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Biomedical subjects

M Heyman

Publications and source records attributed to M Heyman.

At least 109 records · Page 6Linked to original sources
PubMed1988

Antigen absorption by the jejunal epithelium of children with cow's milk allergy.

To establish if intestinal permeability to exogenous antigens is involved in cow's milk allergy (CMA) in infants, 33 children 1 to 24 months old (18 controls and 15 with CMA) were tested for intestinal permeability to the protein marker horseradish peroxidase (HRP). Jejunal biopsies were performed either during the initial period of diagnosis, at the mean (and SE) age of 3 +/- 1 months, and/or 1 yr later, at the age of 13 +/- 2 months, just before and after a milk challenge. A small fragment of the biopsy was studied for histology and the remainder was mounted in an Ussing chamber for simultaneous measurement of mucosal to serosal transport of HRP in its intact and degraded forms and electrical parameters including short-circuit current and conductance. No modification in HRP absorption was noted in control children aged from 2 months to 11 yr, indicating that gut closure probably occurred earlier in life. During the initial period of CMA, transepithelial HRP fluxes were significantly higher, about 8-fold, in children with CMA (intact HRP flux = 48.5 +/- 15.2, 95% confidence interval, 11.2 to 85.7 versus 5.9 +/- 1.2, 95% confidence interval 2.9 to 8.3, in control children). In addition, short-circuit current was increased but conductance was unchanged. After several months on a milk-free diet, HRP flux and short-circuit current returned to control values. Just after the milk challenge and independently of the clinical issue, a slight rise in HRP permeability was observed but it was not significant and remained within control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1987

Intestinal absorption of macromolecules during viral enteritis: an experimental study on rotavirus-infected conventional and germ-free mice.

Epithelial transport and degradation of horseradish peroxidase (HRP), a macromolecular tracer, was studied in conventional and germ-free suckling mice following an experimental infection with rotavirus. Conventional and germ-free mice developed diarrhea from days 2 to 8 postinfection (pi), with growth failure. In mucosal homogenates, infectious virus detected by immunofluorescence on MA 104 cells was present from day 2 through day 8 pi in germ-free mice, but persisted longer (day 13 pi) in conventional mice. Only mild histological lesions were observed during diarrhea, but obvious macrovacuolation of epithelial cells and increased cellular density occurred during the convalescence period (days 9 to 13 pi). Intact and degraded HRP fluxes from mucosa to serosa were measured in vitro on segments of jejunum mounted in Ussing chambers. Both groups of mice developed increased HRP permeability during the experimental period, but at different times after inoculation: during the diarrheal period (days 2 and 3 pi) conventional mouse epithelium absorbed five times more HRP than noninfected controls and during the convalescence period (days 9 to 13 pi) HRP absorption in germ-free mice rose 10-fold as compared to its level before infection. In both cases, this increase in HRP permeability was entirely due to an increase in intact HRP absorption, probably via a transcellular route, and occurred without any alteration in degraded HRP transport. These results indicate that in mice, rotavirus infection causes a transient rise in gut permeability to undegraded proteins. The intestinal microflora seems to affect the timing, magnitude, and duration of this increased permeability.

Animals↗
PubMed1986

Postnatal development of protein absorption in conventional and germ-free mice.

In the jejunal epithelium of adult animals, horseradish peroxidase (HRP) is transported via two functional pathways: a major route involving lysosomal degradation and a minor route allowing transport of the intact protein. The postnatal development of HRP absorption and the influence of conventional microflora were studied in vitro, using jejunal epithelium of conventional and germ-free suckling mice mounted in Ussing chambers. In conventional mice, tritiated peroxidase ([3H]HRP) transport from mucosa to serosa did not change with age except during days 3 and 4, when it increased fivefold. This increase was entirely due to the rise in intact HRP transport and was not related to a decrease in lysosomal cathepsin B and D activities. In germ-free mice, HRP transport developed similarly but decreased by 75% along both pathways. This reduced absorption was associated with lower cathepsin B and D activities. These results strengthen the existence of two transcellular pathways in nonimmunoglobulin protein absorption by the proximal gut with a limiting step situated before the lysosomal system, presumably at the brush-border membrane. Their development is not parallel and does not correlate with gut closure to immunoglobulin transfer.

Animals↗
PubMed1985

Congenital selective malabsorption of glucose and galactose.

