Murine eotaxin: an eosinophil chemoattractant inducible in endothelial cells and in interleukin 4-induced tumor suppression.

Guinea pig eotaxin is a recently described member of the Cys-Cys family of chemokines and is involved in a guinea pig model of asthma. To determine whether eotaxin is a distinctive member of this family and to understand its physiologic role, we have cloned the mouse eotaxin gene and determined its structure and aspects of its biologic function. The sequence relationship between the mouse and guinea pig genes indicates that eotaxin is indeed a distinct member of the chemokine family. Moreover, murine eotaxin maps to a region of mouse chromosome 11 that encodes other Cys-Cys chemokines. In addition, recombinant murine eotaxin protein has direct chemoattractant properties for eosinophils. The eotaxin gene is widely (but not ubiquitously) expressed in normal mice and is strongly induced in cultured endothelial cells in response to interferon gamma. Eotaxin is also induced locally in response to the transplantation of interleukin 4-secreting tumor cells, indicating that it likely contributes to the eosinophil recruitment and antitumor effect of interleukin 4. Such responses suggest that eotaxin may be involved in multiple inflammatory states.     

Nonspecific corticosteroid therapy in patients receiving intra-arterial chemotherapy for hepatic metastases of colorectal origin

Cholestatic jaundice induced by hepatic intra-arterial 5-fluorodeoxyuridine (FUDR) demonstrated marked improvement in three patients following treatment with oral corticosteroids. Subsequent "prophylactic" use allowed continuation of chemotherapy and improved quality of life. Corticosteroid use in selected patients with FUDR-induced cholestatic jaundice may be beneficial.     

Immunologic mechanisms in hypersensitivity pneumonitis: I. Evidence for cell-mediated immunity and complement fixation in pigeon breeders' disease

Immunologic studies were performed on 5 patients with pigeon breeders' disease. Intradermal injection of pigeon serum produced an immediate wheal-and-flare reaction within 15 minutes and a secondary Arthus-type reaction within 4 to 8 hours. Immunofluorescent studies of the secondary reaction site showed IgG, C3, and C4 in 2 patients. Patients' sera produced multiple precipitin bands with pigeon serum when reacted by double diffusion in gel. IgG antibody isolated from each of the patients' serum formed precipitating immune complexes that fixed large amounts of complement (C4) when added to fresh human serum. Peripheral blood lymphocytes from 4 of the 5 patients produced macrophage migration inhibitory factor (MIF) when challenged with dilute pigeon serum. These studies are the first to show complement fixing antibodies and macrophage MIF production by lymphocytes from patients with hypersensitivity lung disease and suggest that both humoral and cellular immunity may be important in the pathogenesis of these disorders.     

Identification of wild-type and mutant p53 peptides binding to HLA-A2 assessed by a peptide loading-deficient cell line assay and a novel major histocompatibility complex class I peptide binding assay

Mutations of the p53 gene are the most frequently observed genetic changes in human cancers; often leading to an overexpression of the wild-type (wt) p53 protein. Demonstrable T cell reactivity against tumor cells overexpressing wt or mutant p53-derived peptides could support the application of such epitopes in cancer immunotherapies. As the binding of peptide to MHC class I molecules is a prerequisite for antigen-specific T cell recognition, we evaluated the ability of wt and mutant p53 peptides to bind to HLA-A2.1 using two independent flow cytometry-based assay systems, the T2 major histocompatibility complex (MHC) class I peptide stabilization assay (stabilization assay) and the peptide-induced MHC class I reconstitution assay (reconstitution assay). The twenty selected wt sequences each conformed to the previously reported HLA-A2.1 peptide binding motif. Seven of the wt p53 and 2/13 mutant p53 peptides derived from the previously chosen wt peptides bound to HLA-A2.1 in both the stabilization and the reconstitution assays. An additional six wt and six mutant p53 peptides, presumably exhibiting lower affinity for HLA-A2.1, were identified only in the reconstitution assay. Those p53 peptides binding HLA-A2.1 may provide useful immunogens for the generation of HLA-A2.1-restricted cytolytic T lymphocytes in vitro and in vivo.     

