Regulatory mechanisms in cell-mediated immune responses. VI. Interaction of H-2 and non-H-2 genes in elaboration of mixed leukocyte reaction suppressor factor

Previous studies have shown that alloantigen-activated spleen T cells produce a soluble factor which suppresses mixed lymphocyte reaction proliferative responses, and that the interaction between suppressor and responder cells is controlled by genes of the H-2 complex. However a defect in the expression of suppressor activity was identified in the mouse strain C57BL/6J. Factor prepared from alloactivated B6 spleen cells failed to suppress MLR responses of syngeneic or H-2 compatible responder cells. Unimpaired suppressor factor production by other H-2 (b) strains and failure of suppressor factor production by a B6 congenic strain, B6.C-H-2(d) isolated the defective gene to the non-H-2 portion of the genome. In addition, the defect appeared to be related specifically to inability to produce an active factor, while the capacity to respond to suppressor molecules was unimpaired. The genetic character of the non-H-2 gene action was identified in F1 hybrid studies. Initially F(1) hybrids of the nondefective histoincompatible strains were studied. Suppressor factor from F1 cells suppressed the responses of both parental strains, and parental factors each suppressed the response of F(1) cells. Adsorption of F(1) factor with Con A-activated thymocytes of either parental strain removed suppressor activity specific for that strain, leaving activity against the other parental strain intact. The data support cedominant expression and production of distinct, parental H-2 haplotype-specific suppressor molecules by F(1) suppressor cells. An F(1) hybrid of the defective B6 strain with nondefective BALB/c produced suppressor factor which was also capable of suppressing both parental strains. Production of a suppressive B6-reactive factor by F(1) cells was verified by adsorption studies. Thus it appears that non-H-2 genes of the BALB/c parent acted in a genetically dominant fashion to provide the function required for expression of B6 suppressor molecules. We conclude that multiple genes control the expression of alloactivated suppressor cell activity, with at least one gene mapped to the I-C subregion of the murine major histocompatibility complex and one or more genes mapped to the non-H-2 gene complement

Acquired constriction ring syndrome as a cause of inconsolable cry in a child: a case report

Acute constriction ring syndrome (ACRS) is a rare clinical condition characterized by formation of a circumferential constriction ring around an appendage or genitalia. Cases are mostly reported in infants and young children. Early recognition and a definitive treatment are of paramount importance in order to avoid irreversible ischemia and possible auto-amputation. We describe a case of a 14-month-old child presented to casualty with a history of refusal to feed and inconsolable cry. Parents noticed a recent swelling of left third toe. On careful examination the child was found to have an acquired constriction ring secondary to a tightly wrapped hair around left third toe. An urgent surgical decompression was done by the orthopaedic team with complete resolution of symptoms. We summarized the pathophysiology of ACRS underlining the need of awareness in treating physicians. The possible medico legal implications should be kept in mind bearing a suggested link with non-accidental injury

A hypothetico-deductive approach to assessing the social function of chemical signalling in a non-territorial solitary carnivore

The function of chemical signalling in non-territorial solitary carnivores is still relatively unclear. Studies on territorial solitary and social carnivores have highlighted odour capability and utility, however the social function of chemical signalling in wild carnivore populations operating dominance hierarchy social systems has received little attention. We monitored scent marking and investigatory behaviour of wild brown bears Ursus arctos, to test multiple hypotheses relating to the social function of chemical signalling. Camera traps were stationed facing bear ‘marking trees’ to document behaviour by different age sex classes in different seasons. We found evidence to support the hypothesis that adult males utilise chemical signalling to communicate dominance to other males throughout the non-denning period. Adult females did not appear to utilise marking trees to advertise oestrous state during the breeding season. The function of marking by subadult bears is somewhat unclear, but may be related to the behaviour of adult males. Subadults investigated trees more often than they scent marked during the breeding season, which could be a result of an increased risk from adult males. Females with young showed an increase in marking and investigation of trees outside of the breeding season. We propose the hypothesis that females engage their dependent young with marking trees from a young age, at a relatively ‘safe’ time of year. Memory, experience, and learning at a young age, may all contribute towards odour capabilities in adult bears

