ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Two independent strategies have established that the transcription factor,Cbfa 1, is a key regulator of both osteoblast differentiation and osteoblast-specific gene expression. Gene targeting experiments in mice have also shown that haploinsufficiency ofCbfa 1expression causes symptoms reminiscent of the Cleidocranial dysplasia syndrome (CCD), a heritable disorder of the skeleton. Direct analysis of theCbfa 1gene in CCD families has revealed a direct correlation between mutations in this gene and disease phenotype.

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

For over a hundred years, the bane of rickets (a disease of bone), has been prominent in those countries that have participated in, and seeded, the industrial revolution. Industrialisation had major effects on the demography of populations, and many people moved to dark, heavily industrialised cities to find work. It soon became apparent that rickets could be cured by supplementing the diet with cod liver oil and exposure to sunlight. This in turn led to the discovery that photoactivation of 7-dehydrocholesterol was required to produce vitamin D, an indispensable regulator of bone mineral metabolism. Although inadequate exposure to light and poor dietary intake are the main causes of rickets and osteomalacia, recent research has confirmed the role of familial, and tumour forms of the disease. This review will describe the recent advances in our knowledge of the molecular defects in X-linked hypophosphataemic rickets (HYP), and oncogenic hypophosphataemic osteomalacia (OHO), Although HYP and OHO have different primary defects, both diseases have similarities that suggest a linked or overlapping pathophysiology. Also, without doubt, the recent cloning of the gene defective in HYP (the PHEX gene), has given researchers a new reagent to explore the molecular regulation of bone and its links to kidney endocrine function. The fact that the PHEX gene codes for a Zn metallopeptidase raises new and intriguing questions, and adds new momentum to the research on diseases of bone mineral metabolism.

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Vitamin D plays a role in a wide variety of biological events such as calcium homeostasis, bone formation and cellular differentiation. An active form of vitamin D acting as a ligand specific vitamin D receptor (VDR), 1 α,25(OH)2D3, is biosynthesized from cholesterol, and during this biosynthesis a renal 25-hydroxylation at the final stage by 25-hydroxyvitamin D31α-hydroxylase is critical. Recent studies isolated the cDNA encoding 1 α-hydroxylase from several species, and revealed that this enzyme belongs to a member of the cytochrome p450 enzyme superfamily, with highest homologies to the p450 hydroxylases for vitamin D derivatives. One of three kinds of hereditary rickets (vitamin D-dependent rickets type I) diplays an autosomal recessive trait and clinical features consistent with a defect of 1 α-hydroxylase activity, and the genetic analysis of the type I patients identified missense mutations of the 1 α(OH)ase gene that result in a loss of this enzymatic activity.

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Recent advances in molecular biology have characterised a new class of chloride channels (CLCs) that are referred to as voltage-gated CLCs, To nine such voltage-gated CLCs (CLC-1 to CLC-7, CLC-Ka and CLC-Kb, which are encoded by the CLCN1 to CLCN7, CLC-Ka and CLC-Kb, respectively) have been identified in mammals. Mutations in two of these, CLC-5 and CLC-Kb, have been defined in the hypercalciuric nephrolithiasis disorders of Dent's and a form of Bartter's syndrome, respectively. In addition, other forms of Bartter's syndrome have been defined with mutations involving the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC2) and the potassium channel ROMK. Finally, mutations of the thiazide-sensitive sodium-chloride cotransporter (NCCT) are associated with Gitelman's syndrome, in which hypocalciuria and hypomagnesaemia are notable features. These molecular genetic studies have increased our understanding of the renal tubular mechanisms that regulate mineral homeostasis.

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Post-renal-transplantation bone disease is a well known entity, Immunosuppressive agents and persistence of hyperparathyroidism have primarily been implicated in its etiology. Renal transplantation patients are unique in that the bone changes occur on a background of pre-existing renal osteodystrophy. This review focuses on post-renal-transplantation bone disease. Unfortunately, the existing data in the review period, besides being scanty, provide conflicting information. This is due to the diversity of immunosuppressive regimens employed, the patient populations studied, diagnostic tools and criteria used by different centers, and the lack of formal trials.

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The activated form of vitamin D3, 1α,25(OH)2D3, not only plays a central role in bone and calcium metabolism, but also has potent antiproliferative and prodifferentiating effects. Moreover, the combined presence of 25(OH)D3-1α-hydroxyiase, as well as the vitamin D receptor in several tissues introduced the idea of a paracrine role for 1 α,25(OH)2D3. By introducing chemical modifications into the flexible molecule 1α,25(OH)2D3, a whole generation of vitamin D analogues was created. Due to a clear dissociation of the antiproliferative and prodifferentiating effects from calcaemic effects, these analogues can be used not only for the treatment of bone disorders but also for non-classical applications. In the present review, a summary is given on the use of the 1α,25(OH)2D3analogues for the treatment of psoriasis, cancer and immune disorders together with new insights in the mechanism of action of these analogues.

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Heat shock proteins, or stress proteins, are molecular chaperones responsible for protein processing and protection against cellular injury through the prevention of inappropriate peptide interactions. The distribution of individual stress proteins varies between regions of the kidney and within: subcellular compartments both in normal and pathological conditions. Novel molecular chaperones have been identified in renal medullary cells which are unique, among mammalian cells, in routinely facing osmotic stress. Heat shock proteins can participate in renal injury as antigenic targets, but their primary role is beneficial, and these proteins may function by interacting with the cytoskeleton to protect against and assist recovery from cellular injury.

ISSN:1062-4821    

出版商:OVID    

年代:1998

数据来源: OVID