[Evaluation of the performance of InnowaveDX MTB/RIF for the detection of Mycobacterium tuberculosis complex and rifampicin resistance].

Objective: To evaluate the performance of Mycobacterium tuberculosis and rifampicin resistance mutation detection kit (InnowaveDX MTB/RIF, referred to as "InnowaveDX") in diagnosing tuberculosis and rifampicin resistance using sputum samples. Methods: From June 19, 2020 to May 16, 2022, patients with suspected tuberculosis were prospectively and consecutively enrolled in Hunan Provincial Tuberculosis Prevention and Control Institute, Henan Provincial Hospital of Infectious Diseases and Wuhan Jinyintan Hospital. A total of 1 328 patients with suspected tuberculosis were finally included. According to the inclusion and exclusion criteria, 1 035 pulmonary tuberculosis patients (357 were confirmed tuberculosis cases and 678 were clinically diagnosed tuberculosis cases) and 180 non-tuberculosis patients were finally included. Sputum samples were collected from all patients for routine sputum smear acid-fastness tests, mycobacterial culture and drug susceptibility testing. Moreover, the diagnostic value of Xpert®MTB/RIF (referred to as "Xpert") and InnowaveDXin detecting tuberculosis and rifampicin resistance was evaluated. Clinical diagnosis and culture results of Mycobacterium tuberculosis were used as reference standards to assess tuberculosis diagnosis, and phenotypic drug sensitivity and Xpert were used as reference standards to assess rifampicin resistance. The sensitivity, specificity, positive predictive value and negative predictive value of the two methods for tuberculosis diagnosis and rifampicin resistance were analyzed. The consistency of the two techniques was analyzed usingkappa test. Results: Taking clinical diagnosis as the reference standard, the detection sensitivity of InnowaveDX [58.0% (600/1 035)] was higher than that of Xpert [51.7% (535/1 035)] in 1035 patients with pulmonary tuberculosis, and the difference was statistically significant (P<0.001). In 270 pulmonary tuberculosis patients with culture-positive pulmonary tuberculosis identified as M.tuberculosis-complex, the positive rates of InnowaveDX and Xpert were both high [99.6%(269/270)and 98.2%(265/270), respectively] and there was no statistical difference. In culture-negative patients with pulmonary tuberculosis, the sensitivity of InnowaveDX was 38.8% (198/511), which was higher than that of Xpert (29.4%, 150/511), and the difference was statistically significant (P<0.001). Taking phenotypic drug-susceptibility testing (DST) as reference, the sensitivity of InnowaveDX to rifampicin resistance was 99.0% (95%CI: 94.7%-100.0%) and the specificity was 94.0%(95%CI: 88.5%-97.4%). With Xpert as the reference, the sensitivity and specificity of InnowaveDX were 97.1% (95%CI: 93.4%-99.1%) and 99.7% (95%CI: 98.4%-100.0%), respectively, and the kappa value was 0.97 (P<0.001). Conclusions: InnowaveDX show a high sensitivity for detecting Mycobacterium tuberculosis, especially in pulmonary tuberculosis patients with a clinical diagnosis and negative culture results. It also showed high sensitivity in detecting rifampicin resistance with DST and Xpert as reference respectively. InnowaveDX is an early and accurate diagnostic tool for TB and drug-resistant TB, particularly suitable for application in low- and middle-income countries.

Risk factors associated with catheter-related venous thrombosis: a meta-analysis.

BACKGROUND: So far, the risk factors of catheter-related venous thrombosis (CRVT) are not fully understood. We use evidence-based medicine to find the risk factors of CRVT by pooling the current studies that reported the risk factors of CRVT, aiming to provide guidance for clinical diagnosis and treatment. METHODS: We searched PubMed, Embase, and Cochrane Library from the establishment of the database to July 2021. We included studies that reported the risk factors of CRVT, and we excluded duplicate publications, research without full text, incomplete information or inability to conduct data extraction, animal experiments, reviews, and systematic reviews. STATA 15.1 was used to analyze the data. RESULTS: The pooled results show that history of venous thrombosis (odds ratio [OR] = 3.75, 95% confidence interval [CI]: 1.02-13.85; P = 0.047), cancer (OR = 1.74, 95% CI: 1.17-2.57; P = 0.006), infection (OR = 2.13, 95% CI:1.33-3.42; P = 0.002), and multilumina (OR = 3.34, 95% CI:1.48-7.54; P = 0.004) will significantly increase the occurrence of CRVT. However, there is no significant correlation between sex, congenital heart disease, bedridden state, sepsis, mechanical ventilation, anticoagulation therapy, insertion site (left), and CRVT. CONCLUSION: Our research results indicate that history of venous thrombosis, cancer, infection and multilumina are possible risk factors for CRVT, and corresponding preventive measures should be taken clinically.

