bluuebunny/crossref_metadata_2025 huggingface dataset:
Report. Robert Boyle for the twenty-ndash;first century
Authors: Hunter Michael
Published: January 2005

In recent years, major steps have been taken in terms of understanding and exploiting the vast archive of Robert Boyle (1627–91), which was presented to The Royal Society in 1769. The collection was first catalogued in the 1980s; since then, it has been extensively used in preparing the definitive editions of Boyle's
Works
(14 vols, 1999–2000) and
Correspondence
(6 vols, 2001), both published by Pickering & Chatto, and the edition of his ‘workdiaries’, which has been available online since 2001. Now, thanks to a generous grant from the Heritage Lottery Fund, various steps have been taken to enhance access to the archive—particularly by electronic means, and especially through the provision of high–quality digitized images of its key components—and thus to increase understanding of Boyle and his significance for the origins of modern science. The project, entitled ‘Robert Boyle for the twenty–first century’, is a joint initiative between Birkbeck (University of London), The Royal Society and Access to Archives. It has three main components: first, the revision of the catalogue of the Boyle archive and its presentation in online, searchable form; second, the creation of digitized images of the entire content of the core volumes of the Boyle Papers and the publication of these on the World Wide Web, some as illustrations to an updated edition of the workdiaries; and third, the provision of introductory material on Boyle aimed at schools on the Boyle website at Birkbeck.
Global problems and global science
Authors: May Robert M.
Published: January 2005

Motivated by recent debates and policy decisions in the UK about bovine spongiform encephalopathy, genetically modified (GM) foods, embryonic stem cell research and other topics, my 2002 Anniversary Address dealt with ‘Science and Society’. Although some of the discussion was general––for instance, the changing nature of the landscape of scientific facts, ideas and uncertainties as a subject moves from the early stages of discovery and exploration toward full understanding—most of the focus was on specific issues in the UK. In particular, I dwelt on protocols for handling science advice in policy making, drawing on UK examples, and indicating some of the shadows that fall between tidy principles and the messy problems that arise in their implementation.
Active galaxies and cluster gas
Authors: Fabian A. C.
Published: January 2005

Two lines of evidence indicate that active galaxies, principally radio galaxies, have heated the diffuse hot gas in clusters. The first is the general need for additional heating to explain the steepness of the X–ray luminosity–temperature relation in clusters, the second is to solve the cooling–flow problem in cluster cores. The inner core of many clusters is radiating energy as X–rays on a time–scale much shorter than its likely age. Although the temperature in this region drops by a factor of about three from that of the surrounding gas, little evidence is found for gas much cooler than that. Some form of heating appears to be taking place, probably by energy transported outward from the central accreting black hole or radio source. How that energy heats the gas depends on poorly understood transport properties (conductivity and viscosity) of the intracluster medium. Viscous heating is discussed as a possibility. Such heating processes have consequences for the truncation of the luminosity function of massive galaxies.
Cooling and clusters: when is heating needed?
Authors: Bryan Greg , Voit Mark
Published: January 2005

There are (at least) two unsolved problems concerning the current state of the thermal gas in clusters of galaxies. The first is to identify the source of the heating which offsets cooling in the centres of clusters with short cooling times (the ‘cooling–flow’ problem). The second to understand the mechanism which boosts the entropy in cluster and group gas. Since both of these problems involve an unknown source of heating it is tempting to identify them with the same process, particularly since active galactic nuclei heating is observed to be operating at some level in a sample of well–observed ‘cooling–flow’ clusters. Here we show, using numerical simulations of cluster formation, that much of the gas ending up in clusters cools at high redshift and so the heating is also needed at high redshift, well before the cluster forms. This indicates that the same process operating to solve the cooling–flow problem may not also resolve the cluster–entropy problem.
AGN and the necessity of feedback
Authors: Benson Andrew J.
Published: January 2005

There is now good observational evidence that some type of feedback process must operate within galaxies. Such a process has long been thought to exist on the basis of theoretical studies of galaxy formation. This feedback is responsible for regulating the rate of star formation and thereby preventing the formation of an overabundance of low–mass galaxies. There is gathering evidence that this feedback process must somehow involve the supermassive black holes thought to dwell in the centres of galaxies.
Active galaxies and radiative heating
Authors: Ostriker Jeremiah P. , Ciotti Luca
Published: January 2005

