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Biomedical subjects

A García

Publications and source records attributed to A García.

At least 181 records · Page 10Linked to original sources

In vivo and in vitro generation of a new altered HLA phenotype in melanoma-tumour-cell variants expressing a single HLA-class-I allele.

A new HLA-class-I altered phenotype is described in melanoma. This phenotype is the result of a combination of HLA-B-locus down-regulation and HLA-haplotype loss. The alteration was found in 2 melanoma cell lines generated from 2 patients; one was derived from an in vivo lesion (FM37) and the other was obtained after in vitro immunoselection (R22.2). The R22.2 cell line was isolated from FM55P, a cell line derived from a primary melanoma, after in vitro treatment with a heterologous HLA-A2-restricted cytotoxic-T-lymphocyte (CTL) clone. Two additional cell lines from patient 55 were obtained from 2 s.c. metastases (FM55M1 and FM55M2). Iso-electric focusing and flow-cytometric studies showed a significant reduction in the expression of both HLA-B alleles in all cell lines studied. The expression of HLA-B-locus products recovered completely after IFN-gamma treatment of FM55P, M1 and M2. In contrast, FM37 and R22.2 tumour cells showed an additional HLA defect: the absence of one HLA haplotype. Simple tandem-repeat polymorphism markers spanning chromosome 6 showed that DNA from the 2 samples (FM37 and R22.2) showed loss of heterozygosity (LOH). In both cases, homozygosity was observed on 6p, which maps the HLA region, the final consequence being a tumour cell that expressed a single HLA-class-I allele (HLA-A3 and HLA-A1 respectively). FM37 cells may thus reflect the in vivo counterpart of resistance to lysis by HLA-A2-restricted tumour-infiltrating lymphocytes.

Alleles↗

Factors associated with outcome in major depression: a 6-month prospective study.

A number of authors have indicated in recent years that the course of depression is not as favourable as previously expected. Research conducted in order to identify predictors of recovery has shown widely different results. In this paper a sample of 90 consecutive patients with non-chronic major depressive disorders (index episode < 6 months) attending four mental health centres in Madrid were followed up prospectively for 6 months, and clinical social and cognitive variables were studied. The patients were treated pharmacologically and controlled. The rate of recovery was measured according to the Hamilton Rating Scale for Depression (HAM-D). Other tools used were: Life Events and Chronic Difficulties, Global Assessment Functioning in the 6 months prior to the onset of episode, Brown Rating Scale for Self-Esteem and Mannheim Interview of Social Support. The results showed that 41 cases recovered (HAM-D score < 8), 29 cases achieved a partial remission, and major depressive disorder persisted in 17 cases (HAM-D score > or = 18). The presence of personality disorders, having suffered a previous episode, GAF score and some aspects of social support were the variables most associated with non full remission in the logistic regression analysis. Personality disorders and the initial HAM-D score were related to non-improvement. Some clinical and cognitive variables maintain a weak relation to outcome and are rejected in logistic regression. This study emphasizes the relationship of personality, and social variables such as social support and previous global functioning, with incomplete recovery in major depression.

Adolescent↗

Unresponsiveness to interferon associated with STAT1 protein deficiency in a gastric adenocarcinoma cell line.

HC class I expression can be up-regulated by interferons (IFN) and other cytokines. Both IFNalpha and IFNgamma have been shown to exert their effects via a recently discovered signalling pathway by inducing tyrosine phosphorylation of their receptors. Receptors for interferons and other cytokines signal through the action of associated protein tyrosine kinases of the JAK family (Janus kinase) and latent cytoplasmic transcriptional activators from the STAT family (signal transducers and activators of transcription). Here we report a gastric adenocarcinoma cell line, AGS, that is defective in its response to either IFNalpha or IFNgamma. AGS cells display selective alterations only in MHC class I inducibility and not in constitutive MHC class I expression. In nuclear extracts of AGS cells, no binding activity to interferon-responsive elements (GAS/ISRE) was observed. We found that AGS cells showed an extremely low level of STAT1 expression, which may be responsible for the absence of biological response to IFN. Because STAT1-deficient cells are highly sensitive to infection by virus, the absence of these proteins may also contribute to the tumor phenotype, giving the tumor a selective advantage, by inhibiting cell growth suppression mediated by IFN and abetting escape from the T cell antitumor response.

Adenocarcinoma↗

The phosphorylation of light-harvesting polypeptides LHIalpha (B870) and LHIIalpha (B800-850) of Rhodobacter capsulatus B10 was higher under chemotrophic oxic than under phototrophic anoxic growth conditions.

