bluuebunny/crossref_metadata_2025 huggingface dataset:
DISCUSSIONS AROUND A SAND‐DRAWING: CREATIONS OF AGENCY AND SOCIETY IN MELANESIA
Authors: Rio Knut
Published: August 2005

This article considers the social circumstances of making a marriage diagram, on the island of Ambrym in Vanuatu. It offers a reconsideration of the rather famous case of the ‘six‐section marriage system’ as demonstrated by Cambridge anthropologist Bernard Deacon. It relates this idea of a system to the indigenous practice of making figurative drawings in the sand. The argument is that the marriage diagram drawn for Bernard Deacon was merely an instance of Vanuatu people's institutionalized capability of totalizing social flows and making them into aesthetic shapes.
CHRONICALLY UNSTABLE BODIES: REFLECTIONS ON AMAZONIAN CORPORALITIES
Authors: Vilaça Aparecida
Published: August 2005

Based on ethnographic material relating to the Wari’ (Rondônia, Brazil), this article questions some of the presuppositions concerning native conceptions of the body present in contemporary anthropological literature by exploring a central dimension of Amazonian corporality – one that has been little explored in ethnographic works on the region – its unstable and transformational character. This dimension only becomes evident when our analysis presumes an expanded notion of humanity – first called to our attention by authors such as Lévy‐Bruhl and Leenhardt – that includes not only those beings we think of as humans, but also other subjectivities such as animals and spirits. Central to the problem's development is a discussion of the relations between body and soul, humanity and corporality.
Multiparameter Evidence Synthesis in Epidemiology and Medical Decision-Making: Current Approaches
Authors: Ades A. E. , Sutton A. J.
Published: August 2005

Alongside the development of meta-analysis as a tool for summarizing research literature, there is renewed interest in broader forms of quantitative synthesis that are aimed at combining evidence from different study designs or evidence on multiple parameters. These have been proposed under various headings: the confidence profile method, cross-design synthesis, hierarchical models and generalized evidence synthesis. Models that are used in health technology assessment are also referred to as representing a synthesis of evidence in a mathematical structure. Here we review alternative approaches to statistical evidence synthesis, and their implications for epidemiology and medical decision-making. The methods include hierarchical models, models informed by evidence on different functions of several parameters and models incorporating both of these features. The need to check for consistency of evidence when using these powerful methods is emphasized. We develop a rationale for evidence synthesis that is based on Bayesian decision modelling and expected value of information theory, which stresses not only the need for a lack of bias in estimates of treatment effects but also a lack of bias in assessments of uncertainty. The increasing reliance of governmental bodies like the UK National Institute for Clinical Excellence on complex evidence synthesis in decision modelling is discussed.
Comparing Clinical Data with Administrative Data for Producing Acute Myocardial Infarction Report Cards
Authors: Austin Peter C. , Tu Jack V.
Published: August 2005

We compared measures of hospital performance by using both administrative and clinical data sources. Hospital-specific mortality outcomes on 10086 patients who had been admitted to 102 hospitals with a diagnosis of acute myocardial infarction in Ontario, Canada, were used as a test-case. Four and six hospitals were identified as having mortality that was statistically significantly higher than expected by using administrative and clinical data respectively, when model-based indirect standardization was used. When using random-effects models, zero and two hospitals were identified as having significantly higher mortality by using administrative and clinical data respectively. Approximately one in four hospitals changed at least two decile rankings when clinical data were used compared with when administrative data were used.
Does the Australian Competition and Consumer Commission Engage in “Trial by Media”?*
Authors: YEUNG KAREN
Published: August 2005

In recent years, heated debate has arisen concerning the media practices of Australia's competition and consumer regulator (“the ACCC”), with a number of industry leaders asserting that the ACCC engages in “trial by media.” The public disquiet surrounding the ACCC's use of the media was so significant that the Australian Parliament established an independent committee of inquiry (“the Dawson Inquiry”) to investigate (amongst other things) whether Australian competition legislation “provides adequate protection for the commercial affairs and reputation of individuals and corporations.” In its report, the Dawson Inquiry observed that widespread misgivings about the ACCC's media practices had emerged from the submissions that it had received. In its recommendations to the Australian Parliament, the Dawson Inquiry recommended that the ACCC should develop a media code of conduct to govern its use of the media, particularly in relation to enforcement proceedings. In making these recommendations, the Dawson Inquiry drew from a hitherto unpublished research study conducted in 2002 that sought to identify the extent to which the ACCC engages in “trial by media.” This article documents the design, methodological bases, and findings of that study in order to facilitate broader dissemination of the research findings upon which the Dawson Inquiry's policy recommendations concerning the ACCC's use of the media were based.
CLOSED‐FORM SOLUTIONS FOR OPTIMAL PORTFOLIO SELECTION WITH STOCHASTIC INTEREST RATE AND INVESTMENT CONSTRAINTS
Authors: Detemple Jér^me , Rindisbacher Marcel
Published: August 2005

We examine the portfolio choice problem of an investor with constant relative risk aversion in a financial market with partially hedgeable interest rate risk. The individual shadow price of the portfolio constraint is characterized as the solution of a new backward equation involving Malliavin derivatives. A generalization of this equation is studied and solved in explicit form. This result, applied to our financial model, yields closed‐form solutions for the shadow price and the optimal portfolio. The effects of parameters such as risk aversion, interest rate volatility, investment horizon, and tightness of the constraint are examined. Applications of our method to a monetary economy with inflation risk and to an international setting with currency risk are also provided.
LATTICE OPTION PRICING BY MULTIDIMENSIONAL INTERPOLATION
Authors: Kargin Vladislav
Published: August 2005

