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S Escobar

Publications and source records attributed to S Escobar.

12 recordsLinked to original sources
PubMed2000

Identification of CD7 as a cognate of the human K12 (SECTM1) protein.

CD7 is a 40-kDa protein found primarily on T, NK, and pre-B cells; the function of the CD7 protein in the immune system is largely unknown. The K12 (SECTM1) protein was originally identified by its location just upstream of the CD7 locus. The K12 gene encodes a transmembrane protein of unknown function. In order to clone a K12-binding protein, we generated a soluble version of the human K12 protein by fusing its extracellular domain to the Fc portion of human IgG(1). Flow cytometry experiments showed that the K12-Fc fusion protein bound at high levels to both human T and NK cells. Precipitation experiments using K12-Fc on (35)S-radiolabeled NK cells lysates indicated that the K12 cognate was an approximately 40-kDa protein. A human peripheral blood T cell cDNA expression library was screened with the K12-Fc protein, and two independent, positive cDNA clones were identified and sequenced. Both cDNAs encoded the same protein, which was CD7. Thus, K12 and CD7 are cognate proteins that are located next to each other on human chromosome 17q25. Additionally, we have cloned the gene encoding the mouse homologue of K12, shown that it maps near the mouse CD7 gene on chromosome 11, and established that the mouse K12 protein binds to mouse, but not human, CD7. Mouse K12-Fc inhibited in a dose-dependent manner concanavalin A-induced proliferation, but not anti-TcRalpha/beta induced proliferation, of mouse lymph node T cells. Human K12-Fc stimulated the up-regulation of CD25, CD54, and CD69 on human NK cells in vitro.

Amino Acid Sequence↗
PubMed1997

Binding to delta and mu opioid receptors by deltorphin I/II analogues modified at the Phe3 and Asp4/Glu4 side chains: a report of 32 new analogues and a QSAR study.

The synthesis and binding affinities of 32 X3Gly4 dual-substitution analogues of the natural opioid heptapeptides deltorphin I and II are reported. A multiple regression QSAR analysis was performed using those results along with literature data for the X3Asp4 and Phe3X4 side chain analogues. Fitting to a three-term potential well model with hydrophobic and van der Waals attraction terms and a steric repulsion term indicates that the delta and mu receptor sites for binding the residue three side chain are similar, and that the binding interaction is primarily van der Waals and secondarily hydrophobic. Further analysis indicates that both sites are more constrained with respect to side chain length than width or thickness, and the mu site appears to be somewhat larger. A binding model consistent with these findings pictures the native third residues Phe ring laying on a step notched out of the receptor surface, pointing toward the back (riser) of the step, and sandwiched between the receptor and ligand. However, the binding sites for the residue four side chains are quite different on delta and mu receptors. Binding to the delta site appears to involve both electrostatic attraction (probably to a partial positive charge) and van der Waals attraction, but not necessarily hydrogen bonding, and more constraint with respect to side chain length than width or thickness. In contrast, there is no evidence for any kind of binding attraction between the side chain of residue four and the mu site, which acts more as steric repulsion site, as though the space that is a pocket on the delta receptor is filled in on the mu receptor. A regression model based only on steric repulsion by van der Waals bulk and/or the effective bulk of a hydration layer accounts for over 80% of the residue four related variation in mu affinity.

Algorithms↗
PubMed1995

Structural analysis of human and murine flt3 ligand genomic loci.

Both the murine and human genomic loci that encode flt3 ligand have been cloned. flt3 ligand is a hematopoietic growth factor that stimulates the proliferation of stem and progenitor cells. The portions of the murine and human flt3 ligand genomic loci encompassing the coding region of the protein are approximately 4.0 kb and 5.9 kb, respectively. The human genomic locus is larger as a result of the presence of repeated sequences within introns I, II, IV, V and VI. The transmembrane isoform of the murine and human flt3 ligand proteins are each encoded within seven exons (1-5 + 7 and 8). Analyses of flt3 ligand cDNA clones show that alternative splicing of a putative sixth exon results in the generation of a soluble form of the flt3 ligand protein. The sizes of each of the exons are well conserved between species. Murine and human flt3 genomic loci have a similar exon: intron structure compared to the genomic loci encoding Steel factor and colony stimulating factor 1. These proteins, which appear to be ancestrally related, are hematopoietic growth factors that stimulate cells via specific and structurally related tyrosine kinase receptors on the cell surface.

Alternative Splicing↗
PubMed1995

Expression of GTP-binding protein alpha subunits in human thymocytes.

In this report, we investigate G protein alpha subunit diversity in human thymocytes, utilizing common properties shared by these genes and reverse transcription-polymerase chain reaction (RT-PCR). Sequence analysis of PCR amplified gene portions, indicate the presence of members from all four G-protein families that have been described thus far. The alpha subunit genes identified are: G alpha i1-3 and G alpha z but not G alpha o from the Gi family, G alpha s from the Gs family, G alpha 11, G alpha q, and G alpha 16 from the Gq family, and G alpha 12 and G alpha 13 from the G12 family. Also in this report we present the nucleotide and predicted amino acid sequences of the human G alpha 13 cloned from a thymocyte cDNA library. The sequence of the human G alpha 13 has not been previously reported. Comparison of this sequence with the reported murine G alpha 13 shows > 90% identity at the deduced amino acid sequence level. We conclude that thymocytes represent a useful experimental system for the study of G protein involvement in immune responses and lymphocyte development.

Amino Acid Sequence↗
PubMed1995

Identification of soluble and membrane-bound isoforms of the murine flt3 ligand generated by alternative splicing of mRNAs.

