[Transient ischemic accidents during pregnancy secondary to congenital protein C deficiency].
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Biomedical subjects
Publications and source records attributed to R Gil.
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The structure of microtubules has been characterized to 3 nm resolution employing time-resolved X-ray scattering. This has revealed detailed structural features of microtubules not observed before in solution. The polymerization of highly purified tubulin, induced by the antitumour drug taxol, has been employed as a microtubule model system. This assembly reaction requires Mg2+, is optimal at a 1:1 taxol to tubulin heterodimer molar ratio, proceeds with GTP or GDP and is intrinsically reversible. The X-ray scattering profiles are consistent with identical non-globular alpha and beta-tubulin monomers ordered within the known helical surface lattice of microtubules. Purified tubulin-taxol microtubules have a smaller mean diameter (approx. 22 nm) than those induced by microtubule associated proteins or glycerol (approx. 24 nm), but nearly identical wall substructure to the resolution of the measurements. This is because the majority of the former consist of only 12 protofilaments instead of the typical 13 protofilaments, as confirmed by electron microscopy of thin-sectioned, negatively stained and ice-embedded taxol microtubules. It may be concluded that taxol induces a slight reduction of the lateral contact curvature between tubulin monomers. The main fringe pattern observed in cryo-electron micrographs is consistent with a simple 12 protofilament 3-start skewed lattice model. Cylindrical closure of this lattice can be achieved by tilting the lattice 0.8 degrees with respect to the microtubule axis. The closure implies a discontinuity in the type of lateral contacts between the tubulin monomers (regardless of whether these are of the -alpha-beta- or the -alpha-alpha-/-beta-beta- type), which indicates that lateral contacts and the subunit specificity of taxol binding are, to a large degree, equivalent.
The blink reflex and stimulodetection of the facial nerve was studied during the first ten days, the 30th and 60th day and at the end of the sixth month in 91 patients with Bell's palsy. In patients with present R1 during the first ten days, there was a remarkable tendency towards a satisfactory recovery without complications. On the contrary using this single test, it is impossible to determine with 100% accuracy, which Bell's palsy will have an unsatisfactory recovery with severe dysfunction. The blink reflex seems to be a useful test for predicting the prognosis in an early stage of the paralysis. The association of the blink reflex and stimulodetection of the facial nerve allows to evaluate the risk of sequelae by the means of different electrophysiological patterns.
Endogenous event-related potentials (and especially the P300 component) have delayed latencies relative to normal controls in patients with dementias of diverse aetiologies. Moreover, the subcortical varieties of dementia tend to affect also the early-stage N1 and P2 components whereas both types of dementias affect the later-stage N2 and P3 components. However it has become obvious that patients with HIV infection are susceptible to develop progressive, AIDS-related dementia, renamed 'HIV encephalopathy' by the Center for Disease Control. Several studies have shown that endogenous, but also early, components of long latency auditory evoked potentials are prolonged in latency in HIV-demented patients. However, these changes may also be present in class II and III patients and may permit the early recognition of HIV encephalopathy.
A computerized EEG (cEEG) study was performed in two groups of patients with dementia of the Alzheimer type (DAT) and with Parkinson's disease with dementia (PDD). Compared to control subjects suffering from Parkinson's disease without dementia, both groups demonstrated similar slowing down of background activity. However, there were more low frequency components, defined as between 2.5-7 Hz, and less topographical differentiation in PDD than in DAT. Furthermore, more severe impairment of cognitive functions was observed in DAT, but their psychometric score correlated with slowing down of EEG only in DMP. These observations emphasize the influence of the subcortical/cortical axis both in dementia of Parkinson's disease and in the neurophysiology of the EEG.
The clinical features of a patient with cholesterol embolism are presented. Histopathological examination showed the typical clefts of cholesterol in the skin and renal vessels. We believe this entity is under-reported in the dermatological literature.
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To assess the function of the sino-atrial node, electrophysiological study with pharmacological autonomic blockade was performed in 3 groups of patients: group I with a-v III zero or II zero type 2 heart block, group II with bifascicular interventricular blocks and group III-controls. Sino-atrial node electrogram was recorded in 81% of patients. Obtained results show, that sino-atrial node dysfunction is uncommon in patients with atrioventricular or interventricular blocks (8.6% and 15% respectively). Electrophysiological assessment of sino-atrial node function seems to be important in the consideration of patients with a-v or interventricular blocks for appropriate type of permanent pacing.
Five patients developed neurological adverse effects as they were treated with amiodarone for 2 to 18 months. The daily maintenance dose did not exceed 400 mg. The neurological manifestations included tremor, ataxia, peripheral neuropathy, dyskinesia, myoclonic jerks, extrapyramidal hypertony, and altered mental status. These side effects resolved within 3 days to 3 months after amiodarone withdrawal. Advanced age, renal failure, diabetes mellitus, and alcoholism seemed to be risk factors for development of amiodarone neurotoxicity. Both peripheral and central nervous systems are involved in these amiodarone-induced complications.
In patients with mitral valve prolapse syndrome (MVP) various electrophysiological abnormalities occur. There are convergent opinions concerning QT distance variability and the influence of autonomic nervous system on ventricular repolarization in this syndrome. In 38 MVP patients (group I) and 24 subjects without this abnormality (group II) ecg was recorded during transvenous right atrial pacing at baseline, after ajmaline administration and after pharmacological autonomic blockade (atropine + propranolol). The following ventricular repolarization parameters were analysed: QTe (distance to the end of T wave), JTe (distance between J point and the end of T wave--so called "pure repolarization"), QTdys (repolarization dispersion) and the corrected QTc.QTe during 90/min right atrial pacing was significantly shorter than QTc in both groups. QTc was abnormally prolonged (above 440 msec) in MVP group. Ajmaline administration prolonged QTe in group II only, whereas autonomic blockade resulted in marked shortening of QTe in MVP group. QTdys was significantly prolonged only after ajmaline administration in group II. Based on above results, the following conclusions are made: 1) Right atrial pacing technique may be used for calculating standardized QT distance, an alternative to corrected QT. 2) Ajmaline test is useless in ventricular repolarization estimations in MVP patients. 3) In MVP patients the influence of adrenergic system on ventricular repolarization at rest appears to be greater than in non-MVP subjects.
