Canine liver transplantation under nva cyclosporine versus cyclosporine

The immunosuppressive qualities and other features of a new cyclosporine (CsA) analogue, Nva 2-cyclosporine (Nva 2-CsA) were examined using canine orthotopic liver allografts. The mean survival time was 11.8±9.6 (SD) days in dogs without treatment, 60.8±34.4 days with Nva 2-CsA and 65.1±33.0 days with CsA. Functional abnormalities indicating toxic side effects were not noted either with Nva 2-CsA or with CsA. Using the same oral dose, the rate of blood level rise and the amount of the rise were greater with Nva2-CsA. Histopathologically, Nva2-CsA the treatment was associated with the same degree of hydropic vocuolation in the pars recta of the proximal tubules as CsA treatment. Thus, in the dog, Nva2-CsA had identical immunosuppressive properties as CsA, with no functionally detectable toxicity affecting the liver and kidney. © 1986 by The Williams & Wilkins Co

Multipurpose High Frequency Electron Spin Resonance Spectrometer for Condensed Matter Research

We describe a quasi-optical multifrequency ESR spectrometer operating in the 75-225 GHz range and optimized at 210 GHz for general use in condensed matter physics, chemistry and biology. The quasi-optical bridge detects the change of mm wave polarization at the ESR. A controllable reference arm maintains a mm wave bias at the detector. The attained sensitivity of 2x10^10 spin/G/(Hz)1/2, measured on a dilute Mn:MgO sample in a non-resonant probe head at 222.4 GHz and 300 K, is comparable to commercial high sensitive X band spectrometers. The spectrometer has a Fabry-Perot resonator based probe head to measure aqueous solutions, and a probe head to measure magnetic field angular dependence of single crystals. The spectrometer is robust and easy to use and may be operated by undergraduate students. Its performance is demonstrated by examples from various fields of condensed matter physics.Comment: submitted to Journal of Magnetic Resonanc

Lack of trust in maternal support is associated with negative interpretations of ambiguous maternal behavior

Attachment theory assumes that children who lack trust in maternal availability for support are more inclined to interpret maternal behavior in congruence with their expectation that mother will remain unavailable for support. To provide the first test of this assumption, early adolescents (9-13 years old) were asked to assess whether ambiguous interactions with mother should be interpreted in a positive or a negative way. In our sample (n = 322), results showed that early adolescents' lack of trust in their mother's availability for support was related to more negative interpretations of maternal behavior. The associations remained significant after controlling for depressive mood. The importance of these findings for our understanding of attachment theory, attachment stability, and clinical practice are discussed

Post-operative cognitive function following general versus regional anesthesia, a systematic review

The effect of anesthetic technique on postoperative outcomes remains in question. This systematic review compares the role of regional versus general anesthesia, with a particular focus on postoperative cognitive function. Potentially relevant articles were identified by searching publicly available computerized databases for this systematic review. Any surgical procedure was accepted with the exception of cardiac, carotid, and neurosurgical procedures. Any regional anesthetic technique was accepted unless combined with a general anesthetic or in conjunction with propofol as a sedative. Any measure of postoperative cognitive function was accepted as long as it was performed no sooner than 7 days postoperatively. Sixteen studies met inclusion criteria and were included in the final analysis. Three studies showed some difference in cognitive function between regional and general anesthesia, whereas the remaining 13 showed no difference between regional and general anesthesia on postoperative cognitive function

Effect of surface conditioning with cellular extracts on Escherichia coli adhesion and initial biofilm formation

Bacterial adhesion and subsequent biofilm formation start with surface conditioning by molecules originating from the surrounding medium and from cell lysis. Different cell extracts e.g. total cell extract (TCE), cytoplasm with cellular debris (CCDE) and periplasmic extract (PE) were tested in agitated 96-well microtiter plates and in a flow cell. Crystal violet assay demonstrated that a polystyrene substratum conditioned with TCE or CCDE decreased initial biofilm formation, however cell adhesion generally increased when PE was used. These results were dependent on conditioning film concentration. Using a parallel plate flow chamber, the use of optimal conditioning film concentrations resulted in all the different cellular extracts reducing biofilm formation. Multifractal analysis was used to generate quantitative data on the number of cell clusters. Surface conditioning with cellular components affected the amount and clustering of bacteria on polystyrene surfaces and their propensity to induce biofilm formation. To the best of our knowledge, this is the first study addressing the effect of cellular surface conditioning of cellular compartments on E. coli adhesion and initial biofilm formation. This work leads to a greater understanding of the factors that influence biofilm formation under flow conditions which are prevalent in food industry

Surface Topography on the Distribution, Density, Dispersion and Clustering of Differently Organised Coccal-Shaped Bacteria

The topographic features of surfaces are known to affect bacterial retention on a surface, but the precise mechanisms of this phenomenon are little understood. Four coccal-shaped bacteria, Staphylococcus sciuri, Streptococcus pyogenes, Micrococcus luteus, and Staphylococcus aureus, that organise in different cellular groupings (grape-like clusters, tetrad-arranging clusters, short chains, and diploid arrangement, respectively) were used. These differently grouped cells were used to determine how surface topography affected their distribution, density, dispersion, and clustering when retained on titanium surfaces with defined topographies. Titanium-coated surfaces that were smooth and had grooved features of 1.02 µm-wide, 0.21 µm-deep grooves, and 0.59 µm-wide, 0.17 µm-deep grooves were used. The average contact angle of the surfaces was 91°. All bacterial species were overall of a hydrophobic nature, although M. luteus was the least hydrophobic. It was demonstrated that the 1.02 µm-wide featured surface most affected Strep. pyogenes and S. sciuri, and hence the surfaces with the larger surface features most affected the cells with smaller dimensions. The 0.59 µm featured surface only affected the density of the bacteria, and it may be suggested that the surfaces with the smaller features reduced bacterial retention. These results demonstrate that the size of the topographical surface features affect the distribution, density, dispersion, and clustering of bacteria across surfaces, and this is related to the cellular organisation of the bacterial species. The results from this work inform how surface topographical and bacterial properties affect the distribution, density, dispersion, and clustering of bacterial retention

Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations

PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Genetic variants in MUTYH are not associated with endometrial cancer risk

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is an autosomal dominant inherited predisposition to a number of epithelial cancers, most notably colorectal and endometrial cancer. Outside of the context of Lynch syndrome there is little evidence for an autosomal dominant or recessive condition that predisposes to endometrial cancer. Recently, genetic variants in MUTYH have been associated with a recessive form of colorectal cancer, known as MUTYH associated polyposis or MAP. MUTYH is involved in base excision repair of DNA lesions and as such a breakdown in the fidelity of this process would necessarily not be predicted to result in a specific disease. At present there is little information about the role of MUTYH in other types of cancer and only one report indicating a possible relationship with endometrial cancer