bluuebunny/crossref_metadata_2025 huggingface dataset:
THE QUEEN WAS ACTUALLY A MAN: ARWĀ BINT AHMAD AND THE POLITICS OF RELIGION
Authors: Traboulsi Samer
Published: February 2003

Arwā bint Ahmad (d. 532/1137) ruled in Yemen for fifty-five years. She played an important political role and at the same time occupied the highest rank in the Ismā'īlī religious hierarchy after that of the imam. Her religious policies, particularly her special relations with the Fatimids, led to the transfer of the Fatimid literary legacy to Yemen, and hence to its preservation following the fall of the Fatimid Caliphate. She likewise organized the new structure of the Yemeni Ismā'īlī da'wa, thus contributing to its survival after the fall of the Sulayhid dynasty. The proposed paper investigates Arwā's career from two different angles: the Fatimid Egyptian and the Yemen Ismā'īlī. The main point will be the way they dealt with the fact that she was a female ruler. The Fatimid caliph-imam al-Mustansir first issued a decree stating that to follow her was a religious duty. He then appointed her to the rank of huğğa, the highest after that of the imam, in order to give her rule a more emphatic legitimacy. The Yemeni Ismā'īlī position is best represented in al-Sultān al-Hattāb's religious tract Gāyat al-mawālīd, where he argues that Arwā's female body was no more than a body envelope covering her original male essence. The fact that Arwā was a woman posed a serious problem for both the Fatimids and the Yemeni Ismā'īlīs. In each case they tried to deal with it in a way that suited their political and religious interests.
OUTWARD AND VISIBLE SIGNS OF CONVERSION IN NINETEENTH-CENTURY KWAZULU-NATAL
Authors: Etherington Norman
Published: February 2003

The article argues that the perpetually vexing question of identifying and verifying religious conversion in mission history can be approached by taking outward texts and signs more seriously. The examples chosen for study are the various missions active in KwaZulu-Natal in the period 1835-1885. Over time African evangelists and churchgoers responded to missionary injunctions to value the materiality of printed texts and to 'put on the raiment of the Lord' in a literal sense. Signs, which might on the surface be regarded as trivial, came in time to be widely regarded as evidence of conversion to a new belief.
AN IGBO ESPERANTO: A HISTORY OF THE UNION IBO BIBLE 1900-1950
Authors: Fulford Ben
Published: February 2003

The Union Ibo Bible was more or less the Bible for the Igbo people of southern Nigeria from 1909 to 1970. The creation of Thomas Dennis of the Church Missionary Society and his co-workers, it has been, since its first conception in 1905, a source of ongoing controversy: the development and unification of the Igbo language was at stake. This article re-examines the history of this Bible, its conception, translation and early reception, and argues that the source of its shortcomings lies deeper than the method of translation or the contemporary Igbo desire to learn English. The Union Bible is the product of the missionary conception, fleshed out by a comparison with the Yoruba, of a single Igbo people speaking a single language. The failure of that translation is the result of the premise consequent to this conception of the Igbo, namely that the Igbo language was ready to be 'united'.
Pulmonary perspective: immunology in diagnosis and treatment of lung cancer
Authors: Weynants P , Marchandise FX , Sibille Y
Published: February 2003

The combination of the limits encountered with current therapies and the increased knowledge of immunology have opened perspectives for the use of immunomodulators in the management of lung cancer patients. Both humoral and cellular immunity are now evaluated in diagnosis and treatment of cancer. Monoclonal antibodies (MoAbs) against tumour-associated antigens are now tested with various imaging techniques to improve detection and staging of lung cancer. MoAbs are also used in therapeutic clinical trials as: 1) mediators of immune effector function; 2) carriers of cytotoxic agents; 3) agents to block tumour growth factor; or 4) anti-idiotype vaccines. Immune effector cells, such as natural killer (NK) cells, T- and B-lymphocytes, macrophages, dendritic cells and neutrophils, are present either within or around tumours and are likely to play a role in cancer. These cells, either alone or with cytokines, could provide new efficient therapeutic approaches, particularly if immunosuppression is involved in tumour progression. In this context, most recent studies using immune cells and molecular bioengineering, could provide additional antitumoral effects. Finally, the discovery of several tumour rejection antigens has revived the dream of designing tumour vaccines and active specific immunotherapy.
Inflammatory cells and activation markers in BAL during acute rejection and infection in lung transplant recipients: a prospective, longitudinal study
Authors: Riise GC , Kjellstrom C , Ryd W , Schersten H , Nilsson F , Martensson G , Andersson BA
Published: February 2003

