Platelet-activating factor is an effector of rapid reactions and an inductor of late responses in immune-mediated injury.
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Biomedical subjects
Publications and source records attributed to A Alonso.
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We report the case histories of three sisters with congenital hydrocephalus associated with stenosis of the cerebral aqueduct. The parents were a young consanguineous couple. In two cases hydrocephalus was detected before birth by ultrasonography. We consider these three cases to be of the rare autosomal form of hereditary hydrocephalus.
An infant with unusual CT and MRI manifestations of postnatally acquired cytomegalovirus (CMV) infection is presented. The child exhibited extensive inflammatory lesions in the periventricular area and at the level of the quadrigeminal plate with the formation of a pseudotumour at this level. The latter produced aqueduct obstruction resulting in hydrocephalus. These findings have not previously been described in the literature.
Primary sarcomas of the lung are extremely rare. Among the most common to occur in this location are leiomyosarcoma, fibrosarcoma, and hemangiopericytoma. Many difficulties are encountered when establishing these sarcoma diagnoses, or one of another pathologic type, because of overlapping histologic features and morphologic similarities between primary and metastatic lesions. In this study, the diagnosis of a primary monophasic synovial sarcoma of the lung was aided by the observation of the X;18 translocation characteristic of this neoplasm. To the best of our knowledge, this is the first cytogenetic report of a primary pulmonary synovial sarcoma.
An in vitro slice preparation of combined hippocampus and entorhinal cortex from adult rats was used to study the modalities of generation and propagation, as well as the pharmacological properties of the epileptiform activity induced by the muscarinic agonist pilocarpine (10 microM). Simultaneous field potentials recordings were made from the medial entorhinal cortex and from the dentate gyrus, CA3 and CA1 subfields. Pilocarpine application induced two types of interictal epileptiform discharges. The first occurred in the entorhinal cortex and consisted of bursts of population spikes lasting 408 +/- 135 ms (n = 20 slices) and repeating at a rate of 0.26 +/- 0.07 Hz (n = 20); this interictal activity propagated to the hippocampus via the perforant path. The second type was only observed in CA3 and CA1 subfields, had shorter duration (82 +/- 16 ms; n = 20) and occurred at a higher rate (1.42 +/- 0.7 Hz; n = 20) than the first type. Ictal epileptiform discharges (duration: 11.5 +/- 4.1 s; rate: 0.002 +/- 0.0009 Hz; n = 10) were also seen in the entorhinal cortex, from where they propagated to the dentate, CA3 and CA1 via the hippocampal trisynaptic loop as revealed by latency analysis and lesion experiments. Ictal and interictal discharges of entorhinal origin disappeared in the hippocampal sectors, but continued to occur in the entorhinal cortex following a cut of the perforant path (n = 5). Fast interictal discharges observed solely in the hippocampus originated in CA3, since sectioning the Schaffer collaterals made them disappear in CA1 (n = 7). All types of epileptiform activity disappeared during application of the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione (10 microM; n = 7). By contrast, the N-methyl-D-aspartate receptor antagonist 3-3(2-carboxy-piperazine-4-yl) propyl-1-phosphonate (10 microM) abolished ictal discharges in the entorhinal cortex and reduced the duration of the interictal events recorded in this area (n = 7). Interictal discharges originating from CA3 continued to occur at a higher rate than in control during application of this N-methyl-D-aspartate receptor antagonist. Our study confirms that the combined hippocampal-entorhinal slice preparation represents a suitable model for understanding the modalities of origin and propagation of epileptiform activity within the limbic system. In this in vitro preparation, the entorhinal cortex is the site of origin for ictal discharges. Moreover, the different types of epileptiform activity induced by this muscarinic agonist have specific, structure-dependent pharmacological profiles. These results are discussed in relation to those obtained in vivo.
