Chemokine receptors that mediate B cell homing to secondary lymphoid tissues are highly expressed in B cell chronic lymphocytic leukemia and non-Hodgkin lymphomas with widespread nodular dissemination

B cell neoplasms present heterogeneous patterns of lymphoid organ involvement, which may be a result of the differential expression of chemokine receptors. We found that chemokine receptor (CCR)7, CXC chemokine receptor (CXCR)4, or CXCR5, the main chemokine receptors that mediate B cell entry into secondary lymphoid tissues and their homing to T cell and B cell zones therein, were highly expressed in B malignancies with widespread involvement of lymph nodes. Conversely, those pathologies with little or no nodular dissemination showed no expression to very low levels of CCR7 and CXCR5 and low to moderate levels of CXCR4. These findings provide evidence for the role of CCR7, CXCR4, and CXCR5 in determining the pattern of lymphoid organ involvement of B tumors. Functional studies were performed on B malignancies expressing different levels of CCR7, CXCR5, and CXCR4. Multiple myeloma (MM) cells did not express CCR7 nor CXCR5 and did not migrate in response to their ligands; a moderate expression of CXCR4 on MM cells was accompanied by a migratory response to its ligand, CXCL12. By contrast, cells from B cell chronic lymphocytic leukemia (B-CLL) expressed the highest levels of these chemokine receptors and efficiently migrated in response to all ligands of CCR7, CXCR4, and CXCR5. In addition, the migration index of B-CLL cells in response to both of the CCR7 ligands correlated with the presence of clinical lymphadenopathy, thus indicating that the high expression of functional chemokine receptors justifies the widespread character of B-CLL, representing a clinical target for the control of tumor cell dissemination.     

Genomic structure and evolution of the ancestral chromosome fusion site in 2q13-2q14.1 and paralogous regions on other human chromosomes

Human chromosome 2 was formed by the head-to-head fusion of two ancestral chromosomes that remained separate in other primates. Sequences that once resided near the ends of the ancestral chromosomes are now interstitially located in 2q13-2q14.1. Portions of these sequences had duplicated to other locations prior to the fusion. Here we present analyses of the genomic structure and evolutionary history of >600 kb surrounding the fusion site and closely related sequences on other human chromosomes. Sequence blocks that closely flank the inverted arrays of degenerate telomere repeats marking the fusion site are duplicated at many, primarily subtelomeric, locations. In addition, large portions of a 168-kb centromere-proximal block are duplicated at 9pter, 9p11.2, and 9q13, with 98%-99% average sequence identity. A 67-kb block on the distal side of the fusion site is highly homologous to sequences at 22qter. A third ~100-kb segment is 96% identical to a region in 2q11.2. By integrating data on the extent and similarity of these paralogous blocks, including the presence of phylogenetically informative repetitive elements, with observations of their chromosomal distribution in nonhuman primates, we infer the order of the duplications that led to their current arrangement. Several of these duplicated blocks may be associated with breakpoints of inversions that occurred during primate evolution and of recurrent chromosome rearrangements in humans.     

Cytotoxic molecule expression and epithelial cell apoptosis in oral and cutaneous lichen planus

We evaluated the expression of T cell-restricted intracellular antigen (Tia-1), granzyme B, and perforin by lymphocytes and the degree of epithelial apoptosis in oral and cutaneous lichen planus (LP) in 51 untreated cases, including 27 oral LP (OLP) and 24 cutaneous LP (CLP) cases. The number of total dermal-positive lymphocytes in OLP and CLP was similar, indicating similar activity of the inflammatory process. Intraepithelial Tia-1-positive, perforin-positive, and granzyme B-positive lymphoid cells were more numerous in OLP than in CLP (P < .05). The epithelial cell apoptotic index (AI) was increased significantly in OLP (P < .05), particularly in erosive-atrophic variants. A linear correlation between AI and the mean +/- SEM number of intraepithelial and dermal perforin+ cells (6.85 +/- 2.44 and 27.48 +/- 10.19, respectively), per 10 high-power fields for OLP and for CLP (1.17 +/- 0.88 and 10.42 +/- 5.74, respectively), was found (intraepithelial, r = 0.50; dermal, r = 0.51; P < .01). These data suggest a pivotal role for perforin in triggering epithelial cell apoptosis. The differences of infiltrating cytotoxic cells and related AI observed in OLP and CLP are in keeping with the clinical behaviors that distinguish these LP variants.     

