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J Serrano

Publications and source records attributed to J Serrano.

At least 37 records · Page 2Linked to original sources
PubMed2003

Distribution of immunoreactivity for the adrenomedullin binding protein, complement factor H, in the rat brain.

Adrenomedullin is a multifunctional amidated peptide that has been found in most nuclei of the CNS, where it plays a neuromodulatory role. An adrenomedullin binding protein has recently been found in plasma and characterized as complement factor H. This regulator of the complement system inhibits the progression of the complement cascade and modulates the function of adrenomedullin. Our study shows the ample distribution of factor H immunoreactivity in neurons of telencephalon, diencephalon, mesencephalon, pons, medulla, and cerebellum in the rat CNS, using immunohistochemical techniques for both light and electron microscopy. Factor H immunoreactivity was found in the cytoplasm, but nuclear staining was also a common finding. Some blood vessels and glial cells were also immunoreactive for factor H. Colocalization studies by double immunofluorescence followed by confocal microscopy revealed frequent coexistence of factor H and adrenomedullin immunoreactivities, thus providing morphological evidence for the potential interaction of these molecules in the CNS. The presence of factor H immunoreactivity in glial cells was confirmed by colocalization with glial fibrillary acidic protein. In summary, factor H is highly expressed in the CNS where it could play important roles in regulating adrenomedullin actions and contributing to an intracerebral complement system.

Adrenomedullin↗
PubMed2003

Prognostic significance of K-ras, p53, bcl-2, PCNA, CD34 in radically resected non-small cell lung cancers.

The aim of this study was to investigate the prognostic significance of a panel of biological parameters in patients with radically resected non-small cell lung cancers (NSCLC). 269 cases with pathological stage I-IIIA NSCLC were retrospectively analysed. Immunohistochemistry was performed to detect protein expression of p53, bcl-2, proliferating cell nuclear antigen (PCNA) and CD34. Polymerase chain reaction (PCR)/direct nucleotide sequencing method was used to detect mutations in K-ras (codons 12, 13, 61, exons 1-2). The Kaplan-Meier estimates of survival were calculated for clinical and biological variables using the Cox model for multivariate analysis. Histological subtype and the pathologic tumour extension (pT) were the most powerful clinical-pathological prognostic factors for survival (P=0.030 and P=0.031, respectively), whereas among the biological parameters, p53 overexpression (P=0.032) and K-ras mutation (P=0.078) had a negative prognostic role, as demonstrated by multivariate analysis. Conversely, bcl-2, PCNA and CD34 expression were not correlated with survival. Statistically significant associations between p53 expression and the squamous cell carcinoma (SCC) subtype, bcl-2 expression and SCC subtype, K-ras mutation and p53 negative expression, p53 and bcl-2, bcl-2 and PCNA overexpression were observed. In conclusion, some biological characteristics such as the K-ras and p53 status may provide useful prognostic information in resected NSCLC patients, in addition to the classical clinico-pathological parameters. However, further studies are needed to clarify the value of adopting biological prognostic factor into clinical practice.

Adult↗
PubMed2003

Results of an upper endoscopy protocol in liver transplant candidates.

OBJECTIVE: our aims is to understand endoscopic findings from a preoperative systematic study of patients with hepatic cirrhosis who were candidates for transplantation and their impact on a protocol for primary and secondary prophylaxis of variceal haemorrhage. PATIENTS AND METHODS: this study involves a retrospective evaluation of upper digestive tract lesions detected before inclusion and a prospective evaluation of new episodes of variceal haemorrhage, associated mortality rates, and factors that are likely to be involved in the development of this condition. Primary prophylaxis with beta-blockers was considered indicated in cases of varices of grande II or greater or with signs associated with increased risk. Secondary prophylaxis was essentially always associated with medical and endoscopic treatment. RESULTS: of 134 patients, there were 9 deaths, with a median time on the waiting list of 3 months. Of all patients, 33.6% presented with high risk oesophageal varices, 11.2 % with gastric varices, 42.6% with portal hypertensive gastropathy, and 26.9% with peptic lesions. Primary prophylaxis was indicated in 33 of 90 patients, and was initiated in almost half of the cases as a results of the study. Optimum fulfiment of the pre-established objectives was 75.3%. The incidence of new haemorrhagic events due to varices was 10.4% and accounted for almost half of the deaths during the monitoring period. The only statistically significant predictive factors were the presence of gastrict varices and previous history. CONCLUSION: upper endoscopy should play a role in the preoperative examination of liver transplant candidates due to the significant impact it has on subsequent management.

Esophageal and Gastric Varices↗
PubMed2002

Adrenomedullin in the central nervous system.

