Tau protein induces bundling of microtubules in vitro: comparison of different tau isoforms and a tau protein fragment.

Expression of tau protein in non-neuronal cells can result in a redistribution of the microtubule cytoskeleton into thick bundles of tau-containing microtubules (Lewis et al.: Nature 342:498-505, 1989; Kanai et al.: J Cell Biol 109:1173-1184, 1989). We reconstituted microtubule bundles using purified tubulin and tau in order to study the assembly of these structures. Taxol-stabilized tubulin polymers were incubated with various concentrations of recombinant human tau and examined by electron microscopy. With increasing concentrations of tau 3 (tau isoform containing three microtubule binding domains) or tau 4 (isoform containing four microtubule binding domains) the microtubules changed orientation from a random distribution to loosely and tightly packed parallel arrays and then to thick cables. In contrast, tau 4L, the tau isoform containing four microtubule binding domains plus a 58-amino acid insert near the N-terminus, showed minimal bundling activity. tau 4-induced bundling could be inhibited by the addition of 0.5 M NaCl or 0.4 mM estramustine phosphate, conditions which are known to inhibit tau binding to microtubules. A tau construct that contained only the microtubule binding domains plus 19 amino acids to the C-terminus was fully capable of bundling microtubules. Phosphorylation of tau 3 with cAMP-dependent protein kinase had no effect on its ability to induce microtubule bundling. These results indicate that tau protein is directly capable of bundling microtubules in vitro, and suggests that different tau isoforms differ in their ability to bundle microtubule filaments.     

The Influence of Routine Completion Arteriography on Outcome following Carotid Endarterectomy

n = 69) normal; Group B (n= 29), abnormal, severe defects; Group C (n= 56), abnormal, mild–moderate defect. RCA detected 32 defects in Group B: 10 internal carotid (ICA), seven endpoint flaps, two kinks, one dissection; 16 external carotid (ECA), 10 severe endpoint defects and six total occlusion; six common carotid (CCA), five irregular proximal shelfs, one web. Thirty of 32 defects were successfully repaired as confirmed by normal repeat RCA studies; one ECA defect was not repaired and the ICA dissection was irreparable. In Group C, 67 mild–moderate defects were identified, but not corrected. These included <30% stenosis in the ICA (12), ECA (18), CCA (24), and vein patch corrugation or irregularity (13). For the entire series the postoperative ICA occlusion rate was 2% (3/154), stroke rate 2.6% (4/154), and a subsequent >50% restenosis rate of 7% (11/154). The yield from routine carotid completion arteriograms was significant, with 19% of studies identifying a severe defect that required repair. Although the difference in stroke rates and restenosis between the different groups did not reach statistical significance, patients with normal intraoperative arteriograms initially or after correction of a significant RCA defect had no early carotid occlusion (p= 0.05, Fisher's exact test) compared to patients with residual RCA defects. All early carotid occlusions occurred in patients with unrepaired defects. We conclude that RCA is an important method of quality control after CEA and exerts a subtle, but real, reduction in postoperative complications.     

The effects of population density and malnutrition on the dynamics of whooping cough.

Liverpool, a seaport in NW England, suffered severely from lethal infectious diseases in the second half of the 19th century: the population was densely crowded and malnourished and life expectancy was low. Time-series analysis shows that the epidemics of whooping cough (i) had an interepidemic interval of 2.9 years, 1863-85, which lengthened to 3.4 years, 1885-1900 (ii) were strongly coherent with wheat prices (P < 0.001) and (iii) also correlated with cycles of seasonal weather conditions. It is suggested from mathematical modelling that the epidemics in this compromised population were maintained (i.e. the system was driven) by an oscillation of malnutrition and by seasonal weather conditions. A model that incorporates both the dynamics of whooping cough and the demographic characteristics of the population is presented. It has been shown to replicate the dynamics of the epidemics and has been used to predict the changes with time of (i) the force of the infection and (ii) the proportion of those infected with whooping cough who died.     

Are common mutations of cystathionine β-synthase involved in the aetiology of neural tube defects?

