Uncovering the dark side of TNF

In the early 1980s, in search of the cytokine that triggers disease- associated weight loss and lethal shock, Anthony Cerami and Bruce Beutler purified “cachectin.” They soon found out that their malevolent cytokine already had another name—tumor necrosis factor (TNF)—and was being lauded as a potential antitumor agent.     

The role of the calcium-sensing receptor in human disease

Following the discovery of the calcium-sensing receptor (CaSR) in 1993, its pivotal role in disorders of calcium homeostasis such as Familial Hypocalciuric Hypercalcemia (FHH) was quickly demonstrated. Since then, it has become clear that the CaSR has immense functional versatility largely through its ability to activate many different signaling pathways in a ligand- and tissue-specific manner. This allows the receptor to play diverse and crucial roles in human physiology and pathophysiology, both in calcium homeostasis and in tissues and biological processes unrelated to calcium balance. This review covers current knowledge of the role of the CaSR in disorders of calcium homeostasis (FHH, neonatal severe hyperparathyroidism, autosomal dominant hypocalcemia, primary and secondary hyperparathyroidism, hypercalcemia of malignancy) as well as unrelated diseases such as breast and colorectal cancer (where the receptor appears to play a tumor suppressor role), Alzheimer's disease, pancreatitis, diabetes mellitus, hypertension and bone and gastrointestinal disorders. In addition, it examines the use or potential use of CaSR agonists or antagonists (calcimimetics and calcilytics) and other drugs mediated through the CaSR, in the management of disorders as diverse as hyperparathyroidism, osteoporosis and gastrointestinal disease.     

Possible role for a human adenovirus in the pathogenesis of celiac disease

Celiac disease in humans is activated by the dietary ingestion of wheat, rye, triticale, barley, and possibly oats. Gliadins in wheat and similar proteins in the other grains are known to activate disease in susceptible individuals. There is a striking association between celiac disease and HLA-B8, -DR3 and/or -DR7, and -DC3. Nonetheless, less than 0.2% of individuals with those serologic HLA specificities develop celiac disease and disease is not always concordant among monozygotic twins. We propose that additional environmental factors may be important in the pathogenesis of celiac disease. To investigate that possibility, we examined a data bank of protein sequences for other proteins that might share amino acid sequence homologies with A- gliadin, an alpha-gliadin component known to activate celiac disease and whose complete primary amino acid sequence is known. These studies demonstrate that A-gliadin shares a region of amino acid sequence homology with the 54-kD E1b protein of human adenovirus type 12 (Ad12), an adenovirus usually isolated from the intestinal tract. The region spans 12 amino acid residues, includes 8 residue identities and an identical pentapeptide, and is hydrophilic in both proteins. Antibody reactive with the 54-kD Ad12 E1b protein cross-reacts with A-gliadin, a 119 amino acid cyanogen bromide peptide of A-gliadin that spans the region of homology and a synthetic heptapeptide of A-gliadin from within the region of homology. We suggest that an encounter of the immune system with antigenic determinants produced during intestinal viral infection may be important in the pathogenesis of celiac disease.     

Chancroid and the role of genital ulcer disease in the spread of human retroviruses

Chancroid is the most prevalent form of genital ulcer disease in developing countries and is undergoing a resurgence in industrialized countries. As a result of a nonspecificity of the clinical findings, the etiologic diagnosis of genital ulcer disease requires laboratory support. Genital ulcer disease is a risk factor for the transmission of human retroviral infections. An understanding of this interaction is emerging and will impact on the treatment and control programs for the agents causing genital ulcer disease.     

The challenges of testosterone deficiency. Uncovering the problem, evaluating the role of therapy

In addition to its relatively uncommon congenital causes, testosterone deficiency in men occurs in a diverse range of clinical conditions. Even healthy men are now known to begin experiencing progressive yet subtle declines in testosterone secretion after age 30. Diagnosis can be challenging, and testosterone replacement therapy does not alleviate all symptoms in all men. Nevertheless, some men can get relief with intramuscular long-acting testosterone esters, transdermal testosterone patches, or transdermal testosterone gel.     

