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Biomedical subjects

J Andrade

Publications and source records attributed to J Andrade.

At least 37 records · Page 2Linked to original sources

Morphological characterization of lung and kidney lesions in C3H/HeJ mice infected with Leptospira interrogans serovar icterohaemorrhagiae: defect of CD4+ and CD8+ T-cells are prognosticators of the disease progression.

Neonates and young C3H/HeJ mice were highly susceptible to lethal infection with Leptospira interrogans serovar icterohaemorrhagiae. The main pathological changes were seen by light microscopy in the lung and kidneys of 3-week-old mice at 11 days after inoculation. Lung histological lesions included small and medium-sized vasculitis with fibrinoid changes, hemorrhages, moderate infiltrate of mononuclear inflammatory cells and fibrin thrombi. In the kidney there was mild to severe acute tubular necrosis associated with interstitial nephritis. Repair of damaged tubules in surviving mice was observed within 17 days after inoculation. Pathological findings of CD4+ and CD8+ cell-depleted mice were clearly more severe than that seen in untreated animals by 17 days after inoculation. Comparatively, CD4+/CD8+ cell-depleted mice had more marked lung and kidney lesions than in the CD8+ or CD4+ cell-depleted mice. A very high level of tubular alterations was seen in the kidneys of all treated groups. Increased degrees of interstitial nephritis also reflected the T-cell subsets depletion related events. Leptospires were clearly demonstrated by immunoperoxidase close to the sites of histological damage in all infected mice. C3H/HeJ mice represent a useful model for further studies in pathogenicity of leptospires and natural resistance of the host.

Animals↗

ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src.

Membrane trafficking is regulated in part by small GTP-binding proteins of the ADP-ribosylation factor (Arf) family. Arf function depends on the controlled exchange and hydrolysis of GTP. We have purified and cloned two variants of a 130-kDa phosphatidylinositol 4, 5-biphosphate (PIP2)-dependent Arf1 GTPase-activating protein (GAP), which we call ASAP1a and ASAP1b. Both contain a pleckstrin homology (PH) domain, a zinc finger similar to that found in another Arf GAP, three ankyrin (ANK) repeats, a proline-rich region with alternative splicing and SH3 binding motifs, eight repeats of the sequence E/DLPPKP, and an SH3 domain. Together, the PH, zinc finger, and ANK repeat regions possess PIP2-dependent GAP activity on Arf1 and Arf5, less activity on Arf6, and no detectable activity on Arl2 in vitro. The cDNA for ASAP1 was independently identified in a screen for proteins that interact with the SH3 domain of the tyrosine kinase Src. ASAP1 associates in vitro with the SH3 domains of Src family members and with the Crk adapter protein. ASAP1 coprecipitates with Src from cell lysates and is phosphorylated on tyrosine residues in cells expressing activated Src. Both coimmunoprecipitation and tyrosine phosphorylation depend on the same proline-rich class II Src SH3 binding site required for in vitro association. By directly interacting with both Arfs and tyrosine kinases involved in regulating cell growth and cytoskeletal organization, ASAP1 could coordinate membrane remodeling events with these processes.

ADP-Ribosylation Factor 1↗

[The Sézary syndrome].

Sézary syndrome is a form of cutaneous T-cell lymphoma and, like mycosis fungoides, results from the malignant proliferation of mature post-thymic T-cell lymphocytes. The main features are the presence of abnormal mononuclear cells (Sezary cells) in the peripheral blood and exfoliative erythroderma. The authors present of a 70-year-old woman admitted to our clinic due to the case pruriginous and exfoliative erythroderma, subcutaneous nodes and lymphadenopathy. The clinical diagnosis of Sézary syndrome was confirmed through the identification of Sézary cells in the peripheral blood by cytochemistry and membrane marker studies and by lymph node histopathology. Genotypic studies excluded the presence of HTLV-I and HTLV-II sequences in DNA samples and confirmed the monoclonal nature and T-cell origin of this lymphoproliferative disease.

Aged↗

Mutation analysis of the BRCA2 gene in breast/ovarian cancer Spanish families: identification of two new mutations.

The recently isolated gene BRCA2 is responsible for about 45% of familial breast cancer and the majority of male breast cancer families. We have screened 12 high risk breast/ovarian Spanish families for mutations in BRCA2, using SSCP followed by direct sequencing. We have found mutations in four of our 12 families (33.3%), including two with male breast cancer. Three of the mutations were frameshift and one was a missense. Two of the mutations have been previously published and two are new mutations.