We review here the case histories and results of in vivo and in vitro tests for eight children with congenital selective glucose and galactose malabsorption (GGM) whom our laboratory has followed up since 1971. Clinically, GGM was manifested by intractable, acidic, sugar-containing diarrhea that started during the neonatal period. Diarrhea only abated when glucose and galactose were removed from the diet. The disease was notable for the absence of other symptoms, although mellituria was a common finding. Defective sugar transport was permanent, but sugar tolerance appeared to increase with age. In vitro, intracellular mucosal glucose concentration (C) was significantly below control level in GGM intestinal tissue for concentrations (M) of 10 and 0.1 mM glucose in the medium. C/M for galactose also decreased, while the C/M ratios for alanine and xylose were within the control range. Glucose influxes across the luminal membrane, net glucose transepithelial fluxes, and electrical parameters were all consistent with defective sodium and glucose cotransport at the brush border membrane of jejunal epithelial cells. However, the present results are also consistent with a small residual active transport system observed only at low glucose concentration in the medium. Further observations are needed to establish the role of glucose transport systems in absorption of other monosaccharides, the relationship between kidney and intestinal sodium-glucose cotransport systems, and their genetic control.

Biological Transport, Active↗
PubMed1984

Macromolecular transport in jejunal mucosa of children with severe malnutrition: a quantitative study.

Small intestinal permeability to horseradish peroxidase (HRP) was assessed in jejunal biopsies of malnourished children. Clinical examination, intestinal function (D-Xylose test), and the histological appearance of the mucosa were assessed in 14 children during the malnutrition phase and in eight children after 3 months of nutritional rehabilitation. Macromolecular permeability was evaluated by measuring transepithelial HRP fluxes from mucosa to serosa (JHRPms) using Ussing chambers. Intact HRP transport, i.e., nondegraded protein transport, was measured by enzyme assay, and tritiated HRP was concomitantly used to measure intact and degraded HRP fluxes (J[3H]HRPms). Electrical parameters (short-circuit current, potential difference, and ionic conductance) were also recorded. Transepithelial HRP fluxes were significantly higher during malnutrition (JHRPms = 8.85 +/- 1.44; J[3H]HRPms = 77.11 +/- 10.66 pmol X h-1 X cm-2) than in the same children after 3 months of nutritional rehabilitation (JHRPms = 2.94 +/- 1.10; J[3H]HRPms = 22.93 +/- 8.15 pmol X h-1 X cm-2). The total ionic conductance, which is an index of paracellular permeability, did not change significantly. Calculated intratissue degradation of the protein did not appear to alter during malnutrition. These results point to a clinical situation in which malnutrition with diarrhea in children is associated with increased intestinal permeability to macromolecules by a mechanism not related to any paracellular leak of the protein, but rather to increased transcellular absorption.

Acute Disease↗
PubMed1984

[Systems of membrane transport, genetics and nutrition; the example of congenital anomalies of intestinal transport in children].

As the plasma membrane of the cell, the intestinal epithelium ensures the selective functions of the entry and exit of nutriments or metabolites. These functions are controlled genetically by structural genes and eventually by regulatory genes which direct the expression of the former. The influence of some essential nutriments also plays a role. These aspects are illustrated for microorganisms. Selective, congenital intestinal malabsorptions, which are hereditary, occur in humans; their study leads to a better understanding of the genetic and nutritional control of transport mechanisms. Known anomalies of the intestinal transport of basic amino acids have been studied by showing the probable relationships with selective reabsorption deficiencies in the renale tubule and possible disorders of the urea cycle. Amino acid transport through the intestinal epithelium may be under a dual genetic control i.e. at the brush border (co-transport with sodium) as well as at the basal-lateral membrane (diffusion). It is emphasized that small peptides must be present in dietary solutions of enteral origin for amino acid absorption to be optimal. Selective malabsorption of glucose and galactose due to loss of the co-transport systems of glucose-sodium and galactose-sodium at the brush border is discussed. A comparison is made with anomalies of glucose reabsorption in the renal tubule. The digestive consequences (watery diarrhea) of the absence of sodium co-transports has been underlined. A generalization is proposed.

Amino Acids↗
PubMed1983

Horseradish peroxidase transport across rabbit jejunum and Peyer's patches in vitro.