Changes in steady-state fluorescence anisotropy of 1 -(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene TMA-DPH) are applied to the detection of lamellar-hexagonal transitions in egg phosphatidylethanolamine. Even low (2 mole%) proportions of diacylglycerol decrease the hexagonal transition temperature considerably, as confirmed by differential scanning calorimetry. Diacylglycerol is also found to promote a lamellar to "isotropic" (Q(224) cubic) transition in mixtures of phosphatidylcholine: phosphatidylethanolamine:cholesterol. This nonreversible transition is also observed by (31)P nuclear magnetic resonance and detected as a large increase in TMA-DPH steady-state anisotropy. The same technique reveals as well that lysophosphatidylcholine counteracts the effect of diacylglycerol and stabilizes the lamellar phase in both transitions. Diacylglycerol and lysophosphatidylcholine are known to respectively promote and inhibit membrane fusion in a variety of systems. These data are interpreted in support of the hypothesis of a highly bent structural fusion intermediate ("stalk"). They also show the interest of lipid-phase studies in predicting and rationalizing membrane fusion mechanisms.
Sixty-two patients with rheumatic mitral valve disease (mean age 42.2 +/- 10.2 years) underwent repair of chordae tendineae between June 1974 and May 1994. Chordal shortening was done in 38 patients, fenestration in 17, resection of secondary chordae in 3, replacement in 2, and transposition in 2. In 41 patients, mitral commissurotomy was also done. Ring annuloplasty was done in all patients. The mean follow-up was 10.2 years (range 2 months to 20 years). The completeness of follow-up during the closing interval (January to July 1994) was 100%. Hospital mortality occurred in four patients (6.5%) and nine patients died during the late follow-up. The actuarial survival curve at 20 years was 65.8% +/- 10%. Six patients with mitral valve dysfunction (restenosis 4, insufficiency 2) and one with aortic valve dysfunction (structural deterioration of bioprosthesis) underwent reoperation. The actuarial curve of freedom from reoperation at 20 years for mitral valve dysfunction was 73.1% +/- 10.5%. In the 49 surviving patients, a Doppler echographic study during the closing interval showed a mean mitral valve area of 1.9 +/- 0.3 cm2. In the 43 patients with a repaired native valve, absent or trivial mitral regurgitation was documented in 35 and mild or moderate regurgitation in 8. In conclusion, repair of chordae tendineae in rheumatic mitral valve disease when feasible is a stable and safe procedure with a low prevalence of reoperation. However, the type of reconstructive operation and experience of the surgical team are major considerations in successful repair of the mitral valve.
Psychodynamic group therapy, by definition, offers group members an opportunity to revisit some of the earliest developmental stages. The authors argue that conflicts around separation and individuation are stimulated with each beginning and ending of an intimate group. The leader of that group is similarly challenged around these primary conflicts. The question of group contagion, difficulties around the capacity to be alone, and the problems of projective identification are explored as they have an impact on leaders in a group. Case examples are offered to illustrate leadership problems along these dimensions.
Cell surface heparan sulfate proteoglycans (HSPGs) participate in molecular events that regulate cell adhesion, migration, and proliferation. The present study demonstrates that soluble heparin-binding proteins or cross-linking antibodies induce the aggregation of cell surface HSPGs and their distribution along underlying actin filaments. Immunofluorescence and confocal microscopy and immunogold and electron microscopy indicate that, in the absence of ligands, HSPGs are irregularly distributed on the fibroblast cell surface, without any apparent codistribution with the actin cytoskeleton. In the presence of ligand (lipoprotein lipase) or antibodies against heparan sulfate, HSPGs aggregate and colocalize with the actin cytoskeleton. Triton X-100 extraction and immunoelectron microscopy have demonstrated that in this condition HSPGs were clustered and associated with the actin filaments. Crosslinking experiments that use biotinylated lipoprotein lipase have revealed three major proteoglycans as binding sites at the fibroblast cell surface. These cross-linked proteoglycans appeared in the Triton X-100 insoluble fraction. Platinum/carbon replicas of the fibroblast surface incubated either with lipoprotein lipase or antiheparan sulfate showed large aggregates of HSPGs regularly distributed along cytoplasmic fibers. Quantification of the spacing between HSPGs by confocal microscopy confirmed that the nonrandom distribution of HSPG aggregates along the actin cytoskeleton was induced by ligand binding. When cells were incubated either with lipoprotein lipase or antibodies against heparan sulfate, the distance between immunofluorescence spots was uniform. In contrast, the spacing between HSPGs on fixed cells not incubated with ligand was more variable. This highly organized spatial relationship between actin and proteoglycans suggests that cortical actin filaments could organize the molecular machinery involved in signal transduction and molecular movements on the cell surface that are triggered by heparin-binding proteins.