There is abundant evidence that heating processes in the central regions of elliptical galaxies have both prevented large–scale cooling flows and assisted in the expulsion of metal rich gas. We now know that each such spheroidal system harbours in its core a massive black hole weighing ca. 0.13% of the mass in stars and also know that energy was emitted by each of these black holes with an efficiency exceeding 10% of its rest mass. Since, if only 0.5% of that radiant energy were intercepted by the ambient gas, its thermal state would be drastically altered, it is worth examining in detail the interaction between the out–flowing radiation and the equilibrium or inflowing gas. On the basis of detailed hydrodynamic computations we find that relaxation oscillations are to be expected with the radiative feedback quite capable of regulating both the growth of the central black hole and also the density and thermal state of the gas in the galaxy. Mechanical input of energy by jets may assist or dominate over these radiative effects.

We propose specific observational tests to identify systems which have experienced strong bursts of radiative heating from their central black holes.
The legacy and large–scale distribution of active galaxies
Authors: Tremaine Scott
Published: January 2005

If accretion onto massive black holes is the power source for active galaxies, then nearby galaxies should contain ‘dead quasars’: black holes that do not shine, either because they are starved for fuel or because they accrete with low radiative efficiency. This article briefly reviews the evidence that most inactive galaxies contain black holes at their centres, and how the local distribution of black holes is related to the population of active galaxies.
Black holes, cooling flows and galaxy formation
Authors: Peacock J. A.
Published: January 2005

Central black holes in galaxies are now well established as a ubiquitous phenomenon, and this fact is important for theories of cosmological structure formation. Merging of galaxy haloes must preserve the proportionality between black hole mass and baryonic mass; the way in which this happens may help solve difficulties with existing models of galaxy formation, which suffer from excessive cooling and thus overproduce stars. Feedback from active nuclei may be the missing piece of the puzzle, regulating galaxy–scale cooling flows. Such a process now seems to be observed in cluster–scale cooling flows, where dissipation of sound waves generated by radio lobes can plausibly balance the energy lost in X–rays, at least in a time–averaged sense.
Reconfiguration of supply chains and implications for transport
Authors: Lemoine Olga W. , Skjoett‐Larsen Tage
Published: January 2005

A large number of firms have reconfigured their supply chains. The general trends entail, among others, the reduction, centralization and re‐location of plants and distribution centers, the design of new distribution systems, and the reduction of the supplier base. The analysis of the implications of such reconfiguration for freight transport has received comparatively little attention, and most of the analysis has focused on the development of different theoretical models showing how changes in logistic structures and decisions could affect the transport demand. Using empirical data from Denmark, this paper sheds some light on the implications of reconfiguration supply chains on transport. Industry mail surveys among Danish firms as well as an in‐depth case study were performed. The consequences of the reconfiguration process on the present and future demand for transport are measured and analyzed in terms of the quantity of transport units used (trucks/containers), and the transport‐work (ton/km).
Statistical characterization of TEM images of silica‐filled rubber
Authors: TSCHESCHEL A. , LACAYO J. , STOYAN D.
Published: January 2005

Transmission electron microscopy is used to study the micro‐dispersion of silica fillers within the polymer matrix of rubber. The resulting grey‐value images are interpreted as realizations of random fields and are characterized by means of variograms. The so‐called Cauchy class is a suitable model for this purpose. Statistical analysis shows that different filler dispersion properties are reflected in different variogram parameters. As a case study, the random field approach is demonstrated for four exemplary rubber compounds.
Combined AFM and confocal fluorescence microscope for applications in bio‐nanotechnology
Authors: KASSIES R. , VAN DER WERF K. O. , LENFERINK A. , HUNTER C. N. , OLSEN J. D. , SUBRAMANIAM V. , OTTO C.
Published: January 2005