Unraveling the genomic basis of congenital heart disease

The genetic, epigenetic, and environmental etiologic basis of congenital heart disease (CHD) for most heart anomalies remains unexplained. In this issue of the JCI, Lahm et al. performed the largest genome-wide association study (GWAS) to date of European individuals with CHD and clinical subtypes. The comprehensive meta-analysis included over 4000 patients and 8000 controls and uncovered common genetic variants that associated with cardiac anomalies. Lahm and colleagues performed single-cell analysis of induced pluripotent stem cells and heart cells, revealing a role for MACROD2, GOSR2, WNT3, and MSX1 in the developing heart. This study advances our understanding of the genetic basis of common forms of CHD.     

维生素C对人体疾病的影响及其在康复预防中的作用

维生素C作为人体中不可缺少的维生素之一,与人体的健康有着密切的关系。适当的在不同年龄段补充适量的维生素C对许多疾病都有预防作用,而许多疾病的发生可能或多或少与维生素C的缺乏有关系,另外维生素C还能和许多其他药物联合用药治疗某些疾病。所以在日常生活中注意不挑食,不偏食,多食绿色蔬菜和水果,适时适量补充维生素C是有必要的。     

An update on the role of free radicals and antioxidant defense in human disease

Mounting clinical and experimental evidence indicates that free radicals play important roles in many physiological and pathological conditions. The wider application of free radical measurement has increased awareness of functional implications of radical-induced impairment of the oxidative/antioxidative balance. In the following review, the role of oxygen free radicals in some human and experimental pathological conditions is described, with particular emphasis on the mechanisms by which they produce oxidative damage to lipids, proteins, and nucleic bases. The role of free radicals and the activation of the antioxidant systems in arteriosclerosis and ageing, diabetes, ischemia/reperfusion injury, ethanol intoxication, and liver steatosis is discussed. Therapeutic approaches to the use of antioxidants have been described and prospects for clinical use have been considered.     

Assessment of the role of pancreatic proteases in human abdominal aortic aneurysms and occlusive disease

Previous studies on the pathogenesis of abdominal aortic aneurysms have shown both elastase-like activity in the aortic wall and a decreased elastin content. The present study, using specific radioimmunoassays for pancreatic elastase 2 (IRE2) and cationic trypsin(ogen) (IRCT), investigates the concentrations of these proteases which are known to circulate in blood, in abdominal aortic aneurysms. Aortic specimens were obtained from 32 patients with aneurysms and 21 patients with atherosclerotic occlusive disease. Aortic tissue, obtained at autopsy from young adults, served as controls. Elastase-like activity was 300% and 800% higher, respectively, in aortic homogenates from aneurysms in comparison to occlusive disease and control aortic tissue. This was associated with 1.4-fold higher level of IRE2 and 2.7-fold higher levels of IRCT as compared to occlusive disease. Although there was no significant difference in the aortic collagen concentration among all 3 groups, the elastin content of aneurysmal aorta was 85% and 74% lower, respectively, in comparison to control and occlusive aorta. The results of this investigation demonstrate the presence of pancreatic elastase 2 and cationic trypsin(ogen) in abdominal aortic aneurysmal tissue and suggest that circulating pancreatic proteases contribute to the pathophysiology of aneurysms of the infrarenal aorta.     

Uncovering the Knowledge Embedded in Clinical Practice

Nursing practice has been studied primarily from a sociological perspective. Thus we have learned much about role relationships, socialization, and acculturation. We have learned less about the knowledge embedded in actual nursing practice–that knowledge that accrues over time in the practice of an applied discipline.
Nurses have not been careful clinical record keepers of their own clinical learning over time. While ample single case studies have been published, few clinical comparisons exist of multiple case studies or clinical observations across patient populations. This lack of charting of our practices and clinical observations deprives nursing theory of the uniqueness and rich-ness of the knowledge embedded in expert clinical practice.
This paper examines the difference between practical and theoretica'l knowledge, provides examples of competence identified from the study of nursing practice, describes aspects of practical knowledge, and outlines strategies for preserving and extending practical knowledge.