Abstract
Capillary fragility is characteristic of severe thrombocytopenia. This mechanical weakness may not be solely accounted for by decreased ability of platelets to repair endothelial breaks. Platelets may have a role in maintaining endothelial hemostasis. This laboratory has demonstrated thinning of capillary endothelium in experimental thrombocytopenia. We now report similar findings in human thrombocytopenia. Capillary endothelium supplying either skin or skeletal muscle was found to have a mean thickness only half that of normal as well as frequent very thinned areas, including some fenestrations. All findings reverted toward normal after four days of prednisone administration at a time the degree of thrombocytopenia was equally severe. These findings are consistent with the hypothesis that platelets are necessary for normal structure and function of endothelial cells and that glucocorticosteroid administration may ameliorate the pathophysiology of thrombocytopenia.
Oral mucosa, saliva, and speech in relation to dentistry are the topics in this chapter. The chapter starts with the normal structure and function of oral mucosa, leading on to a discussion of problems in normal physiology leading to ulceration and to oral precancer and carcinoma. This is followed by a consideration of saliva, its production and properties, and important issues arising from lack of saliva. Swallowing, its phases and control and dental relevance, are next discussed. The concluding section deals with speech, vocalization, phonation, and articulation together with problems of dental relevance, that may arise.
Knowledge of the normal structure and function of the meninges and ventricular system can aid in recognizing and understanding pathologic states. This chapter reviews the meninges, ventricular system, and cerebrospinal fluid (CSF) production. Three layers of meninges cover the brain and spinal cord: dura, arachnoid, and pia. They 1) protect the underlying brain and spinal cord, 2) serve as a support framework for important arteries and veins, and 3) enclose a fluid-filled cavity that is important for normal function of the brain and spinal cord.
ABSTRACT
The 24-member claudin protein family plays a key role in maintaining the normal structure and function of epithelial tight junctions. Previous studies with fibroblast transfectants and naturally sensitive Caco-2 cells have also implicated certain claudins (e.g., Claudin-4) as receptors for Clostridium perfringens enterotoxin (CPE). The present study first provided evidence that the second extracellular loop (ECL-2) of claudins is specifically important for mediating the host cell binding and cytotoxicity of native CPE. Rat fibroblast transfectants expressing a Claudin-4 chimera, where the natural ECL-2 was replaced by ECL-2 from Claudin-2, exhibited no CPE-induced cytotoxicity. Conversely, CPE bound to, and killed, CPE-treated transfectants expressing a Claudin-2 chimera with a substituted ECL-2 from Claudin-4. Site-directed mutagenesis was then used to alter an ECL-2 residue that invariably aligns as N in claudins known to bind native CPE but as D or S in claudins that cannot bind CPE. Transfectants expressing a Claudin-4N149D mutant lost the ability to bind or respond to CPE, while transfectants expressing a Claudin-1 mutant with the corresponding ECL-2 residue changed from D to N acquired CPE binding and sensitivity. Identifying carriage of this N residue in ECL-2 as being important for native CPE binding helps to explain why only certain claudins can serve as CPE receptors. Finally, preincubating CPE with soluble recombinant Claudin-4, or Claudin-4 fragments containing ECL-2 specifically blocked the cytotoxicity on Caco-2 cells. This result opens the possibility of using receptor claudins as therapeutic decoys to ameliorate CPE-mediated intestinal disease.
High blood glucose level (hyperglycemia) is a leading indicator of diabetes mellitus (DM). Erythrocytes are the most abundant cells in the circulation and the first to perceive changes in plasma composition. Long-lasting hyperglycemia affects the structure and function of erythrocytes. The detection of erythrocyte-related indicators can provide a valuable reference for the prevention, diagnosis, and treatment of DM and its complications. This paper reviews the normal structure and function of erythrocytes, the changes in erythrocytes in patients with diabetes, and the role of erythrocytes in the development of diabetic complications to provide more indicators for the early prevention of DM complications and to monitor the therapeutic effect of DM.
The normal structure and function of sperm are prerequisites for successful fertilization and embryonic development, but little is known about how defective sperm are eliminated during mammalian spermatogenesis. Here, we describe a ubiquitin-dependent, sperm quality control mechanism that resides in the mammalian epididymis, the site of sperm maturation and storage. We used immunofluorescence, electron microscopy, western blotting and pulse-chase experiments to show that ubiquitin is secreted by the epididymal epithelium and binds to the surface of defective sperm. Most of the ubiquitinated sperm are subsequently phagocytosed by the epididymal epithelial cells. A portion of defective sperm escapes phagocytosis and can be found in the ejaculate. Cultured epididymal cells maintain their ability to produce ubiquitin and phagocytose the defective sperm, as well as the ubiquitin-coated microspheres, in vitro. The surprising phenomenon of cell-surface ubiquitination in defective sperm provides a possible mechanism for sperm quality control in mammals and a new marker of semen abnormalities in men and animals.
Human thrombocytopenia is associated with structural abnormalities of the endothelium that are ameliorated by glucocorticosteroid administration
