Prominent intrasinusoidal infiltration of the bone marrow by mantle cell lymphoma

Intrasinusoidal infiltration of bone marrow (BM) may accompany several malignant lymphoproliferative disorders. In small B-cell lymphomas, this pattern is considered specific for splenic marginal zone lymphoma (SMZL) when exclusive or prominent, although it may occur in other subtypes of non-Hodgkin's lymphomas (NHLs) as a minor feature. Here we report 2 cases of mantle cell lymphoma (MCL) with a prominent intrasinusoidal BM infiltration pattern. Both patients presented with massive splenomegaly and peripheral blood involvement characterized by markedly atypical lymphocytes, but no lymphadenopathy. The cytological features and the phenotype of the lymphoma cells were diagnostic of MCL. The malignant B cells showed coexpression of B-cell markers (CD20+ and CD79a+), CD5 antigen, and cyclin D1 by immunohistochemistry. We discuss the specificity of an intrasinusoidal growth pattern in the bone marrow, emphasizing the importance of using a broader immunohistochemical panel in the differential diagnosis of intrasinusoidal BM infiltration by NHL.     

A double-blind, placebo-controlled trial by the sublingual route of immunotherapy with a standardized grass pollen extract

Fifty-eight patients with well-documented history of seasonal rhinoconjunctivitis caused by grass pollens were allocated randomly on a double-blind basis to receive either sublingual therapy with a solution of purified, standardized allergen preparation (Stallergenes) or a matched placebo for 17 weeks. The assessment of the effect of oral immunotherapy, done with drops of five-grass allergen extract, was on the clinical symptoms and on the medication score of the authorized rescue treatments. The actively treated patients had significantly (P<0.05 to P<0.01) fewer symptoms of rhinitis (sneezing and rhinorrhea) and of conjunctivitis (redness and tears) during the pollen season than the placebo group. Consumption of nasal solution of sodium cromoglycate and of betamethasone and dexchlorpheniramine was significantly less in the desensitized group (P<0.01). Side-effects were negligible. This study concludes that perlingual immunotherapy with grass pollen extract in grass-pollen-sensitive seasonal hay fever and conjunctivitis patients is effective, easy to perform, inexpensive, and safe.     

Seropositivity for and Intestinal Colonization with Entamoeba histolytica and Entamoeba dispar in Individuals in Northeastern Brazil

In a slum community in northeastern Brazil 20% of a sample population was colonized with Entamoeba histolytica or Entamoeba dispar and 10.6% was colonized with E. histolytica alone. No correlation between seropositivity for anti-GalNAc lectin antibody and colonization was found. These results suggest that colonization does not necessarily produce immunity to reinfection.     

Effects of Orally Administered Epidermal Growth Factor on Enteropathogenic Escherichia coli Infection in Rabbits

The increased intestinal absorption induced by epidermal growth factor (EGF) is associated with diffuse lengthening of brush border microvilli. The aim of this study was to examine the in vivo effects of oral administration of EGF during infection with enteropathogenic Escherichia coli. New Zealand White rabbits (4 weeks old) received orogastric EGF daily starting 3 days prior to infection with enteropathogenic E. coli RDEC-1 and were compared with sham-treated infected animals and uninfected controls. Weight gain, food intake, fecal E. coli, and stool consistency were assessed daily. On day 10, segments of jejunum, ileum, proximal, and distal colon were assessed for gram-negative bacterial colonization, disaccharidase activities, and epithelial ultrastructure. Effects of EGF on E. coli RDEC-1 proliferation were studied in vitro. E. coli RDEC-1 caused diarrhea and reduced weight gain. Seven days postinfection, the small and large intestines were colonized with numerous bacteria, brush border microvilli were disrupted, and maltase and sucrase activities were significantly reduced in the jejunum. Daily treatment with EGF prevented the occurrence of diarrhea and reduction of weight gain. These effects were associated with significant inhibition of E. coli colonization in the small and large intestine, improved jejunal maltase and sucrase activities and reduced microvillous injury. EGF did not affect the proliferation of E. coli in vitro. The findings suggest that EGF protects the gastrointestinal tract against colonization by enteropathogenic E. coli.     

