Virion-bound ICAM-1 and activated LFA-1: a combination of factors conferring resistance to neutralization by sera from human immunodeficiency virus type 1-infected individuals independently of the disease status and phase

The role of the supplementary interaction between virion-bound host ICAM-1 and LFA-1 on target cells in sensitivity to neutralization of human immunodeficiency virus type 1 (HIV-1) is poorly studied. Serum samples from four long-term nonprogressors (LTNPs) and sequential sera from one progressor were used to assess neutralization sensitivity of isogenic ICAM-1-negative and ICAM-1-bearing HIV-1(NL4-3), a prototype of T-cell-line-adapted viruses. We found that virus neutralization sensitivity to the studied sera is not modified by the additional interaction between virally embedded ICAM-1 and LFA-1 under an inactive state. However, expression on the target cell surface of an activated LFA-1 form renders ICAM-1-bearing virus particles, but not viruses devoid of ICAM-1, more refractory to neutralization by sera from three out of four LTNPs and all sequential sera from the person who has experienced a progression of the HIV-1-associated disease. Although no conclusive correlation could be drawn between virus susceptibility to neutralization and the disease status or stages of HIV-1 infection, these findings demonstrate that other nonspecific virus-cell interactions mediated by virion-anchored host proteins and their normal cognate ligands on target cells represent factors that can affect the mechanism of HIV-1 neutralization.     

The atheroprotective effect of 17beta-estradiol depends on complex interactions in adaptive immunity

Estradiol prevents fatty streak formation in chow-fed atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice. We previously reported that fatty streak development of immunodeficient ApoE(-/-)/recombination activating gene 2 (RAG-2(-/-)) double-deficient mice was insensitive to estradiol. In the present work, we demonstrate that the reconstitution of ApoE(-/-)/RAG-2(-/-) with bone marrow from immunocompetent ApoE(-/-)/RAG-2(+/+) mice restores the protective effect of estradiol on fatty streak constitution. We extended this demonstration to the model of low-density lipoprotein receptor-deficient mice, establishing the obligatory role of mature lymphocytes in this process. We then investigated whether the protective effect of estradiol was mediated by a specific lymphocyte subpopulation by studying the hormonal effect on fatty streak constitution in recently developed models of ApoE(-/-) mice deficient in selective T-lymphocyte subsets (either TCRalphabeta+, CD4+, CD8+, or TCRgammadelta+ lymphocytes) or B lymphocytes. In all these specifically immunodeficient mice, estradiol administration to ovariectomized mice conferred protection as in immunocompetent ApoE(-/-) mice, clearly demonstrating that no single lymphocyte subpopulation was specifically required for this effect. These results point to additional lymphocyte-dependent mechanisms such as modulating the interactions among lymphocytes and between lymphocytes and endothelial and/or antigen-presenting cells.     

Fatal Dieulafoy's type ulcer in a case of gastric AL-amyloidosis

Dieulafoy's ulcer is a particular form of gastric ulcer confined to a persistent caliber artery and may lead to severe hemorrhage. We report a case of fatal gastric bleeding in a woman with benign biclonal gammapathy. Autopsy found a typical Dieulafoy's ulcer centered by a persistent caliber artery which wall was thickened by AL-amyloid deposits. Amyloidosis involved the gastric wall, but also middle caliber arteries of the liver, the lung, the pancreas, the kidney and the myocardium. AL-amyloidosis is a rare and late complication of monoclonal gammapathy and may be asymptomatic. Pathogenesis of Dieulafoy's ulcer remains unclear. In our case, local ischemia may have facilitated gastric ulceration, and amyloid deposits may have contributed to arterial rupture.     

