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Biomedical subjects

M Heyman

Publications and source records attributed to M Heyman.

At least 55 records · Page 3Linked to original sources
PubMed1998

Sensitization to cow's milk proteins during refeeding of guinea pigs recovering from polydeficient malnutrition.

We have previously shown that milk sensitization aggravates intestinal dysfunction in the malnourished guinea pigs, suggesting that it may also impair the recovery from malnutrition. To test this hypothesis, the growing guinea pigs were malnourished by feeding only maize for 7 d and then were refed for 21 d with a balanced diet containing either intact or hydrolyzed cow's milk proteins. The control animals received the hydrolyzed milk protein diet for 28 d. After an initial period of total inhibition of growth owing to maize, guinea pigs gained weight regularly, with both balanced diets, and there was no evidence of mucosal damage at the end of the refeeding period. However, refeeding with intact milk proteins induced milk sensitization, which was demonstrated on the systemic level by the presence of anti-beta-lactoglobulin IgG1 antibodies, and on the local level by the intestinal anaphylaxis measured by the increase in short circuit current induced by beta-lactoglobulin (16.4 +/- 2.6 microA/cm2) in jejunal segments mounted in Ussing chambers. Such an immune sensitization was associated with impaired intestinal permeability, as both the ionic conductance (21.0 +/- 1.6 versus 14.6 +/- 0.7 mS/cm2) and the transepithelial fluxes of horseradish peroxidase (537 +/- 203 versus 152 +/- 28 ng/h x cm2) were significantly increased in guinea pigs refed with the intact milk proteins compared with controls. In contrast, there was no difference in intestinal permeability between controls and guinea pigs refed with the hydrolyzed milk protein diet. These data show that sensitization to cow's milk proteins can develop in guinea pigs recovering from severe malnutrition and may impair full intestinal repair.

Anaphylaxis↗
PubMed1998

Primary hepatic low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) associated with primary biliary cirrhosis.

We describe a case of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the liver of a patient with early-stage primary biliary cirrhosis (PBC). The patient, a 62-year old woman, presented with abnormal liver function tests, a positive antimitochondrial antibody titer (1:160), and a liver mass. The resected mass, 6.0 x 5.0 x 4.0 cm, had the features of MALT-type lymphoma. The neoplastic cells were small lymphoid cells of B-cell lineage that surrounded reactive lymphoid follicles and infiltrated bile ductules to form lymphoepithelial lesions. The uninvolved liver had histologic evidence of early stage PBC, characterized by segmental duct destruction with granulomata and an inflammatory infiltrate in the portal triads composed of lymphocytes, plasma cells, and occasional eosinophils. A periportal lymph node showed histologic features of the hyaline-vascular type of Castleman's disease, without evidence of malignant lymphoma. Low-grade B-cell lymphomas of the MALT type rarely arise in the liver and, to our knowledge, have not been reported previously in association with PBC. The association in this case suggests that chronic antigenic stimulation as a result of PBC induced the accumulation of acquired MALT, which subsequently transformed to low-grade B-cell lymphoma.

Female↗
PubMed1997

Production of arachidonic acid metabolites by the colon adenocarcinoma cell line HT29 cl.19A and their effect on chloride secretion.

Eicosanoids were found in large amounts in the colonic mucosa of patients suffering from inflammatory bowel diseases and colonic adenocarcinoma. The aim of this study was to evaluate the role of the intestinal epithelial cells in the arachidonic acid metabolism and their functional response to certain eicosanoids. We used the human adenocarcinoma epithelial cell line HT29 cl.19A cell, which is an in vitro model of colon carcinoma and ion transport. These cells were found to express 5- and 15-lipoxygenase, leukotriene A4 hydrolase and cyclooxygenase-1 and -2 mRNAs. We observed an arachidonic acid metabolism via 5-lipoxygenase pathway despite the lack of FLAP mRNA expression and that certain eicosanoids such as hydroperoxy- and hydroxyeicosatetraenoic acids stimulate chloride secretion.

Arachidonic Acid↗
PubMed1997

Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS).

Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. By some estimates, the disorder may account for upwards of 10% of hereditary deafness. Previous genetic linkage studies localized the gene to a broad interval on human chromosome 7q22-31.1. Using a positional cloning strategy, we have identified the gene (PDS) mutated in Pendred syndrome and found three apparently deleterious mutations, each segregating with the disease in the respective families in which they occur. PDS produces a transcript of approximately 5 kb that was found to be expressed at significant levels only in the thyroid. The predicted protein, pendrin, is closely related to a number of known sulphate transporters. These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.

