Serotyping for homotransplantation V. Evaluation of a matching scheme

An attempt was made to determine whether 36 long-term kidney homograft recipients and their donors were compatible for 7 major leukocyte groups. It was found that 21 of these recipients were surviving 2 to 3 years in spite of incompatibility for 1 or 2 major leukocyte antigens. Survival of mismatched grafts does not itself indicate that the antigens being measured are not transplantation antigens, for it was shown that the 15 recipients with no groups of mismatch were clinically superior to those with group incompatibilities. Moreover, histopathologic scores given to biopsy specimens taken 2 to 3 years after transplantation were significantly correlated with the number of group mismatches. Because the leukocyte groups were determined by cytotoxicity reactions of peripheral blood lymphocytes, the results may have been influenced considerably by chimerism in chronically dialyzed uremic patients or change in lymphocyte antigenicity or susceptibility to lysis upon prolonged immunosuppressive treatment. Although the possibility of these complications could not be ruled out in all instances, it was shown that 52 dialyzed uremic patients and 49 patients who had been treated with immunosuppression for over 1 year did not possess more or less antigens than a random population of normal individuals. It is concluded that: (1) the major leukocyte antigens are histocompatibility antigens, and (2) since survival can be attained at times despite mismatches for these groups, the antigens are of intermediate strength and kidney homograft rejection may occur if excessive numbers of antigens are incompatible or if particular combinations of antigens are mismatched. © 1966 by The Williams and Wilkins Co

Filamentous Biopolymers on Surfaces: Atomic Force Microscopy Images Compared with Brownian Dynamics Simulation of Filament Deposition

Nanomechanical properties of filamentous biopolymers, such as the persistence length, may be determined from two-dimensional images of molecules immobilized on surfaces. For a single filament in solution, two principal adsorption scenarios are possible. Both scenarios depend primarly on the interaction strength between the filament and the support: i) For interactions in the range of the thermal energy, the filament can freely equilibrate on the surface during adsorption; ii) For interactions much stronger than the thermal energy, the filament will be captured by the surface without having equilibrated. Such a ‘trapping’ mechanism leads to more condensed filament images and hence to a smaller value for the apparent persistence length. To understand the capture mechanism in more detail we have performed Brownian dynamics simulations of relatively short filaments by taking the two extreme scenarios into account. We then compared these ‘ideal’ adsorption scenarios with observed images of immobilized vimentin intermediate filaments on different surfaces. We found a good agreement between the contours of the deposited vimentin filaments on mica (‘ideal’ trapping) and on glass (‘ideal’ equilibrated) with our simulations. Based on these data, we have developed a strategy to reliably extract the persistence length of short worm-like chain fragments or network forming filaments with unknown polymer-surface interactions

Links between traumatic brain injury and ballistic pressure waves originating in the thoracic cavity and extremities

Identifying patients at risk of traumatic brain injury (TBI) is important because research suggests prophylactic treatments to reduce risk of long-term sequelae. Blast pressure waves can cause TBI without penetrating wounds or blunt force trauma. Similarly, bullet impacts distant from the brain can produce pressure waves sufficient to cause mild to moderate TBI. The fluid percussion model of TBI shows that pressure impulses of 15-30 psi cause mild to moderate TBI in laboratory animals. In pigs and dogs, bullet impacts to the thigh produce pressure waves in the brain of 18-45 psi and measurable injury to neurons and neuroglia. Analyses of research in goats and epidemiological data from shooting events involving humans show high correlations (r > 0.9) between rapid incapacitation and pressure wave magnitude in the thoracic cavity. A case study has documented epilepsy resulting from a pressure wave without the bullet directly hitting the brain. Taken together, these results support the hypothesis that bullet impacts distant from the brain produce pressure waves that travel to the brain and can retain sufficient magnitude to induce brain injury. The link to long-term sequelae could be investigated via epidemiological studies of patients who were gunshot in the chest to determine whether they experience elevated rates of epilepsy and other neurological sequelae

Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Gravitational physics with antimatter

The production of low-energy antimatter provides unique opportunities to search for new physics in an unexplored regime. Testing gravitational interactions with antimatter is one such opportunity. Here a scenario based on Lorentz and CPT violation in the Standard- Model Extension is considered in which anomalous gravitational effects in antimatter could arise.Comment: 5 pages, presented at the International Conference on Exotic Atoms (EXA 2008) and the 9th International Conference on Low Energy Antiproton Physics (LEAP 2008), Vienna, Austria, September 200

The Notochord, Notochordal cell and CTGF/CCN-2: ongoing activity from development through maturation

