Age-related decline in activation of JNK by TCR- and CD28-mediated signals in murine T-lymphocytes.

c-Jun N-terminal kinase (JNK) is activated when T-lymphocytes are stimulated jointly through the T-cell receptor (TCR) and CD28, and it contributes to T-cell activation and IL-2 production through phosphorylation of transcription factors, including c-Jun. We performed in vitro kinase assays on JNK in CD4(+) T-cells, from young and old mice, activated by antibodies to CD3, CD4, and CD28, and found a approximately 2-fold decline in JNK activity at the peak of activation, but no significant change in the kinetics of stimulation or in the steady-state expression of JNK. We found a similar decline in c-Jun phosphorylation in stimulated CD4(+) T-cells from old mice, suggesting that JNK activation also declined with age in intact cells. Aging does not, however, alter the level of Ras activation by anti-CD3/CD4 +/- anti-CD28 or change the level of Ras protein in CD4(+) cells, suggesting that the JNK defect is due to changes in the regulation of other upstream regulators. Our results suggest that a decline with age in JNK responses may contribute to the decline in proliferation and IL-2 production seen in CD4(+) T-cells from old mice.

Dobutamine thallium 201 perfusion imaging in candidates for lung transplantation.

BACKGROUND: Thallium-201 stress imaging is the most often used noninvasive test for detection of coronary artery disease. Its utility in patients with end-stage lung disease has not been defined. METHODS: Feasibility, safety, and reliability of thallium 201 perfusion imaging was evaluated in 23 consecutive candidates for lung transplantation. All underwent graded dobutamine thallium 201 single photon emission computed tomography imaging. The perfusion imaging results were correlated with results of coronary angiography, radionuclide angiography, and right heart catheterization. RESULTS: The testing was completed without complications in all patients. No perfusion abnormality was detected in five patients, and none had evidence of coronary artery disease on coronary angiography. In 18 patients with abnormal thallium 201 imaging, coronary artery disease was detected in four patients only, and no angiographic data was available in three patients. Thus, in at least 11 of 23 patients, thallium 201 imaging was falsely positive. There was a trend toward lower left ventricular ejection fraction in patients with abnormal thallium 201 imaging. No correlation was found between thallium 201 results, pulmonary artery and right atrial pressures at rest. Possible noncoronary origin of the perfusion defects include the following (1) presence of sarcoid in the myocardium, (2) left ventricular attenuation by hypertrophied right ventricle, and (3) altered left ventricular anatomy, function, and coronary perfusion as a result of right ventricular pressure overload. CONCLUSIONS: Dobutamine thallium 201 stress test can be safely performed in lung transplant candidates. However, its specificity for detection of coronary artery disease is low. Selective use of coronary angiography in patients with multiple risk factors is likely a more cost-effective approach.

Occupational pathogenesis of chlorine

The occupational pathogenesis of chlorine in exposed workers are described and compared with the classic pathogenesis. The exposed group consisted of 82 men with occupational exposure to chlorine.The control group consisted of 46 men who were not exposed, all of them works in the same cellulose processing factory. The exposed group had the symptoms of theclassical pathogenesis to a highly significant degree (p<0,0001) compared to the unexposed control group. We found a number of symptoms signs, disorders and syndromes which are not described in the classical pathogenesis, including: diminished tolerance to alcohol, back pain, pains in the joints dependent on weather conditions, dependent oedema, diminished taste sensitivity, persistent chronic hepatitis, hepatic steatofibrosis, chronic obstructive airways disease, polycythaemia with haemosiderosis and chronic conjunctivitis. The intensity of symptoms and signs was in direct proportion to the duration of exposure to chlorine

Adenosine and its cardiovascular effects.

Adenosine is a new antiarrhythmic agent recently released with the permission of the Food and Drug Administration. It is an endogenously occurring nucleoside indicated for use in the diagnosis and treatment of supraventricular tachycardia. Its greatest utility is in patients with AV nodal reentry. Its antiarrhythmic action is mediated at the cellular level through the potassium channel, causing hyperpolarization of the myocyte membrane potential. In addition to its current indication as an antiarrhythmic agent, adenosine is now being used under an investigational protocol for pharmacologic stress testing. It can be given in conjunction with thallium or used in echocardiography as an imaging tool for patients who can not be adequately exercised. Adenosine's side effect profile is relatively benign and the agent's extremely short half-life makes most adverse reactions clinically insignificant. In this report we attempt to highlight this agent's clinical utility and discuss its future in the cardiovascular pharmacopeia.

Continuous measurements of ATP secretion in vivo.

Blood was withdrawn continuously from femoral veins of anesthetized rabbits at a rate of 0.07 ml/min. Sodium citrate was pumped into the blood to prevent coagulation, and luciferin-luciferase reagent was added to permit the continuous detection of extracellular ATP. Subsequently, the red blood cells were lysed and the platelet count was recorded continuously. Injection of platelet activating factor or collagen into rabbit ear veins caused an almost immediate but short-lived increase in extracellular ATP with a simultaneous but more prolonged decrease in the platelet count. Although both the endoperoxide analog 9,11-azo-PGH2 and ADP also decreased the platelet count, little extracellular ATP was detected after the azo-PGH2 and none after ADP. These studies demonstrate that those agents that cause platelet secretion from rabbit platelets in vitro also cause secretion in vivo. The method described should be useful in evaluating the capacity of antithrombotic drugs to modify platelet secretion in vivo.

Tzaraat--"biblical leprosy".

Tzaraat refers to a group of skin diseases that, according to the Old Testament, renders one ritually unclean. Analysis of the text reveals that there are four categories of lesions discussed. Each category has a primary lesion as well as specific secondary changes. The primary lesions include depigmented lesions on previously healthy skin, lesions on previously abnormal skin, lesions on areas of diffuse alopecia, and lesions of localized alopecia. It is unlikely that these diseases have a modern-day counterpart.

Localized pemphigoid simulating dyshidrosiform dermatitis.

A patient had a localized, persistent vesicular eruption of the feet that was clinically identical to dyshidrosiform dermatitis. Direct and indirect immunofluorescent studies revealed a bullous pemphigoid (BP) pattern. Antibody blocking experiments showed the patient's circulating basement membrane zone antibody to be identical to that of classical BP. Possible pathogenetic mechanisms of localized BP are discussed.

Field ion microscopy of biomolecules.

A new type of image, existing only at field strengths below the denaturation field strengths of molecules, has been discorvered. This type of image has structure, is not symmetrical and thus differs from previously reported low field strength images. The possibility that macromolecules adsorbed on tip surfaces produce such structured images has been exhaustively investigated. The result is that no observation has been found which disproves this hypothesis and many tests conducted in such attempts yielded correlations consistent with this hypothesis. It is therefore concluded that it is highly probable that biomolecules produce structured images and that it is highly improbable that these correlations represent a chance event. On the other hand, these correlations may be due to some cause unknown to the authors; but we consider this possibility to be unlikely. Some micrographs have been obtained which provide a reasonable basis for the hope that tertiary structure information may be defrived from low field strength imaging of partially embedded biomolecules or of biomolecules that are resistant to field denaturation during imaging. Information may presently be obtained from analysis of low field strength ion micrographs about the size and shape of some biomolecules.