UMP/CMPK Is Not the Critical Enzyme in the Metabolism of Pyrimidine Ribonucleotide and Activation of Deoxycytidine Analogs in Human RKO Cells

Human UMP/CMP kinase was identified based on its enzymatic activity in vitro. The role of this protein is considered critical for the maintenance of pyrimidine nucleotide pool profile and for the metabolism of pyrimidine analogs in cells, based on the in vitro study of partially purified enzyme and recombinant protein. However, no detailed study has yet addressed the role of this protein in nucleotide metabolism in cells.Two stable cell lines in which UMP/CMP kinase (mRNA: AF087865, EC 2.7.4.14) can be either up-regulated or down-regulated were developed using Tet-On Gene Expression Systems. The amount and enzymatic activity of UMP/CMP kinase extracted from these two cell lines can be induced up by 500% or down by 95-98%. The ribonucleotides of endogenous pyrimidine as well as the metabolism of exogenous natural pyrimidine nucleosides and their analogs were not susceptible to the altered amount of UMP/CMP kinase in these two stable RKO cell lines. The level of incorporation of pyrimidine nucleoside analogs, such as gemcitabine (dFdC) and troxacitabine (L-OddC), into cellular DNA and their potency in inhibiting cell growth were not significantly altered by up-regulation or down-regulation of UMP/CMP kinase expression in cells.The UMP/CMP kinase (EC 2.7.4.14) expressed in RKO cells is not critical for the phosphorylation of (d)CMP and the maintenance of natural nucleotide pools. It also does not play an important role in the activation of dFdC and L-OddC. The increase by 500% or decrease by 95-98% in the levels of UMP/CMP kinase do not affect steady state levels of dFdC and L-OddC in RKO cells. Overall, the activity and possible mechanisms of recombinant UMP/CMP kinase expressed in the in vitro system can not be extended to that of UMP/CMP kinase expressed in a cell system or an in vivo system

Solisluumurtumien konservatiivinen ja operatiivinen hoito : Systemaattinen kirjallisuuskatsaus 1190 potilaasta

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Disseminated tuberculosis presenting with polymorphonuclear effusion and septic shock in an HIV-seropositive patient: a case report

<p>Abstract</p> <p>Introduction</p> <p>Because a substantial number of patients present with few or atypical symptoms, the recognition of tuberculosis remains challenging. Disseminated tuberculosis presenting with septic shock has already been described in some case reports, but, to the best of our knowledge, it has never been associated with polymorphonuclear effusion.</p> <p>Case presentation</p> <p>We describe the case of a 27-year-old man from western Africa who was seropositive for human immunodeficiency virus. He presented with pleural and abdominal polymorphonuclear effusions and quickly developed septic shock due to disseminated <it>Mycobacterium tuberculosis </it>infection leading to multiple organ failure and death.</p> <p>Conclusion</p> <p>In high-risk patients, <it>Mycobacterium tuberculosis </it>infection should be considered even in exceptional clinical presentations, such as septic shock and polymorphonuclear effusions.</p

Effective Interventions and Decline of Antituberculosis Drug Resistance in Eastern Taiwan, 2004–2008

BACKGROUND: The Taiwan health authority recently launched several tuberculosis (TB) control interventions, which may have an impact on the epidemic of drug-resistant TB. We conducted a population-based antituberculosis drug resistance surveillance program in Eastern Taiwan to measure the proportions of notified TB patients with anti-TB drug resistance and the trend from 2004 to 2008. METHODS AND FINDINGS: All culture-positive TB patients were enrolled. Drug susceptibility testing results of the first isolate of each TB patient in each treatment course were analyzed. In total, 2688 patients were included, of which 2176 (81.0%) were new TB cases and 512 (19.0%) were previously treated cases. Among the 2176 new TB cases, 97 (4.5%) were retreated after the first episode of TB treatment within the study period. The proportion of new patients with any resistance, isoniazid resistance but not multidrug-resistant TB (resistant to at least isoniazid and rifampin, MDR-TB), and MDR-TB was 16.4%, 7.5%, and 4.0%, respectively, and that among previously treated cases was 30.9%, 7.9%, and 17.6%, respectively. The combined proportion of any resistance decreased from 23.3% in 2004 to 14.3% in 2008, and that of MDR-TB from 11.5% to 2.4%. CONCLUSIONS: The proportion of TB patients with drug-resistant TB in Eastern Taiwan remains substantial. However, an effective TB control program has successfully driven the proportion of drug resistance among TB patients downward

The role of mutations in core protein of hepatitis B virus in liver fibrosis

The core protein of hepatitis B virus encompasses B- and T-cell immunodominant epitopes and subdivided into two domains: the N-terminal and the functional C-terminal consisted phosphorylation sites. Mutations of the core gene may change the conformation of the core protein or cause alteration of important epitopes in the host immune response. In this study twenty nine men (mean age 40 ± 9 years old) with chronic hepatitis B were recruited for direct sequencing of the core gene. Serum ALT and HBV DNA level were measured at the time of liver biopsy. The effects of core protein mutations on patients' characteristics and subsequently mutations in B cell, T helper and cytotoxic T lymphocyte (CTL) epitopes and also C-terminal domain of core protein on the activity of liver disease was evaluated. Liver fibrosis was significantly increased in patients with core protein mutation (1.0 ± 0.8 vs 1.9 ± 1.4 for mean stage of fibrosis P = 0.05). Mutations in CTL epitopes and in phosphorylation sites of C-terminal domain of core protein also were associated with higher liver fibrosis (P = 0.003 and P = 0.04; Fisher's exact test for both). Patients with mutation in C-terminal domain had higher serum ALT (62 ± 17 vs 36 ± 12 IU/l, p = 0.02). Patients with mutations in B cell and T helper epitopes did not show significant difference in the clinical features. Our data suggests that core protein mutations in CTL epitopes and C-terminal domain accompanied with higher stage of liver fibrosis may be due to alterations in the function of core protein