Acute rejection of the transplanted lung is a clinical problem, since it decreases graft survival and predisposes the patient to chronic rejection and obliterative bronchiolitis (OB). In an earlier study, we had indications that eosinophil cationic protein (ECP) from activated eosinophils and hyaluronan (HYA) from fibroblasts were associated with acute pulmonary rejection. This prospective longitudinal study was designed to investigate whether molecules from activated inflammatory cells in bronchoalveolar lavage (BAL) fluid could serve as clinically useful diagnostic markers for acute rejection. BAL fluid from 138 bronchoscopies performed in 10 single lung, four bilateral lung and five heart-lung transplant recipients were analysed. Nine patients were studied for a period of more than 1 yr (mean 13.4 months) after surgery. Differential cell counts were made from the BAL fluid. ECP, myeloperoxidase (MPO), HYA and interleukin-8 (IL-8) were used as indirect markers for activation and attraction of eosinophils, neutrophils and fibroblasts, respectively. Fifty four episodes of acute rejection were diagnosed. Two patients developed OB. Nine episodes of bacterial infection, 13 episodes of cytomegalovirus (CMV) pneumonitis, three of Pneumocystis carinii infection and one of respiratory syncytial virus (RSV) infection were diagnosed. The mean levels of ECP, MPO, HYA and IL-8 were all higher during rejection episodes, but differences were not statistically significant compared to no rejection, when the confounding factors of time, concomitant infection, and repeated measures in the same individual had been accounted for. We could not confirm that measurements of eosinophil cationic protein, myeloperoxidase, hyaluronan and interleukin-8 in bronchoalveolar lavage fluid can be used as diagnostic markers for acute rejection in the postoperative follow-up of lung transplant recipients.
Physician-diagnosed asthma and drug utilization in the European Community Respiratory Health Survey
Authors: Janson C , Chinn S , Jarvis D , Burney P
Published: February 2003

The aim of this analysis was to estimate the geographical variation in the prevalence of physician-diagnosed asthma and treatment practice for asthma in young adults. The results are based on an ecological analysis of 34 centres in 14 countries, in which a total of 17,029 randomly selected subjects (52% females, age 20-48 yrs) underwent a structured interview and spirometry as part of the European Community Respiratory Health Survey. The sample was enriched with 2,903 symptomatic subjects when investigating treatment in subjects with physician-diagnosed asthma. The prevalence of physician-diagnosed asthma was highest in New Zealand and Australia (11-13%) and lowest in Erfurt, Germany (1.2%) and Spain (1.5-3.0%). The reported use of antiasthma medication in the last 12 months was also highest in New Zealand and Australia (12-16%) and correlated closely with the prevalence of diagnosed asthma (r=0.89, p<0.001). Herbal remedies against breathing problems had been used by 13% of subjects in Hamburg but the reported use of alternative remedies for breathing problems was low in most other centres. The use of inhaled anti-inflammatory drugs in subjects with physician-diagnosed asthma ranged from 49% in the UK to 17% in Italy and correlated with the prevalence of doctors' consultations within the last 12 months (r=0.66, p<0.05). The prevalence of anti-inflammatory treatment was positively related to the prevalence of nocturnal asthma symptoms (p<0.05). We conclude that there is a wide geographical variation in the prevalence of physician-diagnosed asthma and use of antiasthma medication. The geographical variation in the use of anti-inflammatory drugs among individuals with diagnosed asthma may be related to variations in asthma severity, as well as differences in treatment practices between countries.
Do sputum eosinophils and ECP relate to the severity of asthma?
Authors: Ronchi MC , Piragino C , Rosi E , Stendardi L , Tanini A , Galli G , Duranti R , Scano G
Published: February 2003

There is much evidence that eosinophils play an important role in bronchial epithelial damage in asthma by releasing cationic proteins. However, the extent to which eosinophil inflammation relates to indices of asthma severity in chronic stable asthma is still a matter of debate. We studied 46 clinically stable patients with mild to severe chronic asthma (forced expiratory volume in one second (FEV1) 50-126% of predicted value). The clinical severity of asthma was graded from 1 to 4 according to the Aas scoring system. Twelve normal subjects were also studied as controls. Induction of sputum was performed by hypertonic saline to determine differential cell count, and eosinophil cationic protein (ECP) by the so-called "plug technique". The concentration of ECP was measured by a fluoroimmunoassay. Bronchial hyperresponsiveness was recorded by inhaling progressive concentrations of histamine, and the concentration that caused a 20% decrease in FEV1 (PC20) was calculated. Sputum eosinophils (range 0-61%), sputum ECP (range 24-10,800 microg x L[-1]) and serum ECP (range 4-61 microg x L[-1]) were significantly greater in asthmatics than in normal subjects, and distinguished the most severe group with the highest Aas score from the others. Sputum eosinophils and sputum ECP were strongly related to each other. The relationships between sputum or serum ECP and PC20 (range 0.016-7.5 mg x mL[-1]), and between sputum ECP and FEV1 were found to be weak. In conclusion, sputum outcomes of eosinophil activation and serum eosinophilic cationic protein appear to be useful indicators of disease. They do not accurately reflect current clinical or functional indices of asthma severity in chronic stable patients, and might therefore provide complementary data disease monitoring.
Comparative efficacy and potency of ipratropium via Turbuhaler and pressurized metered-dose inhaler in reversible airflow obstruction
Authors: Bollert FG , Matusiewicz SP , Dewar MH , Brown GM , McLean A , Greening AP , Crompton GK
Published: February 2003

