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  • 1.
    Bak, Zoltan
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Abildgård, Lars
    Lisander, Björn
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences.
    Janerot Sjöberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Transesophageal echocardiographic hemodynamic monitoring during preoperative acute normovolemic hemodilution2000In: Anesthesiology, ISSN 0003-3022, Vol. 92, no 5, p. 1250-1256Article in journal (Refereed)
    Abstract [en]

    Background: Preoperative acute normovolemic hemodilution may compromise oxygen transport. The aims of our study were to describe the hemodynamic effects of normovolemic hemodilution and to determine its effect on systolic and diastolic cardiac function by multiplane transesophageal echocardiography.

    Methods: In eight anesthetized patients (aged 13-51 yr) without heart disease, hemoglobin was reduced in steps from 123 ± 8 (mean ± SD) to 98 ± 3 and to 79 ± 5 g/l. Hemodynamic measurements (intravascular pressures, thermodilution cardiac output, and echocardiographic recordings) were obtained during a stabilization period and at each level of hemodilution. Left ventricular wall motion was monitored continuously, and Doppler variables, annular motion, and changes in ejection fractional area were analyzed off-line.

    Results: During hemodilution, cardiac output by thermodilution increased by 16 ± 7% and 26 ± 10%, corresponding well to the increase in cardiac output as measured by Doppler (difference, 0.32 ± 1.2 l/min). Systemic vascular resistance fell 16 ± 14% and 23 ± 9% and pulmonary capillary wedge pressure increased slightly (2 ± 2 mmHg), whereas other pressures, heart rate, wall motion, and diastolic Doppler variables remained unchanged. Ejection fractional area change increased from 44 ± 7% to 54 ± 10% and 60 ± 9% as a result of reduced end-systolic and increased end-diastolic left ventricular areas.

    Conclusions: A reduction in hemoglobin to 80 g/l during acute normovolemic hemodilution does not normally compromise systolic or diastolic myocardial function as determined by transesophageal echocardiography. Preload, left ventricular ejection fraction, and cardiac output increase with a concomitant fall in systemic vascular resistance.

  • 2.
    Bak, Zoltan
    et al.
    Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Center. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Eriksson, Olle
    Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Arts and Sciences.
    Steinvall, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Janerot Sjöberg, Birgitta
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Hemodynamic Changes During Resuscitation After Burns Using the Parkland Formula2009In: Journal of Trauma, ISSN 0022-5282, E-ISSN 1529-8809, Vol. 66, no 2, p. 329-336Article in journal (Refereed)
    Abstract [en]

    Background: The Parkland formula (2-4 mL/kg/burned area of total body surface area %) with urine output and mean arterial pressure (MAP) as endpoints; for the fluid resuscitation in burns is recommended all over the world. There has recently been a discussion on whether central circulatory endpoints should be used instead, and also whether volumes of fluid should be larger. Despite this, there are few central hemodynamic data available in the literature about the results when the formula is used correctly.

    Methods: Ten burned patients, admitted to our unit early, and with a burned area of >20% of total body sur-face area were investigated at 12, 24, and 36 hours after injury. Using transesophageal echocardiography, pulmonary artery catheterization, and transpulmonary thermodilution to monitor them, we evaluated the cardiovascular coupling when urinary output and MAP were used as endpoints.

    Results: Oxygen transport variables, heart rate, MAP, and left ventricular fractional area, did not change significantly during fluid resuscitation. Left ventricular end-systolic and end-diastolic area and global end-diastolic volume index increased from subnormal values at 12 hours to normal ranges at 24 hours after the burn. Extravascular lung intrathoracal blood volume ratio was increased 12 hours after the burn.

    Conclusions: Preload variables, global systolic function, and oxygen transport recorded simultaneously by three separate methods showed no need to increase the total fluid volume within 36 hours of a major burn. Early (12 hours) signs of central circulatory hypovolemia, however, support more rapid infusion of fluid at the beginning of treatment.