Uptake and transport of horseradish peroxidase (HRP) have been observed in both Peyer's patches (PP) and jejunal epithelium (JE), and the quantities transported across each tissue were compared. Steady-state was reached much faster in PP than in JE. In Ringer solution, no significant difference was found between the HRP fluxes conveyed through PP and JE. In the presence of 10 mM glucose, slight net secretion was observed in JE but not in PP. In both tissues, the transport mechanism was shown to be sensitive to metabolic inhibitors. By contrast, in PP, ammonia did not significantly enhance intact HRP fluxes. Intracellular transfer and catabolism were estimated by measuring transepithelial fluxes of tritiated HRP. In PP, fluxes from mucosa to serosa and from serosa to mucosa were both greatly reduced (9.18 +/- 3.9 and 10.5 +/- 5.1 pmol X h-1 X cm-2, respectively) compared with JE (106.02 +/- 16 and 31.3 +/- 9.3). These results indicate that intact HRP fluxes are similar in PP and JE, but that tritiated HRP fluxes (intact plus degraded HRP fluxes) are smaller in PP. Together, these results suggest that the specific characteristics of HRP transport across PP are fast uptake and reduced degradation.

Animals↗
PubMed1982

Horseradish peroxidase transport across adult rabbit jejunum in vitro.

Quantification and functional characteristics of intact protein uptake, metabolic behavior, and transmission across the intestinal wall were examined using horseradish peroxidase (HRP) transport through adult rabbit jejunum. Transepithelial HRP fluxes were determined with a modified Ussing apparatus. In Ringer solution, no significant difference was found between intact HRP fluxes from mucosa to serosa (JHRPm leads to s) and those from serosa to mucosa (JHRPs leads to m) (3.12 +/- 0.58 and 3.48 +/- 0.45 pmol.h-1.cm-2, respectively). In the presence of 10 mM glucose, slight net secretion was noted. The transport mechanism was shown to be sensitive to metabolic inhibitors, colchicine, and ammonia. Intracellular transfer and catabolism were estimated by measuring transepithelial fluxes of tritiated horseradish peroxidase (J[3H]HRP). Net absorption of 3H equivalent HRP (91 +/- 32 pmol.h-1.cm-2) occurred chiefly in the form of tritiated degraded catabolites of 2-4 kilodaltons. Comparison of the transepithelial fluxes of intact and 3H equivalent HRP made it possible to estimate that 97% of the HRP was degraded while crossing the tissue from mucosa to serosa and 88% while crossing from serosa to mucosa. The saturable absorption observed for JHRPm leads to s became a nonsaturable process for J[3H]HRPm leads to s. These results fit the existence of at least two functional pathways for intestinal protein transport. The main route seems to involve endocytosis, with striking intracellular degradation, possibly during passage through the lysosomal system. The HRP that escapes metabolic degradation is transported by an alternative route requiring the structural and metabolic integrity of the epithelial cells. Although this route only accounts for a small fraction of HRP transport, it may be of immunological importance.

Animals↗
PubMed1982

[Intestinal malabsorption of glucose and galactose. Study of a family].

A girl with congenital glucose-galactose malabsorption and her two parents were studied. Hydrogen breath tests performed on the child during glucose and galactose tolerance tests (0.5 g/kg) were positive (increase in expired pH concentration of 21 p.p.m. and 32.5 p.p.m. from the basal level respectively). This was negative for fructose (2 g/kg). In vitro intestinal transport studies showed: 1) a selective decrease in active glucose accumulation (intracellular concentration 0.34 mM in 0.1 mM glucose bathing solution - controls: 1.58 +/- 0.56 (means +/- SD), and 12.1 mM in 10 mM bathing solution - controls: 38.4 +/- 12.4). 2) absence of net glucose absorption during in vitro Ussing chamber measurements with a marked decrease in mucosal membrane glucose permeability. For the parents, the hydrogen breath test was negative after glucose and galactose ingestion (2 g/kg) and intestinal transport was normal (father; intracellular concentration 1.32 mM and mother 2.04 for 0.1 mM bathing glucose concentration). The marked decrease in brush border permeability explains the absence of net glucose absorption in the child. The parents who are presumed to be heterozygotes did not exhibit any detectable transport defect.

Adult↗
PubMed1981

Relationship between transport of D-xylose and other monosaccharides in jejunal mucosa of children.

