107 research outputs found

    Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma

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    Saliva Viral Load Better Correlates with Clinical and Immunological Profiles in Children with Coronavirus Disease 2019

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    BACKGROUND: Pediatric COVID-19 studies exploring the relationships between NPS and saliva viral loads, clinical and immunological profiles are lacking. METHODS: Demographics, immunological profiles, nasopharyngeal swab (NPS), and saliva samples collected on admission, and hospital length of stay (LOS) were assessed in children below 18 years with COVID-19. FINDINGS: 91 patients were included between March and August 2020. NPS and saliva viral loads were correlated (r=0.315, p=0.01). Symptomatic patients had significantly higher NPS and saliva viral loads than asymptomatic patients. Serial NPS and saliva viral load measurements showed that the log10 NPS (r=-0.532, p<0.001) and saliva (r=-0.417, p<0.001) viral loads for all patients were inversely correlated with the days from symptom onset with statistical significance. Patients with cough, sputum, and headache had significantly higher saliva, but not NPS, viral loads. Higher saliva, but not NPS, viral loads were associated with total lymphopenia, CD3 and CD4 lymphopenia (all p<0.05), and were inversely correlated with total lymphocyte (r=-0.43), CD3 (r=-0.55), CD4 (r=-0.60), CD8 (r=-0.41), B (r=-0.482), and NK (r=-0.416) lymphocyte counts (all p<0.05). Interpretation: Saliva viral loads on admission in children correlated better with clinical and immunological profiles than NPS

    PARP-1 Val762Ala Polymorphism Is Associated with Risk of Cervical Carcinoma

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    PARP-1 is a nuclear enzyme that plays an important role in DNA repair, recombination, proliferation and the genome stability. The PARP-1 Val762Ala polymorphism has been associated with increased risk of developing cancers of the prostate, esophagus and lung. The aim of this study was to determine whether the PARP-1 Val762Ala polymorphism is associated with the risk of cervical carcinoma. MA-PCR was used to genotype the PARP-1 Val762Ala polymorphism in 539 women with cervical carcinoma, 480 women with CIN and 800 controls. The genotyping method was confirmed by the DNA sequencing analysis. The PARP-1 Val762Ala polymorphism was not associated with the risk of CIN. However, women carrying the PARP-1 Ala762Ala genotype were significantly susceptible to cervical carcinoma (OR: 2.70, 95% CI: 1.47–3.70), and the similar results were also found in squamous cell carcinoma (OR: 2.56, 95% CI: 1.47–3.70). In HPV positive population, the PARP-1 Ala762Ala genotype was also associated with increased risk of cervical carcinoma (OR: 5.56, 95% CI: 2.08–14.3). Our results indicate that the PARP-1 Ala762Ala genotype increases the risk of cervical carcinoma

    Electroluminescent Characteristics of DBPPV–ZnO Nanocomposite Polymer Light Emitting Devices

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    We have demonstrated that fabrication and characterization of nanocomposite polymer light emitting devices with metal Zinc Oxide (ZnO) nanoparticles and 2,3-dibutoxy-1,4-poly(phenylenevinylene) (DBPPV). The current and luminance characteristics of devices with ZnO nanoparticles are much better than those of device with pure DBPPV. Optimized maximum luminance efficiencies of DBPPV–ZnO (3:1 wt%) before annealing (1.78 cd/A) and after annealing (2.45 cd/A) having a brightness 643 and 776 cd/m2at a current density of 36.16 and 31.67 mA/cm2are observed, respectively. Current density–voltage and brightness–voltage characteristics indicate that addition of ZnO nanoparticles can facilitate electrical injection and charge transport. The thermal annealing is thought to result in the formation of an interfacial layer between emissive polymer film and cathode

    Isolation of Monoclonal Antibodies with Predetermined Conformational Epitope Specificity

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    Existing technologies allow isolating antigen-specific monoclonal antibodies (mAbs) from B cells. We devised a direct approach to isolate mAbs with predetermined conformational epitope specificity, using epitope mimetics (mimotopes) that reflect the three-dimensional structure of given antigen subdomains. We performed differential biopanning using bacteriophages encoding random peptide libraries and polyclonal antibodies (Abs) that had been affinity-purified with either native or denatured antigen. This strategy yielded conformational mimotopes. We then generated mimotope-fluorescent protein fusions, which were used as baits to isolate single memory B cells from rhesus monkeys (RMs). To amplify RM immunoglobulin variable regions, we developed RM-specific PCR primers and generated chimeric simian-human mAbs with predicted epitope specificity. We established proof-of-concept of our strategy by isolating mAbs targeting the conformational V3 loop crown of HIV Env; the new mAbs cross-neutralized viruses of different clades. The novel technology allows isolating mAbs from RMs or other hosts given experimental immunogens or infectious agents

    B-cell depletion reveals a role for antibodies in the control of chronic HIV-1 infection

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    HIV can be partially contained by host immunity and understanding the basis of this may inform vaccine design. The importance of B-cell function in long-term control is poorly understood. One method of investigating this is in vivo cellular depletion. In this study, we take advantage of a unique opportunity to investigate the role of B cells in an HIV-infected patient. The HIV-1+ patient studied here was not taking antiretroviral drugs and was treated for pre-existing low-grade lymphoplasmacytoid lymphoma by depletion of CD20+ B cells using rituximab. We demonstrate that B-cell depletion results in a decline in autologous neutralizing antibody (NAb) responses and a 1.7 log10 rise in HIV-1 plasma viral load (pVL). The recovery of NAbs results in a decline in pVL. The HIV-1 sequences diversify and NAb-resistant mutants are subsequently selected. These data suggest that B-cell function can contribute to the long-term control of pVL, and that NAbs may be more important in controlling chronic HIV-1 infection than previously suspected