Neural control of fast-regular saccades and antisaccades: an investigation using positron emission tomography

 Regional cerebral blood flow changes related to the performance of two oculomotor tasks and a central fixation task were compared in ten healthy human subjects. The tasks were: (a) performance of fast-regular saccades; (b) performance of voluntary antisaccades away from a peripheral cue; (c) passive maintenance of central visual fixation in the presence of irrelevant peripheral stimulation. The saccadic task was associated with a relative increase in activity in a number of occipitotemporal areas. Compared with both the fixation and the saccadic task, the performance of antisaccades activated a set of areas including: the superior and inferior parietal lobules, the precentral and prefrontal cortex, the cingulate cortex, and the supplementary motor area. The results of the present study suggest that: (a) compared with self-determined saccadic responses the performance of fast regular, reflexive saccades produces a limited activation of the frontal eye fields; (b) in the antisaccadic task the inferior parietal lobes subserve operations of sensory-motor integration dealing with attentional disengagement from the initial peripheral cue (appearing at an invalid spatial location) and with the recomputation of the antisaccadic vector on the basis of the wrong (e.g., spatially opposite) information provided by the same cue. Received: 20 May 1996 / Accepted: 28 January 1997     

HIV env glycoprotein shares a cross-reacting epitope with a surface protein present on activated human monocytes and involved in antigen presentation

A serological cross-reactivity between env gp120 glycoprotein of the human immunodeficiency virus (HIV) and a human cellular surface protein has been defined by a monoclonal antibody (M38) raised against HIV. The cellular antigen is a protein of ca. 80 kDa expressed on a small fraction of mononuclear cells in peripheral blood and in lymph nodes. The protein behaves as an activation antigen of the monocytic lineage since it is expressed by monocytes in plastic-adherent culture conditions and by interferon-gamma-treated monocytes and pro-monocytic U937 cells. The protein is involved in antigen presentation since the antibody efficiently inhibits the proliferation of responsive lymphocytes in autologous tetanus toxoid presentation assays. In the T lymphoblastoid line H9, the protein is present in very small amounts, is not induced by interferon-gamma and increases after HIV infection. Sera from lymphoadenopathy syndrome and acquired immunodeficiency syndrome (AIDS) patients fail to detect the cellular protein, although containing antibodies reacting with gp120. We propose that both viral and cellular structures recognized by the monoclonal antibody (mAb) are involved in interactions with CD4 molecules of T helper lymphocytes and that such molecular mimicry might be relevant in the pathology of HIV infection. This view is supported by the finding that BL/10T4, a CD4-specific mAb, binds to M38 neutralizing its interactions with HIV and with monocytes. mAb M38 thus behaves as the internal image of CD4. This single property would explain all its diverse binding characteristics.     

Cutaneous papillary squamous cell carcinoma. Report of three new cases and review of the literature

Squamous cell carcinoma is one of the most common malignant cutaneous tumors. Several histological variants have been described; the papillary subtype is one of the most infrequent, with only four cases having being reported previously. We report three new cases of this unusual variant of cutaneous squamous cell carcinoma, review the literature and consider the main differential diagnoses. Polymerase chain reaction performed in our three cases did not demonstrate human papilloma virus infection.     

