Esther Israel - Academia.edu (original) (raw)

Papers by Esther Israel

Journal of Crohn's and Colitis, Jan 16, 2018

in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients were switched fro... more in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade ®) to CT-P13 treatment and followed for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score, and C-reactive protein (CRP) for patients with CD and UC, respectively. Results: A total of 167 patients with IBD (116 with CD and 51 with UC) were included. The Baseline demographics according to the Montreal Classification are shown in Figure. Basal remission 87.4% (146 of 167), 12 months post switch 71.7% (109 of 152). Loss of efficacy at 12 months was 15.7%. 9% of patients discontinued CT-P13 during follow-up. CD patient group 88.8% (103 of 116) of patients with CD were in remission at the time of the switch and 69.7% were in remission at 12 months (P > 0.05. In total, 94.0% (109 of 116) of patients with CD completed 12 months of follow-up. The HB score showed significant changes over the 12-month period (median HB score: 1 [0-1] vs. 1 [0-2] (p = 0.001. No significant changes in median CRP levels were observed at 12 months (p = 0.49). UC patient group 84.3% (43 of 51) of patients with UC were in remission at the time of the switch and 76.7% were in remission at 12 months (p > 0.05). In total, 84.3% (43 of 51) of patients with UC completed 12 months of follow-up. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Significant changes in the median CRP level were observed over the same period (0.8 [0-4] vs. 0.23 [0-0.58]) (p = 0.003). Serious adverse events related to medication were reported in 12 of 167 (7.2%). Conclusions: Switching from infliximab RP to CT-P13 is safe and efficacious at 12 months. Loss of efficacy at 12 months was 15.7%.

American Journal of Physiology-gastrointestinal and Liver Physiology, Jun 1, 1987

It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal matur... more It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal maturational process in the rat. It has also been noted that the microvillus membrane (MVM) of newborn animals differs from adult MVM. The purpose of this study is to document whether thyroid hormone can induce closure in vivo in the rat and to relate this effect of thyroxine to the structural and functional maturation of the intestinal MVM. To assess closure, 2-wk-old rats were fed a rat immunoglobulin G (IgG), and serum antibody binding activity was measured 4 h later. The antibody binding activity of treated animals (T) was 1.5-2 times less than that of controls (C) (P less than 0.001), indicating that thyroxine stimulates closure. The MVM similarly showed signs of maturation. Structural maturation was demonstrated by the lower fluidity of the thyroid-treated animals' membranes. Under the influence of thyroxine, the number of receptors on the MVM for IgG had decreased [2.8 X 10(-7) M (C) vs. 1.7 X 10(-7) M (T)], while the Ka remained the same, demonstrating the functional maturation of the MVM. In conclusion, thyroid hormone can induce both structural and functional maturation of the intestinal MVM and can enhance the intestinal mucosal barrier by decreasing the penetration of antibodies.

Pediatrics in Review, May 1, 2012

Biochemical Society Transactions, 1997

FcRn was originally identified as the receptor responsible for IgG binding to the intestinal epit... more FcRn was originally identified as the receptor responsible for IgG binding to the intestinal epithelium of neonatal rats and mice. FcRn transports IgG from milk across the intestinal epithelial cells of the suckling animal. Subsequently, FcRn was detected in tissues involved in the transmission of IgG from mother to fetus: rat fetal yolk sac, mouse fetal yolk sac and human placental syncytiotrophoblast. In addition, FcRn mRNA has been detected in many tissues of adult rats, mice and humans, and FcRn is present in several adult tissues and in cell lines. The selective protection from catabolism of IgG compared with other immunoglobulins is lost in mice that lack functional FcRn. One function of FcRn in tissues that do not transport IgG, and beyond the perinatal period, is thus to rescue circulating IgG from degradation. These recent observations reveal a more widespread use of FcRn than had been supposed.

This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing d... more This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing drugs and dietary supplements, irritable bowel syndrome, and inflammatory bowel disease.

