Chronic renal failure may be accompanied by reversible sympathetic activation, which appears to be mediated by an afferent signal arising in the failing kidneys.

Lumican regulates collagenous matrix assembly as a keratan sulfate proteoglycan in the cornea and is also present in the connective tissues of other organs and embryonic corneal stroma as a glycoprotein. In normal unwounded cornea, lumican is expressed by stromal keratocytes. Our data show that injured mouse corneal epithelium ectopically and transiently expresses lumican during the early phase of wound healing, suggesting a potential lumican functionality unrelated to regulation of collagen fibrillogenesis, e.g. modulation of epithelial cell adhesion or migration. An anti-lumican antibody was found to retard corneal epithelial wound healing in cultured mouse eyes. Healing of a corneal epithelial injury in Lum ؊/؊ mice was significantly delayed compared with Lum ؉/؊ mice. These observations indicate that lumican expressed in injured epithelium may modulate cell behavior such as adhesion or migration, thus contributing to corneal epithelial wound healing.Rapid re-epithelialization is essential for restoration of homeostasis in injured tissues; impaired healing of injured epithelium increases the risks of infection and further damage underlying tissues (1, 2). The cornea provides an ideal model to evaluate interactions of migrating epithelial cells and the extracellular matrix of the underlying basement membrane during wound healing because epithelial injuries of the avascular corneal tissue heal in a bloodless wound field. Various specific proteins such as vinculin (3), keratins (4), CD44 hyaluronan receptors (5), and gelatinases and metalloproteinase inhibitors (6, 7) are up-regulated during corneal epithelial wound healing. These proteins are believed to modulate cell adhesion or migration.Lumican belongs to the family of small leucine-rich proteoglycans (SLRPs) 1 that includes keratocan, mimecan, decorin, biglycan, fibromodulin, epiphycan, and osteoadherin. In the cornea, lumican, keratocan, and mimecan are modified with keratan sulfate glycosaminoglycan chains comprising the keratan sulfate proteoglycans (KSPG) of the stromal extracellular matrix (8 -13). In normal unwounded mouse cornea, lumican mRNA is expressed in stromal keratocytes (14). Lumican KSPG is a key regulator of collagen fibrillogenesis, a process critical to corneal transparency. Mice lacking lumican show an age-dependent corneal opacity and a high proportion of abnormally thick collagen fibers in the corneal stroma (15).Lumican is also widely present as a non-or low-sulfated glycoprotein in connective tissues of many other organ systems, e.g. skeleton, heart, kidney, and lung (14, 16 -18). During mouse embryonic ocular development, lumican is synthesized by keratocytes; detected as a glycoprotein, not as a KSPG (19); and also transiently expressed by the corneal epithelium, neural retina, and epidermis (14). These observations suggest that epithelial tissues possess the capacity to express lumican under certain conditions. Several studies have demonstrated that SLRP proteins can modulate cellular behaviors, i.e. cell migration and prolifera...

Acute hypotension is an important complication of hemodialysis, but the underlying mechanisms remain poorly understood. Because hemorrhage-induced hypovolemia can trigger a sudden decrease in sympathetic activity resulting in bradycardia and vasodilation, we hypothesized that hemodialysis-induced hypovolemia also can trigger the same type of vasodepressor reaction, which would exacerbate the volume-dependent fall in blood pressure. We therefore measured blood pressure, vascular resistance, and sympathetic nerve activity (intraneural microelectrodes) during sessions of maintenance hemodialysis in 7 patients with and 16 patients without a history of hemodialysis-induced hypotension. During hemodialysis, blood pressure at first remained unchanged as calf resistance increased in both hypotension-resistant (from 37±4 to 49±5 U, P < 0.05) and hypotension-prone (from 42±6 to 66±12 U, P < 0.05) patients; sympathetic activity increased comparably in the subset of patients in whom it could be measured. With continued hemodialysis, calf resistance and sympathetic activity increased further in the hypotension-resistant patients, but in the hypotensionprone patients the precipitous decrease in blood pressure was accompanied by decreases in sympathetic activity, vascular resistance, and heart rate as well as symptoms of vasodepressor syncope. On an interdialysis day, both groups of patients increased vascular resistance normally during unloading ofcardiopulmonary baroreceptors with lower body negative pressure and increased heart rate normally during unloading of arterial baroreceptors with infusion of nitroprusside. These findings indicate that in a group of hemodialysis patients without diabetes or other conditions known to impair autonomic reflexes, hemodialysis-induced hypotension is not caused by chronic uremic impairment in arterial or cardiopulmonary baroreflexes but rather by acute, paradoxical withdrawal of sympathetic vasoconstrictor drive producing vasodepressor syncope. (J. Clin.