Pulmonary neutrophil entrapment and resultant oxidative injury is thought to be the primary mechanism of cardiopulmonary bypass (CPB) induced lung injury. Interleukin-8 (IL-8), a potent neutrophil chemoattractant induced by cytokines, including tumor necrosis factor-alpha (TNF), is found in increased concentrations in bronchial alveolar lavage fluid (BALF) in lung inflammation. Since aprotinin reduces TNF release during CPB, the effects of aprotinin on BALF IL-8 concentrations and neutrophil levels were determined after CPB in adult humans. Study patients were equally divided into a control group (n = 8, Group 1) and an aprotin-intreated group (n = 8, Group 2). In vitro neutrophil chemotaxis was done with volunteer neutrophils using three different chemoattractants: 1) N-formyl-1-methionyl-1-leucyl-1-phenylalanine (FMLP); 2) the supernatant of a human bronchial epithelial cell culture line, A549, after 24 h of TNF stimulation with or without aprotinin or N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK) (a potent protease inhibitor), and 3) BALF. Aprotinin treatment significantly (P < 0.05) reduced post-CPB BALF IL-8 concentrations and percentage of neutrophils. In vitro, BALF from Group 1 had significantly greater chemotactic ability when compared with Group 2. The TNF stimulated A549 cell culture supernatant had significantly (P < 0.05) greater chemotactic ability than control supernatant, while aprotinin and TLCK significantly (P < 0.05) reduced this chemotactic ability. These results demonstrate that aprotinin blunts IL-8 production and reduces neutrophil lung accumulation post-CPB.
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We used the spin label electron spin resonance technique to monitor the hydration effect on the molecular dynamics of lipids at C-5, C-12, and C-16 positions of the alkyl chain. Increase in water content of neonatal rat SC leads to an increase in membrane fluidity, especially in the region near the membrane-water interface. The effect is less pronounced deeper inside the hydrophobic core. The reorientational correlation time at the C-16 position of hydrocarbon chains showed a higher change up to approximately 18% (w/w) of water content. This behavior was accompanied by an exponential decay both in elastic modulus and electrical resistance with water content. On the contrary, the segmental motion at C-5 and C-12 positions of the chain and the permeability constant increased in the range of around 18% w/w) up to the fully hydrated condition (58 +/- 7%). Our results give a better characterization of the fluidity of SC and show that it is the principal parameter involved in the mechanism of the permeability of different compounds through skin.
Evidence has suggested that the nucleus basalis magnocellularis has the potential to influence the functional state of the cerebral cortex through topographically organized, widespread projections of the cholinergic cells in that nucleus. It has also been shown that, in addition to the cholinergic neurons, other non-cholinergic magnocellular basal forebrain neurons, some of which have been identified as gamma-aminobutyric acid-ergic, project into the cerebral cortex and thus may also participate in the modulation of its activity. We have performed a comparative study of the intrinsic rhythmic properties of immunohistochemically and morphologically characterized choline acetyltransferase (ChAT)-positive and ChAT-negative cells of the nucleus basalis by means of intracellular recordings in guinea pig brain slices. Our results demonstrate that relatively large, multipolar cholinergic and non-cholinergic neurons each display differential voltage-dependent properties that allow them to discharge rhythmically in spike bursts and spike clusters, respectively, at low frequencies (< 10 Hz). Cholinergic cells display bursts of 2-4 action potentials (at approximately 200 Hz) riding on low-threshold spikes recurring at a low frequency (< 5 Hz) when depolarized from a membrane potential more negative than -55 mV and display low-frequency (< 10-15 Hz) tonic firing when depolarized from a more positive level. In contrast, non-cholinergic cells fire in a unique mode, displaying non-adapting clusters of spikes interspersed with rhythmic subthreshold membrane-potential oscillations when depolarized from levels less negative than -55 mV. The spike clusters repeat rhythmically at relatively low frequencies (2-10 Hz). The intracluster spiking frequency is relatively high and coincides approximately with that of the intervening membrane-potential oscillations (approximately 20-70 Hz). The cluster frequency of the non-cholinergic cells corresponds, in the same manner as the burst frequency of the cholinergic cells, to a delta (1-4 Hz) or theta (4-10 Hz) range of activity, whereas the intra-cluster and tonic spike frequencies of the non-cholinergic cells correspond to high beta to gamma ranges of electroencephalographic activity (19-30 Hz and 30-60 Hz, respectively). We propose that the different modes of oscillatory firing by the cholinergic and non-cholinergic basal forebrain cell populations could collectively contribute to the rhythmic modulation of slow and fast rhythms within the cerebral cortex.