Amino Acid Sequence↗
PubMed1997

Inverse correlation between loss of heterozygosity of the short arm of chromosome 12 and p15ink4B/p16ink4 gene inactivation in childhood acute lymphoblastic leukaemia.

Seventy-four patients with acute lymphoblastic leukaemia (ALL) were analysed with limited allelotyping to detect loss of heterozygosity on chromosome segments 6q, 9p, 12p and 13q in order to detect patterns of genetic alteration. In the case of chromosome 9, analyses were also performed to detect inactivation of the p15ink4B and p16ink4 genes by Southern blot and sequencing techniques. The deletion data from these chromosomes were correlated to each other and to clinical features including prognosis. Allelic loss of these chromosomal regions could be detected in 24% (6q), 15% (12p) and 10% (13q) of the patients respectively, whereas aberrations involving 9p were detected in approximately 50% of the cases. There was an inverse correlation between loss of heterozygosity (LOH) for chromosome 12 and inactivation of the p16ink4 gene. This finding may suggest that a leukaemogenic event on chromosome 12p affects the same pathway of cell-cycle control as p16ink4 inactivation or, alternatively, reflects the fact that these mutations tend to occur in cells of different lineages.

Blotting, Southern↗
PubMed1997

Apical effect of diosmectite on damage to the intestinal barrier induced by basal tumour necrosis factor-alpha.

BACKGROUND: In many digestive diseases the intestinal barrier is weakened by the release of proinflammatory cytokines, including tumour necrosis factor-alpha (TNF alpha). AIM: To investigate the protective effect of apical diosmectite on the intestinal dysfunction induced by the proinflammatory cytokine TNF alpha. METHODS: Filter grown monolayers of the intestinal cell line HT29-19A were incubated for 48 hours in basal medium containing 10 ng/ml TNF alpha and 5 U/ml interferon-gamma (IFN gamma). Next, 1, 10, or 100 mg/ml diosmectite was placed in the apical medium for one hour. Intestinal function was then assessed in Ussing chambers by measuring ionic conductance (G) and apicobasal fluxes of 14C-mannitol (Jman), and intact horseradish peroxidase. In control intestinal monolayers, diosmectite did not significantly modify G, Jman, or intact horseradish peroxidase. RESULTS: After incubation with TNF alpha and IFN gamma, intestinal function altered, as shown by the increases compared with control values for G (22.8 (3.7) v (9.6 (0.5) mS/cm2), Jman (33.8 (7.5) v 7.56 (0.67) micrograms/h x cm2), and intact horseradish peroxidase (1.95 (1.12) v 0.14 (0.04) micrograms/h x cm2). G and Jman were closely correlated, suggesting that the increase in permeability was paracellular. Treatment with diosmectite restored al the variables to control values. CONCLUSIONS: Basal TNF alpha disrupts the intestinal barrier through the tight junctions, and apical diosmectite counteracts this disruption.

Gastrointestinal Agents↗
PubMed1997

Zinc and intestinal anaphylaxis to cow's milk proteins in malnourished guinea pigs.

Zinc supplementation could favor recovery from diarrhea in malnourished children. As the recent experimental evidence suggests that oxidative stress and intestinal anaphylaxis may contribute to the intestinal dysfunction associated with malnutrition, we postulated that zinc could act through antioxidant or antianaphylactic properties. Control (C), malnourished (M), and malnourished zinc-treated (MZ) guinea pigs were, respectively, fed a normal 30% protein diet, a low 4% protein diet, and a low 4% protein diet plus 1800 ppm of zinc. Milk proteins were included in the diets to trigger intestinal anaphylaxis. Milk sensitization was assessed by passive cutaneous anaphylaxis (PCA) against beta-lactoglobulin and by intestinal anaphylaxis measured in Ussing chambers by the increase in short circuit-current after addition of beta-lactoglobulin (deltaIsc(betaLg)). Oxidative stress was assessed by intestinal lipid peroxidation. The intestinal secretion was assessed by deltaIsc induced by inflammatory mediators. Malnutrition increased the level of anti-betaLg reaginic antibodies [PCA = 1.19 +/- 0.79 and 0.69 +/- 0.67 log(l/titer) in M versus C guinea pigs, p = 0.07] and enhanced intestinal anaphylaxis (deltaIsc(betaLg)) = 16.4 +/- 9.9 and 9.1 +/- 5.8 microA/cm2 in M versus C guinea pigs, p = 0.07), without inducing intestinal lipid peroxidation. Moreover, malnutrition enhanced significantly the intestinal secretory response to histamine and 5-hydroxytryptamine. Administration of pharmacologic doses of zinc during malnutrition inhibited the increase in milk sensitization induced by malnutrition, both at the systemic [PCA = 0.35 +/- 0.55 log(l/titer) in MZ guinea pigs, p = 0.03 versus M] and intestinal (deltaIsc(betaLg)) = 2.8 +/- 2.5 microA/cm2 in MZ guinea pigs; p = 0.001 versus M) level, and prevented the hypersecretion in response to histamine and 5-hydroxytryptamine. These data suggest that zinc has antianaphylactic and antisecretory properties that may contribute to its capacity to prevent intestinal dysfunction during malnutrition.

