[Solid, asymptomatic nodules on several toes in a child]. / Derbe, asymptomatische Knoten an mehreren Zehen bei einem Kind.

The term infantile digital fibromatosis describes a benign tumor of the group of fibromatoses. The prevalence rate is approximately 2.5% of all fibromatoses. The etiopathogenesis of infantile digital fibromatosis is unknown. These tumors can appear already at birth, but usually manifest during the first 3 years of life as solid, pink or skin-colored asymptomatic nodules on one or several fingers or toes. Because of the postoperative recurrence rate of 50-75% and the possibility of spontaneous regression, excision is not recommended according to currently available evidence.

Immunohistochemically detected protein nitration indicates sites of renal nitric oxide release in Goldblatt hypertension.

In the kidney, nitric oxide (NO) from the macula densa (MD) is considered an integral modulator of the tubulovascular message system, whereas endothelium-derived NO is a major vasorelaxing factor. The goal of the present study was to determine extracellular pathways of NO in rats with renovascular two-kidney, one clip Goldblatt hypertension (2K1C). To localize NO in the tissue, immunohistochemical detection of NO-dependent tyrosine nitration was performed using a monoclonal antibody against nitrotyrosine. Nitration of phenolic compounds such as tyrosine results from the reaction with peroxynitrite (ONOO ) formed by NO and molecular oxygen or superoxide and may therefore be used as a footprint for local release of NO. Significant nitrotyrosine immunoreactivity was detected in the extraglomerular mesangium (EGM) of the stenotic kidney in 2K1C rats, whereas in the nonclipped contralateral kidney and in control animals no signal was detected at this site. Positive staining of the EGM was paralleled by enhanced NADPH diaphorase (NADPH-d) staining of the adjacent MD, signifying increased type I nitric oxide synthase (NOS) activity in the stenotic kidney. In contrast, in the cortical vasculature selectively enhanced nitrotyrosine immunoreactivity was detected in the arteriolar wall of the nonclipped contralateral kidney, and endothelial NADPH-d signal, indicating NOS Type III activity, was enhanced in parallel. Our results suggest that in MD, stimulation of NOS in the stenotic Goldblatt kidney induces the release of NO into the EGM. From there an NO-dependent intermediate stimulus may reach the glomerular vasculature. Footprints of NO-dependent effects in the vascular smooth muscle layer of the non-clipped contralateral kidney indicate a marked vasodilatory response that may have been caused by enhanced shear stress and/or angiotensin II levels.

Parallel regulation of constitutive NO synthase and renin at JGA of rat kidney under various stimuli.

Four chronic experiments were performed to assess changes in the activity and gene expression of type I nitric oxide synthase (NOS) at the macula densa (MD) and of renin expression and immunoreactivity (IR) at the juxtaglomerular apparatus (JGA) of rat kidney, as follows: 1) two-kidney, one-clip Goldblatt hypertension (2K1C, for 3 and 40 days; sham operation for controls), 2) furosemide treatment (150 mg/kg-1.day-1 ip for 5 days), 3) chronic low-salt diet (0.02%) vs. high-salt diet (3%; both for 11 days), and 4) chronic blockade of NOS by nitro-L-arginine methyl ester (L-NAME, 40 mg.kg-1.day-1 for 2 mo). NOS and renin gene expression, NOS enzyme activity and renin IR were semiquantitatively evaluated with histochemical methods (NADPH diaphorase, in situ hybridization, immunohistochemistry). In 2K1C, marked increases were induced in NOS and renin in the ischemic vs. contralateral kidneys both after 3 and 40 days, respectively (P < 0.05). Related to controls, significant increases in the ischemic kidney were encountered after 3 and 40 days, whereas contralateral suppression of NOS and renin was found only after 40 days. Furosemide treatment resulted in a marked increase of both NOS and renin levels compared with controls (P < 0.05). Salt restriction induced a significant elevation of NOS levels compared with salt loading (P < 0.05), whereas only minor changes were evident in renin levels. L-NAME treatment resulted in a moderate reduction of NOS activity (not significant), whereas renin levels were markedly reduced (P < 0.05). These results show that NOS activity and gene expression are inversely related to chronic changes in renal perfusion, salt balance, and salt transport at the distal tubule in parallel with the known response of renin to these changes. Inhibition of NOS decreases renin levels at the JGA. The histochemical findings support previous concepts that MD-derived NO is involved in the control of renin synthesis.

Topography of nitric oxide synthesis by localizing constitutive NO synthases in mammalian kidney.

Nitric oxide (NO) is generated from L-arginine by NO synthase (NOS). We have investigated the localization of constitutive NOS isoforms in rat, mouse, guinea pig, rabbit, pig, and human kidney. NADPH diaphorase (NADPH-d) reaction was used for histochemical detection of NOS enzyme activity, neuronal NOS (NOS I) and endothelial NOS (NOS III) were identified by specific antibody, and in situ hybridization was applied for NOS I mRNA detection. Strong presence of NOS I in macula densa (MD), previously detected in rat, was found in all species including humans. Additional NOS I-positive cells of the thick ascending limb (TALH) were defined. A clear-cut distinction between Tamm-Horsfall-protein-positive cells of the TALH and NOS I-positive cells of the TALH was shown. Ultrastructurally, NOS I was located in the cytosol. Intimate spatial relation between NOS I-positive cells and renin-containing preglomerular afferent arteriole suggests an effect of MD-derived NO on the juxtaglomerular granular cells. In the renal vasculature, both NADPH-d and NOS III were located in the endothelium of cortical and medullary vessels, whereas the muscle layer was unreactive. The glomerular arterioles showed stronger labeling in the efferent than in the afferent endothelium, and efferent endothelium selectively contained both NOS I and NOS III. The unique morphology of efferent endothelial cells indicates a particular role for NO in this vessel segment. At the capillary level, only the glomerular tuft showed NOS-positive endothelia. A subpopulation of renal nerves containing NADPH-d and NOS I was found in perivascular connective tissue and near pelvic epithelium. These results demonstrate a wide distribution of two constitutive NOS isoforms in the kidney of various animal species including humans. The distinct location of both isoforms in the cortex confirms that NO plays a crucial role in local glomerular signaling events.