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Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome.

Expression of histocompatibility leukocyte antigen (HLA) class I molecules on the cell surface depends on the heterodimer of the transporter associated with antigen processing 1 and 2 (TAP1 and TAP2), which transport peptides cleaved by proteasome to the class I molecules. Defects in the TAP2 protein have been reported in two families with HLA class I deficiency, the so-called bare lymphocyte syndrome (BLS) type I. We have, to our knowledge, identified for the first time a splice site mutation in the TAP1 gene of another BLS patient. In addition, class I heavy chains (HCs) did not form the normal complex with tapasin in the endoplasmic reticulum (ER) of the cells of our patient.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Luminescence studies of the phagocyte response to endotoxin infusion into normal human subjects: multiple discriminant analysis of luminescence response and correlation with phagocyte morphologic changes and release of elastase.

A blood luminescence system (BLS) was employed to analyze blood phagocyte function in response to infusion of endotoxin (4 ng Escherichia coli lipopolysaccharide (LPS)/kg body weight) into 7 healthy human subjects. The subjects were closely monitored clinically, and extensive chemical, hematological and coagulation measurements were taken during the pretreatment, early (symptomatic, 1-8 h post-LPS), and late (asymptomatic, 12-48 h post-LPS) phases of acute inflammation. BLS assessment included measurement of basal and PMA-stimulated phagocyte oxidase and myeloperoxidase (MPO) activities, and also included measurement of circulating (COR) and PAF-primed maximum (MOR) opsonin receptor-dependent phagocytic activities. Basal oxidase activity peaked at T + 1 h and showed an additional peak at T + 24 h post-LPS. The COR activity also peaked at 1-2 h, but remained elevated through T + 24 h post-LPS, while the basal MPO activity peaked only once at T + 1 h. We concluded that while MPO evidence of phagocyte respiratory activation returned to baseline by T + 4 h, COR evidence of receptor expression (receptor alert) remained elevated through T + 24 h. During this early (0-8 h) period, elastase/alpha 1AT complex concentration peaked at T + 3-4 h and again at T + 8 h. Peak numbers of circulating polarized and vacuolated phagocytes also appeared at T + 3 h and 7 h. We concluded that there was biochemical and morphological evidence of continuing phagocyte activity beyond T + 4 h to T + 8 h, and that this corresponded with the period during which the subjects were symptomatic. In addition, the appearance of a second peak of basal oxidase activity at T + 24 h, multiple discriminant analyses of all the luminescence data, and the sustained elevation of lactate suggested that there was a later second stage (T + 12 h to 48 h) of the human response to endotoxin, during which time the subjects were asymptomatic.

Adult↗

MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency.

MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine model of MHCII deficiency (RFX5- or CIITA-deficient mice) that residual MHCII expression by professional antigen-presenting cells (APCs) is sufficient to support activation of adoptively transferred Th cells. Furthermore, upon transplantation of WT thymic epithelium, we observed development of endogenous Th cells with restoration of Th-cell-dependent antibody responses and immunity to cytomegalovirus infection, thus opening the possibility of an alternative treatment regimen for BLS. Residual MHCII expression was further induced by the presence of Th cells and also other stimuli. Analysis of CIITA/RFX5 double-deficient animals revealed that this inducible MHCII expression is genetically independent of the known promoter complex and thus constitutes an alternative MHCII expression pathway. In these experiments, we also detected a novel repressive function of the RFX complex in the absence of CIITA.

Animals↗

Azidothymidine inhibits NF-kappaB and induces Epstein-Barr virus gene expression in Burkitt lymphoma.