Anaphylaxis↗
PubMed1997

Effect of terfenadine on TNF alpha release from peripheral blood mononuclear cells during cow's milk allergy.

BACKGROUND: In infants with cow's milk allergy and intestinal symptoms, peripheral blood mononuclear cells stimulated in vitro with cow's milk proteins, secrete large amounts of the proinflammatory cytokine TNF alpha thus altering intestinal barrier capacity. Terfenadine, an antihistaminic drug, inhibits the release of several inflammatory mediators, including histamine, prostaglandins and leukotrienes. OBJECTIVES: To test the potential ability of terfenadine to inhibit TNF alpha secretion by mononuclear cells from infants with cow's milk allergy. METHODS: Mononuclear cells from infants allergic to cow's milk proteins were stimulated in vitro for 6 days by a mixture of milk proteins (beta-lactoglobulin, alpha-lactalbumin and casein) with or without terfenadine (0.1-1 microM) and culture supernatants were assayed for TNF alpha by enzyme immunoassay. The effect of culture supernatants on intestinal barrier capacity was evaluated by measuring the electrical resistance (index of integrity) of filter-grown HT29-19 A intestinal cells in Ussing chambers. RESULTS: During active cow's milk allergy, mononuclear cells stimulated with cow's milk proteins secreted large amounts of TNF alpha which significantly reduced the electrical resistance of HT29-19 A intestinal cells. There was a dose-dependent decrease in TNF alpha secretion in the presence of terfenadine, with a maximal inhibition of 62% of this secretion at 1 microM. Accordingly, terfenadine-treated mononuclear cells supernatants did not alter the electrical resistance of intestinal HT29.19 A cells. CONCLUSION: These results indicate that in infants with intestinal dysfunction due to cow's milk allergy, terfenadine is a potent inhibitor of the TNF alpha secretion induced by sensitizing milk protein antigens. This inhibition prevents the degradation of intestinal function as measured in an intestinal cell line, in vitro.

Animals↗
PubMed1997

The acute infectious diarrhoeas as diseases of the intestinal mucosa.

One of the intriguing aspects of the acute infectious diarrhoeas is that, while resulting from an infection of the intestinal tract, they only last from a few hours to a few days. The study of the interactions between infectious agents and intestinal epithelium has allowed a better understanding of the cellular and molecular mechanisms that cause the sudden loss of water and electrolytes, the hallmark of acute diarrhoea. These interactions have also led to formulating oral rehydration solutions used worldwide now. They do not, however, allow understanding the short course of most intestinal infections. For that, one has to consider the intestinal epithelium as part of an anatomical and functional system that, including the many types of cells present in the lamina propria, constitutes the intestinal mucosa. Infectious agents interact with the whole of the mucosa, including the cells of the lamina propria. This leads, among other things, to a change in the functions of the epithelial cells and accelerates their turnover. The pathophysiology of the intestinal mucosa leads to better understand the short and benign course of most intestinal infections. It also leads to better understand the physiology of the intestinal mucosa, and the interactions between the body and its nutritional environment.

Acute Disease↗
PubMed1996

The threshold for immune cell reactivity to milk antigens decreases in cow's milk allergy with intestinal symptoms.

