Ciprofloxacin-resistant gonorrhoea.
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Anti-Infective Agents↗
Biomedical subjects
A Tang
Publications and source records attributed to A Tang.
B-cell repertoire formation: role of the recombination signal sequence in non-random V segment utilization.
V, D, and J gene segments rearrange at different frequencies in vivo. Each rearranging gene segment is flanked by a recombination signal sequence (RSS), which is composed of a conserved heptamer and nonamer, separated by a spacer of conserved length but not conserved sequence. We summarize data from our lab and other labs showing that in many cases, but not all, the RSS can account for differences in recombination frequencies observed in vivo. Our approach is to determine the initial frequency of rearrangement of the V genes in vivo, and then place the RSSs of two V genes into a competition recombination substrate to determine the relative frequency with which the two RSSs support recombination. In one example, we have shown that a polymorphism in the heptamer of a Vkappa gene can result in a significant reduction in recombination frequency. This particular allele is prevalent in Navajos and absent in other populations. We suggest that this single change may play a major role in the high susceptibility of Navajos to Haemophilus influenzae infection, since this Vkappa gene is important in the antibody response to this bacteria. We also describe experiments showing that the sequence of the spacer of the RSS can play an important role in relative recombination frequencies.
Animals↗
Sexually transmitted infections in elderly people.
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Adult↗
Metastatic calcification of the cardiac conduction system with heart block: an under-reported entity in chronic renal failure patients.
Systemic metastatic calcification is a common complication of chronic renal failure. Cardiac involvement is particularly ominous, especially when the cardiac conduction system is affected. Conduction defects, arrhythmias, and sudden death have all been reported with conduction system calcification; however, these are relatively under-reported or unrecognized causes of cardiac morbidity and mortality. We describe a 40-year-old man with Von Hippel-Lindau disease who had been maintained on hemodialysis for two years following bilateral nephrectomies for renal cell carcinoma. The patient presented with symptomatic complete heart block that had progressed from Mobitz type I atrioventricular block. Two months later, while being internally paced, the patient died unexpectedly after a complicated hospital admission. Postmortem revealed extensive vascular, myocardial, and conduction system calcification. Conduction system calcification may cause sudden death in chronic renal failure patients during hospital admission, or unexpectedly while the patient is in the community. Knowledge of this condition is necessary to detect it, as the conduction system is not routinely examined. A routine abbreviated conduction system examination is warranted for patients with systemic metastatic calcification, especially if they have sudden death or a known history of heart block.
Adult↗
[Apoptosis and apoptosis-related gene expression in nasopharyngeal carcinoma].
OBJECTIVE: To study apoptosis and expression of apoptosis-related genes in nasopharyngeal carcinoma(NPC). METHODS: Paraffin-embedded tissue blocks from 73 cases of NPC and 20 cases of chronic nasopharyngitis were used in this study. Using terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (Tunel) and immunohisytochemistry S-P method, the apoptotic rate (AR) and expression of p16 and bcl-2 protein were examined. RESULTS: Few apoptotic cells were found in NPC, the AR significantly lower than that of chronic nasopharyngitis (P < 0.01). The frequency of expression of p16 and bcl-2 in NPC was 28.8% (21/73) and 81.2% (59/73), respectively, while that in chronic nasopharyngitis was 90% (18/20) and 15% (3/20), respectively. In NPC, expression of p16 was positively correlated, while bcl-2 negatively correlated with the AR (P < 0.01). According to 3-year follow up, the survival rate was higher in NPC patients with AR > 2.0 and negative bcl-2 expression, whereas that was higher in patients with positive expression of p16. CONCLUSION: Apoptosis is inhibited in NPC which may be related to p16 and bcl-2 gene dysregulation. Apoptosis correlates with prognosis in NPC patients.
Adolescent↗
Decreased morbidity and use of hospital services in English HIV-infected individuals with increased uptake of anti-retroviral therapy 1996-1997. National Prospective Monitoring System Steering Group.