This paper proposes a method for pricing high‐dimensional American options based on modern methods of multidimensional interpolation. The method allows using sparse grids and thus mitigates the curse of dimensionality. A framework of the pricing algorithm and the corresponding interpolation methods are discussed, and a theorem is demonstrated, which suggests that the pricing method is less vulnerable to the curse of dimensionality. The method is illustrated by an application to rainbow options and compared to least squares Monte Carlo and other benchmarks.
A SHORT NOTE ON SECOND‐ORDER STOCHASTIC DOMINANCE PRESERVING COHERENT RISK MEASURES
Authors: Leitner Johannes
Published: August 2005

We improve results on law invariant coherent risk measures satisfying the Fatou property due to Kusuoka (2001; Adv. Math. Econ. 3, 83–95) by considering risk measures which are in addition second order stochastic dominance preserving. In particular, we derive a representation result for such risk measures.
Antiretroviral therapy in HIV‐positive men is associated with increased apolipoprotein CIII in triglyceride‐rich lipoproteins
Authors: Rimland D , Guest JL , Hernández I , Del Rio C , Le NA , Brown WV
Published: September 2005

Objectives

Dyslipidaemia has become a common problem in HIV disease, especially in patients on current antiretroviral therapy. However, the pathogenic mechanisms involved are not well understood or documented using conventional lipid measurements.

Methods

Using a cross‐sectional design, the prevalence of abnormal standard lipid measurements and novel biomarkers for abnormal lipid metabolism was determined in 271 HIV‐positive men from two HIV clinics in Atlanta, GA, USA.

Results

A total of 147 men were treated with protease inhibitors (PIs) for >3 months (54%), 84 were treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) for >3 months (31%) and 40 had not received antiretroviral therapy in the past 3 months (15%). Patients being treated with a PI had higher total cholesterol and triglyceride (TG) levels than patients on no therapy (P<0.05 for each). Patients in the NNRTI group had higher TG, lower high‐density lipoprotein (HDL) levels, and higher low‐density lipoprotein (LDL) levels than patients on no therapy (P<0.05 for each). Patients treated with either PIs or NNRTIs were more likely to have higher apolipoprotein CIII (apoCIII) levels (P<0.05 for each) than patients on no therapy. Elevated TG was associated with disproportionably elevated apoCIII levels in both treatment groups.

Conclusions

In this cross‐sectional study of HIV‐infected men, either PI or NNRTI therapy elevated levels of TG and apoCIII. Higher concentrations of apoCIII in apoB‐containing lipoproteins [very low‐density lipoproteins (VLDLs), intermediate density lipoprotein (IDL) and LDLs] have been predictive of an increased incidence of coronary events in clinical trials and more rapid progression of coronary lesions measured by angiography. These findings, on a background of an older population with additional risk factors of smoking and diabetes, portend future atherosclerotic events in these patients.
Recruitment‐Related Information Sources and Organizational Attractiveness: Can Something Be Done About Negative Publicity?
Authors: Van Hoye Greet , Lievens Filip
Published: August 2005

The present study begins to fill a gap in the recruitment literature by investigating whether the effects of negative publicity on organizational attractiveness can be mitigated by recruitment advertising and positive word‐of‐mouth. The accessibility–diagnosticity model was used as a theoretical framework to formulate predictions about the effects of these recruitment‐related information sources. A mixed 2 × 2 experimental design was applied to examine whether initial assessments of organizational attractiveness based on negative publicity would improve at a second evaluation after exposure to a second, more positive information source. We found that both recruitment advertising and word‐of‐mouth improved organizational attractiveness, but word‐of‐mouth was perceived as a more credible information source. Self‐monitoring did not moderate the impact of information source on organizational attractiveness.
Recruitment Sources and Post‐Hire Outcomes: The Mediating Role of Unmet Expectations
Authors: Moser Klaus
Published: August 2005

Two decades ago it was hypothesized that met expectations mediate the relationship between recruitment sources (internal vs. external) and post‐hire outcomes. The current study tested this mediator hypothesis with new employees and found that those who entered the organization via internal recruitment sources experienced less unmet expectations than employees recruited via external recruitment sources. In addition, unmet expectations mediated the relation between type of recruitment source (internal vs. external) and both job satisfaction and organizational commitment. The study also found a considerable number of employees who reported that they have used multiple recruitment sources.
The development of siblings of children with autism at 4 and 14 months: social engagement, communication, and cognition
Authors: Yirmiya Nurit , Gamliel Ifat , Pilowsky Tammy , Feldman Ruth , Baron‐Cohen Simon , Sigman Marian
Published: August 2005

Aims:  To compare siblings of children with autism (SIBS‐A) and siblings of children with typical development (SIBS‐TD) at 4 and 14 months of age.

Methods:  At 4 months, mother–infant interactional synchrony during free play, infant gaze and affect during the still‐face paradigm, and infant responsiveness to a name‐calling paradigm were examined (n = 21 in each group). At 14 months, verbal and nonverbal communication skills were examined as well as cognition (30 SIBS‐A and 31 SIBS‐TD).

