Abstract:
:Autosomal dominant polycystic kidney disease (ADPKD) is a common and systemic disease characterized by formation of focal cysts. Of the three potential causes of cysts, downstream obstruction, compositional changes in extracellular matrix, and proliferation of partially dedifferentiated cells, evidence strongly supports the latter as the primary abnormality. In the vast majority of cases, the disease is caused by mutations in PKD1 or PKD2, and appears to be recessive at the cellular level. Somatic second hits in the normal allele of cells containing the germ line mutation initiate or accelerate formation of cysts. The intrinsically high frequency of somatic second hits in epithelia appears to be sufficient to explain the frequent occurrence of somatic second hits in the disease-causing genes. PKD1 and PKD2 encode a putative adhesive/ion channel regulatory protein and an ion channel, respectively. The two proteins interact directly in vitro. Their cellular and subcellular localization suggest that they may also function independently in a common signaling pathway that may involve the membrane skeleton and that links cell-cell and cell-matrix adhesion to the development of cell polarity.
journal_name
Annu Rev Medjournal_title
Annual review of medicineauthors
Arnaout MAdoi
10.1146/annurev.med.52.1.93subject
Has Abstractpub_date
2001-01-01 00:00:00pages
93-123eissn
0066-4219issn
1545-326Xpii
52/1/93journal_volume
52pub_type
杂志文章,评审abstract::Proteinuric chronic kidney disease (CKD), once a rare affliction believed to be mainly caused by genetic mutations, has become a global pandemic that severely diminishes the quality of life for millions. Despite the changing face of CKD, treatment options and resources remain woefully antiquated and have failed to arr...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-050311-163340
更新日期:2013-01-01 00:00:00
abstract::Diastolic dysfunction is an important cause of the clinical syndrome of congestive heart failure. Traditionally, the syndrome of pulmonary congestion due to the elevation of left heart filling pressure has been attributed to the depressed ability of the heart to eject blood during systole, with a secondary increase in...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.002211
更新日期:1991-01-01 00:00:00
abstract::Clostridium difficile infection is associated with broad-spectrum antibiotic therapy and is the most common cause of infectious diarrhea in hospital patients. Pathogenic strains of C. difficile produce two protein exotoxins, toxin A and toxin B, which cause colonic mucosal injury and inflammation. Infection may be asy...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.49.1.375
更新日期:1998-01-01 00:00:00
abstract::Although safe and effective agents are currently available to treat osteoporosis, fragility fractures remain a significant problem worldwide. Recent improvements in the understanding of the cellular, biochemical, and molecular pathways of bone biology have led to the development of newer agents to treat osteoporosis, ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-061709-145401
更新日期:2011-01-01 00:00:00
abstract::The standard of care for the evaluation of axillary nodal involvement remains complete lymph node dissection. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this long-held paradigm; indeed, several leading institutions already reserve complete axillary dissection for patients with metastasis to th...
