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Biomedical subjects

W A Walker

Publications and source records attributed to W A Walker.

At least 73 records · Page 4Linked to original sources
PubMed1995

Differentiation and polarity alter the binding of IGF-I to human intestinal epithelial (Caco-2) cells.

This study examined whether insulin-like growth factor-I (IGF-I) bound to specific functioning IGF receptors on the surface of Caco-2 cells and how this binding was affected by the differentiation and polarity of these cells. IGF-I, which increased cell proliferation in a dose-dependent manner, bound to a specific receptor on the surface of Caco-2 cells. Affinity cross-linking with labeled IGF-I followed by reducing sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed M(r)s at 135,000, 270,000 and 355,000 bands, which was inhibited by unlabeled IGF-I. A Scatchard analysis of radioligand-receptor binding showed the presence of a single class of receptors with high affinity for IGF-I. This class of receptors was specific for IGF-I, the affinity of IGF-I to the receptor being four and 150 times greater than IGF-II and insulin, respectively. There was no difference in the affinity of IGF-I to type 1 IGF receptors between less-differentiated [dissociation constant (Kd) = 3.81 nM] and well-differentiated cells (Kd = 3.78 nM); however, well-differentiated cells showed a 2.4-fold higher maximum number of binding sites (Bmax) than less-differentiated cells (3.45 vs. 1.44 x 10(4) sites/cell), indicating an increase in the density of IGF-I receptors with differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1995

Iron saturation alters the effect of lactoferrin on the proliferation and differentiation of human enterocytes (Caco-2 cells).

Recent studies have indicated that lactoferrin may act as a cell mitogen. The effect of human and bovine lactoferrins on the proliferation and differentiation of a human intestinal epithelial cell line (Caco-2) was investigated and compared with that of human transferrin. Caco-2 cells were cultured in serum-free media supplemented with both iron-unsaturated and -saturated forms of the iron-binding proteins. Cell proliferation and differentiation were evaluated by examining growth curves and measuring sucrase and alkaline phosphatase activities of brush border membrane fractions, respectively. The iron-binding status of lactoferrins and transferrin affected the proliferation of Caco-2 cells. The iron-saturated forms of human (S-hLf), bovine (S-bLf) lactoferrins and human transferrin (S-hTf) enhanced cell proliferation, while iron-unsaturated forms (U-hLf, U-bLf, and U-hTf) suppressed it. Iron-binding status also determined the effect of lactoferrin and transferrin on cellular differentiation, but this effect differed for different brush border enzymes. S-hTf enhanced sucrase activity more than S-hLF or S-bLf. Both U-hLf and U-bLf markedly suppressed sucrase activity. U-hTf suppressed alkaline phosphatase activity appreciably, while the other iron-binding proteins showed no significant effect on it. Lactoferrin and transferrin may modulate the proliferation and differentiation of intestinal epithelial cells, but their efficacy depends on their saturation with iron.

Animals↗
PubMed1995

Human milk and intestinal host defense in newborns: an update.

In this update of the role of breast milk ingestion on passive and active protection of the human neonate, new observations and studies are presented that appear to support the concept that preterm and term infants should receive their mother's milk so far as possible. New objective evidence has been presented to support the role of breast milk in the protection of the newborn from intestinal and systemic infections. New concepts of the active role of breast milk growth factors on an accelerated development of the infant's own mucosal barrier function are presented, as well as preliminary data to support the role of breast milk growth factors in gut development. This new area of breast milk function, however, requires extensive clinical studies to support the practical value of breast milk in the development of the infant's own defenses.

Breast Feeding↗
PubMed1994

Uptake, transport and metabolism of exogenous nucleosides in intestinal epithelial cell cultures.

The uptake and transport of nucleosides (adenosine, cytidine, guanosine, thymidine, uridine and inosine) were examined in intestinal cell lines (Caco-2 and IEC-6). Well-differentiated Caco-2 cells took up significantly more uridine and thymidine than less-differentiated cells over 24 h. These differences were reflected in the resulting trichloroacetic acid-soluble (nucleotide, nucleoside and nucleobase) pool sizes rather than in differences in nucleic acid incorporation. IEC-6 cells have smaller soluble pools than Caco-2 cells, and the uptake of nucleosides over 60 min reflected this difference. Caco-2 cells transported significantly more thymidine, cytidine, guanosine, adenosine and inosine into acid-soluble pools than IEC-6 cells. Caco-2 cells were grown on filters to examine the transcellular transport of nucleosides and to examine the chemical form in which nucleosides appeared at the basolateral aspect of the cell monolayer. The pattern of transport varied for individual nucleosides. The transport of cytidine and guanosine was significantly greater in the apical-to-basolateral direction than in the opposite direction over 2 h. No purine nucleoside was transported intact across the Caco-2 cell monolayer in either direction, with the majority of the transported material appearing as nucleobases. Nucleobases also represented the main metabolites of pyrimidines transported. However, some cytidine and uridine were detectable, but each constituted < 20% of transported material. Nucleosides are therefore transported by enterocytes but metabolized during transport.