    Aberrant antigenic expression in extranodal NK/T-cell lymphoma: a multi-parameter study from Thailand

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    <p>Abstract</p> <p>Background</p> <p>Extranodal NK/T-cell lymphoma, nasal type (ENKTL) is not common worldwide, but it is the most common T- and NK-cell lymphomas in many Asian countries. Immunophenotypic profiles were studied based on limited series. The authors, therefore, studied on ENKTL according to characterize immunophenotypic profiles as well as the distribution of EBV subtype and LMP-1 gene deletion.</p> <p>Methods</p> <p>By using tissue microarray (TMA), immunohistochemical study and EBV encoded RNA (EBER) in situ hybridization were performed. T-cell receptor (TCR) gene rearrangement, EBV subtyping, and LMP-1 gene deletion were studied on the available cases.</p> <p>Results</p> <p>There were 22 cases eligible for TMA. ENKTL were positive for CD3 (91%), CD5 (9%), CD7 (32%), CD4 (14%), CD56 (82%), TIA-1 (100%), granzyme B (95%), perforin (86%), CD45 (83%), CD30 (75%), Oct2 (25%), and IRF4/MUM1 (33%). None of them was positive for βF1, CD8, or CD57. TCR gene rearrangement was negative in all 18 tested cases. EBV was subtype A in all 15 tested cases, with 87% deleted LMP-1 gene. Cases lacking perforin expression demonstrated a significantly poorer survival outcome (p = 0.008).</p> <p>Conclusions</p> <p>The present study demonstrated TIA-1 and EBER as the two most sensitive markers. There were a few CD3 and/or CD56 negative cases noted. Interestingly, losses of CD45 and/or CD7 were not uncommon while Oct2 and IRF4/MUM1 could be positive in a subset of cases. Based on the present study in conjunction with the literature review, determination of PCR-based TCR gene rearrangement analysis might not be a useful technique for making diagnosis of ENKTL.</p

    Distinct Subgroups in Hypertrophic Cardiomyopathy in the NHLBI HCM Registry.

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    BACKGROUND: The HCMR (Hypertrophic Cardiomyopathy Registry) is a National Heart, Lung, and Blood Institute-funded, prospective registry of 2,755 patients with hypertrophic cardiomyopathy (HCM) recruited from 44 sites in 6 countries. OBJECTIVES: The authors sought to improve risk prediction in HCM by incorporating cardiac magnetic resonance (CMR), genetic, and biomarker data. METHODS: Demographic and echocardiographic data were collected. Patients underwent CMR including cine imaging, late gadolinium enhancement imaging (LGE) (replacement fibrosis), and T1 mapping for measurement of extracellular volume as a measure of interstitial fibrosis. Blood was drawn for the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (cTnT), and genetic analysis. RESULTS: A total of 2,755 patients were studied. Mean age was 49 ± 11 years, 71% were male, and 17% non-white. Mean ESC (European Society of Cardiology) risk score was 2.48 ± 0.56. Eighteen percent had a resting left ventricular outflow tract (LVOT) gradient ≥30 mm Hg. Thirty-six percent had a sarcomere mutation identified, and 50% had any LGE. Sarcomere mutation-positive patients were more likely to have reverse septal curvature morphology, LGE, and no significant resting LVOT obstruction. Those that were sarcomere mutation negative were more likely to have isolated basal septal hypertrophy, less LGE, and more LVOT obstruction. Interstitial fibrosis was present in segments both with and without LGE. Serum NT-proBNP and cTnT levels correlated with increasing LGE and extracellular volume in a graded fashion. CONCLUSIONS: The HCMR population has characteristics of low-risk HCM. Ninety-three percent had no or only mild functional limitation. Baseline data separated patients broadly into 2 categories. One group was sarcomere mutation positive and more likely had reverse septal curvature morphology, more fibrosis, but less resting obstruction, whereas the other was sarcomere mutation negative and more likely had isolated basal septal hypertrophy with obstruction, but less fibrosis. Further follow-up will allow better understanding of these subgroups and development of an improved risk prediction model incorporating all these markers

    Current treatment options for recurrent nasopharyngeal cancer

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    Loco-regional control rate of nasopharyngeal carcinoma (NPC) has improved significantly in the past decade. However, local recurrence still represents a major cause of mortality and morbidity in advanced stages, and management of local failure remains a challenging issue in NPC. The best salvage treatment for local recurrent NPC remains to be determined. The options include brachytherapy, external radiotherapy, stereotactic radiosurgery, and nasopharyngectomy, either alone or in different combinations. In this article we will discuss the different options for salvage of locally recurrent NPC. Retreatment of locally recurrent NPC using radiotherapy, alone or in combination with other treatment modalities, as well as surgery, can result in long-term local control and survival in a substantial proportion of patients. For small-volume recurrent tumors (T1–T2) treated with external radiotherapy, brachytherapy or stereotactic radiosurgery, comparable results to those obtained with surgery have been reported. In contrast, treatment results of advanced-stage locally recurrent NPC are generally more satisfactory with surgery (with or without postoperative radiotherapy) than with reirradiation
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