Annals of Internal Medicine, Oct 1, 1991

Journal of Immunology, Jun 15, 1995

There is considerable evidence to suggest that an FcR similar in structure to class I MHC Ags, ne... more There is considerable evidence to suggest that an FcR similar in structure to class I MHC Ags, neonatal Fc receptor (FcRn), transports IgG across the intestinal epithelium of suckling mice. However, this has not previously been shown definitively, nor has it been shown whether FcRn is the only, or even the major, IgG transporter in the neonatal mouse gut. We report here that neonatal mice homozygous for a targeted disruption of the p2microglobulin (&m) gene, which encodes one subunit of FcRn, had reduced FcRn a-chain at the lumenal plasma membrane of intestinal cells. These mice had strikingly lower serum IgG levels during the first month after birth than littermates that possessed functional FcRn. Furthermore, we found by fostering mice on mothers with a different IgG allotype that all of the IgG in sera of P2rn-l-mice was endogenous, and that none was obtained from milk. We conclude that FcRn is the only transporter of IgG from mother to young in the mouse. The onset of IgG synthesis in mice that received no milk IgG lagged behind that in siblings with normal IgG transport, suggesting that maternal IgG stimulates Ab production in the neonate. We noted no difference between the IgG concentrations in the milk of P2m-" and P2rnflmice, indicating that FcRn is not involved in the secretion of IgG into milk.

Immunology, Dec 1, 1996

The mechanisms that regulate immunoglobulin G (IgG) catabolism are little understood. We have pre... more The mechanisms that regulate immunoglobulin G (IgG) catabolism are little understood. We have previously found unusually low IgG concentrations in sera of mice homozygous for a targeted disruption of the f12-microglobulin gene. We therefore investigated whether this might result, at least in part, from increased clearance of IgG from the systemic circulation in mice lacking 12microglobulin. We compared the half-lives of radiolabelled mouse IgGl injected intravenously into f2-microglobulin-/mice and wild-type or heterozygous siblings. The clearance of 1251_ labelled IgGl was strikingly more rapid in the mice lacking #2-microglobulin. #2-microglobulin-/mice lack functional molecules of the MHC class I-related Fc receptor, FcRn. Some mutations in mouse IgGl that increase its clearance have recently been shown to prevent binding to FcRn in the gut. To determine whether the slower degradation of immunoglobulin in mice with 12microglobulin correlated with the ability of the antibody to bind FcRn, we measured the clearance of chicken IgY, which does not bind this receptor. The 1251-labelled IgY was catabolized equally rapidly in #2-microglobulin-deficient and wild-type mice. We compared the half-lives of the four subclasses of mouse IgG in f2-microglobulin-/-, +1-, and +/+ mice to determine whether the difference we had noted for IgGl was peculiar to this subclass. The '25I-labelled IgG of all subclasses, with the possible exception of IgG2b, was degraded more rapidly in the B2microglobulin-deficient mice than in heterozygous or wild-type siblings. These data suggest that FcRn can protect IgG from degradation, and is therefore important in maintaining IgG levels in the circulation.

Gastroenterology, Sep 1, 1991

An &week-old white male infant presented for assessment of poor weight gain, anemia, and jaundice... more An &week-old white male infant presented for assessment of poor weight gain, anemia, and jaundice. He was born at 37 weeks' gestation after an uncomplicated pregnancy and weighed 2.95 kg. He was exclusively breastfed until 4 weeks of age when, because of poor weight gain, supplementation with iron-fortified cow's milk formula was begun. At 6 weeks of age, he had developed a clear nasal discharge and slight cough and was noted by his pediatrician to be mildly jaundiced. Because of progressive lethargy, pallor, and jaundice, he was referred to a pediatric gastroenterologist at 8 weeks of age. There was no family history of anemia or metabolic or liver disease and no history of exposure to medications or toxins during pregnancy or in the first 8 weeks of life, with the exception of amoxicillin begun on the day before referral for suspected otitis media. Upon physical examination on admission, the infant was pale, wasted, and lethargic and had mild scleral icterus. He was afebrile with a pulse rate of 13O/min and a respiratory rate of 36/min. He weighed 3.23 kg (< 5th percentile for age), his length was 55 cm (between 10th and 25th percentile for age), and head circumference was 39.5 cm (50th percentile for age). The weight-for-height ratio was <5th percentile. There were no rashes, bruising, or edema. The baby had mild chest hyperexpansion with occasional rhonchi and a soft ejection systolic murmur at the cardiac base. The liver was palpable 4 cm below the right costal margin with a 6-cm span to percussion in the midclavicular line. The spleen was not palpable, and there was no ascites. The stool was pale yellow, and results of Hemoccult (SmithKline Diagnostics, Inc., San Jose, CA) were negative. Laboratory investigations showed a hemoglobin of 69 g/L (6.9 g/dL) with a normal mean corpuscular volume and mean corpuscular hemoglobin concentration, and a reticulocyte count of 10%. The blood smear showed a normochro