  • 3.
    Brauckhoff, M.
    et al.
    Department of General, Visceral, and Vascular Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle/Saale, Germany.
    Stock, K.
    Department of Diagnostic Radiology, Martin-Luther-University of Halle-Wittenberg, Halle-Wittenberg, Germany.
    Stock, S.
    Department of Diagnostic Radiology, Martin-Luther-University of Halle-Wittenberg, Halle-Wittenberg, Germany.
    Lorenz, K.
    Department of General, Visceral, and Vascular Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle/Saale, Germany.
    Sekulla, C.
    Department of General, Visceral, and Vascular Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle/Saale, Germany.
    Brauckhoff, K.
    Department of General, Visceral, and Vascular Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle/Saale, Germany.
    Thanh, P.N.
    Department of General, Visceral, and Vascular Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle/Saale, Germany.
    Gimm, Oliver
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Spielmann, R.P.
    Department of Diagnostic Radiology, Martin-Luther-University of Halle-Wittenberg, Halle-Wittenberg, Germany.
    Dralle, H.
    Department of General, Visceral, and Vascular Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Straße 40, 06097 Halle/Saale, Germany.
    Limitations of intraoperative adrenal remnant volume measurement in patients undergoing subtotal adrenalectomy2008In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 32, no 5, p. 863-872Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies have shown that a minimum of approximately one-third of one normal adrenal gland is required for sufficient adrenocortical stress capacity. Correlation between intraoperative measurement, determination of remnant size by computed tomography (CT), and adrenocortical stress capacity has not been examined so far. Methods: Twenty-two patients with familial pheochromocytoma (n = 13), sporadic pheochromocytoma (n = 3), and adrenocortical tumors (n = 6) who underwent unilateral or bilateral subtotal adrenalectomy (STAE, 28 adrenal remnants) were prospectively studied. Patients were examined in a multi-slice CT to determine residual adrenal tissue and by ACTH test 4 days and 3 months postoperatively. Results: There was a slight significant correlation between intraoperative and CT calculated volumes (r = 0.77, p < 0.001). However, volumes assessed by CT were almost doubled compared with intraoperative determination (p < 0.001). Although recovery of adrenal function could be observed, no significant changes of remnant volumes could be detected within 3 months. In patients with familial pheochromocytoma, there was a significant correlation between residual adrenal volume and stimulated cortisol levels (P < 0.001). A distinct minimum of adrenal volume for intact adrenocortical stress capacity could not be exactly determined, however, in one patient with only 10% residual adrenal tissue intact stress capacity was found. Conclusions: Residual adrenal tissue of approximately 10-15% offers intact stress capacity. However, an exact determination of the size of an adrenal remnant after STAE has limitations. CT gives larger volumes compared with intraoperative determination. For calculation of a volume-function correlation of residual adrenal tissue, in clinical practice, the determination of relative adrenal residual volume is acceptable. © 2008 Société Internationale de Chirurgie.

  • 4.
    Brauckhoff, Michael
    et al.
    University Halle Wittenberg.
    Machens, Andreas
    University Halle Wittenberg.
    Hess, Soeren
    University Halle Wittenberg.
    Lorenz, Kerstin
    University Halle Wittenberg.
    Gimm, Oliver
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL. Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Brauckhoff, Katrin
    University Halle Wittenberg.
    Sekulla, Carsten
    University Halle Wittenberg.
    Dralle, Henning
    University Halle Wittenberg.
    Premonitory symptoms preceding metastatic medullary thyroid cancer in MEN 2B: An exploratory analysis2008In: SURGERY, ISSN 0039-6060, Vol. 144, no 6, p. 1044-1050Article in journal (Refereed)
    Abstract [en]

    Background. More than 90% of M918T carriers with multiple endocrine neoplasia type 2B (MEN 2B) harbor de novo mutations in the REarranged during Transfection (RET) protooncogene. DNA-based screening for RET germline mutations is rarely useful for early diagnosis, which thus is contingent on the clinical ascertainment of MEN 2B-specifitc symptoms as soon as they emerge. Little information exists about the presence of these symptoms in infancy.

    Methods. Detailed information was gathered regarding the development of MEN 2B-associated symptoms from the parents of 25 M918T RET carriers and 50 age- and sex-matched, controls with the use of a disease-specific questionnaire.

    Results. Until the end of the study, at a median age of 16 2 (range, 0.5-34.9 years), all 25 M918T RET carriers had developed medullary thyroid cancer. By that time, 96%, 91%, 71%, 75%, and 28% Of carriers displayed oral manifestations, ocular abnormalities, intestinal symptoms, musculoskeletal malformations, and pheochromocytoma, respectively. During the first year of life, fewer than 20% of carriers were found to express the typical MEN 2B phenotype, whereas 86% and 61% of these children, but none of the controls, were noted for their inability to cry tears and for constipation.