Results:  Most SIBS‐A were functioning as well as the SIBS‐TD at 4 and 14 months of age. However, some differences in early social engagement and later communicative and cognitive skills emerged. Synchrony was weaker in the SIBS‐A dyads, but only for infant‐led interactions. Infant SIBS‐A revealed more neutral affect during the still‐face procedure and were less upset by it than was true for the SIBS‐TD. A surprising result was that significantly more SIBS‐A responded to their name being called by their mothers compared to SIBS‐TD. At 14 months, SIBS‐A made fewer nonverbal requesting gestures and achieved lower language scores on the Bayley Scale. Six SIBS‐A revealed a language delay of 5 months and were responsible for some of the significant differences between SIBS‐A and SIBS‐TD. Furthermore, infant SIBS‐A who showed more neutral affect to the still face and were less able to respond to their name being called by their mothers initiated fewer nonverbal joint attention and requesting behaviors at 14 months, respectively.

Discussion:  Focused on the genetic liability for the broad phenotype of autism as well as the possible influence of having a sibling with autism.
The control of stomata by water balance
Authors: Buckley Thomas N.
Published: August 2005

It is clear that stomata play a critical role in regulating water loss from terrestrial vegetation. What is not clear is how this regulation is achieved. Stomata appear to respond to perturbations of many aspects of the soil–plant–atmosphere hydraulic continuum, but there is little agreement regarding the mechanism (or mechanisms) by which stomata sense such perturbations. This review discusses feedback and feedforward mechanisms by which hydraulic perturbations are putatively transduced into stomatal movements, in relation to generic empirical features of those responses. It is argued that a metabolically mediated feedback response of stomatal guard cells to the water status in their immediate vicinity (‘hydro‐active local feedback’) remains the best explanation for many well‐known features of hydraulically related stomatal behaviour, such as transient ‘wrong‐way’ responses and the equivalence of hydraulic supply and demand as stomatal effectors. Furthermore, many curious phenomena that appear inconsistent with feedback, such as ‘apparent feedforward’ humidity responses and ‘isohydric’ behaviour (water potential homeostasis), are in fact expected to emerge from the juxtaposition of hydro‐active local feedback and the well‐known hysteretic and threshold‐like effect of water potential on xylem hydraulic resistance.

ContentsSummary1I.Introduction2II.Background: stomatal hydromechanics2III.The parsimony of hydro‐active local feedback4IV.Feedforward, or feedback plus? Emergent properties of marginally stable feedback control8V.Conclusions14Acknowledgements14References14Appendix17
DNA repair mechanisms in plants: crucial sensors and effectors for the maintenance of genome integrity
Authors: Bray Clifford M. , West Christopher E.
Published: August 2005

As obligate phototrophs, plants harness energy from sunlight to split water, producing oxygen and reducing power. This lifestyle exposes plants to particularly high levels of genotoxic stress that threatens genomic integrity, leading to mutation, developmental arrest and cell death. Plants, which with algae are the only photosynthetic eukaryotes, have evolved very effective pathways for DNA damage signalling and repair, and this review summarises our current understanding of these processes in the responses of plants to genotoxic stress. We also identify how the use of new and emerging technologies can complement established physiological and ecological studies to progress the application of this knowledge in biotechnology.

Contents

Summary
1

I.
Introduction
1

II.
Photoreactivation
4

III.
Excision repair pathways: BER, NER, mismatch repair
7

IV.
DNA double‐strand break repair
10

V.
Molecular responses to genotoxic stress
13

VI.
Conclusions and future prospects
14

Acknowledgements
15

References
15
CERVICAL CANCER AND CYTOLOGY SCREENING IN NEW ZEALAND
Authors: Green G. H.
Published: August 2005

Cytology screening, used in New Zealand since 1955 at an intensity comparable to that in Canada generally, has not favourably affected incidence and mortality rates for cervical cancer; these have actually risen significantly in 20 to 34‐year‐old New Zealand women. Canadian claims that mortality falls are related to intensity of cytological screening are not justifiable, so that the significance of the‘pre‐cancers’revealed by cytology and the value ofpopulation screening would seem to be doubtful.
THE PATTERN OF PRESENTATION OF CARCINOMA OF THE UTERINE CERVIX IN EAST ANGLIA 1960 TO 1975
Authors: de Bono Anne M. , Kingsley Pillers E. M. , Kirk N. M.
Published: August 2005

Changes in the pattern of presentation of carcinoma of the uterine cervix between 1960 and 1975 were studied using the records of 3193 patients registered with the East Anglian Cancer Registration Bureau. Between 1963 and 1968, an increased registration rate for invasive tumours was largely attributable to increased registrations of Stage I and I1 lesions in the 35 to 49 age group. After 1970 the registration rate for lesions of all stages in this age group declined. Over the same period the 50 to 64 age group showed a tendency for an increased proportion of registrations to be of Stage I or I1 lesions. There was little change in pattern in the over‐65 age group. The possible relation of these changes to the introduction of a cervical cytology screening programme and the implications for future screening policies are discussed.
DISTINCTION OF BENIGN FROM MALIGNANT OVARIAN CYSTS BY ULTRASOUND
Authors: Meire H. B. , Farrant Pat , Guha T.
Published: August 2005

The ultrasonic characteristics of benign and malignant cystic ovarian tumours have been reviewed. The value of each of eight different ultrasonic features has been assessed and the specificity of each for confirmation or exclusion of malignancy is indicated. In combination they permit correct differentiation in 91 per cent of cases.
SECRETION PATTERNS OF PLASMA‐PROGESTERONE, 17‐HYDROXYPROGESTERONE AND 20 α HYDROXYPREGN‐4‐EN‐3‐ONE IN EARLY NORMAL PREGNANCY
Authors: Harrison R. F. , Youssefnejadian E. , Brodovcky Hilary , Johnson M. , Dewhurst Sir John
Published: August 2005

