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Biomedical subjects

A Nadal

Publications and source records attributed to A Nadal.

At least 55 records · Page 3Linked to original sources
PubMed1997

Plasma albumin induces calcium waves in rat cortical astrocytes.

Changes in intracellular calcium were monitored in cultured cortical astrocytes stimulated with albumin. Albumin elicited intracellular calcium mobilisation from intracellular stores, inducing repetitive intracellular calcium oscillations. The oscillations were not blocked by ryanodine, a blocker of the Ca-induced Ca release mechanism, and the release occurred from the same store as is accessed by glutamate and bradykinin, both of which release calcium by an IP3-dependent mechanism. Calcium signals induced by albumin appear therefore to occur via a pure IP3-dependent mechanism. When albumin was applied to confluent monolayers of astrocytes, the oscillations in individual cells were initially unsynchronised, but after several minutes of application, the Ca2 oscillations were observed to synchronise and spread through the astrocyte network as a wave. These intercellular calcium waves were inhibited by the gap junction blocker halothane. Using the fluorescence recovery after photobleaching (FRAP) technique, we demonstrate that the development of propagated waves with prolonged exposure to albumin does not result from an increase in cell coupling. The development of calcium waves on exposure to albumin may be important in the formation of glial scars in the CNS after breakdown of the blood-brain barrier.

Animals↗
PubMed1997

Hyperplastic lesions of the larynx. Experience of the Barcelona group.

Squamous carcinoma of the larynx arises from pre-existing lesions, the so-called "preneoplastic lesions". Hyperplastic lesions represent a part of their spectrum, from both clinical and biological points of view. On morphologic grounds, the most characteristic feature with prognostic value in the evaluation of preneoplastic lesions is dysplasia. It is not only nuclear alterations that are seen in the process of malignant transformation, the cytoplasmic pattern of cytokeratins changes through neoplastic progression, with a progressive reduction of the molecular weight of the produced species. Dysplasia also associates with gross alterations of the DNA content. This is in agreement with our finding of alterations of genes participating in the control of the cell cycle, p53 and p21(WAF1/cip1). p53 overexpression is detected in non-invasive squamous lesions (even in the absence of obvious dysplasia) and p21(WAF1/cip1) shows a dramatic change in the pattern of expression in dysplastic epithelium compared with the normal. However, not all genes participating in the control of the cell cycle are altered in early lesions. Overexpression of cyclin D1, a common phenomenon in advanced carcinomas, is not likely to participate in the early phases of neoplastic development.

Biomarkers, Tumor↗
PubMed1997

[Ischemic heart disease and postoperative mortality in major vascular surgery. An up-to-date diagnostic approach].

BACKGROUND: The aim of this study is to evaluate the efficacy the dobutamine stress echocardiography in predicting the perioperative cardiac risk of patients undergoing major vascular surgery. METHODS: Seventy-seven consecutive and not selected patients, undergoing a surgical treatment requiring aortic cross clamping, were assessed also with a transthoracic dobutamine stress echocardiography. With electrocardiographic and echocardiographic monitoring ventricular ischemia or wall motion abnormalities, 5 micrograms/kg per min of chlorhydrate dobutamine for 5 minutes were infused, followed by other 10 micrograms/kg per min increased up to 40 micrograms/kg per min. During the last 4 minutes 0.25 mg of atropin were infused increasingly up to 1 mg. RESULTS: Of all these patients, 26 had a stress ischemia but only 4 cases underwent a coronary angiography and only 2 of these underwent a preventive myocardial revascularization. Due to poor cardiac conditions pointed out with the dobutamine stress, 3 patients were not treated surgically. With an aggressive intra- and perioperative monitoring 73 patients underwent a surgical treatment: they were 28 aorto-bifemoral, 3 aorto-aortic grafts, 1 aorto-bisiliac thoraco-abdominal interposition graft, and 20 aorto-bifemoral, 4 aorto-femoral, 1 aorto-aortic thoraco-abdominal, 1 aorto-renal by-pass and 7 aorto-iliac-femoral thromboendoarterectomies. In the postoperative period 4 cardiac ischemic complications and 2 deaths (2.5%) were observed. CONCLUSIONS: According to our personal opinion, stress echocardiography can be considered a test with a excellent feasibility and safety rate, not expensive and with a good reproducibility and reliability. It allowed to predict the cardiac risk in our patients suggesting not only the surgical but also the anesthesiologic and the perioperative therapeutic management.