We have recently described a novel hematopoietic growth factor, referred to as the flt3 ligand, that stimulates the proliferation of sub-populations of hematopoietic cells that are enriched for stem and progenitor cells. This factor is a transmembrane protein that undergoes proteolytic cleavage to generate a soluble form of the protein. We have isolated additional flt3 ligand isoforms by PCR that contain an extra exon and encode what are predicted to be either a soluble form of the ligand or a longer version of the transmembrane protein. We have also isolated cDNAs from murine T cell libraries that encode an isoform of the flt3 ligand that has an unusual C-terminus. This isoform results from a failure to splice out an intron during mRNA processing. The protein encoded by this cDNA is expressed on the cell surface, where it is biologically active. However, this novel isoform does not appear to give rise to a soluble form of the protein. Regulation of mRNA splicing is likely to control the generation of cell bound or soluble forms of this hematopoietic growth factor. Genetic mapping studies localize the gene encoding the flt3 ligand to the proximal portion of mouse chromosome 7 and to human chromosome 19q13.3.

Alternative Splicing↗
PubMed1995

Expression of the flt3 receptor and its ligand on hematopoietic cells.

Expression of the flt3 tyrosine kinase receptor and its ligand were examined on various murine and human hematopoietic cell lines. Surface expression of flt3 receptor and flt3 ligand were detected by flow cytometry using biotinylated human flt3 ligand or biotinylated soluble human flt3 receptor Fc fusion protein (flt3R-Fc), respectively. Flt3 receptor and ligand expression were also examined by Northern blot analysis. Flt3 receptor was expressed on the surface of only two of nine murine cell lines and nine of 15 human cell lines, with positive cells representing the B cell, early myeloid, and monocytic lineages. Staining for surface expression of the flt3 ligand revealed that seven of nine murine cell lines and nine of 15 human cell lines screened were positive by flow cytometry. All murine and human cell lines assayed were positive for flt3 ligand RNA expression by Northern blot analysis, but not all cell lines expressing flt3 ligand mRNA had detectable surface expression. Cells expressing the flt3 ligand were of the myeloid, B cell and T cell lineages at various stages of differentiation. Only the OCI-AML-5, NALM-6, and AML-193 cell lines coexpressed both surface flt3 receptor and ligand. The myeloid leukemic M1 cell terminally differentiate into macrophage-like cells under the influence of leukemia inhibitory factor (LIF). We found that LIF-stimulated M1 cells down-regulated surface expression and mRNA levels of the flt3 receptor, but up-regulated expression of the flt3 ligand. Although we could demonstrate that the flt3 receptor was functional in the M1 cell line, flt3 ligand could not induce the M1 cells to differentiate.

Animals↗
PubMed1970

Intestinal absorption of calcium-47 after treatment with oral oestrogen-gestogens in senile osteoporosis.

Intestinal absorption of radiocalcium was measured in 15 postmenopausal women with osteoporosis before and after six months' treatment with an oral oestrogen-gestogen combination. Comparison with a control group indicated a significant improvement in intestinal absorption after treatment. Though there is no evidence that oestrogens have an anabolic effect on human bone, these results indicate that they affect the intestinal absorption of calcium directly.

Aged↗
PubMedDate not supplied

[Total gastrectomy in newborn infant].

Total gastrectomy is rarely indicated in childhood and when necessary it involves multiple ulterior therapeutic problems, mainly nutritional, which need a meticulous physiological approach to avoid further complications, as illustrated by the following patient who, at age 15 months, was submitted to total gastric resection, Y en Roux esophagojejunal anastomosis and splenectomy, because of peritonitis secondary to dehiscence of a recent esophagogastric anastomosis for partial gastric resection due to gastric volvulus and necrosis, which in turn were associated to diaphragmatic relaxation. The patient was admitted to our hospital one month later with signs of acute calorie-protein malnutrition (W/A 60% and W/H 68%, NCHS standards) requiring combined parenteral and enteral nutritional support (via central venous catheter and jejunostomy tube for 15 and 35 days respectively) together with intramuscular vitamin B 12, oral iron and oral vitamin supplements before it became possible to fed him only by mouth. Prophylaxis against Streptococcus pneumonia infections with monthly benzatin penicillin was also instituted. Mean daily weight increases of 16 g, W/A 68% and W/H 74% were thus achieved before hospital discharge, without evidence of dumping syndrome nor alkaline reflux.

Gastrectomy↗
PubMedDate not supplied

[Modular diet and parenteral support in persistent diarrhea].

Eleven infants with protracted diarrhea were treated with modular diet and short-term parenteral nutrition. Mean age at admission was 3.7 months with males predominating. Enteropathogenic E. coli, classic serotypes, were isolated from 7 patients and rotavirus from one. A child with combined, severe immunodeficiency died. Milk protein intolerance was diagnosed in another patient. Balance studies and peroral biopsies were performed. Malnutrition was more frequent and hospital stay was longer in those infants who developed nosocomial infections. Even though this treatment shortened the duration of the hospitalization, the negative nutritional impact persisted: Weight/Age (NCHS) decreased from 84% to 61%, with rapid recovery after discharge. Fecal lactic acid excretion was increased on admission to 1,296 mg x day and disaccharidase activity was decreased. The modular diet decreased both fecal volume and lactic acid excretion.

Diarrhea, Infantile↗
PubMedDate not supplied

[Refractory diarrhea].

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Diarrhea, Infantile↗
PubMedDate not supplied

[The modular diet].

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Diarrhea, Infantile↗