Early Effects of Abaloparatide on Bone Formation and Resorption Indices in Postmenopausal Women With Osteoporosis

Anabolic osteoporosis drugs improve bone mineral density by increasing bone formation. The objective of this study was to evaluate the early effects of abaloparatide on indices of bone formation and to assess the effect of abaloparatide on modeling-based formation (MBF), remodeling-based formation (RBF), and overflow MBF (oMBF) in transiliac bone biopsies. In this open-label, single-arm study, 23 postmenopausal women with osteoporosis were treated with 80 μg abaloparatide daily. Subjects received double fluorochrome labels before treatment and before biopsy collection at 3 months. Change in dynamic histomorphometry indices in four bone envelopes were assessed. Median mineralizing surface per unit of bone surface (MS/BS) increased to 24.7%, 48.7%, 21.4%, and 16.3% of total surface after 3 months of abaloparatide treatment, representing 5.5-, 5.2-, 2.8-, and 12.9-fold changes, on cancellous, endocortical, intracortical, and periosteal surfaces (p < .001 versus baseline for all). Mineral apposition rate (MAR) was significantly increased only on intracortical surfaces. Bone formation rate (BFR/BS) was significantly increased on all four bone envelopes. Significant increases versus baseline were observed in MBF on cancellous, endocortical, and periosteal surfaces, for oMBF on cancellous and endocortical surfaces, and for RBF on cancellous, endocortical, and intracortical surfaces. Overall, modeling-based formation (MBF + oMBF) accounted for 37% and 23% of the increase in bone-forming surface on the endocortical and cancellous surfaces, respectively. Changes from baseline in serum biomarkers of bone turnover at either month 1 or month 3 were generally good surrogates for changes in histomorphometric endpoints. In conclusion, treatment with abaloparatide for 3 months stimulated bone formation on cancellous, endocortical, intracortical, and periosteal envelopes in transiliac bone biopsies obtained from postmenopausal women with osteoporosis. These increases reflected stimulation of both remodeling- and modeling-based bone formation, further elucidating the mechanisms by which abaloparatide improves bone mass and lowers fracture risk. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Harn- und Analinkontinenz im Alter

Three to four million women suffer from urinary incontinence (UI) in Germany. This number will rise further as life expectancy increases, and there is an annual incidence of newly occurring UI of about 1%. Two thirds of all women with UI suffer additional symptoms of fecal incontinence. The type of incontinence present is diagnosed on the basis of the patient's history, clinical findings, and functional testing. The findings should be interpreted in an age-adjusted manner to avoid overrating (e.g. urethral closure pressure at rest=100?age in cm H₂O). The management of elderly patients focuses on conservative approaches with bladder and intestinal training as well as dietary measures serving to counteract the age-related loss of intellectual abilities. Local estrogen application has a positive effect on all forms of incontinence. Surgical approaches aim at improving symptoms since forced restoration of continence in elderly patients frequently induces voiding disorders.     

Ampullary but not periampullary duodenal diverticula are an etiologic factor for chronic pancreatitis

BACKGROUND: Duodenal diverticula are common incidental findings. Although a definite treatment is rarely required, an association with biliary and pancreatic diseases is often suggested. Our aim was to determine the frequency of complications in relation to the location of the diverticulum. METHODS: We reviewed 64 patients with extraluminal duodenal diverticula. In 24 of these patients the diverticulum was treated surgically. The incidence of symptoms and complications is analyzed and follow-up in 88% of operated patients is presented. RESULTS: Thirty-one patients presented with ampullary, 36 patients with periampullary diverticula. Three patients had both types of diverticula. The indication for surgery in 24 patients was chronic pancreatitis (n = 12), chronic pain (n = 6), diverticular perforation (n = 3), bleeding (n = 2), or jaundice (n = 1). In 7 out of 31 patients with ampullary and none out of 36 patients with periampullary diverticula, chronic pancreatitis was considered to be induced by the diverticulum. Morbidity in 24 operated patients was 17%, no patient died. At follow-up all patients were free of symptoms. CONCLUSION: Extraluminal duodenal diverticula are frequently found. They rarely cause symptoms and need no surgical treatment. While ampullary duodenal diverticula can cause chronic pancreatitis, periampullary duodenal diverticula are no etiologic factor.