OBJECTIVE: To investigate the relationship between changing morbidity patterns, the use of hospital services by HIV-infected patients and the uptake of antiretroviral therapy (ART) in England. DESIGN: Prospective serial cross-sectional analyses based on data collected through the National Prospective Monitoring System (NPMS), a multi-centre prospective monitoring system. SETTING: HIV-infected patients seen in 10 clinics, five London and five non-London, during the three semesters, 1 January 1996 to 30 June 1997. MAIN OUTCOME MEASURES: The mean use of hospital services per patient-year, mean new HIV-related opportunistic illnesses per 1000 patient-years and percentage uptake of ART. RESULTS: The use of inpatient services changed particularly among AIDS patients. The mean number of inpatient days for AIDS patients decreased from 19.7 [95% confidence interval (CI) 13.7-25.7] in 1996 to 11.2 (95% CI 6.1-15.6) per patient-year in 1997. Concurrently the number of new AIDS-defining events decreased significantly from 567 (95% CI 529-607) to 203 (95% CI 183-225) per 1000 patient-years. The overall uptake of ART increased significantly from 33% (95% CI 31-35%) to 50% (95% CI 48-52%), and a switch from mono or dual to triple therapy or quadruple or more therapy was observed. However, by mid-1997 only 29% (95% CI 26-32%) of asymptomatic patients and 51% (95% CI 49-54%) of patients with symptomatic non-AIDS were on ART, compared with 69% (95% CI 66-71%) of AIDS patients. CONCLUSION: The observed reduction in new AIDS-defining events has led to a reduction in the need for inpatient hospital care and has been associated with an increased uptake of ART, including a switch to triple therapy. All of these factors are likely to have contributed to the observed reduction in mortality among English AIDS patients. As the overall uptake of ART remained relatively low in English centres further improvements can be anticipated. However, the medium to long-term effects of these treatment regimens will need to be closely monitored.
Anti-HIV Agents↗
Prediction of sustained ventricular tachycardia inducible by programmed stimulation in patients with coronary artery disease. Utility of clinical variables.
BACKGROUND: Cardiologists often use clinical variables to determine the need for electrophysiological studies to stratify patients for risk of sudden death. It is not clear whether this is rational in patients with coronary artery disease, left ventricular dysfunction, and nonsustained ventricular tachycardia. METHODS AND RESULTS: We analyzed the first 1721 patients enrolled in the Multicenter UnSustained Tachycardia Trial to determine whether clinical variables could predict which patients would have inducible sustained monomorphic ventricular tachycardia. The rate of inducibility of sustained ventricular tachycardia was significantly higher in patients with a history of myocardial infarction and in men compared with women. There was a progressively increased rate of inducibility with increasing numbers of diseased coronary arteries. There was a significantly lower rate of inducibility in patients with prior coronary artery bypass surgery and in patients who also had noncoronary cardiac disease. The rate of inducibility was higher in patients of white race, patients with recent (</=6 weeks) angina, left ventricular dyskinesis, and in patients with greater numbers of fixed thallium defects. Inducibility was more likely in patients who had a prior myocardial infarction complicated by congestive heart failure, ventricular tachycardia, or fibrillation </=48 hours after the onset of infarction. Although these associations are statistically significant, the accuracy of the clinical variables in discriminating between patients with and those without inducible ventricular tachycardia is only modest (receiver operator characteristic area <0.70). CONCLUSIONS: Multiple clinical variables are independently associated with inducible sustained ventricular tachycardia. However, they have limited utility to guide clinical decisions regarding the use of electrophysiological testing for risk stratification in this patient population.
Aged↗
Requirement for T-cell apoptosis in the induction of peripheral transplantation tolerance.
The mechanisms of allograft tolerance have been classified as deletion, anergy, ignorance and suppression/regulation. Deletion has been implicated in central tolerance, whereas peripheral tolerance has generally been ascribed to clonal anergy and/or active immunoregulatory states. Here, we used two distinct systems to assess the requirement for T-cell deletion in peripheral tolerance induction. In mice transgenic for Bcl-xL, T cells were resistant to passive cell death through cytokine withdrawal, whereas T cells from interleukin-2-deficient mice did not undergo activation-induced cell death. Using either agents that block co-stimulatory pathways or the immunosuppressive drug rapamycin, which we have shown here blocks the proliferative component of interleukin-2 signaling but does not inhibit priming for activation-induced cell death, we found that mice with defective passive or active T-cell apoptotic pathways were resistant to induction of transplantation tolerance. Thus, deletion of activated T cells through activation-induced cell death or growth factor withdrawal seems necessary to achieve peripheral tolerance across major histocompatibility complex barriers.
Abatacept↗
Immunogenicity and protective efficacy of DNA vaccines encoding secreted and non-secreted forms of Mycobacterium tuberculosis Ag85A.
