Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of Plasmodium yoelii merozoite surface protein 1 (MSP119) and their role in immunity to malaria

MSP1₁₉ is one of the leading malaria vaccine candidates. However, the mechanism of protection is not clear. To determine whether MSP1₁₉-specific effector T cells can control parasitaemia, we analysed the specificity of T cells induced following immunization with recombinant forms of P. yoelii MSP1₁₉ and asked whether they could protect mice. There was no evidence that effector T cells were capable of protecting since: (1) immunization of mice with yMSP1₁₉, but not defined epitopes, was able to induce protection; and (2) long term MSP1₁₉-specific CD4⁺ T cell lines were incapable of adoptively transferring protection. In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic antibody response to MSP1₁₉ after either challenge with MSP1₁₉ or parasite. Thus, MSP1₁₉ contains multiple T cell epitopes but such epitopes are the targets of helper T cells for antibody response but not of identified effector T cells capable of controlling parasitaemia .     

In vitro synthesis and immunoregulation of antibody to hepatitis B surface antigen in man

Abstract Peripheral blood mononuclear cells (PBMC) from 16 chronic hepatitis B surface antigen (HBsAg) carriers and from 10 immune individuals (anti-HBs and/or anti-HBc core antigen positive) were studied for their ability to synthesize antibody to hepatitis B viral antigens in vitro . Pokeweed mitogen (PWM)-stimulated B lymphocytes from carriers, synthesized polyclonal IgG and IgM normally but did not synthesize detectable antibody to HBsAg (anti-HBs) even in the presence of T lymphocyte help and the absence of T lymphocyte suppression from immune individuals. In contrast, B lymphocytes from 80% of immune individuals synthesized anti-HBs in vitro. In cell-mixing experiments, T lymphocytes from carriers were found to provide normal helper function for immunoglobulin and anti-HBs production by B lymphocytes from immune individuals. In addition, the degree of suppressor T lymphocyte activity of chronic carriers was not sufficient to explain the lack of anti-HBs production.
The effect of purified HBsAg on anti-HBs synthesis by PBMC from immune individuals was determined. Incubating PBMC for periods ranging from 10 min to 10 days in the presence of concentrations of HBsAg varying from 10 pg/ml to 10 μg/ml had no effect on the synthesis of anti-HBs by PBMC. These results suggest that chronic HBsAg carriers lack circulating B lymphocytes capable of producing anti-HBs and that this cannot be explained by the presence of large amounts of circulating HBsAg.     

Aging in America in the Twenty‐first Century: Demographic Forecasts from the MacArthur Foundation Research Network on an Aging Society

Context: The aging of the baby boom generation, the extension of life, and progressive increases in disability‐free life expectancy have generated a dramatic demographic transition in the United States. Official government forecasts may, however, have inadvertently underestimated life expectancy, which would have major policy implications, since small differences in forecasts of life expectancy produce very large differences in the number of people surviving to an older age. This article presents a new set of population and life expectancy forecasts for the United States, focusing on transitions that will take place by midcentury. Methods: Forecasts were made with a cohort‐components methodology, based on the premise that the risk of death will be influenced in the coming decades by accelerated advances in biomedical technology that either delay the onset and age progression of major fatal diseases or that slow the aging process itself. Findings: Results indicate that the current forecasts of the U.S. Social Security Administration and U.S. Census Bureau may underestimate the rise in life expectancy at birth for men and women combined, by 2050, from 3.1 to 7.9 years. Conclusions: The cumulative outlays for Medicare and Social Security could be higher by $3.2 to $8.3 trillion relative to current government forecasts. This article discusses the implications of these results regarding the benefits and costs of an aging society and the prospect that health disparities could attenuate some of these changes.     