PubMed, May 1, 1993

In humans, the prenatal transfer of IgG from mother to foetus is facilitated by a receptor for Ig... more In humans, the prenatal transfer of IgG from mother to foetus is facilitated by a receptor for IgG on the placenta. However, amniotic fluid contains IgG of maternal origin, and transfer of swallowed IgG into the circulation from the foetal intestine represents another potential pathway of passive immunization. In this study we assayed for a foetal intestinal IgG receptor to support the hypothesis of this alternate pathway of antibody transfer. Microvillous membrane (MVM) from small bowel of aborted foetuses (18 weeks gestation) were probed with [125I]IgG to detect specific IgG binding sites. Binding was pH dependent and was maximal at pH 6. Competitive inhibition of the binding of [125I]IgG was noted with the addition of increasing amounts of unlabelled IgG. Scatchard analysis showed one binding site with a dissociation constant of 1.58 x 10(-7), similar to that of the IgG receptor described on the suckling rat intestine. The binding of labelled IgG to the human MVM receptor was Fc mediated. These observations provide evidence for an Fc receptor on the human foetal intestine.

Springer eBooks, 1987

In this paper, we have tried to provide evidence for the association between the microvillus memb... more In this paper, we have tried to provide evidence for the association between the microvillus membrane immaturity of young infants/animals and the enhanced attachment and uptake of intestinal antigens and toxins. Finally, we have reviewed observations that growth factors that alter the newborn MVM composition towards maturity may also affect the handling of antigens by the intestinal surface.

Academic Medicine, Nov 1, 2019

Pediatrics in Review, May 1, 2012

Clinical Gastroenterology and Hepatology, May 1, 2020

The New England Journal of Medicine, Jan 27, 2005

... A diagnostic procedure was performed. Differential Diagnosis. Dr. Lynne L. Levitsky: May we r... more ... A diagnostic procedure was performed. Differential Diagnosis. Dr. Lynne L. Levitsky: May we review the bone-age radiograph? ... Klin Wochenschr 1991;69:825-829 CrossRef | Medline. 7. Forsberg G , Hernell O , Melgar S , Israelsson A , Hammarstrom S , Hammarstrom ML . ...

The American Journal of Gastroenterology, Oct 1, 2010

Journal of Pediatric Gastroenterology and Nutrition, Feb 5, 2021

Supplemental Digital Content is available in the text ABSTRACT Objectives: Experimental studies h... more Supplemental Digital Content is available in the text ABSTRACT Objectives: Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established. Methods: This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined. Results: Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30 ng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (P = 0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, P = 0.034). Conclusions: Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.

Journal of Magnetic Resonance Imaging, May 30, 2019

Background: MR enterography (MRE) is the primary modality for evaluating small bowel disease in p... more Background: MR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established. Purpose: To determine whether MRE imaging features are associated with clinical recurrence. Study Type: Retrospective. Populations: Pediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified. Field Strength/Sequence: 1.5T including T 2-weighted single-shot fast spin echo, balanced steady-state free precession, diffusion-weighted, and contrast-enhanced multiphase T 1-weighted gradient recalled echo sequences. Assessment: MREs were reviewed by three radiologists independently for mural thickening, T 2-weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's-related treatment escalation, surgery, or hospitalization. Statistical Tests: Fisher's exact test, Wald chi-square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features. Results: Of 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T 2-weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786). Data Conclusion: MRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6-month period, indicating a potential role for surveillance imaging to assess for subclinical active disease. Level of Evidence: 3 Technical Efficacy: Stage 5

New England Journal of Medicine, 2022

This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing d... more This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing drugs and dietary supplements, irritable bowel syndrome, and inflammatory bowel disease.