We present a custom‐designed atomic force fluorescence microscope (AFFM), which can perform simultaneous optical and topographic measurements with single molecule sensitivity throughout the whole visible to near‐infrared spectral region. Integration of atomic force microscopy (AFM) and confocal fluorescence microscopy combines the high‐resolution topographical imaging of AFM with the reliable (bio)‐chemical identification capability of optical methods. The AFFM is equipped with a spectrograph enabling combined topographic and fluorescence spectral imaging, which significantly enhances discrimination of spectroscopically distinct objects. The modular design allows easy switching between different modes of operation such as tip‐scanning, sample‐scanning or mechanical manipulation, all of which are combined with synchronous optical detection. We demonstrate that coupling the AFM with the fluorescence microscope does not compromise its ability to image with a high spatial resolution. Examples of several modes of operation of the AFFM are shown using two‐dimensional crystals and membranes containing light‐harvesting complexes from the photosynthetic bacterium Rhodobacter sphaeroides.
Shape discrimination by total curvature, with a view to cancer diagnostics
Authors: GARDNER R. J. , HOBOLTH A. , JENSEN E. B. V. , SØRENSEN F. B.
Published: January 2005

This paper investigates the use of total curvature for shape discrimination of objects via profiles of their planar sections (not assumed to be star shaped). Methods of estimating total curvature from observation of a finite number of points on the boundary of the object are investigated, including a simple discrete approximation method and various interpolation methods. Total curvature is capable of revealing shape differences on a local scale, as demonstrated by the analysis of two data sets of malignant and normal or benign tumour cell nuclear profiles.
Single‐particle visualization of assembly: I. Dimerization in a planar zone
Authors: WANG H. , WU I. , YANG Q. , CATALANO C. E. , SERWER P.
Published: January 2005

Single‐particle fluorescence microscopy of association/dissociation is required for analysis of biological assembly reactions. Toward achieving this goal, Wang et al. (J. Microsc., 2004, 213, 101–109) used molten agarose to concentrate thermally diffusing particles in a thin zone of solution next to the surface of a coverglass (plane of concentration). The present study details the first real‐time, single‐particle analysis of the association/dissociation of thermally diffusing particles in the plane of concentration. The test particles were procapsids of bacteriophage λ (radius = 31 nm). Quantification of thermal motion was developed and used to determine whether co‐diffusing particles were bound to each other. The data are explained by (1) the presence of a molten agarose‐generated barrier that is 93–155 nm from the coverglass surface, and (2) non‐random orientation of procapsid dimers in the plane of concentration.
Evaluation of syphilis in patients with HIV infection in Nigeria
Authors: Nnoruka E. N. , Ezeoke A. C. J.
Published: January 2005

Objective  To document the manifestations of syphilis among patients with concurrent HIV infection over a 12‐month period.

Method  Descriptive, cross‐sectional, hospital‐based study of all adult patients with syphilis and HIV infection who attended the skin clinic of the University of Nigeria, Teaching Hospital, Enugu, between July 2000 and June 2001. A standardized questionnaire was used to record age, sex, marital status, occupation and risk factor for HIV infection; initial site of onset of rash/ulcers, duration of the illness, any concomitant affection of mucosa, hair and nails as well as treatments received by each patient prior to presentation. Morphological distribution of lesions, mucosal surface (conjuctival, vulval and rectal) examinations and documentation of concomitant disorders with HIV were noted by the examining dermatologist. Lesional biopsy and dark‐field microscopy were undertaken to confirm diagnosis where serologic (non‐treponemal and treponemal specific) tests for syphilis were inconsistent with clinical suspicion. Each patient had a routine chest x‐ray, mantoux and purified protein derivative (PPD) status taken.

Results  Thirty‐one patients (21 males) with concurrent syphilis and HIV were seen during the study period. Primary syphilis was diagnosed in nine (29%), secondary syphilis in 20 (64.5%) and latent syphilis in two (6.5%). Neurosyphilis was not observed. Prevalence of syphilis for these patients with concurrent HIV was 2.1%. Mean duration of syphilis was 3.9 months ± 1.4 and lesions of greatest concern occurred mainly on the genitalia. The glans penis was affected in 10 (32.3%) cases, the penile shaft in seven (22.6%), the oral cavity in five (16.1%), the rectum in six (19.4%) and the vulva in three (0.9%) cases. Nine (29.1%) patients had a history of primary syphilitic chancre, 19 (61.3%) had a past history of sexually transmitted disease (STD) – particularly genital ulcers – while three (9.7%) could not recall any past history of STD. Eighteen (59.3%) had a history of unprotected sex, 16 (51.7%) had multiple sexual partners, four (13.3%) had had oral sex, and one anal sex (3.3%); none admitted to being bisexual. Other relevant risk factors for HIV transmission were blood transfusion within 5 years for three (9.7%) and intravenous drug use in two (6.5%). Some patients had more than one condition as a potential source of exposure. Serological tests were weakly reactive in 17 (48.4%), strongly reactive in nine (29%) and non‐reactive in five (16.1%) patients. Three patients exhibited prozone phenomenon. Treatment comprised the syndromic approach, which currently is advocated for use in primary healthcare centres without facilities for aetiological diagnosis of sexually transmitted infections.

