Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the relationships of the cellular constituents of the retinal vasculature--astrocytes, microglia and pericytes--to the differentiating endothelium in human fetal retina. The vascular endothelium was stained using NADPH-diaphorase histochemistry in 12 human fetal retinae ranging in gestational age from 15-22 weeks. Specimens were double labeled using antibodies against glial fibrillary acid protein, alpha smooth muscle actin, or major histocompatibility complex class II antigens to label astrocytes, contractile cells and microglia, respectively. In addition, specimens of 12, 14, 16 and 20 weeks gestation were hybridized in situ for VEGF expression. In retinal wholemounts the vascularized area comprised four lobes that converged on the optic disc. The vascular network was more dense in the temporal lobes than in the nasal lobes, and different growth patterns were evident. Astrocytes were distributed in two layers--one associated with the optic axons and a deeper layer associated with the developing vessels. In retinae younger than 20 weeks, astrocytes in the deep layer were only loosely associated with the developing vessels and extended as far as 150 microns ahead of the most peripheral vessels. A closer register between retinal vessels and the distribution of astrocytes was evident in the nasal region of retinas older than 20 weeks. In situ hybridization demonstrated expression of VEGF mRNA in the vascular layer, superficial to the ganglion cell layer, at the margins of the vascularized zone. Differences were evident in the density of astrocyte coverage of developing vessels and in the extent of VEGF expression in different regions of the retina: the relationship of these differences to differentiation gradients in the neural retina is discussed. Intensely immunoreactive microglia were observed in the vascular layer, associated with the vascular endothelium as far as the most peripheral loops, but not beyond. Alpha smooth muscle actin-containing cells covered the proximal parts of large arteries, but not corresponding veins; they were absent from arterial side-arm branches, as well as the newly formed and small diameter vessels in the age range studies. The results suggest that microglia, contractile cells and astrocytes have distinct temporo-spatial relationships to the differentiating vascular endothelium in human retinas and that VEGF expression at the vascular front, presumably by astrocytes, is associated with the spread of the retinal vasculature, as described in other species.
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PMID:Development of the human retinal vasculature: cellular relations and VEGF expression. 946 88

Nitric oxide (NO) is an important mediator in the relaxation of cavernosal smooth muscle. The present study examines the existence and location of the constitutive isoform eNOS (endothelial NO synthase) accompanying the already substantiated neurogenic NOS (nNOS) in the human corpus cavernosum of men with and without erectile dysfunction. Activities of NOS enzymes were examined in specimens of 11 potent and nine long-term impotent patients by means of light and electron microscopy using NADPH-diaphorase staining and immunohistochemical eNOS-specific, smooth muscle actin-specific and nNOS-specific markers. Cavernosal smooth muscle shows a distinct expression of eNOS. In contrast to the weaker expression of eNOS and nitrinergic innervation found in larger veins, the small intracavernosal helicine arteries express large quantities of eNOS and possess a dense nitrinergic innervation. Long-term impotent patients display a broad heterogeneity in eNOS expression and nitrinergic innervation while no overall correlation between NOS expression and erectile function was observed. The expression of eNOS indicates eNOS as a main source of NO alongside nNOS. The differentiated localization of eNOS supports at least a role of this isoform in vascular regulation.
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PMID:Evidence for the involvement of endothelial nitric oxide synthase from smooth muscle cells in the erectile function of the human corpus cavernosum. 963 46

The postoperative intestinal dysmotility seen in intestinal atresia (IA) is usually found in association with a dilatation of the proximal intestinal segment, but the etiology of this disorder is not yet fully understood. A chick IA model was made by cutting the postumbilical midgut on d 11 in ovo. The operated chicks were euthanized 2 d after hatching. The samples were divided into two groups according to the extent of the dilatation of proximal ileal segments. Cryostat sections were processed for immunohistochemistry by the use of antisera to protein gene product 9.5, vasoactive intestinal polypeptide, substance-P, and alpha-smooth muscle actin and were also stained by NADPH-diaphorase. Tn highly dilated proximal segments, a decreased number of protein gene product 9.5-positive fibers was found in both the circular muscle and submucous layers. The number of nerve fibers positive for vasoactive intestinal polypeptide, substance-P, and NADPH-diaphorase also decreased in the circular muscle layer, particularly in the deep muscular plexus. Hypertrophy and an alteration of the staining intensities in the circular muscle layer were also revealed by a-smooth muscle actin staining. The nerve distribution of the distal segments was indistinguishable from that of the age-matched controls and the sham-operated group. Abnormalities in the intramural nerves are only found in the proximal ileal segment of the IA models. The abnormal nerve distribution of the proximal segment might thus be implicated in the postoperative dysmotility of the intestine in IA.
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PMID:Alterations of the intramural nervous distributions in a chick intestinal atresia model. 989 Jun 5