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Biomedical subjects

M Alonso

Publications and source records attributed to M Alonso.

At least 163 records · Page 9Linked to original sources

Molecular cloning of CD1a (T6), a human epidermal dendritic cell marker related to class I MHC molecules.

To investigate the structure, function, and control of CD1a, we have cloned a 1.6-kbp cDNA which encodes the expressed CD1a protein and includes untranslated 5' and 3' sequences and the poly-A tail. As the protein recognized by the monoclonal antibody OKT6, CD1a is a useful marker for Langerhans cells (LC). CD1a is found on these cells and on thymocytes, suggesting an important immunologic role for this molecule. We constructed a cDNA library in lambda gt10 using mRNA from MOLT-4, a cell line that expresses the CD1a surface antigen. We then screened the library with an oligonucleotide synthesized according to a known partial sequence for CD1a, and subcloned the cDNA and its restriction fragments into pGEM for sequencing and probe production. Based on this sequence the CD1a protein is predicted to consist of three extracellular domains (alpha 1-3), a hydrophobic transmembrane region, and a cytoplasmic tail. DNA 5' to the alpha 1 region may undergo alternative exon splicing. There is high sequence identity between the beta-2 microglobulin binding region of MHC I molecules and CD1a. The secondary structure predicted for CD1a is very similar to the actual structure of HLA-A2, a classical MHC I molecule. The similarity includes the beta pleated sheets and alpha helices which form the antigen binding groove of the alpha-1 and alpha-2 domains. The homology predicted between CD1a and HLA-A2 in these regions appears to exist on the level of secondary structure despite low primary nucleotide and amino acid sequence identity. The structural data and probes we have developed should facilitate studies of the function of CD1a as well as novel investigations of LC.

Amino Acid Sequence↗

[Oat cell carcinoma of the esophagus].

Extrapulmonary locations of undifferentiated small cell carcinoma of the "oat cell" type are uncommon. In spite of its rarity, the appearance of this type of tumor has been described in various organs of the economy. Of these, the esophagus is the most common location, constituting 0.05 to 7.6% of esophageal carcinomas. Of uncertain histopathologic origin, these tumors are characterized by their extreme aggressiveness, which carries a poor short term prognosis. Surgery, radiotherapy and chemotherapy, separately or in combination, have produced discouraging results in the treatment of primitive esophageal "oat cell" carcinoma. In this paper are presented four cases of esophageal "oat cell" carcinoma treated in the Hospital de la Santa Cruz y San Pablo in 1979-1988, out of a total of 260 carcinomas in the same location. The clinical evolution and pathological findings of this type of tumor are commented. The literature on this unusual histological type of carcinoma is reviewed.

Aged↗

Pancreatitis and hyperparathyroidism.

Hypercalcaemia is considered to be a rare cause of pancreatitis but the true cause-and-effect relationship between hyperparathyroidism and pancreatic inflammatory disease remains controversial. Over 100 patients have been reported in whom both processes have occurred concurrently, but doubts have been expressed as to whether or not this association is due to chance. We report 10 new cases of hypercalcaemic hyperparathyroidism associated with different types of pancreatitis. Seven patients had primary hyperparathyroidism and three had hyperparathyroidism after renal transplantation. Two experienced acute pancreatitis after parathyroidectomy. Of the remaining eight patients, five had hypercalcaemia equal to or above 120 mg/l. The prevalence of pancreatitis in our series of 86 cases of primary hyperparathyroidism is 8 per cent. Acute and chronic calcifying types of pancreatitis were observed. Three patients died of the disease, two of them after renal transplantation. It is suggested that pancreatitis may complicate the clinical course of hyperparathyroidism, particularly when hypercalcaemia is moderate to severe and/or there are other risk factors such as treatment with steroids and azathioprine after renal transplantation.

Adult↗

Prostaglandin E2 and the increase of intracellular cAMP inhibit the expression of interleukin 2 receptors in human T cells.

We have analyzed the effect mediated by prostaglandin E2 (PGE2) and different reagents that increase intracellular cAMP on the expression of the p55 subunit (CD25) of interleukin 2 receptors (IL 2R), on the levels of CD25-specific mRNA and on the expression of high affinity IL 2R. In purified T cells, activated either by an anti-CD3 monoclonal antibody or phytohemagglutinin, the addition of PGE2 (10(-6) M), forskolin (5 X 10(-5) M), cholera toxin (0.2 microgram/ml) or dibutyryl cAMP (dBcAMP) (10(-4) M) decreased the cell surface expression of IL 2R by reducing (40%-78% inhibition) the proportions of CD25+ cells as well as the expression of high affinity IL 2R, detectable after 24 h. Furthermore, it was observed that PGE2 reduced the concentration of IL 2R-specific mRNA after a 6-h period of activation, indicating that its regulatory activity takes place at a pretranslational level. The addition of exogenous recombinant IL 2 only partially reversed the inhibition, thus suggesting that PGE2 and increased intracellular concentration of cAMP directly interfered with CD25 expression and that their effect could not be merely attributed to a lack of IL 2-dependent positive feedback. Cells cultured under the same conditions in the presence of phorbol myristate acetate, that activates protein kinase C, were refractory to the cAMP-mediated regulation. Finally, we demonstrate that both PGE2 and dBcAMP inhibit the generation of inositol metabolites after T cell activation, thus indicating that these reagents interfere with early signal transduction mechanisms which precede the synthesis of IL 2R.

Antigen-Antibody Reactions↗

Retroperitoneal malignant fibrous histiocytoma.

