The use of trimeric isoleucine-zipper fusion proteins to study surface-receptor-ligand interactions in natural killer cells

The ligands for several activating natural killer (NK) cell receptors have not been identified to date. Soluble receptor fusion proteins can be used to stain target cells for the presence of these unidentified ligands. Here, we describe the generation and use of soluble type I NK cell receptor isoleucine-zipper (ILZ) fusion proteins of the immunoglobulin (Ig) superfamily. ILZ-fusion proteins are easy to produce and purify. They form trimeric complexes in solution and display a higher binding avidity than classical immunoglobulin-fusion proteins. ILZ-fusion proteins do not interact with Fc-receptors and can therefore be used to block receptor-ligand interactions in cellular assays. This makes ILZ-fusion proteins a valuable tool to study receptor-ligand interactions in NK cells and other cellular systems.     

Prednisolone plus low-dose aspirin improves the implantation rate in women with autoimmune conditions who are undergoing in vitro fertilization

Objective: To evaluate the effect of prednisolone plus low-dose aspirin (PSL/LDA) in women with autoimmune conditions who were enrolled in an IVF-ET program.

Design: A retrospective clinical study.

Setting: In vitro fertilization unit, Niigata University Hospital, Niigata, Japan.

Patient(s): Three hundred seven women who underwent IVF-ET between January 1996 and December 1997.

Intervention(s): Prednisolone (10 mg/d) and aspirin (81 mg/d) were administered to the women with autoantibodies who chose to participate.

Main Outcome Measure(s): Pregnancy and implantation rates with IVF-ET.

Result(s): Women undergoing IVF who had positive antinuclear antibodies, with or without antiphospholipid antibodies, had significantly lower pregnancy and implantation rates than did women without autoantibodies (14.8% versus 21.7% and 6.8% versus 10.4%, respectively). The administration of PSL/LDA to women with antinuclear antibodies significantly improved the outcome of IVF-ET (40.6% pregnancy rate and 20.3% implantation rate).

Conclusion(s): A high proportion of women who are undergoing IVF-ET have autoantibodies, which are associated with poor IVF outcomes. The administration of PSL/LDA to these women may improve their implantation rate.     

Castleman disease and mimickers: Clinicopathological findings of atypical lymphoproliferative disorders associated with autoimmune disease

Atypical lymphoproliferative disorders (LPDs) related with autoimmune disease (AID) show marked clinicopathological diversity, which are defined as three distinct clinicopathological subtypes such as those resembling Castleman disease (CD), atypical paracortical hyperplasia with lymphoid follicles (APHLF), and atypical lymphoplasmacytic and immunoblastic proliferation (ALPIB). We studied excisional biopsy specimens from 31 patients with atypical LPDs associated with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren syndrome (SjS). The lesions in these 31 cases were classified into 6 (19.4%) cases resembling CD, 14 (45.2%) cases of APHLF, and 11 (35.5%) cases of ALPIB. Five cases (83.3%) resembling CD were in the active stage with systemic symptoms and multicentric lymphadenopathy. Thirteen cases (92.9%) of APHLF showed systemic symptoms, multicentric lymphadenopathy and abnormal laboratory findings. Histologic findings for cases resembling CD were rare in patients with RA and SjS. In AID patients, histologic findings for cases resembling CD or APHLF findings correlated with disease activity and multicentric lymphadenopathy. Six cases (54.5%) of ALPIB were in the active phase with systemic symptoms and multicentric lymphadenopathy. ALPIB tended to be unrelated to AID activity, especially in the majority of patients with no abnormal laboratory findings. Atypical LPDs associated with AID is a group of diseases that may be overdiagnosed and overtreated. The diagnosis of atypical LPDs associated with AID requires an understanding of the histological findings as well as a comprehensive assessment of the presence of systemic symptoms, the distribution of lymphadenopathy, and abnormal laboratory findings.     