Molecular characterisation of two mumps virus genotypes circulating during an epidemic in Lithuania from 1998 to 2000

Summary.  An epidemic of mumps in Lithuania started in December 1998 and continued until May 2000. The total registered number of cases was about 11.000 of a total of 3,7 million inhabitants in Lithuania (29,7 cases/10000). Virus- containing samples were collected from 80 patients treated at the hospital of Kaunas from October 1999 until the end of the epidemic. Out of the 80 patients with parotitis, meningitis was observed in 11 patients and orchitis in 22 of 69 male patients. Twenty-seven virus strains were genotyped by nucleotide sequencing of the small hydrophobic (SH) protein gene, and the 57 amino acid sequences of the gene were deduced. Twenty-five virus strains belonged to the C genotype and two were of the D genotype. By phylogenetic analysis the virus strains causing meningitis grouped in a separate cluster, designated C1, within the C genotype. Another group of ten of the 25 genotype C strains exhibited an amino acid triplet at amino acid positions 28 to 30 of the protein, consisting of valine, alanine and serine, instead of the previously recognised valine, valine and serine combination of genotype C. The amino acid alanine at position 29 was found in combination with the amino acid serine at position 48. This variant was designated C2 and it was associated with parotitis. The amino acid alanine at position 29 and serine in position 48 of the C2 genotype may constitute a marker of low neurovirulence compared to other genotype C strains. Received July 9, 2001 Accepted October 23, 2001     

Sensitization to sunflower pollen and lung functions in sunflower processing workers

BACKGROUND: This study aimed to investigate whether exposure to sunflower pollen (Helianthus annuus) increases both sensitization and respiratory symptoms, and whether or not it affects lung functions in sunflower processing workers. METHODS: The largest sunflower processing factories in the Thrace region of Turkey participated in this study. Workers from the units directly exposed to sunflower seed enrolled as the study group (n = 102) and workers who were not directly exposed to Helianthus annuus pollen (n = 102) were the control group. Detailed questionnaires covering respiratory and allergic symptoms were completed, and skin prick tests and lung function tests were performed. RESULTS: We found a very high rate (23.5%) of sensitization to Helianthus annuus in the study group compared to the controls (P<0.001). Logistic regression analysis showed that the risk of sensitization to H. annuus was increased 4.7-fold (odds ratio = 4.17, 95%) confidence interval = 1.3-16.7) if subjects were exposed to sunflower pollen in the workplace. While asthmatic symptoms and allergic skin diseases were not different between the two groups, workers in the study group had a higher rate of allergic rhinitis and conjunctivitis (P<0.05). We found that pulmonary function was significantly impaired in the study group (P<0.01). Using a multivariate analysis model, inclusion in the study group was found to be a predictive factor for impairment of lung function (P=0.002). CONCLUSIONS: We conclude that sunflower pollen has high allergenic potential, especially when there is close contact, and exposure to sunflower pollen in the workplace can result in impairment in lung function.     

Bifidobacterial lipoglycan as a new cause for false-positive platelia Aspergillus enzyme-linked immunosorbent assay reactivity

We previously hypothesized that a lipoglycan of Bifidobacterium bifidum subsp. pennsylvanicum cross-reacts with the Platelia Aspergillus (PA) enzyme-linked immunosorbent assay (ELISA) based on the presence of galactofuranosyl epitopes in the cell wall (M. A. S. H. Mennink-Kersten, R. R. Klont, A. Warris, H. J. M. Op den Camp, and P. E. Verweij, Lancet 363:325-327, 2004). We tested this hypothesis by testing bacterial suspensions of different bifidobacterial species and other gram-positive and -negative bacteria with the PA ELISA, which is used to detect circulating galactomannan for the serodiagnosis of invasive aspergillosis. Furthermore, neonatal fecal samples were enumerated for bifidobacteria by fluorescence in situ hybridization (FISH) and tested for PA ELISA reactivity. All bifidobacteria, except B. infantis and B. adolescentis, showed reactivity 6- to 600-fold higher compared to the controls (i.e., Micrococcus luteus and Propionibacterium freudenreichii, which contain a cell wall lipomannan). Eggerthella lenta showed a 25-fold-higher reactivity. ELISA reactivity was clearly shown to be associated with bacterial lipoglycans containing a beta-1,5-galactofuranosyl chain. All neonatal feces showed PA ELISA reactivity and associated numbers of bifidobacteria. Since high concentrations of bifidobacteria are present in the human gut, these bacteria or excreted lipoglycan may cause false serum PA ELISA reactivity in selected patient groups, especially neonates.     