Plasma levels of progesterone, 17‐hydroxyprogesterone and 20 α hydroxypregn‐4‐en‐3‐one were established from 4 to 16 weeks gestation by sampling 15 normal patients twice weekly. Apart from a peak at week 5, the mean levels of progesterone remained constant at about 24 ng/ml until week 10 and then rose progressively to 40 ng/ml at week 16.20 α hydroxypregn‐4‐en‐3‐one remained within the 7 to 9 ng/ml range apart from a peak at week 5. A significant decrease in mean levels of 17‐hydroxy‐progresterone was noted from week 5 to a nadir of 3 ng/ml at week 11. It would appear that the main hormone production of progesterones in pregnancy has been taken over by the placental unit by the 10th week.
MATERNAL HAEMOGLOBIN CONCENTRATION, HAEMATOCRIT AND RENAL HANDLING OF URATE IN PREGNANCIES ENDING IN THE BIRTHS OF SMALL‐FOR‐DATES INFANTS
Authors: Dunlop W. , Furness C. , Hill L. M.
Published: August 2005

In nine patients who gave birth to babies below the fifth centile in weight, serum urate concentration and fractional reabsorption of urate were significantly higher than in 25 control patients whose babies were of normal birth weight. Haemoglobin concentration and haematocrit were also significantly increased in the small‐for‐dates group. All of these changes may reflect depletion of extracellular fluid volume.
SERUM PROLACTIN AND GONADOTROPHIN LEVELS BEFORE AND AFTER LUTEINIZING HORMONE‐RELEASING HORMONE IN THE INVESTIGATION OF AMENORRHOEA
Authors: Bergh T. , Nillius S. J. , Wide L.
Published: August 2005

An intravenous luteinizing hormone‐releasing hormone (LRH) test was performed in 287 women with amenorrhoea. Prolactin, progesterone and oestrogens in serum were also measured. Twenty‐four women with premature ovarian failure and 9 with gonadal dysgenesis had raised basal follicle‐stimulating hormone (FSH) levels. Neither the basal luteinizing hormone (LH) level nor the gonadotrophin responses after LRH gave a better separation of this group of women with irreversible ovarian failure. Measurement of prolactin levels were valuable in that 15 of 42 patients with hyperprolactinaemia had a radiologically abnormal pituitary fossa, whereas pituitary fossa abnormalities were found in only 11 of 245 normoprolactinaemic women. It was thought that 181 women had functional amenorrhoea; 54 per cent of these women had developed amenorrhoea in relation to weight loss and 32 per cent in relation to discontinuation of oral contraceptives. A strong correlation was found between the body weight and the basal gonadotrophin levels. The basal LH levels were correlated with serum oestrogen levels, the basal FSH level and the LH response to LRH. Most of the patients with low basal LH values had developed amenorrhoea in relation to self‐imposed weight loss. The responses to LRH were often impaired in the underweight patients but became normal after weight gain. The polycystic ovary syndrome (PCO) could not be diagnosed by measuring either basal or LRH‐stimulated gonatrophin levels. Single FSH and prolactin determinations in serum seemed to be the only indispensible hormone assays in the routine clinical evaluation of amenorrhoea.
THE OUTCOME OF PREGNANCY AFTER CONE BIOPSY OF THE CERVIX: A CASE‐CONTROL STUDY
Authors: Jones Jane M. , Sweetnam P. , Hibbard B. M.
Published: August 2005

We investigated the outcome of pregnancy after cone biopsy of the cervix. We found that preterm delivery and low birth weight were commoner and the mean duration of labour longer in women who had a cone biopsy than amongst matched controls. Rapid labour (under two hours) was not significantly more common after cone biopsy.
A STUDY OF CRYOSURGERY FOR DYSPLASIA AND CARCINOMA IN SITU OF THE UTERINE CERVIX
Authors: Elmfors B. , Stormby N.
Published: August 2005

We studied 22 patients with a histopathological diagnosis of severe dysplasia and 89 patients with a diagnosis of carcinoma in situ of the uterine cervix. Twenty patients (18 per cent) had negative cervical smears for four to six years after diagnosis by biopsy of the cervix. The 91 patients with persistently abnormal smears were treated by cryosurgery, using a double freeze technique with nitrous oxide. Seventy‐four (86 per cent) had persistently normal cervical smears after one treatment and eight after a second treatment while nine patients required coni‐zation for recurrently abnormal cervical smears. The duration of follow‐up was five or six years in 48 patients (53 per cent). In a subsidiary study, material was obtained for histological examination from 72 patients with normal smears by endocervical curettage and multiple biopsies of the cervix; 8 showed slight atypia and 2 had residual carcinoma in situ.
CHANGES IN FAT, FAT‐FREE MASS AND BODY WATER IN HUMAN NORMAL PREGNANCY
Authors: Pipe N. G. J. , Smith T. , Halliday D. , Edmonds C. J. , Williams C. , Coltart T. M.
Published: August 2005

Measurements of body weight, total body water and total body potassium (40K) were made serially on three occasions during pregnancy and once post partum in 27 normal pregnant women. Skinfold thickness and fat cell diameter were also measured. A model of body composition was formulated to permit the estimation of changes in fat, lean tissue and water content of the maternal body. Total maternal body fat increased during pregnancy, reaching a peak towards the end of the second trimester before diminishing. Serial measurements of fat cell diameter showed poor correlation, whilst total body fat calculated from skinfold thickness correlated well with our estimated values for total body fat in pregnancy.
INTRAPARTUM FETAL MONITORING WITH THE CEREBRAL FUNCTION MONITOR
Authors: Maynard D. E. , Cohen R. J. , Viniker D. A.
Published: August 2005

