Response to foot-and-mouth disease vaccines in newborn calves. Influence of age, colostral antibodies and adjuvants

Oil-emulsified (OE) and aqueous (Aq) vaccines were prepared with the same batch of inactivated A24 8345 foot and mouth disease virus (FMDV). Calves born to vaccinated dams did not respond to the Aq vaccine 30 or 90 days post partum. When the OE vaccine was used on a similar group of calves, no responses were elicited up to 21 days post partum. However, calves 30 or more days old responded like adult cattle to the OE vaccine. When the OE vaccine was used in colostral antibody-free calves 3-30 days old, all animals showed good antibody responses but, in calves vaccinated 3 or 7 days post partum, antibodies were detectable only after a considerable period of time. Our results show that both passively acquired colostral antibodies and age are important in the response of very young calves to FMDV oil vaccines. From a practical point of view, in endemic areas where adult cattle are periodically vaccinated, vaccination of calves between 30 and 60 days post partum with OE vaccines would lead to high levels of herd protection.     

Chronic low level physical activity as a determinant of high density lipoprotein cholesterol and subfractions

Physical activity has been associated with reduced risk of coronary heart disease. A mechanism for the reduced risk may be through increased high density lipoprotein cholesterol (HDL-C) and subfractions, in particular HDL2-C. Research associated with increased physical activity investigating HLD-C have assessed the effects of intense aerobic activity. The current research evaluated the relationship between low intensity, long duration activity to HDL-C and subfractions in 35 active postal carriers. Measurements of physical activity via the Large Scale Integrated monitor and reported miles walked, and lipoproteins were assessed at 3-month intervals over a 1-year period. Reported miles walked/day (5.3) was significantly correlated with HLD2-C (r = 0.50, P = 0.003) and approached significance for HDL-C (r = 0.29, P = 0.06). The Large Scale Integrated measures were correlated with HDL-C (r = 0.44, P = 0.008) and HDL2-C (r = 0.44, P = 0.007). Controlling for either age, alcohol consumption, body mass index, or leisure time activity did not reduce the relationship between reported miles walked or Large Scale Integrated readings and HDL2-C, suggesting that the increased HDL-C was the result of long duration, low intensity physical activity.     

Transformation of meaning perspectives in clients with rheumatoid arthritis.

The purpose of this qualitative study was to examine the process of transformation of personal beliefs, values, feelings, and knowledge (meaning perspectives) underlying occupational change in a small group of clients with rheumatoid arthritis during home-based rehabilitation. A grounded theory approach used to collect and analyze data concurrently included: (1) a sample of five adult clients diagnosed with rheumatoid arthritis in occupational therapy, (2) data collection through 28 semi-directed interviews, and (3) data analysis using the constant comparison method. The study identified meaning perspectives of these clients with rheumatoid arthritis and explored the transformation of perspectives related to the modification of occupational performance. The study suggests that the exploration of meaning perspective transformation by clients and therapists could be a potential part of rehabilitation intervention.     

Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis.

BACKGROUND: The benefit-to-risk ratio of vitamin K antagonists (VKA), relative to active comparators, especially low-molecular-weight heparins (LMWH), for preventing venous thromboembolism in patients undergoing major orthopedic surgery is debated. OBJECTIVES: We performed a meta-analysis of all randomized trials in orthopedic surgery comparing adjusted doses of VKA to control treatments. PATIENTS AND METHODS: An exhaustive literature search, both manual and computer-assisted, was performed. Studies were selected on the basis of randomization procedure (VKA vs. a control group). At least one of the following outcome measures was to be evaluated: deep vein thrombosis (DVT), pulmonary embolism (PE), death, major hemorrhage or wound hematoma. Four reviewers assessed each article to determine eligibility for inclusion and outcome measures. RESULTS: VKAs were more effective than placebo or no treatment in reducing DVT [567 patients, relative risk (RR) = 0.56, 95% confidence interval (CI) 0.37, 0.84, P < 0.01] and clinical PE (651 patients, RR = 0.23, 95% CI 0.09, 0.59, P < 0.01). These results were obtained at the cost of a higher rate of wound hematoma (162 patients, RR = 2.91, 95% CI 1.09, 7.75, P = 0.03). VKAs were also more effective than intermittent pneumatic compression (534 patients, RR = 0.46, 95% CI 0.25, 0.82, P = 0.009) in preventing proximal DVT. In contrast, VKAs were less effective than LMWH in preventing total DVT and proximal DVT (9822 patients, RR = 1.51, 95% CI 1.27, 1.79, P < 0.001; and 6131 patients, RR = 1.51, 95% CI 1.04, 2.17, P = 0.028, respectively). The differences between VKA and LMWH in major hemorrhage and wound hematoma were not significant. CONCLUSIONS: In patients undergoing major orthopedic surgery, VKAs are less effective than LMWH, without any significant difference in the bleeding risk.     