Mildly elevated maternal plasma homocysteine (Hcy) levels (hyperhomocysteinemia) have recently been observed in some neural tube defect (NTD) pregnancies. Plasma levels of Hcy are governed by both genetic and nutritional factors and the aetiology of NTDs is also known to have both genetic and nutritional components. We therefore examined the frequency of relatively common mutations in the enzyme cystathionine β-synthase (CBS), which is one of the main enzymes that controls Hcy levels, in the NTD population. Neither the severely dysfunctional G307S CBS allele nor the recently reported 68 bp insertion/I278T CBS allele was observed at increased frequency in the cases relative to controls. We therefore conclude that loss of function CBS alleles do not account for a significant proportion of NTDs in Ireland.     

A critical reflection on the personal impact of managerial hegemony within nurse education

This paper, written by two male nurse teachers, describes and analyses their experience of working in a nurse education culture permeated by the philosophy of business management The introduction of business management practices to nurse education is discussed as a reflection of the current political hegemony of market forces and individualism The authors discuss the implications for nurse teachers of being continually exposed to these politically motivated forces which increasingly provide the paradigm for service developments within the United Kingdom health services In discussing the impact of this exposure it is argued that at the personal level individual teachers are experiencing a degree of apathy and personal dissonance which undermines their professional value system, resulting in emotional distress and a crisis of identity It provides a critical reflection on the way organizational dynamics and power relations influence the subjective sense-making of individuals The authors use a multiplicity of perspectives, including those provided by individual psychology, power relations, feminism and personhood, to argue for the need to develop an alternative paradigm which is characterized by the valuing of individual persons, empathic sensitivity and the fostering of creativity been important to us from a personal and professional     

Intraligamentous injection of sclerosing solutions (prolotherapy) for spinal pain: a critical review of the literature.

BACKGROUND CONTEXT: The injection of various solutions aimed at producing a sclerosing effect has been used to treat soft tissues injuries (eg, inguinal hernia) for more than 100 years. In the 1930s, this treatment approach was applied to injured joints in an attempt to stimulate connective tissue repair. Although several studies have been published about this method of treatment for various orthopedic and spinal indications (termed prolotherapy), its use remains controversial. PURPOSE: To conduct a critical review of the literature on prolotherapy for spinal pain. STUDY DESIGN/SETTING: Critical review of the literature. METHODS: Computerized medical literature databases (Medline, CINAHL, Mantis, Cochrane Central Register of Controlled Trials) were searched to uncover all published information about the use of sclerosing injections in humans with spinal pain disorders. Search results were reviewed for relevance, and information was abstracted from full-text articles. RESULTS: Our search uncovered almost 200 reference materials in various media related to prolotherapy, including 31 clinical studies related to spinal pain. There were 26 observational cohorts and 5 randomized clinical trials (RCTs). Indications in these studies were low back pain (22), neck pain (3), cervical headaches (3) and dorsal or thoracic pain (3). A total of 20 sclerosing solutions were used in these studies; the most common was a mixture of dextrose 12.5%, glycerin 12.5%, phenol 1.25% and lidocaine 0.25%. Wide variations were found in treatment protocols, such as dose, number of treatments and use of adjunct therapies. Most cohort studies were only of moderate quality and varied greatly in the substances injected and the use of co-interventions. Most clinical studies reported positive results such as decreased pain or disability, although differences between treatment and control groups did not always reach statistical significance. Commonly reported adverse reactions to this treatment include temporary postinjection pain and stiffness. A handful of more serious adverse events were reported in the 1950s and 1960s with stronger or unknown solutions. CONCLUSION: Prolotherapy describes a variety of treatment approaches rather than a specific protocol. Results from clinical studies published to date indicate that it may be effective at reducing spinal pain. Great variation was found in the injection and treatment protocols used in these studies that preclude definite conclusions. Future research should focus on those solutions and protocols that are most commonly used in clinical practice and have been used in trials reporting effectiveness to help determine which patients, if any, are most likely to benefit from this treatment.     

Optimizing Techniques for Determining Body Composition

<正> KEY POINTS  Accurate body composition assessments are vital to monitoring growth, training outcomes, health, and nutritional status of athletes.  Body composition assessment in athletes and other relies on non-invasive indirect methods that are based on theoretical models. Any errors in the theoretical models will produce errors in the indirect methods. performance.     

Fatal thermal injury

Two fatal cases of thermal injury are described, one of which was the result of heat stroke and the other was the result of the uncommon condition, neuroleptic malignant syndrome. The clinical profiles, management and post-mortem findings of these two separate conditions are compared to highlight their important differences.