Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1

Longitudinal studies in Sudan show ethnic differences in incidence and clinical phenotypes associated with Leishmania donovani. Immunologically, bias in type 1 vs type 2 cytokine responses is important. To determine whether polymorphisms at IL4/IL9 or IFNGR1 contribute to susceptibility, we examined 59 multicase families of visceral leishmaniasis (VL) with/without post Kala-azar dermal leishmaniasis (PKDL). Multipoint nonparametric analysis (Allegro) linked IL4/IL9 to VL per se (P=0.002). Transmission disequilibrium testing with robust variance estimates confirmed association in the presence of linkage between VL per se and IL4 (P=0.008) but not IL9. Stepwise logistic regression analysis showed both IL4RP2 and IL4RP1 markers contributed significantly to the association, suggesting a common disease-associated haplotype. In contrast, IFNGR1 was linked (P=0.031) and associated (P=0.007) to PKDL but not VL or VL per se. Hence, polymorphism in a type 2 cytokine gene influences underlying susceptibility to VL, whereas IFNGR1 is specifically related to susceptibility to PKDL.     

Diagnosis of Helicobacter pylori infection in children: comparison of a salivary immunoglobulin G antibody test with the [(13)C]urea breath test

The prevalence of Helicobacter pylori infection in a population-based sample of 477 children (mean age plus minus standard deviation, 5.8 plus minus 0.5 years) determined by the [(13)C]urea breath test ([(13)C]UBT) was 10.7% (95% confidence interval [CI], 8.1 to 13.8%), and that determined by salivary enzyme-linked immunosorbent assay (ELISA) was 11.9% (95% CI, 9.2 to 15.2%). Compared to the [(13)C]UBT, the sensitivity and specificity of the salivary ELISA were 80.9% (95% CI, 66.3 to 90.4%) and 95.3% (95% CI, 92.7 to 97.1%), respectively.     

Pathological aspects of immunization of mice against influenza virus infection.

Groups of mice were immunized against influenza Ao/NWS virus by a single intranasal administration of inactivated homologous virus, by 2 intranasal doses of vaccine separated by an interval of 2 weeks, or by 2 intraperitoneal doses of the same vaccine. When subjected 2 weeks later to a standard challenge of 6 x 10(5) egg infecting units Ao/NWS virus instilled intranasally, mortality fell significantly from 64% in unimmunized mice to 39% in mice given a single intranasal dose of vaccine and to 29% in animals which received double intranasal vaccine. The best protection was conferred by double intraperitoneal immunization, after which mortality was 10%. Immunity waned with time, since the mortality of mice doubly immunized by the respiratory route and challenged 30 weeks later was 49%. Intrapulmonary lymphoid tissue developed in large amounts in a proportion of mice immunized by all methods and challenged after an interval of 2 weeks. Attention is drawn to this reaction as a possible unfavourable consequence of vaccination. There were no lesions in the lungs or central nervous system after immunization without subsequent challenge. The importance of histopathology in vaccine trials in experimental animals is emphasized by the consistently higher detection rate of lesions in lungs by histological examination than by visual inspection alone.     

Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms

Impaired expression of the FMR1 gene is responsible for the fragile X mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein with RNA-binding properties. Its complex alternative splicing leads to several isoforms, whose abundance and specific functions in the cell are not known. We have cloned in expression vectors, cDNAs corresponding to several isoforms. Western blot comparison of the pattern of endogenous FMR1 proteins with these transfected isoforms allowed the tentative identification of the major endogenous isoform as ISO 7 and of a minor band as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other isoforms (ISO 4, ISO 5) were not expressed at detectable levels. Surprisingly, in immunofluorescence studies, the transfected splice variants that exclude exon 14 sequences (and have alternate C-terminal regions) were shown to be nuclear. Such differential localisation was however not seen in subcellular fractionation studies. Analysis of various deletion mutants suggests the presence of a cytoplasmic retention domain encoded in exon 14 and of a nuclear association domain encoded within the first eight exons that appear however to lack a typical nuclear localisation signal.      

Ligand induced internalization of epidermal growth factor receptors by A431 cells decreases at high cell densities in culture.

Internalization of epidermal growth factor (EGF) receptors by human A431 epidermoid carcinoma cells was studied at various culture densities. The extent of EGF receptor internalization was measured by quantitation of internalized 125I-EGF during incubation at 37 degrees C for 30 min. When cell culture density was below 1 x 10(5) cells/cm2 receptor internalization was active; 30-40% excess moles of ligand over the moles of surface EGF receptors were internalized during this period. However, when culture density increased to above 1.5 x 10(5) cells/cm2 receptor internalization became less extensive, as only 30-50% of ligand bound to the cell surface underwent internalization during 30 min incubation. In parallel with this reduction in receptor internalization, the degradation rate of 35S-methionine labeled EGF receptors was reduced at a high culture density. In contrast with this regulation of receptor internalization, the affinity of EGF receptors for the ligand increased as culture density increased. The extent of EGF-dependent receptor phosphorylation was found to be constant at all culture densities tested. Thus, the observed low level of receptor internalization at high culture densities was not attributable to lower responsiveness of receptors to EGF. These data suggest the presence of an as yet unidentified cell density-dependent mechanism for regulating receptor internalization in cultured A431 cells.     

Burosumab for the Treatment of Tumor-Induced Osteomalacia

Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..     

Needle biopsy of renal allografts: comparison of two techniques

Two techniques for renal allograft biopsy were retrospectively evaluated to compare relative safety and efficacy. After ultrasound (US) localization of the kidney and biopsy with a hand-held 14-gauge cutting needle, an adequate specimen was obtained in 74 of 77 cases (96%). Major complications occurred in six of these 77 cases (8%). One hundred four biopsies were performed by using a smaller 18-gauge cutting needle with a spring-loaded biopsy "gun" and real-time US guidance. With this newer technique, specimens adequate for diagnosis were obtained in 99 biopsies (95%). There was a single major complication with this technique (1%). The 18-gauge needle with real-time US guidance yields comparably adequate specimens with a lower frequency of complications.     

胰腺多房性潴留性囊肿1例

0　引言　胰腺多房性潴留性囊肿极为罕见,我科收治1例,报道如下.1　病例报告　患者,男,29岁,因发现右上腹包块11d入院,缘于11d前无明显诱因感右上腹痛,仅局限于右上腹部,无肩背部放散痛,伴间歇性发热,体温最高达38.3℃,经抗炎,对症治疗无效.并逐渐可触及右上腹有一肿块,在当地医院行穿刺检查为脓血性液体.镜检发现炎性细胞,B超示:胆囊窝下方及右肾内侧及腹腔动脉,下腔静脉外前方可见异常区,大小约9.1cm×6.6cm×7.6cm,边界清楚,形态不规则,内呈蜂窝状,可见多个大小不等的液性暗区,CT示:右上腹部上腔静脉前方6.0cm×9.0cm肿块和周围组织粘…