Lumican is one of the major keratan sulfate proteoglycans (KSPG) in vertebrate corneas. We previously cloned the murine lumican cDNA. This study determines the structure of murine lumican gene (Lum) and its expression during mouse embryonic developments. The mouse lumican gene was isolated from a bacterial artificial chromosome mouse genomic DNA library and characterized by polymerase chain reaction and Southern hybridization. The lumican gene spans 6.9 kilobase pairs of mouse genome. The gene consists of three exons and two introns. Exon 1 constitutes 88 bases (b) of untranslated sequence. Exon 2 is 883 b and contains most of the coding sequence of lumican mRNA, and exon 3 has 152 b of coding sequence and 659 b of 3 noncoding sequence. The mouse lumican gene has a TATCA element, a presumptive TATA box, which locates 27 b 5-upstream from the transcription initiation site. Northern hybridization and in situ hybridization indicate that in early stages of embryonic development, day 7 post coitus the embryo expresses little or no lumican. Thereafter, different levels of lumican mRNA can be detected in various organ systems, such as cornea stroma, dermis, cartilage, heart, lung, and kidney. The cornea and heart are the two tissues that have the highest expression in adult. Immunoblotting studies found that KSPG core proteins became abundant in the cornea and sclera by postnatal day 10 but that sulfated KSPG could not be detected until after the eyes open. These results indicate that lumican is widely distributed in most interstitial connective tissues. The modification of lumican with keratan sulfates in cornea is concurrent with eye opening and may contribute to corneal transparency.Corneal strength and transparency depend upon the development and maintenance of an organized extracellular matrix, including uniformly small diameter collagen fibrils with lamellae of consistent interfibrillar spacing. The collagen fibrils of adjacent lamella sheets are perpendicular to one another (1, 2).The mechanism that governs the formation of collagen lamellae in cornea stroma is not well understood. It has been suggested, however, that the ratios of different collagen types in making up the fibrillar corneal collagen and other extracellular specialized matrix components, e.g. proteoglycans and glycoprotein are essential for the development of a transparent cornea (1,(3)(4)(5)(6)(7)(8). In addition to interaction with collagen fibrils, proteoglycans in stroma also play a role in corneal hydration due to their high negative charge of sulfated carbohydrate moieties (9 -11).The hydrophilic properties of the stroma result from stromal proteoglycans that constitute the second most abundant biological materials in stroma, after collagen (12, 13). The keratan sulfate proteoglycans (KSPGs) 1 are uniquely abundant in the cornea, constituting the major proteoglycans of the corneal stroma. Currently, three corneal KSPG core proteins have been identified, i.e. keratocan, lumican, and mimican (osteoglycin), which were previously designated 3...

The full-length cDNA of mouse K12 keratin was characterized by sequencing overlapping cDNA clones isolated from a mouse cornea cDNA library. Using Northern blot hybridization, the radio-labeled cDNA hybridized to a 1.9 kb mRNA from adult cornea, but not from other mouse tissues including snout, esophagus, tongue, and skin. During mouse development, corneas do not express K12 mRNA until 4 days postnatal when the epithelium begins to stratify as judged by Northern blot and in situ hybridization. In situ hybridization with 3H-labeled cDNA probe and immunohistochemical studies with antibodies against a synthetic oligo-peptide deduced from rabbit K12 cDNA demonstrate that this mouse K12 keratin is expressed in all cell layers of adult corneal epithelium, and the suprabasal layers, but not the basal layer of the limbal epithelium. Epidermal growth factor (EGF) has been shown to promote epithelium stratification of cultured chicken and human corneas in vitro. To examine whether EGF can promote K12 expression, EGF was administered to neonatal mice. The results indicate that EGF retards K12 expression by corneal epithelial cells, even though it promotes corneal epithelial stratification during mouse development. Taken together, our results demonstrate that the expression of K12 keratin is cornea-specific, differentiation-dependent, and developmentally regulated.