Nano-C60 cytotoxicity is due to lipid peroxidation

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C₆₀, a fullerene aggregate that readily forms when pristine C₆₀ is added to water. Nano-C₆₀ was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses 50 ppb (LC₅₀=2–50 ppb, depending on cell type) after 48 h exposure. This water-soluble nano-C₆₀ colloidal suspension disrupts normal cellular function through lipid peroxidation; reactive oxygen species are responsible for the membrane damage. Cellular viability was determined through live/dead staining and LDH release. DNA concentration and mitochondrial activity were not affected by the nano-C₆₀ inoculations to cells in culture. The integrity of cellular membrane was examined by monitoring the peroxy-radicals on the lipid bilayer. Subsequently, glutathione production was measured to assess the cell's reaction to membrane oxidation. The damage to cell membranes was observed both with chemical assays, and confirmed physically by visualizing membrane permeability with high molecular weight dyes. With the addition of an antioxidant, l-ascorbic acid, the oxidative damage and resultant toxicity of nano-C₆₀ was completely prevented.     

Memory T lymphocytes generated by Mycobacterium bovis BCG vaccination reside within a CD4 CD44lo CD62 ligand(hi) population

In the lungs of mice vaccinated with Mycobacterium bovis BCG, there was an accumulation of CD4 cells expressing the activated effector phenotype CD44hi CD62 ligandlo) (CD62Llo) which were capable of secreting gamma interferon. Upon cell transfer, however, cells expressing a resting/na?ve phenotype (CD44lo CD62Lhi) were capable of protecting the recipients from a virulent challenge infection, suggesting the emergence of T-cell memory from within this subset.     

Chromosome neighborhood composition determines translocation outcomes after exposure to high-dose radiation in primary cells

Radiation exposure is an occupational hazard for military personnel, some health care professionals, airport security screeners, and medical patients, with some individuals at risk for acute, high-dose exposures. Therefore, the biological effects of radiation, especially the potential for chromosome damage, are major occupational and health concerns. However, the biophysical mechanisms of chromosome instability subsequent to radiation-induced DNA damage are poorly understood. It is clear that interphase chromosomes occupy discrete structural and functional subnuclear domains, termed chromosome territories (CT), which may be organized into ‘neighborhoods’ comprising groups of specific CTs. We directly evaluated the relationship between chromosome positioning, neighborhood composition, and translocation partner choice in primary lymphocytes, using a cell-based system in which we could induce multiple, concentrated DNA breaks via high-dose irradiation. We critically evaluated mis-rejoining profiles and tested whether breaks occurring nearby were more likely to fuse than breaks occurring at a distance. We show that CT neighborhoods comprise heterologous chromosomes, within which inter-CT distances directly relate to translocation partner choice. These findings demonstrate that interphase chromosome arrangement is a principal factor in genomic instability outcomes in primary lymphocytes, providing a structural context for understanding the biological effects of radiation exposure, and the molecular etiology of tumor-specific translocation patterns.     

Juvenile rhesus monkeys have more colonic granulomas than adults after primary infection with<Emphasis Type="Italic"> Schistosoma mansoni</Emphasis>

Adults and children have differences in their susceptibility to schistosomiasis. Whether this age-dependent innate susceptibility influences parasite-caused granulomogenesis is difficult to assess in humans. Therefore, we exposed juvenile and adult female rhesus monkeys to primary infection with Schistosoma mansoni. Hepatic and intestinal granuloma formation was observed in both pre-pubescent and adult monkeys. Two distinct stages of granulomas were discerned, the exudative and the productive stage. In the intestine, more granulomas were generated in the colon than in the ileum. In contrast to the adult animals, the juvenile rhesus monkeys had higher numbers of colonic granulomas, these higher numbers being predominantly of the more advanced productive stage. Juvenile animals had a statistically non-significant increased worm burden. These results suggest that juvenile rhesus monkeys have a significantly more intense and advanced colonic response towards entrapped S. mansoni eggs after primary schistosome infections and, thereby, are more susceptible to parasite infection.Research protocols involving non-human primates received ethical clearance by the Institutional Animal Care and Use Committee of the Biomedical Primate Research Centre (Rijswijk, The Netherlands), according to Dutch Law.