Journal of Crohn's and Colitis, Jan 16, 2018

in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients were switched fro... more in patients with Crohn's disease (CD) and ulcerative colitis (UC). All patients were switched from infliximab RP (Remicade ®) to CT-P13 treatment and followed for up to 12 months. The efficacy endpoint was the change in clinical response assessed at 0 and 12 months, according to the Harvey-Bradshaw score and partial Mayo score, and C-reactive protein (CRP) for patients with CD and UC, respectively. Results: A total of 167 patients with IBD (116 with CD and 51 with UC) were included. The Baseline demographics according to the Montreal Classification are shown in Figure. Basal remission 87.4% (146 of 167), 12 months post switch 71.7% (109 of 152). Loss of efficacy at 12 months was 15.7%. 9% of patients discontinued CT-P13 during follow-up. CD patient group 88.8% (103 of 116) of patients with CD were in remission at the time of the switch and 69.7% were in remission at 12 months (P > 0.05. In total, 94.0% (109 of 116) of patients with CD completed 12 months of follow-up. The HB score showed significant changes over the 12-month period (median HB score: 1 [0-1] vs. 1 [0-2] (p = 0.001. No significant changes in median CRP levels were observed at 12 months (p = 0.49). UC patient group 84.3% (43 of 51) of patients with UC were in remission at the time of the switch and 76.7% were in remission at 12 months (p > 0.05). In total, 84.3% (43 of 51) of patients with UC completed 12 months of follow-up. No significant changes in the median partial Mayo score (p = 0.87) were observed at 12 months. Significant changes in the median CRP level were observed over the same period (0.8 [0-4] vs. 0.23 [0-0.58]) (p = 0.003). Serious adverse events related to medication were reported in 12 of 167 (7.2%). Conclusions: Switching from infliximab RP to CT-P13 is safe and efficacious at 12 months. Loss of efficacy at 12 months was 15.7%.

American Journal of Physiology-gastrointestinal and Liver Physiology, Jun 1, 1987

It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal matur... more It has been noted that the closure of the intestinal barrier to immunoglobulins is a normal maturational process in the rat. It has also been noted that the microvillus membrane (MVM) of newborn animals differs from adult MVM. The purpose of this study is to document whether thyroid hormone can induce closure in vivo in the rat and to relate this effect of thyroxine to the structural and functional maturation of the intestinal MVM. To assess closure, 2-wk-old rats were fed a rat immunoglobulin G (IgG), and serum antibody binding activity was measured 4 h later. The antibody binding activity of treated animals (T) was 1.5-2 times less than that of controls (C) (P less than 0.001), indicating that thyroxine stimulates closure. The MVM similarly showed signs of maturation. Structural maturation was demonstrated by the lower fluidity of the thyroid-treated animals&#39; membranes. Under the influence of thyroxine, the number of receptors on the MVM for IgG had decreased [2.8 X 10(-7) M (C) vs. 1.7 X 10(-7) M (T)], while the Ka remained the same, demonstrating the functional maturation of the MVM. In conclusion, thyroid hormone can induce both structural and functional maturation of the intestinal MVM and can enhance the intestinal mucosal barrier by decreasing the penetration of antibodies.

Pediatrics in Review, May 1, 2012

Biochemical Society Transactions, 1997

FcRn was originally identified as the receptor responsible for IgG binding to the intestinal epit... more FcRn was originally identified as the receptor responsible for IgG binding to the intestinal epithelium of neonatal rats and mice. FcRn transports IgG from milk across the intestinal epithelial cells of the suckling animal. Subsequently, FcRn was detected in tissues involved in the transmission of IgG from mother to fetus: rat fetal yolk sac, mouse fetal yolk sac and human placental syncytiotrophoblast. In addition, FcRn mRNA has been detected in many tissues of adult rats, mice and humans, and FcRn is present in several adult tissues and in cell lines. The selective protection from catabolism of IgG compared with other immunoglobulins is lost in mice that lack functional FcRn. One function of FcRn in tissues that do not transport IgG, and beyond the perinatal period, is thus to rescue circulating IgG from degradation. These recent observations reveal a more widespread use of FcRn than had been supposed.

