Lymphocyte apoptosis, macrophage function and disease activity in systemic lupus erythematosus (SLE)

INTRODUCTION: Increased lymphocyte apoptosis and defects in macrophage removal of apoptotic cells have been suggested to contribute to the development of SLE. The aim of this study was to investigate the relationship between peripheral lymphocyte apoptosis, macrophage function as determined by the serum levels of neopterin …published_or_final_versio

Synaptic Mitochondria Are Critical for Mobilization of Reserve Pool Vesicles at Drosophila Neuromuscular Junctions

SummaryIn a forward screen for genes affecting neurotransmission in Drosophila, we identified mutations in dynamin-related protein (drp1). DRP1 is required for proper cellular distribution of mitochondria, and in mutant neurons, mitochondria are largely absent from synapses, thus providing a genetic tool to assess the role of mitochondria at synapses. Although resting Ca2+ is elevated at drp1 NMJs, basal synaptic properties are barely affected. However, during intense stimulation, mutants fail to maintain normal neurotransmission. Surprisingly, FM1-43 labeling indicates normal exo- and endocytosis, but a specific inability to mobilize reserve pool vesicles, which is partially rescued by exogenous ATP. Using a variety of drugs, we provide evidence that reserve pool recruitment depends on mitochondrial ATP production downstream of PKA signaling and that mitochondrial ATP limits myosin-propelled mobilization of reserve pool vesicles. Our data suggest a specific role for mitochondria in regulating synaptic strength

Positive Outcomes of HAART at 24 Months in HIV-Infected Patients in Cambodia.

OBJECTIVES: African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-poor settings. The long-term virological outcome and clinico-immunological criteria of success remain important questions. We report the outcomes at 24 months of antiretroviral therapy (ART) in patients treated in a Médecins Sans Frontières/Ministry of Health programme in Cambodia. METHODS: Adults who started HAART 24 +/- 2 months ago were included. Plasma HIV-RNA levels were assessed by real-time polymerase chain reaction. Factors associated with virological failure were analysed using logistic regression. RESULTS: Of 416 patients, 59.2% were men; the median age was 33.6 years. At baseline, 95.2% were ART naive, 48.9% were at WHO stage IV, and 41.6% had a body mass index less than 18 kg/m. The median CD4 cell count was 11 cells/microl. A stavudine-lamivudine-efavirenz-containing regimen was initiated predominantly (81.0%). At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53 (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to follow-up. Estimates of survival were 85.5% at 24 months. Of 346 tested patients, 259 (74.1%) had CD4 cell counts greater than 200 cells/microl and 306 (88.4%) had viral loads of less than 400 copies/ml. Factors associated with virological failure at 24 months were non-antiretroviral naive, an insufficient CD4 cell gain of less than 350 cells/microl or a low trough plasma ART concentration. In an intention-to-treat analysis, 73.6% of patients were successfully treated. CONCLUSION: Positive results after 2 years of advanced HIV further demonstrate the efficacy of HAART in the medium term in resource-limited settings

LAPTM4B Targeting as Potential Therapy for Hepatocellular Carcinoma

HCC is one of the most common cancers worldwide with high prevalence, recurrence, and lethality. The curative rate is not satisfactory. LAPTM4B is a novel driver gene of HCC first indentified by our group. It is over-expressed in 87.3% of HCC. The expression levels of the encoded LAPTM4B-35 protein in HCC is also over-expressed in 86.2% of HCC and shows a significant positive correlation with pathological grade, metastasis, and recurrence, and a negative correlation with postoperative overall- and cancer free- survival of HCC patients. Moreover, HCC cells showing high expression of LAPTM4B-35 show a strong tendency to metastasize and enhanced drug resistance. Overexpression of this gene promotes tumorigenesis, faster growth of human HCC xenografts and metastasis in nude mice, and leads to anti-apoptosis, deregulation of proliferation, enhancement of migration and invasion, as well as multi-drug resistance. In addition, overexpression of LAPTM4B-35 leads to accumulation of a number of oncoproteins and to down-regulation of a number of tumor suppressing proteins. By contrary, knockdown of endogenous LAPTM4B-35 via RNAi results in remarkable inhibition of xenograft growth and metastasis of human HCC in nude mice. Also, RNAi knockdown of LAPTN4B-35 can reverse the cellular and molecular malignant phenotypes noted above