The antiviral compound azidothymidine (AZT), alone or in combination with other agents, induces apoptosis in early-passage, Epstein-Barr virus-positive Burkitt lymphoma (EBV+ BL) lines and has clinical activity in EBV+ BL. We report here a mechanism of AZT's antitumor activity. The nuclei of these cells contain activated nuclear factor-kappaB (NF-kappaB) subunits p50, c-Rel, RelB, and p52, but not p65. Treatment of primary EBV+ BL lines with AZT inhibited NF-kappaB within 1 to 2 hours. This was followed by up-regulation of EBV gene expression including viral thymidine kinase (vTK) and apoptosis. Subclones of EBV+ BL cells that demonstrated activated p65 were resistant to AZT. In EBV+ BLs, AZT but not ganciclovir (GCV) was highly phosphorylated to its monophosphate form (AZT-MP). Phosphorylation, as well as apoptosis, was markedly enhanced in the presence of hydroxyurea. AZT inhibits NF-kappaB and up-regulates EBV gene expression in primary EBV+ BLs. AZT with hydroxyurea may represent an inexpensive, targeted regimen for endemic BL.

Apoptosis↗

Out-of-hospital administration of albuterol for asthma by basic life support providers.

BACKGROUND: Each year, approximately 40,000 patients with acute asthma are transported by the Fire Department of New York City (NYC) Emergency Medical Services (EMS). Out-of-hospital administration of bronchodilator therapy has, however, been restricted by scope of practice to advanced life support (ALS) providers. Since the rapid availability of ALS units cannot always be assured, some individuals with acute asthma may receive only basic life support (BLS) measures in the field. OBJECTIVES: To demonstrate that basic emergency medical technicians (EMT-Bs) are able to effectively administer nebulized albuterol to asthma patients in the out-of-hospital environment. METHODS: This was a prospective, observational cohort study of 9-1-1 asthma calls received by the NYC EMS system for patients between the ages of 1 and 65 years. Baseline peak expiratory flow rate (PEFR) and other clinical measures were obtained prior to and following BLS administration of one or two treatments with nebulized albuterol. RESULTS: Data were available for 3,351 patients over a one-year study period. One out-of-hospital albuterol treatment was given in 60%, while 40% of the patients received two. The PEFRs increased from 40.4% predicted (SD +/-21.0) to 54.8% predicted (SD +/-26.1), for a posttreatment improvement of 14.4% points (95% CI = 13.8 to 15.1). Other clinical outcome measures, including dyspnea index, respiratory rate, and use of accessory muscles, also showed improvement. CONCLUSIONS: This study demonstrates that EMT-Bs can effectively administer albuterol to acute asthma patients in the out-of-hospital environment.

Administration, Inhalation↗

First aid and basic life support skills training early in the medical curriculum: curriculum issues, outcomes, and confidence of students.

BACKGROUND: The importance of training physicians and other health care professionals in first aid and basic life support (BLS) is now widely recognized. The Faculty of Medicine and Health Sciences of the United Arab Emirates University have been offering formal training in these skills to 1st-year medical students since 1989. The aim of this study was to determine the efficacy of the program and the extent to which it provides students with confidence to perform skills on their own after training. DESCRIPTION: 165 of 180 male and female students comprising 3 cohorts (91.7% response rate) completed a self-administered anonymous questionnaire. The questionnaire contained open- ended and Likert-type questions regarding course organization, content, strengths and weaknesses, teaching--learning approaches, and skills development and confidence. The authors analyzed assessment outcomes and associations between self-perceived levels of confidence and ability to practice. EVALUATION: Students were uniformly enthusiastic and highly motivated by the program. Self-assessed confidence in ability to perform skills on their own after completing the program was moderately correlated with perceived frequency of opportunity to practice many skills. There was nevertheless a consistent desire for more practice time. CONCLUSIONS: The results suggest that the program provides students with sound basic knowledge and adequate practical skills in first aid and BLS and that adequacy of time and physical and human resources are important prerequisites to facilitate practice and engender confidence in skills.

Cardiopulmonary Resuscitation↗

Effects of sublethal ammonia exposure on swimming performance in rainbow trout (Oncorhynchus mykiss).