Conclusion  Our cases with concurrent syphilis and HIV/AIDS had unusual manifestations, responded to treatment more slowly and died sooner than cases described in Western literature due to generally lower levels of health.
Temporal relationship between the occurrence of fresh noma and the timing of linear growth retardation in Nigerian children
Authors: Enwonwu Cyril O. , Phillips Reshma S. , Ferrell Christine D.
Published: January 2005

Background  Fresh noma (cancrum oris) occurs predominantly in children <4 years of age. The key risk factors are poverty, malnutrition and infections. Evolution from an intraoral inflammation to a grotesque oro‐facial gangrene is very rapid.

Objective  We assessed potential relationship between the occurrence of fresh noma and linear growth retardation (LGR) which is prevalent in deprived Third World infants/children between ages 3 and 30 months. LGR is attributed to malnutrition and chronic immunostimulation by environmental antigens.

Design  Anthropometric evaluation of children (n = 91) with fresh noma, ages 0–8 years, in relation to US National Center for Health Statistics Reference values was carried out. Age‐matched noma‐free, poor village children (n = 151) from similar communities as noma cases, and elite urban children (n = 132) served as control groups. Heights and weights were measured and the height for age (HAZ), weight for age (WAZ) and weight for height (WHZ) scores calculated as indices of stunting, underweight and wasting respectively. Serum level of interleukin (IL)‐18, a multifunctional cytokine, was also measured.

Results  In the age groups 0–4 and 4–8 years, the percentages of noma children <−2.0SD were 91% and 67% respectively. The corresponding values for the village children were 37% and 24% and significantly different (P < 0.001) from the noma group. Only 7% of the elite children aged 4–8 years were stunted. Low body weight and wasting were prominent features of village and noma groups, but more marked in the latter. Associated with noma was a profound increase (P < 0.001) in IL‐18 in comparison with urban controls, and a 34% non‐statistically significant increase relative to the village control group. Among other functions, IL‐18 induces several pro‐inflammatory cytokines and the matrix metalloproteinases, influences long bone growth, and consequently may be relevant to growth retardation seen in poor village children and noma victims.

Conclusion  These results suggest that occurrence of fresh noma was probably programmed very early in life by malnutrition and chronic infections resulting from replacement of breast milk with contaminated, inferior substitutes. Although not investigated, we speculate that children with fresh noma might also be victims of intrauterine growth retardation as noma is most prevalent during the infantile phase of child growth which starts at mid‐gestation and tails off at 4 years.
Disparities in parasitic infections, perceived ill health and access to health care among poorer and less poor schoolchildren of rural Côte d'Ivoire
Authors: Raso Giovanna , Utzinger Jürg , Silué Kigbafori D. , Ouattara Mamadou , Yapi Ahoua , Toty Abale , Matthys Barbara , Vounatsou Penelope , Tanner Marcel , N'Goran Eliézer K.
Published: January 2005

