Muscle strength, volume and activation following 12-month resistance training in 70-year-old males

In elderly males muscle plantar flexor maximal voluntary contraction (MVC) torque normalised to muscle volume (MVC/VOL) is reduced compared to young males as a result of incomplete muscle activation in the elderly. The aim of the present study was to determine the influence of a 12-month resistance training programme on muscle volume, strength, MVC/VOL, agonist activation and antagonist coactivation of the plantarfexors in elderly males. Thirteen elderly males aged 70 years and over (range 70–82 years), completed a 12-month whole body resistance-training programme (TRN), training three times a week. Another eight males (range 18–30 years), who maintained their habitual physical activity for the same 12-month period as the TRN group acted as controls (CTRL). Isometric plantarflexor maximal voluntary contraction (MVC) torque increased in the TRN group by 20% (P<0.01), from 113.1±22.0 Nm to 141.5±19.2 Nm. Triceps surae volume (TS VOL) assessed using MRI, increased by 12%, from 796.3±78.9 cm³ to 916.8±144.4 cm³ . PF activation, measured using supramaximal double twitch interpolation, increased from 83.6±11.0% pre training, to 92.1±7.6% post training (P<0.05). Dorsiflexion MVC and antagonist coactivation (assessed using surface electromyography) did not change with training. Plantarflexor MVC torque normalized for triceps surae muscle volume (MVC/VOL) was 142.6±32.4 kN m^–2 before training and 157.0± 27.9 kN m^–2 after training (a non-significant increase of 8%). No significant change in any measurement was observed in the CTRL group. This study has shown that the gain in muscle strength in response to long-term (12-month) training in older men is mostly accounted for by an increased muscle volume and activation.     

CD10 is expressed in a subset of chromophobe renal cell carcinomas.

CD10 has been considered a useful marker in the diagnosis of renal carcinomas, because of its expression in clear cell and papillary renal cell carcinomas and its absence in chromophobe renal cell carcinomas. On the other hand, chromophobe renal cell carcinoma expresses parvalbumin, which is absent in clear cell and papillary renal cell carcinomas. To further address the relevance of these markers, we studied the expression of CD10 and parvalbumin in 42 samples of chromophobe renal cell carcinoma (seven of which had aggressive features, including invasion beyond the renal capsule, renal vein invasion, metastases, or sarcomatoid transformation), 75 clear cell renal cell carcinomas (eight metastatic) and 51 papillary renal cell carcinomas (two metastatic). CD10 was found in 100% of clear cell renal cell carcinomas, 63% of papillary renal cell carcinomas and in all metastatic cases of both types. At variance with previous studies, we found CD10 expression in from 30 to 90% of the neoplastic cells, in 11 of 42 (26%) chromophobe renal cell carcinomas. The CD10-positive cases included five of the seven (71%) chromophobe renal cell carcinoma with aggressive features. Statistical analysis showed significant association of CD10-positive tumors with clinicopathologic aggressiveness (P=0.003) and mitotic figures (P=0.04). Parvalbumin was strongly expressed in all primary and metastatic chromophobe renal cell carcinomas. Western blot analysis was utilized to confirm the expression of both CD10 and parvalbumin in chromophobe renal cell carcinomas.     

Vilse, a conserved Rac/Cdc42 GAP mediating Robo repulsion in tracheal cells and axons

Slit proteins steer the migration of many cell types through their binding to Robo receptors, but how Robo controls cell motility is not clear. We describe the functional analysis of vilse, a Drosophila gene required for Robo repulsion in epithelial cells and axons. Vilse defines a conserved family of RhoGAPs (Rho GTPase-activating proteins), with representatives in flies and vertebrates. The phenotypes of vilse mutants resemble the tracheal and axonal phenotypes of Slit and Robo mutants at the CNS midline. Dosage-sensitive genetic interactions between vilse, slit, and robo mutants suggest that vilse is a component of robo signaling. Moreover, overexpression of Vilse in the trachea of robo mutants ameliorates the phenotypes of robo, indicating that Vilse acts downstream of Robo to mediate midline repulsion. Vilse and its human homolog bind directly to the intracellular domains of the corresponding Robo receptors and promote the hydrolysis of RacGTP and, less efficiently, of Cdc42GTP. These results together with genetic interaction experiments with robo, vilse, and rac mutants suggest a mechanism whereby Robo repulsion is mediated by the localized inactivation of Rac through Vilse.     