OBJECTIVE: To determine the efficacy of Ag85A-DNA against challenge with a highly virulent human clinical isolate of Mycobacterium tuberculosis (CSU37) and to compare the potencies of two types of Ag85A-DNA vaccines; those expressing secreted and non-secreted forms of the protein. DESIGN: Ag85A-DNA vaccinated mice were challenged with a highly virulent clinical isolate of M. tuberculosis (CSU37) in order to compare the efficacy of these vaccines. In vitro studies were also performed. RESULTS: Enhanced humoral and cellular responses were induced in mice vaccinated with the secreted Ag85A-DNA compared to the non-secreted Ag85A-DNA. In addition, secreted Ag85A-DNA conferred protective immunity against infection with M. tuberculosis (CSU37). CONCLUSIONS: DNA vaccines encoding M. tuberculosis Ag85A have been shown to induce potent humoral and cellular immune responses leading to protection from M. tuberculosis (Erdman) challenge in mouse models. In this study we demonstrate that Ag85A can confer protection in a rigorous challenge model using a highly virulent human clinical isolate of M. tuberculosis (CSU37). This challenge model appears able to discriminate between DNA vaccines of differing potencies, as the more immunogenic DNA construct encoding a secreted form of Ag85A was protective, whereas the less immunogenic DNA construct encoding a non-secreted form of Ag85A was not.
Acyltransferases↗
Patient satisfaction with HIV service provision in NPMS hospitals: the development of a standard satisfaction questionnaire. NPMS Steering Group.
A self-completion satisfaction questionnaire evaluating the standard of care of HIV outpatient services was developed as part of the National Prospective Monitoring System on the Use, Cost and Outcome of HIV Service Provision in English Hospitals (NPMS). The questionnaire was designed in conjunction with service users and health care professionals, and piloted in three London and three non-London HIV clinics. In addition to testing alternative methods of administering the questionnaire, the pilot provided satisfaction scores on a variety of aspects of service provision for participating clinics. The questionnaire was completed by 548 respondents and was most effectively collected using a sealed box in the clinic waiting area. Mean satisfaction scores for the attitude and skills of staff members was 4.7 (95% CI 4.6-4.7) but satisfaction scores were significantly lower for the clinic environment with a mean of 4.1 (95% CI 4.1-4.2). Satisfaction scores did not differ significantly by gender, age, sexual orientation, ethnic group, employment status or severity of symptoms. London respondents were more satisfied with the clinic environment and seeing preferred members of staff than their non-London counterparts, however there were no other differences between clinics. The questionnaire functioned well in practice and provided meaningful and useful information for individual clinics as well as at aggregate level.
Acquired Immunodeficiency Syndrome↗
A regional survey of chest drains: evidence-based practice?
Although the use of chest drains is common in medicine, there appear to be wide variations in practice. A survey was therefore conducted to establish the current status of chest drain management in the Northwest region. A questionnaire targeted consultants practising in the specialties of chest medicine, general surgery, accident & emergency and cardiothoracic surgery. The questionnaire consisted of five sections encompassing aspects of the insertion, day-to-day care and removal of chest drains. With an overall response rate of 75.3% (110/146), important variations in every major aspect of the practice of chest drains were found between the specialties and to a large extent within each specialty. We have made a number of recommendations which aim to encourage good practice and reduce unnecessary complications, including the adoption of standardised protocols for inserting and managing chest drains.
Chest Tubes↗
Management of difficult anogenital warts.
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Adjuvants, Immunologic↗
[Expression of vascular endothelial growth factor and tumor angiogenesis correlates with biological behaviors of nasopharyngeal carcinoma].
OBJECTIVE: To study the correlation between tumor angiogenesis and biological behaviors of nasopharyngeal carcinoma(NPC). METHOD: Angiogenesis was assessed by the microvessel dinsity(MVD) and expression of vascular endothelial growth factor(VEGF) was detected using immunohistochemical S-P method. Paraffin-embedded specimens from 65 patients with NPC and 15 with benign nasopharyngeal tumors, 15 with tumor-free nasopharyngeal mucosac were detected. RESULT: Expressions of VEGF and MVD in NPC group were higher than that of nonmetastic carcinoma group. The relationship between expressions of VEGF and MVD and the clinical staging present statistic significance. CONCLUSION: MVD and expression of VEGF are highly correlated with biological behaviors of NPC, which may serve as a parameter for determining tumor biological metastatic potential and prognosis. Angiogenesis inhibitors might be helpful in preventing NPC from metastasis.
Adult↗
[Bilateral large vestibular aqueduct syndrome (7 cases reported)].
OBJECTIVE: To explore the CT features and the auditory threshold in patients with bilateral large vestibular aqueduct syndrome. METHOD: The diameter of vestibular aqueduct in CT and the auditory threshold in each ears of seven patients were measured. RESULT: Asymmetry of the enlarged vestibular aqueduct was found in all patients of whom the side the vestibular aqueduct enlarged was found having a greater hearing loss than the other side in the same patient (paried t-test; P < 0.05). CONCLUSION: The measurement of vestibular aqueduct may be useful in determining the prognosis of patients with large vestibular aqueduct syndrome.
