Gestalt descriptions embodiments and medical image interpretation

In this paper I will argue that medical specialists interpret and diagnose through technological mediations like X-ray and fMRI images, and by actualizing embodied skills tacitly they are determining the identity of objects in the perceptual field. The initial phase of human interpretation of visual objects takes place during the moments of visual perception before we are consciously aware of the perceived. What facilitate this innate ability to interpret are experiences, learning and training that become humanly embodied skills. These embodied skills are actualized during the moments of visual perception. My argument is that biology, society and instruments constitute unique individual ontologies influencing specialist readings of the technological output, in other words, putting limits on the “truth-to-nature” relation, which is so much sought for in science.     

Increased sensitivity of the cough reflex in progressive systemic sclerosis patients with interstitial lung disease

Cough is a common presenting symptom of interstitial lung disease (ILD). The aim of this study was to examine the cough reflex in patients with progressive systemic sclerosis (PSS), with and without associated ILD. The cough reflex to inhalation of chloride deficient solutions and capsaicin was determined in patients with PSS with associated ILD (n=12), compared to patients with PSS without ILD (n=12). In addition, patients with a chronic dry cough (n=12) and healthy subjects (n=10) without cough were studied. Cough responses to inhalation of isotonic solutions containing 150, 75, 37.5 and 0 mM Cl- ions and of capsaicin (0.9-500 mM) were measured. PSS patients with ILD reported a significantly higher cough score than PSS patients without ILD (p<0.03). ILD patients coughed more than those without ILD to Cl- of 37.5 and 0 mM (19.1+/-5.0 vs 6.2+/-1.9 coughs x min(-1) (p<0.03), and 29.2+/-5.0 vs 14.1/-4.1 coughs x min(-1) (p<0.04), respectively). The log concentration of capsaicin causing two or five coughs was lower in PSS with ILD compared to PSS without ILD (0.74+/-0.15 mM vs 2.12+/-0.26 mM; p<0.002). Patients with chronic dry cough had a similar degree of response to low-chloride and capsaicin solutions as patients with PSS and ILD, whilst healthy controls had a similar degrees of response to PSS patients. There is an increased cough reflex in patients with interstitial lung disease, which may represent sensitization of airway sensory nerves. This may be the basis for the chronic dry cough in patients with interstitial lung disease.     

Structural requirements for PAK activation by Rac GTPases

The Rho family GTPases, Rac1 and Rac2, regulate a variety of cellular functions including cytoskeletal reorganization, the generation of reactive oxygen species, G1 cell cycle progression and, in concert with Ras, oncogenic transformation. Among the many putative protein targets identified for Rac (and/or Cdc42), the Ser/Thr kinase p21-activated kinase (PAK) is a prime candidate for mediating some of Rac's cellular effects. This report shows that Rac1 binds to and stimulates the kinase activity of PAK1 approximately 2- and 4-5-fold, respectively, better than Rac2. Mutational analysis was employed to determine the structural elements on Rac and PAK that are important for optimal binding and activation. The most notable difference between the highly homologous Rac isomers is the composition of their C-terminal polybasic domains. Mutation of these six basic residues in Rac1 to neutral amino acids dramatically decreased the ability of Rac1 to bind PAK1 and almost completely abolished its ability to stimulate PAK activity. Moreover, replacing the highly charged polybasic domain of Rac1 with the less charged domain of Rac2 (and vice versa) completely reversed the PAK binding/activation properties of the two Rac isomers. Thus, polybasic domain differences account for the disparate abilities of Rac1 and Rac2 to activate PAK. PAK proteins also contain a basic region, consisting of three contiguous lysine residues (Lys66-Lys67-Lys68), which lies outside of the previously identified Cdc42/Rac-binding domain. Mutation of these Lys residues to neutral residues decreased PAK binding to activated Rac1 and Rac2 (but not Cdc42) and greatly reduced PAK1 activation by Rac1, Rac2, and Cdc42 proteins in vivo. In contrast, mutation of lysines 66-68 to basic Arg residues did not decrease (and in some cases enhanced) the ability of Rac1, Rac2, and Cdc42 to bind and activate PAK1. Our studies suggest that the polybasic domain of Rac is a novel effector domain that may allow the two Rac isomers to activate different effector proteins. In addition, our results indicate that a basic region in PAK is required for PAK activation and that binding of Rac/Cdc42 to PAK is not sufficient for kinase activation.     

Genetic risks of in vitro fertilization

In-vitro fertilization (IVF) with embryo transfer is a well established therapy in infertility. With the increase of andrological problems as reasons for IVF the question of possible genetic risks is gaining additional attention. For the patients, the incidence of congenital malformations in their offspring resulting from IVF as well as the incidence of spontaneous abortions are of particular interest. In this review population genetic data of congenital malformations are compared to those found in IVF populations. On average, congenital malformations occur in 3% of all livebirths in an unselected population, whereas there were 1.5% newborns with congenital malformations reported in the IVF population. This is well within this basic background risk for congenital malformations. Bearing maternal age and especially careful follow-up of early pregnancies after IVF in mind, the rate of spontaneous abortions after IVF (21 to 27%) is also not significantly increased above the rate of 15% in the unselected general population. The introduction of microinvasive techniques into IVF has given the question of possible genetic risks for the offspring from IVF using these techniques, a great deal of topical interest. The range of indications of subzonal or intracytoplasmatic sperm injection (ICSI) includes andrological problems to a high degree which themselves could be the result of chromosomal anomalies or hereditary disorders. One example is the vas deferens aplasia in one form of CF mutations. Cytogenetic and clinical genetic evaluation should be recommended especially in cases of andrological or idiopathic sterility and infertility. Some examples of autosomal dominant syndromes in which clinical genetic evaluation and genetic counselling are advisable are listed in a summarizing table.     

