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ObjectiveTo validate manual muscle testing MMT for strength assessment in juvenile and adult dermatomyositis DM and polymyositis PM.MethodsPatients with PMDM 73 children and 45 adults were assessed at baseline and reevaluated 6–9 months later. We compared Total MMT a group of 24 proximal, distal, and axial muscles and Proximal MMT 7 proximal muscle groups tested bilaterally on a 0–10 scale with 144 subsets of 6 and 96 subsets of 8 muscle groups tested unilaterally. Expert consensus was used to rank the best abbreviated MMT subsets for face validity and ease of assessment.ResultsThe Total, Proximal, and best MMT subsets had excellent internal reliability Total MMT rs 0.91–0.98, and consistency Cronbachs α 0.78–0.97. Inter and intrarater reliability were acceptable Kendalls W 0.68–0.76, rs 0.84–0.95. MMT subset scores correlated highly with Total and Proximal MMT scores and with the Childhood Myositis Assessment Scale, and correlated moderately with physician global activity, functional disability, magnetic resonance imaging, and axial and distal MMT scores, and, in adults, with creatine kinase level. The standardized response mean for Total MMT was 0.56 in juveniles and 0.75 in adults. Consensus was reached to use a subset of 8 muscles neck flexors, deltoids, biceps, wrist extensors, gluteus maximus and medius, quadriceps, and ankle dorsiflexors that performed as well as the Total and Proximal MMT, and had good face validity and ease of assessment.ConclusionThese findings aid in standardizing the use of MMT for assessing strength as an outcome measure for myositis.

EMPLOYMENT LAW HANDBOOK: AN ADVISOR'S HANDBOOK By TAMARA LEWIS [Legal Action Group, 2005, 6th ed., 739 pp., £28.00 (paperback)]EMPLOYMENT TRIBUNAL CLAIMS: TACTICS AND PRECEDENTS By NAOMI CUNNINGHAM [Legal Action Group, 2005, 396 pp., £25.00 (paperback)]DISCRIMINATION LAW: TEXT, CASES AND MATERIALS By AILEEN MCCOLGAN [Hart Publishing, 2005. 2nd edn., 757 pp., £25 (paperback)]FAMILY LAW AND FAMILY VALUES Edited By MAVIS MACLEAN [Hart Publishing, 2005, 342 pp., £22.00 (paperback)]TRUSTS AND EQUITY By NIGEL STOCKWELL and RICHARD EDWARDS [Pearson Longman, 2005, 7th edn., 556 pp., £29.99 (paperback)]HAYTON AND MARSHALL: CASES AND COMMENTARY ON THE LAW OF TRUSTS AND EQUITABLE REMEDIES By DAVID HAYTON and CHARLES MITCHELL [Sweet & Maxwell, 2005, 12th edn., 985 pp., £32.95 (paperback)]MODERN INTELLECTUAL PROPERTY LAW By CATHERINE COLSTON and KIRSTY MIDDLETON [Cavendish Publishing Ltd., 2005, 2nd ed., 808 pp., £35.95 (paperback)]INSURANCE LAW: DOCTRINE AND PRINCIPLES By JOHN DOWRY and PHILIP RAWLINGS [Hart Publishing, 2005, 2nd edn, 447 pp., £25.00 (paperback)]MASON & MCCALL SMITH'S LAW AND MEDICAL ETHICS Edited By KENYON MASON and GRAEME LAURIE [Oxford University Press, 2005, 7th ed., 774 pp., £21.99 (paperback)]LEGAL CONUNDRUMS IN OUR BRAVE NEW WORLD By BARONESS HELENA KENNEDY QC [Sweet and Maxwell, 2004, 57 pp., £17.95 (paperback)]CRIMINAL LAW By CATHERINE ELLIOTT and FRANCES QUINN [Pearson Education, 2006, 6th ed. xxvi + 420 pp., £22.99 (paperback)]DRUGS, ADDICTION AND THE LAW By LEONARD JASON‐LLOYD [ELM Publications, 10th ed., 232 pp., £29.95 (loose‐leaf with updating service)]THE VIOLENT WORKPLACE By P. A. J. WADDINGTON, DOUG BADGER and RAY BULL [Willan Publishing, 2006, xii + 204 pp., £25.00 (hardback)]ENVIRONMENTAL LAW By J. THORNTON and S. BECKWITH [Sweet and Maxwell, 2004, 2nd ed., 447 pp., £24.95 (paperback)]

Objectives:To determine if an educational intervention in the acute stage of whiplash injury may improve the recovery rate. Methods:Consecutive subjects were randomized to one of two treatment groups: educational intervention or usual care. The intervention group received an educational pamphlet based on the current evidence. The control group did not receive these materials but received usual emergency department care and a standard nondirected discharge information sheet. Both groups underwent follow‐up by telephone interview at two weeks and three months. The primary outcome measure of recovery was the patient's response to the question, “How well do you feel you are recovering from your injuries?”Results:A total of 112 subjects agreed to participate. Age, gender, precollision employment level and health, initial symptoms, collision parameters, and emergency treatments were similar between the groups. At two weeks postcollision, 7.3% in the treatment group reported recovery compared with 8.8% in the control group (absolute risk difference, −1.5%; 95% confidence interval =−12.6% to 9.7%). At three months postcollision, 21.8% in the treatment group reported complete recovery compared with 21.0% in the control group (absolute risk difference, 0.8%; 95% confidence interval =−14.4% to 16.0%). At three months, there were no clinically or statistically significant differences between groups in severity of remaining symptoms, limitations in daily activities, therapy use, medications used, lost time from work, or litigation. Conclusions:An evidence‐based educational pamphlet provided to patients at discharge from the emergency department is no more effective than usual care for patients with grade 1 or 2 whiplash‐associated disorder.