Five cases of malignant fibrous histiocytoma located in the retroperitoneum are reported. Paraneoplastic syndrome, abdominal mass, tendency to local recurrence, laborious therapy and poor prognosis are the clinical characteristics of this tumor. Accuracy of actual diagnosis is evaluated and pathological features are analyzed.

Adult↗

Effects of intravenous ajmaline on atrial excitability and conduction in man.

Slow conduction of early extrastimuli and short refractory periods are some of the factors underlying atrial fibrillation in man. In order to study the effect of ajmaline, a class I antiarrhythmic agent, on these variables, we have performed electrophysiologic studies in 13 patients with and without atrial arrhythmias, before and after the intravenous administration of 1 mg kg-1 of ajmaline chlorhydrate. During paced rhythm with a 600 ms cycle length, extrastimuli were applied to the right atrial appendage, and conduction to the low septal right atrium and the coronary sinus were measured. Ajmaline prolonged P wave duration from 111 +/- 15 to 140 +/- 24 ms (P less than 0.001), conduction of baseline stimuli to low septal right atrium from 69 +/- 14 to 95 +/- 21 ms (P less than 0.001) and to coronary sinus from 127 +/- 18 to 165 +/- 29 ms (P less than 0.001). Atrial effective refractory period increased from 207 +/- 23 to 255 +/- 27 ms (P less than 0.001). Maximum conduction delay of early extrastimuli decreased at the low septal right atrium from 43 +/- 22 to 29 +/- 16 ms (P less than 0.25) and at the coronary sinus from 47 +/- 22 to 21 +/- 14 ms (P less than 0.001). These results show interesting electrophysiologic effects of ajmaline on atrial tissue, with reversion of some of the abnormalities underlying atrial fibrillation, and suggest an antiarrhythmic effect.

Ajmaline↗

Crossed chemoprophylaxis assay between adriamycin and cis-platinum in recurrent superficial bladder tumor.

Of 146 patients with superficial bladder carcinoma, 66 (35 primary and 31 recurrent from failure of thiotepa chemoprophylaxis) relapsed following transurethral resection (TUR) and chemotherapy with adriamycin or cis-platinum. A new TUR was carried out. In case of progression in the number of tumors, size, stage or grade, treatment was begun with the other drug. If the tumor had the same characteristics, treatment was continued with the same drug. In both the primary and recurrent tumors with or without progression, cis-platinum controlled the tumor better than adriamycin, rescuing it from the latter and obtaining a recurrence index and disease-free interval as with cis-platinum alone. These results are more conclusive in primary tumors.

Cisplatin↗

[Plasmid content in strains of Azospirillum sp].

In this work, the plasmid content of 22 strains of A. brasilense and 7 of A. lipoferum, isolated from different regions of Argentina was analyzed. Of the several methods for the extraction of plasmids, a modification of that of Kado and Liu was found to be the most appropriate for the isolation of a larger number of high molecular weight plasmids. Out of 29 strains analyzed, 26 were found to contain between one and four plasmids, all of them of high molecular weight (Figure 3, Table 1); 44% of the plasmid-containing strains showed one large plasmid of similar electrophoretic mobility and of approximately 100 Mdal.

Culture Media↗

Increased serum beta2-microglobulin levels in active celiac disease.

Sixty-eight sera from 36 children with celiac disease (CD) were collected in a 4-year study, and the levels of beta2-microglobulin (beta2M), orosomucoid, alpha1-antitrypsin, and C-reactive protein (CRP) were measured. A simultaneous intestinal biopsy was taken in all the patients and used to classify them. The values of beta2M were 1.94 +/- 0.49 mg/L in group A (inactive CD with normal intestinal biopsy) and 2.58 +/- 0.76 mg/L in group B (active CD with flat mucosa). These levels were higher than in the normal controls (1.87 +/- 0.49 mg/L, p less than 0.005) and in the other 19 patients with chronic diarrhea of another cause (1.72 +/- 0.63 mg/L, p less than 0.005). CRP values were generally normal; orosomucoid and alpha1-antitrypsin were variable and they did not correlate with beta2M levels. Beta2M was increased at the time of diagnosis in seven of eight (87.5%) of the CD children and only in three of 19 (15.7%) of nonceliac patients with chronic diarrhea of another cause (p less than 0.005). In 12 children with CD, serial studies were possible. The highest beta2M level coincided with a flat mucosa in 10 cases. The increase of beta2M could be related to the intestinal infiltration or even to the lymphocyte activation. It may also be a useful noninvasive method for evaluating the activity of CD.

Acute-Phase Proteins↗

Unusual viruslike particles in chronic non-A, non-B hepatitis in childhood.

Liver biopsies from 16 children with clinical and pathologic evidence of chronic hepatitis have been examined by electron microscopy for cytoplasmic and nuclear changes. Parallel studies by radioimmunoassay on sera from the same patients support the diagnosis of all these cases as non-A, non-B hepatitis (NANB). Ultrathin sections of the liver biopsies demonstrated in one case intranuclear hepatitis B virus-like core particles, 25 nm diameter. In a second biopsy from the same patient, the corelike particles could still be observed. This finding could be used either to support the thesis that a NANB virus is a member of the hepadnavirus group or to reflect the existence of seronegative cases of chronic HBV infection. Furthermore, we have observed in some mononuclear cells from the inflammatory infiltrate of a portal tract, some structures that resemble virus budding. There is a striking similarity between the morphology of these particles (which are enveloped and possess projections) and the ultrastructure of retrovirus.

Antigens, Viral↗