[Prevalence and transmission of pyrazinamide-resistant Mycobacterium tuberculosis in Hunan Province,China].

Objective: To provide a scientific reference for the prevention and treatment of pyrazinamide-resistant tuberculosis (PZA-R TB), we analyzed the prevalence and risk factors of pyrazinamide-resistant tuberculosis in Hunan province and described the genotyping and clustering characteristics of the pyrazinamide-resistant Mycobacterium tuberculosis (PZA-R MTB) isolates. Methods: The drug susceptibility test results of first-line anti-tuberculosis drugs including isoniazid (INH), rifampicin (RFP), streptomycin (SM), ethambutol (EMB) and pyrazinamide (PZA), and the characteristics of patients were collected from 3 862 tuberculosis patients in Hunan Chest Hospital (Institute of Tuberculosis Control and Prevention) from January 2016 to December 2018. The prevalence of PZA-R TB was calculated and risk factors were analyzed by univariate and multivariable logistic regression analysis. Two hundred and twelve Mycobacterium tuberculosis isolates selected from June 2017 to June 2018 were genotyped using the 24-loci MIRU-VNTR system. The genetic difference value (h), and the Hunter-Gaston index (HGI) were used to evaluate the resolution and variation for the 24 loci. MIRU-VNTR results were analyzed using BioNumerics 5.0 software to conduct cluster analysis. Clustered isolates were further analyzed by pncA gene sequencing. Results: The rate of PZA-R TB among tuberculosis patients and MDR patients was 14.7%(566/3 862) and 60.5%(511/844), respectively. Multivariable logistic regression analysis showed that patients who were INH mono-resistance and MDR had a higher risk of developing PZA resistance, compared with TB patients who were pan-sensitive to anti-TB drugs (INH, RFP, SM, and EMB). The adjusted OR value (95%CI) was 13.08(5.67-30.18), 298.41(164.88-540.08), respectively, and P values were all less than 0.01. Clustering analysis showed that 65 strains formed 19 clusters, the clustering rate was 30.7%(65/212). Of 19 clusters, eight clusters had at least two isolates with identical pncA mutation types within each cluster. In eight clusters, cluster 4, 6, 16 had four, three, and two patients who lived in the same county, respectively, thus providing probable epidemiological links for the recent transmission of PZA-R Mycobacterium tuberculosis. At least 47.6%(101/212) of PZA drug-resistant TB patients were suggestive of primary drug resistance caused by transmission. Conclusions: The prevalence of PZA-R TB was severe in Hunan province. PZA susceptibility testing should be performed for isolates resistant to any first-line anti-tuberculosis drugs, especially for MDR-MTB isolates. Nearly half of tuberculosis patients were suggestive of primary drug resistance caused by transmission. The prevention and treatment strategy of PZA-R TB should focus on the standardized treatment and management of patients as well as control of the source of infection.

Hyperglyceridaemia-induced acute pancreatitis in pregnancy: Experience from a tertiary hospital in Singapore.

Acute pancreatitis (AP) is a serious condition that can occur suddenly in pregnancy. We present a case of sudden onset of epigastric pain with severely deranged serum triglyceride levels in a 32-year-old Vietnamese primigravida with no significant past medical history in the Singapore General Hospital. The patient was managed in the intensive care unit, with plasmapheres and intravenous insulin and was eventually a healthy term foetus was delievered via ceasarian section. This case showcased multidisciplinary co operation between the obstetrics, anaesthetic, endocrinology and intensive care team and serves as a reminder to consider this rare condition for future similar presentations.

[The derivation and vulidafion of a prediction rule for hypoxemia in infants with Pierre Robin sequence after weaning].