Diagnosis, Differential↗
PubMed1996

Albumin stimulates uptake of calcium into subcellular stores in rat cortical astrocytes.

1. When albumin from either plasma or serum is applied at low concentrations to cortical astrocytes a decrease in the level of [Ca2+]i is observed. At higher concentrations trains of calcium spikes are seen. 2. Removal of the polar lipids which are normally bound to native albumin abolishes the ability to induce spikes, but the decrease in [Ca2+]i is unaffected. The decrease is abolished by the denaturation of albumin and is not reproduced by a number of other proteins, and is therefore a specific action of albumin. We conclude that native albumin has a dual agonist action: the decrease in [Ca2+]i is induced by the albumin protein molecule, while the spikes are induced by a lipid normally bound to it. 3. The decrease is rapid (fastest tau = 12 s) and the rate is dependent on the concentration of albumin. [Ca2+]i falls from 77 nM to around 34 nM in the presence of saturating levels of albumin, and this level appears to be maintained indefinitely. 4. The decrease is due to an uptake of calcium into subcellular stores, as it is not abolished by removal of external Ca2+ or Na+ but is abolished by thapsigargin and cyclopiazonic acid, which are specific inhibitors of the endoplasmic reticulum Ca(2+)-ATPase. 5. When the state of store filling after albumin application is probed with a pulse of glutamate it can be seen that stores fill with the same time course as the decrease in [Ca2+]i. The low level of [Ca2+]i in albumin must therefore be maintained by a suppression of calcium influx rather than by a continued uptake into stores. 6. The calcium uptake potentiates the efficacy of low concentrations of calcium-releasing agonists such as glutamate and bradykinin by almost an order of magnitude. 7. A possible function for the calcium uptake caused by albumin is to potentiate the production of calcium spike trains by promoting refilling of calcium stores in the intervals between spikes. The uptake may play a role in the response of astrocytes to damage in the CNS.

Aniline Compounds↗
PubMed1996

Activation of L-arginine transport (system y+) and nitric oxide synthase by elevated glucose and insulin in human endothelial cells.

1. Modulation of L-arginine transport (system y+) and release of nitric oxide (NO) and prostacyclin (PGI2) by elevated glucose and insulin were investigated in human cultured umbilical vein endothelial cells. 2. Elevated glucose induced a time- (6-12 h) and concentration-dependent stimulation of L-arginine transport, which was reversible and associated with a 3-fold increase in intracellular cGMP accumulation (index of NO synthesis) and 75% decrease in PGI2 production. 3. Elevated glucose had no effect on the initial transport rates for L-serine, L-citrulline, L-leucine, L-cystine or 2-deoxyglucose. 4. Resting membrane potential was unaffected by elevated glucose whereas basal intracellular [Ca2+] increased from 65 +/- 5 nM to 136 +/- 16 nM. 5. Insulin induced a protein synthesis-dependent stimulation of L-arginine transport and increased NO and PGI2 production in cells exposed to 5 mM glucose. 6. In cells exposed to high glucose, insulin downregulated elevated rates of L-arginine transport and cGMP accumulation but had no effect on the depressed PGI2 production. 7. Our findings suggest that insulin's normal stimulatory action on human endothelial cell vasodilator pathways may be impaired under conditions of sustained hyperglycaemia.

Arginine↗
PubMed1996

Detection of the bcl-1 rearrangement at the major translocation cluster in frozen and paraffin-embedded tissues of mantle cell lymphomas by polymerase chain reaction.

