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.     

Clinical and biological evolution of HIV-1 seroconverters in Abidjan, Côte d'Ivoire, 1997-2000

OBJECTIVE: To describe the clinical and biologic evolution of HIV-1 infection in Africa. METHODS: One hundred four HIV-1-infected individuals were identified prospectively from regular blood donors in Abidjan, C?te d'Ivoire. The date of seroconversion was estimated from results of sequential serologic tests. Biologic and clinical follow-up was performed every 6 months, starting as early as possible after seroconversion. Case management followed national guidelines. RESULTS: The median interval between estimated seroconversion and study inclusion was 9.7 months, and the median window of seroconversion was 2.8 months. At baseline, all but two patients were asymptomatic; the median CD4 + cell count was 527/mm 3 (interquartile range [IR], 395-684), and the median plasma HIV RNA level was 4.6 log 10 copies/ml (IR, 3.8-4.9). The median follow-up was 23.9 months, and 95% of the patients received primary prophylaxis with co-trimoxazole for opportunistic infections. Of the patients, 1 presented with wasting syndrome, 3 developed tuberculosis, and 17 had a Centers for Disease Control and Prevention category B-defining event. The 3-year AIDS-free and symptom-free probabilities were 96.7% (95% confidence interval [CI], 87.0-99.2] and 79.3% (95% CI, 67.5-87.2), respectively. During the first 3 years of follow-up, we observed that the median plasma viral load stabilized at >4 log 10 copies/ml and that the median CD4 + cell count declined by 20 to 25/mm 3 per year. CONCLUSION: These African seroconverters were moderately immunosuppressed. The median HIV RNA level was high and varied very little during the first 3 years, and there were few clinical events.     

Persistent multiple pulmonary nodules in a nonimmunocompromised woman after varicella-related myelitis treated with acyclovir

Persistent multiple pulmonary nodules were observed on the chest X ray of a nonimmunocompromised woman 6 months after she was treated with acyclovir for a varicella-related myelitis without respiratory symptoms. Early antiviral therapy given for varicella infections might decrease the intensity of clinical symptoms without actually preventing the occurrence of varicella-zoster virus-related lesions such as the persistent pulmonary nodules reported here.     

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.     

Inflammatory malignant fibrous histiocytomas and dedifferentiated liposarcomas: histological review, genomic profile, and MDM2 and CDK4 status favour a single entity

Inflammatory malignant fibrous histiocytoma (inflammatory MFH) is a very rare tumour that occurs most often in the retroperitoneum. So far, it has been considered to be a special subtype of MFH. As it is now widely accepted that most retroperitoneal pleomorphic MFHs are dedifferentiated liposarcomas, the present study compared histological features, genomic profile (CGH analysis), and MDM2 and CDK4 status (immunohistochemistry, FISH, and quantitative PCR) in inflammatory MFHs from 12 patients and dedifferentiated liposarcomas that had an inflammatory MFH component from eight patients. Metaphase cytogenetic and FISH analyses were also performed on one inflammatory MFH. Histological review showed areas of well-differentiated liposarcoma in nine inflammatory MFHs. CGH analysis showed 12q13-15 amplification or gain in six of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Immunohistochemistry showed positivity of tumour cells for MDM2 in every tumour in both groups and for CDK4 in ten and seven inflammatory MFHs and dedifferentiated liposarcomas, respectively. Metaphase cytogenetic and FISH analysis performed on one inflammatory MFH showed the presence of a supernumerary large marker chromosome and ring chromosome with high-level amplification of both MDM2 and CDK4 genes. FISH analysis on paraffin wax-embedded sections showed amplifications of MDM2 and CDK4 in seven of seven inflammatory MFHs and in seven of seven dedifferentiated liposarcomas. Quantitative PCR showed amplification of MDM2 in six and of CDK4 in seven of nine inflammatory MFHs. In conclusion, this study strongly suggests that most so-called inflammatory MFHs are dedifferentiated liposarcomas.     

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.     

Human immunodeficiency virus 1 favors the persistence of infection by activating macrophages through TNF

Macrophages play a major role in HIV-1 persistence. In the present paper, we demonstrate that the absence of apoptosis in HIV-1-infected primary human monocyte-differentiated macrophages (MDM) correlates with an increase in anti-apoptotic (Bcl-2 and Bcl-x(L)) and a decrease in pro-apoptotic (Bax and Bad) proteins. This is associated with macrophage activation as shown by tumor necrosis factor (TNF) production and NF-kappaB activation upon infection. TNF production was shown to be involved in the upregulation of Bcl-2 and Bcl-x(L) because this increase was abolished by an anti-TNF anti-serum or an inhibitor of TNF synthesis. In parallel, inhibition of TNF production induced an increase in the number of apoptotic cells. Furthermore, using an inhibitor of NF-kappaB activation, we demonstrated that TNF-induced upregulation of Bcl-x(L) and Bcl-2 occurs, respectively, through a NF-kappaB-dependent and an NF-kappaB-independent pathway.     

International proficiency study of a consensus L1 PCR assay for the detection and typing of human papillomavirus DNA: evaluation of accuracy and intralaboratory and interlaboratory agreement

The PGMY L1 consensus primer pair combined with the line blot assay allows the detection of 27 genital human papillomavirus (HPV) genotypes. We conducted an intralaboratory and interlaboratory agreement study to assess the accuracy and reproducibility of PCR for HPV DNA detection and typing using the PGMY primers and typing amplicons with the line blot (PGMY-LB) assay. A test panel of 109 samples consisting of 29 HPV-negative (10 buffer controls and 19 genital samples) and 80 HPV-positive samples (60 genital samples and 20 controls with small or large amounts of HPV DNA plasmids) were tested blindly in triplicate by three laboratories. Intralaboratory agreement ranged from 86 to 98% for HPV DNA detection. PGMY-LB assay results for samples with a low copy number of HPV DNA were less reproducible. The rate of intralaboratory agreement excluding negative results for HPV typing ranged from 78 to 96%. Interlaboratory reliability for HPV DNA positivity and HPV typing was very good, with levels of agreement of >95% and kappa values of >0.87. Again, low-copy-number samples were more prone to generating discrepant results. The accuracy varied from 91 to 100% for HPV DNA positivity and from 90 to 100% for HPV typing. HPV testing can thus be accomplished reliably with PCR by using a standardized written protocol and quality-controlled reagents. The use of validated HPV DNA detection and typing assays demonstrating excellent interlaboratory agreement will allow investigators to better compare results between epidemiological studies.     

Jumping translocations in multiple myeloma

Jumping translocations (JT) have been defined as nonreciprocal translocations involving a same donor chromosome arm or chromosome segment onto two or more recipient chromosomes in different cell lines in the same patient, leading to a mosaic karyotype. This definition has been expanded to also include extra copies of a same donor segment on different recipient chromosomes in a single clone. Six patients with multiple myeloma and JT involving chromosome arm 1q were identified among 37 patients presenting with chromosome 1 abnormalities. All six patients had an advanced disease and a short survival. The literature review allowed us to identify 24 additional patients with JT. Chromosomes 16 and 19 were the recipients in 11 (45.8%) and 6 (25%) of these 24 patients, respectively. Breakpoints on the recipient chromosomes were pericentromeric in 46.2% and telomeric in 40.4% of the breakpoints recorded. Since telomeres are made of (TTAGGG)n tandem DNA repeats that are also found in the pericentromeric heterochromatic regions (interstital telomeric sequences), it is presumed that jumping translocations arise through illegimate recombination between telomere repeat sequences and interstitial telomeric sequences.