Ipratropium bromide (IB), typically delivered by pressurized metered dose inhaler (pMDI), is used to treat patients with reversible airways obstruction. Use of the pMDI, unlike the Turbuhaler (TH), demands co-ordination of actuation with inspiration for efficient use. Two studies were carried out to compare the relative efficacy and potency of IB delivered by TH or pMDI. Both studies were of a randomized, double-blind and cross-over design. For the efficacy study, 15 patients received a cumulative dose of 160 microg IB via TH or pMDI as doses of 20, 20, 40 and 80 microg at 45 min intervals on two days. Forced expiratory volume in one second (FEV1) was measured prior to and 40 min after dosing. For the potency study, 33 patients received 10, 20 or 40 microg of IB via TH, 20 microg IB via pMDI, or placebo, on five days. FEV1 was recorded prior to and 15-360 min after dosing. For the efficacy study, there was no difference in FEV1 response to a cumulative dose of IB via pMDI and TH. More than 80% of the maximum effect was seen at the lowest dose (20 microg of IB). Regarding the potency study, the FEV1 response to 20 microg IB administered via pMDI was similar to that of 10 microg via TH; 20 microg via TH was significantly more effective than 20 microg via pMDI (p<0.05). In conclusion, the efficacy study showed that maximum FEV1 occurred at low doses of IB, negating any opportunity to identify differences between devices. The potency study indicated that the 10 microg dose via TH was of similar efficacy to the 20 microg dose via pMDI, confirming an efficacy ratio of 1.5-2.0:1 for the TH device.
Dead space and slope indices from the expiratory carbon dioxide tension-volume curve
Authors: Kars AH , Bogaard JM , Stijnen T , de Vries J , Verbraak AF , Hilvering C
Published: February 2003

The slope of phase 3 and three noninvasively determined dead space estimates derived from the expiratory carbon dioxide tension (PCO2) versus volume curve, including the Bohr dead space (VD,Bohr), the Fowler dead space (VD,Fowler) and pre-interface expirate (PIE), were investigated in 28 healthy control subjects, 12 asthma and 29 emphysema patients (20 severely obstructed and nine moderately obstructed) with the aim to establish diagnostic value. Because breath volume and frequency are closely related to CO2 elimination, the recording procedures included varying breath volumes in all subjects during self-chosen/natural breathing frequency, and fixed frequencies of 10, 15 and 20 breaths x min(-1) with varying breath volumes only in the healthy controls. From the relationships of the variables with tidal volume (VT), the values at 1 L were estimated to compare the groups. The slopes of phase 3 and VD,Bohr at 1 L VT showed the most significant difference between controls and patients with asthma or emphysema, compared to the other two dead space estimates, and were related to the degree of airways obstruction. Discrimination between no-emphysema (asthma and controls) and emphysema patients was possible on the basis of a plot of intercept and slope of the relationship between VD,Bohr and VT. A combination of both the slope of phase 3 and VD,Bohr of a breath of 1 L was equally discriminating. The influence of fixed frequencies in the controls did not change the results. The conclusion is that Bohr dead space in relation to tidal volume seems to have diagnostic properties separating patients with asthma from patients with emphysema with the same degree of airways obstruction. Equally discriminating was a combination of both phase 3 and Bohr dead space of a breath of 1 L. The different pathophysiological mechanisms in asthma and emphysema leading to airways obstruction are probably responsible for these results.
Paired phrenic nerve stimuli for the detection of diaphragm fatigue in humans
Authors: Polkey MI , Kyroussis D , Hamnegard CH , Hughes PD , Rafferty GF , Moxham J , Green M
Published: February 2003

The transdiaphragmatic pressure (Pdi) elicited by paired bilateral phrenic nerve stimulation may be viewed as the sum of the Pdi values produced by the first (t1) and second (t2) stimulus. The Pdi at t2 (P[di,t2]) is a function of the interstimulus interval. A reduction in the ratio obtained by dividing Pdi,t2 at 10 Hz (P[di,t2,10]) by Pdi at 100 Hz (P[di,t2,100]) (t2(10:100)) has been proposed as a test of low frequency diaphragm fatigue. The aim of the present study was to establish whether this change could also be detected using paired cervical magnetic nerve stimulation (pCMS), and whether t2(10:100) was influenced by lung volume. We studied healthy subjects at functional residual capacity (FRC), at 0.5 and 1.0 L below FRC, and at 0.5, 1.0 and 1.5 L above FRC. The subjects were then subjected to a fatiguing protocol (2 min of maximal isocapnic ventilation (MIV)). Studies were repeated at FRC 20 and 60 min after MIV and between these times at 1.0 L below and 1.5 L above FRC. In the unfatigued state, t2(10:100) had a negative relationship with increasing lung volume (r2=0.98, p=0.002). After MIV there was a fall in the Pdi elicited by a single stimulus (mean fall at 20 min 17.9% and at 60 min 14.6%, p<0.03 for both). t2(10:100) fell by a mean 28.1% after 20 min and mean 22.9% at 60 min (p<0.03 for both). This change was mainly mediated by a fall in the P[di,t2,10]. The t2(10:100) was not able to distinguish between fatigue and acute hyperinflation. We conclude that paired cervical magnetic nerve stimulation may be used to detect low frequency diaphragm fatigue but that it remains important to control for lung volume.
Pleural diseases related to metastatic malignancies
Authors: Sahn SA
Published: February 2003

Pleural effusions associated with malignancy (either malignant or paramalignant) pose diagnostic and therapeutic dilemmas for the clinician. This article reviews the common causes of malignant and paramalignant pleural effusions, pathogenesis, clinical presentation, chest radiography, pleural fluid characteristics, diagnosis, prognosis, and treatment. Talc, used either by poudrage or slurry, is the most effective agent used for pleurodesis. Talc, which needs to be sterilized, has no clinically important immediate, short-term or long-term adverse effects.
Semantic evidence for functional categories in interlanguage grammars
Authors: Slabakova Roumyana
Published: February 2003

This study investigates how semantic properties of functional categories are acquired by second language (L2) learners in an instructional setting. The following properties of the functional category (FC) of AspectP are under investigation:

1) English simple present tense cannot denote an ongoing event;

2) progressive morphology is needed for an ongoing interpretation; and

3) English bare verbal forms denote closed, or completed, events.