Adrenomedullin (AM) is a novel vasodilator peptide first purified from human pheochromocytoma by tracing its capacity to stimulate cAMP production in platelets. AM immunoreactivity is widely distributed in the central nervous system (CNS) and in the rat has been demonstrated by immunohistochemical techniques to be present in many neurons throughout the brain and spinal cord, as well as in some vascular endothelial cells and perivascular glial cells. Electron microscopy shows that the immunoreactivity is located mainly in the neuronal cytoplasm, but also occurs in the cell nucleus in some cells of the caudate putamen and olfactory tubercle. Biochemical analyses suggest that higher molecular forms, presumably precursor forms, may predominate over fully processed AM in some brain areas. The expression of AM immunoreactivity is increased in cortical neurons, endothelial cells, and perivascular processes after a simulation of ischemia by oxygen and glucose deprivation. Immunohistochemical, electrophysiological, and pharmacological studies suggest that AM in the CNS can act as a neurotransmitter, neuromodulator, or neurohormone, or as a cytoprotective factor in ischemic/hypoxic conditions, in addition to its vasodilator role.

Adrenomedullin↗
PubMed2002

Adrenomedullin expression is up-regulated by ischemia-reperfusion in the cerebral cortex of the adult rat.

Changes in the pattern of adrenomedullin expression in the rat cerebral cortex after ischemia-reperfusion were studied by light and electron microscopic immunohistochemistry using a specific antibody against human adrenomedullin (22-52). Animals were subjected to 30 min of oxygen and glucose deprivation in a perfusion model simulating global cerebral ischemia, and the cerebral cortex was studied after 0, 2, 4, 6, 8, 10 or 12 h of reperfusion. Adrenomedullin immunoreactivity was elevated in certain neuronal structures after 6-12 h of reperfusion as compared with controls. Under these conditions, numerous large pyramidal neurons and some small neurons were intensely stained in all cortical layers. The number of immunoreactive pre- and post-synaptic structures increased with the reperfusion time. Neurons immunoreactive for adrenomedullin presented a normal morphology whereas non-immunoreactive neurons were clearly damaged, suggesting a potential cell-specific protective role for adrenomedullin. The number and intensity of immunoreactive endothelial cells were also progressively elevated as the reperfusion time increased. In addition, the perivascular processes of glial cells and/or pericytes followed a similar pattern, suggesting that adrenomedullin may act as a vasodilator in the cerebrocortical circulation. In summary, adrenomedullin expression is elevated after the ischemic insult and seems to be part of CNS response mechanism to hypoxic injury.

Adrenomedullin↗
PubMed2002

Coexistence of translocated cytochrome c and nitrated protein in neurons of the rat cerebral cortex after oxygen and glucose deprivation.

Changes in the distribution of immunoreactive cytochrome c and protein nitration were studied in the rat cerebral cortex after oxygen and glucose deprivation by bright field, confocal and electron microscopy. In control cerebral cortex, nitrotyrosine immunoreactivity indicating protein nitration was found mostly in the neuronal nuclear region, with only a small amount distributed in the cytosol, whereas cytochrome c immunoreactivity was found at the inner membrane and in the intermembrane space of the mitochondria. During the recovery phase after oxygen and glucose deprivation, cytochrome c immunoreactivity was released from the intermembrane space of swollen mitochondria into the surrounding cytosol. The cytosol now also displayed nitrotyrosine immunoreactivity, which had diminished in the nuclear region. Both immunoreactivities were dispersed throughout the soma and processes of the cortical neurons. These changes were largely prevented by the administration of cyclosporin A, which inhibits both the mitochondrial permeability transition and the neuronal isoform of nitric oxide synthase while blocking the induction of the inducible isoform. Ischemia/reperfusion injury increases the production of nitric oxide, reactive oxygen species and intracellular factors that damage the mitochondria and liberate apoptotic factors. We suggest that translocation of cytochrome c from the mitochondria to the cytosol, which has been shown to precede the mitochondrial permeability transition, could result from peroxynitrite-mediated nitration. This phenomenon is attenuated by cyclosporin A administration, suggesting a neuroprotective role for this agent.

Animals↗
PubMed2002

Assessment of the diagnostic capacity of planar scintigraphy and SPECT with 99mTc-HMPAO-labelled leukocytes in superficial and deep sternal infections after median sternotomy.

