A functional role for specific spliced variants of the alpha7beta1 integrin in acetylcholine receptor clustering

The clustering of acetylcholine receptors (AChR) on skeletal muscle fibers is an early event in the formation of neuromuscular junctions. Recent studies show that laminin as well as agrin can induce AChR clustering. Since the alpha7beta1 integrin is a major laminin receptor in skeletal muscle, we determined if this integrin participates in laminin and/or agrin-induced AChR clustering. The alternative cytoplasmic domain variants, alpha7A and alpha7B, and the extracellular spliced forms, alpha7X1 and alpha7X2, were studied for their ability to engage in AChR clustering. Immunofluorescence microscopy of C2C12 myofibers shows that the alpha7beta1 integrin colocalizes with laminin-induced AChR clusters and to a much lesser extent with agrin-induced AChR clusters. However, together laminin and agrin promote a synergistic response and all AChR colocalize with the integrin. Laminin also induces the physical association of the integrin and AChR. High concentrations of anti-alpha7 antibodies inhibit colocalization of the integrin with AChR clusters as well as the enhanced response promoted by both laminin and agrin. Engaging the integrin with low concentrations of anti-alpha7 antibody initiates cluster formation in the absence of agrin or laminin. Whereas both the alpha7A and alpha7B cytoplasmic domain variants cluster with AChR, only those isoforms containing the alpha7X2 extracellular domain were active. These results demonstrate that the alpha7beta1 integrin has a physiologic role in laminin-induced AChR clustering, that alternative splicing is integral to this function of the alpha7 chain, and that laminin, agrin, and the alpha7beta1 integrin interact in a common or convergent pathway in the formation of neuromuscular junctions.     

Meta-analysis as a clinical tool in nephrology

We have developed a new two-step method for targeting cytotoxic drugs to tumour cells. The method firstly involves the binding to tumour cells of antibody-phospholipase C immunoconjugates or fusion proteins. Further to washing or clearance of the immunoconjugates, liposomes are introduced which are specifically lysed at the tumour site by PLC to release their cytotoxic contents in the vicinity of the tumour cells. For two alternative human cell lines, a synergistic inhibition of cell proliferation was seen for combined treatment with a specific immunoconjugate and daunorubicin encapsulated liposomes. For tumour xenografts in mice, the combined treatment resulted in an inhibition of tumour growth although with no eradication of tumours at the doses used. The two-step antibody-PLC/liposome approach offers broad possibilities for the precise delivery of payloads of cytotoxic drugs to tumour sites.     

Anion selectivity of a sapphyrin-modified silica gel HPLC support

A sapphyrin-modified silica gel support for use in high-performance liquid chromatography was prepared by attaching a sapphyrin monocarboxylic acid to aminopropyl silica gel through an amide bond. The anion retention characteristics of this modified silica gel were tested by exploring the extent to which a specific anion in the mobile phase would act to affect the rate at which AMP was eluted from an HPLC column containing this functionalized stationary phase. In general, it was found that phosphate and arsenate anions were more effective as eluents than carboxylic acids and halides, a result that was interpreted in terms of these former species binding better to sapphyrin (and hence being more effective in terms of displacing AMP) than other anions tested. Support for the contention that phosphate anions will bind to sapphyrin subunits covalently tethered to the silica gel came from solid state 31P NMR spectroscopic analyses. These revealed that the 31P nucleus undergoes a 5 ppm upfield shift, relative to control, when allowed to interact with the sapphyrin-containing support.     

Bone density and fracture risk in men

We evaluated different definitions of osteoporosis in a population-based sample of 348 men (age 22-90 years) compared with 351 women (age 21-93 years). Thirty-six men (10%) and 46 women (13%) had a history of osteoporotic fracture (hip, spine, or distal forearm due to moderate trauma at >/= age 35). In logistic regression analysis, osteoporotic fracture risk was associated with bone mineral density (BMD) at all sites (neck, trochanter, total hip, lumbar spine, and total wrist) in both genders (p < 0.001) except spinal BMD in men. After adjusting for age, total hip BMD was the strongest predictor of fracture risk in women (odds ratio [OR] per 1 SD decline, 2.4; 95% confidence interval [CI], 1.6-3.7), while wrist BMD was best in men (OR, 1.5; 95% CI, 1.1-2.0). Among men but not women, bone mineral apparent density (BMAD) was a better predictor of fracture than BMD (wrist BMAD OR, 1.7; 95% CI, 1.3-2.3). Hip BMD/BMAD decreased linearly from age 20 years onward in both genders, while spinal BMD/BMAD declined after age 40 in women but not in men. In both genders, total wrist BMD/BMAD decreased after age 50. By World Health Organization criteria, the age-adjusted prevalence of osteoporosis at the hip, spine, or wrist was 35% among women >/=50 years of age. A similar approach (BMD > 2.5 SD below the young male mean) produced an osteoporosis prevalence rate in men >/=50 years of age of 19%. Thus, bone density predicts fracture risk in men as it does in women, and the prevalence of osteoporosis in men, using sex-specific normal values, is substantial. These observations indicate a need for better prevention and treatment strategies for men.     