The growth regulating factor CTGF/CCN-2 is an integral factor in growth and development, connective tissue maintenance, wound repair and cell cycle regulation. It has recently been reported that CTGF/CCN-2 is involved in very early development having been detected in early notochord formation in zebrafish using CTGF/CCN-2 promoter-driven green fluorescent protein (GFP) plasmids. In these studies fluorescence was detected early in the developing embryos, a finding of considerable significance in that CTGF/CCN-2 deficient mutant mice die early after birth due to severe cartilage and skeletal dysplasia and respiratory failure. Such findings confirm the importance of CTGF/CCN-2 in development and of the necessary and sufficient role of this molecule in formation of the skeleton, extracellular matrix and chondrogenesis. Of particular relevance to the relationship between the notochordal cell and CTGF/CCN-2 there is a remarkable sub-species of canine, the ‘non-chondrodystrophic’ canine that is protected from developing degenerative disc disease (DDD). These animals are unique in that they preserve the population of notochordal cells within their disc nucleus (NP) and these cells secrete CTGF/CCN-2. We have detected CTGF/CCN-2 within conditioned medium developed from the notochordal cells of these animals (NCCM) and used this conditioned medium to demonstrate robustly increased proteoglycan production. The addition of recombinant human CTGF/CCN-2 to totally serum-free media containing cultures of bovine NP cells replicated the robustly increased aggrecan gene expression found with NCCM alone strongly suggesting the importance of the effect of CTGF/CCN-2 in notochordal cell biology within the disc nucleus of non-chondrodystrophic canines. The chondrodystrophic canine, another sub-species on the other hand are almost totally devoid of notochordal cells and they develop DDD profoundly and early. These two sub-species of canine reflect a naturally occurring animal model that is an excellent example of differential notochordal cell survival and possible associated developmental differences in extracellular maintenance

Bonobo personality traits are heritable and associated with vasopressin receptor gene 1a variation

Despite being closely related, bonobos and chimpanzees show remarkable behavioral differences, the proximate origins of which remain unknown. This study examined the link between behavioral variation and variation in the vasopressin 1a receptor gene (Avpr1a) in bonobos. Chimpanzees are polymorphic for a ~360 bp deletion (DupB), which includes a microsatellite (RS3) in the 5′ promoter region of Avpr1a. In chimpanzees, the DupB deletion has been linked to lower sociability, lower social sensitivity, and higher anxiety. Chimpanzees and bonobos differ on these traits, leading some to believe that the absence of the DupB deletion in bonobos may be partly responsible for these differences, and to the prediction that similar associations between Avpr1a genotypes and personality traits should be present in bonobos. We identified bonobo personality dimensions using behavioral measures (Sociability(B), Boldness(B), Openness(B), Activity(B)) and trait ratings (Assertiveness(R), Conscientiousness(R), Openness(R), Agreeableness(R), Attentiveness(R), Extraversion(R)). In the present study we found that all 10 dimensions have nonzero heritabilities, indicating there is a genetic basis to personality, and that bonobos homozygous for shorter RS3 alleles were lower in Attentiveness(R) and higher in Openness(B). These results suggest that variations in Avpr1a genotypes explain both within and between species differences in personality traits of bonobos and chimpanzees

Sensorineural hearing loss after concurrent chemoradiotherapy in nasopharyngeal cancer patients

<p>Abstract</p> <p>Background</p> <p>Sensorineural hearing loss (SNHL) is one of the major long term side effects from radiation therapy (RT) in nasopharyngeal cancer (NPC) patients. This study aims to review the incidences of SNHL when treating with different radiation techniques. The additional objective is to determine the relationship of the SNHL with the radiation doses delivered to the inner ear.</p> <p>Methods</p> <p>A retrospective cohort study of 134 individual ears from 68 NPC patients, treated with conventional RT and IMRT in combination with chemotherapy from 2004-2008 was performed. Dosimetric data of the cochlea were analyzed. Significant SNHL was defined as > 15 dB increase in bone conduction threshold at 4 kHz and PTA (pure tone average of 0.5, 1, 2 kHz). Relative risk (RR) was used to determine the associated factors with the hearing threshold changes at 4 kHz and PTA.</p> <p>Results</p> <p>Median audiological follow up time was 14 months. The incidence of high frequency (4 kHz) SNHL was 44% for the whole group (48.75% in the conventional RT, 37% with IMRT). Internal auditory canal mean dose of > 50 Gy had shown a trend to increase the risk of high frequency SNHL (RR 2.02 with 95% CI 1.01-4.03, p = 0.047).</p> <p>Conclusion</p> <p>IMRT and radiation dose limitation to the inner ear appeared to decrease SNHL.</p