Splenectomy causes auto-antibody formation

Serum from 45 splenectomised patients was screened for 8 auto antibodies and compared with controls, either age and sex matched (35) or the same patients measured before splenectomy (10). Sixteen splenectomised patients had demonstrable auto-antibodies compared with 7 controls (p less than 0.05). Three patients who did not have auto-antibodies before splenectomy developed them after an interval of a few months. It is suggested that splenectomy-leads to loss of suppressor cell activity and this permits the development of auto-antibodies.     

A biomechanical comparison between the single-axis and multi-axis total knee arthroplasty systems for the stand-to-sit movement

BACKGROUND: Compared to the design of a traditional multi-axis total knee arthroplasty, the single-axis arthroplasty studied has a fixed flexion/extension center of rotation in the femoral component. The influence of this characteristic on functional daily activity, i.e., stand-to-sit, is not well understood. The purpose of this study was to investigate the effect of different arthroplasty designs on knee kinematic and lower limb muscular activation for the stand-to-sit movement. METHODS: Sixteen unilateral, posterior-stabilized knee arthroplasty participants (8 single-axis and 8 multi-axis) with excellent Knee Society scores performed 4 trials of the stand-to-sit test. Three-dimensional video analysis of whole body and joint kinematics and electromyography analysis of quadriceps and hamstrings were conducted. One-way ANOVAs were used for statistical analyses (alpha=0.05). FINDINGS: The multi-axis group showed some functional adaptations while sitting down. The single-axis group exhibited less arthroplasty limb quadriceps electromyography and hamstring co-activation electromyography than the multi-axis group. For the arthroplasty limb, single-axis demonstrated less abduction angular displacement and reached peak abduction earlier than the multi-axis arthroplasty limb. The estimated effect size for this study was 0.196. INTERPRETATION: The single-axis design requires less eccentric knee extensor muscle activation and exhibits greater medio-lateral stability than the multi-axis designs. Findings from this study could provide useful information to orthopedic knee surgeons and rehabilitative specialists.     

Cross-reactive cytotoxic responses. H-2 restricted are more specific than anti-H-2 responses

Cross-reactive T-cell cytotoxicity is seen when cytotoxic responses are generated in mixed lymphocyte cultures either between mouse strans which differ at the major histocompatibility complex, H-2, or between H-2b mutant strains and the strain from which they were derived. This cross-reactivity can be measured with [51Cr] labeled target cells from a number of different H-2 haplotypes, and the pattern of cross-reaction indicates that the target antigens are unlikely to be any of the serologically defined public specificities. In contrast, the specificity of H-2 restricted cytotoxic responses, such as that to the male-specific antigen, H-Y, is exquisite, and male cells from strains of mice carrying H-2 haplotypes other than the responder have never been found to act as appropriate targets. The contrast between the specificity of anti-H-2 and H-2 restricted responses may argue for a greater idiotypic homogeneity of the cells makiing H-2 restricted responses, and the greater specificity of these responses may be necessary for their biological function.     

The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse

Catecholamines and alpha(1)-adrenergic receptors (alpha(1)-ARs) cause cardiac hypertrophy in cultured myocytes and transgenic mice, but heart size is normal in single KOs of the main alpha(1)-AR subtypes, alpha(1A/C) and alpha(1B). Here we tested whether alpha(1)-ARs are required for developmental cardiac hypertrophy by generating alpha(1A/C) and alpha(1B) double KO (ABKO) mice, which had no cardiac alpha(1)-AR binding. In male ABKO mice, heart growth after weaning was 40% less than in WT, and the smaller heart was due to smaller myocytes. Body and other organ weights were unchanged, indicating a specific effect on the heart. Blood pressure in ABKO mice was the same as in WT, showing that the smaller heart was not due to decreased load. Contractile function was normal by echocardiography in awake mice, but the smaller heart and a slower heart rate reduced cardiac output. alpha(1)-AR stimulation did not activate extracellular signal-regulated kinase (Erk) and downstream kinases in ABKO myocytes, and basal Erk activity was lower in the intact ABKO heart. In female ABKO mice, heart size was normal, even after ovariectomy. Male ABKO mice had reduced exercise capacity and increased mortality with pressure overload. Thus, alpha(1)-ARs in male mice are required for the physiological hypertrophy of normal postnatal cardiac development and for an adaptive response to cardiac stress.     

Towards evidence based emergency medicine: best BETs from Manchester Royal Infirmary. Routine use of antibiotic ointment and wound healing

A short cut review was carried out to establish whether topical antibiotics improved the outcome of simple wounds. Altogether 71 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.     

Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background

To understand the role of the calcium-sensing receptor (CasR) in the skeleton, we used a genetic approach to ablate parathyroid glands and remove the confounding effects of elevated parathyroid hormone (PTH) in CasR-deficient mice. CasR deficiency was transferred onto the glial cells missing 2-deficient (Gcm2-deficient) background by intercrossing CasR- and Gcm2-deficient mice. Superimposed Gcm2 deficiency rescued the perinatal lethality in CasR-deficient mice in association with ablation of the parathyroid glands and correction of the severe hyperparathyroidism. In addition, the double homozygous CasR- and Gcm2-deficient mice demonstrated healing of the abnormal mineralization of cartilage and bone associated with CasR deficiency, indicating that rickets and osteomalacia in CasR-deficient mice are not due to an independent function of CasR in bone and cartilage but to the effect of severe hyperparathyroidism in the neonate. Analysis of the skeleton of 6-week-old homozygous CasR- and Gcm2-deficient mice also failed to identify any essential, nonredundant role for CasR in regulating chondrogenesis or osteogenesis, but further studies are needed to establish the function of CasR in the skeleton. In contrast, concomitant Gcm2 and CasR deficiency failed to rescue the hypocalciuria in CasR-deficient mice, consistent with direct regulation of urinary calcium excretion by CasR in the kidney. Double Gcm2- and CasR-deficient mice provide an important model for evaluating the extraparathyroid functions of CasR.     

Plasmin activates the lymphangiogenic growth factors VEGF-C and VEGF-D

Vascular endothelial growth factor (VEGF) C and VEGF-D stimulate lymphangiogenesis and angiogenesis in tissues and tumors by activating the endothelial cell surface receptor tyrosine kinases VEGF receptor (VEGFR) 2 and VEGFR-3. These growth factors are secreted as full-length inactive forms consisting of NH2- and COOH-terminal propeptides and a central VEGF homology domain (VHD) containing receptor binding sites. Proteolytic cleavage removes the propeptides to generate mature forms, consisting of dimers of the VEGF homology domain, that bind receptors with much greater affinity than the full-length forms. Therefore, proteolytic processing activates VEGF-C and VEGF-D, although the proteases involved were unknown. Here, we report that the serine protease plasmin cleaved both propeptides from the VEGF homology domain of human VEGF-D and thereby generated a mature form exhibiting greatly enhanced binding and cross-linking of VEGFR-2 and VEGFR-3 in comparison to full-length material. Plasmin also activated VEGF-C. As lymphangiogenic growth factors promote the metastatic spread of cancer via the lymphatics, the proteolytic activation of these molecules represents a potential target for antimetastatic agents. Identification of an enzyme that activates the lymphangiogenic growth factors will facilitate development of inhibitors of metastasis.