Sternal infection is a rare complication of median sternotomy but is associated with considerable morbidity and mortality, particularly in the case of deep sternal infection (mediastinitis). Successful treatment depends on early diagnosis and on the location (deep or superficial) of the infection. Radiological techniques have many limitations, and although 67Ga scintigraphy is effective, it delays diagnosis by 48 h. We assessed the diagnostic capacity of planar scintigraphy and single photon emission computed tomography (SPECT) with 99mTc-hexamethylpropylene amine oxime (HMPAO)-labelled leukocytes in deep sternal infections after median sternotomy. We prospectively studied 41 patients with clinical suspicion of deep sternal infection 4 and 20 h after administration of the tracer. The final diagnosis was deep sternal infection in nine patients and superficial sternal infection in 10, with infection being ruled out in 22 patients. Planar scintigraphy did not detect any of the deep sternal infections at either 4 h or 20 h. SPECT correctly identified eight of the nine deep sternal infections at 4 h and all seven at 20 h, with no false positive results. Planar scintigraphy identified 16 of the 18 superficial sternal infections at 4 h and all of them at 20 h. SPECT identified 17 of these 18 infections at 4 h and all of them at 20 h. Other infections unrelated to the sternotomy were identified in seven patients. Leukocytes labelled with 99mTc-HMPAO are a highly reliable method for the early diagnosis of sternal infections after median sternotomy. Use of SPECT allows determination of the depth of the infection and differentiation of superficial from deep sternal infections. It is also possible to detect other sites of infection, thus providing alternative diagnoses.

Adult↗
PubMed2002

Immunocytochemical light- and electron-microscopic studies of growth hormone, prolactin and somatomammotroph cells in female goat.

We have studied the structural and ultrastructural changes that occur in growth hormone (GH), prolactin (PRL) and somatomammotroph (SMT) cells of female goats of the Murciano-Granadina breed during different physiological stages: prepuberty, anestrus, pregnancy and lactation. Serial sections were stained with double immunolabeling, alkaline phosphatase and avidin-biotin complex for light microscopy, and immunogold labeling was used for electron microscopy. These techniques allowed the identification of GH, PRL and SMT cells, which were evenly distributed throughout the whole pars distalis. PRL cells were the most frequent. Both PRL and GH cells showed morphological changes that may be related to a given physiological stage. These changes include the number of cells and the number and size of the secretory granules. SMT cells were clearly identified by having two types of monohormonal secretory granule showing single labeling, in spite of their similar ultrastructural characteristics to the other adenohypophysary cells. They are found in low percentages (0.6%). We postulate that cell aggregates which look like SMT syncytia may be artifacts caused by interdigitation of PRL and GH cells, and that cells which are normally taken to be SMT cells are not an interconversion stage between monohormonal cells.

Animals↗
PubMed2002

Frequency and clinical characteristics of rapid-onset fatal and near-fatal asthma.

The onset of fatal and near-fatal asthma attacks can be rapid. The objective of this study was to determine the frequency and clinical characteristics of rapid-onset asthma (ROA) in patients suffering fatal and near-fatal crises. Two-hundred and twenty patients with fatal or near-fatal attacks were enrolled in a multicentre, prospective study. ROA was defined as a crisis developing in < or =2 h. Data on patient and clinical characteristics were collected, and spirometric and allergy studies were performed when the patients were in a stable condition. Forty-five attacks (20%) were ROA and 175 (80%) were slow-onset asthma (SOA). The triggers for SOA and ROA attacks were different, with the ROA group having a significantly lower rate of suspected respiratory infection (7% versus 38%), higher rates of fume/irritant inhalation (9% versus 1%) and a higher intake of nonsteroidal antiinflammatory drugs (14% versus 3%). The ROA group exhibited significantly higher rates of impaired consciousness (63% versus 44%), absence of lung sounds upon admission (68% versus 42%), fewer hours of mechanical ventilation (13 h versus 28 h) and fewer days of hospitalization (8 days versus 9.5 days) than the SOA group. The 20% frequency of rapid-onset fatal and near-fatal attacks in this study suggests that rapidly developing attacks may not be rare. These findings also support a distinct clinical profile for rapid-onset asthma marked by differences in triggers, severity of exacerbation and clinical course.

Adult↗
PubMed2002

Physiology and pathophysiology of nitric oxide in the nervous system, with special mention of the islands of Calleja and the circunventricular organs.

