Interaction between LIS1 and doublecortin, two lissencephaly gene products

Mutations in either LIS1 or DCX are the most common cause for type I lissencephaly. Here we report that LIS1 and DCX interact physically both in vitro and in vivo. Epitope-tagged DCX transiently expressed in COS cells can be co-immunoprecipitated with endogenous LIS1. Furthermore, endogenous DCX could be co-immunoprecipitated with endogenous LIS1 in embryonic brain extracts, demonstrating an in vivo association. The two protein products also co-localize in transfected cells and in primary neuronal cells. In addition, we demonstrate homodimerization of DCX in vitro. Using fragments of both LIS1 and DCX, the domains of interaction were mapped. LIS1 and DCX interact with tubulin and microtubules. Our results suggest that addition of DCX and LIS1 to tubulin enhances polymerization in an additive fashion. In in vitro competition assays, when LIS1 is added first, DCX competes with LIS1 in its binding to microtubules, but when DCX is added prior to the addition of LIS1 it enhances the binding of LIS1 to microtubules. We conclude that LIS1 and DCX cross-talk is important to microtubule function in the developing cerebral cortex.     

Aging has a complex effect on a rat model of ischemic stroke

Stroke in humans is usually associated with advanced age. Nevertheless, almost all animal models of ischemic stroke are based on young animals. The present study was designed to assess the effect of age on the development of ischemic injury in a model of focal brain ischemia in rats. Two age groups of Wistar rats were used: young adult (3 months) and old (24-26 months). Under halothane anesthesia, polyethylene microspheres (50 microm in diameter) were injected into the left common carotid artery following a temporary occlusion of the external carotid artery. Sham-operated rats underwent the same procedure but were injected with an identical volume (100 microl) of saline only. Rats of both experimental groups displayed neurological impairment after surgery. However, contrary to expectation, the young rats were more affected than the old rats. Young rats displayed an abrupt 30% decrement in neurological functions in the first week and then showed a partial functional recovery into a 12% decrement from the second week on. Old rats developed the neurological impairment gradually over a 2-week period (6.3% in the first week and 11% in the second week and thereafter). One month later, rats were tested in a water maze task. Again, performance was more impaired in the young ischemic rats than in the old rats. Histological evaluation revealed more extensive neurological damage in young ischemic as compared to old rats. Thus, although increased age has a critical effect on the evolution of the neurological impairment following focal brain ischemia and stroke, its effects in the rat model were more pronounced in the young animals.     

Transient synovitis of the hip in children: role of US

Transient synovitis of the hip remains a common diagnostic problem for the clinician. The physical signs are not pathognomonic of the condition, and the classic technical examinations are of little help. Therefore, the authors retrospectively studied the value of hip arthrosonography in 46 children with clinical symptoms suggesting pathologic hip conditions. In 20 of the 21 patients with a final diagnosis of transient synovitis, articular effusion was detected on ultrasound (US). Conventional radiography showed an increased medial joint space in only eight of these patients. Increased echogenicity of the articular fluid was found in both transient synovitis and septic arthritis. The high sensitivity of US in detecting intraarticular fluid was demonstrated by cadaver studies.     

Iron supplementation in female blood donors deferred by copper sulfate screening

Female blood donors with low hematocrit levels detected by copper sulfate screening were selected randomly to receive either 75 mg of iron per day, as ferrous gluconate, or a calcium phosphate placebo. Their ferritin, serum iron, total iron-binding capacity, zinc protoporphyrin, and hemoglobin values, as well as their suitability to donate blood, were determined initially (Visit 1) and at four follow-up visits (Visits 2-5). By the second visit, the serum ferritin and iron values of donors receiving iron supplementation differed significantly from those of donors receiving placebo. By the fifth visit, a less marked but significant increase in hemoglobin had occurred in the iron group, but not in the placebo group. At no time was there a significant difference between the groups' suitability to donate blood, with each group donating at almost half of their visits. The authors conclude that iron supplementation at this dose level in deferred female blood donors improves their iron status and hemoglobin levels, but does not significantly increase their suitability to donate blood as compared with the suitability of placebo-treated donors.     

Total radical trapping antioxidant potential (TRAP) and exercise

The relationship between physical activity, physical fitness and total radical trapping antioxidant potential (TRAP) was examined in the Northern Ireland Health and Activity Survey. This was a cross-sectional population study (n = 1600) using a two-stage probability sample of the population. TRAP was calculated using the sum of the individual serum antioxidant concentrations (urate, protein thiols, ascorbate, alpha tocopherol and bilirubin) multiplied by their respective stoichiometric values. Physical fitness was determined by estimation of VO2max by extrapolation from submaximal oxygen uptake, and physical activity was recorded by computer-assisted interview. Mean serum TRAP concentrations were significantly higher in males (653 +/- 8.2 mumol/l, mean +/- SEM) compared to females (564 +/- 8.0 mumol/l) (p < 0.0001). Both male and female smokers had significantly lower TRAP values than non-smokers (males p < 0.0001, females p = 0.02). In females, there was a positive relationship of TRAP with age (p < 0.001) and body mass index (p < 0.001) but a negative relationship with physical fitness (p < 0.05). The known beneficial effects of exercise and activity do not appear to be directly mediated through increased antioxidant status.      