BACKGROUND: In cow's milk allergy (CMA) with intestinal symptoms, peripheral blood mononuclear cells (PBMCs) secrete tumor necrosis factor-alpha (TNF-alpha), altering intestinal function. However, the type of cow's milk protein (CMP) that triggers symptoms (intact or intestinally processed) is not known, and neither is the minimal amount required. METHODS: PBMCs were isolated from infants with active CMA or cured infants just before a new challenge and stimulated with intact or intestinally processed CMP. Supernatants were tested for cytokine content and for their ability to perturb intestinal barrier capacity, measured in Using chambers in HT29-19A intestinal cells. RESULTS: PBMCs from infants with active CMA secreted more TNF-alpha, when they were stimulated with intact rather than intestinally processed CMPs, and more TNF-alpha than PBMCs from cured infants. Accordingly, supernatants from PBMCs stimulated with intact but not intestinally processed CMPs significantly increased intestinal permeability. The CMP concentration required to trigger TNF-alpha secretion capable of altering intestinal function was very small in infants with active CMA (approximately 2 micrograms/ml), but about 300 times higher in cured infants. CONCLUSION: Intact rather than intestinally processed proteins stimulate PBMCs to release TNF-alpha and alter intestinal barrier capacity. The threshold for PBMC reactivity to milk antigens drops considerably during active CMA with intestinal symptoms.

Animals↗
PubMed1996

Laparoscopic splenectomy in patients with hematologic diseases.

OBJECTIVE: The authors review their initial experience with laparoscopic splenectomy in patients with hematologic diseases. Efficacy, morbidity, and mortality of the technique are presented, and other patient recovery parameters are discussed. SUMMARY BACKGROUND DATA: Laparoscopic splenectomy is performed infrequently and data regarding its safety and efficacy are scarce. Factors such as a high level of technical difficulty, the potential for sudden, severe hemorrhage, and slow accrual of operative experience due to a relatively limited number of procedures are responsible. The potential patient benefits from the development of a minimally invasive form of splenectomy are significant. METHODS: Clinical follow-up, a prospective longitudinal database, and review of medical records were analyzed for all patients referred for elective splenectomy for hematologic disease from March 1992 to March 1995. RESULTS: Laparoscopic splenectomy was attempted in 43 patients and successfully completed in 35 (81%). Therapeutic platelet response to splenectomy occurred in 82% of patients with immune thrombocytopenic purpura and hematocrit level increased in 60% of patients with autoimmune hemolytic anemia undergoing successful laparoscopic splenectomy. The morbidity rate was 11.6% (5 of 43 patients), and the mortality rate was 4.7% (2 of 43 patients). Return of gastrointestinal function occurred in patients 23.1 hours after laparoscopic splenectomy and 76 hours after conversion to open splenectomy (p < 0.05). Mean length of stay was 2.7 days after laparoscopic splenectomy and 6.8 days after conversion to open splenectomy (p < 0.05). CONCLUSION: Laparoscopic splenectomy may be performed with efficacy, morbidity, and mortality rates comparable to those of open splenectomy for hematologic diseases, and it appears to retain other patient benefits of laparoscopic surgery.

Adolescent↗
PubMed1996

p16INK4/p15INK4B gene inactivation is a frequent event in malignant T-cell lines.

The cell cycle regulators p16INK4 and p15INK4B have been mapped to the minimal region of overlap for chromosome 9p21 deletions, observed in a number of malignancies, suggesting that they could be tumor suppressor genes (TSGs). In the case of p16INK4 this has been further substantiated by the finding of small intragenic mutations. In this study we have investigated the p16INK4 and p15INK4B genes in 16 malignant T-cell lines by means of Southern blot, PCR and sequence analysis. p16INK4 allelic deletions occurred in 15 of 16 cell lines; 12 of which were homozygous and 3 hemizygous. In 1 cell line (DND 41) the remaining p16INK4 allele carried a microdeletion of 29 bp of exon 2, supporting the concept that p16INK4 is a target TSG for deletions on 9p21. Most p16INK4 deletions also included the p15INK4B gene. However, 4 of the cell lines deleted for p16INK4 showed no evidence of p15INK4B loss, indicating that p15INK4B is not the target in these cell lines.

Base Sequence↗
PubMed1996

Intestinal paracellular permeability during malnutrition in guinea pigs: effect of high dietary zinc.