The t(11;14)(q13;q32) translocation and its molecular counterpart bcl-1 rearrangement are highly characteristic of mantle cell lymphomas (MCLs). Most of these translocations occur at the major translocation cluster (MTC) in a tight area that makes this rearrangement identifiable by the polymerase chain reaction (PCR). In this study, the specificity and sensitivity of the PCR technique in the identification of bcl-1 rearrangement and its suitability to amplify the t(11;14) MTC in fixed, paraffin-embedded tissues were analyzed. Genomic DNA was obtained from 21 MCLs and 1 chronic lymphocytic leukemia (CLL) with the t(11;14) translocation. The bcl-1 rearrangement was studied by Southern blot with the MTC, p94PS, and PRAD-1 probes. Polymerase chain reaction was performed using a JH consensus primer and specific primers for chromosome II in the MTC region. bcl-1 rearrangement was identified by Southern blot in the MTC in nine (43%) MCLs and in the p94PS region in the CLL. Polymerase chain reaction analysis of genomic DNA showed that the nine MCLs with MTC rearrangement also had an amplifiable band of the expected size (100%). No amplifiable products were detected in the negative MCLs or in the CLL. The specificity of the PCR products was confirmed by hybridization with an internal MTC oligonucleotide probe. Amplifiable DNA was obtained from the paraffin blocks of 7 cases with MTC rearrangement and 11 negative tumors. bcl-1 rearrangement was detected in this DNA of 6 positive MCLs (86%) by PCR and in none of the negative cases. In conclusion, this study demonstrates that the PCR technique is highly sensitive and specific for the detection of the bcl-1 rearrangement at the MTC. It can be used with both high molecular weight DNA and DNA obtained from formalin-fixed, paraffin-embedded tissues.

Base Sequence↗
PubMed1995

Plasma albumin is a potent trigger of calcium signals and DNA synthesis in astrocytes.

Cells in the central nervous system are normally prevented from coming into contact with albumin and other protein components of blood by the existence of a tight blood-brain barrier. Astrocytes and other glial cells proliferate to form glial scars when the blood-brain barrier is breached. In this report we show that albumin is an important blood component responsible for inducing astrocyte proliferation. Albumin also generates maintained trains of calcium spikes in astrocytes. Neither activity depends on blood coagulation, as albumins from both serum and plasma are approximately equally effective. Methanol extraction of albumin abolishes both actions, and recombination of the methanol-extracted factor with extracted albumin restores full activity indistinguishable from that of native albumin. The factor is sensitive to lipase, and the solvent extraction profile is that of a polar lipid.

Animals↗
PubMed1995

p53 expression in normal, dysplastic, and neoplastic laryngeal epithelium. Absence of a correlation with prognostic factors.

p53 expression has been examined in 89 squamous cell carcinomas of the larynx (34 glottic, 28 supraglottic, 18 transglottic, 8 pyriform sinus, and 1 subglottic) obtained from 88 patients surgically treated in our centre. In addition, 59 laryngeal samples including normal respiratory epithelium and non-invasive squamous cell lesions were also tested. Frozen sections were immunostained with PAb 1801 and the results were correlated with pathological features, DNA ploidy and S-phase of the tumours, disease-free interval, and survival of the patients. p53 immunoreactivity was observed in 57 (64 per cent) carcinomas. None of the eight samples of normal respiratory epithelium was positive. p53-positive cells were seen in 8 of 23 (35 per cent) squamous cell metaplasias, 6 of 19 (32 per cent) low-grade dysplasias and 5 of 10 (50 per cent) high-grade dysplasias. No correlation was found between p53 expression in carcinomas and their clinical and pathological characteristics, DNA ploidy, or proliferative activity. Neither disease-free nor overall survival showed differences between p53-positive and p53-negative cases. These findings indicate that p53 may play a role in an early stage of malignant transformation of a subset of squamous cell carcinomas of the larynx, but seems not to be associated with further progression of the tumours.

Adult↗
PubMed1995

Assessment of histopathologic changes in the colonic biopsy in acute graft-versus-host disease.

The authors reviewed 78 colonic biopsies from 63 patients undergoing bone marrow transplantation (BMT), 56 allogeneic and 7 autologous, to assess different morphologic changes related with intestinal acute graft-versus-host disease (A-GVHD). Only five biopsies were done before the 20th day after BMT. The authors studied the presence of ulcers and atrophy in the mucosa, the nuclear atypia, and inflammatory infiltrate in the surface epithelium, and the architectural abnormalities, as well as dilation of the glands, and the presence of crypt abscesses. The authors explored the glandular epithelium for apoptosis and intraepithelial lymphocytes. They examined the lamina propria for inflammatory infiltrate, especially for so-called "focal periglandular infiltrate (FPGI)," edema fibrosis, increase of capillary vessels and presence of muciphages and clusters of enterochromaffin cells. Cases were grouped according to clinical symptoms and histologic diagnosis of A-GVHD in skin or liver. Group A had 15 asymptomatic cases (control). Group B had 20 cases from asymptomatic patients with a histologically proven A-GVHD. Group C had 43 cases with gastrointestinal symptoms and histologically proven A-GVHD. Then, the relative frequency of every histologic feature previously described were compared in the different groups by means of an univariate analysis. Apoptosis of the glandular epithelium was found in 48 cases, two of them in patients carrying an auto-BMT. Focal periglandular infiltrate was found in 11 cases that was associated with apoptosis (P < .03, Fisher's exact test). In this series, the presence of FPGI was linked with finding apoptosis in a given specimen with a probability of 91%. Glandular architectural changes and dilation were also more frequent in group C than in groups A and B when compared in the univariate analysis.