In Rhodobacter capsulatus B10 (wild type) both alpha subunits of the light-harvesting complexes are phosphorylated during photosynthetic membrane synthesis. During the process of insertion of these polypeptides, there is a dephosphorylation resulting in intracytoplasmic membranes in which no radioactive phosphate could be detected. Moreover, we show that their phosphate-specific contents depends on the growth conditions, the highest being observed under oxic conditions. When photosynthetic membrane synthesis was induced under light and anaerobiosis, a decrease in the phosphate-specific contents ensued. An inverse relationship exists between specific phosphorylation levels and the degree of membrane differentiation. The phosphorylation is thus a transient phenomenon characteristic of the photosynthetic membrane synthesis governed by the external redox conditions constituting an additional post-transcriptional level of regulation.

Autoradiography↗

[Anatomopathological bases of latent ventricular dysfunction in insulin-dependent diabetics].

INTRODUCTION AND OBJECTIVES: The natural history of diabetic cardiomyopathy remains unclear, mainly due to concurrent coronary disease or hypertension. Since the presence of confounding factors is less likely in youngsters, they constitute a suitable study model to analyze early stages of diabetic cardiomyopathy. PATIENTS AND METHODS: We screened 33 young normotensive asymptomatic patients with type I diabetes mellitus. Mean age was 28 +/- 8 y (range 18 to 46 y) and there were 14 men. RESULTS: 2-D Echo showed normal left ventricular size and wall motion in all patients but one. Radionuclide basal ejection fraction was 56.5 +/- 6.6% and increased to 63 +/- 7.4% (p < 0.02) on exercise. According to Rozansky criteria, 16 patients had an abnormal response. Abnormal stress sestamibi was detected in 18 patients and only 3 had reversible defects. Coronary angiography was performed in 11 patients with at least one abnormal non-invasive study response. Coronary angiography revealed normal vessels in all patients and left anterior descending blood flow velocity (Doppler) increased 4 fold after papaverine infusion. Left ventricular biopsies showed hypertrophy (either nuclear or cellular) in 11, myocytolysis in 6, interstitial fibrosis in 9 and lipid deposits in 4. Morphometric analysis of cardiac samples comparing the diabetic group and a control group showed that the volume fraction of fibrosis (0.19 +/- 0.06 vs 0.10 +/- 0.06; p < 0.01), fiber area -mu2- (1,062 +/- 547 vs 600 +/- 167; p < 0.02) and fiber diameter -mu- (24.2 +/- 3.3 vs 15.1 +/- 3.4; p < 0.001) were higher in the former; and volume fraction of the myocytes was higher in the latter (0.71 +/- 0.006 vs 0.89 +/- 0.07; p < 0.001). CONCLUSIONS: Left ventricular dysfunction, not related to coronary atherosclerosis or small vessel disease, is frequent in asymptomatic young diabetic patients. Abnormal pathologic findings are common in the type of cell hypertrophy, interstitial fibrosis, myocytolysis and lipid deposits.

Adolescent↗

[Cardiac transplant in single ventricle].

Univentricular heart is an uncommon congenital heart disease. A select group of these patients (those with severe pulmonary stenosis or atresia) can reach adult age with different degrees of heart failure and severe chronic hypoxemia. Patients with adequate pulmonary tree development are likely to undergo heart transplantation when usual palliative techniques are contraindicated. Three cases of univentricular heart with pulmonary stenosis in which heart transplantation was the optimal choice are reported. Different techniques used to assess pulmonary tree development are analysed.

Adolescent↗

Competence of health professionals to check the carotid pulse.

Our objective was to establish the proportion of Emergency Room and Intensive Care doctors and nurses able to locate the carotid pulse in less than 5 s, and identify the variables that influence this ability. The method followed was locating the carotid pulse in a healthy male adult volunteer with normal blood pressure in two situations (stretcher or floor) and with the neck in either a neutral or in an extended position. We recorded the gender, age, and previous training in cardiopulmonary resuscitation (CPR) of each participant and the time spent in detecting the pulse in each of the four possible positions. A model of logistic regression was constructed to determine if the patient's position had any influence on the proportion of health workers capable of finding the pulse within 5 s. The average age of the 72 subjects studied was 33.4 years (SD = 6.6); 80% of the participants had CPR training. Thirty-one participants (43.1%; CI 95%, 31.4-55.3%) required more than 5 s to detect the pulse, although only three (4.2%; CI 95%, 0.9-11.7%) required more than 10 s. The variable 'no CPR training' was associated with the inability to detect the pulse within 5 s. The detection of the pulse was easier with an extended neck. A significant proportion of nurses and doctors were slow to locate the carotid pulse on a healthy, young volunteer with normal blood pressure. No relation was found between gender or age of the participants. More attention should be given to carotid pulse detection in CPR training.