All three properties are not instantiated in Bulgarian. Only the first two properties are explicitly taught in English classrooms in Bulgaria, while the third is not. A Truth Value Judgement Task, a guided composition task and a proficiency test were administered to 112 Bulgarian learners of English and 24 native speaker controls. Results indicate that L2 learners at all proficiency levels are aware of the English aspectual contrasts.These findings suggest that L2 learners are able to acquire interpretable formal features not transferable from their native language. Furthermore, they are able to acquire properties of the grammar that are not explicitly taught in language classrooms.
Contributions of the study of Japanese as a second language to our general understanding of second language acquisition and the definition of second language acquisition research
Authors: Wakabayashi Shigenori
Published: February 2003

Japanese has figured frequently in second language acquisition (SLA) research, but more often than not it appears as the first language (L1) rather than the target. In this article, first I discuss the problems addressed and the insights obtained in these studies. I then consider two issues. One is what the field of SLA research should include. I suggest that it should include two categories, namely Core SLA Research, where second language (L2) linguistic knowledge is investigated, and Broad SLA research, where researchers study factors that influence the development of L2 knowledge. The other issue is what we can expect in Core SLA research concerning the L2 acquisition of Japanese. This article illustrates how studies of the L2 acquisition of Japanese can contribute to our understanding of SLA.
The place(s) of matter: matter out of place – public understandings of air pollution
Authors: Bickerstaff Karen , Walker Gordon
Published: February 2003

This article reflects on the key findings and insights offered by recent work on public understandings of air pollution, which has begun to adopt some of the concepts and methodologies associated with social constructionism. We begin with a brief discussion of debates in the social sciences generally, and human geography specifically, regarding the precepts of ‘social constructionism', before setting out the ‘heterogeneous’ mode that we adopt in this paper. In this light, we trace briefly the fairly narrow empirical, methodological and conceptual preoccupations of early air pollution perception work. These accounts usefully situate the remainder of the paper, which focuses on the recent body of research that explores public understandings of air pollution, with quite different approaches to theory and data collection to that which has gone before. The argument we develop asserts that a constructionist interpretation, in revealing ‘complexity’ and the entangled interaction of society-environment-technology, raises serious questions about the dominant political discourse of air pollution and the policy responses which it legitimates. The issues raised by this review, we believe, offer a fresh perspective and the potential to progress not only our understanding and management of air pollution risks but also the contribution of geographers to a challenging research terrain.
The ‘Little Ice Age’ – only temperature?
Authors: Nesje Atle , Dahl Svein Olaf
Published: February 2003

Understanding the climate of the last few centuries, including the ‘Little Ice Age’, may help us better understand modern-day natural climate variability and make climate predictions. The conventional view of the climate development during the last millennium has been that it followed the simple sequence of a ‘Mediaeval Warm Period’, a cool ‘Little Ice Age’ followed by warming in the later part of the nineteenth century and during the twentieth century. This view was mainly based on evidence from western Europe and the North Atlantic region. Recent research has, however, challenged this rather simple sequence of climate development in the recent past. Data presented here indicate that the rapid glacier advance in the early eighteenth century in southern Norway was mainly due to increased winter precipitation: mild, wet winters due to prevailing ‘positive North Atlantic Oscillation (NAO) weather mode’ in the first half of the eighteenth century; and not only lower summer temperatures. A comparison of recent mass-balance records and ‘Little Ice Age’ glacier fluctuations in southern Norway and the European Alps suggests that the asynchronous ‘Little Ice Age’ maxima in the two regions may be attributed to multidecadal trends in the north–south dipole NAO pattern.
Creating the Model of a Clinical Practice: The Case of Emergency Medicine
Authors: Hockberger Robert S. , La Duca Anthony , Orr Nancy A. , Reinhart Mary Ann , Sklar David P.
Published: February 2003

Medical schools and specialty societies have struggled to define a core content for medical students and practitioners but, to date, have been stymied by both political considerations and the sheer burden of the innumerable decisions that must be made to define the essence of a medical specialty. Six professional organizations representing the field of emergency medicine recently collaborated with the National Board of Medical Examiners to accomplish this objective by developing a Model of the Clinical Practice of Emergency Medicine. This document will provide support for the development of medical school and residency curricula, training program accreditation standards, board certification test specifications, and organizational agendas for postgraduate education, research, and patient advocacy for the specialty of emergency medicine. The authors present a description of the model and the process that was used to develop it with the belief that other medical disciplines that face similar issues and challenges could benefit from a similar undertaking.
Can the Bispectral Index Monitor Quantify Altered Level of Consciousness in Emergency Department Patients?
Authors: Gill Michelle , Green Steven M. , Krauss Baruch
Published: February 2003

