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P David

Publications and source records attributed to P David.

At least 19 recordsLinked to original sources
PubMed1992

The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen.

Immunoglobulin G fractions from patients with Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disease of neuromuscular transmission, immunoprecipitate 125I-labeled omega-conotoxin GVIA-labeled calcium channels solubilized from rat brain. A 58-kDa antigen was detected by probing Western blots of partially purified calcium channels with LEMS plasma and IgG and was shown to be the relevant antigen in omega-conotoxin receptor immunoprecipitation. Monoclonal antibody 1D12, produced by immunizing mice with synaptic membranes, has properties similar to these autoimmune IgGs in both immunoprecipitation and Western blotting assays. 1D12 antigen was purified by immunoaffinity chromatography and shown to bind LEMS IgG. The antigen was identified by screening a rat brain cDNA library with 1D12 and was found to have strong homology to the synaptic vesicle membrane protein synaptotagmin. Our results indicate therefore that these antibodies immunoprecipitate omega-conotoxin receptors by binding to synaptotagmin that is associated with calcium channels. We suggest that the interaction between synaptotagmin and the voltage-gated calcium channel plays a role in docking synaptic vesicles at the plasma membrane prior to rapid neurotransmitter release and that autoantibody binding to a synaptotagmin-calcium-channel complex may be involved in the etiology of LEMS.

Antibodies, Monoclonal↗
PubMed1992

Guanidinium derivatives act as high affinity antagonists of Na+ ions in occlusion sites of Na+,K(+)-ATPase.

We have screened various alkyl- and arylguanidinium derivatives as possible competitors of Na+ or Rb+ for the cation sites on renal Na+,K(+)-ATPase. Alkyl-monoguanidinium or alkylbisguanidinium (BisG) compounds (chain lengths of C3 to C10) competitively inhibit the occlusion of Rb+ and Na+ with an order of affinities C10 greater than C8 greater than C6 greater than C4 greater than C3. BisG compounds are approximately twice as effective as the equivalent alkylmonoguanidinium compounds. In media of high ionic strength, affinities of tens of micromolar are observed, e.g. 26 microM for BisG 8. m-(mXBG)- and p-xylylenebisguanidinium were synthesized and were found to compete with Rb+ or Na+ with intrinsic affinities of 7.7 and 8.2 microM, respectively. The hydrophobicity rather than the degree of proximity of the guanidinium groups in all BisG compounds appears to determine the binding affinity. A systematic search has been made of conditions in occlusion assays for which the inhibitor affinities are highest. When the pH is raised from 7.0 to 8.5, a 5-fold increase in affinity is observed, suggesting that the guanidinium derivatives compete with protons at sites of pKa approximately 7.5. Replacing Tris-HCl with choline chloride-containing media raised apparent affinities approximately 2-fold. All guanidinium derivatives stabilize the E1 conformation of fluorescein-labeled Na+,K(+)-ATPase, acting as competitive Na+ analogues. In media containing only 1 mM Tris-HCl, pH 8.55, very high affinities were observed for binding to the fluorescein-labeled enzyme (e.g. 0.08 microM for mXBG). In very low ionic strength medium, the inhibition was still competitive with Rb+ ions. However, there was also evidence for nonspecific adsorption to the membranes. The following findings show that mXBG, a typical guanidinium derivative, behaves as a Na(+)-like antagonist. (a) It inhibits Na+,K(+)-ATPase activity, competing strongly with Na+ but only weakly with K+ ions. (b) It inhibits phosphorylation from ATP, competing with Na+ ions. (c) Like Na+ ions, it blocks phosphorylation from inorganic phosphate. Based on these results, we propose that the guanidinium group binds to a relatively wide vestibule at the cytoplasmic surface; but, unlike Na+ or K+ ions, it cannot pass into a narrower region of the cation transport path within the membrane. Therefore, it blocks the occlusion and active transport of cations. In the future, high affinity guanidinium derivatives may serve the purpose of locating cation-binding domains of the pump protein after being converted to reactive affinity or photoaffinity covalent labels.