We report a trial of the technical feasibility of monitoring the state of the fetal brain during labour using the Cerebral Function Monitor (CFM). This device was developed for long‐term monitoring of the electroencephalogram (EEG). A tripolar scalp electrode allows removal of the fetal electrocardiograph (ECG) from the fetal EEG. Technically satisfactory recordings were obtained from 15 fetuses during labour for periods of up to 6½ hours before delivery. There were alterations of CFM trace with fetal distress and also during general anaesthesia for Caesarean section.
CONTINUOUS MEASUREMENT OF TRANSCUTANEOUS FETAL OXYGEN TENSION DURING LABOUR
Authors: Weber T. , Secher N. J.
Published: August 2005

Transcutaneous scalp oxygen tension (tcPO2) was measured during labour in 40 fetuses, using a modified Clark electrode (Radiometer, Copenhagen). In 24 of the fetuses the recordings were of good quality during the second stage of labour. After delivery the acid‐base status and oxygenation of the umbilical cord blood was measured. A correlation was found between the tcPO2 and umbilical artery oxygen saturation (r = 0.56, p<0.01) and umbilical artery PO2 (r = 0.56, p<0.01). Furthermore, a positive correlation was found between the area beneath the recorded tcPO2 curve during the last 10 minutes and the umbilical artery pH (r = 0.50, p <0.05). The data suggest that continuous transcutaneous PO2 measurement may be of value in monitoring high risk patients during labour.
AMNIOTIC FLUID PALMITIC ACID/STEARIC ACID RATIOS, LECITHIN/SPHINGOMYELIN RATIOS AND PALMITIC ACID CONCENTRATIONS IN THE ASSESSMENT OF FETAL LUNG MATURITY IN DIABETIC PREGNANCIES
Authors: Anderws A. G. , Brown J. B. , Jeffery P. E. , Horacek I.
Published: August 2005

The lecithin/sphingomyelin (L/S) ratio, palmitic acid concentration and palmitic to stearic acid (P/S) ratio were estimated on samples of amniotic fluid obtained from 66 patients with diabetes. These were compared with similar estimates on amniotic fluid obtained from 127 non‐diabetic patients. At 35 to 40 weeks, significant differences were observed between the L/S ratio and palmitic acid concentration in diabetics and non‐diabetics, whereas the P/S ratio was similar in the two groups. The amniotic fluid L/S ratio, palmitic acid concentration, and P/S ratio were estimated on amniotic fluid obtained from 20 diabetic patients within 48 hours of induction, and the clinical outcome of the newborn infant was used to assess the predictive value of the three parameters. In 19 out of the 20 diabetics the P/S ratio correctly predicted fetal lung maturity, whereas the palmitic acid concentration was correct in 12 patients and the L/S ratio in only 10 patients.
CIRCULATING LEVELS OF PREGNANCY SPECIFIC β1 GLYCOPROTEIN IN PREGNANCIES COMPLICATED BY DIABETES MELLITUS
Authors: Grudzinskas J. G. , Gordon Y. B. , Davies Humphreys J. , Brudenell M. , Chard T.
Published: August 2005

Circulating levels of SP1 were measured in 20 insulin dependent diabetic women during the third trimester of pregnancy. With one exception, SP1 levels were between the 80 percent confidence limits of the normal range. The exception was a patient who was delivered of a normal infant at 37 weeks but had consistently low levels of SP1 from 32 weeks until delivery, suggesting a specific defect in SP1 synthesis.
PRIMARY CARCINOMA OF THE FALLOPIAN TUBE ASSOCIATED WITH TUBERCULOUS SALPINGITIS A CASE REPORT
Authors: Vinall P. S. , Buxton N. , Cowen P. N.
Published: August 2005

A patient with co‐existent carcinoma and tuberculosis of the Fallopian tube is described. Tuberculosis was diagnosed by the finding of numerous typical granulomata throughout the uterus, tubes and ovaries, and by exclusion of other possible causes of these; and carcinoma by the finding of solid tumour, with a marked anisocytic appearance, invading submucosa. Despite the well recognised epithelial hyperplasia seen in tuberculous salpingitis, there remains no evidence that the occurrence of carcinoma in such cases is other than fortuitous.
Down‐regulation of muscarinic acetylcholine receptor M2 adversely affects the expression of Alzheimer's disease‐relevant genes and proteins
Authors: Zuchner Thole , Schliebs Reinhard , Perez‐Polo J. Regino
Published: August 2005