Nitric oxide (NO) has been recognized as a key regulatory factor in many physiological processes, including central nervous system function, development, and phatophysiology. NO is produced by a class of enzymes known as NO synthases (NOS) and in normal adult animals only the neuronal isoform (nNOS) is detectable. During cortical development, nNOS was found at E14 in neuroblasts of the marginal zone and its expression raised to a zenith by P5, decreasing afterwards until reaching a steady level by P10. At that time, nNOS was found mainly in pyramidal neurons. Interestingly, the inducible isoform of the enzyme (iNOS) was also active from P3 to P7, but it disappeared almost completely by P20. The neurodegeneration observed during normal aging and following hypoxic accidents seems to be the result of cumulative free radical damage, and excessive production of NO may be at the basis of the cascade. After ischemic events we observed an elevation in the number of neurons expressing nNOS coincident with an elevation in Ca2+-dependent NOS activity for up to 120 min. After this period, nNOS activity began to decrease but it was substituted by a rapid increase in Ca2+-independent activity coincident with the histological appearance of previously undetectable iNOS-immunoreactive neurons. These increases in NO production were accompanied by specific patterns of protein nitration, a process that seems to result in loss of protein function. In particular, we observed a correlation between exposure to ischemia-reperfusion and nitration of cytochrome c. This process was coincident with the exit of the cytochrome from the mitochondria to the surrounding cytoplasm, an early event in neuronal apoptosis. Interestingly, most of the morphological and molecular changes associated with ischemic damage were prevented by treatment with inhibitors of NO production, indicating a clear path in the search for efficacious drugs in the battle against cerebrovascular accidents.

Animals↗
PubMed2001

Inducible activation of c-Myc in adult myocardium in vivo provokes cardiac myocyte hypertrophy and reactivation of DNA synthesis.

c-Myc, a protooncogene, mediates both proliferative and cellular growth in many cell types. Although not expressed in the adult heart under normal physiological conditions, Myc expression is rapidly upregulated in response to hypertrophic stimuli. Although Myc is capable of sustaining hyperplastic growth in fetal myocytes, the effects of its re-expression in adult postmitotic myocardium and its role in mediating cardiac hypertrophy are unknown. To determine the effects of de novo Myc activity in adult postmitotic myocardium in vivo, we created a novel transgenic model in which Myc is expressed and inducibly activated specifically in cardiac myocytes. Activation of Myc in adult myocardium was sufficient to reproduce the characteristic changes in myocyte size, protein synthesis, and cardiac-specific gene expression seen in cardiac hypertrophy. Despite the increased cardiac mass, left ventricular function remained normal. Activation of Myc also provoked cell cycle reentry in postmitotic myocytes, which led to increased nuclei per myocyte and DNA content per nuclei.

Animals↗
PubMed2001

Neuronal and inducible nitric oxide synthase expression and protein nitration in rat cerebellum after oxygen and glucose deprivation.

A perfusion model of global cerebral ischemia was used for the immunohistochemical study of changes in the glutamate-nitric oxide (NO) system in the rat cerebellum and cerebellar nuclei during a 0-14 h reperfusion period after 30 min of oxygen and glucose deprivation, with and without administration of 1.5 mM N(omega)-nitro-L-arginine methyl ester (L-NAME). While immunostaining for N-methyl-D-aspartate receptor subunit 1 (NMDAR1) showed no marked changes during the reperfusion period, neuronal NO synthase (nNOS) immunostaining increased in stellate and basket cells, granule cells and neurons of the cerebellar nuclei. However, global cerebellar nNOS concentrations determined by Western blotting remained largely unchanged in comparison with actin expression. Inducible NOS (iNOS) immunostaining appeared in Purkinje cells and neurons of the cerebellar nuclei after 2-4 h of reperfusion and intensified during the 6-14 h period. This was reflected by an increase in global cerebellar iNOS expression determined by Western blotting. Immunostaining for protein nitrotyrosine was seen in Purkinje cells, stellate and basket cells, neurons of the cerebellar nuclei and glial cells in controls, and showed a progressive translocation in Purkinje cells and neurons of the cerebellar nuclei from an initial perinuclear or nuclear location towards the periphery. At the end of the reperfusion period the Purkinje cell apical dendrites were notably retracted and tortuous. Prior and concurrent L-NAME administration eliminated nitrotyrosine immunostaining in controls and blocked or reduced most of the postischemic changes observed. The results suggest that while nNOS expression may be modified in certain cells, iNOS is induced after a 2-4 h period, and that changes in protein nitration may be associated with changes in cell morphology.

Animals↗
PubMed2001

Phonon dispersion curves in wurtzite-structure GaN determined by inelastic x-ray scattering.

We have investigated the lattice dynamics of a wurtzite GaN single crystal by inelastic x-ray scattering. Several dispersion branches and phonons at high-symmetry points have been measured, including the two zone-center Raman- and infrared-inactive silent modes. The experiments have been complemented by ab initio calculations. They are in very good agreement with our measurements, not only for phonon energies, but also for scattering intensities, thus validating the correctness of the eigenvectors. Other phenomenological and ab initio theories exhibit significant differences.

Journal Article↗