Adenosine↗
PubMed1994

Uptake of antigens: role in gastrointestinal disease.

The intestine is exposed to a wide variety of macromolecules. Because macromolecules are antigenic, mechanisms have evolved in the gastrointestinal tract to regulate their absorption. Macromolecular uptake can be beneficial in delivering essential factors for growth and in sampling the antigenic milieu of the gastrointestinal tract. Specific transport mechanisms exist to execute this physiological absorption. However, inappropriate and uncontrolled antigen transport may occur in disease states, or as a prelude to disease states in the gastrointestinal tract. Such transport may result in immune responses that are harmful. In this review we examine both physiological transport of macromolecules through epithelia and through M cells. We also discuss uncontrolled transport and its relation to disease states. We conclude by examining the interrelationship between antigen transport and an altered immune system in the establishment of gastrointestinal disease.

Animals↗
PubMed1994

Children with congenital heart disease: a nutrition challenge.

Growth in children with congenital heart disease (CHD) is often compromised. For several decades, investigators have tried to identify the factors affecting growth in children with CHD. Cardiac malformations are undoubtedly responsible for malnutrition, which may range from mild undernutrition to severe failure to thrive (FTT). Malnutrition may then significantly undermine the outcome of corrective surgical operations and postoperative recovery. Mechanisms linking CHD to malnutrition may be related either to decreased energy intake and/or to increased energy requirements. Decreased energy intake can involve deficiencies of specific nutrients, or insufficient total caloric intake. Increased respiratory rate accompanying congestive heart failure may be responsible for increased energy requirements. Different types of cardiac malformations and consequent interventions may have different effects on growth and require diverse strategies. Most treatment strategies aim to facilitate "catch-up" growth, providing extra calories and protein that exceed the Recommended Dietary Allowance for age. However, there is no generally accepted set of guidelines that define appropriate caloric intake for catch-up growth. We attempt to identify the most important causes of malnutrition and highlight the most effective nutrition strategies for children with CHD.

Energy Intake↗
PubMed1994

Profile of IGF-binding proteins secreted by intestinal epithelial cells changes with differentiation.

Previous reports have shown that gastrointestinal epithelial cells produce insulin-like growth factor-binding proteins (IGF-BP), which modulate the actions of IGF. This study aims to examine the relationship between differentiation and IGF-BP secretion by human intestinal epithelial cells and the effect of growth factors on their production. Caco-2 cells were cultured in serum-free media. IGF-BP secretion into the incubation media was analyzed by Western ligand blotting and immunoblotting. Caco-2 cells produced IGF-BP-2, IGF-BP-3, and IGF-BP-4. Secretion of IGF-BP-2 and IGF-BP-3 increased with differentiation, but IGF-BP-4 secretion diminished. The effect of exogenous growth factors on IGF-BP secretion was maximal at earlier stages of differentiation. IGF-I stimulated mainly IGF-BP-3 production, but epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) stimulated predominantly IGF-BP-4 secretion. Adding an anti-EGF receptor antibody to block autocrine TGF-alpha activity inhibited IGF-BP-4 production but stimulated IGF-BP-2 and IGF-BP-3. In conclusion, the profile of IGF-BP secretion changes with differentiation. IGF-I and EGF (or TGF-alpha) stimulate different types of IGF-BP, with autocrine TGF-alpha activity being a factor affecting IGF-BP production during differentiation.

Antibodies↗
PubMed1993

Insulin-like growth factor binding protein profile secreted by human intestinal epithelial cells varies with polarity.

The actions of insulin-like growth factors (IGFs) are modulated by interaction with a family of secreted binding proteins (IGFBPs). We have now demonstrated in intestinal epithelial cells (Caco-2) that the secretion of different members of this family depends on the cell surface secreting them. Polarized monolayers of cells secreted IGFBP-3 mainly into the medium adjacent to the apical surface, while IGFBP-2 was secreted predominantly through the basolateral surface. The secretion of IGFBP-1 and -4 was equivalent from both surfaces. However, administration of epidermal growth factor (EGF) induced polarized secretion of IGFBP-4 by increasing secretion from the apical surface more than from the basolateral aspect. It did not affect the polarity of the other IGFBPs. We believe that this is the first evidence that epithelial cells can interact with extrinsic agents in a polarized fashion at sites other than the membrane surface.

Adenocarcinoma↗
PubMed1993

Penetrating injuries of the aortic arch and its branches.

