Cytosolic Ca2+ acts by two separate pathways to modulate the supply of release-competent vesicles in chromaffin cells

Recovery from depletion of the readily releasable pool of vesicles (RRP) in adrenal chromaffin cells was studied at differing basal [Ca2+]i or following protein kinase C (PKC) activation by phorbol esters. Following depletion, the pool size was estimated at varied times from cell capacitance jumps in response to paired depolarizations. The experimentally observed RRP recovery time course and steady-state size could be predicted from the measured [Ca2+]i signal assuming a Michaelis-Menten-type regulation of the vesicle supply by Ca2+. An elevated recruitment activity was observed at increased [Ca2+]i even when protein kinase C was blocked, but maximum effects could be obtained only after stimulation of PKC by phorbol esters or by prolonged elevations in [Ca2+]i. We suggest that, in chromaffin cells, elevated cytosolic Ca2+ modulates exocytotic plasticity via PKC-dependent and -independent pathways.     

Assessment of acute myocardial necrosis after cardiopulmonary resuscitation and cardioversion by means of combined thallium-201/technetium-99m pyrophosphate tomography

Diagnosis of acute myocardial necrosis by means of conventional electrocardiographic criteria or the release of cardiac enzymes is often difficult or even impossible in patients with out-of-hospital cardiac arrest due to ventricular fibrillation with subsequent cardiopulmonary resuscitation including several DC countershocks. Simultaneous thallium-201/technetium-99m pyrophosphate (PYP) tomography was prospectively applied to 57 patients without typical clinical or electrocardiographic signs of acute myocardial infarction within 48 h after successful resuscitation from out-of-hospital cardiac arrest. Scintigraphic evidence of acute necrosis was present in 23/57 patients (40%). Increased 99mTc-PYP uptake in the pericardial tissue was found in 24 patients (42%). Maximal creatine kinase (CK) concentration was increased in 50/57 patients (88%). CK-MB activity averaged 68+/-52 U/l in patients with positive and 17+/-13 U/l in patients with negative tomograms (P<0.0005), demonstrating the validity of 201Tl/99mTc-PYP tomography. It may be concluded that simultaneous 201Tl/99mTc-PYP tomography is a valuable tool for evaluation of myocardial necrosis after cardiopulmonary resuscitation including DC countershock. Acute myocardial necrosis, as indicated by scintigraphy, represents a potential trigger for the occurrence of ventricular fibrillation. Therefore, 201Tl/99mTc-PYP tomography can be recommended in order to guide further diagnostic and therapeutic interventions in patients after cardiopulmonary resuscitation in whom the underlying cause of the occurrence of ventricular fibrillation is obscure.     

Early-onset Alzheimer''s disease due to mutations of the presenilin-1 gene on chromosome 14: a 7-year follow-up of a patient with a mutation at codon 139

In recent years, several factors have altered the spectrum of respiratory infections and their likelihood of response to empiric treatment. Altered microbial resistance has led to the possible need for specific etiologic diagnosis in some hospital-acquired infections in the normal host. In the immune-compromised host, the spectrum of atypical presentations and unusual organisms limits the clinician's ability to choose effective empiric therapies. In the normal host, bronchoscopic diagnosis seems to be most useful in the groups with severe community-acquired pneumonia or poor response to therapy for community-acquired pneumonia. The group of patients with ventilator-associated pneumonia has been well-researched and the bronchoscopic techniques tend to show increased sensitivity over other diagnostic means, but this has not been proven to alter morbidity, mortality, or cost effectiveness. The immune-compromised host is commonly infected by organisms not easily diagnosed by other means and is thus unable to be treated empirically. Bronchoscopic diagnostic techniques play a larger and more clearly delineated role in these populations, including the patient populations with solid organ transplants, bone marrow transplants, and AIDS.     

Influence of topically and systemically active steroids on circulating leukocytes in Crohn's disease

OBJECTIVE: Budesonide, although only topically active, is effective in the treatment of Crohn's disease. This study was performed to compare the clinical efficacies of budesonide and prednisolone in relation to the activation status of circulating leukocytes. METHODS: Twenty-four patients with active Crohn's disease were randomized to treatment with either budesonide or 6-methylprednisolone. Clinical response was monitored by the Crohn's disease activity index, C-reactive protein, and orosomucoid. Expression of CD25 and CD71 on T cells and CD64 on neutrophils was determined by flow cytometry. The release of TNF-alpha and IL-1beta by peripheral blood mononuclear cells was measured by ELISA. RESULTS: After 2 wk of treatment a clinical response was observed in both groups, but it was more accentuated in patients treated with prednisolone. At baseline an upregulation of CD71 and CD64, but not CD25, was found in active patients. Prednisolone significantly decreased the expression of CD64 and the release of TNF-alpha and IL-1beta, but did not alter the expression of CD25 and CD71. Budesonide treatment failed to exert any effect on circulating leukocytes. CONCLUSIONS: The inability of budesonide to downregulate activated circulating leukocytes may contribute to the somewhat lower clinical efficacy of this topical steroid in the treatment of active Crohn's disease.     

Wall functions for numerical simulation of turbulent natural convection along vertical plates

This paper presents new wall functions of velocity and temperature for natural convection along vertical plates based on dimensional analysis and experimental data. Because only fluid properties and local parameters are included, the proposed wall functions are suitable for numerical simulation and are expected to be also valid in non-isothermal flows in cavities. Moreover, a certain analogy of length, velocity, and temperature scales between natural and forced convection has been found.     

A parallel sorting algorithm for a novel model of computation

The computational complexity of a parallel algorithm depends critically on the model of computation. We describe a simple and elegant rule-based model of computation in which processors apply rules asynchronously to pairs of objects from a global object space. Application of a rule to a pair of objects results in the creation of a new object if the objects satisfy the guard of the rule. The model can be efficiently implemented as a novel MIMD array processor architecture, the Intersecting Broadcast Machine. For this model of computation, we describe an efficient parallel sorting algorithm based on mergesort. The computational complexity of the sorting algorithm isO(nlog² n), comparable to that for specialized sorting networks and an improvement on theO(n ^1.5) complexity of conventional mesh-connected array processors.