Competition at silent synapses in reinnervated skeletal muscle

Synaptic connections are made and broken in an activity-dependent manner in diverse regions of the nervous system. However, whether activity is strictly necessary for synapse elimination has not been resolved directly. Here we report that synaptic terminals occupying motor endplates made electrically silent by tetrodotoxin and alpha-bungarotoxin block were frequently displaced by regenerating axons that were also both inactive and synaptically ineffective. Thus, neither evoked nor spontaneous activation of acetylcholine receptors is required for competitive reoccupation of neuromuscular synaptic sites by regenerating motor axons

The clinical features of the piriformis syndrome: a systematic review

Piriformis syndrome, sciatica caused by compression of the sciatic nerve by the piriformis muscle, has been described for over 70 years; yet, it remains controversial. The literature consists mainly of case series and narrative reviews. The objectives of the study were: first, to make the best use of existing evidence to estimate the frequencies of clinical features in patients reported to have PS; second, to identify future research questions. A systematic review was conducted of any study type that reported extractable data relevant to diagnosis. The search included all studies up to 1 March 2008 in four databases: AMED, CINAHL, Embase and Medline. Screening, data extraction and analysis were all performed independently by two reviewers. A total of 55 studies were included: 51 individual and 3 aggregated data studies, and 1 combined study. The most common features found were: buttock pain, external tenderness over the greater sciatic notch, aggravation of the pain through sitting and augmentation of the pain with manoeuvres that increase piriformis muscle tension. Future research could start with comparing the frequencies of these features in sciatica patients with and without disc herniation or spinal stenosis

A Judd illusion in far-aiming: evidence of a contribution to action by vision for perception

The present study addresses the role of vision for perception in determining the location of a target in far-aiming. Participants (N = 12) slid a disk toward a distant target embedded in illusory Judd figures. Additionally, in a perception task, participants indicated when a moving pointer reached the midpoint of the Judd figures. The number of hits, the number of misses to the left and to the right of the target, the sliding error (in mm) and perceptual judgment error (in mm) served as dependent variables. Results showed an illusory bias in sliding, the magnitude of which was comparable to the bias in the perception of target location. The determination of target location in far-aiming is thus based on relative metrics. We argue that vision for perception sets the boundary constraints for action and that within these constraints vision for action autonomously controls movement execution, but alternative accounts are discussed as well

Isolation-by-Distance and Outbreeding Depression Are Sufficient to Drive Parapatric Speciation in the Absence of Environmental Influences

A commonly held view in evolutionary biology is that speciation (the emergence of genetically distinct and reproductively incompatible subpopulations) is driven by external environmental constraints, such as localized barriers to dispersal or habitat-based variation in selection pressures. We have developed a spatially explicit model of a biological population to study the emergence of spatial and temporal patterns of genetic diversity in the absence of predetermined subpopulation boundaries. We propose a 2-D cellular automata model showing that an initially homogeneous population might spontaneously subdivide into reproductively incompatible species through sheer isolation-by-distance when the viability of offspring decreases as the genomes of parental gametes become increasingly different. This simple implementation of the Dobzhansky-Muller model provides the basis for assessing the process and completion of speciation, which is deemed to occur when there is complete postzygotic isolation between two subpopulations. The model shows an inherent tendency toward spatial self-organization, as has been the case with other spatially explicit models of evolution. A well-mixed version of the model exhibits a relatively stable and unimodal distribution of genetic differences as has been shown with previous models. A much more interesting pattern of temporal waves, however, emerges when the dispersal of individuals is limited to short distances. Each wave represents a subset of comparisons between members of emergent subpopulations diverging from one another, and a subset of these divergences proceeds to the point of speciation. The long-term persistence of diverging subpopulations is the essence of speciation in biological populations, so the rhythmic diversity waves that we have observed suggest an inherent disposition for a population experiencing isolation-by-distance to generate new species