Acute cardiac failure, pulmonary edema, and ischemia of the brain, cord, and other structures pose special problems with trauma to the aortic arch and its branches. Data on 93 such cases are reported. Diagnosis was made by clinical examination in hemodynamically unstable patients and led to immediate operation in 61.3%. Patients in stable condition had angiography, which localized the injury and allowed planning of incision and bypass shunts. In left subclavian artery injuries, anterior thoracotomy was best for proximal control regardless of wound entry sites; midline sternotomy with sternocleidomastoid extension was usually adequate for other vessels. Flow was reestablished in all carotid injuries; there were no neurological complications. Temporary or permanent bypass shunts during periods of proximal aortic occlusion were valuable in decreasing cardiac afterload, maintaining circulation to the brain, and allowing an unhurried methodical approach to the hematoma. Occlusion of one or more venae cavae alleviated acute cardiac dilatation during brief periods of ascending aortic clamping. Associated trauma contributed to the high mortality.

Adult↗
PubMed1993

Multiple tumor emboli after pneumonectomy.

Systemic arterial tumor embolization is a rare complication after pulmonary resection. It may occur with primary or metastatic pulmonary malignancies, and is more frequently associated with pneumonectomy than with lesser pulmonary resections. Despite the rarity of this complication, tumor emboli should be considered in the etiology of extremity, cerebral, or multiorgan ischemia occurring during the perioperative period in patients undergoing pulmonary resections for malignancy.

Aortic Diseases↗
PubMed1993

Uptake and transport of macromolecules by the intestine: possible role in clinical disorders (an update).

The intestine is exposed to a wide variety of macromolecules. Because macromolecules are antigenic, mechanisms have evolved in the gastrointestinal tract to regulate their absorption. Macromolecular uptake can be beneficial in delivering essential factors for growth and in sampling the antigenic milieu of the gastrointestinal tract. Specific transport mechanisms exist to execute this physiological absorption. However, inappropriate and uncontrolled antigen transport may occur in disease states or as a prelude to disease states in the gastrointestinal tract. Such transport may result in immune responses that are harmful. This review examines physiological transport of macromolecules through epithelia and through M cells. It also considers uncontrolled transport and its relation to disease states. The review concludes with an examination of the interrelationship between antigen transport and an altered immune system in the establishment of gastrointestinal disease.

Animals↗
PubMed1993

Bacterial toxin interaction with the developing intestine.

An important approach to the major health problem of bacterial infection in young children has been to examine bacterial toxin binding to microvillus membrane receptors, the signal transduction produced by that interaction and the mechanisms of fluid secretion in the developing intestine as a basis for toxigenic diarrhea in the infant population. These studies indicate that receptor binding and effector responses may be subjected to developmental regulation. This regulation process of toxin interaction with the developing intestine may have an enhanced or harmful effect or, under some circumstances, may have a beneficial effect and be protective to the vulnerable child. Specific mechanisms for the developmental control of receptor expression may involve the regulation of individual glycosyltransferases responsible for the addition of receptor sugar sequences to glycolipids and/or glycoproteins, presumably at the transcriptional level. Furthermore, although highly speculative at this point, the differential expression of signal transducers (e.g., guanine nucleotide-regulatory proteins or G proteins) and ion transporters (e.g., Na+,K(+)-stimulated adenosine triphosphatase, the Cl- channels, etc.) during development may also alter the neonatal host's responsiveness. Therefore, the developmental control of microvillus membrane receptors, signal transduction mechanisms, and ion transport systems in the gastro-intestinal tract may in part contribute to the altered host sensitivity in toxigenic diarrhea of infancy.

Animals↗
PubMed1993

Nucleotide supplements alter proliferation and differentiation of cultured human (Caco-2) and rat (IEC-6) intestinal epithelial cells.

The effect of exogenous nucleotides on the proliferation and differentiation of enterocytes was comparatively studied using a human colon tumor cell line (Caco-2) and a normal rat small intestinal crypt cell line (IEC-6). Caco-2 cells exhibited more active endogenous nucleic acid metabolism than did IEC-6 cells, as evidenced by greater cellular pools of nucleotides and their metabolites. To determine the supplemental nutritional effect of nucleotides, a mixture containing equal amounts (10 mg/L) of AMP, CMP, IMP, GMP and UMP was added to the culture medium. The results showed that a nucleotide supplement under normal culture conditions did not affect proliferation and differentiation of Caco-2 cells. In contrast, nucleotide supplements under normal culture conditions promoted proliferation of IEC-6 cells. The addition of nucleotides to the culture medium also enhanced differentiation of IEC-6 cells when grown on an extracellular matrix (Matrigel). Furthermore, when glutamine levels were less than optimal (nutritional stress conditions), nucleotide supplements enhanced growth and maturation of both cell lines. We conclude that the de novo biosynthesis of nucleotides is sufficient to support proliferation of tumor Caco-2 cells but not of the normal crypt IEC-6 cells. Thus, nucleotide supplements may enhance normal enterocyte growth and maturation as well as spare the need for exogenous glutamine in cell maintenance and development.

Adenosine Monophosphate↗