journal_title:Annual review of medicine
pub_type: 杂志文章
doi:10.1146/annurev.med.51.1.525
更新日期:2000-01-01 00:00:00
abstract::The endothelium is a physical barrier between the blood and vascular smooth muscle, a source of enzymes activating and deactivating cardiovascular hormones and a site of production of relaxing and contracting factors. In addition, the endothelium is a source of growth inhibitors and promoters of vascular smooth muscle...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.44.020193.002143
更新日期:1993-01-01 00:00:00
abstract::The primary or hereditary form of distal renal tubular acidosis (dRTA), although rare, has received increased attention recently because of dramatic advances in the understanding of its genetic basis. The final regulation of renal acid excretion is effected by various acid/base transporters localized in specialized ce...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.52.1.471
更新日期:2001-01-01 00:00:00
abstract::Complementary and alternative medicine (CAM) consists of diverse clinical interventions that are practiced because of their popularity rather than the prior demonstration of safety and efficacy required for conventional agents. CAM therapies can be grouped into five categories: biologically based therapies, manipulati...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.55.091902.103657
更新日期:2004-01-01 00:00:00
abstract::The Adult Respiratory Distress Syndrome is a complication of many illnesses such as sepsis, pneumonia and trauma afflicting over 150,000 patients per year. While progress in intensive care medicine has increased the survival rates in many of these underlying illnesses, major obstacles remain in the successful therapy ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.36.020185.001211
更新日期:1985-01-01 00:00:00
abstract::Clonal populations of cells can be identified by a number of different independent approaches, including analyses of karyotype, gene rearrangements, deletions or point mutations, X-linked polymorphisms, and integration of virus into the genome. Assessment of clonality has yielded valuable and surprising clues to the p...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.002423
更新日期:1991-01-01 00:00:00
abstract::Calorie restriction (CR) is the most effective and reproducible intervention for increasing lifespan in a variety of animal species, including mammals. CR is also the most potent, broadly acting cancer-prevention regimen in experimental carcinogenesis models. Translation of the knowledge gained from CR research to hum...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.54.101601.152156
更新日期:2003-01-01 00:00:00
abstract::Thyroid cancer is rapidly increasing in incidence, but the mortality rate remains flat. Debate has arisen over the need to detect or treat most thyroid cancers early, given their favorable natural history. The appropriate extent of surgery for thyroid cancer is also controversial: some researchers advocate partial and...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-061512-105739
更新日期:2014-01-01 00:00:00
abstract::Cystic fibrosis (CF) lung disease reflects the failure of airways defense against chronic bacterial infection. Studies of CF cultures, transgenic mice, and CF patients suggest that the initiating event in CF airways disease pathogenesis is reduced airway surface liquid (ASL) volume, i.e., dehydration. CF ASL volume re...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.58.071905.105316
更新日期:2007-01-01 00:00:00
abstract::The role of the complement system in mediating human renal disease has long been recognized in immune-complex excess syndromes such as systemic lupus erythematosus and in dense deposit disease in which no immunoglobulin (Ig) is present. Over the past 15 years, mutations in complement regulatory genes have been demonst...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-072211-110606
更新日期:2013-01-01 00:00:00
abstract::New discoveries are expanding our knowledge of mechanisms involved in amyotrophic lateral sclerosis (ALS) pathogenesis. Some recent advances in our understanding of motoneuron death in familial ALS (fALS) and sporadic ALS (sALS) are reviewed, with emphasis on molecular similarities that may further unite these phenoty...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.46.1.133
更新日期:1995-01-01 00:00:00
abstract::Remarkable progress made in the past few years has brought pancreatic islet transplantation to the threshold of human clinical trials. Islet transplants have reversed diabetes in experimental animals and prevented or reversed early diabetic complications in the recipients. Methods have been developed that prevent reje...
journal_title:Annual review of medicine
pub_type: 临床试验,杂志文章,评审
doi:10.1146/annurev.me.37.020186.000341
更新日期:1986-01-01 00:00:00
abstract::This brief review highlights the rise in asthma mortality witnessed in many countries. It outlines the multifactorial character of this phenomenon, which in most instances is a complex interplay between physician, patient, and environment. The pathophysiology of airflow obstruction and in particular the role of hyperi...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.47.1.161
更新日期:1996-01-01 00:00:00
abstract::Following the "finished," euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better unde...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-051010-162644
更新日期:2012-01-01 00:00:00
abstract::Obesity is perhaps the most significant public health problem facing the United States today. Obese patients are at increased risk for numerous medical problems, which can adversely affect surgical outcome. However, these risks have not uniformly translated into increased or prohibitive operative morbidity and mortali...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.49.1.215
更新日期:1998-01-01 00:00:00
abstract::Significant progress has been made in identifying changes in cholinergic, monoaminergic, and peptidergic neurotransmitter systems in the brains of individuals with Alzheimer's disease. Moreover, neurobiological approaches are beginning to reveal the relationships between these neurotransmitter abnormalities and histol...