Differences in the state of health between rural and urban populations living in Africa have been described, yet only few studies analysed inequities within poor rural communities. We investigated disparities in parasitic infections, perceived ill health and access to formal health services among more than 4000 schoolchildren from 57 primary schools in a rural area of western Côte d'Ivoire, as measured by their socioeconomic status. In a first step, we carried out a cross‐sectional parasitological survey. Stool specimens and finger prick blood samples were collected and processed with standardized, quality‐controlled methods, for diagnosis of Schistosoma mansoni, soil‐transmitted helminths, intestinal protozoa and Plasmodium. Then, a questionnaire survey was carried out for the appraisal of self‐reported morbidity indicators, as well as housing characteristics and household assets ownership. Mean travel distance from each village to the nearest health care delivery structure was provided by the regional health authorities. Poorer schoolchildren showed a significantly higher infection prevalence of hookworm than better‐off children. However, higher infection prevalences of intestinal protozoa (i.e. Blastocystis hominis, Endolimax nana and Iodamoeba bütschlii) were found with increasing socioeconomic status. Significant negative associations were observed between socioeconomic status and light infection intensities with hookworm and S. mansoni, as well as with several self‐reported morbidity indicators. The poorest school‐attending children lived significantly further away from formal health services than their richer counterparts. Our study provides evidence for inequities among schoolchildren's parasitic infection status, perceived ill health and access to health care in a large rural part of Côte d'Ivoire. These findings call for more equity‐balanced parasitic disease control interventions, which in turn might be an important strategy for poverty alleviation.
Pseudomonas aeruginosa isolates recovered from clinical and environmental samples in Buea, Cameroon: current status on biotyping and antibiogram
Authors: Ndip R. N. , Dilonga H. M. , Ndip L. M. , Akoachere J. F. K. , Nkuo Akenji T.
Published: January 2005

Objective  The study was aimed at determining the prevalent biotypes of Pseudomonas aeruginosa in the environment of Buea and the susceptibility of isolates to antibiotics.

Methods  One hundred and fifty clinical specimens (urine, wound and sputum) collected from patients attending various health institutions in Buea, and 50 environmental swabs from furniture, appliances and surroundings of these institutions were screened for P. aeruginosa using standard microbiological and biochemical methods. Antimicrobial susceptibility of the isolates was determined by the disc diffusion assay.

Results  Fifty‐one (25.5%) of the 200 specimens were positive for the organism with urine (30%) being the most common source of isolation. Biochemical characterization grouped the isolates into eight biotypes with biotypes B III (25.59%), B II (23.53%) and B I (21.57%) being the most prevalent. Antimicrobial susceptibility results of isolates revealed 13 antibiotype patterns based on resistance to the antimicrobial agents investigated. The resistance pattern, cefotaxime, gentamicin and tetracycline (CTXR GENR TETR) was the most common (21.6%) amongst the isolates. Over 40% of the isolates exhibited multi‐drug resistance to five or more antibiotics, especially environmental isolates. However, there was a significant difference (P < 0.05) in the susceptibility of isolates to ciprofloxacin (98%), amikacin (90.2%) and netilmicin (80.4%) compared with other drugs used in the study.

Conclusion  A combination of biotyping and antibiogram, which are relatively cheap and routinely available methods in our environment, could be useful for clinical and epidemiological studies particularly in laboratories in the developing world with limited resources.
Spatial effects of the social marketing of insecticide‐treated nets on malaria morbidity
Authors: Abdulla S. , Gemperli A. , Mukasa O. , Armstrong Schellenberg J. R. M. , Lengeler C. , Vounatsou P. , Smith T.
Published: January 2005

Randomized controlled trials have shown that insecticide‐treated nets (ITNs) have an impact on both malaria morbidity and mortality. Uniformly high coverage of ITNs characterized these trials and this resulted in some protection of nearby non‐users of ITNs. We have now assessed the coverage, distribution pattern and resultant spatial effects in one village in Tanzania where ITNs were distributed in a social marketing programme. The prevalence of parasitaemia, mild anaemia (Hb <11 g/dl) and moderate/severe anaemia (Hb <8 g/dl) in children under five was assessed cross‐sectionally. Data on ownership of ITNs were collected and inhabitants’ houses were mapped. One year after the start of the social marketing programme, 52% of the children were using a net which had been treated at least once. The ITNs were rather homogeneously distributed throughout the village at an average density of about 118 ITNs per thousand population. There was no evidence of a pattern in the distribution of parasitaemia and anaemia cases, but children living in areas of moderately high ITN coverage were about half as likely to have moderate/severe anaemia (OR 0.5, 95% CI: 0.2, 0.9) and had lower prevalence of splenomegaly, irrespective of their net use. No protective effects of coverage were found for prevalence of mild anaemia nor for parasitaemia. The use of untreated nets had neither coverage nor short distance effects. More efforts should be made to ensure high coverage in ITNs programmes to achieve maximum benefit.
Experience of targeting subsidies on insecticide‐treated nets: what do we know and what are the knowledge gaps?
Authors: Worrall Eve , Hill Jenny , Webster Jayne , Mortimer Julia
Published: January 2005