Adult↗

Nicotinamide inhibits inducible nitric oxide synthase enzyme activity in macrophages by allowing nitric oxide to inhibit its own formation.

Nitric oxide (NO) production by macrophages is mainly regulated by induction of nitric oxide synthase (iNOS) by cytokines and microbial products. Nicotinamide (NIC) inhibits NO production by activated macrophages in a dose dependent manner. NIC also inhibits NOS enzyme activity in extracts from activated macrophages. The inhibition was noncompetitive with L-arginine (Ki 13.37 +/- 4.40 mM, n=3), uncompetitive versus NADPH (Ki 3.06 +/- 0.17 mM, n=3) and tetrahydrobiopterin. Finally, the inhibition by nicotinamide was fully reversed by scavenging NO with hemoglobin. We suggest that NIC acts by allowing NO to inhibit its own formation.

Animals↗

'Oops!': performance correlates of everyday attentional failures in traumatic brain injured and normal subjects.

Insufficient attention to tasks can result in slips of action as automatic, unintended action sequences are triggered inappropriately. Such slips arise in part from deficits in sustained attention, which are particularly likely to happen following frontal lobe and white matter damage in traumatic brain injury (TBI). We present a reliable laboratory paradigm that elicits such slips of action and demonstrates high correlations between the severity of brain damage and relative-reported everyday attention failures in a group of 34 TBI patients. We also demonstrate significant correlations between self- and informant-reported everyday attentional failures and performance on this paradigm in a group of 75 normal controls. The paradigm (the Sustained Attention to Response Task-SART) involves the withholding of key presses to rare (one in nine) targets. Performance on the SART correlates significantly with performance on tests of sustained attention, but not other types of attention, supporting the view that this is indeed a measure of sustained attention. We also show that errors (false presses) on the SART can be predicted by a significant shortening of reaction times in the immediately preceding responses, supporting the view that these errors are a result of 'drift' of controlled processing into automatic responding consequent on impaired sustained attention to task. We also report a highly significant correlation of -0.58 between SART performance and Glasgow Coma Scale Scores in the TBI group.

Activities of Daily Living↗

Demonstration of leptospiral antigens on tissues using monoclonal antibodies and avidin-biotin peroxidase staining.

Glycolipoprotein (GLP) cytotoxin was extracted from Leptospira interrogans serovar canicola. The silver staining profile of GLP subjected to SDS-PAGE under denaturing conditions showed a number of bands in the mol. weight range of 14-66 kDa. Mouse Monoclonal Antibodies (MAbs) IgG3 recognizing a band near to 24 kDa of leptospiral GLP were produced (clone number MGLP-01). The agglutinating property of MAbs was established by microscopic agglutination test (MAT) using 25 different serovars as antigens. Only the homologous serovar was agglutinated by MAbs suggesting that the recognized epitope is a specific surface-exposed antigen. The MAbs were applied to demonstration of leptospiral antigens in tissue damage by avidin-biotin immunoperoxidase staining. Golden hamsters were experimentally infected with a virulent strain of L. interrogans serovar canicola. Histologically kidneys stained by routine hematoxylin and eosin showed changes characterized by injury of tubular epithelial cells leading to acute tubular necrosis (ATN). Typical, well-defined morphologic leptospires or finely granular deposits were found by immunoperoxidase staining near to blood vessels, within inflammatory infiltrates and intraluminal in proximal and distal parts of the nephron. Binding of leptospiral antigens to capillary endothelial cells, tubular epithelial cells and macrophages were also demonstrated. This entails a basis for further studies either in research or in diagnostic histopathology.

Animals↗

Eye-movements and visual imagery: a working memory approach to the treatment of post-traumatic stress disorder.

It has been claimed that the symptoms of post-traumatic stress disorder (PTSD) can be ameliorated by eye-movement desensitization-reprocessing therapy (EMD-R), a procedure that involves the individual making saccadic eye-movements while imagining the traumatic event. We hypothesized that these eye-movements reduce the vividness of distressing images by disrupting the function of the visuospatial sketchpad (VSSP) of working memory, and that by doing so they reduce the intensity of the emotion associated with the image. This hypothesis was tested by asking non-PTSD participants to form images of neutral and negative pictures under dual task conditions. Their images were less vivid with concurrent eye-movements and with a concurrent spatial tapping task that did not involve eye-movements. In the first three experiments, these secondary tasks did not consistently affect participants' emotional responses to the images. However, Expt 4 used personal recollections as stimuli for the imagery task, and demonstrated a significant reduction in emotional response under the same dual task conditions. These results suggest that, if EMD-R works, it does so by reducing the vividness and emotiveness of traumatic images via the VSSP of working memory. Other visuospatial tasks may also be of therapeutic value.