    Conclusion. Because the classic MEW 2B phenotype is rare during the first year of life, more emphasis should be placed on the more subtle features of the syndrome. Additional studies are needed to validate the usefulness of the symptoms "inability to cry" and "constipation" for earlier diagnosis of MEAT 2B.

  • 5.
    Ekström, T
    et al.
    Östergötlands Läns Landsting.
    Johansson, KE
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Effects of anti-reflux surgery on chronic cough and asthma in patients with gastro-oesophageal reflux disease2000In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 94, no 12, p. 1166-1170Article in journal (Refereed)
    Abstract [en]

    This two-group prospective study evaluated the effect of anti-reflux surgery (fundoplication) on 24 patients with severe gastro-oesophageal reflux disease (GORD) and concomitant asthma (n = 13) or chronic cough (n = 11). Twenty-four hour oesophageal pH monitoring and lung function tests (FEV1, FVC) were done before and within 1 year after anti-reflux surgery. A diary was kept by the patient during the 4-week period prior to surgery and during 4-week periods 6 and 12 months postoperatively, with daily monitoring of peak expiratory flow rate, respiratory and reflux symptoms and medication. In non-asthmatic patients, coughing was reduced by 47% and 80% during the day and night, respectively, 12 months after surgery (Pless than0.01). Concomitant hoarseness and expectoration were also significantly reduced (Pless than0.05). No effect on lung function was seen. In patients with asthma, small, non-significant reductions in asthma symptom scores and consumption of rescue medication were seen Twenty-two patients were completely free from their GORD symptoms after surgery. In conclusion, anti-reflux surgery in patients with GORD had a more favourable effect on concomitant cough than concomitant asthma

  • 6.
    Howell, Viive M
    et al.
    University of Sydney.
    Clarkson, Adele
    University of Sydney.
    Nelson, Anne E
    CSIRO, Australia.
    Delbridge, Leigh W
    University of Sydney.
    Robinson, Bruce G
    Van Andel Research Institute.
    Gimm, Oliver
    Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Marsh, Deborah J
    University of Sydney.
    Accuracy of Combined Protein Gene Product 9.5 and Parafibromin Markers for Immunohistochemical Diagnosis of Parathyroid Carcinoma2009In: JOURNAL OF CLINICAL ENDOCRINOLOGY and METABOLISM, ISSN 0021-972X, Vol. 94, no 2, p. 434-441Article in journal (Refereed)
    Abstract [en]

    Context: Parafibromin, encoded by HRPT2, is the first marker with significant benefit in the diagnosis of parathyroid carcinoma. However, because parafibromin is only involved in up to 70% of parathyroid carcinomas and loss of parafibromin immunoreactivity may not be observed in all cases of HRPT2 mutation, a complementary marker is needed.

    Objective: We sought to determine the efficacy of increased expression of protein gene product 9.5 (PGP9.5), encoded by ubiquitin carboxyl-terminal esterase L1 (UCHL1) as an additional marker to loss of parafibromin immunoreactivity for the diagnosis of parathyroid carcinoma.

    Design: In total, 146 parathyroid tumors and nine normal tissues were analyzed for the expression of parafibromin and PGP9.5 by immunohistochemistry and for UCHL1 by quantitative RT-PCR. These samples included six hyperparathyroidism-jaw tumor syndrome-related tumors and 24 sporadic carcinomas.

    Results: In tumors with evidence of malignancy, strong staining for PGP9.5 had a sensitivity of 78% for the detection of parathyroid carcinoma and/or HRPT2 mutation and a specificity of 100%. Complete lack of nuclear parafibromin staining had a sensitivity of 67% and a specificity of 100%. PGP9.5 was positive in a tumor with the HRPT2 mutation L64P that expressed parafibromin. Furthermore, UCHL1 was highly expressed in the carcinoma/hyperparathyroidism-jaw tumor syndrome group compared to normal (P &lt; 0.05) and benign specimens (P &lt; 0.001).

    Conclusion: These results suggest that positive staining for PGP9.5 has utility as a marker for parathyroid malignancy, with a slightly superior sensitivity (P = 0.03) and similar high specificity to that of parafibromin.

