent Toxoplasma infection, with prevalences of 32% and 41%, respectively.     

Asymmetric polyarthritis as an initial presentation of Rosai‐Dorfman disease

Rosai‐Dorfman disease (RDD) is a rare benign reactive lymphoproliferative disorder characterised by a histopathological pattern with sinus histiocytosis and hemophagocytosis. It usually presents with fever, elevated erythrocyte sedimentation rate, cervical lymphadenopathy, other lymph node and extra‐nodal site involvement. We present the case of a 25‐year‐old female patient with polyarthritis mimicking rheumatoid arthritis (RA). When the para‐aortic lymph node was biopsied, it showed extensive histiocytic proliferation; some clusters of plasma cells, lymphocytes and rare multinucleated cells were seen, suggesting a diagnosis of RDD. There is nothing in the literature regarding the polyarthritic presentation of the disease. To the best of our knowledge, our patient is the first case of RDD presenting with a clinical picture mimicking atypical seronegative RA.