Adolescent↗
Decreased frequency of rearrangement due to the synergistic effect of nucleotide changes in the heptamer and nonamer of the recombination signal sequence of the V kappa gene A2b, which is associated with increased susceptibility of Navajos to Haemophilus influenzae type b disease.
Navajos and genetically related populations have a 10-fold increased incidence of Haemophilus influenzae type b (Hib) disease compared with control populations. The Vkappa gene A2 is used to encode the majority of anti-Hib Abs, and these are the highest affinity anti-Hib Abs. Navajos carry a different allele of the A2 gene segment (A2b) that is defective in its ability to undergo V-J recombination. The A2b allele has only three nucleotide changes from the commonly occurring A2a allele, two of which could potentially affect its ability to recombine. In this study we used two independent in vitro assays to test whether the nucleotide change found in the A2b promoter and/or in the A2b recombination signal sequence (RSS) might be responsible for the decrease in recombination frequency observed in vivo. Using a luciferase reporter gene assay, we found no significant difference between A2a and A2b promoter activities. However, the competition recombination substrate assay showed a 4.5-fold reduction in the relative frequency of recombination of the A2b RSS compared with A2a. We show that this decreased frequency is due to a synergistic effect of the unique nucleotide change present in the heptamer of the A2b RSS and the shared nucleotide change present in the nonamer of both A2b and A2a. This in vitro relative frequency of rearrangement is not significantly different from that observed in vivo; therefore, the A2b RSS is probably the factor associated with the increased susceptibility to Hib disease among individuals carrying the A2b allele.
Alleles↗
Sequence of the spacer in the recombination signal sequence affects V(D)J rearrangement frequency and correlates with nonrandom Vkappa usage in vivo.
Functional variable (V), diversity (D), and joining (J) gene segments contribute unequally to the primary repertoire. One factor contributing to this nonrandom usage is the relative frequency with which the different gene segments rearrange. Variation from the consensus sequence in the heptamer and nonamer of the recombination signal sequence (RSS) is therefore considered a major factor affecting the relative representation of gene segments in the primary repertoire. In this study, we show that the sequence of the spacer is also a determinant factor contributing to the frequency of rearrangement. Moreover, the effect of the spacer on recombination rates of various human Vkappa gene segments in vitro correlates with their frequency of rearrangement in vivo in pre-B cells and with their representation in the peripheral repertoire.
B-Lymphocytes↗
DNA vaccines against tuberculosis.
DNA plasmids encoding Mycobacterium tuberculosis antigen 85 (Ag85) were tested as vaccines in animal models. Ag85 DNA induced relevant immune responses (i.e. T helper (Th) cells, Th1 cytokines and cytotoxic T lymphocytes) and was protective in mouse and guinea pig models of mycobacterial disease. Therefore, DNA vaccination holds promise as an effective means of preventing tuberculosis in humans. Furthermore, this technique is amenable to identifying the protective antigens of M. tuberculosis.
Acyltransferases↗
V(H) replacement is unlikely to contribute significantly to receptor editing due to an ineffectual embedded recombination signal sequence.
Receptor editing is a process consisting of replacement of pre-existing H or L chain rearrangements by secondary rearrangements. This process could serve to remove autoreactive specificities, or to rescue loci with non-functional rearrangements. At the H chain locus, functional replacement of a V(H)DJ(H) rearrangement by an upstream V(H) requires the presence of an embedded RSS located in reverse orientation near the 3' end of the V(H) segment. Although most V(H) genes contain a fairly consensus embedded heptamer, the nonamer sequence bears little resemblance to the consensus RSS nonamer. Therefore, the physiologic rate of H chain editing by V(H) replacement is yet unknown. In this study, we used both conventional and sensitive competition recombination substrate assays to determine the recombination frequency of the V(H)1X embedded RSS relative to consensus and non-consensus RSS's. Results show no detectable recombination of the 81X embedded RSS in a recombination substrate, and the competition substrate allows us to estimate that the 81X embedded RSS recombines at least 1300 fold less often than a consensus RSS. This suggests that V(H) gene replacement is not responsible for the decrease in representation of the 81X gene during differentiation. Furthermore, since the sequence of the embedded RSS is very similar for many V(H) genes, our results suggest that receptor editing of the H chain will be an infrequent event, leaving L chain editing as the main mode of avoiding autoreactive specificities in vivo.
Gene Rearrangement, B-Lymphocyte, Heavy Chain↗