Widespread coverage of vulnerable populations with insecticide‐treated nets (ITNs) constitutes an important component of the Roll Back Malaria (RBM) strategy to control malaria. The Abuja Targets call for 60% coverage of children under 5 years of age and pregnant women by 2005; but current coverage in Africa is unacceptably low. The RBM ‘Strategic Framework for Coordinated National Action in Scaling‐up Insecticide‐Treated Netting Programmes in Africa’ promotes coordinated national action and advocates sustained public provision of targeted subsidies to maximise public health benefits, alongside support and stimulation of the private sector. Several countries have already planned or initiated targeted subsidy schemes either on a pilot scale or on a national scale, and have valuable experience which can inform future interventions. The WHO RBM ‘Workshop on mapping models for delivering ITNs through targeted subsidies’ held in Zambia in 2003 provided an opportunity to share and document these country experiences. This paper brings together experiences presented at the workshop with other information on experiences of targeting subsidies on ITNs, net treatment kits and retreatment services (ITN products) in order to describe alternative approaches, highlight their similarities and differences, outline lessons learnt, and identify gaps in knowledge. We find that while there is a growing body of knowledge on different approaches to targeting ITN subsidies, there are significant gaps in knowledge in crucial areas. Key questions regarding how best to target, how much it will cost and what outcomes (levels of coverage) to expect remain unanswered. High quality, well‐funded monitoring and evaluation of alternative approaches to targeting ITN subsidies is vital to develop a knowledge base so that countries can design and implement effective strategies to target ITN subsidies.
Safety of the combination of chloroquine and methylene blue in healthy adult men with G6PD deficiency from rural Burkina Faso
Authors: Mandi Germain , Witte Steffen , Meissner Peter , Coulibaly Boubacar , Mansmann Ulrich , Rengelshausen Jens , Schiek Wolfgang , Jahn Albrecht , Sanon Mamadou , Wüst Kirsten , Walter‐Sack Ingeborg , Mikus Gerd , Burhenne Jürgen , Riedel Klaus‐Dieter , Schirmer Heiner , Kouyaté Bocar , Müller Olaf
Published: January 2005

New drug combinations against falciparum malaria which are both effective and affordable for Sub‐Saharan African populations are urgently needed. The combination of the well‐known drugs chloroquine (CQ) and methylene blue (MB) is such a promising new regimen. However, there is some concern that MB could cause development of haemolysis in patients with glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, a condition which is prevalent in malaria‐endemic regions. Against this background, 74 G6PD‐deficient but otherwise healthy adult men were given a 3‐day oral regimen of a total of 1500 mg CQ and 780 mg MB in the District Hospital of Nouna in north‐western Burkina Faso. Haemolysis did not occur, haemoglobin levels remained stable or even rose in the study participants, and the drug regimen was well tolerated. Therefore, standard dosages of MB appear to be safe in G6PD‐deficient African populations with predominantly class III G6PD deficiency.
Follow up of the regression of the placenta left in situ in an advanced abdominal pregnancy using the Cavalieri method
Authors: Cetinkaya Mehmet B. , Kokcu Arif , Alper Tayfun
Published: January 2005

In this abdominal pregnancy, the dead fetus was delivered through an abdominal incision at the 36th gestational week. The placenta invaded the small intestine and the omentum was left in situ. The placental degeneration was monitored using serial serum β‐human chorionic gonadotropin values. In certain periods, the follow up of the placental regression was carried out using the Cavalieri method with abdominal ultrasound. It was seen that the placental volume had decreased by 83% at the end of 1 year. To the best of our knowledge, this is the first time this method has been used for this purpose.
Heterozygous hemophilia developed during pregnancy
Authors: Fukada Yukihito , Shima Takashi , Kawashima Shigeki , Hirata Shuji , Hoshi Kazuhiko
Published: January 2005