Emerging strengths in Asia Pacific bioinformatics

The 2008 annual conference of the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation set up in 1998, was organized as the 7th International Conference on Bioinformatics (InCoB), jointly with the Bioinformatics and Systems Biology in Taiwan (BIT 2008) Conference, Oct. 20–23, 2008 at Taipei, Taiwan. Besides bringing together scientists from the field of bioinformatics in this region, InCoB is actively involving researchers from the area of systems biology, to facilitate greater synergy between these two groups. Marking the 10th Anniversary of APBioNet, this InCoB 2008 meeting followed on from a series of successful annual events in Bangkok (Thailand), Penang (Malaysia), Auckland (New Zealand), Busan (South Korea), New Delhi (India) and Hong Kong. Additionally, tutorials and the Workshop on Education in Bioinformatics and Computational Biology (WEBCB) immediately prior to the 20th Federation of Asian and Oceanian Biochemists and Molecular Biologists (FAOBMB) Taipei Conference provided ample opportunity for inducting mainstream biochemists and molecular biologists from the region into a greater level of awareness of the importance of bioinformatics in their craft. In this editorial, we provide a brief overview of the peer-reviewed manuscripts accepted for publication herein, grouped into thematic areas. As the regional research expertise in bioinformatics matures, the papers fall into thematic areas, illustrating the specific contributions made by APBioNet to global bioinformatics efforts

Measurement of Exclusive B Decays to Final States Containing a Charmed Baryon

Using data collected by the CLEO detector in the Upsilon(4S) region, we report new measurements of the exclusive decays of B mesons into final states of the type Lambda_c^+ p-bar n(pi), where n=0,1,2,3. We find signals in modes with one, two and three pions and an upper limit for the two body decay Lambda_c^+ pbar. We also make the first measurements of exclusive decays of B mesons to Sigma_c p-bar n(pi), where n=0,1,2. We find signals in modes with one and two pions and an upper limit for the two body decay Sigma_c p-bar. Measurements of these modes shed light on the mechanisms involved in B decays to baryons.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Measurement of the Masses and Widths of the Sigma_c^++ and Sigma_c^0 Charmed Baryons

Using data recorded by the CLEO II and CLEO II.V detector configurations at CESR, we report new measurements of the masses of the Sigma_c^{++} and Sigma_c^0 charmed baryons, and the first measurements of their intrinsic widths. We find M(Sigma_c^{++}) - M(Lambda_c^+) = 167.4 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^{++}) = 2.3 +- 0.2 +- 0.3 MeV, and M(Sigma_c^0) - M(Lambda_c^+) = 167.2 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^0) = 2.5 +- 0.2 +- 0.3 MeV, where the uncertainties are statistical and systematic, respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PRD, Rapid Communications. Reference [13] correcte

A Chitinase from Aeromonas veronii CD3 with the Potential to Control Myxozoan Disease

Background: The class Myxosporea encompasses about 2,400 species, most of which are parasites of fish and cause serious damage in aquaculture. Due to the concerns about food safety issues and limited knowledge of Myxozoa life cycle and fish immune system, no chemicals, antibiotics or immune modulators are available to control myxozoa infection. Therefore, little can be done once Myxozoa establishment has occurred. Methodology/Principal Findings: In this paper we isolated Aeromonas veronii CD3 with significant myxospore shell valvedegrading ability from pond sediment. A 3,057-bp full-length chitinase gene was consequently cloned, and the corresponding mature, recombinant chitinase (ChiCD3) produced by Escherichia coli had substantial chitinase activity. The deduced sequence of ChiCD3 contained one catalytic domain, two chitin-binding domains, and one putative signal peptide. ChiCD3 had an optimal activity at 50uC and pH 6.0, and retained more than 50 % of its optimal activity under warm water aquaculture conditions (,30uC and pH,7.0). After incubation with ChiCD3, 38.064.8 % of the myxospores had damaged shell valves, whereas myxospores incubated with commercially available chitinases remained intact. Conclusion/Significance: This study reveals a new strategy to control myxozoan disease. ChiCD3 that has capacity to damage the shell valve of myxospores can be supplemented into fish feed and used to control Myxozoa-induced disease

Dynamic in vitro measurement of patellar movement after total knee arthroplasty: an in vitro study

BACKGROUND: Changing the kinematic behaviour of patellar movement could be one of the reasons for anterior knee pain after implantation of a total knee arthroplasty (TKA). The aim of the current study was to measure the potential influence on patellar kinematics of patellar resurfacing during TKA. METHODS: Patellar movement before and after TKA with and without patellar resurfacing was measured under dynamic conditions in an in vitro cadaver simulation. Physiologic Musculus quadriceps forces were applied to five physiologic human knee specimens undergoing simulated isokinetic extension motions, patellar movement was measured using an ultrasonic measurement system. Thereafter, the Interax(® )I.S.A.-prosthesis system was implanted without and with resurfacing the patella, and patellar movement was again measured. RESULTS: The physiologic patella center moved on a semilunar path up to 6.4 mm (SD 6.4 mm) medially during extension. After TKA, the unresurfaced patella showed significantly less medial translation (p = 0.04) than the resurfaced patella. Subsequent resurfacing of the patella then resulted in a return to mediolateral positioning of the patella similar to the physiological case, whereas the resurfaced patella tilted up to twice as much as physiologic. CONCLUSION: The results of this study suggest that resurfacing of the patella during TKA can result in a restoration of the physiologic mediolateral shift of the patellofemoral joint while angulation of the patella remains unphysiologic