The variable domain of nonassembled Ig light chains determines both their half-life and binding to the chaperone BiP

Not much is known about the features that determine the biological stability of a molecule retained in the endoplasmic reticulum (ER). Ig light (L) chains that are not secreted in the absence of Ig heavy (H) chain expression bind to the ER chaperone BiP as partially folded molecules until they are degraded. Although all Ig L chains have the same three-dimensional structure when part of an antibody molecule, the degradation rate of unassembled Ig L chains is not identical. For instance, the two nonsecreted murine Ig L chains, kappaNS1 and lambdaFS62, are degraded with half-lives of approximately 1 and 4 hr, respectively, in the same NS1 myeloma cells. Furthermore, the BiP/lambdaFS62 Ig L chain complex appears to be more stable than the BiP/kappaNS1 complex. Here, we used the ability of single Ig domains to form an internal disulfide bond after folding as a measure of the folding state of kappaNS1 and lambdaFS62 Ig L chains. Both of these nonsecreted L chains lack the internal disulfide bond in the variable (V) domain, whereas the constant (C) domain was folded in that respect. In both cases the unfolded V domain provided the BiP binding site. The stability of BiP binding to these two nonsecreted proteins was quite different, and both the stability of the BiP:Ig L chain complex and the half-life of the Ig L chain could be transferred from one Ig L chain isotype to the other by swapping the V domains. Our data suggest that the physical stability of BiP association with an unfolded region of a given light chain determines the half-life of that light chain, indicating a direct link between chaperone interaction and delivery of partially folded substrates to the mammalian degradation machinery.     

Factors influencing readmission to hospital. I. Tetraplegia

Tetraplegia produces exceptionally severe physical impairment causing disability which demands almost total dependence on others for the activities of daily living but there is no impairment of mental function. The tetraplegic is, therefore, capable of influencing his environment and those features of it which may lead to the need for readmission to hospital. Of the factors studied relating to readmission to hospital, only age and occupational status of the patient at the time of his paralysis are of significance.     

Application of contact laser scalpel in thoracic surgery

The authors have carried out 296 transthoracic and endoscopic YAG-laser operations in various diseases of bronchopulmonary system. Sapphire and quartz applicator-tips were used as a contact scalpel. The procedures of laser operations with the use of the contact mode are described in detail and comparative evaluation of both types of thermal applicator-tips is given. The combination of cutting and coagulation properties of the contact laser scalpel enables its use in various operations on the lung and pleura including thoracoplastic interventions as well as accomplishment of an endoscopic photoresection of endobronchial tumors.     

Structural requirements for the cytotoxicity of the N-terminal region of HIV type 1 Nef

We have found that the hemolytic and cytotoxic activities of myristoylated Nef N-terminal peptides require a net positive charge in the first seven amino residues of the sequence. The activities are considerably less dependent on the secondary structure of the peptides. Film balance studies showed that both active and inactive peptides interacted with neutral phospholipid monolayers, suggesting that binding to neutral lipids was not a sufficient condition for lytic activity. It was also found that nonmyristoylated N-terminal peptide did not interact to the same extent with the monolayer, indicating that myristoylation was essential for lipid interaction. It is considered that the positively charged residues of the proximate N terminus of Nef interact with acidic lipids of biological membranes, reinforcing the weak membrane-targeting properties of the myristyl chain. Parallels are drawn between this mode of interaction with membranes and that of members of the Src family of proteins, which are also myristoylated and have positively charged residues in their proximate N termini. In particular, these proteins and Nef also have serine residues in their proximal N-terminal regions, which when phosphorylated could neutralize the positive charge and thus provide a mechanism for modulating membrane interaction.     

Telemedicine in Australia. Recent developments

To assess the frequency and natural history of swallowing problems following an acute stroke, 121 consecutive patients admitted within 24 hours of the onset of their stroke were studied prospectively. The ability to swallow was assessed repeatedly by a physician, a speech and language therapist, and by videofluoroscopy. Clinically 51% (61/121) of patients were assessed as being at risk of aspiration on admission. Many swallowing problems resolved over the first 7 days, through 28/110 (27%) were still considered at risk by the physician. Over a 6-month period, most problems had resolved, but some patients had persistent difficulties (6, 8%), and a few (2, 3% at 6 months) had developed swallowing problems. Ninety-five patients underwent videofluoroscopic examination within a median time of 2 days; 21 (22%) were aspirating. At 1 month a repeat examination showed that 12 (15%) were aspirating. Only 4 of these were persistent; the remaining 8 had not been previously identified. This study has confirmed that swallowing problems following acute stroke are common, and it has been documented that the dysphagia may persist, recur in some patients, or develop in others later in the history of their stroke.     

Modification of lethal radiation injury in mice by postradiation exposure to low-intensity centimeter-band radio frequency waves

A clearly pronounced modification of acute radiation injury of mice has been obtained by prolonged action (for up to 23 hours) of low-intensity (5 +/- 1.5 mu Wt/cm2) radiofrequency radiation in the ranges of 2-8, 8-18 and 19-27 GHz with a swing frequency of 12-14 Hz, applied immediately after exposure to lethal dose of gamma-radiation. Survival of mice and average life duration of killed mice were increased.     

Calmodulin-stimulated cyclic nucleotide phosphodiesterase (PDE1C) is induced in human arterial smooth muscle cells of the synthetic, proliferative phenotype

The diversity among cyclic nucleotide phosphodiesterases provides multiple mechanisms for regulation of cAMP and cGMP in the cardiovascular system. Here we report that a calmodulin-stimulated phosphodiesterase (PDE1C) is highly expressed in proliferating human arterial smooth muscle cells (SMCs) in primary culture, but not in the quiescent SMCs of intact human aorta. High levels of PDE1C were found in primary cultures of SMCs derived from explants of human newborn and adult aortas, and in SMCs cultured from severe atherosclerotic lesions. PDE1C was the major cAMP hydrolytic activity in these SMCs. PDE expression patterns in primary SMC cultures from monkey and rat aortas were different from those from human cells. In monkey, high expression of PDE1B was found, whereas PDE1C was not detected. In rat SMCs, PDE1A was the only detectable calmodulin-stimulated PDE. These findings suggest that many of the commonly used animal species may not provide good models for studying the roles of PDEs in proliferation of human SMCs. More importantly, the observation that PDE1C is induced only in proliferating SMCs suggests that it may be both an indicator of proliferation and a possible target for treatment of atherosclerosis or restenosis after angioplasty, conditions in which proliferation of arterial SMCs is negatively modulated by cyclic nucleotides.     

Application of plasma scalpel for cholecystectomy

107 male patients with diabetes mellitus type II (DM) combined with hypertension aged 62 to 76 years were divided into 5 groups comparable by DM but different by characteristics of hypertension, ischemic heart disease or other associated diseases the presence of which determined the choice of one or another drugs against hypertension. These drugs belonging to 5 groups (calcium antagonists, inhibitors of angiotensin converting enzymes, beta-blockers, alpha-blockers, agonists of imidasoline receptors) were compared in monotherapy and combined therapy for hypotensive activity and safety. It was found that monotherapy with corinfar, capoten, and cint had a potent hypotensive effect, atenolol and prasosin had moderate hypotensive efficacy and caused side effects more frequently. In differentiated use of the above drugs negative effects on associated diseases did not occur.