Successful autologous skeletal myoblast transplantation into infarcted myocardium in a variety of animal models has demonstrated improvement in cardiac function. We evaluated the safety and feasibility of transplanting autologous myoblasts into infarcted myocardium of patients undergoing concurrent coronary artery bypass grafting (CABG) or left ventricular assist device implantation (LVAD). In addition, we sought to gain preliminary information on graft survival and any potential improvement of cardiac function. Eighteen patients with a history of ischemic cardiomyopathy participated in a phase I, nonrandomized, multicenter pilot study of autologous skeletal myoblast transplantation concurrent with CABG or LVAD implantation. Twelve patients with a history of previous myocardial infarction (MI) and a left ventricular ejection of less than 30% were enrolled in the CABG arm. In a second arm, six patients underwent LVAD implantation as a bridge to heart transplantation and were required to donate their heart for testing at the time of heart transplant. Myoblasts were successfully transplanted in all patients without any acute injection-related complications or significant long-term unexpected adverse events. Follow-up PET scans showed new areas of viability within the infarct scar in CABG patients. Echocardiography measured an average improvement in left ventricular ejection fraction (LVEF) from 25% to 34%. Histological evaluation in four out of five patients who underwent heart transplantation documented survival and engraftment of the skeletal myoblasts within the infarcted myocardium. These interim results demonstrate survival, feasibility, and safety of autologous myoblast transplantation and suggest that this modality may offer a potential therapeutic treatment for end-stage heart disease.

The United States is developing a costly bio-umbrella to protect its citizens against biothreats that do not now–and may never–exist.

Changes in blood dendritic cell (BDC) counts (CD123hiBDC and CD11c+BDC) and expression of CD62L, CCR7, and CD49d were analyzed in healthy donors, multiple myeloma (MM), and non-Hodgkin lymphoma (NHL) patients, who received granulocyte-colony stimulating factor (G-CSF) containing peripheral blood stem cell (PBSC) mobilization protocols. Low-dose G-CSF in healthy donors (8-10 μg/kg/d subcutaneously) and high-dose G-CSF in patients (30 μg/kg/d) increased CD123hiBDC (2- to 22-fold, mean 3.7 × 106/L-17.7 × 106/L and 1.9 × 106/L-12.0 × 106/L) in healthy donors and MM but decreased CD11c+BDC (2- to 10-fold, mean 5.7 × 106/L-1.6 × 106/L) in NHL patients, on the day of apheresis, compared with steady state. After apheresis, CD123hiBDC counts remained high, whereas low CD11c+BDC counts tended to recover in the following 2-5 days. Down-regulation of CD62L and up-regulation of CCR7 on CD123hiBDC were found in most healthy donors and MM patients. CD49d expression was unchanged. Thus, PBSC mobilization may change BDC counts by altering molecules necessary for BDC homing from blood into tissues.

Changes in blood dendritic cell (BDC) counts (CD123hiBDC and CD11c+BDC) and expression of CD62L, CCR7, and CD49d were analyzed in healthy donors, multiple myeloma (MM), and non-Hodgkin lymphoma (NHL) patients, who received granulocyte-colony stimulating factor (G-CSF) containing peripheral blood stem cell (PBSC) mobilization protocols. Low-dose G-CSF in healthy donors (8-10 μg/kg/d subcutaneously) and high-dose G-CSF in patients (30 μg/kg/d) increased CD123hiBDC (2- to 22-fold, mean 3.7 × 106/L-17.7 × 106/L and 1.9 × 106/L-12.0 × 106/L) in healthy donors and MM but decreased CD11c+BDC (2- to 10-fold, mean 5.7 × 106/L-1.6 × 106/L) in NHL patients, on the day of apheresis, compared with steady state. After apheresis, CD123hiBDC counts remained high, whereas low CD11c+BDC counts tended to recover in the following 2-5 days. Down-regulation of CD62L and up-regulation of CCR7 on CD123hiBDC were found in most healthy donors and MM patients. CD49d expression was unchanged. Thus, PBSC mobilization may change BDC counts by altering molecules necessary for BDC homing from blood into tissues.

The technical challenges in the development of a quality‐controlled registry of percutaneous coronary interventions (PCIs) are currently unknown. This article describes the authors' experience in the development of a regional, quality‐controlled PCI registry. In 1996, 16 centers in Michigan were invited to participate in a multicenter PCI registry. Nine centers agreed to a pilot data collection and, as of July 2001, eight centers are still actively collecting data. An Oracle database was developed by the coordinating center. A common data collection form and a standard set of definitions were agreed on during several meetings. Data validity was insured through review of each form by a trained nurse, by automatic database diagnostic routines, and by site visits that included a review of the catheterization laboratory logs and a review of randomly selected charts. The average number of forms requiring query resolution was 33% in 1997 (range 7–76%), and it decreased to 5% in 1999 (range 1.4–10%). The most commonly queried variables were outcomes prior to discharge, lesion category, lesion complexity, date of birth, device used, gender, postprocedural percent stenosis, presence of left main disease, and MI date. Invalid dates, identification of the doctor, the presence of duplicate forms, and of duplicate outcomes were additional common queries generated by the internal diagnostic routines. In conclusion, the number of queries and diagnostic reports generated in the database suggests that the development of a quality‐controlled PCI registry requires the institution of a careful diagnostic and data quality assessment system.

