Maintenance of glia in the optic lamina is mediated by EGFR signaling by photoreceptors in adult Drosophila.

The late onset of neurodegeneration in humans indicates that the survival and function of cells in the nervous system must be maintained throughout adulthood. In the optic lamina of the adult Drosophila, the photoreceptor axons are surrounded by multiple types of glia. We demonstrated that the adult photoreceptors actively contribute to glia maintenance in their target field within the optic lamina. This effect is dependent on the epidermal growth factor receptor (EGFR) ligands produced by the R1-6 photoreceptors and transported to the optic lamina to act on EGFR in the lamina glia. EGFR signaling is necessary and sufficient to act in a cell-autonomous manner in the lamina glia. Our results suggest that EGFR signaling is required for the trafficking of the autophagosome/endosome to the lysosome. The loss of EGFR signaling results in cell degeneration most likely because of the accumulation of autophagosomes. Our findings provide in vivo evidence for the role of adult neurons in the maintenance of glia and a novel role for EGFR signaling in the autophagic flux.

Comparative chest computed tomography findings of non-tuberculous mycobacterial lung diseases and pulmonary tuberculosis in patients with acid fast bacilli smear-positive sputum.

BACKGROUND: Early diagnosis and treatment of nontuberculous mycobacterial lung diseases (NTM-LD) and pulmonary tuberculosis (PTB) are important clinical issues. The present study aimed to compare and identify the chest CT characteristics that help to distinguish NTM lung disease from PTB in patients with acid-fast bacilli (AFB) smear-positive sputum. METHODS: From January 2009 to April 2012, we received 467 AFB smear-positive sputum specimens. A total of 95 CT scans obtained from the 159 patients were analyzed, 75 scans were from patients with PTB and 20 scans from NTM-LD. The typical chest CT findings of mycobacterial diseases were analyzed. RESULTS: In patients with PTB, the prevalence of pleural effusion (38.7% vs. 15.0%; P = 0.047), nodules < 10 mm in size (76.0% vs. 25.0%; P < 0.001), tree-in-bud pattern (81.3% vs. 55.0%; P = 0.021), and cavities (31.1% vs. 5.0%; P = 0.018) were significantly higher than patients with NTM. Of the 20 patients with NTM lung diseases, bronchiectasis and cystic changes were significantly higher than patients with PTB (20.0% vs. 4.0%; P = 0.034). In multivariate analysis, CT scan findings of nodules was independently associated with patients with diagnoses of PTB (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02-0.30). Presence of bronchiectasis and cystic changes in CT scans was strongly associated with patients with NTM-LD (OR, 33.04; 95% CI, 3.01-362.55). CONCLUSIONS: The CT distinction between NTM-LD and PTB may help radiologists and physicians to know the most likely diagnoses in AFB-smear positive patients and avoid unnecessary adverse effects and the related costs of anti-TB drugs in endemic areas.

Epidemiology of human herpesvirus type 8 and parvovirus B19 infections and their association with HIV-1 among men who have sex with men and injection drug users in Taiwan.