This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing d... more This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing drugs and dietary supplements, irritable bowel syndrome, and inflammatory bowel disease.

Annals of Internal Medicine, Oct 1, 1991

Journal of Immunology, Jun 15, 1995

There is considerable evidence to suggest that an FcR similar in structure to class I MHC Ags, ne... more There is considerable evidence to suggest that an FcR similar in structure to class I MHC Ags, neonatal Fc receptor (FcRn), transports IgG across the intestinal epithelium of suckling mice. However, this has not previously been shown definitively, nor has it been shown whether FcRn is the only, or even the major, IgG transporter in the neonatal mouse gut. We report here that neonatal mice homozygous for a targeted disruption of the p2microglobulin (&m) gene, which encodes one subunit of FcRn, had reduced FcRn a-chain at the lumenal plasma membrane of intestinal cells. These mice had strikingly lower serum IgG levels during the first month after birth than littermates that possessed functional FcRn. Furthermore, we found by fostering mice on mothers with a different IgG allotype that all of the IgG in sera of P2rn-l-mice was endogenous, and that none was obtained from milk. We conclude that FcRn is the only transporter of IgG from mother to young in the mouse. The onset of IgG synthesis in mice that received no milk IgG lagged behind that in siblings with normal IgG transport, suggesting that maternal IgG stimulates Ab production in the neonate. We noted no difference between the IgG concentrations in the milk of P2m-" and P2rnflmice, indicating that FcRn is not involved in the secretion of IgG into milk.

Immunology, Dec 1, 1996

The mechanisms that regulate immunoglobulin G (IgG) catabolism are little understood. We have pre... more The mechanisms that regulate immunoglobulin G (IgG) catabolism are little understood. We have previously found unusually low IgG concentrations in sera of mice homozygous for a targeted disruption of the f12-microglobulin gene. We therefore investigated whether this might result, at least in part, from increased clearance of IgG from the systemic circulation in mice lacking 12microglobulin. We compared the half-lives of radiolabelled mouse IgGl injected intravenously into f2-microglobulin-/mice and wild-type or heterozygous siblings. The clearance of 1251_ labelled IgGl was strikingly more rapid in the mice lacking #2-microglobulin. #2-microglobulin-/mice lack functional molecules of the MHC class I-related Fc receptor, FcRn. Some mutations in mouse IgGl that increase its clearance have recently been shown to prevent binding to FcRn in the gut. To determine whether the slower degradation of immunoglobulin in mice with 12microglobulin correlated with the ability of the antibody to bind FcRn, we measured the clearance of chicken IgY, which does not bind this receptor. The 1251-labelled IgY was catabolized equally rapidly in #2-microglobulin-deficient and wild-type mice. We compared the half-lives of the four subclasses of mouse IgG in f2-microglobulin-/-, +1-, and +/+ mice to determine whether the difference we had noted for IgGl was peculiar to this subclass. The '25I-labelled IgG of all subclasses, with the possible exception of IgG2b, was degraded more rapidly in the B2microglobulin-deficient mice than in heterozygous or wild-type siblings. These data suggest that FcRn can protect IgG from degradation, and is therefore important in maintaining IgG levels in the circulation.