Acute Disease↗
PubMed1994

PRAD-1/cyclin D1 gene amplification correlates with messenger RNA overexpression and tumor progression in human laryngeal carcinomas.

PRAD-1 is a putative oncogene localized on chromosome 11q13 which encodes cyclin D1, a novel cyclin involved in cell cycle regulation. Amplification of this gene has recently been reported in several human tumors including breast and head and neck carcinomas. In this study we have analyzed the presence of PRAD-1/cyclin D1 gene amplification and mRNA overexpression in a series of 46 matched normal mucosas and squamous cell carcinomas of the larynx. PRAD-1/cyclin D1 was found to be amplified 2- to 12-fold in 17 carcinomas (37%). DNA amplification correlated with advanced local invasion (P = 0.0015), presence of lymph node metastases (P = 0.0078), and stage IV of the tumors (P = 0.0021). mRNA overexpression was found in 15 of the 43 (35%) cases examined and it was also significantly associated with advanced local invasion (P = 0.0025) and stage IV carcinomas (P = 0.0032). A significant association was observed between gene amplification and mRNA overexpression (P < 0.0001) with only 3 discordant cases (2 amplifications with no overexpression and 1 overexpressed carcinoma with no gene amplification). Furthermore, the degree of DNA amplification correlated with the levels of mRNA expression (r = 0.6; P = 0.024). These findings suggest that the PRAD-1/cyclin D1 gene may be an important target of 11q13 amplifications in laryngeal carcinomas and the activation of this gene may be involved in the progression of these tumors. Its association with advanced-stage tumors indicates that PRAD-1/cyclin D1 gene amplification and overexpression may be of prognostic significance.

Adult↗
PubMed1994

Metabolic regulation of intracellular calcium concentration in mouse pancreatic islets of Langerhans.

Intracellular Ca2+ concentration ([Ca2+]i) handling during K(+)-induced Ca2+ loads was studied in single islets of Langerhans. K(+)-induced depolarization caused a rapid and transient rise in [Ca2+]i. After K+ removal [Ca2+]i declined with a time course usually fitted by the sum of two exponential functions. Partial Na+ removal increased the resting [Ca2+]i level, indicating the existence of a Na+/Ca2+ exchange, but only slightly impaired the recovery from Ca2+ loads. Metabolic poisoning with CN- increased the resting Ca2+ level and slowed down the recovery from Ca2+ loads. Removal of external Na+ in islets poisoned with CN- strongly inhibited Ca2+ removal mechanisms. An increase in the glucose concentration from 0 to 16 mM (in the presence of diazoxide) resulted in a decrease in the resting [Ca2+]i and an acceleration of [Ca2+]i recovery from K+ loads. These results suggest that the main mechanism responsible for Ca2+ homeostasis is dependent on metabolic energy and that such energy can be provided by glucose metabolism.

Animals↗
PubMed1993

Fluorescence digital image analysis of glucose-induced [Ca2+]i oscillations in mouse pancreatic islets of Langerhans.

At intermediate glucose concentrations, [Ca2+]i (intracellular calcium) measured in single islets of Langerhans undergo oscillations that are caused by glucose-induced bursting of electrical activity. Using digital video imaging of fura-2--loaded islets, we have analyzed the spatial distribution of [Ca2+]i in response to the natural secretagogue glucose and the KATP channel blocker tolbutamide. When the glucose level is increased, [Ca2+]i first increases and then starts to oscillate with a synchronous pattern through the islet. The synchrony is maintained even during nonrhythmic oscillatory patterns. In the presence of tolbutamide, [Ca2+]i increases in all the islet regions, suggesting that the calcium signal is derived mainly from the beta-cell population. These results demonstrate that the islets behave as a functional syncytium in response to stimulatory glucose levels, canceling out heterogeneities at the single cell level.