Polymorphonuclear leukocyte phagocytic function increases in plasminogen knockout mice

BACKGROUND: Mice lacking plasminogen (PG(-/-)) require alternative pathways of fibrinolysis for survival. This may depend on polymorphonuclear leukocytes (PMN) that can clear soluble and insoluble fibrin(ogen) through PG-independent processes. Our objective was to demonstrate that PMNs from PG(-/-) mice exhibit increased Mac-1 dependent phagocytic activity, which may explain their increased fibrin(ogen)lytic activity compared with wild type (PG(+/+)) mice. METHODS: Phagocytic activity of PMNs from PG(-/-) and PG(+/+) mice was compared following exposure to Staphylococcus aureus (S. aureus) particles and the expression of Mac-1 was assessed in parallel by flow cytometric analysis. Resistance to phorbol-12-myristate-13-acetate (PMA)-induced cell death was compared between PMNs from the different genotypes. RESULTS: Stimulation of PG(-/-) PMNs by opsonized S. aureus diluted in PG(-/-) plasma significantly increased phagocytosis (15-fold) compared with stimulation of PG(+/+) PMNs in PG(+/+) plasma. Incubation of PG(-/-) PMNs with PG(+/+) plasma (control) or PG(-/-) plasma supplemented with human PG inhibited this increased phagocytic activity. Mac-1 cell surface density increased 6.2+/-1.0-fold in PG(-/-) PMNs versus 2.9+/-0.6-fold in PG(+/+) PMNs (P<0.01) indicating that Mac-1 may be associated with increased phagocytic activity. Supporting this, treatment of PG(-/-) PMNs with an anti-Mac-1 antibody in PG(-/-) plasma inhibited phagocytic activity. In addition, physiologic PG blocked Mac-1 accessibility at the surface of PMNs. Addition of PMA resulted in 33% death of PMNs from PG(-/-) mice versus 68% in PG(+/+) controls (P<0.001). CONCLUSIONS: PMNs from PG(-/-) mice exhibit a Mac-1 dependent increase in phagocytic activity that is suppressed with human PG, an anti-Mac-1 antibody or the plasma from PG(+/+) mice. The propensity for PMNs from PG(-/-) mice to be activated in response to PMA together with their relative resistance to PMA-toxicity may contribute to increased PMN half-life and enhanced fibrin(ogen) clearance in the setting of PG deficiency.     

High-quality embryos maintain high pregnancy rates in passive smokers but not in active smokers

This study assesses the effect of passive and active smoking on pregnancy rates after IVF with transfer of high-quality embryos. In a cohort study, women attending the IVF unit in 2006–2007 with favourable parameters for pregnancy (<38 years; less than three IVF cycles, transfer of two highest-grade embryos) grouped by smoking status were included. The cohort included 237 patients/cycles: 42 smokers, 195 non-smokers. The clinical pregnancy rate was significantly lower in smokers (35.7% versus 55.4%,P = 0.021, OR = 0.44 (95% CI 0.22–0.89)), even after conditional stratification on covariates (passive smoker, passive or partner smoker, age group). The live-birth rate was lower in smokers (28.6% versus 42.6%), but the difference was not statistically significant(OR = 0.54 (0.26–1.11)). Among non-smokers, there was no difference in pregnancy rate by passive or partner smoking. On logistic regression, variables predicting pregnancy were age <35 years (P = 0.008, OR = 2.58 (1.2–5.2)) and non-smoking (P = 0.003,OR = 3.47 (1.51–7.98)). In conclusion, transfer of high-quality embryos does not overcome the negative effect of active smoking on pregnancy rate in IVF treatment. The endometrium is apparently involved in the mechanism underlying IVF failure in smokers.     

Cancer patient expectations of and communication with oncologists and oncology nurses: the experience of an integrated oncology and palliative care service

The purpose of this study was to evaluate ambulatory cancer patients' knowledge of their diagnosis and stage, their expectations of medical and nursing staff, and issues related to communication with the professional staff. A structured interview was conducted with each of 103 consecutive cancer patients attending the Oncology Day Hospital of the Shaare Zedek Medical Center. There were 77 women and 26 men, and their median age was 56 (18-86) years. Their religious status was elicited: 48% described themselves as religious, 25% as traditional, and 27% as secular. According to their physicians, 41 were in remission, 11 had stable disease, 47 had progressive disease and in 4 the disease status was unknown. Patients tended to underestimate the status of their disease: among those with progressive disease, 36% stated that their disease was stable or in remission. Overwhelmingly, patients expected that their oncologists should be patient and skilled in diagnostic procedures (98%), tactful, considerate and therapeutically skilled (90-95%), and skilled in the management of pain and the psychosocial consequences of cancer (75-85%). When there is bad news to be transmitted, 92% of patients indicated that they would want disclosure, while 6% indicated that they would want the news withheld from them but passed on to their family members. Most patients were very satisfied with the clarity of the information they received about their disease (85%) and the sensitivity with which it was transmitted (90%). Although 88% of patients reported that they relied on their oncologist for therapeutic decision making, 45% indicated that they had sought a second opinion and 32% reported seeking the opinion of a rabbinical medical broker. Almost all, 97%, of patients indicated that they felt comfortable seeking advice from their oncologist, and the oncologist was the staff member most often sought out for both information (69%) and support (66%). The data indicate high patient expectations of nursing and medical oncology staff members' skills and behaviors. Despite expressing a high level of satisfaction, a substantial percentage of patients had an inaccurate understanding of their disease status.