Objectives: A daily part of emergency medicine practice includes assessing patients with altered levels of consciousness (ALOC). The authors hypothesized that a bispectral index monitor (BIS), a processed electroencephalographic monitor traditionally used to monitor patients under anesthesia, would represent an objective quantification of impairment of consciousness. They compared the BIS score with the Glasgow Coma Scale score (GCS) in emergency department (ED) patients with ALOC. Methods: The authors performed a convenience sampling of ED adults presenting with ALOC (GCS ≤ 14). Patients with abnormal baseline mental status were excluded, as were those who were unable to tolerate the forehead BIS leads. The blinded BIS value was recorded after the treating physician assigned a GCS to the patient. The BIS and GCS measurements were then correlated. Results: Data were obtained for 38 patients (20 male, 18 female). The median age was 42 years (range 14 to 93 years). Despite being statistically significant (p = 0.0165), the correlation between the GCS and the BIS score was only moderate (Spearman's rho = 0.387) and displayed wide variability. For example, when the GCS was between 3 and 5, the corresponding BIS scores ranged from 47 to 98. When the GCS was between 12 and 14, the corresponding BIS scores ranged from 56 to 98. Receiver operating characteristic curves for BIS at each GCS threshold demonstrated low discriminatory power (areas under the curve range 0.61 to 0.73). Conclusions: BIS monitoring does not reliably correlate with GCS in ED patients with ALOC, and does not appear to have potential to accurately quantify impairment of consciousness in this setting.
Differential Regulation of Gonadotropin-Releasing Hormone (GnRH)I and GnRHII Messenger Ribonucleic Acid by Gonadal Steroids in Human Granulosa Luteal Cells
Authors: Khosravi Shahram , Leung Peter C. K.
Published: February 2003

In humans, reproduction was generally believed to be controlled by only one form of GnRH (called mammalian GnRH or GnRHI). However, recently, a second form of GnRH, analogous to chicken GnRHII, was discovered in several tissues, including the human ovary. The regulation and function of GnRHI in the hypothalamus has been well studied. However, the function and regulation of GnRHI, and particularly GnRHII in the ovary, is less well understood. Because gonadal sex steroids are one of the main regulators of reproduction, we investigated, in the present study, the regulation of GnRHI and GnRHII mRNA expression by 17β-estradiol (E2) and RU486 (a progesterone antagonist) in human granulosa luteal cells (hGLCs).

The levels of the mRNA transcripts encoding the two GnRH forms were examined using semiquantitative RT-PCR followed by Southern blot analysis. With time in culture, GnRHI and GnRHII mRNA levels significantly increased, by 120% and 210%, at d 8 and d 1, respectively. The levels remained elevated until the termination of these experiments at d 10. A 24-h treatment of hGLCs with E2 (10−9 to 10−7m) resulted in a dose-dependent decrease and increase in mRNA expression of GnRHI and GnRHII, respectively. E2 (10−9m) significantly decreased GnRHI mRNA levels (by 55%) and increased GnRHII mRNA levels (by 294%). Time-course studies demonstrated that E2 (10−9m) significantly decreased GnRHI mRNA levels in a time-dependent manner, with maximal inhibition of 77% at 48 h. In contrast, GnRHII mRNA levels significantly increased in a time-dependent fashion, reaching a maximum level of 280% at 24 h. Cotreatment of hGLCs with E2 and tamoxifen (an E2 antagonist) reversed the inhibitory and stimulatory effects of E2 on the mRNA expression of GnRHI and GnRHII, respectively. Time- and dose-dependent treatment with RU486 did not affect GnRHI mRNA levels in hGLCs. In contrast, RU486 treatment significantly increased GnRHII mRNA levels in hGLCs in a time- and dose-dependent fashion, with a maximum increase being observed at 24 h (with 10−5m RU486). In summary, the present study demonstrated that the expression of GnRHI and GnRHII at the transcriptional level is differently regulated by E2 and P4 in hGLCs.
Homocysteine Levels and C677T Polymorphism of Methylenetetrahydrofolate Reductase in Women with Polycystic Ovary Syndrome
Authors: Orio Francesco , Palomba Stefano , Di Biase Sebastiano , Colao Annamaria , Tauchmanova Libuse , Savastano Silvia , Labella Donato , Russo Tiziana , Zullo Fulvio , Lombardi Gaetano
Published: February 2003

The aim of this study was to investigate the homocysteine (Hcy) levels and the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), a crucial factor of the Hcy metabolism in young women with polycystic ovary syndrome (PCOS).

Seventy young women with PCOS and another 70 healthy women with low folate intake were enrolled. Cases and controls were matched for age, body mass index, and allele frequency. Hcy, vitamin B12, and folate levels were measured, and a genetic analysis of 5,10-MTHFR at nucleotide 677 was performed in all subjects.

No difference in mean Hcy levels was observed between PCOS women in comparison to the control group. Considering the different MTHFR polymorphism, no significant difference was found in serum Hcy levels between subjects with PCOS and controls showing CC (10.4 ± 3.1 vs. 9.7 ± 2.9 μmol/liter ± sd) and CT genotypes (10.9 ± 3.8 vs. 11.0 ± 3.2 μmol/liter ± sd). In subjects with a TT homozygous state, a significant (P < 0.05) difference was observed between PCOS and control women (11.5 ± 3.9 vs. 22.0 ± 7.8 μmol/liter ± sd).