Animals↗
PubMed1992

The M20 IL-1 inhibitor prevents onset of adjuvant arthritis.

Cytokines, specifically IL-1 and TNF, have been implicated as important mediators of joint destruction in rheumatoid arthritis (RA). Elevated levels of IL-1 in the joint fluid of patients with RA have been reported, as well as the presence of IL-1 inhibitory activity. We have reported the characterization of an inhibitor derived from a myelomonocytic cell line cloned in our laboratory which is specific for IL-1. This IL-1 inhibitor is protein in nature which specifically inhibits activity in vitro and in vivo. Previous studies showed that the inhibitor reduced acute inflammatory reactions associated with IL-1 (fever, leukocytosis, local foot pad swelling, lymph node enlargement and acute phase reactants). Thus it was of interest to study whether the M20 IL-1 inhibitor could modify adjuvant-induced chronic inflammation in rats, which is often used as a model for human RA. Administration of complete Freund's adjuvant (CFA) into Lewis rats, resulted in a severe adjuvant arthritis (AA) which reached peak severity after 14 days. Daily administration of IL-1 inhibitor, beginning after injection of CFA, abolished the appearance of AA. The parameters investigated were: joint swelling (the increase in diameter of joints), peri-articular erythema, limping of the rats and histological examination. The effect of the M20 IL-1 inhibitor was shown to be dose dependent and the IL-1 inhibitor alone had no adverse effects. These results indicate that the M20 IL-1 inhibitor may have a role in the treatment of AA and may be used to reduce pathological processes in joint inflammation.

Animals↗
PubMed1992

[MRI of the wrist joint].

Due to the development of new surface coils and the use of thin slices, MRI has become an essential diagnostic tool in wrist pathology. After several technical considerations, the authors describe the normal MRI appearance of the various anatomical structures of the wrist, particularly the triangular fibrocartilaginous complex of the wrist and the elements of the carpal tunnel. They review the principal indications for MRI: chronic diseases such as carpal tunnel syndrome and traumatic ligamentous and cartilaginous lesions. The bone marrow lesions detected in the presence of occult fractures and osteonecrosis of the lunate or scaphoid are then briefly considered. The diagnostic criteria of median nerve compression (carpal tunnel syndrome) include morphological and signal changes in the nerve, abnormal palmar convexity of the flexor retinaculum and signs of tenosynovitis of the intracarpal flexor tendons. However, in practice, MRI is only useful when there is disagreement between the clinical and EMG findings and in postoperative recurrences, in which case it may reveal insufficient section of the retinaculum or the presence of exuberant postoperative fibrosis responsible for persistent nerve compression. Traumatic tears of the triangular fibrocartilage are characterised by a linear high signal intensity image (on T1 and T2 weighted sequences), usually situated in the periphery of the articular disk. Degenerative lesions tend to be central, within the disk and are frequently observed after the age of 40 years.

Carpal Bones↗
PubMed1992

Intracranial arterial aneurysms: a review of neurosurgical results.

The results of elective surgery for intracranial aneurysms are now excellent, with a 90% cure rate, but they do not reflect the overall results of treatment of aneurysmal pathology. Despite improvements in microsurgical techniques, these results remain disappointing (56.4% cured, 27.3% dead in the 1983 co-operative study, this is mainly due to the severity of the initial haemorrhage caused by rupture of the aneurysms, but also to the problems encountered in transferring patients, as quickly as possible, to a specialized surgical unit. Only an early care of symptomatic patients will improve these results by reducing the frequency of rebleeding and vasospasm. The most dangerous complications to which patients who survived the first haemorrhage are exposed.

Aneurysm, Ruptured↗
PubMed1991

Characterization of lanthanides as competitors of Na+ and K+ in occlusion sites of renal (Na+,K+)-ATPase.