Objective: To set up a prediction scoring system for the hypoxemia in infants with Pierre Robin sequence after weaning and evaluate its clinical value. Methods: Data of consecutive patients from November 2016 to June 2019, who underwent mandibular distraction osteogenesis in Guangzhou Women and Children's Medical Center, were retrospectively analyzed (n=148). All the cases were divided into two groups according to the appearance of hypoxemia after weaning. They were randomly divided into the derivation cohorc (2/3,n=100) and the validation cohort (1/3,n=48). Single factor and multiple logistic regression analysis were used to select the independent risk factors related to hypoxemia and establish a prediction model. A prediction scoring system was developed in accordance with assigning of the value of each variable ß in the model. Internal verification of scoring system by validation population. Data of consecutive patients from July 2019 to November 2019, who underwent mandibular distraction osteogenesis, were prospectively analyzed (n=26). The diagnostic accuracy were conducted to evaluate the clinical value of the scoring system. Results: The logistic regression demonstrated that age at operation, pulmonary infection and the length of distraction less than 5 mm at weaning were the independent risk factors for hypoxemia. The P value of logistic regression model in Hosmer and Lemeshow goodness of fit test was 0.848, and a prediction scoring system was established accordingly. The area under the ROC curve of the scoring system was 0.890, and the optimum critical value was 53. The sensitivity, specificity, accuracy of the model were 78.6%(11/14),86.1%(74/86), 85.0%(85/100) respectively. The predictive effectiveness of the scoring system in the retrospective validation population was similar to that in the modeling population. 26 patients were included in the prospective analysis. The area under ROC curve of the scoring system was 0.870. The sensitivity, specificity and accuracy were 80.0%(5/6),95.0%(20/21), 96.1%(25/26) respectively. Conclusion: The prediction scoring system established in the study are efficacious for the hypoxemia in infants with Pierre Robin sequence after weaning.

Decitabine treatment for acute myeloid leukemia relapse after allogeneic hematopoietic stem cell transplantation.

Therapeutic options for patients with relapse of acute myeloid leukemia (AML) after allo-SCT are limited. Here, we present a case of a 49-year female with AML who underwent myeloablative allo-SCT from a matched sibling donor. Seven months after transplantation she developed cGVHD and suffered from extramedullary plus concurrent medullary relapse. The presence of CNS extramedullary disease is unique. Our patient was treated with decetabine. After one cycle the patient achieved complete remission and full donor chimerism without severe side effects or the occurrence of GVHD. Our case report, together with previous studies, provides strong evidence that decitabine may be a suitable treatment option for AML relapse after allogeneic transplantation, especially in patients who developed GVHD.

Body height and the spread of spinal anaesthesia for caesarean section: a prospective controlled trial.

BACKGROUND: No conclusive evidence exists on the effect of patient height on the spread of spinal anaesthesia. Our aim was to measure the ED50 and ED95 values of intrathecal ropivacaine in taller and shorter patients, and thus investigate the hypothesis that the spinal dose requirement in shorter patients is lower than that in taller patients undergoing caesarean section. METHODS: In this study, 270 pregnant women were assigned to the taller (Group T) or shorter group (Group S) based on their heights. Subjects in both groups were further randomly assigned to one of nine subgroups based on the dosage of intrathecal isobaric ropivacaine to be administered (7, 8, 9, 10, 11, 12, 13, 14 or 15 mg respectively). RESULTS: The ED50 and ED95 values of ropivacaine were 9.24 mg and 13.36 mg in Group S, and 10.11 mg and 14.63 mg in Group T, with no inter-group difference (P = 0.886). There was a significant inter-group difference in the incidence of hypotension and the changes in mean arterial pressure after spinal anaesthesia using 15 mg ropivacaine. The dose of ephedrine administered in Group S was higher than that in Group T when 15 mg ropivacaine was administered (P = 0.031). CONCLUSION: The taller and shorter patients did not respond differently to modest intrathecal doses of ropivacaine. However, a larger dose of ropivacaine was associated with an increased incidence of hypotension in shorter patients compared to that in taller patients.

Hypoxia enhances periodontal ligament stem cell proliferation via the MAPK signaling pathway.