Multicentre hospital drug utilization study on the prophylaxis of venous thromboembolism. The Venous Thromboembolism Study Group of the Spanish Society of Clinical Pharmacology.

1. Thromboembolic disease (TED) is an important cause of in-hospital morbidity and mortality. Although different prophylactic approaches have been shown to be effective and cost-effective, surveys have suggested that they are underused. The aim of this study was to estimate the prevalence of use of TED prophylaxis in our hospitals. 2. All patients admitted on a specified day to the Internal Medicine and General Surgery wards of seven Spanish university hospitals were included in the study. They were identified cross-sectionally and followed up until discharge or for 15 days. Information about the following variables was collected: risk factors for venous thromboembolism, prophylactic measures used (if any), contraindications to the use of each specific drug or other prophylactic measure, and dosage schedule of the drug used, if any. 3. Nine hundred and thirty-nine patients (53% men) were studied. The most common risk factors for venous thromboembolism were: age > or = 40 years (802; 85%), major surgery (298; 32%), immobilization > or = 6 days (285; 30%), obesity (241; 26%), and cancer (202; 22%). 4. Prophylactic measures were used in 320 patients (34%). Of these, 297 (93%) received heparin, mainly as low molecular weight heparins (248, 78%); physical measures were rarely used. 5. Five hundred and eighty-three patients (62%) fulfilled criteria for moderate or high risk of venous thromboembolism; only 275 (47%) of them received any form of prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sequence variation within botulinum neurotoxin serotypes impacts antibody binding and neutralization

The botulinum neurotoxins (BoNTs) are category A biothreat agents which have been the focus of intensive efforts to develop vaccines and antibody-based prophylaxis and treatment. Such approaches must take into account the extensive BoNT sequence variability; the seven BoNT serotypes differ by up to 70% at the amino acid level. Here, we have analyzed 49 complete published sequences of BoNTs and show that all toxins also exhibit variability within serotypes ranging between 2.6 and 31.6%. To determine the impact of such sequence differences on immune recognition, we studied the binding and neutralization capacity of six BoNT serotype A (BoNT/A) monoclonal antibodies (MAbs) to BoNT/A1 and BoNT/A2, which differ by 10% at the amino acid level. While all six MAbs bound BoNT/A1 with high affinity, three of the six MAbs showed a marked reduction in binding affinity of 500- to more than 1,000-fold to BoNT/A2 toxin. Binding results predicted in vivo toxin neutralization; MAbs or MAb combinations that potently neutralized A1 toxin but did not bind A2 toxin had minimal neutralizing capacity for A2 toxin. This was most striking for a combination of three binding domain MAbs which together neutralized >40,000 mouse 50% lethal doses (LD(50)s) of A1 toxin but less than 500 LD(50)s of A2 toxin. Combining three MAbs which bound both A1 and A2 toxins potently neutralized both toxins. We conclude that sequence variability exists within all toxin serotypes, and this impacts monoclonal antibody binding and neutralization. Such subtype sequence variability must be accounted for when generating and evaluating diagnostic and therapeutic antibodies.     

Distribution of fusimotor axons to intrafusal muscle fibres in cat tenuissimus spindles as determined by the glycogen-depletion method.