In order to clarify the relationship between the transport of D-xylose, D-glucose, and Na in human gut, several characteristics of D-xylose uptake were examined in jejunal biopsies from 47 children (45 with normal intestinal function and 2 with glucose-galactose malabsorption). Standard in vitro techniques were used, with the following results: In tissue accumulation experiments with Ringer solution, the intracellular D-xylose concentration (C) was not significantly different from the medium D-xylose concentration (M) (C/M = 1.10 +/- 0.08). D-Xylose uptake was not affected by the disappearance of the Na electrochemical gradient in the presence of ouabain or DNP (C/M = 1.02 +/- 0.16 and 0.96 +/- 0.04, respectively). However, in Na-free solution, D-xylose uptake decreased (C/M = 0.47 +/- 0.08). The influx of 10 mM D-xylose across the luminal membrane (Jmcxyl = 1.34 mumol/h . cm2) was not significantly influenced by 2 mM phlorizin (Jmcxyl - 1.25 mumol/h . cm2), which is a competitive inhibitor of D-glucose transport. Removal of Na from the incubation medium, reduced Jmcxyl by 55%. Galactose (40 mM) and fructose (40 mM) did not inhibit Jmcxyl (2.18 and 2.27 mumol/h . cm2, respectively). In Ussing chambers, D-xylose did not stimulate the short-circuit current (Isc), neither did it interfere with the increase in Isc induced by glucose. In the congenital absence of glucose and galactose active transport, D-xylose entry into the cell was unaltered. These results support the concept that in jejunal mucosa of children, D-xylose is at least in part, transported by a system that is different from those for fructose and Na-dependent D-glucose (hexose) transport.

Adolescent↗
PubMed1980

Xylose transport pathways in rabbit ileum.

The D-xylose transepithelial transport mechanism was examined in rabbit ileum in vitro. The net flux of D-xylose (Jxylnet) from mucosa to serosa is abolished in the presence of 10(-4) M ouabain. D-Xylose stimulates the net flux of sodium (JNanet) and the short-circuit current (Isc) equally. The D-xylose concentration at which delta Isc reaches half its maximal value is 70 +/- 5 mM. The steady-state intracellular D-xylose concentration ([X]c) is lower than the extracellular concentration in all the situations examined. However, [X]c is Na dependent. The unidirectional influx across the luminal membrane (Jxyl m leads to c) decreases by 50% in the absence of Na; the Na-dependent Jxyl m leads to c is entirely inhibited by D-galactose (40 mM). However, in the absence of Na, Jxyl m leads to c is not inhibited by D-galactose, D-fructose, D-mannose, 2-deoxy-D-glucose or phloretin. In the absence of Na, J xyl m leads to c is a linear function of extracellular D-xylose concentrations up to 300 mM. In the presence of 10 mM D-glucose, there is a linear relationship between transepithelial D-xylose permeability, and polyethylene glycol (4,000 mol wt) permeability. These results indicate the possible existence of a cellular and a paracellular route for D-xylose and related molecules.

Animals↗
PubMed1980

Cystinuria: reduced lysine permeability at the brush border of intestinal membrane cells.

Na-dependent L-lysine epithelial transport was assessed in vitro by measuring the intracellular accumulation and unidirectional influx across the enterocyte brush border membrane. Pieces of jejunum were obtained by peroral biopsies from 27 "control" children and 2 cystinuric patients. In these patients, the following observations are recorded: 1) Na-dependent lysine intracellular accumulation is eliminated; 2) Na-independent accumulation persists (the accumulation ratio is 1.69 +/- 0.34); 3) Na-intracellular concentration is significantly higher in cystinuric patients (60.2 +/- 4.2 mEq/liter) than in controls (42.0 +/- 4.2 mEq/liter), and 4) lysine influx at the luminal membrane is measurable only in tracer amounts, both in the presence of Na (0.17 +/- 0.03 mumole/h cm2) and in it absence (0.22 +/- 0.09 mumole/h cm2). These results suggest a specific loss of Na-dependent L-lysine transport at the luminal membrane of the enterocyte in both the patients with cystinuria. The basolateral membrane is probably permeable to L-lysine.

Adult↗
PubMed1979

Possible sodium and D-glucose cotransport in isolated jejunal epithelium of children.