Triggering of L-selectin (gp90MEL-14) induces homotypic lymphocyte adhesion by a mechanism independent of LFA-1

The L-selectin adhesion receptor plays a central role in regulating leukocyte adhesion to endothelial cells. The data presented in this report demonstrate that triggering of L-selectin results in a rapid and vigorous homotypic adhesion among normal lymphocytes as well as lymphoblastoid cells, thereby providing evidence for a novel cell-cell adhesion function of L-selectin. The cellular adhesion event induced by mAb MEL-14 was dependent on metabolic energy, an intact cytoskeleton, and the activation of intracellular protein kinases. Cell clustering did not require cross-linking of L-selectin molecules and occurred in the complete absence of divalent cations. Analysis of adhesion receptor expression and antibody inhibition experiments indicated that cluster formation did not involve LFA-1, alpha 4 integrins, beta 1 integrins, beta 7 integrins, or CD44.     

Medium-term patency and anatomic changes after direct bronchial artery revascularization in lung and heart-lung transplantation with the internal thoracic artery conduit

OBJECTIVE: To examine the relationship of estrogen-induced changes in lipids and lipoproteins with alterations in the coagulation system. METHODS: Coagulation and lipid indices were measured in 31 postmenopausal women, ages 40-60 years, after a 3-month course of 0.625-mg conjugated equine estrogen. We analyzed changes in variables from baseline to 3 months using t tests for paired samples or the Wilcoxon matched-pairs signed-rank test. RESULTS: Unopposed estrogen replacement therapy produced statistically significant decreases in antithrombin-III antigen (P = .006) and activity (P = .001) and total protein S (P = .003) and a significant increase in protein C antigen (P = .017). C4b-binding protein also decreased significantly from baseline to 3 months (P < .001). Mean fibrinogen level decreased by 18.2 mg/dL, not a statistically significant change (P = .213). Estrogen produced the expected statistically significant changes in lipids and lipoproteins. Several correlations between changes in lipids and lipoproteins and coagulation indices were statistically significant. Protein C antigen and activity changes correlated directly with high-density lipoprotein cholesterol changes (r = .52, P < or = .005; r = .38, P < or = .05; respectively), and protein C antigen also correlated directly with increases in apoprotein A-I (r = .54, P < or = .005). Triglyceride changes correlated directly with changes in protein C antigen (r = .36, P < or = .05) and activity (r = .49, P < or = .005) and inversely with C4b-binding protein (r = -.58, P < or = .01). Apoprotein B was correlated with free protein S (r = .48, P < or = .01). CONCLUSIONS: Although several estrogen-induced changes may decrease atherosclerotic potential and hypercoagulability, others may promote coagulability. These divergent effects may be manipulated pharmacologically by other estrogen compounds or by the addition of various progestins.     

Two signaling mechanisms for activation of alphaM beta2 avidity in polymorphonuclear neutrophils

Circulating polymorphonuclear neutrophils (PMN) are quiescent, nonadherent cells that rapidly activate at sites of inflammation, where they develop the capacity to perform a repertoire of functions that are essential for host defense. Induction of integrin-mediated adhesion, which requires an increase in integrin avidity, is critical for the development of these effector functions. Although a variety of stimuli can activate integrins in PMN, the signaling cascades involved are unclear. Phosphatidylinositol (PI) 3-kinase has been implicated in integrin activation in a variety of cells, including PMN. In this work, we have examined activation of the PMN integrin alphaM beta2, assessing both adhesion and generation of the epitope recognized by the activation-specific antibody CBRM1/5. We have found that PI 3-kinase has a role in activation of alphaM beta2 by immune complexes, but we have found no role for it in alphaM beta2 activation by ligands for trimeric G protein-coupled receptors, including formylmethionylleucylphenylalanine (fMLP), interleukin-8, and C5a. Cytochalasin D inhibition suggests a role for the actin cytoskeleton in immune complex activation of alphaM beta2, but cytochalasin has no effect on fMLP-induced activation. Similarly, immune complex activation of the Rac/Cdc42-dependent serine/threonine kinase Pak1 is blocked by PI 3-kinase inhibitors, but fMLP-induced activation is not. These results demonstrate that two signaling pathways exist in PMN for activation of alphaM beta2. One, induced by FcgammaR ligation, is PI 3-kinase-dependent and requires the actin cytoskeleton. The second, initiated by G protein-linked receptors, is PI 3-kinase-independent and cytochalasin-insensitive. Pak1 may be in a final common pathway leading to activation of alphaM beta2.