BACKGROUND/PURPOSE: Human herpesvirus 8 (HHV-8), the causal agent of Kaposi's sarcoma (KS), is transmitted sexually among men who have sex with men (MSM), but little is known of its transmission among injection drug users (IDUs). By contrast, human parvovirus B19 (B19), a causative agent for anemia, is most frequently detected in IDUs. The aim of this study was to investigate the associations between HHV-8 infection and human immunodeficiency virus type 1 (HIV-1), and between B-19 and HIV-1 among MSM and IDUs patients. METHODS: Serum samples from 553 IDUs and 231 MSM were analyzed for anti-HHV-8 lytic and anti-B19 viral structural capsid protein 2 (VP-2) antibodies using enzyme immunoassay, indirect immunofluorescence, and immunoblot assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations between different viral infections. RESULTS: HIV-1-seropositive MSM had significantly higher rates of HHV-8 infection than seronegative MSM (32.3% and 15.4%, respectively; OR = 2.62, 95% CI = 1.37-5.02). Among HIV-1/AIDS patient groups, MSM had significantly higher HHV-8 seropositive rates (32.3% vs. 6.6%, p < 0.0001) and lower B19 infection rates (35.4% vs. 78.8%, p < 0.001) than IDUs. In addition, HIV-1-infected MSM were 5.95 times (95% CI = 3.38-10.46) more likely to be infected with HHV-8 than male HIV-1-infected IDUs. By contrast, male IDUs were 6.74 times odds (95% CI = 4.28-10.61) more likely to contract B19 infection than MSM. CONCLUSION: In Taiwan, MSM have a significantly higher prevalence for HHV-8 than IDUs. The contrasting risks of HHV-8 and B19 infections between different HIV-1/AIDS groups suggest that the efficiency of viral infection is affected by their distinct transmission routes.

Identifying epitopes responsible for neutralizing antibody and DC-SIGN binding on the spike glycoprotein of the severe acute respiratory syndrome coronavirus.

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) uses dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) to facilitate cell entry via cellular receptor-angiotensin-converting enzyme 2. For this project, we used recombinant baculoviruses expressing different lengths of SARS-CoV spike (S) protein in a capture assay to deduce the minimal DC-SIGN binding region. Our results identified the region location between amino acid (aa) residues 324 to 386 of the S protein. We then generated nine monoclonal antibodies (MAbs) against the S protein to map the DC-SIGN-binding domain using capture assays with pseudotyped viruses and observed that MAb SIa5 significantly blocked S protein-DC-SIGN interaction. An enhancement assay using the HKU39849 SARS-CoV strain and human immature dendritic cells confirmed our observation. Data from a pepscan analysis and M13 phage peptide display library system mapped the reactive MAb SIa5 epitope to aa residues 363 to 368 of the S protein. Results from a capture assay testing three pseudotyped viruses with mutated N-linked glycosylation sites of the S protein indicate that only two pseudotyped viruses (N330Q and N357Q, both of which lost glycosylation sites near the SIa5 epitope) had diminished DC-SIGN-binding capacity. We also noted that MAb SIb4 exerted a neutralizing effect against HKU39849; its reactive epitope was mapped to aa residues 435 to 439 of the S protein. We offer the data to facilitate the development of therapeutic agents and preventive vaccines against SARS-CoV infection.

Increased seroprevalence of human herpesvirus 8 in patients with hematological disorders.

Human herpesvirus 8 (HHV8) has been consistently linked to Kaposi's sarcoma and many hematological diseases such as pleural effusion lymphoma, multicentric Castleman's disease, some lymphoproliferative diseases and posttransplantation bone marrow failure. However, whether patients with hematological disorders are at a higher risk of HHV8 infection has not been determined. In this study, indirect immunofluorescence was used to detect antibodies against lytic antigens of HHV8 in 265 patients with hematological disorders. Our data showed that 24.5% of patients (65/265) were seropositive for HHV8 IgG antibody, which was significantly higher than in our general population (p < 0.001). A significantly higher seropositive rate can be found in patients with lymphoma, leukemia, autoimmune cytopenias and myeloproliferative disorders, but not in patients with myeloma or aplastic anemia. No difference in the seropositive rate is associated with gender or age. We conclude that some patients with hematological disorders are at a higher risk of HHV8 infection.

Detection of bcr-abl gene expression at a low level in blood cells of some patients with essential thrombocythemia.

