Osteocyte ultrastructure in renal osteodystrophy

Summary The ultrastructure of the osteocyte has been studied in 80 needle biopsies from the iliac crest of uremic subjects with renal osteodystrophy.Different types of osteocytes were present in the osseous trabeculae. Those recognizable in completely uncalcified osteoid tissue looked like normal osteocytes, even though the matrix was not mineralized. Those present in hypomineralized areas showed enlarged and irregular lacunae when examined under the light microscope; under the electron microscope these osteolytic-like changes were not evident and were found to have been produced by defective calcification of the perilacunar matrix. Osteocytes placed in matrix whose mineralization was normal were often surrounded by a border of crystals protruding side-to-side from the bone matrix into the lacunar space. Other osteocytes were placed in unusually wide lacunae. They showed evidence of osteolytic activity, chiefly consisting of irregularity of the lacunar wall, presence of flocculent, granular and filamentous material in the pericellular space, and calcification of mitochondria. Degenerating and degenerate osteocytes were also recognizable.     

The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited

Phenylketonuric and hyperphenylalaninaemic patients in the population of the Republic of Ireland were screened for mutations at the human phenylalanine hydroxylase (PAH) locus. A composite data set for the island of Ireland was generated by merging the findings of this study with extant data for Northern Ireland. Analysis of this data on the basis of the four historic provinces (Munster, Leinster, Connacht and Ulster) revealed genetic diversity that is informative in terms of demographic forces that shaped the Irish population. R408W, the predominant Irish PAH mutation associated with haplotype 1.8, reached its highest relative frequency in the most westerly province, Connacht. This suggests that the gradient of R408W-1.8 observed across north-western Europe continues into Ireland and peaks in Connacht. Spatial autocorrelation analysis demonstrated that the gradient is consistent with a localised cline of R408W-1.8 likely to have been established by human migration. This and parallel allele frequency clines may represent the genetic traces of the Palaeolithic colonisation of Europe, a pattern not substantially altered in north-western Europe by subsequent Neolithic migrations. An analysis of mutant allele distributions in Ulster, Scotland and the rest of Ireland confirmed that Ulster has been a zone of considerable admixture between the Irish and Scottish populations, indicating a proportion of Scottish admixture in Ulster approaching 46%. Mutations primarily associated with Scandinavia accounted for 6.1% of mutations overall, illustrating the influence of Viking incursions on Irish population history.     

Walking modality affects respiratory muscle action and contribution to respiratory effort

We hypothesized that walking at increased speed or increasing gradient might have different effects on chest wall kinematics and respiratory muscle power components, and contribute differently to respiratory effort sensation. We measured the volumes of chest wall compartments by optoelectronic plethysmography, esophageal, gastric and transdiaphragmatic (P _di) pressures, and the sensation of the respiratory effort by a Borg scale in five normal subjects walking both at ascending gradient with constant speed (AG) and at ascending speed with constant gradient (AS). Chest wall kinematics, evaluated by displacement of chest wall compartments, did not show any significant difference between AS and AG. Muscle power, calculated as the product of mean flow and mean pressure, increased similarly, but its partitioning into pressure and velocity of shortening differed in the two modes. A greater increase in the pressure developed by the abdominal muscles (P _abm) (4.06-fold), and in the velocity of shortening of both rib cage inspiratory muscles (v _rcm,i) (2.01-fold) and the diaphragm (v _di) (1.90-fold) was associated with a lower increase in the pressure developed by the rib cage inspiratory muscles (P _rcm,i) (1.24-fold) and P _di (0.99-fold) with AG. Instead, with AS, a lower increase in P _abm (2.12-fold), v _rcm,i (1.66-fold) and v _di (1.54-fold) was associated with a greater increase in P _rcm,i (1.56-fold) and P _di (1.97-fold). A combination of P _abm and v _di during AG (Wald ²=23.19, P<0.0000), with the addition of P _rcm,i during AS (Wald ²=29.46, P<0.0000), was the best predictor of Borg score. In conclusion, the general strategy adopted by respiratory centers during different walking modes does not differ in terms of ventilation, chest wall kinematics, and respiratory muscle power production, whereas it does in terms of partitioning of power into pressure and velocity of shortening, and respiratory muscle contribution to respiratory effort sensation. Combinations of different patterns of flow and pressure generation made the respiratory effort sensation similar during AS and AG modes.     

Luminal surface microgeometry affects platelet adhesion in small-diameter synthetic grafts

One of the major problems when using small-diameter vascular grafts in arterial reconstruction is the development of platelet-rich thrombi as a consequence of blood contact with artificial surfaces. The degree of occlusion is certainly affected by the thrombogenicity of the internal surface that seems to play a key role in patency and long-term wound healing of grafts. In this study, the blood compatibility of Cardiothane (CA) vascular grafts was investigated. The CA material, a blend of polyurethane and polydimethylsiloxane that has shown relatively good physical and biocompatibility properties, was manufactured into vascular grafts by the instrument named "spray-machine". Grafts with different luminal surface porosity were produced using increasing CA concentrations by the "spray-machine" and the blood compatibility was evaluated in vitro by a circulation system in which the human blood was allowed to interact with the material in a well-controlled setting. The samples of circulating blood were collected at different times of circulation and platelet adhesion and activation were studied. Grafts with a highly porous luminal surface induced a lower adhesion and activation of platelets in vitro than the low-porosity ones. These results underlined the importance of the microgeometry of the graft luminal surface in the interaction with blood.     

Detection of minor and major satellite DNA in cytokinesis-blocked mouse splenocytes by a PRINS tandem labelling approach

A protocol for the simultaneous visualization of minor and majorsatellite DNA by primed in situ DNA synthesis PRINS was developedin cytokinesis–blocked murine splenocytes. After individuationof optimal experimental conditions, a micronucleus MN test wascarried out by treating splenocytes in vitro with the clastogenicagent mitomycin C and the aneugenic compound Colcemid. It wasfound that PRINS gives highly reproducible results, also comparablewith the literature on MN results obtained by fluorescent insitu hybridization FISH. Therefore the PRINS methodology maybe proposed as a fast alternative to FISH for the characterizationof induced MN. ¹To whom correspondence should be addressed     

Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study

A systematic analysis of both tumors and the surrounding urothelium to help identify what lies behind the mechanism of multifocal tumor development has not yet been performed. In this study we investigated chromosome 1, 7, 9, and 17 aneusomy in 25 superficial papillary carcinomas and in 51 tissue samples taken from sites of macroscopically uninvolved urothelium surrounding the tumors, using the fluorescence in situ hybridization method. Our data demonstrated a close genetic relationship between all examined tumors and normal-appearing mucosa. Numeric aberrations of chromosomes 1, 7, 9, and 17 were found to exhibit similar patterns in all analyzed specimens, although with different frequencies.