Adult trout Oncorhynchus mykiss fitted with a dorsal aortic catheter were exposed to 288+/-15 micromol l(-1) (mean +/- S.E.M.) total ammonia for 24h in water at a pH of 8.39+/-0.02, while swimming at a speed equivalent to 0.75 bodylengths s(-1) (BLs(-1)) in a Brett-type tunnel respirometer. The fish were then exposed to stepwise increments in swimming speed (0.25 BLs(-1) every 30 min) until exhaustion. Measurements of oxygen uptake (M(O2)) and plasma total ammonia levels and pH were made at each speed. Control trout were treated identically but without exposure to ammonia. Ammonia exposure caused an increase in plasma total ammonia level to 436+/-34 micromol l(-1), compared to 183+/-30 micromol l(-1)in control animals (N=6). A significant reduction in total plasma ammonia level was found in both groups during exercise, despite a large negative concentration gradient in those exposed to an elevated concentration of ammonia in water, which may indicate an active excretory process. The overall increase in plasma ammonia levels in exposed trout was associated with a significant reduction in critical swimming speed (U(crit)) to 1.61+/-0.17BL s(-1) from 2.23+/-0.15BL s(-1) in control animals. Ammonia-exposed trout had a significantly higher maintenance metabolic rate (MMR) than control fish, when estimated as the y-intercept of the relationship between swimming speed and M(O2). Active metabolic rate (AMR, maximum M(O2) as measured at U(crit)) was significantly lower in ammonia-exposed animals, leading to a profound reduction in factorial aerobic scope (AMR/MMR). Reduced U(crit) was also linked to a reduction in maximum tailbeat frequency. Calculation of membrane potentials (E(M)) in the white muscle of fish swum to U(crit) revealed a significant partial depolarisation of white muscle in ammonia-exposed fish. This may have prevented white muscle recruitment and contributed to the reduced maximum tailbeat frequency and overall impairment of swimming performance in the ammonia-exposed fish.

Ammonia↗

Analyses of specific and total antibody responses of rabbits to four kinds of immunogens.

As a basic study to investigate suitable conditions to immunize rabbits with drug-immunogens, two highly sensitive and accurate enzyme immunoassays (EIAs) for specific antibody to viomycin (VM) and blasticidin S (BLS) were developed using the corresponding standard antibody, the solid-phase antigens, and enzyme-labeled goat anti-rabbit immunoglobulin G (IgG) antibody as immunological reagents. The accuracy of the assay results with these newly developed EIAs was demonstrated. The new EIAs as well as two previously developed EIAs, EIA for antibody specific to neocarzinostatin (NCS) and a sandwich EIA for rabbit IgG, were applied for analyses of the changes in contents of total and specific antibodies in rabbit antisera samples collected during immunizations with four antigens. Total IgG levels increased from 7.0-9.9 mg/ml to 30-50 mg/ml in all rabbits immunized under the same immunizing schedule, despite the use of four kinds of antigens. The highest level of specific antibodies, anti-BLS, anti-VM and anti-NCS, was 0.5 mg/ml in each case.

Animals↗

Emergency medical personnel training: I. An historical perspective.

The status of Emergency Medical Technicians has evolved from an undefined role with few rules, regulations, or standards to an established health care profession and a nationally administered program. The evolution of this profession received major impetus from the 1966 report by the National Academy of Science/National Research Council that provided recommended training standards. Development of a training course curriculum for basic life support (BLS) followed. The need for coordinated training of Emergency Medical Technical Technicians was recognized, and funds became available to aid in the national standardization of education, examination, certification, and recertification procedures for EMTs. Concomitant with the attempt to standardize BLS training, advanced life support (ALS) programs grew in number. By 1977 the National Standard Training Curriculum became available and was soon followed by a national certification exam. As states have the option to accept or reject the federal standards embodied in the national training course, there remains variation among programs offered by each state. Because of the difference in need for specific emergency services among the states at a time of increased professional mobility, arguments still exist regarding the desirability of federally mandated training and certification programs.

Allied Health Personnel↗

[Thyroglobulin-binding and anti-thyroglobulin antibody-secreting lymphocytes in human peripheral blood (author's transl)].