Reduced Neutrophil Apoptosis in Diabetic Mice during Staphylococcal Infection Leads to Prolonged Tnfα Production and Reduced Neutrophil Clearance

Diabetes is a frequent underlying medical condition among individuals with Staphylococcus aureus infections, and diabetic patients often suffer from chronic inflammation and prolonged infections. Neutrophils are the most abundant inflammatory cells during the early stages of bacterial diseases, and previous studies have reported deficiencies in neutrophil function in diabetic hosts. We challenged age-matched hyperglycemic and normoglycemic NOD mice intraperitoneally with S. aureus and evaluated the fate of neutrophils recruited to the peritoneal cavity. Neutrophils were more abundant in the peritoneal fluids of infected diabetic mice by 48 h after bacterial inoculation, and they showed prolonged viability ex vivo compared to neutrophils from infected nondiabetic mice. These differences correlated with reduced apoptosis of neutrophils from diabetic mice and were dependent upon the presence of S. aureus and a functional neutrophil respiratory burst. Decreased apoptosis correlated with impaired clearance of neutrophils by macrophages both in vitro and in vivo and prolonged production of proinflammatory tumor necrosis factor alpha by neutrophils from diabetic mice. Our results suggest that defects in neutrophil apoptosis may contribute to the chronic inflammation and the inability to clear staphylococcal infections observed in diabetic patients

Geographical variation in cardiovascular incidence: results from the British Women's Heart and Health Study

BACKGROUND: Prevalence of cardiovascular disease (CVD) in women shows regional variations not explained by common risk factors. Analysis of CVD incidence will provide insight into whether there is further divergence between regions with increasing age. METHODS: Seven-year follow-up data on 2685 women aged 59-80 (mean 69) at baseline from 23 towns in the UK were available from the British Women's Heart and Health Study. Time to fatal or non-fatal CVD was analyzed using Cox regression with adjustment for risk factors, using multiple imputation for missing values. RESULTS: Compared to South England, CVD incidence is similar in North England (HR 1.05 (95% CI 0.84, 1.31)) and Scotland (0.93 (0.68, 1.27)), but lower in Midlands/Wales (0.85 (0.64, 1.12)). Event severity influenced regional variation, with South England showing lower fatal incident CVD than other regions, but higher non-fatal incident CVD. Kaplan-Meier plots suggested that regional divergence in CVD occurred before baseline (before mean baseline age of 69). CONCLUSIONS: In women, regional differences in CVD early in adult life do not further diverge in later life. This may be due to regional differences in early detection, survivorship of women entering the study, or event severity. Targeting health care resources for CVD by geographic variation may not be appropriate for older age-groups

Influence of maternal and social factors as predictors of low birth weight in Italy

Abstract Background The purpose of this study is to provide insight into the determinants of low birth weight (LBW) in Italy. Methods The study was carried out in a non-teaching hospital in Catanzaro (Italy). All LBW and very LBW newborns (200) were included in the study and a random sample of 400 newborns weighing ≥ 2500 g was selected. Data were collected from the delivery certificates during one year. Smoking activity of mother and familiar and/or social support during pregnancy was gathered through telephone interviews. Results Overall annual LBW rate was 11.8%. Among LBW newborn there were 125 preterm and 75 term. Younger mothers, those who smoked during pregnancy, and had fewer prenatal care visits were more likely to deliver a LBW child; moreover, preterm newborns, delivered by caesarean section, and twin or multiple birth were significantly more likely to have a LBW. The comparison of very LBW ( Conclusion Several modifiable factors affect the risk of LBW, even when universal access to health care is freely available, but socio-economic status appears to correlate only to very LBW.</p