Insights into Genetic Characteristics and Virological Features of Endemic Avian Influenza A (H9N2) Viruses in Egypt from 2017–2021

From 2010 to 2013, genotype I avian influenza A(H9N2) viruses of the G1-lineage were isolated from several poultry species in Egypt. In 2014, novel reassortant H9N2 viruses were detected in pigeons designated as genotype II. To monitor the subsequent genetic evolution of Egyptian A(H9N2) viruses, we characterized the full genomes of 173 viruses isolated through active surveillance from 2017 to 2022. In addition, we compared the virological characteristics and pathogenicity of representative viruses. Phylogenetic analysis of the HA indicated that all studied sequences from 2017–2021 were grouped into G1-like H9N2 viruses previously detected in Egypt. Phylogenetic analysis indicated that the Egyptian A(H9N2) viruses had undergone further reassortment, inheriting four genes (PB2, PB1, PA, NS) from genotype II, with their remaining segments deriving from genotype I viruses (these viruses designated as genotype III). Studying the virological features of the two most dominant genotypes (I and III) of Egyptian H9N2 viruses in vitro and in vivo indicated that both replicated well in mammalian cells, but did not show any clinical signs in chickens, ducks, and mice. Monitoring avian influenza viruses through surveillance programs and understanding the genetic and antigenic characteristics of circulating H9N2 viruses are essential for risk assessment and influenza pandemic preparedness.     

HZ08有关物质的色谱-质谱结构鉴定

 目的 采用色谱-质谱联用技术对HZ08的有关物质进行结构鉴定。方法 采用Sapphire C₁₈ (4.6 mm×250 mm, 5 μm)色谱柱,甲醇-甲酸醋酸铵溶液(1 L中含有甲酸1.0 mL和醋酸铵2.0 g)流动相梯度洗脱,对HZ08及其酸、碱、光照破坏的有关物质进行分离;电喷雾正离子化测定各有关物质的一级和二级质谱,进行解析鉴定。结果 HZ08中检测到1个含量超过0.1%的有关物质,酸破坏生成4个主要降解有关物质,碱破坏和光照破坏各生成1个主要降解杂质;并通过联用技术和有机反应机制解析确证它们的结构。结论 色谱-质谱联用技术能够有效的鉴定药物有关物质,HZ08有关物质鉴定结果对其质量控制和工艺优化提供了参考依据。
     

Correlation between echocardiographic superior vena cava flow and short-term outcome in infants with asphyxia

Objectives

To assess the relationship between superior vena cava (SVC) flow and short-term outcome in infants with perinatal asphyxia.

Methods

Infants in sequence born after more than 35 weeks of gestation who had been hospitalized at the NICU and normal neonatal wards of Wakayama Medical University between May 2005 and September 2010 were recruited for this observational cohort study. The study eligibility criterion was the presence of perinatal asphyxia, as evidenced by abnormal fetal heart rate monitoring and an Apgar score of 7 or less at 1 min or need for resuscitation using positive pressure ventilation. SVC flow was measured in the first three days of life by Doppler echocardiography as described by Kluckow and Evans. Short-term outcome was defined as poor if MRI demonstrated bilateral lesions of the basal ganglia and thalamus and/or multicystic encephalomalacia due to hypoxic ischemia.

Results

In the head cooling group, SVC flow in infants with a good outcome was lower than that in infants with a poor outcome at 12 h (36.9 ± 7.7 vs 113.4 ± 42.4 ml/kg/min (p = 0.01)), 24 h (75.2 ± 25.3 vs 155.6 ± 45.7 ml/kg/min (p = 0.03)), and 48 h (92.5 ± 34.2 vs 161.1 ± 46.7 ml/kg/min (p = 0.04)) after birth. SVC flow decreased promptly after introduction of head cooling in infants who had a good outcome, whereas it increased gradually after head cooling in those who had a poor outcome.

Conclusion

We speculate that regulation of brain circulation is disrupted in infants with asphyxia who show a poor outcome.