Human peripheral blood lymphocytes were studied with the use of fluorescinated human thyroglobulin (FITC-Tg) for the presence of cells which bind human FITC-Tg (Tg-BL) and which secrete a thyroglobulin antibody (Tg-SL) by culturing them for 5 days with pokeweed mitogen. In seven out of fifteen (47%) patients with Hashimoto's thyroiditis, an average of 0.18% of lymphocytes were able to bind FITC-Tg, while only one out of six (17%) patients with Graves' disease was able to bind them. No Tg-BLs were detected in five patients with miscellaneous autoimmune diseases and five normal subjects. Tg-BLs were identified as B lymphocytes by their inability to make rosettes with sheep red blood cells. Tg-SLs were detected in six out of eight (75%) patients with Hashimoto's thyroiditis and two out of five (40%) patients with Graves' disease. The positive rates of Tg-BL and Tg-SL were fairly well correlated with the thyroglobulin antibody titers.

Antibodies↗

[Analysis of the intra-hospital attending of ventricular fibrilation/ventricular taquicardia simulated events].

OBJECTIVE: To analyze the time intervals between the beginning of the Ventricular Fibrilation/Ventricular Taquicardia (VF/VT) and the main procedures made. METHODS: Twenty VF/VT simulations were performed and filmed in a hospital environment, using a static mannequin, on random days at random times. All teams had the same level of skills. The times (in sec.) related to basic life support (BLS) - arrival of the team (AT), confirmation of the arrest (CAT), beginning of the CPR (IT) and the times related to the advanced life support (ALS) - 1st defibrillation (DT), 1st dose of adrenalin (AT) and orotracheal intubation (OTIT). The variables were analyzed and compared in two groups: intensive care unit (ICU) and wards with telemetry (TLW). RESULTS: The results in both groups was in that order (GW x ICU ) - AT (70.2+38.7 x 38.6+49.2); CCA (89.4+57.1 x 71+63.9); SC (166.8+81.1 x 142+66.2); FD (282.5+142.8 x 108.4+52.5); FE (401.4+161.7 x 263.3+122.8) e OI (470.3+150.6 x 278.8+98.8). Shows the comparison of the average times between the two groups. CONCLUSION: The differences noted in relation to DT, AT and OTIT favorable to ICU are associated to the facility of performance of the ALS maneuvers in such environment. The BLS-related times were similar in both groups, which reinforce the need for the use of semi-automatic defibrillators, even in a hospital environment.

Advanced Cardiac Life Support↗

Effective protection against experimental Taenia solium tapeworm infection in hamsters by primo-infection and by vaccination with recombinant or synthetic heterologous antigens.

The disease caused by Taenia solium is progressively being recognized as a growing global threat for public human health and pig husbandry that requires the development of effective control measures. A central participant in the taeniasis/cysticercosis transmission network is the human carrier of the adult tapeworm because of its great potential in spreading the infection. Herein, evidence is presented that a primary infection of golden hamsters with orally administered T. solium cysticerci improved the host's resistance against a secondary infection. Likewise, previous vaccination increased the hamster's resistance. Similar high levels of protection (> 78%) were induced by systemic or oral vaccination with the S3Pvac anticysticercosis synthetic peptide vaccine or the highly immunogenic recombinant chimera based on the protective peptide KETc1 bound to Brucella spp. lumazine synthase (BLS-KETc1). Increased resistance after primo-infection and vaccination possibly results from changes in the immune conditions prevailing in the host's intestine. The contribution to protection from the KETc1 and BLS epitopes in a chimeric vaccine is under study. Preventive vaccination of definitive hosts of T. solium against the tapeworm, the most relevant step in the taeniasis/cysticercosis transmission, may greatly impact the dynamics of endemic disease and has not been studied or tried previously.

Animals↗

Injuries at work in the US adult population: contributions to the total injury burden.