Changes in EEG activity and hypothalamic temperature as indices for non-REM sleep to REM sleep transitions

A shift of physiological regulations from a homeostatic to a non-homeostatic modality characterizes the passage from non-NREM sleep (NREMS) to REM sleep (REMS). In the rat, an EEG index which allows the automatic scoring of transitions from NREMS to REMS has been proposed: the NREMS to REMS transition indicator value, NIV [J.H. Benington et al., Sleep 17 (1994) 28-36]. However, such transitions are not always followed by a REMS episode, but are often followed by an awakening. In the present study, the relationship between changes in EEG activity and hypothalamic temperature (Thy), taken as an index of autonomic activity, was studied within a window consisting of the 60s which precedes a state change from a consolidated NREMS episode. Furthermore, the probability that a transition would lead to REMS or wake was analysed. The results showed that, within this time window, both a modified NIV (NIV(60)) and the difference between Thy at the limits of the window (Thy(D)) were related to the probability of REMS onset. Both the relationship between the indices and the probability of REMS onset was sigmoid, the latter of which saturated at a probability level around 50-60%. The efficacy for the prediction of successful transitions from NREMS to REMS found using Thy(D) as an index supports the view that such a transition is a dynamic process where the physiological risk to enter REMS is weighted at a central level.     

Human papillomavirus typing with GP5+/6+ polymerase chain reaction reverse line blotting and with commercial type-specific PCR kits.

BACKGROUND: Infection with human papillomavirus (HPV) is a necessary step in the progression to cervical cancer. Many methods for HPV testing are currently available, most developed to detect pools of HPV types. OBJECTIVES: To evaluate the HPV typing by molecular methods and to compare commercial kits with an established laboratory method. STUDY DESIGN: Eighty-four cervical samples found to be positive for HPV DNA by GP5+/6+-polymerase chain reaction-enzyme immunoassay-reverse line blotting (PCR-EIA-RLB) were re-tested with two commercial methods, INNO-LiPA and Amplisense HPV typing, able to identify the HPV type predicted by PCR-EIA-RLB in 76 and 67 samples, respectively. RESULTS: The INNO-LiPA assay revealed HPV DNA in 75/76 samples (98.7%; 95% CI, 0.93-0.99) that would contain HPV types identifiable by this assay. The Amplisense HPV assay revealed HPV DNA in 58/67 samples (86.6%; 95% CI, 0.76-0.93) containing HPV types detectable by this assay. For samples with a single infection, the unweighted kappa for concordance of HPV typing was 0.87 (95% CI, 0.78-0.97) for PCR-EIA-RLB versus INNO-LiPA, 0.94 (95% CI, 0.87-0.99) for INNO-LiPA versus Amplisense HPV, and 0.82 (95% CI, 0.70-0.94) for PCR-EIA-RLB versus Amplisense HPV typing. PCR-EIA-RLB revealed 12 multiple infections, INNO-LiPA revealed 14, and Amplisense HPV revealed 5. The agreement among tests for samples with multiple infections was lower, giving kappa values of 0.44 (95% CI, 0.18-0.70) for PCR-EIA-RLB versus INNO-LiPA, 0.52 (95% CI, 0.19-0.85) for PCR-EIA-RLB versus Amplisense HPV and 0.43 (95% CI, 0.12-0.74) for INNO-LiPA versus Amplisense HPV. CONCLUSIONS: In HPV-positive samples, the agreement among tests for HPV typing was high for single infections but markedly lower for infections with multiple HPV types.     

Synergistic interaction of topographic features in the production of bone-like nodules on Ti surfaces by rat osteoblasts

The objective of this study was to study the responses of osteoblast-like cells to rough Titanium (Ti)-coated epoxy surfaces of differing topographic complexity. Four topographies were studied: polished (PO), coarse-blasted (CB), acid-etched (AE) and coarse-blasted+acid-etched (SLA). Rat osteoblasts were cultured on these surfaces and their morphology, thickness as well as the number and size of bone-like nodules measured. To determine cell shape and cell thickness, fluorescein-5-thiosemicarbazide was used to stain the cell components including the cell membrane, the stained cells were optically sectioned using epifluorescent microscopy and the optical sections were computationally reconstructed to obtain three-dimensional images in which cell volume and cell thickness could be determined. Similarly optical sections of bone-like nodules labeled with tetracycline were also reconstructed to determine their size. The different surface topographies were found to alter the thickness and morphology of osteoblasts cultured on these surfaces. Osteoblasts produced significantly more and larger nodules on SLA compared to other surfaces. Nevertheless and perhaps surprisingly, given the evidence in various cell populations that cell shape can affect cell differentiation, cell thickness was not directly correlated with an increase in bone-like nodule formation. Data were analyzed by factorial analysis of variance. In this way the primary effect of each surface treatment ( i.e. blasting and acid etching) could be assessed as well as their interaction. Both the acid etching and blasting processes significantly affected the number and size of bone-like nodules cultured on Ti surfaces. Moreover there were significant interaction effects indicating that surface topographic features can act synergistically to enhance bone formation. This result suggests that a useful approach to the optimization of surfaces for bone production could involve systematic investigation of combinations of processes each of which produces distinct surface topographical features.     