Adult↗

To treat? To befriend? To prevent? Patients' and GPs' views of the doctor's role.

OBJECTIVE: To examine and compare patients' and GPs' views of the doctor's role and patients' reasons for going to the doctor. DESIGN: A cross sectional questionnaire survey. SETTING: General practices across England. SUBJECTS: 501 patients and 68 GPs. MAIN OUTCOME MEASURES: Beliefs about the doctors' role and beliefs about patients' reasons for going to the doctor in terms of illness treatment, a psychosocial approach and preventive health care. RESULTS: A majority of both patients and GPs agreed that the doctor's role was primarily to treat illness. However, whereas patients showed greater endorsement for preventive health care and a belief that the doctor's role was to keep people healthy, GPs showed greater support for an emphasis on personal problems. In terms of patients' reasons for visiting their doctor, a majority of both patients and GPs agreed that illness prevention and illness treatment were important. However, more patients believed that patients visit the doctor for illness prevention than GPs, more of whom felt that patients seek help with their personal problems. CONCLUSION: The results indicate a mismatch between patients' and GPs' beliefs, which has implications for understanding the impact of recent changes in primary care and the effects on GPs' job satisfaction.

Adult↗

Investigations of hypesthesia: using anesthetics to explore relationships between consciousness, learning, and memory.

This paper discusses the ways in which anesthetic agents can be used to investigate the role of awareness in learning and memory. It reviews research into learning during light, subclinical anesthesia, termed hypesthesia. This research suggests that the effects of anesthetics on implicit and explicit memory are roughly comparable, although implicit memory for simple stimuli may resist the effects of very low doses of anesthetic. In addition, this paper reports experimental data demonstrating that long-term retention of information is prevented by doses of anesthetic that are low enough to permit awareness and even shortterm memory of auditory stimuli. Overall, these findings are consistent with the hypothesis (e.g., Caseley-Rondi, 1996) that frontal lobe function is particularly sensitive to anesthetics. They raise theoretical and practical questions about the necessity of consciousness for learning and about interpretation of the evidence for learning during surgery under general anesthesia.

Anesthesia, General↗

The coherent frequency in the electroencephalogram as an objective measure of cognitive function during propofol sedation.

Ten volunteers were studied during six stages of propofol sedation, namely awake (no propofol), light sedation (small dose of propofol), deep sedation (large dose), deep sedation with stimulation of the ulnar nerve, then light sedation again (small dose), and awake (recovery). Light and deep sedation were defined in terms of performance on a test of cognitive function: the within-list recognition (WLR) test. At each stage, the steady-state auditory evoked potential was measured at different stimulating frequencies to derive the frequency needed to achieve the maximal coherence index. This frequency is called the "maximum coherent frequency". WLR performance correlated with infusion dose (r = -0.71), plasma propofol concentration (r = -0.75), and maximum coherent frequency (r = 0.75). When the correlations were examined for the propofol sedation stages only, there remained a strong correlation between WLR performance and maximum coherent frequency (r = 0.47, P < 0.005), but no significant correlations between infusion dose and WLR (r = -0.11) or infusion dose and plasma concentration (r = 0.13). These data suggest that maximum coherent frequency provides a better measure of depth of sedation than does the dose of propofol alone.

Anesthesia Recovery Period↗

Protection from nicotinamide inhibition of interleukin-1 beta-induced RIN cell nitric oxide formation is associated with induction of MnSOD enzyme activity.

We have studied the long-term effects of nicotinamide (NIC) on the synthesis of NO by insulin producing cells. NIC delays the formation of nitrite by interleukin (IL)-1 beta-(IL-1, 25 U/ml)-stimulated RINm5F cells, and previous exposure of cells to IL-1 for 15 h prevents this effect. The delay is associated with a lack of cytokine-induced inducible nitric oxide synthase (iNOS) enzyme activity in cell extracts. NIC (20 mM) inhibits NO synthase (NOS) activity in extracts from cells incubated with IL-1 for 6 h and 24 h, and oxyhemoglobin counteracts this inhibition. Hence, NIC could scavenge O2- and allow NO to inhibit the enzyme. The NO donor SIN-1 inhibits in a concentration-dependent manner iNOS activity, and the effect is potentiated by NIC. In intact cells, protection from NIC is associated with IL-1-induced expression of MnSOD activity, and reversible blockade of iNOS expression with pyrrolidine dithiocarbamate counteracts the NIC effect. We conclude that O2- plays a role in preventing NO inhibition of iNOS. The loss of this action coincides with the induction of MnSOD enzyme activity. In addition, the stimulation by NIC of IL-1-induced nitrite production in pyrrolidine dithiocarbamate-treated cells is a novel action that should be considered when the drug is proposed as potential agent for the prevention of insulin-dependent diabetes mellitus.