Beta‐amyloid peptides play a major role in the pathogenesis of Alzheimer's disease (AD). Therefore, preventing beta‐amyloid formation by inhibition of the beta site amyloid precursor protein‐cleaving enzyme (BACE) 1 is considered as a potential strategy to treat AD. Cholinergic mechanisms have been shown to control amyloid precursor protein processing and the number of muscarinic M2‐acetylcholine receptors is decreased in brain regions of patients with AD enriched with senile plaques. Therefore, the present study investigates the effect of this M2 muscarinic receptor down‐regulation by siRNA on total gene expression and on regulation of BACE1 in particular in SK‐SH‐SY5Y cells. This model system was used for microarray analysis after carbachol stimulation of siRNA‐treated cells compared with carbachol stimulated, non‐siRNA‐treated cells. The same model system was used to elucidate changes at the protein level by using two‐dimensional gels followed by Matrix Assisted Laser Desorption Ionization Time‐of‐Flight Mass Spectrometry (MALDI‐TOF) analysis. Taken together, the results indicate that the M2 acetylcholine receptor down‐regulation in brains of patients with AD has important effects on the expression of several genes and proteins with major functions in the pathology of AD. This includes beta‐secretase BACE1 as well as several modulators of the tau protein and other AD‐relevant genes and proteins. Moreover, most of these genes and proteins are adversely affected against the background of AD.
A model for dynamic regulation of choline acetyltransferase by phosphorylation
Authors: Dobransky Tomas , Rylett R. Jane
Published: August 2005

Choline acetyltransferase (ChAT) synthesizes the neurotransmitter acetylcholine (ACh) and is a phenotypic marker for cholinergic neurons. Cholinergic neurons in brain are involved in cognitive function, attentional processing and motor control, and decreased ChAT activity is found in several neurological disorders including Alzheimer's disease. Dysregulation of ChAT and cholinergic communication is also associated with some spontaneous point‐mutations in ChAT that alter its substrate binding kinetics, or by disruption of signaling pathways that could regulate protein kinases for which ChAT is a substrate. It has been identified recently that the catalytic activity and subcellular distribution of ChAT, and its interaction with other cellular proteins, can be modified by phosphorylation of the enzyme by protein kinase‐C and Ca2+/calmodulin‐dependent protein kinase II; these kinases appear also to mediate some of the effects of β‐amyloid peptides on cholinergic neuron functions, including the effects on ChAT. This review outlines a new model for the regulation of cholinergic transmission at the level of the presynaptic terminal that is mediated by hierarchically‐regulated, multi‐site phosphorylation of ChAT.
Calpain‐mediated truncation of dihydropyrimidinase‐like 3 protein (DPYSL3) in response to NMDA and H2O2 toxicity
Authors: Kowara Renata , Chen Qianfa , Milliken Melissa , Chakravarthy Balu
Published: August 2005

Dihydropyrimidinase‐like protein 3 (DPYSL3), a member of TUC (TOAD‐64/Ulip/CRMP), is believed to play a role in neuronal differentiation, axonal outgrowth and, possibly, neuronal regeneration. In primary cortical cultures, glutamate (NMDA) excitotoxicity and oxidative stress (H2O2) caused the cleavage of DPYSL3, resulting in the appearance of a doublet of 62 kDa and 60 kDa. Pre‐treatment of cell cultures with calpain inhibitors, but not caspase 3 inhibitor, before exposure to NMDA or H2O2 completely blocked the appearance of the doublet, suggesting calpain‐mediated truncation. Furthermore, in vitro digestion of DPYSL3 in cell lysate with purified calpain revealed a cleavage product identical to that observed in NMDA‐ and H2O2‐treated cells, and its appearance was blocked by calpain inhibitors. Analysis of the DPYSL3 protein sequence revealed a possible cleavage site for calpain (Val‐Arg‐Ser) on the C‐terminus of DPYSL3. Collectively, these studies demonstrate for the first time that DPYSL3 is a calpain substrate. The physiological relevance of the truncated DPYSL3 protein remains to be determined.
Dopamine release in PC12 cells is mediated by Ca2+‐dependent production of ceramide via sphingomyelin pathway
Authors: Jeon Hyung Jun , Lee Dong Hoon , Kang Mi Sun , Lee Mi‐Ock , Jung Kwang Mook , Jung Sung Yun , Kim Dae Kyong
Published: August 2005

A presynaptic membrane disturbance is an essential process for the release of various neurotransmitters. Ceramide, which is a tumor suppressive lipid, has been shown to act as a channel‐forming molecule and serve as a precursor of ceramide‐1‐phosphate, which can disturb the cellular membrane. This study found that while permeable ceramide increases the rate of dopamine release in the presence of a Ca2+‐ionophore, A23187, permeable ceramide‐1‐phosphate provoked its release even without the ionophore. The treatment of PC12 cells with the ionophore at concentrations < 2 µm produced ceramide via the sphingomyelin (SM) pathway with a concomitant release of dopamine, and no cell damage was observed. The addition of a Ca2+ chelator, EGTA, to the medium inhibited the increase in the release of both the ceramide and dopamine. This suggests that ceramide might be produced by Ca2+ and is implicated in the membrane disturbance associated with the release of dopamine as a result of its conversion to ceramide‐1‐phosphate. Consistent with these results, this study detected a membrane‐associated and neutral pH optimum sphingomyelinase (SMase) whose activity was increased by Ca2+. Together, these results demonstrate that ceramide can be produced via the activation of a neutral form of SMase through Ca2+, and is involved in the dopamine release in concert with Ca2+.
The endocannabinoid system in the brain of Carassius auratus and its possible role in the control of food intake
Authors: Valenti M. , Cottone E. , Martinez R. , De Pedro N. , Rubio M. , Viveros M. P. , Franzoni M. F. , Delgado M.J. , Di Marzo V.
Published: August 2005