The major bcr-abl fusion gene is seen as a major marker of chronic myeloid leukemia (CML). However, whether the bcr-abl transcript can be detected in patients with essential thrombocythemia (ET) is still a matter of controversy. We detected the messenger RNA expression of the bcr-abl gene using reverse transcription-polymerase chain reaction in peripheral-blood leukocytes (PBLs) from 63 patients with myeloproliferative disorders (including CML, ET, and polycythemia vera [PV]) and 51 normal, healthy volunteers. The bcr-abl transcript was detected in 4 of the 30 ET patients (13.3%), 17 of the 17 CML patients (100%), none of the 16 PV patients (0%), and 1 of the 51 normal subjects (1.9%). Compared with the normal controls, ET patients have a greater tendency to express the bcr-abl transcript in PBLs (P=.06, Fisher's exact test). Further semiquantitative analysis showed that the intensity of bcr-abl transcript expression in 4 ET patients and a normal individual was 10(3) to 10(4) times less than that in the CML patients. We conclude that the bcr-abl transcript can be detected in the PBLs of Philadelphia chromosome (Ph)-negative ET patients but that the level of expression is markedly less than that in CML patients. The clinical significance of this finding merits further investigation.

Circulating levels of thrombopoietic and inflammatory cytokines in patients with acute myeloblastic leukemia and myelodysplastic syndrome.

BACKGROUND: The regulation of megakaryocytopoiesis and thrombopoiesis appears to be under the control of an array of hematopoietic growth factors. The regulatory mechanism of endogenous cytokines in circulating platelet counts of thrombocytopenic patients with acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS) is still not clear. METHODS: We measured the serum levels of both thrombopoietic and inflammatory cytokines in peripheral blood and bone marrow samples collected from 52 patients with either AML or MDS along with 35 normal control samples. The levels of thrombopoietin (TPO), interleukin (IL)-11, IL-6, IL-8 and stem cell factor (SCF) were determined by ELISA. RESULTS: Platelet counts in the AML/MDS patients during initial diagnosis, chemotherapy and complete remission were 71.2 +/- 11.6, 47.2 +/- 6.1 and 181.4 +/- 26.3 x10(9)/l, respectively. The median value of TPO in AML/MDS patients during diagnosis was 150.6 pg/ml and increased significantly during chemotherapy (median: 828 pg/ml; p < 0.05) but then decreased following complete remission (median: 221.4 pg/ml). However, these levels were all significantly higher in patients than in normal subjects (p < 0.05, p < 0.05 and p < 0.05; respectively), and no significant change was noted in the levels of IL-11 and SCF during treatment of patients or in normal controls. The level of IL-6 was not detectable in normal serum samples but was markedly increased in the AML/MDS patients (median level during diagnosis: 6.7 pg/ml; chemotherapy: 25 pg/ml; complete remission: 7 pg/ml). The level of IL-8 in patients with AML and MDS was markedly elevated during diagnosis (median: 27.5 pg/ml; range: 0-1,587 pg/ml), but decreased to the level of the normal controls when patients were under chemotherapy or in complete remission. CONCLUSIONS: The endogenous levels of TPO, IL-6 and IL-8 are elevated in the thrombocytopenic patients with AML and MDS. Our results are consistent with previous mechanistic studies and suggest that TPO and IL-6 may be active mediators of platelet production.

Bone marrow samples from patients with aplastic anemia are not infected with parvovirus B19 and Mycobacterium tuberculosis.

The majority of patients with aplastic anemia (AA) have an idiopathic form of the disease. The aim of this study was to detect the presence of parvovirus B19 DNA and Mycobacterium tuberculosis (MTB) DNA by nested polymerase chain reaction (N-PCR) assays in the bone marrow biopsy samples from 30 patients with idiopathic AA. Serologic assays for parvovirus B19 were based on indirect antibody capture enzyme-linked immunosorbent assay. Our results indicate that neither parvovirus B19 DNA nor MTB DNA could be demonstrated in any of the bone marrow samples by N-PCR. Moreover, IgM antibody against parvovirus B19 also was undetectable in the serum samples of 17 patients. Thus, our results suggest that parvovirus B19 and MTB are not associated with AA and, consequently, do not have a role in the pathogenesis of this disease.