Complications of rhytidectomy

In a recent study of rhytidectomy patients, the most common complications were hematoma, inflammation, crusting, hypertrophic scars, hair loss, and changes in ear lobe appearance. The nurse's role in early detection and prevention cannot be overlooked. This article will review these complications and less common ones, emphasizing the known etiologies, signs and symptoms, and the nurse's role in assessment and intervention.     

The validity of a nursing assessment and monitoring of signs and symptoms scale in ICU and non-ICU patients

PURPOSE: This study examined the validity of medical-record-based nursing assessment and monitoring of signs and symptoms (nursing surveillance) in predicting patients who were admitted to ICUs and those admitted to non-ICUs. The association of this assessment and monitoring with differences in an intermediate patient outcome, instability at discharge, was also explored. Patients admitted to either setting with a diagnosis of acute myocardial infarction, cerebrovascular accident, congestive heart failure, or pneumonia, were included in the study. METHOD: A secondary analysis was carried out using a subset of data originally collected for a quality-of-care study. Data from the medical records of 11,246 patients (52% female, 48% male) with a mean age of 76.4 years were used in the present study. RESULTS: ICU patients (n = 3969) were found to have a longer length of stay and to be sicker on admission than non-ICU patients (n = 7277). Overall, patients in the ICU received significantly higher nursing assessment and monitoring of signs and symptoms scores than non-ICU patients. Nursing assessment and monitoring of signs and symptoms scores were lower for patients discharged with greater instability for three of the four diseases (cerebrovascular accidents, congestive heart failure, and pneumonia).     

Expansions of T-cell subsets expressing particular T-cell receptor variable regions in chronic beryllium disease

Bisphosphonates are currently the most important class of antiresorptive drugs used for the treatment of metabolic bone diseases. Although the molecular targets of bisphosphonates have not been identified, these compounds inhibit bone resorption by mechanisms that can lead to osteoclast apoptosis. Bisphosphonates also induce apoptosis in mouse J774 macrophages in vitro, probably by the same mechanisms that lead to osteoclast apoptosis. We have found that, in J774 macrophages, nitrogen-containing bisphosphonates (such as alendronate, ibandronate, and risedronate) inhibit post-translational modification (prenylation) of proteins, including the GTP-binding protein Ras, with farnesyl or geranylgeranyl isoprenoid groups. Clodronate did not inhibit protein prenylation. Mevastatin, an inhibitor of 3-hydroxy-3-methylglutatyl (HMG)-CoA reductase and hence the biosynthetic pathway required for the production of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, also caused apoptosis in J774 macrophages and murine osteoclasts in vitro. Furthermore, alendronate-induced apoptosis, like mevastatin-induced apoptosis, could be suppressed in J774 cells by the addition of farnesyl pyrophosphate or geranylgeranyl pyrophosphate, while the effect of alendronate on osteoclast number and bone resorption in murine calvariae in vitro could be overcome by the addition of mevalonic acid. These observations suggest that nitrogen-containing bisphosphonate drugs cause apoptosis following inhibition of post-translational prenylation of proteins such as Ras. It is likely that these potent antiresorptive bisphosphonates also inhibit bone resorption by preventing protein prenylation in osteoclasts and that enzymes of the mevalonate pathway or prenyl protein transferases are the molecular targets of the nitrogen-containing bisphosphonates. Furthermore, the data support the view that clodronate acts by a different mechanism.     

Sensory and objective characteristics of broiler meat from commercial broilers fed rendered whole-hen meal

A 40-year-old Japanese man with psoriatic arthritis (PA) involving the spine, sacroiliac and peripheral joints presented with dyspnoea and ankle oedema. Blood pressure was 180/110 and 114/80 mmHg in the right and left upper arms, respectively. Examinations showed left ventricular dilatation and diffuse hypokinesis of the left ventricle, with no involvement of the coronary arteries. Aortography detected total occlusion of the left subclavian artery and stenosis of the origin at the right renal artery. Dilated cardiomyopathy and Takayasu's arteritis associated with PA was diagnosed. A few cases of PA have been reported in association with cardiovascular diseases, but the association of these three diseases has not been documented in the literature to date. Dermatologists need to be aware of cardiovascular manifestations in patients with PA, because cardiovascular diseases are not rare in other seronegative spondyloarthropathies.