Clinical and molecular epidemiology of human bocavirus in respiratory and fecal samples from children in Hong Kong

Background. Human bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory tract infections in children. We conducted the first systematic prospective clinical and molecular study using nasopharyngeal aspirates (NPAs) and fecal samples. Methods. NPAs negative for influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, and coronavirus and fecal samples from patients with acute gastroenteritis were included. On the basis of results from a pilot study using 400 NPAs from all age groups, a prospective 12-month study was conducted to detect HBoV in 1200 NPAs and 1435 fecal samples from patients <18 years old by polymerase chain reaction. The complete genome sequences of HBoVs from 12 NPAs and 12 fecal samples were determined. Results. Of the 400 NPAs collected in the pilot study, 20 (5.0%) were found to contain HBoV, all from children <5 years old. In the subsequent prospective study of pediatric patients, HBoV was detected in 83 (6.9%) of 1200 NPAs. Upper and lower respiratory tract infections were equally common. HBoV was detected in 30 (2.1%) of 1435 fecal samples. Fever and watery diarrhea were the most common symptoms. The seasonality of HBoV in NPAs and fecal samples was similar. Codetection with other pathogens occurred in 33% and 56% of NPAs and fecal samples, respectively, from patients with HBoV infection. Genomes of HBoVs from NPAs and fecal samples displayed minimal sequence variations. Conclusions. HBoV was detected in fecal specimens in children with acute gastroenteritis. A single lineage of HBoV was associated with both respiratory tract and enteric infections. © 2007 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

GdxSi grown with mass-analyzed low energy dual ion beam epitaxy technique

Semiconducting gadolinium silicide GdxSi samples were prepared by mass-analyzed low-energy dual ion beam epitaxy technique. Auger electron spectroscopy depth profiles indicate that the gadolinium ions are implanted into the single-crystal silicon substrate and formed 20 nm thick GdxSi film. X-ray double-crystal diffraction measurement shows that there is no new phase formed. The XPS spectra show that one type of silicon peaks whose binding energy is between that of silicide and silicon dioxide, and the gadolinium peak of binding energy is between that of metal Gd and Gd2O3. All of these results indicate that an amorphous semiconductor is formed. (C) 2002 Elsevier Science B.V. All rights reserved

Determination of the intrinsic velocity field in the M87 jet

A new method to estimate the Doppler beaming factor of relativistic large-scale jet regions is presented. It is based on multiwaveband fitting to radio-to-X-ray continua with synchrotron spectrum models. Combining our method with available observational data of proper motions, we derive the intrinsic velocity as well as the viewing angles to the line of sight for eight knotty regions down the M87 jet. The results favor the 'modest beaming' scenario along the jet, with Doppler factors varying between 2-5. The inner jet of M87 suffers sharp deceleration, and the intrinsic speed remains roughly constant down the outer jet. The orientation of the inner jet regions is fully consistent with the result of 10deg-19deg to the line of sight suggested by previous Hubble Space Telescope (HST) proper motion studies of the M87 jet. The outer jet, however, shows systematic deflection off the inner jet to much smaller inclination (<<10deg). Further calculation of knot A suggests this deflection can be regarded as evidence that the outer jet suffers some departure from equipartition. The nucleus region of the M87 jet should have a viewing angle close to its first knot HST-1, i.e. ~15deg, which favors the idea that M87 may be a misaligned blazar. This work provides some hints about the overall dynamics of this famous extragalactic jet.Comment: 11 pages, 3 figures, 4 tables, MNRAS, 2009, in pres