Nineteen focus groups were conducted with parents of secondary students in Australia about important messages they give at home regarding sexual behavior and sexual responsibility. Parents indicated that sexuality is an important part of their children's lives and they want their own children to be better informed than they were as adolescents. They believe it is both unethical and futile to try to dictate the sexual decisions of their children; instead they strive to provide them with the knowledge and skills to make informed choices. Both fathers and mothers clearly value sex within relationships over casual sex, and encourage their children to protect themselves and others when engaging in sexual behavior. They expressed appreciation of school sexuality education programs and said they made it easier to talk about sex at home. There was strong support for safer sex messages in schools and in the media. Most opposed abstinence-until-marriage messages, explaining not only why they wouldn't work but what consequences could be expected.

Poverty and homelessness are popularly conceptualized as urban phenomena. This tendency is reinforced by media and lack of academic research and persists despite increasing evidence that poverty and homelessness are as prevalent in rural as in urban areas. This paper compares data collected from educators in several rural and urban counties in Iowa. It looks at actual levels of poverty and reported homelessness, and compares the perceptions of the severity and causes of homelessness as reported by rural and urban educators. It concludes that the difficulties faced by poor people in rural areas are compounded by the tendency of small town and rural residents to accept popular conceptions of homelessness and to view poverty and homelessness as resulting from individual failings rather than from societal and community level problems. [ABSTRACT FROM AUTHOR]

This paper presents the results of an exploratory study conducted to determine the impact of the progressive work and family policies implemented in the Sydney Water Corporation. Sydney Water used this study to identify intervention strategies to assist the corporation to realize the full potential of their family‐friendly policies, so employees can not only balance work and family, but also balance career and family too. The study indicates these policies are highly regarded by employees in assisting them to balance their work and family responsibilities, particularly by the part‐time workforce. It is also apparent there are concerns that real career advancement costs are associated with accessing flexible work practices. In line with recent literature, there is a perception that the legitimacy of flexible work practices is questionable, and that employees who access family‐friendly policies may be disadvantaged with respect to their career advancement prospects. This is a clear disincentive for accessing alternate work practices, and presents a challenge to all organizations, not just Sydney Water.

ABSTRACTMarked changes in phyto- and zooplankton assemblage and abundance were observed in a regulated, shallow, hypertrophic lake following temporary drawdown and refilling. Despite significant increases in the ambient concentrations of nitrogen and phosphorus, levels of chlorophyll-afell from a mean of 260 νg·L−1before drawdown and refilling to 70 μg·L−1thereafter. The concentration of chlorophyll-afell to 3 μg·L−1during aspring clearwater phase previously unobserved in Zeekoevlei, but observed in other, adjacent shallow lakes. This clearwater phase was characterized by an increase in mean water transparency from 0.3 to 0.75 m. A marked swing towards an algal assemblage comprised of chlorophyte species occurred during aseasonal period historically-dominated by cyanophytes. Levels of pH and dissolved oxygen declined with the reduced phytoplankton activity in the lake. The zooplankton assemblage was dominated by large-bodied cladocerans, this in contrast to dominance by cyclopoid copepods.It is hypothesized that reduced grazing pressure on the zooplankton, brought about by loss offish from the lake, and in combination with other, as yet unidentified forcing functions, contributed to the observed changes. It is suggested that the implementation of the temporary drawdown and refilling of the lake served to reinitiate seasonal biotic characteristics which would have been common in this and other shallow seasonal waters prior to the introduction of water level regulation. It is further suggested that this procedure should be repeated on an annual basis in order to further entrench beneficial effects and improvements in water quality, and without loss of recreational amenity value.