There is high incidence of periodontal disease in high-altitude environments; hypoxia may influence the proliferation and clone-forming ability of periodontal ligament stem cells (PDLSCs). The MAPK signaling pathway is closely correlated with cell proliferation, differentiation, and apoptosis. Thus, we isolated and cultured PDLSCs under hypoxic conditions to clarify the impact of hypoxia on PDLSC proliferation and the underlying mechanism. PDLSCs were separated and purified by the limiting dilution method and identified by flow cytometry. PDLSCs were cultured under hypoxic or normoxic conditions to observe their cloning efficiency. PDLSC proliferation at different oxygen concentrations was evaluated by MTT assay. Expression of p38/MAPK and MAPK/ERK signaling pathway members was detected by western blotting. Inhibitors for p38/MAPK or ERK were applied to PDLSCs to observe their impacts on clone formation and proliferation. Isolated PDLSCs exhibited typical stem cell morphological characteristics, strong abilities of globular clone formation and proliferation, and upregulated expression of mesenchymal stem cell markers. Stem cell marker expression was not statistically different between PDLSCs cultured under hypoxia and normoxia (P > 0.05). The clone number in the hypoxia group was significantly higher than that in the control (P < 0.05). PDLSC proliferation under hypoxia was higher than that of the control (P < 0.001). p38 and ERK1/2 phosphorylation in hypoxic PDLSCs was markedly enhanced compared to that in the control (P < 0.05). Either P38/MAPK inhibitor or ERK inhibitor treatment reduced clone formation and proliferation. Therefore, hypoxia enhanced PDLSC clone formation and proliferation by activating the p38/MAPK and ERK/MAPK signaling pathways.

Limits to metallic conduction in atomic-scale quasi-one-dimensional silicon wires.

The recent observation of ultralow resistivity in highly doped, atomic-scale silicon wires has sparked interest in what limits conduction in these quasi-1D systems. Here we present electron transport measurements of gated Si:P wires of widths 4.6 and 1.5 nm. At 4.6 nm we find an electron mobility, µ(el)≃60 cm²/V s, in excellent agreement with that of macroscopic Hall bars. Metallic conduction persists to millikelvin temperatures where we observe Gaussian conductance fluctuations of order δG∼e²/h. In thinner wires (1.5 nm), metallic conduction breaks down at G≲e²/h, where localization of carriers leads to Coulomb blockade. Metallic behavior is explained by the large carrier densities in Si:P δ-doped systems, allowing the occupation of all six valleys of the silicon conduction band, enhancing the number of 1D channels and hence the localization length.

Relative importance of seed drying rate, desiccation tolerance, and cryotolerance for the conservation of Ardisia elliptica, A. brunnescens and A. virens.

BACKGROUND: The pan-tropical genus Ardisia has more than 400 species and is of high horticultural and medicinal value. Due to overexploitation it is important to conserve the germplasm of this genus. OBJECTIVE: To investigate the feasibility and methods of cryopreservation for long-term seed storage of three Ardisia species: A. elliptica Thunb., A. brunnescens Walker, and A. virens Kurz. METHODS: We tested whether rapid desiccation can increase desiccation tolerance and cryotolerance, and whether the thawing rate can affect cryopreservation success. Seeds were subjected to three desiccation treatments: 1) activated silica gel at 25 +/- 2 degree C, and 4% relative humidity (RH); 2) saturated NaCl solution in closed jars in 25 +/- 2 degree C and 75% RH; and 3) air-drying at room conditions at 27 +/- 2 degree C and RH 60% for different desiccation durations (12h, 24h, 48h, 96h, and 196h). Seeds were then assessed for desiccation tolerance and cryotolerance after rapid thawing (direct immersion in 36 degree C water bath for 2 min) or slow thawing (at 27°C for 1 h). RESULTS: For all three species, desiccation method and duration significantly affected cryotolerance (P < 0.0001). Fast desiccation did not improve germination compared to slower desiccation (P < 0.01). Whereas A. elliptica germination was unaffected by desiccation duration, drying time significantly (P < 0.0001) affected germination percentage in the other two species especially after 48h. Although slow thawing improved cryotolerance of A. brunnescens seeds (P < 0.05), there was no significant effect of thawing rate on A. elliptica. A. virens seed did not survive cryopreservation. CONCLUSIONS: Cryopreservation protocols of Ardisia species may be species-specific and should be established for each species in the genus so that cryopreservation can be used as a successful conservation strategy.

First Report of Two Distinct Phytoplasma Species, 'Candidatus Phytoplasma cynodontis' and 'Candidatus Phytoplasma asteris,' Simultaneously Associated with Yellow Decline of Wodyetia bifurcata (Foxtail Palm) in Malaysia.