  • 7.
    Keita, Åsa V
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Ericson, Ann-Charlott
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Stress-induced barrier disruption of the follicle-associated epithelium involves corticotropin-releasing hormone, vasoactive intestinal peptide and mast cells2010In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 22, no 7, p. 770-e222Article in journal (Refereed)
    Abstract [en]

    Background The follicle-associated epithelium (FAE) is specialized in uptake and sampling of luminal antigens and bacteria. We previously showed that stress increased FAE permeability in rats. An increased uptake may alter antigen exposure in Peyers patches leading to intestinal disease. The aim of this study was to elucidate mechanisms involved in the acute stress-induced increase in FAE permeability. Methods Rats were pretreated i.p. with corticotropin-releasing hormone receptor (CRH-R) antagonist, neurokinin receptor 1 (NK-1R) antagonist, atropine, the mast cell stabilizer doxantrazole (DOX), or NaCl, and submitted to 1-h acute water avoidance stress. FAE tissues were mounted in Ussing chambers for measurements of permeability to 51Cr-EDTA, horseradish peroxidase (HRP) and chemically killed Escherichia coli K-12. Further, FAE segments were exposed in vitro in chambers to CRH, substance P (SP), carbachol, and DOX. Neurotransmitter- and receptor distribution was studied by immunohistochemistry. Key Results Stress-induced increases in uptake across FAE of HRP and E. coli were reduced by DOX, CRH-R antagonist and atropine, whereas the NK-1R antagonist decreased 51Cr-EDTA permeability. Exposure to CRH and carbachol increased HRP and E. coli passage, whereas SP increased bacterial and 51Cr-EDTA permeability. DOX counteracted all of these effects. Immunohistochemistry revealed CRH, acetylcholine, SP, and their receptors on mast cells within the Peyers patches, subepithelial dome, and adjacent villi. Conclusions & Inferences Corticotropin-releasing hormone and acetylcholine signaling affect mainly transcellular permeability while SP seems more selective toward the paracellular pathways. Our findings may be of importance for the understanding of the pathogenesis of stress-related intestinal disorders.

  • 8.
    Steinvall, Ingrid
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Bak, Zoltan
    Linköping University, Department of Medicine and Health Sciences, Anesthesiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Sjöberg, Folke
    Linköping University, Department of Clinical and Experimental Medicine, Burn Unit . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Plastic Surgery, Hand surgery UHL.
    Acute kidney injury is common, parallels organ dysfunction or failure, and carries appreciable mortality in patients with major burns: a prospective exploratory cohort study2008In: Critical Care, ISSN 1364-8535, E-ISSN 1466-609X, Vol. 12, no R124Article in journal (Refereed)
    Abstract [en]

    Introduction: The purpose of this study was to determine the incidence, time course, and outcome of acute kidney injury after major burns and to evaluate the impact of possible predisposing factors ( age, gender, and depth and extent of injury) and the relation to other dysfunctioning organs and sepsis.

    Method: We performed an explorative cohort study on patients with a TBSA% (percentage burned of total body surface area) of 20% or more who were admitted to a national burn centre. Acute kidney injury was classified according to the international consensus classification of RIFLE ( Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease). Prospectively collected clinical and laboratory data were used for assessing organ dysfunction, systemic inflammatory response, and sepsis.

    Results: The incidence of acute kidney injury among major burns was 0.11 per 100,000 people per year. Of 127 patients, 31 (24%) developed acute kidney injury (12% Risk, 8% Injury, and 5% Failure). Mean age was 40.6 years (95% confidence interval [CI] 36.7 to 44.5), TBSA% was 38.6% (95% CI 35.5% to 41.6%), and 25% were women. Mortality was 14% and increased with increasing RIFLE class (7% normal, 13% Risk, 40% Injury, and 83% Failure). Renal dysfunction occurred within 7 days in 55% of the patients and recovered among all survivors. Age, TBSA%, and extent of full thickness burns were higher among the patients who developed acute kidney injury. Pulmonary dysfunction and systemic inflammatory response syndrome were present in all of the patients with acute kidney injury and developed before the acute kidney injury. Sepsis was a possible aggravating factor in acute kidney injury in 48%. Extensive deep burns (25% or more full thickness burn) increased the risk for developing acute kidney injury early (risk ratio 2.25).