Prevalence and characterization of a binary toxin (actin-specific ADP-ribosyltransferase) from Clostridium difficile

In addition to the two large clostridial cytotoxins (TcdA and TcdB), some strains of Clostridium difficile also produce an actin-specific ADP-ribosyltransferase, called binary toxin CDT. We used a PCR method and Southern blotting for the detection of genes encoding the enzymatic (CDTa) and binding (CDTb) components of the binary toxin in 369 strains isolated from patients with suspected C. difficile-associated diarrhea or colitis. Twenty-two strains (a prevalence of 6%) harbored both genes. When binary toxin production was assessed by Western blotting, 19 of the 22 strains reacted with antisera against the iota toxin of C. perfringens (anti-Ia and anti-Ib). Additionally, binary toxin activity, detected by the ADP-ribosyltransferase assay, was present in only 17 of the 22 strains. Subsequently, all 22 binary toxin-positive strains were tested for the production of toxins TcdA and TcdB, toxinotyped, and characterized by serogrouping, PCR ribotyping, arbitrarily primed PCR, and pulsed-field gel electrophoresis. All binary toxin-positive strains also produced TcdB and/or TcdA. However, they had significant changes in the tcdA and tcdB genes and belonged to variant toxinotypes III, IV, V, VII, IX, and XIII. We could differentiate 16 profiles by using typing methods, indicating that most of the binary toxin-positive strains were unrelated.     

Frequent carriage of Panton-Valentine leucocidin genes by Staphylococcus aureus isolates from surgically drained abscesses

Between 1 February and 15 April 2002, 95 patients were admitted to Gaston Bourret Territorial Hospital (New Caledonia, France) for drainage of community-acquired soft tissue abscesses. Staphylococcus aureus was detected in 68 cases (72%). Two-thirds of the patients with S. aureus infection had furuncles, which were located on the limbs in 82% of cases. The median interval between symptom onset and hospital admission was 5.7 days. Three-quarters of the patients were Melanesians living in tribes. Fifty-four S. aureus isolates were screened for toxin genes. Panton-Valentine leucocidin (PVL) genes were detected in 48 isolates (89%), the exfoliative toxin A gene was detected in 1 isolate, and no toxin genes were detected in 4 isolates. S. aureus nasal carriage was detected in 39.7% of patients with S. aureus infections. Two infecting S. aureus strains and two nasal carriage strains were resistant to methicillin. Comparative pulsed-field gel electrophoresis, performed in 16 cases, showed that five of six patients with PVL-positive nasal carriage strains were infected by the same strains. In contrast, 8 of 10 patients with PVL-negative nasal carriage strains were infected by PVL-positive strains. PVL genes thus appear to be a major virulence factor in both primary and secondary S. aureus skin infections.     

Pneumocystis carinii f. sp. hominis is not infectious for SCID mice

The infectious power of Pneumocystis carinii f. sp. hominis was explored by inoculating SCID mice intranasally with either P. carinii f. sp. hominis or P. carinii f. sp. muris isolates. Only mice inoculated with mouse parasites developed Pneumocystis pneumonia, as assessed by microscopy and PCR. These results suggest that humans do not contract pneumocystosis from animals.     

Differential modulation of Ca(v)2.1 channels by calmodulin and Ca2+-binding protein 1

Ca(v)2.1 channels, which mediate P/Q-type Ca2+ currents, undergo Ca2+/calmodulin (CaM)-dependent inactivation and facilitation that can significantly alter synaptic efficacy. Here we report that the neuronal Ca2+-binding protein 1 (CaBP1) modulates Ca(v)2.1 channels in a manner that is markedly different from modulation by CaM. CaBP1 enhances inactivation, causes a depolarizing shift in the voltage dependence of activation, and does not support Ca2+-dependent facilitation of Ca(v)2.1 channels. These inhibitory effects of CaBP1 do not require Ca2+, but depend on the CaM-binding domain in the alpha1 subunit of Ca(v)2.1 channels (alpha12.1). CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 in discrete microdomains of neurons in the hippocampus and cerebellum. Our results identify an interaction between Ca2+ channels and CaBP1 that may regulate Ca2+-dependent forms of synaptic plasticity by inhibiting Ca2+ influx into neurons.