In rare cases, patients with heterozygous hemophilia show bleeding tendency due to a low factor VIII activity of <20%. Here we describe a case of heterozygous hemophilia that developed during pregnancy. The patient was a 33‐year‐old Japanese woman whose father and brother both showed elevated nasal bleeding tendencies. However, they had received no medication for this condition. At 26 weeks’ gestation she experienced heavy nasal bleeding. The prothrombin time and platelet count were normal, but the activated partial thromboplastin time was prolonged. Premature rupture of the membrane occurred, and an emergency cesarean section was carried out at 28 weeks’ gestation. A diagnosis of heterozygous hemophilia was made after the cesarean section. Hemophilia crisis and heterozygous hemophilia require special obstetric care, with close liaison with a hematologist. Guidelines for the management of such cases should be available and observed.
Tourniquet technique prevents profuse blood loss in placenta accreta cesarean section
Authors: Ikeda Tomoaki , Sameshima Hiroshi , Kawaguchi Hideki , Yamauchi Noriyuki , Ikenoue Tsuyomu
Published: January 2005

Aim: Profuse bleeding in placenta accreta is life‐threatening even under well‐prepared cesarean sections.

Methods: We used a tourniquet technique to temporally shut off blood flow through the uterine and ovarian vessels at the level of the uterine cervix. The tourniquet consisted of manual compression followed by a rubber tube.

Results: Total blood loss in cesarean section and hysterectomy in the two cases in which we applied this technique was significantly reduced compared with that in the two cases without it.

Conclusion: This technique not only prevented massive bleeding from the accreted placentation, but also allowed physicians time to consider the necessity of subsequent hysterectomy.
The actin‐binding protein profilin I is localized at synaptic sites in an activity‐regulated manner
Authors: Neuhoff Henrike , Sassoè‐Pognetto Marco , Panzanelli Patrizia , Maas Christoph , Witke Walter , Kneussel Matthias
Published: January 2005

Morphological changes at synaptic specializations have been implicated in regulating synaptic strength. Actin turnover at dendritic spines is regulated by neuronal activity and contributes to spine size, shape and motility. The reorganization of actin filaments requires profilins, which stimulate actin polymerization. Neurons express two independent gene products − profilin I and profilin II. A role for profilin II in activity‐dependent mechanisms at spine synapses has recently been described. Although profilin I interacts with synaptic proteins, little is known about its cellular and subcellular localization in neurons. Here, we investigated the subcellular distribution of this protein in brain neurons as well as in hippocampal cultures. Our results indicate that the expression of profilin I varies in different brain regions. Thus, in cerebral cortex and hippocampus profilin I immunostaining was associated predominantly with dendrites and was present in a subset of dendritic spines. In contrast, profilin I in cerebellum was associated primarily with presynaptic structures. Profilin I immunoreactivity was partially colocalized with the synaptic molecules synaptophysin, PSD‐95 and gephyrin in cultured hippocampal neurons, indicating that profilin I is present in only a subset of synapses. At dendritic spine structures, profilin I was found primarily in protrusions, which were in apposition to presynaptic terminal boutons. Remarkably, depolarization with KCl caused a moderate but significant increase in the number of synapses containing profilin I. These results show that profilin I can be present at both pre‐ and postsynaptic sites and suggest a role for this actin‐binding protein in activity‐dependent remodelling of synaptic structure.
Inhibitory avoidance learning altered ensemble activity of amygdaloid neurons in rats
Authors: Chang Chun‐Hui , Liang Keng‐Chen , Yen Chen‐Tung
Published: January 2005

