The visceromotor and somatic afferent nerves of the penis.

INTRODUCTION: Innervation of the penis supports erectile and sensory functions. AIM: This article aims to study the efferent autonomic (visceromotor) and afferent somatic (sensory) nervous systems of the penis and to investigate how these systems relate to vascular pathways. METHODS: Penises obtained from five adult cadavers were studied via computer-assisted anatomic dissection (CAAD). MAIN OUTCOME MEASURES: The number of autonomic and somatic nerve fibers was compared using the Kruskal-Wallis test. RESULTS: Proximally, penile innervation was mainly somatic in the extra-albugineal sector and mainly autonomic in the intracavernosal sector. Distally, both sectors were almost exclusively supplied by somatic nerve fibers, except the intrapenile vascular anastomoses that accompanied both somatic and autonomic (nitrergic) fibers. From this point, the neural immunolabeling within perivascular nerve fibers was mixed (somatic labeling and autonomic labeling). Accessory afferent, extra-albugineal pathways supplied the outer layers of the penis. CONCLUSIONS: There is a major change in the functional type of innervation between the proximal and distal parts of the intracavernosal sector of the penis. In addition to the pelvis and the hilum of the penis, the intrapenile neurovascular routes are the third level where the efferent autonomic (visceromotor) and the afferent somatic (sensory) penile nerve fibers are close. Intrapenile neurovascular pathways define a proximal penile segment, which guarantees erectile rigidity, and a sensory distal segment.

Role of oxidative stress in cardiac dysfunction of PPARalpha-/- mice.

This study was designed to determine the effects of PPARalpha lack on cardiac mechanical performance and to identify potential intracellular mechanisms linking PPARalpha pathway deficiency to cardiac contractile dysfunction. Echocardiography, ex vivo papillary muscle assays, and in vitro motility assays were used to assess global, intrinsic ventricular muscle performance and myosin mechanical properties, respectively, in PPARalpha(-/-) and age-matched wild-type mice. Three-nitrotyrosine formation and 4-hydroxy-2-nonenal protein-adducts, both markers of oxidative damage, were analyzed by Western blot analysis and immunolabeling. Radical scavenging capacity was analyzed by measuring protein levels and/or activities of the main antioxidant enzymes, including catalase, glutathione peroxidase, and manganese and copper-zinc superoxide dismutases. Echocardiographic left ventricular fractional shortening in PPARalpha(-/-) was 16% lower than that in wild-type. Ex vivo left ventricular papillary muscle exhibited reduced shortening velocity and isometric tension (three- and twofold, respectively). In vitro myosin-based velocity was approximately 20% slower in PPARalpha(-/-), indicating that myosin itself was involved in the contractile dysfunction. Staining of 3-nitrotyrosine was more pronounced in PPARalpha(-/-), and myosin heavy chain was the main nitrated protein. Formation of 3-nitrotyrosine myosin heavy chain was twofold higher in PPARalpha(-/-) and 4-hydroxy-2-nonenal protein-adducts were threefold higher. The expression and activity of manganese superoxide dismutase were respectively 33% and 50% lower in PPARalpha(-/-), with no changes in copper-zinc superoxide dismutase, catalase, or glutathione peroxidase. These findings demonstrate that PPARalpha pathway deficiency impairs cardiac function and also identify oxidative damage to myosin as a link between PPARalpha deficiency and contractile dysfunction.

Expression, hormonal regulation, and subcellular localization of CCAAT/enhancer-binding protein-beta in rat and human thyrocytes.

The expression pattern of CCAAT/enhancer binding protein-beta (C/EBP-beta) was investigated in thyroid cells and tissues. Translation of C/EBP-beta mRNA results in the production of two isoforms, liver-enriched transcriptional activating protein (LAP) and liver-enriched transcriptional inhibitory protein (LIP), the latter lacking the transactivation domain. We found that LAP and LIP are expressed in the rat thyroid gland and in the FRTL-5 and PCCL3 rat thyroid cell lines. Thyrotropin (TSH), insulin, and serum withdrawal from cultures of thyroid cells induced downregulation of LAP and LIP expression. Subsequent activation of the cyclic adenosine monophosphate (cAMP) and insulin signaling pathways reinduced both isoforms. Vectors expressing rat LAP and LIP were constructed to study the effect of C/EBP-beta isoforms on the activity of the sodium iodide symporter (NIS) promoter in PCCL3 cells. The cAMP-stimulated activity of the NIS promoter was decreased by overexpression of LAP, whereas LIP had no significant effect. Expression of C/EBP-beta was studied by immunohistochemistry in normal human thyroid and papillary cancer tissues. C/EBP-beta immunostaining was always restricted to the nuclei of the normal thyrocytes. In contrast, C/EBP-beta was expressed mainly in the cytoplasm of thyroid papillary carcinoma cells. These data suggest that this factor may play important roles in the regulation of thyroidspecific genes and processes, and that its functions are altered in human thyroid carcinoma.