Adult↗

Benign intracardiac teratoma detected prenatally. Case report and review of the literature.

Primary cardiac tumors are rare and, until recently, were mostly incidental postmortem findings. Nowadays, due to the widespread use of prenatal ultrasound scans, we are able to diagnose them in utero. We present a case of an intracardiac teratoma diagnosed at 38 weeks, menstrual age. Previous scans had been normal. Labor was induced, and a female infant with an Apgar score of 9 and 4, at 1 and 5 min, was delivered. Her condition worsened rapidly. She died 16 h after birth. Necropsy was performed, and a cystic, mature teratoma of 4 cm was found in the interventricular septum, growing into the right ventricle. No other anomalies were found. This probably represents the first case of an intracardiac, benign teratoma diagnosed prenatally.

Fatal Outcome↗

Predictive value of 99Tcm-sestamibi gated SPET for long-term myocardial perfusion and functional recovery after an acute myocardial infarction.

We assessed the predictive value of 99Tcm-sestamibi gated single photon emission tomography (SPET) for changes in perfusion and functional outcome after an acute myocardial infarction and compared the findings on functional recovery with echocardiography using low-dose dobutamine. Gated 99Tcm-sestamibi SPET and radionuclide angiocardiography were performed in 17 patients 4-10 days after an acute myocardial infarction. Six months later, both isotopic studies and rest-dobutamine echocardiography were performed to assess outcome. Perfusion improved in six of seven severely hypoperfused segments (positive predictive value = 85.7%) that showed wall thickening but not in any of 28 segments (negative predictive value = 100%) without wall thickening. The mean ejection fraction improved from 47.7 to 52.3% (P = 0.018). Furthermore, there was a greater improvement in ejection fraction in the group of patients in whom wall thickening predicted a recovery in perfusion (9.0 vs 3.7%, P = 0.01). A comparison of the assessment of functional recovery between gated SPET and dobutamine echocardiography showed good agreement (81.4%). We conclude that the presence of wall thickening in severely hypoperfused segments on 99Tcm-sestamibi gated SPET is predictive of changes in perfusion and functional recovery after acute myocardial infarction, thus identifying the presence of viable myocardium. In contrast, segments showing hypoperfusion and dysfunction after an acute myocardial infarction probably contain scar tissue only.

Adult↗

Intestinal leiomyosarcoma as the cause of severe hemoperitoneum.

Leiomyosarcomas represent 10-20% of malignant tumors in the small bowel and 1% of those located in the large bowel. These tumors have aspecific symptoms depending on their size, location and histology. Intestinal leiomyosarcomas may be the cause of numerous types of surgical emergency. We report 2 cases of intestinal leiomyosarcoma in the jejunum and transverse colon. Both were diagnosed during an emergency exploratory celiotomy. The clinical features on admission were similar to those of acute abdomen. The main cause of surgical emergency was an extremely rare complication of gastrointestinal leiomyosarcoma: a severe hemoperitoneum. We briefly describe the surgical emergencies caused by intestinal leiomyosarcomas as well as the surgical methods employed in these cases.

Colonic Neoplasms↗

Charcot-Marie-Tooth disease type 1A with 17p duplication in infancy and early childhood: a longitudinal clinical and electrophysiologic study.

OBJECTIVE: We describe longitudinal clinical and electrophysiologic evaluation of Charcot-Marie-Tooth disease type 1A (CMT-1A) in infancy and early childhood. BACKGROUND: The clinical picture and electrophysiologic evaluation of CMT-1A during the age of nerve conduction maturation have not been documented. DESIGN/METHODS: Twenty at-risk children from six unrelated CMT-1A families were examined in the first 5 years of life. Initial ages were 1 month to 4 years (mean, 1.5 years) and final ages 4 to 19 years (mean, 9 years). All subjects had two or more motor and sensory conduction velocities (MCV and SCV), corrected distal motor latencies (DML), and F-waves. RESULTS: Twelve children were affected. Initially, two of these (17%) had symptoms, whereas five (42%) were symptomatic at the end. Numbers of abnormal examinations at the beginning was six (50%) and at conclusion was 10 (83%). None of the patients were disabled. From 2 years of age, all affected children had abnormal MCV, SVC, F-waves, and DML. Prolonged DML was already present in the first months of life and preceded slowing of MCV in three cases. CONCLUSION: The electrophysiologic studies were concordant with the presence or absence of the CMT-1A DNA duplication. In most CMT-1A patients, symptoms appear in early childhood, although the florid clinical picture does not occur until the second decade of life. Serial electrophysiologic studies can detect the CMT-1A gene carrier in infancy.