In conclusion, our data show that in PCOS women, the serum Hcy levels are normal, and the C677T polymorphism of MTHFR does not influence the Hcy levels like in controls.
A mosaic genetic screen for genes necessary forDrosophilamushroom body neuronal morphogenesis
Authors: Reuter John E. , Nardine Timothy M. , Penton Andrea , Billuart Pierre , Scott Ethan K. , Usui Tadao , Uemura Tadashi , Luo Liqun
Published: February 2003

Neurons undergo extensive morphogenesis during development. To systematically identify genes important for different aspects of neuronal morphogenesis, we performed a genetic screen using the MARCM system in the mushroom body (MB) neurons of the Drosophila brain. Mutations on the right arm of chromosome 2 (which contains ∼20% of the Drosophilagenome) were made homozygous in a small subset of uniquely labeled MB neurons. Independently mutagenized chromosomes (4600) were screened, yielding defects in neuroblast proliferation, cell size, membrane trafficking, and axon and dendrite morphogenesis. We report mutations that affect these different aspects of morphogenesis and phenotypically characterize a subset. We found that roadblock, which encodes a dynein light chain, exhibits reduced cell number in neuroblast clones, reduced dendritic complexity and defective axonal transport. These phenotypes are nearly identical to mutations in dynein heavy chain Dhc64 and in Lis1, the Drosophilahomolog of human lissencephaly 1, reinforcing the role of the dynein complex in cell proliferation, dendritic morphogenesis and axonal transport. Phenotypic analysis of short stop/kakapo, which encodes a large cytoskeletal linker protein, reveals a novel function in regulating microtubule polarity in neurons. MB neurons mutant for flamingo,which encodes a seven transmembrane cadherin, extend processes beyond their wild-type dendritic territories. Overexpression of Flamingo results in axon retraction. Our results suggest that most genes involved in neuronal morphogenesis play multiple roles in different aspects of neural development,rather than performing a dedicated function limited to a specific process.
A discrete transcriptional silencer in thebamgene determines asymmetric division of theDrosophilagermline stem cell
Authors: Chen Dahua , McKearin Dennis M.
Published: February 2003

The Drosophila germline lineage depends on a complex microenvironment of extrinsic and intrinsic factors that regulate the self-renewing and asymmetric divisions of dedicated stem cells. Germline stem cells (GSCs) must express components of the Dpp cassette and the translational repressors Nanos and Pumilio, whereas cystoblasts require the bam andbgcn genes. Bam is especially attractive as a target of GSC differentiation factors because current evidence indicates that bamis both necessary and sufficient for cystoblast differentiation. In this paper, we have sought to distinguish between mutually exclusive transcriptional or post-transcriptional mechanisms as the primary regulators of bam expression in GSCs and cystoblasts. We find that bamtranscription is active in young germ cells but is repressed specifically in GSCs. Activation depends on a 50 bp fragment that carries at least one germ cell-specific enhancer element. A non-overlapping 18 bp sequence carries a transcriptional silencer that prevents bam expression in the GSC. Promoters lacking this silencer cause bam expression in the GSC and concomitant GSC loss. Thus, asymmetry of the GSC division can be reduced to identifying the mechanism that selectively activates the silencer element in GSCs.
TlxandPax6co-operate genetically to establish the pallio-subpallial boundary in the embryonic mouse telencephalon
Authors: Stenman Jan , Yu Ruth T. , Evans Ronald M. , Campbell Kenneth
Published: February 2003

We have examined the role of Tlx, an orphan nuclear receptor, in dorsal-ventral patterning of the mouse telencephalon. Tlx is expressed broadly in the ventricular zone, with the exception of the dorsomedial and ventromedial regions. The expression spans the pallio-subpallial boundary, which separates the dorsal (i.e. pallium) and ventral (i.e. subpallium) telencephalon. Despite being expressed on both sides of the pallio-subpallial boundary, Tlx homozygous mutants display alterations in the development of this boundary. These alterations include a dorsal shift in the expression limits of certain genes that abut at the pallio-subpallial boundary as well as the abnormal formation of the radial glial palisade that normally marks this boundary. The Tlx mutant phenotype is similar to, but less severe than, that seen in Small eye(i.e. Pax6) mutants. Interestingly, removal of one allele ofPax6 on the homozygous Tlx mutant background significantly worsens the phenotype. Thus Tlx and Pax6 cooperate genetically to regulate the establishment of the pallio-subpallial boundary. The patterning defects in the Tlx mutant telencephalon result in a loss of region-specific gene expression in the ventral-most pallial region. This correlates well with the malformation of the lateral and basolateral amygdala in Tlx mutants, both of which have been suggested to derive from ventral portions of the pallium.
Sox5andSox6are required for notochord extracellular matrix sheath formation, notochord cell survival and development of the nucleus pulposus of intervertebral discs
Authors: Smits Patrick , Lefebvre Véronique
Published: February 2003

The notochord has major roles in vertebral column formation: indirectly by inducing sclerotome cell differentiation; and directly by forming the nucleus pulposus of intervertebral discs. Sox5 and Sox6 encode Sry-related HMG box transcription factors that act redundantly to promote chondroblast differentiation in all cartilages of the mouse embryo. We show that Sox5 and Sox6 are expressed in the notochord cell lineage and required for notochord late development.