The foxtail palm (Wodyetia bifurcata), an Australian native species, is an adaptable and fast-growing landscape tree. The foxtail palm is most commonly used in landscaping in Malaysia. Coconut yellow decline (CYD) is the major disease of coconut associated with 16SrXIV phytoplasma group in Malaysia (1). Symptoms consistent with CYD, such as severe chlorosis, stunting, general decline, and death were observed in foxtail palms from the state of Selangor in Malaysia, indicating putative phytoplasma infection. Symptomatic trees loses their green and vivid appearance as a decorative and landscape ornament. To determine the presence of phytoplasma, samples were collected from the fronds of 12 symptomatic and four asymptomatic palms in September 2012, and total DNA was extracted using the CTAB method (3). Phytoplasma DNA was detected in eight symptomatic palms using nested PCR with universal phytoplasma 16S rDNA primer pairs, P1/P7 followed by R16F2n/R16R2 (2). Amplicons (1.2 kb in length) were generated from symptomatic foxtail palms but not from symptomless plants. Phytoplasma 16S rDNAs were cloned using a TOPO TA cloning kit (Invitrogen). Several white colonies from rDNA PCR products amplified from one sample with R16F2n/R16R2 were sequenced. Phytoplasma 16S rDNA gene sequences from single symptomatic foxtail palms showed 99% homology with a phytoplasma that causes Bermuda grass white leaf (AF248961) and coconut yellow decline (EU636906), which are both members of the 16SrXIV 'Candidatus Phytoplasma cynodontis' group. The sequences also showed 99% sequence identity with the onion yellows phytoplasma, OY-M strain, (NR074811), from the 'Candidatus Phytoplasma asteris' 16SrI-B subgroup. Sequences were deposited in the NCBI GenBank database (Accession Nos. KC751560 and KC751561). Restriction fragment length polymorphism (RFLP) analysis was done on nested PCR products produced with the primer pair R16F2n/R16R2. Amplified products were digested separately with AluI, HhaI, RsaI, and EcoRI restriction enzymes based on manufacturer's specifications. RFLP analysis of 16S rRNA gene sequences from symptomatic plants revealed two distinct profiles belonging to groups 16SrXIV and 16SrI with majority of the 16SrXIV group. RFLP results independently corroborated the findings from DNA sequencing. Additional virtual patterns were obtained by iPhyclassifier software (4). Actual and virtual patterns yielded identical profiles, similar to the reference patterns for the 16SrXIV-A and 16SrI-B subgroups. Both the sequence and RFLP results indicated that symptoms in infected foxtail palms were associated with two distinct phytoplasma species in Malaysia. These phytoplasmas, which are members of two different taxonomic groups, were found in symptomatic palms. Our results revealed that popular evergreen foxtail palms are susceptible to and severely affected by phytoplasma. To our knowledge, this is the first report of a mixed infection of a single host, Wodyetia bifurcata, by two different phytoplasma species, Candidatus Phytoplasma cynodontis and Candidatus Phytoplasma asteris, in Malaysia. References: (1) N. Nejat et al. Plant Pathol. 58:1152, 2009. (2) N. Nejat et al. Plant Pathol. J. 9:101, 2010. (3) Y. P. Zhang et al. J. Virol. Meth. 71:45, 1998. (4) Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.

Characteristics, risk factors and outcomes of critically ill patients with active TB.

BACKGROUND: TB continues to impose a significant healthcare burden despite advancement in diagnostics and increased availability of effective antimicrobials. Recent years have seen a resurgence of the disease in association with increasing life expectancy and use of immunosuppressive therapy. Mortality remains high in TB patients requiring admission to critical care units.METHODS: We conducted a retrospective study in two public hospitals to determine factors associated with mortality in patients with TB requiring critical care admission. All patients aged ≥21 years with a diagnosis of active TB involving any organ system at the time of a critical care admission were eligible. The primary outcome measure was 30-day mortality.RESULTS: Over the study period of 4 years, 148 patients were identified. Overall 30-day mortality was 36.5%. Based on multivariate analysis, factors which independently correlated with 30-day mortality include higher APACHE II (Acute Physiology and Chronic Health Evaluation II) score, acid-fast bacilli smear positivity, initiation of anti-TB treatment prior to critical care admission and need for renal replacement therapy.CONCLUSION: TB in critically ill patients continues to be associated with significant mortality. The factors identified to be associated with poor survival outcomes in our study were largely related to greater disease burden and potential for suboptimal treatment.

[Restratifying the prognosis of acute myeloid leukemia patients with CEBPA double mutations based on CSF3R mutations and measurable residual disease].