Lanthanides are useful probes in Ca2+ binding proteins, including sarcoplasmic reticulum (Ca2+,Mg2+)-ATPase. Here, we report that lanthanides compete with Rb+ and Na+ for occlusion in renal (Na+,K+)-ATPase. The lanthanides appear to bind at a single site and act as competitive antagonists, without themselves becoming occluded. All lanthanides tested are effective with the order of potencies Pr greater than Nd greater than La greater than Eu greater than Tb greater than Ho greater than Er, but differences are small. The presence of Mg2+ ions does not affect competition of La3+ with Na+ or K+ suggesting that the effects are not exerted via divalent metal sites. Lanthanides compete with Rb+ and Na+ in membranes digested with trypsin so as to produce 19-kDa and smaller fragments of the alpha-chain (Karlish, S.J.D., Goldshleger, R., and Stein, W. D. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 4566-4570), also suggestive of a direct interaction of lanthanides with Na+ and K+ sites. Effects of lanthanides on conformational changes of fluorescein-labeled (Na+,K+)-ATPase are Na(+)-like. They stabilize the E1 state and compete with K+ ions. The Ki for La3+ is 0.445 microM. The apparent affinity in fluorescence assays is proportional to enzyme concentration (Ki = 32.4*[protein] + 0.445 microM La3+), suggesting that lanthanides are also bound nonspecifically (possibly to phospholipids). Direct assays confirm that Tb3+ binding is nonspecific. Measurements of the rate of various conformational transitions show that the rate of E2(K+)----E1(X) (X = Na+ or La3+) is significantly inhibited by La3+ compared to Na+. La3+ ions also slightly accelerate the rate of the E1----E2(K+) conformational transition. The dissociation rate of La3+ has been measured by monitoring the rate of E1(La3+)----E2(K+). It is 1.741 s-1 at 25 degrees C. Based on this value, it is unlikely that La3+ ions are stably occluded, consistent with the conclusion from occlusion experiments. In the future, lanthanides bound to monovalent cation sites with high affinity may become useful probes for location and characterization of sites, although it will be necessary to take into account the large amount of nonspecific binding.

Amino Acid Transport Systems, Neutral↗
PubMed1991

Estimating maternal mortality in Djibouti: an application of the sisterhood method.

In many developing countries even crude estimates of the level of maternal mortality are lacking and the prospects of fulfilling this need using conventional sources of vital registration and health service statistics are not encouraging. The constraint this imposes on the effective planning, management and evaluation of the programmes now being launched to reduce these neglected deaths is self-evident. It is less obvious how the majority of developing countries can be expected to meet the call for reliable estimates of maternal mortality by 1995. The sisterhood method provides a means of obtaining population-based estimates using household surveys for data collection. This paper describes the application of the method in Djibouti in the context of a rapid multi-purpose household survey in difficult field circumstances. In recent years the reduction of the level of maternal mortality in developing countries has become a priority for both national governments and international agencies. Attention has been drawn to the wide range of levels within and between countries and to the huge discrepancies in the lifetime risk of maternal death for women in the developed compared with the developing world. This risk has been estimated to range from 1 in 19 in West Africa to almost 1 in 10,000 in Northern Europe.

Adolescent↗
PubMed1990

Polyurethane arterial prosthesis: experimental evaluation.

Two types of microporous polyurethanes have been evaluated both in vitro and in vivo. In vitro polyurethane disks have been seeded by endothelial cells from bovine aortic origin and from fresh human greater omentum. Various pretreatments permit comparison of six different experimental groups. The benefit of poly L lysine, laminin, fibronectin and previous astrocyte cell seeding is shown. The cell proliferation was assessed daily, using trypan blue in Malassez cells. Cell identification was performed by class I MHC antigen characterization and factor VIII staining. In vivo, 4 mm polyurethane arterial prostheses were implanted as carotid interpositions. Evaluation of polyurethane, both in vitro and in vivo, failed to demonstrate a satisfactory hemocompatibility of the material. However, previous treatment of polyurethane with laminin, fibronectin, and astrocyte cell seeding improves the biologic characteristics of the raw material.