Background: Gene therapy of human tumors with adenovirus vectors presents a clinical research challenge and a potential opportunity in cancer therapy. One of the research challenges is that endpoints like tumor reduction, time to recurrence, and survival do not provide information about whether a potential therapeutic infects the targeted cells or whether the transferred gene functions or induces a cellular response. Therefore, a flow cytometric approach was developed for a wildtype, p53 encoding adenoviral vector (Ad-p53) that provides (1) the relative level of p53 transferred by p53 immunoreactivity, (2) mdm2 immunoreactivity as an assay of p53 activity, and (3) estimates of the percentage of infected cells by dual parameter analysis (p53 versus mdm2). Methods: Three prostate cancer cell lines (PC-3, LNCaP, DU 145) that are null, wild-type, and mutant for p53, respectively, and two ovarian cancer cell lines (PA1, MDAH 2774) that are wild-type and mutant for p53, respectively, were tested for immunoreactivity and lack of cross-reactivity with the monoclonal antibodies, DO-7 (anti-p53) and IF2 (anti-mdm2). Optimal dual staining conditions for a flow cytometric assay employing saturating levels of antibody were developed and tested by infection of PC-3, PA1, and MDAH 2774 with Ad-p53 or a control virus, Ad-luc. Dual staining with DO-7 and propidium iodide was used to determine any biological effect of the transferred gene. Results: Neither DO-7 nor IF2 showed appreciable cross-reactions by Western blot analysis of representative prostate or ovarian cell lines. By flow cytometric titration, DO-7 appears to be a high avidity antibody (saturation staining of 10⁶ DU 145 cells with 0.5ug) whereas IF2 appears less so (optimum signal to noise ratio at 1ug/10⁶ cells). Infection with Ad-p53 was detected at 6 to 48 hours post infection as a uniform relative increase in p53 levels over background p53 levels. Coincident increases in mdm2 immunoreactivity were also detected. DNA content measurements of PA1 and MDAH 2774 cells indicated that G1 arrest and/or apoptosis occurred subsequent to Ad-p53 infection. p53 and mdm2 levels and DNA content distributions for Ad-luc infected cells were equivalent to uninfected cells. Conclusions: A flow cytometric approach to measure the efficacy of an Ad-p53 gene therapy vector was developed that detects not only the gene transferred but also the activity of the transferred gene product. Cytometry (Comm. Clin. Cytometry) 38:201–213, 1999.  © 1999 Wiley-Liss, Inc.

Many intracellular pathways are set in motion by the binding of tumor necrosis factor (TNF) to its cell surface receptor. Major steps in the TNF‐mediated cytotoxicity cascade include G protein‐coupled activation of phospholipases, generation of free radicals, and damage to nuclear DNA by endonucleases. Ultimately the cells undergo apoptosis and die. Understanding how TNF initiates these pathways will facilitate the rational design of pharmaceuticals that can attenuate or potentiate the action of this important cytokine.— Larrick, J. W.; Wright, S. C. Cytotoxic mechanism of tumor necrosis factor‐α. FASEB J.4: 3215‐3223; 1990.

This article describes procedures used to enable a 10-year-old language- impaired pupil to use the Paget Gorman Signing System (PGSS) and DataPac strategies in reading. The pupil suffers from a variety of language deficiencies, of which labelling and word retrieval problems were the most severe. Short intervention sessions over a period of seven months were given, involving the use of words from the fuzzbuzz scheme. The results, which showed some improvement in the pupil's performance, are given. The contribution of the intervention sessions is discussed.

The paper reports an articulatory and perceptual study of a connected speech process, the assimilation of a final alveolar to a following velar or bilabial. Our EPG investigations show that this assimilatory process is gradual in articulatory terms, not discrete, as assumed in most phonological theories. The main question considered is that of the perceptual correlates of this articulatory gradualness. An experiment was devised in which phonetically trained listeners were asked (a) to identify a word followed in a carrier phrase by a velar or a bilabial as having an (underlying) final alveolar or a final velar or bilabial, and (b) to characterize the degree to which words identified as having an alveolar are assimilated to the following velar or bilabial. Results suggest (I) that there is no discrete perceptual boundary between the various types of articulation (including the underlying velars/bilabials) presented on the tape; and (2) there is some evidence that assimilations may never be 'complete', but may show a residual tongue body configuration characteristic of an alveolar, even when there is no discernible (either articulatorily or auditorily) alveolar gesture. Consequences for phonetics/ phonology and logopaedics are considered, and suggestions for further research are made.

Differential screening of two libraries made from whole, immature maize tassels was used to isolate six cDNAs which show enhanced levels of expression in male flowers. MFS1, MFS2, MFS4, MFS10and MFS18, which were isolated from a 5 cm tassel library, are expressed throughout tassel growth up until mature pollen is produced in the anthers. MFS14, which was isolated from a 10–12 cm tassel library, has a narrower window of expression associated with microsporogenesis and declines as mature pollen is produced. MFS18mRNA accumulates in the glumes and in anther walls, paleas and lemmas of mature florets. MFS18mRNA is particularly associated with the vascular bundle in the glumes and encodes a polypeptide of 12 kDa, rich in glycine, proline and serine that has similarities with other plant structural proteins. In contrast, MFS14mRNA accumulates in the tapetum and encodes a polypeptide of 13 kDa that is rich in alanine. The MFS14 and MFS18 proteins are basic (isolectric points of 11.56 and 9.54, respectively) and both have hydrophobic N‐termini which display all the characteristics of signal peptides, indicating that these proteins may be secreted.

This paper reports a descriptive study examining the relationship between the information processing dimensions of simultaneous and sequential synthesis and children's ability to recognise and notate meter. One hundred and sixty-one Grade 3, 5, and 6 students who were enrolled in two primary schools comprised the sample. The students' ability to distinguish between duple and triple meter was studied using a Meter Recognition Test which enabled the separate examination of three musical elements. namely pitch, rhythm, and dynamics. The results of analyses showed significant correlations between both simultaneous and sequential processing competencies and notational ability, between meter recognition and both simultaneous and sequential processing scores, and between meter recognition and notational ability. Additionally, children with high simultaneous processing ability were advantaged on simple rhythm items, while those with high sequential competence outperformed their peers on more complex rhythm tasks.