Histological study of the proximal and distal segments of the embryonic outflow tract and great arteries

The normal development of the ventricular outlets and proximal region of the great arteries is a controversial subject. It is known that the conus, truncus arteriosus (truncus), and aortic sac participate; however, there are some doubts as to the actual prospective fate of the truncus. Some authors propose that it gives origin to the proximal region of the great arteries and that the myocardial cells of its wall become smooth muscle. Nevertheless, others think that the truncus only forms the arterial valve apparatus and that therefore the myocardial cells transform into fibroblasts. As a first approach to beginning to elucidate which process occurs, the aim of this article was to study the histological changes in the wall of these components of the developing heart in chick embryos whose hearts had been labeled at the truncoconal boundary at stage 22HH, tracing the changes up to stage 36HH. Also, the histological constitution of the wall of the pulmonary arterial trunk and its valve apparatus were studied in the posthatching and adult hearts of chickens and rats. The conus and truncus walls were always encircled by a myocardial sleeve from the outset of their development. Between stages 26HH to 28HH, the truncal myocardial cells adjacent to the mesenchymal tissue of the ridges began to lose cell-to-cell contacts and invaded the extracellular matrix. At stage 24HH, the aortic sac began to project into the pericardial cavity and became divided into two channels by the aortic-pulmonary septum at stage 26HH. The wall of the aortic sac is mostly constituted by a compact mesenchymal tissue. Initially, it does not have smooth muscle but this starts to appear at stage 30HH. The insertion ring of the valves, a broad structure, was formed by mesenchymal tissue. Both structures were always covered by a myocardial sleeve. The leaflets developed from the truncal ridges, the segment immediately proximal to the aortic sac. Our results indicate that the proximal region of the pulmonary and aortic arteries do not originate from the truncus arteriosus; rather, we found that they take origin from the aortic sac. Thus, our findings agree with the proposal that the myocardial cells of the external sleeve of the truncus become fibroblastic and suggest that the insertion ring of the arterial valves has a dual origin: fibroblasts produced by truncal myocardial transdiferentiation and the mesenchymal tissue of the proximal region of the truncal ridges, while the leaflets have their origin from the truncal ridges. We discuss the fact that, because the truncus arteriosus does not give origin to the trunks of the aortic and pulmonary arteries, it may be necessary to modify terminology. Based on our results, together with the new findings obtained by in vivo labeling, immunostaining, a chimeric approach, and ultrastructural studies, we propose a developmental model that correlates the fate of the conus, truncus, and aortic sac with the normal morphogenesis of the ventricular outlet tracts and the trunks of the great arteries. (c) 2005 Wiley-Liss, Inc.     

Chronic sclerosing sialadenitis (Kuttner's tumor): unusual presentation with bilateral involvement of major and minor salivary glands

In 1896 Kuttner reported four cases which he described as induration of the submandibular gland. Histologically, they showed chronic inflammation and fibrosis. Sporadic cases of this entity that have come to be known as Kuttner's tumor or chronic sclerosing sialadenitis of the submandibular gland and have been reported throughout the 20th century. This inflammatory tumor has been under-recognized, and awareness of its importance and probable immunologic background have recently become evident. We report an unusual case of chronic sclerosing sialadenitis, affecting both parotid glands, both submandibular glands, and minor salivary glands of the oral cavity, and explore the immunohistochemical profile of this entity.     

NK-active cytokines IL-2, IL-12, and IL-15 selectively modulate specific protein kinase C (PKC) isoforms in primary human NK cells.

Natural killer (NK) cell function is largely modulated by growth factors and cytokines. In particular, interleukin (IL)-2, IL-12, and IL-15 have major effects on the proliferative and cytotoxic activities of NK cells against tumor and virus-infected cells. It is thought that the members of the protein kinase C (PKC) family of serine/threonine kinases play an important role in mediating the pleiotropic effects of cytokines on their target cells. We have investigated the downstream effects generated in purified human NK cells by IL-2, IL-12, and IL-15 on PKCalpha and PKCepsilon--a canonical and a novel isoform of PKC, respectively. By means of Western blotting, PKC activity assays, and immunofluorescence performed on highly purified preparations of primary human NK cells, we demonstrate that: 1) the three cytokines have similar effects on PKCalpha and PKCepsilon activities; 2) whereas PKCepsilon activity is induced by cytokine stimulation, PKCalpha activity is inhibited; and 3) both the induction of PKCepsilon and the inhibition of PKCalpha functional activity are relatively early events in NK cells, while longer cytokine stimulations do not generate significant variations in enzyme activity, suggesting that the activation of both the canonical and novel isoforms of PKC are events required in the early phases of cytokine-induced NK cell stimulation.