BACKGROUND: Zinc has been shown to have beneficial effects in vitro on epithelial barrier function, and in vivo to reduce intestinal permeability in malnourished children with diarrhoea. AIMS: To determine whether malnutrition alters intestinal paracellular permeability, and whether zinc prevents such alterations. METHODS: Guinea pigs were fed a normal protein diet (NP group), a low protein diet (LP group), or a low protein diet enriched with 1800 ppm zinc (LPZn group) for three weeks. Intestinal permeability was measured on jejunal segments mounted in Ussing chambers by measuring ionic conductance and mucosal to serosal fluxes of 14C-mannitol, 22Na, and horseradish peroxidase. Tight junction morphology was assessed on cryofracture replicas. RESULTS: Mannitol and Na fluxes and ionic conductance increased in the LP group compared with the NP group but remained normal in the LPZn group. Accordingly, jejunal epithelia from the LP group, but not from the LPZn group, showed a small decrease in number of tight junctional strands compared with epithelia from the NP group. Neither malnutrition nor zinc treatment modified horseradish peroxidase fluxes. CONCLUSIONS: Malnutrition is associated with increased intestinal paracellular permeability to small molecules, and pharmacological doses of zinc prevent such functional abnormality.

Animals↗
PubMed1996

Anaphylactic intestinal response to milk proteins during malnutrition in guinea pigs.

We investigated whether sensitization to cow's milk occurs during malnutrition and alters intestinal ion and macromolecular transport. Malnourished guinea pigs received a low-protein diet containing either 4% soy or 4% milk proteins, and well-nourished sensitized controls received 26% soy plus 4% milk proteins. To assess milk sensitization, we measured immunoglobulin (Ig) G and passive cutaneous anaphylactic (PCA) responses to beta-lactoglobulin (beta-Lg) and the intestinal anaphylaxis, reflected by the rise in short-circuit current (delta Isc) induced by beta-Lg in tissues mounted in Ussing chambers. To assess intestinal function, we measured ionic conductance and unidirectional fluxes of -14C-mannitol and -3H-horseradish peroxidase (HRP). In malnourished animals fed milk proteins, IgG, PCA, and delta Isc (beta-Lg) increased more than in well-nourished animals. Ionic conductance and mannitol permeability rose in both malnourished groups. Malnourished animals fed milk proteins also displayed enhanced permeability to HRP. These data suggest that increased paracellular permeability is due to malnutrition per se, whereas increased macromolecular transport seems to require both malnutrition and sensitization. They indicate that intestinal anaphylaxis in response to milk proteins is persistent and even enhanced during experimental malnutrition.

Analysis of Variance↗
PubMed1996

Carbachol, but not forskolin, increases mucosal-to-serosal transport of intact protein in rat ileum in vitro.

The effects of the secretagogues forskolin and carbachol on protein uptake in isolated ileum of rats were studied. The mucosal-to-serosal transport of horseradish peroxidase (HRP, mol mass 40 kDa) was measured in Ussing chambers, and afterwards tissues were processed for electron microscopy. In the absence of secretagogues, the flux of enzymatically active HRP was 5 pmol.cm-2.h-1 at a mucosal concentration of 10 microM. Electron micrographs showed vesicles filled with active HRP in enterocytes but no HRP activity in intercellular spaces. Forskolin decreased HRP activity in the cells. Carbachol increased the amount of HRP-filled vesicles in enterocytes and induced HRP filling in some intercellular spaces and tight junctions in the upper parts of the villi. The transepithelial flux of intact HRP increased more than 2.5-fold. This effect was suppressed by atropine. We conclude that cholinergic activation can increase the uptake of intact protein via endocytosis and the transepithelial passage by the induction of a diffusional paracellular pathway. We speculate that the increased transport of intact protein through the intestinal barrier may influence immunologic sensitization to food allergens.

Animals↗
PubMed1996

Psychopathology in offspring of mothers with borderline personality disorder: a pilot study.

OBJECTIVE: Children of mothers with borderline personality disorder (BPD) were hypothesized to be at greater risk for psychopathology, particularly impulse spectrum disorders, than children of mothers with other personality disorders. METHOD: Twenty-one index children were compared with 23 children of mothers with a nonborderline personality disorder. Diagnoses were obtained using the Kiddie Schedule for Affective Disorders and Schizophrenia-Episodic Version (KSADS-E) and the Child Diagnostic Interview for BPD (CDIB), and functioning was rated with the Child Global Assessment Schedule (CGAS). Physical, sexual, and verbal abuse, as well as family violence and placements, were also assessed. RESULTS: The children of the borderline mothers, as compared with controls, had more psychiatric diagnoses, more impulse control disorders, a higher frequency of child BPD, and lower CGAS scores. There were no differences between the groups for trauma. CONCLUSION: The offspring of borderline mothers are at high risk for psychopathology.

Adolescent↗