The funding context of higher education is examined, together with some of the constraints and imperatives to which it gives rise. The history, constitution and operation of the Southern Universities Purchasing Consortium's Libraries Project Group are discussed. The paper closes with a discussion of possible future roles for purchasing consortia.

Recent evidence indicates that cell death through apoptosis may be an important mechanism to prevent tumor development. Therefore, agents that inhibit apoptosis may function as tumor promotors. The purpose of this study was to determine the effects of nicotine on the process of apoptosis. The results demonstrate that nicotine inhibits apoptosis induced by diverse stimuli including tumor necrosis factor (TNF), UV light, chemotherapeutic drugs, and calcium ionophore. This phenomenon was observed in normal and transformed cells derived from a variety of species and tissues, including tumor cell types related to tobacco use. The major nicotine metabolite, cotinine, also inhibited apoptosis, whereas N‐nitrosodiethylamine, a carcinogen found in tobacco, was without effect. Therefore, nicotine‐mediated inhibition of apoptosis may contribute to the pathogenesis of tobacco‐related cancer as well as decrease the efficacy of cancer therapies.—Wright, S. C., Zhong, J., Zheng, H., Larrick, J. W. Nicotine inhibition of apoptosis suggests a role in tumor production, FASEB J.7: 1045‐1051; 1993.

The present study describes how four severely language - impaired pupils participated in an intervention programme aimed towards improving their word - finding skills. Short intervention sessions that concentrated upon a combination of both elaboration and retrieval techniques were conducted over a period of 4 weeks. Four control subjects received language therapy that was unrelated to word - finding activities. The subjects were matched for age, sex and word - finding difficulties. Results revealed that the two groups differed significantly on the accuracy of word retrieval. The four subjects that had received specific intervention improved in their ability to retrieve words. Two - tailed t - tests indicated that the improvement was highly significant at the probability level of p < 0.01 between the stages of testing. The contribution of the intervention sessions towards facilitating word - finding strategies of the four children is discussed.L'étude présente décrit de quelle fagon quatre élèves souffant d'un déficit langagier sévère ont participé à un programme d'intervention en vue d'améliorer leurs capacityés a retrouver lews mots. Sur une durée de quatre semaines Us ont suivi des sessions de courte durée mettant I'accent sur un mélange de techniques à la fois d'élaboration et de retrouvaille de vocabulaire. Quatre sujets de contrôle ont recu une thérapie du langage sans rapport avec des activités de retrouvaille de vocabulaire. Les sujets étaient appariés selon lˆàge, le sexe et leurs difficultés à retrouver leurs mots. Les résultats ont révélé que les deux groupes ont différé de manière significative quant aà lˆexactitude de leurs procédés de retrouvaille de vocabulaire, les quatre sujets qui avaient bénéficié d'interventions spécifiques ayant amélioré leur capacityé à retrouver leurs mots. Des tests de t à queue double ont indiqué que lˆamélioration était hautement significative avec une probabilityé de p < 0.01 entre les différents stades des tests. Une discussion examine la contribution des sessions d'intervention en ce qui concerne lˆamelioration des stratégies de retrouvaille de vocabulaire chez les quatre enfants.Die vorliegende Studie beschreibt die Teilnahme von vier schwer sprachbehinderten Schülerlnnen an einem Interventionsprogramm zur Förderung ihrer Wortfindungsfähigkeit. Kurze Interven - tionssitzungen, die auf eine Kombination von Elaborations - und Wortfindungstechniken fokussierten, wurde über eine Periode von 4 Wochen durchgeführt. Vier Kontrollpersonen, gepaart nach Alter, Geschlecht und Wortfindungsschwierigkeiten, erhielten Sprachtherapie, die mit Wortfindungsaktivitaten nichts zu tun hatte. Die Ergebnisse von Nachtests zeigten einen signifikanten Unterschied zwischen den Gruppen. Die Schülerlnnen im Interventionsprogramm konnten ihr Wortfindungsvermögen steigern. Zweiseitige t - Tests wiesen einen hoch - signifikanten Unterschied zwischen dem Vor - und Nachtest (p < 0.01) auf. Der Beitrag der Interventionssitzungen zur Förderung von Wortfindungsstrategien wird erörtert.

The present studies describe a new function for calmodulin‐dependent protein kinase II (CaM‐KII) in signal transduction leading to apoptosis. Both tumor necrosis factor α (TNF) and UV light rapidly stimulated Ca2+‐independent activity of CaM‐KII in the monocytic leukemia, U937. Two mechanistically different inhibitors of CaM‐KII blocked activation of CaM‐KII and prevented DNA fragmentation and death. Activation of CaM‐KII during apoptosis and inhibition of DNA fragmentation by the two CaM‐KII inhibitors were reproduced in several other lines including KG1a, HL‐60, and YAC‐1. However, K562, which is relatively resistant to apoptosis induced by either TNF or UV light, did not activate CaM‐KII in response to these stimuli. A variant derived from U937 that is resistant to TNF‐ or UV light‐induced apoptosis also lacked a CaM‐KII response. Activation of Cam‐KII was blocked by two protease inhibitors, VAD‐fmk and TPCK, but not by other inhibitors of serine proteases. Both inhibitors of CaM‐KII and the protease inhibitors blocked activation of AP24, a serine protease originally isolated from apoptotic cells that induces DNA fragmentation in nuclei. Our evidence supports a model in which proteolytic activity functions upstream of CaM‐KII. This kinase then leads to activation of AP24, which transmits signals to the nucleus to initiate DNA fragmentation.—Wright, S. C., Schellenberger, U., Ji, L., Wang, H., Larrick, J. W. Calmodulin‐dependent protein kinase II mediates signal transduction in apoptosis. FASEB J.11, 843–849 (1997)