Objective: This investigation aims to assess the impact of CSF3R mutations and the presence of measurable residual disease (MRD) on the prognosis of patients with CEBPA double mutations who have acute myeloid leukemia (AML) . Methods: The prognostic significance of these two factors was examined in the present study, which included 66 patients with complete genetic mutations and sequential MRD information. Results: Following the second course of chemotherapy, the MRD status and CSF3R mutations of these patients were linked to their long-term prognosis. CSF3R mutated patients showed inferior relapse-free survival (RFS) (5-year RFS: 15.2% vs 38.7% , P=0.006) and overall survival (OS) (5-year OS: 18.2% vs 60.6% , P=0.038) compared with those with wild-type CSF3R. After the second course of chemotherapy, patients with negative MRD had an RFS of 64 months and an OS of not reaching, which was significantly longer than that of patients with positive MRD (15 and 48 months, and the P value were 0.004 and 0.050, respectively) . CSF3R mutations (HR=0.317, 95% CI 0.129-0.779, P=0.012) , WT1 mutations (HR=0.304, 95% CI 0.115-0.804, P=0.016) , and NRAS mutations (HR=0.153, 95% CI 0.061-0.385, P<0.001) were all independently associated with a poor prognosis for RFS, and CSF3R mutations and positive MRD tended to be independently associated with a poor prognosis for OS, according to the results of a Cox proportional-hazards model analysis (P values were 0.071 and 0.088, respectively) . The patients were divided into three groups based on their CSF3R mutation status and MRD status following treatment: wide-type CSF3R and negative MRD, mutated CSF3R or positive MRD, and mutated CSF3R and positive MRD, which showed significantly different RFS (P<0.001) and OS (P=0.006) . Conclusion: Both CSF3R mutations and positive MRD were associated with poor outcome in AML patients with CEBPA double mutations. An integrity model based on these two factors may be beneficial for accurately evaluating the prognosis of these patients.

Protein phosphatases in cell signalling.

Protein phosphorylation is the most common post-translational modification and plays a role in all known pathways of signal transduction. Net phosphorylation is a result of the balance of activities of protein kinases and phosphatases. There is increasing evidence that the regulated removal of phosphate groups from proteins, catalyzed by protein phosphatases, is required for the downstream activation of other signalling proteins.

Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist.

STUDY DESIGN: Animal proof of principle study. OBJECTIVES: To determine whether capromorelin, a compound that causes defecation by stimulating ghrelin receptors within the lumbosacral defecation centers, is effective after spinal cord injury (SCI), and whether SCI significantly alters sensitivity to the compound. SETTING: University of Melbourne and Austin Hospital, Melbourne, Australia. METHODS: Rats were subjected to spinal cord contusion injury or were sham-operated. At 6 weeks after surgery, effects of capromorelin on blood pressure, heart rate and propulsive contractions of the colorectum were investigated. RESULTS: Capromorelin caused robust propulsive activity in the colorectum soon after its application. The compound was similarly effective in naïve, sham-operated and spinal cord-injured rats. Blood pressure increases caused by capromorelin were not exaggerated after SCI, and there was no evidence of phasic blood pressure increases when the colon was contracted by the compound. CONCLUSION: Capromorelin is a therapeutic compound that could potentially be used to relieve constipation by triggering defecation in spinal cord-injured patients.

The linkage of genes for the human interferon-induced antiviral protein and indophenol oxidase-B traits to chromosome G-21.

13 independent mouse-human somatic cell hybrid clones derived from beta-propiolactone-inactivated Sendai stimulated cell fusion of human cells with mouse cells were tested for their sensitivities to human and mouse interferon. All of them were protected by mouse interferon and only six of the clones were protected by both human and mouse interferon. Only the six that were protected by human interferon were shown to express the human dimeric form of indophenol oxidase. Complete chromosomal analysis of the clones indicated human chromosome G-21 to be the only human chromosome in common for the six clones which had both phenotypes present. Nine subclones were derived from one of the clones expressing both phenotypes. Eight of the nine subclones were shown to retain both phenotypes, whereas one subclone lost both. Chromosomal analysis of the subclones indicated the loss of chromosome G-21 from the subclone which lost both phenotypes. It is apparent from these findings that the gene(s) for indophenol oxidase (IPO-B) and the gene(s) for the antiviral protein are syntenic and that they are linked to human chromosome G-21.

Expression of cytosolic and thiolated proteome of Musca domestica larvae under oxidative challenge.