InSox5–/–/Sox6–/–embryos, the notochord formed a typical rod-like structure. It fulfilled its inductive functions, as indicated by expression of sonic hedgehog and sclerotome specification. However, the notochord failed to become surrounded with an extracellular matrix sheath. This phenotype was associated with a downregulation of extracellular matrix genes, including the genes for collagen 2, aggrecan and perlecan in both notochord cells and surrounding chondrocytic cells of presumptive inner annuli and vertebral bodies. The mutant notochord then underwent an aberrant, fatal dismantling after sclerotome cell migration. Its cells became removed first from intervertebral spaces and then from vertebral bodies, and it progressively underwent apoptosis. Meanwhile, the development of inner annuli and vertebral bodies was dramatically impaired. Consequently, the vertebral column ofSox5–/–/Sox6–/–fetuses consisted of a very deficient cartilage and was devoid of nuclei pulposi. InSox5–/–/Sox6+/– and more severely inSox5+/–/Sox6–/–embryos, the notochord sheath was thinner, but cells survived. By birth,nuclei pulposi were rudimentary, and its cells poorly swelled and still expressing sonic hedgehog.

Hence, Sox5 and Sox6 are required for notochord extracellular matrix sheath formation, notochord cell survival and formation of nuclei pulposi. Through these roles and essential roles in cartilage formation, they are central transcriptional regulators of vertebral column development.
Structural-proliferative units and organ growth: effects of insulin-like growth factor 2 on the growth of colon and skin
Authors: Bennett William R. , Crew Tracey E. , Slack Jonathan M. W. , Ward Andrew
Published: February 2003

Many epithelial renewal tissues in vertebrates are organised into structural-proliferative units. We have examined the effect of IGF2 dose on the structure of structural-proliferative units in skin and colon. The mouse strains used were the Igf2 knockout, wild type and K:Igf2, a transgenic in which Igf2 is overexpressed under control of a keratin promoter.

For both skin and colon, the histological organisation of structural-proliferative units was unaltered with increasing IGF2 dose,although there was a higher fraction of dividing cells in the proliferative compartment. In the colon an increase in IGF2 dose increases the overall area of the epithelium. This is due to an increase in the number of crypts with no change of cell size or of crypt area. Growth stimulation appears to be due to a reduction in the duration of crypt fission. The conclusion is that the IGF2 pathway can stimulate the multiplication of colonic crypts independently of stimulating increased cell proliferation.

The results for the skin are consistent with this. An increase of IGF2 dose increases the proportion of dividing cells in the basal layer, the thickness of the epidermis and the total area of the epidermis.

By comparison with Drosophila, these results show no effects on cell size, but do show the possibility of inducing disproportionate growth. These differences may represent properties of the SPU organisation that is characteristic of vertebrate tissues.
Targeted deletion of a branchial arch-specific enhancer reveals a role ofdHANDin craniofacial development
Authors: Yanagisawa Hiromi , Clouthier David E. , Richardson James A. , Charité Jeroen , Olson Eric N.
Published: February 2003

The basic helix-loop-helix transcription factor dHAND is expressed in the mesenchyme of branchial arches and the developing heart. Mice homozygous for adHAND (Hand2) null mutation die early in embryogenesis from cardiac abnormalities, precluding analysis of the potential role ofdHAND in branchial arch development. Two independent enhancers control expression of dHAND in the heart and branchial arches. Endothelin-1 (ET-1) signaling regulates the branchial arch enhancer and is required for dHAND expression in the branchial arches. To determine the potential role of dHAND in branchial arch development and to assess the role of the ET-1-dependent enhancer in dHAND regulation in vivo, we deleted this enhancer by homologous recombination. Mice lacking thedHAND branchial arch enhancer died perinatally and exhibited a spectrum of craniofacial defects that included cleft palate, mandibular hypoplasia and cartilage malformations. Expression of dHAND was abolished in the ventolateral regions of the first and second branchial arches in these mutant mice, but expression was retained in a ventral domain where the related transcription factor eHAND is expressed. We conclude thatdHAND plays an essential role in patterning and development of skeletal elements derived from the first and second branchial arches and that there are heterogeneous populations of cells in the branchial arches that rely on different cis-regulatory elements for activation of dHANDtranscription.
Prolyl isomerase Pin1: a catalyst for oncogenesis and a potential therapeutic target in cancer
Authors: Ryo Akihide , Liou Yih-Cherng , Lu Kun Ping , Wulf Gerburg
Published: February 2003

Phosphorylation of proteins on serine or threonine residues preceding proline (Ser/Thr-Pro) is a major intracellular signaling mechanism. The phosphorylated Ser/Thr-Pro motifs in a certain subset of phosphoproteins are isomerized specifically by the peptidyl-prolyl cis-trans isomerase Pin1. This post-phosphorylation isomerization can lead to conformational changes in the substrate proteins and modulate their functions. Pin1 interacts with a number of mitotic phosphoproteins, and plays a critical role in mitotic regulation. Recent work indicates that Pin1 is overexpressed in many human cancers and plays an important role in oncogenesis. Pin1 regulates the expression of cyclin D1 by cooperating with Ras signaling and inhibiting the interaction ofβ-catenin with the tumor suppressor APC and also directly stabilizing cyclin D1 protein. Furthermore, PIN1 is an E2F target gene essential for the Neu/Ras-induced transformation of mammary epithelial cells. Pin1 is also a critical regulator of the tumor suppressor p53 during DNA damage response. Given its role in cell growth control and oncogenesis, Pin1 could represent a new anti-cancer target.
A mouse homologue ofDrosophila pinscan asymmetrically localize and substitute forpinsfunction inDrosophilaneuroblasts
Authors: Yu Fengwei , Morin Xavier , Kaushik Rachna , Bahri Sami , Yang Xiaohang , Chia William
Published: February 2003