Power and peak blood lactate at 5050 m with 10 and 30 s ‘all out’ cycling

Anecdotal observations suggest that the reduction in peak lactate accumulation in blood ([La]_{b peak}) after exhausting exercise, in chronic hypoxia vs. normoxia, may be related to the duration of the exercise protocol, being less pronounced after short supramaximal exercise than after incremental exercise (IE) lasting several minutes. To test this hypothesis, six healthy male Caucasians (age 36.8 ± 7.3, x¯ ± SD) underwent three exercise protocols on a cycle ergometer, at sea level (SL) and after 21 ± 10 days at 5050 m altitude (ALT): (1) 10 s, (2) 30 s ‘all out’ exercise and (3) IE leading to exhaustion in ～20–25 min. ‘Average’ power output (p¯) was calculated for 10 or 30 s ‘all out’; maximal power output (P_max) was determined for IE. Lactate concentration in arterialized capillary blood ([La]_b) was measured at rest and at different times during recovery; the highest [La]_b during recovery was taken as [La]_{b peak}. No significant differences in p¯ were observed between SL and ALT, for either 10 or 30 s ‘all out’ exercise; P_max during IE was significantly lower at ALT than at SL. [La]_{b peak} after 10 s ‘all out’ was unaffected by chronic hypoxia (7.0 ± 0.9 at ALT vs. 6.3 ± 1.8 mmol L^–1 at SL). After 30 s ‘all out’ the [La]_{b peak} decrease, at ALT (10.6 ± 0.6 mmol L^–1) vs. SL (12.9 ± 1.4 mmol L^–1), was only ～50% of that observed for IE (6.7 ± 1.6 mmol L^–1 vs. 11.3 ± 2.8 mmol L^–1). Muscle power output and blood lactate accumulation during short supramaximal exercise are substantially unaffected by chronic hypoxia.     

Processing of influenza HA protein in MDCK cells: Components with different mobilities in polyacrylamide gel electrophoresis and their precursor-product relationships

Summary In influenza virus-infected MDCK cells labelled with¹⁴C-chlorella hydrolysate or³⁵S-methionine a virus-specific protein component is revealed migrating slightly faster than HA protein in polyacrylamide gel electrophoresis. Under chase conditions the component disappears either completely or partially, with a concomitant intensification of the HA band. The rate and extent of this transition are strain-dependent. Both the HA band and the faster moving component are not revealed if the cells are labelled in the presence of 20mM of D-glucosamine. In primary cell cultures of chick embryos a single HA band with a mobility similar to that of the faster moving component in MDCK cells has been observed. It is suggested that the transition of the label from the faster moving component to the HA band reflects the final step of HA processing specific for MDCK cells.With 7 Figures     

Antibiotic resistance in exopolysaccharide-forming Staphylococcus epidermidis clinical isolates from orthopaedic implant infections

The opportunistic pathogen Staphylococcus epidermidis is able to produce biofilm and to frequently cause implant infections. In recent years, it has also exhibited an increasing antimicrobial drug resistance. Here, the resistance to a panel of 16 different antibiotics in 342 clinical strains of S. epidermidis from orthopaedic implant infections has been investigated. The isolates were pheno- and genotyped for extracellular polysaccharide production, relevant to staphylococcal biofilm formation, in order to ascertain possible associations with antibiotic resistance. Approximately 10% of the isolates were found to be sensitive to all screened antibiotics. In all, 37-38% were resistant to beta-lactams such as oxacillin and imipenem, while the resistance to penicillin, ampicillin, cefazolin, cefamandole, was consistently observed in over 80% of the strains. Erythromycin- and clindamycin- resistant strains were approximately 41% and 16%, respectively. Of the isolates, 10% was resistant to chloramphenicol, 23% to sulfamethoxazole and 26% to ciprofloxacin. Resistance to vancomycin was never observed. Interestingly, exopolysaccharide-producing strains exhibited a significantly higher prevalence in the resistance to the four aminoglycosides (gentamicin, amikacin, netilmicin, tobramycin), to sulfamethoxazole and to ciprofloxacin with respect to non-producing isolates. Moreover, multiple resistance to antibiotics was more frequent among exopolysaccharide-forming strains.     

Molecular detection of Histoplasma capsulatum var. capsulatum in human clinical samples

We developed a seminested PCR for the diagnosis of histoplasmosis that amplifies a portion of the Histoplasma capsulatum H antigen gene. This assay is highly sensitive and specific, being able to detect genomic material corresponding to less than 10 yeast cells without cross-reaction against other bacterial or fungal pathogens.