Animals↗
PubMed1990

A case of epidermal nevus syndrome with carotid malformation.

Epidermal Nevus Syndrome (ENS) is characterized by linear verrucous lesions of the skin and congenital anomalies including bone deformities, eye and central nervous system (CNS) malformations. We describe a case of ENS associated with an abnormality of the carotid artery which is considered a risk for stroke.

Adult↗
PubMed1990

[Magnetic resonance imaging in knee injuries].

Of all the diagnostic imaging techniques for the injured knee, Magnetic Resonance Imaging (MRI) has been shown the most worthwhile. Indications for standard X rays, arthrography and ultrasonography are briefly reviewed. Advantages of MRI, the technical aspects and the sequences used are explained. After a short description of the signals of all the common anatomic components of the knee, we describe MR findings in meniscal pathology, tenoligamentous lesions and cartilage and bone injuries.

Humans↗
PubMed1990

Apparently primary malignant melanoma of the cerebellopontine angle. One case.

We report a case of primary malignant melanoma of the cerebellopontine angle. This tumour showed RMI features that were totally different from those reported for secondary melanomas, and therefore its nature could not be suspected before surgery. Intracranial primary melanomas are so rare that no other published case is available for comparison, and our tentative explanations for the atypical RMI signals cannot be supported by evidence from the literature.

Cerebellar Neoplasms↗
PubMed1990

Multiple sclerosis. Magnetic resonance imaging, evoked potentials and cerebrospinal fluid analysis.

We have studied 27 patients with multiple sclerosis (22 definite, 5 probable) by magnetic resonance imaging (MRI), visual evoked potentials (VEPs), brainstem auditory evoked potentials (BAEPs), and oligoclonal bands (OBs) in cerebrospinal fluid (CSF), MRI was altered in 92.5% of the cases, the presence of OBs in CSF was revealed in 73.1% of the examined patients, the frequency of evoked potentials (EPs) alteration was VEPs = 59.3% and BAEPs = 29.6%, at least one of the two EPs occurred positive in 66.6% of the cases. Our data confirm the more sensitive value of MRI compared with OBs and EPs studies in assessing MS, and stress the utility of the combined use of these tests.

Adolescent↗
PubMed1989

[Diagnosis of diseases of the spinal cord and the vertebral column].

Magnetic resonance imaging (MRI) nowadays plays a predominant role in the diagnosis and evaluation of spinal canal pathologies and has reduced the other exploratory methods, including computerized tomography (CT) and myelography, to an ancillary role. These pathologies are divided into three groups: those where MRI is the only imaging method (syringomyelia, tumours in the spinal canal, phakomatoses, external pachymeningitis, spinal cord injuries, myelitis); those where MRI is the initial method and is completed by other examinations (vascular malformations, dysraphism, myelopathies due to cervical osteoarthritis) and those where MRI still play a lesser role than CT (degenerative lesions of the lumbar column).

Humans↗
PubMed1989

A microtest plate assay of functional excitatory amino acid receptors.

A microtest plate assay of functional excitatory amino acid receptors present on cultured chick embryo retinal cells has been developed. It is based on measurements of excitatory amino acid-mediated increase in 22Na+ influx into retinal cells adhering to each of the 96 wells of microtest plates. Dose-dependent responses to L-glutamate, kainate and N-methyl-D-aspartate but not to quisqualate can be measured. These responses are selectively inhibited by antagonists of excitatory amino acids. The assay is reliable, fast to perform and parsimonious in terms of the volume and thus of amount of the drug applied. It allows a single investigator to perform, in one day, measurements of the effects of known or putative glutamatergic ligands in more than 100 different conditions.

Animals↗