Asymmetric cell division is a fundamental mechanism used to generate cellular diversity in invertebrates and vertebrates. In Drosophila,asymmetric division of neuroblasts is achieved by the asymmetric segregation of cell fate determinants Prospero and Numb into the basal daughter cell. Asymmetric segregation of cell fate determinants requires an apically localized protein complex that includes Inscuteable, Pins, Bazooka, DmPar-6,DaPKC and Gαi. Pins acts to stabilize the apical complex during neuroblast divisions. Pins interacts and colocalizes with Inscuteable, as well as maintaining its apical localization. We have isolated a mouse homologue of pins (Pins) and characterized its expression profile. Mouse PINS shares high similarity in sequence and structure with Pins and other Pins-like proteins from mammals. Pins is expressed in many mouse tissues but its expression is enriched in the ventricular zone of the developing central nervous systems. PINS localizes asymmetrically to the apical cortex of mitotic neuroblasts when ectopically expressed in Drosophila embryos. Like Pins, its N-terminal tetratricopeptide repeats can directly interact with the asymmetric localization domain of Insc,and its C-terminal GoLoco-containing region can direct localization to the neuroblast cortex. We further show that Pins can fulfill all aspects of pins function in Drosophila neuroblast asymmetric cell divisions. Our results suggest a conservation of function between the fly and mammalian Pins homologues.
Sterol-rich plasma membrane domains in the fission yeastSchizosaccharomyces pombe
Authors: Wachtler Volker , Rajagopalan Srividya , Balasubramanian Mohan K.
Published: February 2003

Sterol-rich membrane domains exist in unicellular and multicellular eukaryotes. They are thought to provide a structural framework for interactions among a subset of proteins by selectively incorporating some proteins while excluding others. Although most studies have focused on the biophysical and biochemical properties of sterol-rich membrane domains and incorporated proteins, relatively little is known about their intracellular distribution. Using a cytological approach we show here that in the fission yeast Schizosaccharomyces pombe, sterols are enriched in the plasma membrane at the growing cell tips and at the site of cytokinesis. The distribution of sterols is regulated in a cell-cycle-dependent manner and requires a functional secretory pathway. By manipulating the integrity of sterol-rich membrane domains using sterol sequestering agents and genetic means, we show that these domains are important for multiple processes regulating cytokinesis. In these cells, defects in proper maintenance of the actomyosin ring and/or its attachment to the overlying plasma membrane were observed. Furthermore, the stability of a plasma membrane protein that colocalises with sterol-rich membrane domains was compromised. Taken together,our studies establish S. pombe as a genetically tractable model organism in which to study the role(s) of sterol-rich membrane domains in cell polarity and cytokinesis.
Teleconsultations: who uses them and how?
Authors: Jaatinen Pekka T , Forsström Jari , Loula Pekka
Published: February 2003

A literature survey was carried out to identify papers describing teleconsulting applications. From 1259 potentially relevant articles identified through Medline, 128 articles were selected for review. The majority of these had been published in the Journal of Telemedicine and Telecare (50 articles, or 39%). We analysed different user groups, equipment and implementation issues, and the type of connections. In 101 studies (79%) the teleconsultations were between doctors, in 11 they were between patient and doctor, in seven between patient and nurse, and in nine between nurse and doctor. Studies of consultations between patients and health-care professionals were thus quite rare. Surgery was the most common specialty in which teleconsultation was described. The teleconsultations were realtime or mainly realtime in 72% of articles. In 39% of studies the primary focus was on videoconferencing. The most common means of connection was by ISDN digital lines (38%). There were very few mentions of how to ensure data protection or to maintain patient confidentiality. We conclude that, for the majority of teleconsultation needs, asynchronous communication is the most flexible and cost-effective approach. Realtime videoconferencing can be justified only in particular circumstances.
A four-year study of telephone support for oncology patients using a non-supervised call centre
Authors: Ferrer-Roca O , Subirana R
Published: February 2003

A non-supervised call centre was used to allow oncology patients to contact their personal doctors 24 hours a day. Incoming patient calls to the centre were automatically routed to the doctor's mobile phone or office telephone. Over four years, an average of 407 calls were made each year, by an average of 274 oncology patients. The average number of emergency hospital visits was 24 per year (0.09 per patient), compared with 42 per year (0.16 per patient) during the year before the telephone service began. The average number of outreach visits was 783 (2.9 per patient) per year during the study, in comparison with 722 (2.8 per patient) before it began. The average number of non-emergency hospital admissions was 41 (0.15 per patient) per year in comparison with 42 (0.17 per patient) before the study. Calls were short (typically 3-5 min) and the majority (88%) were made on the patient's initiative. Outreach patients in receipt of chemotherapy were the principal users (making 88% of all calls). Excluding the initial investment cost, the income received was approximately the same as the running costs of the call centre in two of the three years for which data were available.