Signal transduction pathways involved in apoptotic cell death are poorly understood, although recent studies have implicated sphingomyelin hydrolysis and generation of the second messenger, ceramide. Previous work in this laboratory demonstrated that a serine protease termed AP24 was activated by TNF or UV light and induced DNA fragmentation in isolated nuclei. This study extended these findings to examine the role of these enzymes in apoptosis of the U937 cell line and the mechanism of resistance of its variant, U9‐TR. Although this subclone was selected by growth in TNF, it was unexpectedly found to resist apoptosis induced by UV light, but was still sensitive to anti‐Fas‐induced DNA fragmentation. Here we show that in contrast to normal U937 cells, UV light and TNF both failed to activate neutral or acidic sphingomyelinase or AP24 in the U9‐TR variant. However, anti‐Fas activated both neutral and acidic sphingomyelinase in the variant comparable to that seen in parental U937. The U9‐TR variant could be sensitized to TNF or UV light activation of both sphingomyelinase and DNA fragmentation by the protein phosphatase inhibitors okadaic acid and caly‐culin A. Furthermore, exogenous bacterial‐derived sphingomyelinase caused U9‐TR activation of AP24 and DNA fragmentation comparable to that in the parental U937. Exposure of permeabilized U937 cells to ceramide caused internucleosomal DNA cleavage that was blocked by an inhibitor of AP24. Taken altogether, these findings demonstrate that TNF or UV light activate sphingomyelinase that leads to generation of ceramide resulting in activation of AP24 and DNA fragmentation in sensitive cells. A selective defect in signals leading to sphingomyelinase activation can confer resistance to apoptosis even though the variant is still sensitive to downstream apoptotic signals such as nuclear DNA fragmentation by activated exogenous AP24.—Wright, S. C., Zheng, H., Zhong, J. Tumor cell resistance to apoptosis due to a defect in the activation of sphingomyelinase and the 24 kDa apoptotic protease (AP24). FASEB J.10, 325‐332 (1996)

Recent evidence supports the concept that tumor growth in vivo depends on evasion of normal homeostatic control mechanisms that operate through induction of cell death by apoptosis. This study tested the hypothesis that a common property shared by known or suspected tumor promoters is the ability to block the process of apoptosis. A total of 10 tumor promoters were tested and all were found to inhibit DNA fragmentation and cell death of 7 different cell lines triggered into apoptosis by diverse agents. Resistance to apoptosis could be induced rapidly (within 1 h) by treating with relatively high concentrations of promoters. However, low physiological concentrations of promoters could also induce complete resistance to apoptosis after prolonged exposure (5‐15 days of culture). Like tumor promotion in vivo, promoter‐induced resistance to apoptosis was reversible after culturing in the absence of promoter. These findings provide new insight into the mechanism of tumor promotion and suggest a novel in vitro screening assay to detect new tumor‐promoting agents in the environment.— Wright, S. C., Zhong, J., Larrick, J. W. Inhibition of apoptosis as a mechanism of tumor promotion. FASEB J.8: 654‐660; 1994.

The effect of two therapy methods in the treatment of word-finding problems during a confrontational picture-naming situation are com pared in two groups of severely language-impaired children. A treat ment technique that promotes the strengthening of the children's seman tic networking and encourages the use of self-cuing (semantic treatment) is contrasted with an approach that fosters the child's phonological awareness and supports the use of phonological self-cuing (phonologic al treatment). A course of 15 sessions of treatment over five weeks is undertaken by each subject. The results are measured one week after the end of treatment. Those subjects receiving the semantic treatment indicate a highly significant improvement in naming untrained pictures, but the phonological treatment group makes no significant improve ment. Reasons for this and the efficacy of the two methods is examined, and possible clinical implications are discussed.

Although nursing homes are potentially important sites for geriatric research, previous reports have identified impediments to subject recruitment in this setting. We are conducting five simultaneous clinical studies in a 725‐bed nursing home. Utilizing a systematic subject recruitment methodology designed to minimize patient and staff burden, we have recruited over 100 subjects. The average recruitment rate over two years from nursing home residents meeting study entry criteria was 43%. The rate was highest (81%) for a study of urinary incontinence offering direct benefit to participants, and lowest (28% and 14% respectively) for physiologic studies of vasopressin regulation and dermal vitamin D production, offering no direct benefit. Studies of syncope and dementia which benefitted groups affected by these problems but not controls, had intermediate recruitment rates (46 and 44%, respectively, P < .002 compared to incontinence). Thus, clinically relevant projects, sensitive to the needs of the patient and institution, can recruit subjects from the nursing home.