NEUROMUSCULAR AND CLINICAL EFFECTS OF MIVACURIUM CHLORIDE IN HEALTHY ADULT PATIENTS DURING NITROUS OXIDE-ENFLURANE ANAESTHESIA

We have studied the effects of mivacurium after induction ofanaesthesia with alfentanH-propofol in healthy adult oral surgicalpatients. Anaesthesia was maintained with nitrous oxide and0.75% (end-tidal) enflurane in oxygen after nasotracheal intubation.Recordings were made of the rectified compound adductor polliciselectromyogram in response to train-of-four (TOF) ulnar nervestimulation. First and fourth TOF responses were defined asT1 and T4. with T1 suppression referenced to pre-mivacuriumT1 height (Tc). Onset times (mean (SEM)) to 90% T1 suppressionwere 2.5 (0.2), 2.1 (0.3) and 1.6 (0.1) min, respectively, aftermivacurium 0.15 mg kg^–1 (n=18) and 0.2mg kg^–1 (n=18)as 5-s boluses and 0.2mg kg^–1 over 30 s (n = 9). Intubatingconditions 2 min after 0.15 mg kg^–1 were good to excellentand not improved by a further 30-s delay or by use of a 0.2-mgkg^–1 dose. Recovery to T1/Tc of 5% occurred on averagein 12–13 min irrespective of dose. Thereafter, mivacuriuminfusions commenced at 8–10 µg kg^–1 min^–1re adjusted at intervals of at least 3 min to achieve T1/Tcin the range 1–10%. Mean duration of infusion was 58 (3.4)min and mean infusion rate after a 15-min stabilization periodwas 6.6 (range 2.3–12.9) fig kg^–1min. On cessationof infusions, spontaneous recovery from T1/Tc fie 8% (1.0%)to T4:T1 = 0.7 took 17 (1.2) min. Neostigmine 0.04 mg kg^–1or edro-phonium 0.75mg kg evoked recovery from T1/Tc 9% (SEM1.2% and 1.0%, respectively) to T4:T1 = 0.7 in 11 (0.6) and8 (0.9) min (both P < 0.001 vs spontaneous recovery). Presented in part at the Anaesthetic Research Society, LondonMeeting, November 1989     

Intravenous Adenosine Can Reveal Accessory Pathways Not Revealed By Routine Electrophysiological Testing

This article describes a patient in whom the administration of adenosine revealed the presence of an accessory pathway when electrophysiological testing had failed to do so.     

Intravenous Adenosine Reveals Intermittent Preexcitation by Direct and Indirect Effects on Accessory Pathway Conduction

In some patients with accessory pathways preexcitation occurs intermittently during sinus rhythm. In these patients the antegrade refractory period of the accessory pathway may either exceed the sinus cycle length under some circumstances, or conduction block in the accessory pathway may be variable. The ability of intravenous adenosine to unmask intermittent preexcitation was determined in patients with intermittent preexcitation but absent preexcitalion at the time of study. Six patients undergoing assessment of the Wolff-Parkinson-White syndrome received incremental doses of intravenous adenosine (3, 6, and 12 mg). Adenosine administration was repeated in three patients after intravenous β blockade (propranolol 0.2 mg/kg). Adenosine unmasked preexcitation in all patients. P delta intervals with preexcited beats were substantially shorter Ihan resting PR intervals in all cases (range 40–80 msec shorter). In 4/6 patients preexcitation was seen early, coincident with the onset of atrioventricular nodal block. In 4/6 patients preexcitation was seen late during the secondary sinus tachycardia that follows the direct cardiac effects of adenosine. Two patients exhibited early preexcitation and late preexcitation. Beta blockade failed to prevent early preexcitation (2/2 patients) but abolished preexcitation related to sinus tachycardia (3/3 patients). Early preexcitation, coincident with the onset of AV nodal block, suggests a direct effect of adenosine on accessory pathway conduction. Late preexcitation, occurring during secondary sinus tachycardia, and abolished by β blockade, suggests enhanced accessory pathway conduction due to sympathetic activation.