Cannabinoid receptors and the endocannabinoids anandamide and 2‐arachidonoylglycerol have been suggested to regulate food intake in several animal phyla. Orthologs of the mammalian cannabinoid CB1 and CB2 receptors have been identified in fish. We investigated the presence of this endocannabinoid system in the brain of the goldfish Carassius auratus and its role in food consumption. CB1‐like immunoreactivity was distributed throughout the goldfish brain. The prosencephalon showed strong CB1‐like immunoreactivity in the telencephalon and the inferior lobes of the posterior hypothalamus. Endocannabinoids were detected in all brain regions of C. auratus and an anandamide‐hydrolysing enzymatic activity with features similar to those of mammalian fatty acid amide hydrolase was found. Food deprivation for 24 h was accompanied by a significant increase of anandamide, but not 2‐arachidonoylglycerol, levels only in the telencephalon. Anandamide caused a dose‐dependent effect on food intake within 2 h of intraperitoneal administration to satiated fish and significantly enhanced or reduced food intake at low (1 pg/g body weight) or intermediate (10 pg/g) doses, respectively, the highest dose tested (100 pg/g) being inactive. We suggest that endocannabinoids might variously contribute to adaptive responses to food shortage in fish.
Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's disease
Authors: Jenkins Bruce G. , Andreassen Ole A. , Dedeoglu Alpaslan , Leavitt Blair , Hayden Michael , Borchelt David , Ross Christopher A. , Ferrante Robert J. , Beal M. Flint
Published: August 2005

Huntington's disease is a neurodegenerative illness caused by expansion of CAG repeats at the N‐terminal end of the protein huntingtin. We examined longitudinal changes in brain metabolite levels using in vivo magnetic resonance spectroscopy in five different mouse models. There was a large (>50%) exponential decrease in N‐acetyl aspartate (NAA) with time in both striatum and cortex in mice with 150 CAG repeats (R6/2 strain). There was a linear decrease restricted to striatum in N171‐82Q mice with 82 CAG repeats. Both the exponential and linear decreases of NAA were paralleled in time by decreases in neuronal area measured histologically. Yeast artificial chromosome transgenic mice with 72 CAG repeats, but low expression levels, had less striatal NAA loss than the N171–82Q mice (15% vs. 43%). We evaluated the effect of gene context in mice with an approximate 146 CAG repeat on the hypoxanthine phosphoribosyltransferase gene (HPRT). HPRT mice developed an obese phenotype in contrast to weight loss in the R6/2 and N171–82Q mice. These mice showed a small striatal NAA loss (21%), and a possible increase in brain lipids detectable by magnetic resonance (MR) spectroscopy and decreased brain water T1. Our results indicate profound metabolic defects that are strongly affected by CAG repeat length, as well as gene expression levels and protein context.
Serofendic acid prevents 6‐hydroxydopamine‐induced nigral neurodegeneration and drug‐induced rotational asymmetry in hemi‐parkinsonian rats
Authors: Inden Masatoshi , Kitamura Yoshihisa , Kondo Jun‐ichi , Hayashi Kousuke , Yanagida Takashi , Takata Kazuyuki , Tsuchiya Daiju , Yanagisawa Daijiro , Nishimura Kaneyasu , Taniguchi Takashi , Shimohama Shun , Sugimoto Hachiro , Akaike Akinori
Published: August 2005

Serofendic acid was recently identified as a neuroprotective factor from fetal calf serum. This study was designed to evaluate the neuroprotective effects of an intranigral microinjection of serofendic acid based on behavioral, neurochemical and histochemical studies in hemi‐parkinsonian rats using 6‐hydroxydopamine (6‐OHDA). Rats were injected with 6‐OHDA in the presence or absence of serofendic acid, or were treated with serofendic acid on the same lateral side, at 12, 24 or 72 h after 6‐OHDA lesion. Intranigral injection of 6‐OHDA alone induced a massive loss of tyrosine hydroxylase (TH)‐immunopositive neurons in the substantia nigra pars compacta (SNpc). Either simultaneous or 12 h post‐administration of serofendic acid significantly prevented both dopaminergic neurodegeneration and drug‐induced rotational asymmetry. Immunoreactivities for oxidative stress markers, such as 3‐nitrotyrosine (3‐NT) and 4‐hydroxy‐2‐nonenal (4‐HNE), were markedly detected in the SNpc of rats injected with 6‐OHDA alone. These immunoreactivities were markedly suppressed by the co‐administration of serofendic acid, similar to the results in vehicle‐treated control rats. In addition, serofendic acid inhibited 6‐OHDA‐induced α‐synuclein expression and glial activation in the SNpc. These results suggest that serofendic acid protects against 6‐OHDA‐induced SNpc dopaminergic neurodegeneration in a rat model of Parkinson's disease.
γ‐Secretase complexes containing N‐ and C‐terminal fragments of different presenilin origin retain normal γ‐secretase activity
Authors: Strömberg Kia , Hansson Emil M. , Laudon Hanna , Bergstedt Susanne , Näslund Jan , Lundkvist Johan , Lendahl Urban
Published: August 2005