Gastroenterology, Sep 1, 1991

An &week-old white male infant presented for assessment of poor weight gain, anemia, and jaundice... more An &week-old white male infant presented for assessment of poor weight gain, anemia, and jaundice. He was born at 37 weeks' gestation after an uncomplicated pregnancy and weighed 2.95 kg. He was exclusively breastfed until 4 weeks of age when, because of poor weight gain, supplementation with iron-fortified cow's milk formula was begun. At 6 weeks of age, he had developed a clear nasal discharge and slight cough and was noted by his pediatrician to be mildly jaundiced. Because of progressive lethargy, pallor, and jaundice, he was referred to a pediatric gastroenterologist at 8 weeks of age. There was no family history of anemia or metabolic or liver disease and no history of exposure to medications or toxins during pregnancy or in the first 8 weeks of life, with the exception of amoxicillin begun on the day before referral for suspected otitis media. Upon physical examination on admission, the infant was pale, wasted, and lethargic and had mild scleral icterus. He was afebrile with a pulse rate of 13O/min and a respiratory rate of 36/min. He weighed 3.23 kg (< 5th percentile for age), his length was 55 cm (between 10th and 25th percentile for age), and head circumference was 39.5 cm (50th percentile for age). The weight-for-height ratio was <5th percentile. There were no rashes, bruising, or edema. The baby had mild chest hyperexpansion with occasional rhonchi and a soft ejection systolic murmur at the cardiac base. The liver was palpable 4 cm below the right costal margin with a 6-cm span to percussion in the midclavicular line. The spleen was not palpable, and there was no ascites. The stool was pale yellow, and results of Hemoccult (SmithKline Diagnostics, Inc., San Jose, CA) were negative. Laboratory investigations showed a hemoglobin of 69 g/L (6.9 g/dL) with a normal mean corpuscular volume and mean corpuscular hemoglobin concentration, and a reticulocyte count of 10%. The blood smear showed a normochro

PubMed, May 1, 1993

In humans, the prenatal transfer of IgG from mother to foetus is facilitated by a receptor for Ig... more In humans, the prenatal transfer of IgG from mother to foetus is facilitated by a receptor for IgG on the placenta. However, amniotic fluid contains IgG of maternal origin, and transfer of swallowed IgG into the circulation from the foetal intestine represents another potential pathway of passive immunization. In this study we assayed for a foetal intestinal IgG receptor to support the hypothesis of this alternate pathway of antibody transfer. Microvillous membrane (MVM) from small bowel of aborted foetuses (18 weeks gestation) were probed with [125I]IgG to detect specific IgG binding sites. Binding was pH dependent and was maximal at pH 6. Competitive inhibition of the binding of [125I]IgG was noted with the addition of increasing amounts of unlabelled IgG. Scatchard analysis showed one binding site with a dissociation constant of 1.58 x 10(-7), similar to that of the IgG receptor described on the suckling rat intestine. The binding of labelled IgG to the human MVM receptor was Fc mediated. These observations provide evidence for an Fc receptor on the human foetal intestine.

Springer eBooks, 1987

In this paper, we have tried to provide evidence for the association between the microvillus memb... more In this paper, we have tried to provide evidence for the association between the microvillus membrane immaturity of young infants/animals and the enhanced attachment and uptake of intestinal antigens and toxins. Finally, we have reviewed observations that growth factors that alter the newborn MVM composition towards maturity may also affect the handling of antigens by the intestinal surface.

Academic Medicine, Nov 1, 2019

Pediatrics in Review, May 1, 2012

Clinical Gastroenterology and Hepatology, May 1, 2020

The New England Journal of Medicine, Jan 27, 2005

... A diagnostic procedure was performed. Differential Diagnosis. Dr. Lynne L. Levitsky: May we r... more ... A diagnostic procedure was performed. Differential Diagnosis. Dr. Lynne L. Levitsky: May we review the bone-age radiograph? ... Klin Wochenschr 1991;69:825-829 CrossRef | Medline. 7. Forsberg G , Hernell O , Melgar S , Israelsson A , Hammarstrom S , Hammarstrom ML . ...