OBJECTIVES: We estimated the contribution of nonfatal work-related injuries on the injury burden among working-age adults (aged 18-64 years) in the United States. METHODS: We used the 1997-1999 National Health Interview Survey (NHIS) to estimate injury rates and proportions of work-related vs non-work-related injuries. RESULTS: An estimated 19.4 million medically treated injuries occurred annually to working-age adults (11.7 episodes per 100 persons; 95% confidence interval [CI]=11.3, 12.1); 29%, or 5.5 million (4.5 per 100 persons; 95% CI=4.2, 4.7), occurred at work and varied by gender, age, and race/ethnicity. Among employed persons, 38% of injuries occurred at work, and among employed men aged 55-64 years, 49% of injuries occurred at work. CONCLUSIONS: Injuries at work comprise a substantial part of the injury burden, accounting for nearly half of all injuries in some age groups. The NHIS provides an important source of population-based data with which to determine the work relatedness of injuries. Study estimates of days away from work after injury were 1.8 times higher than the Bureau of Labor Statistics (BLS) workplace-based estimates and 1.4 times as high as BLS estimates for private industry. The prominence of occupational injuries among injuries to working-age adults reinforces the need to examine workplace conditions in efforts to reduce the societal impact of injuries.

Adult↗

Family expenditures before and after retirement: a research model for measuring priorities.

Economic pressures of contemporary American society have had an impact on many families. This article focuses on how elderly, intact couples allocated their retirement dollars. Bureau of Labor Statistics (BLS) family budget expense categories were used as a basis to develop expense categories. The couples were asked what changes, if any, they made in expenditures after retirement and if they would allocate their money differently if they were free to do so. Most of them had changed expenses after retirement. Some of their expenditures had increased rather than decreased in importance since retirement. Only two expenditure categories, food and transportation, were ranked the same as the BLS ranking by at least 30 percent of the couples. The empirical usefulness of the methodology reported in this paper was illustrated with a sample of elderly couples. However, it seems applicable not only for the elderly but also for families in all stages of the family life cycle.

Aged↗

Creating a new learning experience: "The story of art" and "Prudent art".

The signs and symptoms of an impending cardiac arrest and the appropriate interventions are two concepts that need to be taught in the American Heart Association's Basic Life Support (BLS) course. CPR education is also required annually for all hospital employees who are direct caregivers. Developing teaching strategies that renew interest in the content and facilitate learning and retention is a challenge for BLS instructors. "The Story of Art" and "Prudent Art" utilize narrative and visual images to teach the signs and symptoms of an impending cardiac arrest and appropriate interventions. This article describes the development of this creative learning experience.

Audiovisual Aids↗

Current concepts in cardiopulmonary resuscitation in adults.

Cardiopulmonary resuscitation (CPR) provides artificial circulation and ventilation during cardiopulmonary arrest. CPR is further categorised as basic life support (BLS), advanced cardiac life support (ACLS) and postresuscitation support. BLS consists of provision of a patent upper airway, ventilation and circulation of blood by closed chest cardiac compressions. ACLS includes use of specialised equipment to maintain the airway, early defibrillation and pharmacologic therapy. Successful outcome from an arrest depends on the total duration of an arrest and early defibrillation, as ventricular fibrillation is the most common cardiac rhythm found in adult cardiac arrest. Initial drug therapy during CPR aims at correction of arterial hypoxaemia and restoring coronary and cerebral perfusion. Oxygen and epinephrine constitute the mainstay of drug therapy during CPR. In patients with ventricular tachycardia, lidocaine is the drug of choice, followed by bretylium. Magnesium has proved to be useful in both refractory pulseless ventricular tachycardia and fibrillation. Atropine has not been demonstrated to improve outcome from arrest but can be administered in bradyasystolic cardiac arrest. The routine administration of bicarbonate and calcium is no longer recommended but situations exist where they can be used appropriately. Administration of drugs during CPR should preferably be via a central route, but epinephrine, lidocaine and atropine can be administered via the endotracheal tube if intravenous access has not been established. Postresuscitation care includes mechanical ventilation if necessary to optimise oxygenation and ventilation and steps to maintain vital organ and optimal brain protection, which includes avoidance of hypertension, hypotension and hyperglycaemia.