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Cloning and sequencing of RCS1, Saccharomyces cerevisiae gene whose product seems to be involved in timing the budding event of the cell cycle, is described. A haploid strain in which the 3'-terminal region of the chromosomal copy of the gene has been disrupted produces cells that are, on average, twice the size of cells of the parental strain. The critical size for budding in the mutant is similarly increased, and the disruption mutation is dominant in a diploid heterozygous for the RCS1 gene. Spores from this diploid have a reduced ability to germinate, the effect being more pronounced in the spores carrying the disrupted copy of RCS1. However, disrupted cells recover from alpha-factor treatment equally as well as wild-type cells.
Cytogenetic, flow cytometric, cytophotometric and morphometric analyses were performed on 22 previously untreated, primary solid breast carcinomas. Although the cell nuclei as the primary object of these studies were the same in all the tumors, distinct features were evaluated in each case to determine to what degree the results obtained by these techniques are comparable. From the cytogenetic viewpoint, six tumors had a modal number in the diploid range, seven were in the triploid range, and two in the tetraploid range; seven tumors had no modal number. These data correlate with the flow cytometry and cytophotometry results obtained, with DNA values slightly higher than their respective chromosomal modes. However, no correspondence between chromosomal modes and mean nuclear area was found. Chromosomal markers have been identified that particularly affect chromosomes 1 (p11, q21-qter), 11 and 16, although no common markers existed in all cases. Cytogenetics is the most sensitive technique, but the low yield (22 out of 140 tumors assayed) considerably restricts its value in any prospective breast cancer study.
Auditory evoked potentials are recorded in 12 subjects 4 times per day: 08 30, 11 30, 14 30 and 18 30. The daily variations of N1, P2, N2 and P3 are studied globally and according to the (morning- or evening) type of subjects. The latency of N2 decreases during the day; it possibly reflects variations in vigilance. The P3 amplitude varies according to the subject typology: for morning-type subjects, P3 is higher in the afternoon than in the morning, and for evening-type subjects, P3 decreases from morning to evening. These evolutions possibly reflect the effort in attention required by different tasks.
The blink reflex was studied in 38 cases with lateral medullary lesions (Wallenberg syndrome). Twenty-one blink reflexes were abnormal. The most common abnormality is an afferent delay in the late reflex on the side of the lesion with a normal early reflex. This abnormality is not pathognomonic of the Wallenberg syndrome. The physiopathogeny is discussed.
On the surface of phagocytes, C3b receptors (CR1) bind C3b-coated particles and promote their ingestion after activation by appropriate stimuli such as lymphokines or the chemoattractant formyl methionyl leucyl phenylalanine (fMLP) and fibronectin. The aims of the present study were 1) to define at the electron microscopic level the nature of the process responsible for CR1 internalization and 2) to dissect the mechanism by which a physiological activator (fMLP) stimulates this process. CR1 was visualized either by the immunogold technique or by quantitative electron microscopic autoradiography using a monoclonal anti-CR1 antibody. Both techniques revealed that after anti-CR1 binding, CR1 cluster on the neutrophil surface in a time-, temperature-, and antibody-dependent fashion, but do not concentrate in coated pits. CR1 internalization requires receptor cross-linking (does not occur in the presence of Fab fragments of anti-CR1) and intact microfilaments. It results in the association of the internalized material with large flattened vacuoles, organized in stacks. Together with the surface localization of CR1 close to cytoplasmic projections (ruffles), these observations suggest that uptake of CR1 occurs through a macropinocytotic process. Eventually, CR1 concentrate in lysosomal structures. fMLP markedly stimulates this pattern of CR1 internalization without affecting their clustering or their lack of association with coated pits. Stimulation by fMLP is inhibited by pertussis toxin, unaffected by preventing receptor-triggered cytosolic free calcium [Ca2+]i elevations, and mimicked by phorbol myristate acetate. Taken together our data demonstrate 1) that, in neutrophils, CR1 is internalized via a coated pit independent macropinocytotic process, dependent on intact microfilaments and receptor cross-linking; 2) that, in the same cells, fMLP is internalized via the classical coated pits pathway; and 3) that fMLP amplifies CR1 uptake possibly via protein kinase C stimulation.
Aculeacin A is a lipopeptide that inhibits beta-glucan synthesis in yeasts. A number of Saccharomyces cerevisiae mutants resistant to this antibiotic were isolated, and four loci (ACR1, ACR2, ACR3, and ACR4) whose products are involved in the sensitivity to aculeacin A of yeast cells were defined. Mutants containing mutations in the four loci were also resistant to echinocandin B, another member of this lipopeptide family of antibiotics. In contrast, acr1, acr3, and acr4 mutants were resistant to papulacandin B (an antibiotic containing a disaccharide linked to two fatty acid chains that also inhibits beta-glucan synthesis), but acr2 mutants were susceptible to this antibiotic. This result defines common and specific steps in the entry and action of aculeacin A and papulacandin B. The analysis of double mutants revealed an epistatic effect of the acr2 mutation on the other three mutations. Cell walls of the four different mutants did not show significant alterations in composition with respect to the parental strain, and in vitro glucan synthase activity was also unaffected. However, cell surface hydrophobicity in three of the mutants was considerably decreased with respect to the parental strain.
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