AP24 is a serine protease that is activated during TNF or UV light-induced apoptosis and stimulates DNA fragmentation in isolated nuclei. The present study determined whether apoptosis induced by chemotherapeutic drugs resulted in activation of AP24 and examined the possible relationship to caspase activity. We showed that an inhibitor of AP24, DK120, could block DNA fragmentation induced in three leukemia cell lines (U937, HL-60, and CEM) by various DNA-damaging drugs including etoposide, camptothecin, chlorambucil, and the CC1065-related drug, YW201. Etoposide-induced activation of intracellular DEVD-pNa cleaving activity and apoptosis was suppressed by low micromolar concentrations of cell-permeable inhibitors of caspase-3. Furthermore, these inhibitors also suppressed activation of AP24. In contrast, DK120 did not prevent etoposide activation of DEVD-pNa cleaving activity, nor did it prevent cleavage of poly(ADP-ribose) polymerase. AP24 isolated from apoptotic cells following treatment with etoposide activated DNA fragmentation in isolated normal nuclei and was inhibited by DK120, but not by caspase inhibitors. This evidence shows that activation of caspase 3-like proteases generates signals that contribute to the activation of AP24 which may then induce nuclear DNA fragmentation in chemotherapeutic drug-induced apoptosis.

CAP18 is an antimicrobial protein found in specific granules of PMNs. The human CAP18 (HCAP18) gene was cloned from a human genomic phage library. Sequence analysis revealed the HCAP18 gene to have 4 exons spanning 3 kb, including 700 bp of upstream DNA. Using 3′ RACE no homologs of human HCAP18 were found in human bone marrow or leukocyte populations. By PCR analysis of a somatic cell mapping panel and fluorescence in situ hybridization of a genomic clone to metaphase chromosomes the gene was mapped to chromosome band 3p21.3. Like several other genes expressed late in PMN development the CAP18 gene did not contain typical TATA box or CCAAT sequences. Expression in Cos 7 cells permitted limited mapping of the promoter function in upstream fragments of the HCAP18 gene. Western blot, Northern blot and RT-PCR analysis show HCAP18 to be produced specifically in granulocytes. This work forms the groundwork for future analysis of the genetic regulation of this antimicrobial protein during PMN differentiation.

Evaluations of the effect of interventions on the terminally ill focus on outcomes such as patient satisfaction and quality of life. Due to the theoretical nature of these measures, researchers must rely on patients andfamily members asprimary data sources. Family members of terminally ill patients were queried concerning their motives for participation in the National Hospice Study and their reactions to an intensive interview schedule. Of those contacted, 94% agreed to the interview. The most frequently cited reasons for participating in the study were the desire to help other families facing a serious illness and the desire to help the hospice movement. Responses indicated a real enthusiasm for study participation in spite of the stressful nature of the terminally ill patient's situation.

Decreased neutrophil alkaline phosphatase (NAP) synthesis is a classical feature of Philadelphia (Ph) positive chronic phase chronic myeloid leukemia (CML). Whether this aberration is an integral leukemic property of the cell or results from mediation by other factors is unclear. During a-interferon (α-IFN) based therapy the relationship between Ph chromosome suppression and NAP synthesis was examined. Four categories of response were observed in 19 patients studied sequentially. Significantly, persistent low NAP activity was observed in one patient in complete cytogenetic remission, while a second group of 7 patients demonstrated normal NAP activity in spite of persistence of the Ph chromosome in 100% of metaphases. In the absence of various clinical influences that can modulate NAP activity in chronic phase CML, the results reinforce the observation that the BCWABL fusion gene product is not a key factor influencing NAP activity in CML.

The present study surveyed the views of parents about the education of students with special needs in regular classrooms. The survey involved 81 parents of students without disabilities and 29 parents of students with special needs. The children attended an Australian primary school. The school provided special education to 35 students with special needs and some of their education was provided in regular classrooms. Both groups of parents provided a range of supportive comments, but also expressed concerns about the implementation of special education in regular classrooms. Specific concerns included the extra time and added stress of educating children with special needs in the regular classroom, the potential disruption and disadvantage to other students, and the lack of support and resources, which may decrease the amount of learning. These views are consistent with those expressed by teachers and students without special needs as reported in the companion paper (Wright & Sigafoos, 1997) to the present study.

The present study surveyed teachers and students without disabilities regarding the inclusion of students with disabilities at an Australian primary school. The school provided special education to 35 students with special needs and some of their education was provided in regular classrooms alongside peers without disabilities. Fifteen regular classroom teachers and 109 classroom peers without special needs completed questionnaires. Both groups provided a range of supportive comments about regular classroom placements for student with special needs, but also expressed concerns about the implementation of special education in regular classrooms. Specific concerns included the extra time and added stress of educating children with special needs in the regular classroom setting, potential disruption and disadvantage to other students and the lack of support and resources. Unless these concerns are addressed, placement of students with special needs in regular classrooms may generate stress, concern, and even possibly resentment among some teachers and students without disabilities.

Twenty-five patients with major ABO blood group incompatibility between donor and recipient underwent allogeneic bone marrow transplantation using erythrocyte depletion of the bone marrow infusate prior to administration. Over 95% of the original erythrocyte content of the marrows was removed, while retaining 75% of the mononuclear cell content and 57% of the granulocyte-monocyte colony-forming units. Recipients, well hydrated and premedicated with corticosteroids, diphenhydramine, and mannitol, tolerated infusions well. The frequency of engraftment, rate of recovery of peripheral blood leukocytes, granulocytes, and platelets, and the incidence of graft-versus-host disease was similar to that observed following ABO blood group compatible bone marrow transplantation. Erythroid development following ABO blood group incompatible transplantation was significantly impaired until hemagglutinins fell to 1:4 or lower, at which time recovery of erythrocytes was detected in the peripheral blood. The erythrocyte hypoplasia associated with incompatible hemagglutinins was temporary. Erythrocyte purging is a safe and effective technique to perform bone marrow transplantation across major ABO blood group incompatibilities.