Adult↗

Characteristics of individuals with integrated pensions.

Employer pensions that integrate benefits with Social Security have been the focus of relatively little research. Since changes in Social Security benefit levels and other program characteristics can affect the benefit levels and other features of integrated pension plans, it is important to know who is covered by these plans. This article examines the characteristics of workers covered by integrated pension plans, compared to those with nonintegrated plans and those with no pension coverage. Integrated pension plans are those that explicitly adjust their benefit structure to help compensate for the employer's contributions to the Social Security program. There are two basic integration methods used by defined benefit (DB) plans. The offset method causes a reduction in employer pension benefits by up to half of the Social Security retirement benefit; the excess rate method is characterized by an accrual rate that is lower for earnings below the Social Security taxable maximum than above it. Defined contribution (DC) pension plans can be integrated along the lines of the excess rate method. To date, research on integrated pensions has focused on plan characteristics, as reported to the Bureau of Labor Statistics (BLS) through its Employee Benefits Survey (EBS). This research has examined the prevalence of integration among full-time, private sector workers by industry, firm size, and broad occupational categories. However, because the EBS provides virtually no data on worker characteristics, analyses of the effects of pension integration on retirement benefits have used hypothetical workers, varying according to assumed levels of earnings and job tenure. This kind of analysis is not particularly helpful in examining the potential effects of changes in the Social Security program on workers' pension benefits. However, data on pension integration at the individual level are available, most recently from the Health and Retirement Study (HRS), a nationally representative survey of individuals aged 51-61 in 1992. This dataset provides the basis for the analysis presented here. The following are some of the major findings from this analysis. The incidence of pension integration in the HRS sample is 32 percent of all workers with a pension (14 percent of all workers). The HRS can also identify integrated DC plans, a statistic that is not available from BLS data. The rate of integration for workers with only DC plans is 8 percent. After controlling for other variables, several socio-demographic characteristics are significantly related to the incidence of integration. The probability of having an integrated pension is 4.6 percentage points less for men compared to women. Non-Hispanic blacks are 6.4 percentage points less likely than non-Hispanic whites to have integrated pensions. Union members are 14 percentage points less likely to have integrated pensions, while workers with less than a graduate level education are at least 15 percentage points more likely to have a pension that is integrated. Some earnings and pension characteristics are also significantly correlated with pension integration. Earnings are positively related, with the probability of having an integrated pension increasing by 2 percentage points for an increase of $1,000 in annual pay. An even larger effect comes from earning at or above the Social Security taxable maximum. Workers at or above this income level are 10 percentage points more likely to have an integrated plan, but for those with more than one plan the probability of pension integration goes up by 13 percentage points.

Bias↗

Effects of subsurface heterogeneity on natural bioremediation at a gasoline spill site.

A test cell of 3-m by 6-m located at the mid-point of a gasoline spill site was selected to test the hypothesis that the rate of hydrocarbon biodegradation is influenced by the spatial distribution of the electron acceptors, aqueous geochemistry, and microbial population. Multilevel samplers (MLSs) were installed at four corners of the test cell for groundwater sampling. Sampling ports were placed at 0.3-m intervals from 1.5 to 4.8 m below land surface (bls). A 0.91-m by 12.7-cm sediment core (from 3.3 to 4.2 m bls) in the center of the MLSs was collected. The core was cut into 7 sections, and each was used for sediment extractions, microbial enumeration, grain size distribution, and microcosm studies. Groundwater analytical results indicate that iron reduction was the dominant biodegradation process within this test cell. Iron-reducing process caused the preferential removal of certain compounds. Microbial enumeration results show that the distribution of microbial population varied with depth and sediment materials. Lower microbial population was observed in those sections with higher portion of clayey materials. The less permeable materials would limit the bacterial transport, decrease the bioavailability of Fe(III) to iron-reducing bacteria, and thus cause the low biodegradation activity. Results suggest that using blended sediments for biodegradation rate measurements may provide misleading results.

Biodegradation, Environmental↗