Animals↗

Respiratory burst is decreased by human hyperlipemic serum in rat peritoneal macrophages.

The effect of hyperlipemic human serum on superoxide anion (O2-) production by rat peritoneal macrophages was investigated. Phorbol myristate acetate (PMA)-stimulated O2- production was inhibited when cells were preincubated with hyperlipemic human serum. This inhibition was specifically carried out by a lipid fraction and was dependent on both cholesterol and triglyceride serum levels. This inhibitory effect was not exerted by a direct effect on NADPH-oxidase activity, nor by a putative superoxide dismutase activity present in the serum. With human neutrophils, we observed a decreased mobility of the cytosolic factor p47-phox to the membrane during the activation process, caused by hyperlipemic serum. We did not find any effect of hyperlipemic serum on NO2- production by cultured rat macrophages. These results suggest that a pathological increase of circulating plasma lipids may be associated with an impaired inflamatory capacity of macrophages.

Animals↗

Learning during anaesthesia: a review.

Can learning occur during general anaesthesia? This paper reviews the studies which have addressed this issue and finds some evidence of implicit memory for intra-operative events, even with clinically adequate anaesthesia. This has implications both for clinical practice and for psychological theories of learning and awareness. However, since many of the studies have been opportunistic, neither the anaesthetic techniques nor the paradigms used to assess memory have been standardized. Methodological improvements are discussed, in particular the need for a reliable means of monitoring awareness during anaesthesia. These improvements would enable researchers to determine the conditions under which learning occurs and would provide information about the role of consciousness in learning.

Anesthesia, General↗

Inhibitory effect of cyclosporin A and FK506 on nitric oxide production by cultured macrophages. Evidence of a direct effect on nitric oxide synthase activity.

Casein-elicited peritoneal macrophages from mice were cultured either alone or with interferon-gamma (IFN-gamma) and bacterial lipopolysaccharide (LPS), and the effect of cyclosporin A (CsA) and FK506 on NO2- production (due technical difficulties NO2- was taken as the index for NO) was analysed. We observed an inhibitory effect of CsA and FK506 on NO2- production. The IC50 for NO2- production by casein-elicited macrophages was 0.1 microgram/ml for CsA and 0.3 microgram/ml FK506. The effect of both drugs was dose-dependent and was more clear in non-stimulated macrophages. The presence of IFN-gamma and LPS in the culture increased NO2- production by casein-elicited macrophages and partially eliminated the inhibition exerted by CsA and FK506. Both drugs acted directly on the nitric oxide synthase (NOS), since CsA and FK506 reduced by 35% and by 17%, respectively, NOS activity in the crude cytosolic fraction. However, CsA and FK506 did not alter 14CO2 production from [1-14C]glucose, suggesting that the pentose monophosphate pathway activity was not modified. These data add new insight into the interpretation of the immunosuppressive properties of both drugs.

Amino Acid Oxidoreductases↗

[Severe depression and risk factors in Buenos Aires].

A study on prevalence of depression and its risk factors in 18 year old males with residence in the city of Buenos Aires was performed in 1991 during a mass medical examination of aptitude for the Military Service. An anonyme, self administered questionnaire was given to 553 youngsters in a probability sample. From findings in that study it was deemed necessary a deepen analysis on severe depression and its possible associations with ideas of suicide. Prevalence at severe depression was 4.5% and strong association was found with sadness in depression was 4.5% and strong association was found with sadness in childhood (RR 12.73), boredom (RR 10.56), retiring (RR 8.28) and nervousness (RR 3.89) as well as drugs abuse by brothers (RR 3.48) and family conflicts (RR 2.43). Possibility of having ideas of suicide is thirty three times more when depression exists. The attributable risk of suicide due to severe depression is 75%. Keeping in mind this health problem in youngsters might help to establish collective and individual strategic measures toward prevention.

Adolescent↗