    Conclusions: Acute kidney injury is common, develops soon after the burn, and parallels other dysfunctioning organs. Although acute kidney injury recovered in all survivors, in higher acute kidney injury groups, together with cardiovascular dysfunction, it correlated with mortality.

  • 9.
    Wang, X.-Y.
    et al.
    Intestinal Disease Research Program, McMaster University, Hamilton, Ont., Canada.
    Zarate, N.
    Intestinal Disease Research Program, McMaster University, Hamilton, Ont., Canada, Centre for Academic Surgery, Alexandra Wing, Royal London Hospital, Whitechapel, London E1 1BB, United Kingdom.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Bourgeois, J.M.
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
    Liu, L.W.C.
    Intestinal Disease Research Program, McMaster University, Hamilton, Ont., Canada.
    Huizinga, J.D.
    Intestinal Disease Research Program, McMaster University, Hamilton, Ont., Canada.
    Ultrastructural injury to interstitial cells of Cajal and communication with mast cells in Crohn's disease2007In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 19, no 5, p. 349-364Article in journal (Refereed)
    Abstract [en]

    Crohn's disease associated dysmotility has been attributed to fibrosis and damage to enteric nerves but injury to interstitial cells of Cajal (ICC) could also be involved. We assessed ICC in specimens obtained from patients with Crohn's disease and determined the relation between ICC and the inflammatory infiltrate, particularly mast cells (MC) using quantitative immunohistochemistry and electron microscopy. Ultrastructural injury to ICC was patchy in all ICC subtypes but ICC-Auerbach's plexus (AP) showed damage more frequently, i.e. swelling of mitochondria, decreased electron density, autophagosomes and partial depletion of the cytoplasm. Light microscopy confirmed a significant decrease in c-kit immunoreactivity for ICC-AP and an increased number of MC in the muscularis externa. Electron microscopy showed MC exhibiting piecemeal degranulation and making frequent and selective membrane-to-membrane contact with all types of injured ICC which suggests chronic release of granule content to affect ICC. Extent of ICC injury was not associated with duration of the disease. In conclusion, ultrastructural injury and loss of ICC-AP is evident in Crohn's disease. Epidemiological and morphological data suggest that ICC have the capacity to regenerate in spite of the chronic insult. The muscularis hosts a marked number of MC that exhibit piecemeal degranulation associated with ICC and may facilitate ICC maintenance. © 2007 The Authors.

  • 10.
    Yang, P.
    et al.
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
    Xing, Z.
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
    Berin, C.M.
    Department of Medicine, Division of Clinical Immunology, Mount Sinai School of Medicine, New York, NY, United States.
    Söderholm, Johan D
    Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
    Feng, B.
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
    Wu, L.
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
    Yeh, C.
    Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
    TIM-4 Expressed by Mucosal Dendritic Cells Plays a Critical Role in Food Antigen-Specific Th2 Differentiation and Intestinal Allergy2007In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 133, no 5, p. 1522-1533Article in journal (Refereed)
    Abstract [en]

    Background & Aims: Food allergy accounts for significant morbidity. The etiology and immune mechanisms of food allergy, however, have remained poorly understood. In this study, we aimed to determine the role of T-cell immunoglobulin-domain and mucin-domain (TIM)-4, a recently identified member of cell surface molecules, in the pathogenesis of intestinal allergy in a murine model. Methods: We report that TIM-4 as well as costimulatory molecules were up-regulated in intestinal mucosal dendritic cells by in vitro or in vivo exposure to Staphylococcus enterotoxin B (SEB). SEB-conditioned intestinal dendritic cells loaded with a food macromolecule ovalbumin (OVA) induced potent OVA-specific T-helper (Th)2 lymphocyte responses in vitro and such Th2 responses were inhibited completely by TIM-4 blockade. Results: In vivo exposure to both SEB and OVA resulted in OVA-specific Th2 differentiation and intestinal allergic responses including increased serum immunoglobulin E and Th2 cytokine levels, activation of OVA-specific Th2 cells detected both ex vivo and in situ, and mast cell degranulation. Of importance, in vivo abrogation of TIM-4 or its cognate ligand TIM-1 by using a polyclonal antibody remarkably dampened Th2 differentiation and intestinal allergy. Conclusions: Our study thus identifies TIM-4 as a novel molecule critically required for the development of intestinal allergy. © 2007 AGA Institute.

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