Animals↗
PubMed1992

The relationship between glucose-induced K+ATP channel closure and the rise in [Ca2+]i in single mouse pancreatic beta-cells.

1. Intracellular calcium [Ca2+]i and channel activity were simultaneously recorded in single, dissociated mouse beta-cells kept in culture for 1-3 days. [Ca2+]i was estimated from microfluorometric ratio methods using Indo-1. Channel activity was measured using the cell-attached configuration of the patch-clamp technique. 2. At low glucose concentrations (0.3 mM), resting K+ATP channel activity was prevalent. Increasing glucose up to 16 mM, produced a gradual decrease in K+ATP channel activity over a time course of 90-120 s (temperature = 23 degrees C) and an increase in [Ca2+]i. 3. In the majority of experiments, glucose elicited biphasic action currents (action potentials) which preceded the rise in [Ca2+]i. There was a close correlation between spike frequency and the levels of [Ca2+]i. 4. The sulphonylurea tolbutamide (1 mM) blocked K+ATP channels in 10-20 s. K+ATP channel blockade was associated with a quick rise in [Ca2+]i. 5. When K+ATP channel activity was stimulated in the presence of diazoxide (100 microM), increasing the glucose concentration from 3 to 16 mM produced a decrease in [Ca2+]i. Only when diazoxide was removed did glucose produce an increase in [Ca2+]i. 6. In a small population of cells, glucose (16 mM) produced a small decrease in K+ATP channel activity but not an increase in [Ca2+]i. In such cells, tolbutamide blocked K+ATP channels and produced an increase in [Ca2+]i. 7. These results demonstrate a close correlation between K+ATP channel activity and [Ca2+]i in beta-cells. The findings are consistent with the model in which glucose metabolism produces a rise in [Ca2+]i through the blockade of K+ATP channels, membrane depolarization and calcium current activation.

Animals↗
PubMed1991

Widespread synchronous [Ca2+]i oscillations due to bursting electrical activity in single pancreatic islets.

Pancreatic beta cells, tightly organized in the islet of Langerhans, secrete insulin in response to glucose in a calcium-dependent manner. The calcium input required for this secretory activity is thought to be provided by an oscillatory electrical activity occurring in the form of "bursts" of calcium action potentials. The previous observation that islet intracellular free Ca2+ levels undergo spontaneous oscillations in the presence of glucose, together with the fact that islet cells are coupled through gap junctions, hinted at a highly effective co-ordination between individual islet cells. Through the use of simultaneous recordings of intracellular calcium and membrane potential it is now reported that the islet calcium waves are synchronized with the beta cell bursting electrical activity. This observation suggests that each calcium wave is due to Ca2+ entering the cells during a depolarized phase of electrical activity. Moreover, fura-2 fluorescence image analysis indicates that calcium oscillations occur synchronously across the whole islet tissue. The maximal phase shift between oscillations occurring in different islet cells is estimated as 2 s. This highly co-ordinated oscillatory calcium signalling system may underlie pulsatile insulin secretion and the islet behaviour as a secretory "syncytium". Since increasing glucose concentration lengthens calcium wave and burst duration without significantly affecting wave amplitude, we further propose that it is the fractional time at an enhanced Ca2+ level, rather than its amplitude, that encodes for the primary response of insulin-secreting cells to fuel secretagogues.

Action Potentials↗
PubMed1986

Survival after intestinal mucormycosis in acute myelogenous leukemia.

A young woman with acute myelocytic leukemia developed acute lower gastrointestinal bleeding immediately after a first remission induction of her leukemia. After the site of bleeding was located in the descending colon, a necrotic bleeding ulcer was resected. Histologic examination of the ulcer established the diagnosis of gastrointestinal mucormycosis. Treatment with amphotericin B was administered because of the high risk of dissemination. The patient has been followed for 9 months with no evidence of relapse of infection. Survival after gastrointestinal mucormycosis in acute leukemia has not previously been reported in the English language literature. Success in managing mucormycosis depends on the adherence to the recommended principles of early aggressive diagnostic measures, excisional surgery, amphotericin B therapy, and control of the underlying predisposing condition.

Adult↗