The γ‐secretase complex processes substrate proteins within membranes and consists of four proteins: presenilin (PS), nicastrin, Aph‐1 and Pen‐2. PS harbours the enzymatic activity of the complex, and there are two mammalian PS homologues: PS1 and PS2. PS undergoes endoproteolysis, generating the N‐ and C‐terminal fragments, NTF and CTF, which represent the active species of PS. To characterize the functional similarity between complexes of various PS composition, we analysed PS1, PS2, and chimeric PS composed of the NTF from PS1 and CTF from PS2, or vice versa, in assembly and function of the γ‐secretase complex. Chimeric PSs, like PS1 and PS2, undergo normal endoproteolysis when introduced into cells devoid of endogenous PS. Furthermore, PS2 CTF can, at least partially, restore processing in a truncated PS1, which cannot undergo endoproteolysis. All PS forms enable maturation of nicastrin and cleave full length Notch receptors, indicating that both PS1 and PS2 are present at the cell surface. Finally, when co‐introduced as separate molecules, NTF and CTF of different PS origin reconstitute γ‐secretase activity. In conclusion, these data show that endoproteolysis, NTF–CTF interactions, and the assembly and activity of γ‐secretase complexes are very conserved between PS1 and PS2.
A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival
Authors: Anderson Alexandra A. , Kendal Claire E. , Garcia‐Maya Mitla , Kenny Anna V. , Morris‐Triggs Samantha A. , Wu Teresa , Reynolds Richard , Hohenester Erhard , Saffell Jane L.
Published: August 2005

Neural cell adhesion molecule (NCAM) contributes to axon growth and guidance during development and learning and memory in adulthood. Although the Ig domains mediate homophilic binding, outgrowth activity localizes to two membrane proximal fibronectin‐like domains. The first of these contains a site identified as a potential FGF receptor (FGFR) activation motif (FRM) important for NCAM stimulation of neurite outgrowth, but its activity has hitherto remained hypothetical. Here, we have tested the effects of a domain‐specific antibody and peptides corresponding to the FRM in cellular assays in vitro. The first fibronectin domain antibody inhibited NCAM‐stimulated outgrowth, indicating the importance of the domain for NCAM function. Monomeric FRM peptide behaved as an inverse agonist; low concentrations specifically inhibited neurite outgrowth stimulated by NCAM and cellular responses to FGF2, while saturating concentrations stimulated FGFR‐dependent neurite outgrowth equivalent to NCAM itself. Dendrimeric FRM peptide was 125‐fold more active and stimulated FGFR activation, FGFR‐dependent and FGF‐mimetic neurite outgrowth and cell survival (but not proliferation). We conclude that the FRM peptide contains NCAM‐mimetic bioactivity accounted for by stimulation of FGF signalling pathways at the level of or upstream from FGF receptors, and discuss the possibility that FRM comprises part of an FGFR activation site on NCAM.
An extraordinary degree of structural specificity is required in neural phospholipids for optimal brain function: n‐6 docosapentaenoic acid substitution for docosahexaenoic acid leads to a loss in spatial task performance
Authors: Lim Sun‐Young , Hoshiba Junji , Salem Norman
Published: August 2005

This study was conducted to determine whether provision of preformed dietary docosapentaenoic acid (DPAn‐6) can replace docosahexaenoic acid (DHA) for brain function as assessed by spatial task performance. A newly modified artificial rearing method was employed to generate n‐3 fatty acid‐deficient rats. Newborn pups were separated from their mothers at 2 days of age and given artificial rat milk containing linoleic acid (LA), or LA supplemented with 1% DHA (DHA), 1% DPAn‐6 (DPA) or 1% DHA plus 0.4% DPAn‐6 (DHA/DPA). The animals were then weaned onto similar pelleted diets. At adulthood, behavioural tasks were administered and then the brains were collected for fatty acid analysis. The LA and DPA groups showed a lower (63–65%) brain DHA than the dam‐reared, DHA and DHA/DPA groups and this loss was largely compensated for by an increase in brain DPAn‐6. The brain fatty acid composition in the DPA group was the same as that in the LA group at adulthood. In the Morris water maze, the LA and DPA groups exhibited a longer escape latency than the dam‐reared and DHA groups and had a defect in spatial retention. In conclusion, DPAn‐6 could not replace DHA for brain function, indicating a highly specific structural requirement for DHA.
Activation of mitogen‐activated protein kinases in hamster brains infected with 263K scrapie agent
Authors: Lee Hyun‐Pil , Jun Yong‐Cheol , Choi Jin‐Kyu , Kim Jae‐Il , Carp Richard I. , Kim Yong‐Sun
Published: August 2005

We investigated the expression, activation and distribution of c‐Jun N‐terminal kinases (JNKs), p38 mitogen‐activated protein kinases (p38 MAPKs) and extracellular signal‐regulated kinases (ERKs), using western blotting and immunohistochemistry, in the brains of hamsters infected with 263K scrapie agent, to clarify the role of these kinases in the pathogenesis of prion disease. The immunoblot analysis demonstrated that activation of JNK, p38 MAPK and ERK in whole brain homogenates was increased in infected animals. Phosphorylation of cAMP/calcium responsive element binding protein (CREB), a downstream transcription factor of active ERK, was significantly increased in scrapie‐infected hamsters. The immunohistochemical study showed that active ERK was enhanced in infected hamsters compared with controls. Active ERK immunoreactivity was observed within neurons in the dentate gyrus and in glial fibrillary acidic protein (GFAP)‐positive reactive astrocytes of infected animals. The expression level of c‐Jun mRNA as well as protein, a substrate of active JNK, was increased in infected animals. A significant increase in JNK activity upon glutathione S‐transferase (GST)‐c‐Jun was observed in infected compared with control animals. Phospho‐c‐Jun immunoreactivity was observed only in neurons of the thalamus in infected groups. These findings indicated that the JNK pathway was activated in the scrapie‐infected group. The chronological activation of MAPKs using immunoblot analysis indicates that the kinases are sequentially activated during the pathophysiology of prion disease. Taken together, these results lend credence to the notion that MAPK pathways are dysregulated in prion disease, and also indicate an active role for this pathway in disease pathogenesis.