The study was aimed to investigate the expression of cytosolic and thiolated proteins of Musca domestica larvae under oxidative stress. Proteins from acute treatment of hydrogen peroxide (LC50 = 21.52% (v/v)) on 3rd stage larvae of housefly were extracted and purified using an activated Thiol Sepharose® for thiolated protein purification. Two dimensional gel electrophoresis was used for visualizing and analyzing expression of cytosolic and thiolated proteins. Protein spots with more than 5 fold of expression change were identified using liquid chromatography- tandem mass spectrometry (LC-MS/MS). The cytosolic proteins were actin, tropomyosin, ubiquitin, arginine kinase, pheromone binding protein/general odorant binding protein, and ATP: guanidino phosphotransferase. The thiolated proteins with more than 5 fold change in expression as an effect to the acute treatment were fructose bisphosphate aldolase, short chain dehydrogenase and lactate/malate dehydrogenase. The proteins identified in the study should provide vital information for future reference in oxidative stress defence and response occurring in houseflies.

High SUV uptake on FDG-PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG-PET/CT staging in lymphoma.

BACKGROUND: Data assessing the role of positron emission tomography (PET)/computed tomography (CT) imaging in lymphoma staging is still being accumulated and current staging is based primarily on CT. This study aims to compare the value of PET/CT over conventional CT and bone marrow biopsy (BMB) in the initial evaluation of patients with lymphoma. METHODS: Data on 122 patients with PET/CT scans as part of their initial staging were prospectively collected and reviewed. All patients had complete staging, including BMB. RESULTS: Among the 122 patients, 101 had non-Hodgkin's lymphoma (NHL) and 21 had Hodgkin's lymphoma (HL). Compared with conventional CT, PET/CT upstaged 21 (17%) cases [B-cell non-Hodgkin's lymphoma (B-NHL), 12; T-cell non-Hodgkin's lymphoma (T-NHL), 3; HL, 6]. Of significance, in 13 patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-avid splenic lesions, four had normal CT findings. A maximum FDG uptake of >10 standardized uptake value (SUV) seems to significantly correlate with an aggressive B-cell lineage (odds ratio 2.47, 95% confidence interval 2.23-2.70). Overall, PET scan was concordant with BMB results in 108 (89%) and discordant in 14 (11%) cases. In HL, our data show that PET scan and marrow results agreed in 19 of the cases (90%), being concordantly negative in 18 cases and concordantly positive in one, giving a negative predictive value (NPV) of 100%, sensitivity of 100% and specificity of 90%. Of note, all 13 with early-stage HL had negative PET/CT scan and BMB. In NHL, all 17 cases of T-NHL had concordant PET and BMB results. In patients with aggressive B-NHL, BMB and PET/CT agreed in 58 patients (92%) and disagreed in five (8%), while the corresponding rates in indolent B-cell lymphoma were 14 (67%) and seven patients (33%), respectively. All seven were falsely negative. CONCLUSIONS: PET/CT upstages 17% of cases and detects occult splenic involvement. This may have potential therapeutic and prognostic implications. SUV >10 may predict for an aggressive histology. Except for indolent B-NHL, our data show that PET scans have a good overall NPV in excluding lymphomatous bone marrow involvement. This is particularly true of early-stage HL, suggesting that BMB may be safely omitted in this group.

An early event in the interferon-induced transmembrane signaling process.

Human interferon stimulates a transient two- to threefold increase in the concentration of diacylglycerol and inositol tris-phosphate within 15 to 30 seconds of cell exposure to interferon. Antibodies to interferon inhibit this effect. The stimulation was measurable in isolated cell membranes exposed to interferon. Human alpha and beta, but not gamma, interferon stimulate this increase in cells containing the appropriate interferon receptor. The effect was proportional to the number of interferon receptors. Both the diacylglycerol increase and antiviral effects induced by interferon could be correlated in terms of dose dependence. Thus, a transient diacylglycerol increase is an early event in the interferon-induced transmembrane signaling process.

Human chromosome 21 dosage: effect on the expression of the interferon induced antiviral state.

Human primary skin fibroblasts trisomic for chromosome 13, 18, or 21 and diploid human skin fibroblasts were induced for an antiviral response with human interferon. The cells that were trisomnic for chromosome 21 were three to seven times more sensitive to protection by human interferon than the normal diploid or trisomic 18 or 13 fibroblasts. The differential response in trisomnic 21 cells is consistent with the known assignment of the human antiviral gene to chromosome 21.