The American Journal of Gastroenterology, Oct 1, 2010

Journal of Pediatric Gastroenterology and Nutrition, Feb 5, 2021

Supplemental Digital Content is available in the text ABSTRACT Objectives: Experimental studies h... more Supplemental Digital Content is available in the text ABSTRACT Objectives: Experimental studies have shown that vitamin D has an immunomodulatory effect on the innate and adaptive immune systems. Associations between vitamin D deficiency and development or progression of inflammatory bowel diseases (IBDs) are reported, but a cause-and-effect relationship between pretreatment 25 hydroxyvitamin D [25(OH)D] levels and response to anti-tumor necrosis factor-α (anti-TNF) therapy is not established. Methods: This retrospective study evaluated pediatric IBD patients who had 25(OH)D levels drawn within 3 months of initiating infliximab and/or adalimumab treatment. Demographic features, Paris classification, baseline 25(OH)D levels, disease activity, and laboratory results before and after 3 months of anti-TNF therapy were collected. The interaction between vitamin D insufficiency at induction and lack of response to anti-TNF therapy at 3 months was determined. Results: Of the 383 patients, 76 met inclusion criteria. Sixty-five patients (85.5%) had Crohn disease (CD) and 11 (14.5%) had ulcerative colitis. Seven patients had 25(OH)D levels obtained during both infliximab and adalimumab induction; hence 83 subjects were evaluated (infliximab: 70 patients, adalimumab: 13 patients). 25(OH)D <30 ng/mL was found in 55 of 83 (66.3%) subjects. There were no differences in gender, IBD type, disease activity scores between vitamin D-sufficient and vitamin D-insufficient groups. In CD, proximal gastrointestinal tract inflammation was associated with vitamin D insufficiency (P = 0.019), but other Paris classification parameters and laboratory results were similar in 2 groups. Early termination of anti-TNF therapy was significantly higher in patients who had vitamin D insufficiency (14.5% vs 0%, P = 0.034). Conclusions: Vitamin D insufficiency before anti-TNF treatment may result in poor response to induction therapy.

Journal of Magnetic Resonance Imaging, May 30, 2019

Background: MR enterography (MRE) is the primary modality for evaluating small bowel disease in p... more Background: MR enterography (MRE) is the primary modality for evaluating small bowel disease in pediatric Crohn's patients. Standard clinical practice includes imaging patients at diagnosis and during symptomatic recurrence. The role for MRE in surveillance of asymptomatic Crohn's patients has not yet been established. Purpose: To determine whether MRE imaging features are associated with clinical recurrence. Study Type: Retrospective. Populations: Pediatric Crohn's patients who underwent MRE while asymptomatic, defined by pediatric gastroenterologists using a physician global assessment; 35 MREs were identified. Field Strength/Sequence: 1.5T including T 2-weighted single-shot fast spin echo, balanced steady-state free precession, diffusion-weighted, and contrast-enhanced multiphase T 1-weighted gradient recalled echo sequences. Assessment: MREs were reviewed by three radiologists independently for mural thickening, T 2-weighted hyperintensity, diffusion restriction, hyperenhancement, vasa recta engorgement, and overall assessment of disease activity. Two pediatric gastroenterologists reviewed patient medical records for 6 months following MRE to evaluate for recurrence, defined as Crohn's-related treatment escalation, surgery, or hospitalization. Statistical Tests: Fisher's exact test, Wald chi-square test, and model selection by Akaike information criterion minimization were used to assess statistical significance of MRE imaging features. Results: Of 35 MREs identified, seven cases demonstrated clinical recurrence at 6 months (20%); 28 cases remained in remission (80%). Imaging features of active disease were present in 86% of patients with recurrence compared to 29% of patients in remission (P = 0.01). Wall thickening, T 2-weighted hyperintensity, hyperenhancement, and diffusion restriction were significantly associated with recurrence. Multivariate regression analysis determined diffusion restriction to be the best predictor of recurrence within 6 months (P = 0.001, area under the curve 0.786). Data Conclusion: MRE performed on young asymptomatic Crohn's patients can identify patients who have a high probability of developing clinical recurrence in a 6-month period, indicating a potential role for surveillance imaging to assess for subclinical active disease. Level of Evidence: 3 Technical Efficacy: Stage 5

New England Journal of Medicine, 2022

This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing d... more This chapter covers healthy eating and dietary guidelines in adolescence, performance-enhancing drugs and dietary supplements, irritable bowel syndrome, and inflammatory bowel disease.