Parietal Cell and Intrinsic Factor Antibodies in a Finnish Rural Population Sample

Parietal cell and intrinsic factor antibodies were studied in the sera of 156 inhabitants of Pornainen. Parietal cell antibodies were found in 8 per cent of the ‘random sample’, consisting of 135 subjects, and in 34 per cent of the ‘high risk group’ consisting of 29 subjects with decreased gastric secretion. Intrinsic factor antibodies were found in 3 cases in the ‘high risk group’. Two of these had manifest and one latent pernicious anaemia. It seemed that the determination of gastric antibodies may be of some value in screening for severe atrophic gastritis and pernicious anaemia.     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.     

How the Innate Immune System Senses Trouble and Causes Trouble

The innate immune system is the first line of defense in response to nonself and danger signals from microbial invasion or tissue injury. It is increasingly recognized that each organ uses unique sets of cells and molecules that orchestrate regional innate immunity. The cells that execute the task of innate immunity are many and consist of not only “professional” immune cells but also nonimmune cells, such as renal epithelial cells. Despite a high level of sophistication, deregulated innate immunity is common and contributes to a wide range of renal diseases, such as sepsis-induced kidney injury, GN, and allograft dysfunction. This review discusses how the innate immune system recognizes and responds to nonself and danger signals. In particular, the roles of renal epithelial cells that make them an integral part of the innate immune apparatus of the kidney are highlighted.     

Characterization of a Factor H Mutation That Perturbs the Alternative Pathway of Complement in a Family with Membranoproliferative GN

Complement C3 activation is a characteristic finding in membranoproliferative GN (MPGN). This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. Deficiency of complement factor H has long been associated with MPGN. More recently, heterozygous genetic variants have been reported in sporadic cases of MPGN, although their functional significance has not been assessed. We describe a family with MPGN and acquired partial lipodystrophy. Although C3 nephritic factor was shown in family members with acquired partial lipodystrophy, it did not segregate with the renal phenotype. Genetic analysis revealed a novel heterozygous mutation in complement factor H (R83S) in addition to known risk polymorphisms carried by individuals with MPGN. Patients with MPGN had normal levels of factor H, and structural analysis of the mutant revealed only subtle alterations. However, functional analysis revealed profoundly reduced C3b binding, cofactor activity, and decay accelerating activity leading to loss of regulation of the alternative pathway. In summary, this family showed a confluence of common and rare functionally significant genetic risk factors causing disease. Data from our analysis of these factors highlight the role of the alternative pathway of complement in MPGN.     

Probiotics and prebiotics in neonatal necrotizing enterocolitis: New opportunities for translational research

Neonatal necrotizing enterocolitis (NEC) in premature infants has been recognized as a defined disease entity for at least four decades. Although survival has increased due to the advent of more sophisticated intensive care, incidence and long term health impacts due to NEC remain unchanged and no preventive therapy is currently available. Different probiotic strains of bacteria have been examined in their ability to prevent NEC with varied but encouraging results. Undigestable prebiotic sugars known to promote the growth of probiotic bacteria in the colon have been used in neonates with no clear benefit. The literature on NEC and probiotics is now cluttered with more reviews and meta-analyses than number of clinical trials. On the other hand, significant new information is available on microbiota and their impact on gut immunity. This review attempts to reiterate the risk factors of NEC and the pathogenesis of NEC with special reference to gut permeability. The reader is then introduced to gut microbiota, uniqueness and differences among probiotic strains, and how multiple resident flora talk to each other in the community setting in the human gut. After presenting a concise review of available clinical research results, the reader is challenged to question as to why no precise answer is available at present. Some modalities to examine the complex microflora and changes in the neonatal gut are then proposed including non-invasive methods and mathematical modeling. The review concludes by attracting the reader's attention to known immunomodulators of inflammation and injury. Justice to this review will be done only if the readers, clinical, and basic science investigators from multiple fields gather courage for a paradigm shift and embark on understanding the pathophysiology of the disease and attempt to discern the difference from equally preterm, equally vulnerable neonates that do not develop NEC. Learning about the developing microbiota in neonatal gut and its immunological impacts on the host in the face of many variables will provide a leap in our pursuit to select better, if not the best candidate probiotics, and put them to work against this stubborn disease that continues to take a toll on our precious neonates and the society.     

加味温胆汤对急性心肌梗死后心力衰竭大鼠心肌能量代谢和超微结构的影响

目的通过对急性心肌梗死后心力衰竭(HFMI)大鼠模型给药治疗,评估加味温胆汤对大鼠心肌能量代谢水平和心肌超微结构的影响。方法SD雄性大鼠随机分为两组,每组15只,造模组通过手术结扎冠状动脉左前降支造模,假手术组完成穿刺但并未结扎左前降支,术后饲养72 h,对两组大鼠进行慢性心衰评分并加以比较。将造模组15只大鼠分为3组,每组5只,中药组经口喂加味温胆汤,曲美他嗪组给予曲美他嗪溶液,对照组喂养生理盐水,给药4周后空腹抽取3组鼠尾静脉血,检测并比较各组大鼠心肌能量代谢因子:血清肌钙蛋白(cTnI)、心肌过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)水平;进行超声检查,测定并比较左室射血分数(LVEF);采集心肌样本进行HE染色(核染)和Masson染色(纤染),对心肌超微结构完整性进行评分。结果治疗4周后,中药组、曲美他嗪组大鼠LVEF数值均较治疗前显著增加(P<0.05),对照组与治疗前相比降低(P<0.05),但治疗后中药组大鼠LVEF数值高于曲美他嗪组(P<0.05);与治疗前相比,3组大鼠血清cTnI、PGC-1α表达水平差异有统计学意义(P<0.05),中药组<曲美他嗪组<对照组;治疗4周后,3组大鼠心肌超微结构完整性评分比较差异也具有统计学意义(P<0.05),中药组<曲美他嗪组<对照组。结论加味温胆汤对急性心肌梗死后心力衰竭大鼠的心肌能量代谢具有促进作用,对心肌超微结构的完整性具有保护作用,并能有效改善大鼠的心功能。