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Blood conservation methods are commonly practiced throughout most hospitals that conduct cardiothoracic surgery. In an effort to reduce patients' exposure to homologous blood products and due to cost effectiveness of blood conservation techniques, this present study combines autotransfusion of the remaining blood in the extracorporeal circuit and ultrafiltration of the plasma effluent, and describes the resulting product. Seven patients, greater than 19 years of age, requiring cardiopulmonary bypass (CPB) were incorporated into this study. Exclusion criteria included age limitation. At termination of CPB, the remaining blood in the circuit was transferred to an autotransfusion machine and processed. Plasma (1054 +/- 206 ml) effluent was collected directly from the centrifugal bowl and processed through a ultrafiltrator, with a constant flow rate and negative pressure, until the plasma effluent concentrated down to an end processed volume of approximately 150 ml. The following variables were either measured or calculated: plasma-concentrate volumes per three minute interval, inlet/outlet pressures of an ultrafiltrator, transmembrane pressure (TMP), plasma free hemoglobin, fibrinogen, total protein, and colloid osmotic pressure. The average ultrafiltrate volume taken off from the plasma effluent was 828 +/- 237 ml, with an average ultrafiltrate volume of 115 ml in every three minute interval. The TMP did not change over the first 15 minutes of processing but became significantly elevated at the 18th minute interval and continued to increase and reach a maximum TMP of 286.5 +/- 2.1 mmHg at the end of concentration. Fibrinogen levels increased from pre-concentration values of 118.2 +/- 64 to 317 +/- 177 mg/dl (p = .03) along with increases in plasma free hemoglobin from 97.7 +/- 46 to 402.1 +/- 180 mg/dl (p = .0002). The total protein concentration increased by over 330% from baseline values. Ultrafiltrating plasma effluent from autotransfused cell salvaged CPB circuit contents could prove beneficial, but further study is required to discover ways to separate unfavorable products, such as activated platelet-leukocyte products and reduced plasma free hemoglobin, and to lower heparin concentrations of the plasma-concentrate.
Study of the characteristics of the hormone-refractory period in 32 patients with disseminated prostate cancer who had achieved a complete response to total androgen suppression, appreciating in all of them a subclinical or asymptomatic stage and a clinical or symptomatic one. The subclinical stage was characterized by raised PSA levels and ranged between 3-35 months; at 12 months 59% of patients had advanced to the symptomatic stage, while at 24 months this percentage is 84%. The clinical stage extends from appearance of symptoms to the patient's death, ranging from 3 to 32 months; at 12 months 41% has died; and 91% at 2 years.
A 40 year old male patient diagnosed as having pulmonary thromboembolism, was found to have a right atrial mass, after being subjected to an echocardiogram, a CT thoracic Scan and magnetic resonance imaging. An intracardiac exploration by cardiopul-monary bypass was performed. The mass was located and excised, but in fact found to be an extracardiac, inflammatory and cavitated mass. The wall of the right atrium was infiltrated due to the inflammatory process. This case illustrates the advantage of echocardiography, followed by surgery, in the clinical diagnosis and also shows how to treat cardiac masses and tumors.
The H1 class of histones comprises several main-type, S-phase dependent isoforms and, in addition, a sperm-specific H1t and a peculiar subtype, H1 zero, which is confined to highly differentiated cells. In contrast to main type histone genes, the H1 zero gene expression does not strictly depend on DNA replication. Also in contrast to the other H1 subtype genes, the mammalian H1 zero gene is not included in a histone gene cluster and its mRNA differs in structure, size and mode of processing from other histone mRNAs. The regulation of expression of the H1 zero gene varies from main type H1 genes in several respects. This is manifested in the promoter structure which contains sequence elements that are also found in main type H1 promoters, but also shows regulatory motifs which appear to be involved in a developmental regulation of the H1 zero gene, such as a retinoic acid receptor binding site, which has been described in the mammalian H1 zero gene promoter.