Some experimental data in human jejunum suggest a Na dependence for glucose absorption and a glucose dependence for Na absorption. However, the relationship between these two transport processes is not yet known. Na+ and D-glucose absorptions were, therefore, measured simultaneously, in vitro, in isolated jejunal mucosa of children. The results are as follows: 1) the steady-state accumulation of D-glucose (C/M glucose) is a function of the Na concentration gradient between cell and medium (C/M Na). In Ringer solution, C/M glucose = 3.97 and C/M Na = 0.29; in the presence of 10(-4) M ouabain, C/M glucose = 1.63 and C/M Na = 0.60, and in Na free solution, C/M glucose = 0.99. In the presence of phloridzin, C/M Na is not statistically different from that in Ringer, but C/M glucose is significantly decreased. 2) The influx of D-glucose at the luminal membrane is a function of Na concentration in the bathing solution; it has the value of 4.41 mumole/hr cm2 in the presence of Na and of 1.65 mumole/hr cm2 in absence of Na. 3) The short-circuit current is a saturable function of D-glucose and of 3-O-D-methylglucose. The Kt for glucose is 8.01 mM. These results support the concept of a coupling between Na and D-glucose absorptions at the luminal membrane of jejunal mucosa of children.

Animals↗
PubMed1975

[Relationship between the structure and activity of a histamine-blocking serum glycoprotein].

A plasmatic glycoprotein is submitted to a mild periodate oxydation and its pharmacological activity is studied. This glycoprotein contains much N acetyl Neuraminic Acid (NANA = 15 p. cent), and it reduces the biological activity of histamine on smooth muscle such as guinea pig ileum. See article. We also identify the 8 NANA and 7 NANA derivaties. Th only 8 carbon derivative is obtained when about one mole of m-periodate is consumed for one mole of NANA. The 7 carbon derivative appears as soon as the consumption of a second mole leads ta a second cleavage. These results prove that the oxydation islimited to the sole N acetyl neuraminic acid and more precisely to the lateral polyhydroxylic chain. Under these conditions, pharmacological activity gradually decreases, it disappears as soon as the lateral polyhydroxylic chain is completely cut off.

Animals↗
PubMedDate not supplied

Phenotypic and functional characterization of intestinal epithelial exosomes.

Intestinal epithelial cells (IEC) are located at a strategic position between the external environment and the most extended lymphoid tissue in the body. Besides their central role in the absorption of nutrients, IEC also provide antigenic information to the immune system and are involved in the balance tolerance/allergy to food antigens. Like professional antigen presenting cells, IEC have been shown to secrete 30- to 90-nm diameter vesicles named exosomes, in a polarized way, either from their apical or basolateral side. These vesicles carry molecules involved in adhesion and antigen presentation, comprising major histocompatibility complex (MHC) class I and class II molecules, tetraspan proteins, CD26/dipeptidyl-peptidase IV, and A33 antigen, a molecule essentially restricted to the intestinal epithelium. Invariant chain, transferrin receptor, and Na-K-ATPase are not expressed on epithelial exosomes. In vivo, in mice, epithelial exosomes carrying MHC/ovalbumin peptide complexes induce specific immune responses when injected intraperitoneally. A33 antigen, an Ig-like molecule highly specific for intestinal epithelial cells and enriched in epithelial exosomes, is found at the surface of cells entering mesenteric lymph nodes suggesting exosome migration from the epithelial layer to the gut associated lymphoid system. Taken together, intestinal epithelial exosomes released at the basolateral surface of enterocytes could be antigen-carrying structures constituting a link between luminal antigens and the local immune system and acting as sensors of the antigenic information present in the intestinal lumen.

Animals↗
PubMedDate not supplied

A comparison of the families of mothers with borderline and nonborderline personality disorders.

The purpose of this study was to evaluate the families of procreation of mothers with borderline personality disorder (BPD) on measures of family stability, family satisfaction, and family environment. Families of nine BPD mothers were compared with families of 14 mothers with other personality disorders using a semi-structured interview to evaluate family history, the Family Environment Scale (FES), and the Family Satisfaction Scale (FSS). Families of procreation of BPD mothers were more unstable than comparison group families. FES scores of BPD mothers were significantly lower than controls in cohesion and organization, but not in conflict. Instability and low family cohesion are common in families of BPD mothers, and may place their children at increased risk for development of psychopathology.

Adolescent↗