Power and the Praise Poem: Southern African Voices in History. Leroy Vail and Landeg White, (University Press ofVirginia/James Currey, 1991, pb £11.95).Mating. Norman Rush, (Jonathan Cape, 1992, hb. £15.99, Vintage, 1993, ph.£5.99).The Natal Papers of 'John Ross'. Charles Rawden Maclean, (Ed.) Stephen Gray, (University of Natal Press: Pietermaritzburg, 1992, pb (SA) R57-57).Cetshwayo's Dutchman. Cornelius Vijn, (Ed. and trans.) J W Colenso, Bishop of Natal, 1880. (Greenhill Books: London, 1988, hb).Dambudzo Marechera: A Source Book on his Life and Work. Flora Veit-Wild, (HdnsZell Publishers, 1992, hb).Cemetery of Mind. Dambudzo Marechera, (Baobab Books, Harare, 1992, pb. £6.50).Pawns. Charles Samupindi, (Baobab Books, Harare, 1992, pb. £6.50).Fruits and Other Poems. Titus Moetsabi, (Zimbabwe Publishing House, Harare, 1992, pb.£5.00).Third World Express. Mongane Wally Serote, (David Philip, Cape Town & Johannesburg, 1992, pb. R24.95).Guava Juice. Sandile Dikeni, (Mayibuye Booh, Bellville [Cape], 1992, pb.)Emergency Poems. Keith Gottschalk, (Mayibuye Books, Bellville [Cape], 1992, pb.)Gardens of Struggle. Barry Feinbu'rg, (Mayibuye Books, Bellville [Cape], 1992, pb.)The Coffee Shop Poems. Karen Press, (Snailpress, Plumstead [Cape], 1993, pb.)Avalon Court. Gladys Thomas, (Skotaville Publishers, Braamfontein, 1992, pb. £5).The View from the Stockade. Landeg White, (Dangaroo Press, 1991, pb.)Bounty. Landeg White, (Dangaroo Press, 1993, pb.)The First Life of Adamastor. Andre Brink, (Seeker & Warburg, 1993, pb. £7.99).Stedman and Joanna - a Love in Bondage. Beryl Gilroy, (Vantage Press USA, 1991, hb).Nehanda. Yvonne Vera (Baobab Books, 1993, pb. £6.25).War Child. Stephen Gray (Serif, 1993, pb. £9.99).Cultural Struggle & Development in Southern Africa. (ed.) Preben Kaarsholm (London: James Currey, and Harare: Baobab, and Portsmouth, New Hampshire, Heinemann, 1991, hb. £30, pb. £11.95).The Chattering Wagtails of Mikuyu Prison. Jack Mapanje, (Heinemann, 1993, pb. £5.99).One Dark Body. Charlotte Watson Sherman, (Women's Press, 1993, pb. £6.99).

The association of hemolytic anemia and other autoimmune cytopenias with chronic lymphocytic leukemia (CLL) is well known. The etiology of these immune syndromes is still uncertain, despite evidence that the putative cell of origin of the B-CLL cell produces naturally occurring autoantibodies. Cyclosporine A is effective in treating the immune manifestations associated with CLL and, occasionally, has shown anti-leukemic activity. We report two cases in which cyclosporine A treatment of autoimmune hemolytic anemia resulted in reduction of CLL cell burden. We then discuss the possible mechanism of action of cyclosporine A and the nature of the autoimmune processes involved.

Patients developing Hodgkin's disease (HD) after a diagnosis of chronic lymphocytic leukemia (CLL), are frequently included in a series of patients with Richter's syndrome (RS). We sought to determine the natural history of the association of CLL and HD. Over a 21 year period, 1374 patients with CLL have been registered in our computer data base. Seven cases of CLL and HD have been documented and confirmed. The median age of these patients was 71 years (range 44-77) and clinical features included male gender (86%), B symptomatology (86%), rapidly progressive lymphadenopathy (71%), prior CLL therapy (71%), advanced Ann Arbor stage (86%), marrow involvement with HD (43%), and autoimmune hemolytic anemia (29%). HD was documented by excisional lymph node biopsy in six cases and splenectomy in one. Mixed cellularity HD was shown in six and nodular sclerosis in one. Five of the biopsies revealed intervening areas consistent with small lymphocytic lymphoma. The Sternberg-Reed (SR) cells were CD15+ in 6/7 cases, and Ki-1+ in the 6 patients tested. CD45 and CD20 staining of the SR cells was nonreactive. The median time to development of HD was 45 months (range 0 to 96). The overall responses to different chemotherapy regimens was approximately 25% with only one CR. Six patients have died at 3,9,10,13,15 and 36 months and one patient is alive with progressive disease at 11 months. Our data suggests that CLL patients have a heightened risk for HD, features of advanced HD on presentation, and a poor response rate with short survival.