Expression of BAFF (BLyS) in T cells infiltrating labial salivary glands from patients with Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterized by lymphocytic infiltration of the salivary glands. Most of the infiltrating cells are T cells, but other features of the disease include polyclonal B-cell activation, systemic production of autoantibodies, and increased risk of developing B-cell non-Hodgkin's lymphoma. Recently, a new tumour necrosis factor, the B-cell activating factor (BAFF; also known as BLyS), has been implicated in the polyclonal activation of B cells. Using immunohistochemistry, this study evaluated BAFF expression in labial salivary gland biopsies from 14 patients with pSS, 14 normal controls, and two patients with sarcoidosis. Labial salivary gland samples from seven patients with pSS, seven controls, and one patient with sarcoidosis were double-stained using indirect immunofluorescence. RT-PCR analysis was also performed on lip biopsy samples from two patients and two controls. In all 14 pSS specimens, infiltrating inflammatory cells strongly expressed BAFF protein, as did some ductal epithelial cells, but acinar cells were negative. Some B cells were present in the vicinity of the BAFF-positive cells. In the 14 normal labial salivary glands, some ductal cells were moderately positive, but acinar cells were negative. In the labial salivary glands from the two patients with sarcoidosis, infiltrating lymphocytes were not stained. BAFF mRNA expression was confirmed by RT-PCR in salivary glands from pSS patients. Double immunofluorescence revealed T cells and macrophages to be the main cell types expressing BAFF in salivary glands from pSS patients. In conclusion, BAFF may be expressed by T cells at the site of autoimmune damage and could play a role in the pathogenesis of pSS, particularly by triggering the activation of self-antigen-driven autoimmune B cells.

Angiographic right and left ventricular function in arrhythmogenic right ventricular dysplasia.

We prospectively documented right ventricular (RV) and left ventricular (LV) volumes and ejection fractions in a large series of patients with arrhythmogenic RV dysplasia/cardiomyopathy (ARVD/C). Eighty-five patients with ARVD/C and 11 controls underwent 2 successive orthogonal right and left monoplane x-ray-digitized cineangiographies. Volumes were calculated using the hemielliptical RV and ellipsoidal LV models. All controls and 58 of 85 patients (ARVD/C-I) had a RV ejection fraction > or =35% and 27 patients had a RV ejection fraction <35% (ARVD/C-II). Tricuspid annulus plane systolic excursion (TAPSE) was lower in ARVD/C-II than in ARVD/C-I patients (6 +/- 3 vs 14 +/- 3 mm) and controls (16 +/- 2 mm) (each p <0.001). In patients with ARVD/C, TAPSE was positively related to RV ejection fraction (r = 0.79) and to crista supraventricularis shortening (r = 0.81) (each p <0.001). Sensitivity and specificity of TAPSE <12 mm in identifying patients with RV ejection fraction <35% were 96% and 78%, respectively. LV ejection fraction was > or =50% in 68 patients, 40% to 49% in 10, and <40% in 7. Diffuse RV outflow tract aneurysm was observed in 9 patients, all belonging to ARVD/C-II, and this sign identified patients with LV ejection fraction <40% with 86% sensitivity and 96% specificity. In conclusion, 68% of ARVD/C patients had normal RV ejection fraction and RV volumes, and 80% of ARVD/C patients had normal LV ejection fraction. Decreased TAPSE <12 mm and a diffuse RV outflow tract aneurysm were sensitive and specific indicators of RV ejection fraction <35% and LV ejection fraction <40%, respectively.

RANK (receptor activator of nuclear factor-kappaB) and RANKL expression in multiple myeloma.

The new members of the tumour necrosis factor (TNF) receptor-ligand family, receptor activator of nuclear factor-kappaB ligand (RANKL) and its receptor RANK, play a crucial role in osteoclast differentiation and activation. An increased expression of RANKL and/or RANK may be involved in the excessive bone resorption observed in multiple myeloma (MM). We used immunohistochemistry to study RANK and RANKL expression in bone marrow (BM) biopsies obtained at diagnosis in 15 MM patients, six patients with monoclonal gammopathy of undetermined significance (MGUS) and 10 normal BM biopsies. Plasma cells were not labelled with anti-RANKL or anti-RANK antibodies. In all biopsies, RANKL was expressed in endosteal bone surface, around vessels and in cells characterized by cytoplasmic expansions. These last cells did not express CD45 and were vimentin positive, corresponding to bone marrow stromal cells. Numerous stromal cells expressed RANKL in MM and MGUS specimens, with a greater expression in MM than in MGUS. Very few cells were stained with anti-RANKL in normal BM specimens. With the anti-RANK antibody, small mononuclear cells in the bone microenvironment were positive and were identified as erythroblast cells. In conclusion, we showed that RANKL was expressed in reticular stromal cells, with a greater intensity in myeloma specimens. These results suggest that RANKL overexpressed by bone marrow stromal cells may contribute to the high rate of bone resorption observed in MM.