1. The distribution of fusimotor axons to bag1, bag2 and chain muscle fibres in cat tenuissimus spindles has been studied using a modification of the glycogen-depletion technique of Edstrrom & Kugelberg (1968). Single fusimotor axons were stimulated intermittently at 40-100/sec for long periods (30-90 sec) during blood occlusion. Portions of muscle containing the activated spindles were quick-frozen, fixed in absolute ethanol during freeze-substitution, and then embedded in paraffin wax. Serial transverse sections were stained for glycogen using the periodic acid-Schiff method, and examined for depletion. 2. Dynamic gamma axons (i.e. those that increase the dynamic index of primary-ending responses to ramp stretches of large amplitude) depleted bag1 fibres almost exclusively. 3. Static gamma axons (i.e. those that reduce or abolish the dynamic index) depleted both bag and chain fibres. Bag1 and bag2 fibres were depleted about equally. 4. A single static gamma axon may activate both bag and chain fibres in one spindle (the most common pattern), chain fibres only in another, and bag fibres only in a third spindle. 5. Static gamma axons with conduction velocities less than 25 m/sec also had a non-selective distribution, but no depletion was observed in bag2 fibres. 6. The zones of depletion produced by dynamic gamma axons were distributed more or less equally in the intra- and extracapsular parts of spindle poles, whereas those produced by static gamma axons were mainly intracapsular. 7. The results are compared with the glycogen-depletion studies of Brown & Butler (1973, 1975) and our own study of the distribution of static gamma axons to spindles in which all other motor axons had degenerated (Barker, Emonet-Dénand, Laporte, Proske & Stacey, 1973). The implications of the finding that both static gamma and dynamic gamma axons activate bag1 fibres are discussed.     

Myotubularin, a phosphatase deficient in myotubular myopathy, acts on phosphatidylinositol 3-kinase and phosphatidylinositol 3-phosphate pathway

Myotubular myopathy (MTM1) is an X-linked disease, characterized by severe neonatal hypotonia and generalized muscle weakness, with pathological features suggesting an impairment in maturation of muscle fibres. The MTM1 gene encodes a protein (myotubularin) with a phosphotyrosine phosphatase consensus. It defines a family of at least nine genes in man, including the antiphosphatase hMTMR5/Sbf1 and hMTMR2, recently found mutated in a recessive form of Charcot-Marie-Tooth disease. Myotubularin shows a dual specificity protein phosphatase activity in vitro. We have performed an in vivo test of tyrosine phosphatase activity in Schizosaccharomyces pombe, indicating that myotubularin does not have a broad specificity tyrosine phosphatase activity. Expression of active human myotubularin inhibited growth of S.pombe and induced a vacuolar phenotype similar to that of mutants of the vacuolar protein sorting (VPS) pathway and notably of mutants of VPS34, a phosphatidylinositol 3-kinase (PI3K). In S.pombe cells deleted for the endogenous MTM homologous gene, expression of human myotubularin decreased the level of phosphatidylinositol 3-phosphate (PI3P). We have created a substrate trap mutant which shows relocalization to plasma membrane projections (spikes) in HeLa cells and was inactive in the S.pombe assay. This mutant, but not the wild-type or a phosphatase site mutant, was able to immunoprecipitate a VPS34 kinase activity. Wild-type myotubularin was also able to directly dephosphorylate PI3P and PI4P in vitro. Myotubularin may thus decrease PI3P levels by down-regulating PI3K activity and by directly degrading PI3P.     

Production of specific anti-rat 5-HT1A receptor antibodies in rabbits injected with a synthetic peptide

Polyclonal antibodies were raised by the repeated injection of rabbits with a synthetic peptide corresponding to a highly selective portion (amino acid residues 243 to 268) of the amino acid sequence of the rat 5-HT1A receptor. The anti-peptide antiserum allowed the immunoprecipitation of 5-HT1A receptors but not of other 5-HT1 sites solubilized from rat hippocampal membranes. Immunoautoradiographic labelling of rat brain sections with the anti-peptide antiserum was superimposed with the autoradiographic distribution of 5-HT1A sites labelled by the selective radioligand [3H]8-OH-DPAT.