Adolescent↗

Importance of mixed chimerism to predict relapse in persistently BCR/ABL positive long survivors after allogeneic bone marrow transplantation for chronic myeloid leukemia.

Determination of hematological chimerism could be helpful in understanding the biology of leukemic relapse after allogeneic bone marrow transplant (BMT) for chronic myeloid leukemia (CML), because the detection of malignant residual cells carrying the bcr/abl message by qualitative RT-PCR is of limited value in predicting disease progression for individual patients. We have studied the chimerism pattern and the bcr/abl status by Southern-blot in 15 CML patients (M/F:6/9) transplanted with unmanipulated BM from HLA identical sibling donors, persistently bcr/abl positive by RT-PCR. The median age of the series was 31 years (18-49) and disease status at BMT was: chronic phase: 11, accelerated phase: 3 and blast crisis: 1 patient. Of the 15 patients, 9 are alive and in complete remission (CR), 4 have died in CR and 2 are alive but suffered relapse at + 19 and +26 months post-BMT. The median follow-up is 81 months (13,7-168). Rearrangement of the BCR gene was performed by Southern-blot using P32-labeled transprobe-1. PCR analysis of chimerism was assessed using primers for the following VNTR loci: D1S80, D1S111, 33.1, APO-B, YNZ-22, lambdag3 and DXS52. Seventy-nine samples were analyzed (median per patient 5 (range 2-9)). Thirteen patients showed complete chimerism and lacked BCR rearrangement over time by Southern-blot. The 2 patients who relapsed showed mixed chimera status from +9 and +5 months respectively until the end of the study. Persistent BCR rearrangement was observed in these 2 patients from +12 and +11 months respectively. Our data suggest that mixed chimerism may predict hematologic or cytogenetic relapse by several months in those patients who are persistently PCR-positive post-BMT.

Adult↗

[Acute hepatocellular lesion induced by amoxicillin-clavulanic acid].

Since first description in 1988, numerous cases of amoxycillin-clavulanic acid hepatotoxicity have been reported. Most of them are cholestatic hepatitis. A case of acute hepatocellular injury by amoxycillin-clavulanic acid is reported in a 23-years-old male, with a favourable outcome after 18 weeks.

Acute Disease↗

[Evaluation of left ventricular contraction using heart tomography with technetium 99m tetrofosmin in synchrony with ECG. Correlation with bidimensional echocardiography].

BACKGROUND: Echocardiography is a standard method of evaluating segmental and global left ventricular function in clinical practice. The aim of this study was to determine if segmental and global ventricular function determined from Gated SPECT myocardial imaging adequately coincides with echocardiographic data. PATIENTS AND METHODS: We studied 23 patients with ischemic heart disease referred for clinical 99mTc tetrofosmin Gated SPECT imaging. The results were compared with those obtained using a standard rest echocardiographic assessment. Both studies were performed within a 24-48 hour period. Segmental results in both studies were analyzed by semiquantitative visual scoring using a two or three-point grading system and a summed score was obtained to determine global left ventricular function. RESULTS: There was a good segmental score agreement between both techniques for wall motion (77.5%; kappa = 0.49) and less for wall thickening (85%; kappa = 0.36). There were non significant statistical differences in the global left ventricular function with both techniques by wall motion (echocardiography 15.3 +/- 5.4 vs tetrofosmin 14.9 +/- 4.4; p = NS) and wall thickening (echocardiography 12.7 +/- 2.3 vs tetrofosmin 12.4 +/- 1.8; p = NS) scores. Correlation for global wall motion (r = 0.81; p < 0.0001) and wall thickening (r = 0.72; p = 0.0001) scores between the two modalities was good. CONCLUSIONS: Gated SPECT 99mTc tetrofosmin myocardial imaging is a valid method to assess segmental and global left ventricular function and agrees well with echocardiography.

Aged↗