journal_title:Annual review of medicine
pub_type: 杂志文章
doi:10.1146/annurev.me.36.020185.002025
更新日期:1985-01-01 00:00:00
abstract::MicroRNAs (miRNAs) are small, noncoding RNAs with important functions in development, cell differentiation, and regulation of cell cycle and apoptosis. MiRNA expression is deregulated in cancer by a variety of mechanisms including amplification, deletion, mutation, and epigenetic silencing. Several studies have now sh...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.59.053006.104707
更新日期:2009-01-01 00:00:00
abstract::Antisense technology exploits oligonucleotide analogs to bind to target RNAs via Watson-Crick hybridization. Once bound, the antisense agent either disables or induces the degradation of the target RNA. Antisense agents can also alter splicing. During the past decade, much has been learned about the basic mechanisms o...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.55.091902.104408
更新日期:2004-01-01 00:00:00
abstract::Cardiac resynchronization therapy (CRT) is well established as a treatment for patients with moderate to severe heart failure on optimal medical therapy. Early studies demonstrated improved functional capacity and evidence of reverse remodeling; more recently, CRT has been associated with a survival benefit in advance...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.57.051804.122251
更新日期:2007-01-01 00:00:00
abstract::CCR5 antagonists inhibit HIV-1 entry by blocking the interaction of HIV-1 with the CCR5 cellular receptor. In patients with established HIV-1 infection, some viral strains use an alternative coreceptor for HIV-1 entry, CXCR4; CCR5 antagonists are not effective in patients harboring these viral strains. Coreceptor trop...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-052010-145454
更新日期:2012-01-01 00:00:00
abstract::Brain imaging is increasingly applied in psychiatry, both for clinical evaluation and as a research tool. Computerized tomography (CT) and magnetic resonance imaging (MRI) have documented that structural brain abnormalities occur in some types of psychiatric patients, particularly those who suffer from schizophrenia. ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.39.020188.002003
更新日期:1988-01-01 00:00:00
abstract::Over the past several years a combination of diverse steps has culminated in a significant improvement in our ability to save ischemic extremities. Encompassing all phases of vascular surgery, these advances in diagnosis, therapy, and long-term management are outlined. These and future improvements hold promise for ex...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.38.020187.002013
更新日期:1987-01-01 00:00:00
abstract::New insights into atherosclerosis, the most common disease affecting coronary arteries, may change therapeutic strategies from largely symptomatic to causal. Atherosclerotic plaques contain a lipid-related, immune-mediated inflammation, with release of secretory products capable of changing plaque morphology. Plaques ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.med.52.1.289
更新日期:2001-01-01 00:00:00
abstract::Acute myocardial infarction is caused by coronary thrombosis on an ulcerated atheroma. We now believe that the predominant cause of this intimal disruption is the rupture of the atheroma through the intimal surface, caused by enzymes released by activated macrophages. The subsequent clinical course following atheroma ...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.42.020191.000343
更新日期:1991-01-01 00:00:00
abstract::Cardiometabolic disease (CMD), such as type 2 diabetes mellitus and cardiovascular disease, contributes significantly to morbidity and mortality on a global scale. The gut microbiota has emerged as a potential target to beneficially modulate CMD risk, possibly via dietary interventions. Dietary interventions have been...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev-med-062218-023720
更新日期:2020-01-27 00:00:00
abstract::Eccrine sweat is produced by millions of miniscule glands buried in the skin. Eccrine sweating from the general body surface is an extremely important function in human thermoregulation; disturbances either in the control of sweating activity or in the glands themselves can result in problems ranging from minor social...
journal_title:Annual review of medicine
pub_type: 杂志文章,评审
doi:10.1146/annurev.me.34.020183.002241
更新日期:1983-01-01 00:00:00