Biomedical subjects

Gerald Gleich

Publications and source records attributed to Gerald Gleich.

4 recordsLinked to original sources

PubMed2005

Thrombotic microangiopathy associated with the hypereosinophilic syndrome.

BACKGROUND: Hypereosinophilic syndrome (HES), defined as persistent marked eosinophilia of unknown origin complicated by end organ damage, is thought to be due to activation of eosinophils and release of substances that are toxic to various cells and tissues. An association between hypereosinophilia and kidney damage is not well documented. METHODS: We describe two patients with the HES, acute renal failure, and thrombocytopenic hemolytic anemia. Renal biopsy pathology and immunohistochemistry for activated eosinophils were performed. RESULTS: Renal biopsy revealed glomerular thrombosis, proliferative arteritis, and glomerular and tubulointerstitial eosinophil infiltrates. Ultrastructurally, subendothelial glomerular fibrin deposits and numerous luminal platelets characteristic of thrombotic microangiopathy (TMA) were present. Abundant degranulated eosinophils were localized in glomeruli and the interstitium. Immunofluorescence with specific antibody to eosinophil granule major basic protein (MBP) showed striking extracellular MBP deposition within glomeruli, a marker of eosinophil degranulation. Both patients developed TMA. High-dose glucocorticoids achieved sustained decrease of blood eosinophils and improvement of renal function. CONCLUSION: To our knowledge these are the first documented cases of TMA associated with HES. We propose that products released from degranulated eosinophils caused endothelial injury and microvascular thrombosis. Recognition of this serious renal complication associated with blood eosinophilia should prompt early diagnosis and treatment.

Acute Kidney Injury↗

PubMed2005

Eosinophils alter colonic epithelial barrier function: role for major basic protein.

Mucosal eosinophils increase in a number of gastrointestinal diseases that are often associated with altered epithelial barrier function, including food allergic enteropathies and inflammatory bowel diseases. Although eosinophils are known to secrete biologically active mediators including granule proteins, their role in gastrointestinal diseases is uncertain. The aim of this study was to determine the impact of eosinophils on intestinal barrier function. Epithelial barrier function was determined in a coculture of eosinophils and T84 epithelial cells and in a murine model of T helper (Th) type 2-mediated colitis. Coculture conditions resulted in decreased transepithelial resistance (TER) and increased transepithelial flux. Cell-free coculture supernatants contained a > or =5-kDa soluble factor that also diminished TER; these supernatants contained the eosinophil-granule proteins major basic protein (MBP) and eosinophil-derived neurotoxin (EDN). T84 barrier function decreased significantly when basolateral surfaces were exposed to native human MBP but not EDN. Additional studies identified downregulation of the tight junctional molecule occludin as at least one mechanism for MBP action. MBP-null mice were protected from inflammation associated with oxazolone colitis compared with wild-type mice. In conclusion, MBP decreases epithelial barrier function and in this manner contributes to the pathogenesis of inflammatory bowel diseases.

Animals↗

PubMed2002

Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate.

BACKGROUND & AIMS: Eosinophilic esophagitis (EE) shares symptoms with gastroesophageal reflux disease but has distinctive pathologic features and unknown immunopathology. Treatments with antigen restriction or systemic immunosuppression pose problems with compliance and side effects. Topically applied steroids offer an attractive alternative treatment. The aims of this study were to determine the immunopathologic features of EE and the effectiveness of antigen-specific diet restriction (DR) and topical immunosuppression. METHODS: A prospective trial was conducted examining the impact of DR and swallowed fluticasone propionate (FP) on pediatric patients with EE. Clinicopathologic features, including immunohistochemical analysis of the esophageal mucosa, were measured before and after treatment. RESULTS: Immunohistochemical analysis of 11 prospectively identified children showed a significantly greater number of mucosal CD3 and CD8 lymphocytes, as well as CD1a antigen-presenting cells compared with normal controls. DR did not induce clinical improvement in any patients, whereas all children who completed treatment with FP had resolution of symptoms. Posttreatment analysis of proximal and distal esophageal mucosa showed a significant reduction in the number of eosinophils, as well as CD3(+) and CD8(+) lymphocytes compared with pretreatment sections. CONCLUSIONS: EE is characterized by immunologically active esophageal mucosa. FP, not DR, effectively relieves symptoms. FP significantly reduces mucosal inflammation associated with EE.

Adolescent↗

PubMed2002

A role for humoral mechanisms in the pathogenesis of Devic's neuromyelitis optica.

Devic's disease [neuromyelitis optica (NMO)] is an idiopathic inflammatory demyelinating disease of the CNS, characterized by attacks of optic neuritis and myelitis. The mechanisms that result in selective localization of inflammatory demyelinating lesions to the optic nerves and spinal cord are unknown. Serological and clinical evidence of B cell autoimmunity has been observed in a high proportion of patients with NMO. The purpose of this study was to investigate the importance of humoral mechanisms, including complement activation, in producing the necrotizing demyelination seen in the spinal cord and optic nerves. Eighty-two lesions were examined from nine autopsy cases of clinically confirmed Devic's disease. Demyelinating activity in the lesions was immunocytochemically classified as early active (21 lesions), late active (18 lesions), inactive (35 lesions) or remyelinating (eight lesions) by examining the antigenic profile of myelin degradation products within macrophages. The pathology of the lesions was analysed using a broad spectrum of immunological and neurobiological markers, and lesions were defined on the basis of myelin protein loss, the geography and extension of plaques, the patterns of oligodendrocyte destruction and the immunopathological evidence of complement activation. The pathology was identical in all nine patients. Extensive demyelination was present across multiple spinal cord levels, associated with cavitation, necrosis and acute axonal pathology (spheroids), in both grey and white matter. There was a pronounced loss of oligodendrocytes within the lesions. The inflammatory infiltrates in active lesions were characterized by extensive macrophage infiltration associated with large numbers of perivascular granulocytes and eosinophils and rare CD3(+) and CD8(+) T cells. There was a pronounced perivascular deposition of immunoglobulins (mainly IgM) and complement C9neo antigen in active lesions associated with prominent vascular fibrosis and hyalinization in both active and inactive lesions. The extent of complement activation, eosinophilic infiltration and vascular fibrosis observed in the Devic NMO cases is more prominent compared with that in prototypic multiple sclerosis, and supports a role for humoral immunity in the pathogenesis of NMO. Based on this study, future therapeutic strategies designed to limit the deleterious effects of complement activation, eosinophil degranulation and neutrophil/macrophage/microglial activation are worthy of further investigation.

Antibody Formation↗