In this study, we examined single‐unit activity in the amygdala before and after a rat had acquired an inhibitory avoidance task. Long‐Evans rats with microwires chronically implanted into the central nucleus (CeA) or basolateral complex (BLC) of the amygdala were acclimatized to the apparatus of a step‐through inhibitory avoidance task for three sessions. On the fourth session, rats in the experimental group received an inescapable footshock (3 mA, 1 s) as they stepped from the lit side into the dark side of the task apparatus, whereas rats in the control group received the same amount of shock on a different apparatus. All rats were tested for retention in the task apparatus 1 day after shock training. The experimental rats showed better retention than the controls as they stayed longer in the lit side. Ensemble unit activities were recorded in the amygdala nuclei from the indwelling wire bundles during the acclimation and test sessions. The data collected from well‐isolated amygdala units showed that neuronal discharge habituated from the first to the third acclimation session. In the test session, the experimental group, but not the control group, showed elevated firing rates in the CeA or BLC neurons located on either side of the brain. These findings provide the first piece of evidence showing that learning of an inhibitory avoidance task leads to an increase in amygdala neuronal discharges during a retention test.
Activation of group II mGlu receptors blocks the enhanced drug taking induced by previous exposure to amphetamine
Authors: Kim Jeong‐Hoon , Austin Jennifer D. , Tanabe Lauren , Creekmore Elizabeth , Vezina Paul
Published: January 2005

Repeated exposure to amphetamine (AMPH) leads to the development of behavioural sensitization that can be demonstrated in rats as enhanced locomotor responding to and self‐administration of the drug. Glutamate systems are known to participate in the induction and expression of sensitization by psychostimulants. Group II metabotropic glutamate receptors (mGluRs), because they negatively regulate both vesicular and nonvesicular glutamate release, are thus well positioned to gate its expression. Here we report that the expression of locomotor sensitization by AMPH is completely prevented by a systemic injection of the selective group II mGluR agonist LY379268 at a dose that produced no effects when administered alone. The activation of group II mGluRs in AMPH‐sensitized rats also reduced the enhanced overflow of both dopamine and glutamate normally observed in the nucleus accumbens, a brain region critical for the generation of locomotor and drug self‐administration behaviours. To directly determine the effect of group II mGluR activation on enhanced drug self‐administration, AMPH‐sensitized rats were allowed to self‐administer a mixture of LY379268 and AMPH. These rats continued to self‐administer but did not exhibit the enhanced work output and drug intake observed in AMPH‐sensitized rats self‐administering AMPH alone. Thus, activating group II mGluRs prevents the expression of different manifestations of AMPH sensitization including enhanced self‐administration of the drug. These receptors may represent a potentially important target for therapeutic intervention directed at drugs of abuse.
Caspase‐independent retinal ganglion cell death after target ablation in the neonatal rat
Authors: Spalding Kirsty L. , Dharmarajan Arun M. , Harvey Alan R.
Published: January 2005

In neonatal rats, superior colliculus (SC) ablation results in a massive and rapid increase in retinal ganglion cell (RGC) death that peaks about 24 h post‐lesion (PL). Naturally occurring cell death during normal development, and RGC death after axonal injury in neonatal and adult rats, has primarily been ascribed to apoptosis. Given that normal developmental cell death is reported to involve caspase 3 activation, and blocking caspase activity in adults reduces axotomy‐induced death, we examined whether blocking caspases in vivo reduces RGC death after neonatal SC lesions. Neither general nor specific caspase inhibitors increased neonatal RGC survival 6 and 24 h PL. These inhibitors were, however, effective in blocking caspases in another well‐defined in vitro apoptosis model, the corpus luteum. Caspase 3 protein and mRNA levels in retinas from normal and SC‐lesioned neonatal rats were assessed 3, 6 and 24 h after SC removal using immunohistochemistry, western and northern blots and quantitative real‐time polymerase chain reaction. Terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL) was used to independently monitor retinal cell death. The polymerase chain reaction data showed a small but insignificant increase in caspase 3 mRNA in retinas 24 h PL. Western blot analysis did not reveal a significant shift to cleaved (activated) caspase 3 protein. There was a small increase in the number of cleaved caspase 3 immunolabelled cells in the ganglion cell layer 24 h PL but this represented only a fraction of the death revealed by TUNEL. Together, these data indicate that, unlike the situation in adults, most lesion‐induced RGC death in neonatal rats occurs independently of caspase activation.
Expression of the repressor element‐1 silencing transcription factor (REST) is influenced by insulin‐like growth factor‐I in differentiating human neuroblastoma cells
Authors: Di Toro Rosanna , Baiula Monica , Spampinato Santi
Published: January 2005

The repressor element‐1 (RE‐1) silencing transcription factor (REST) interacts with an RE‐1 cis element and represses the transcription of neuron‐specific genes in neuronal progenitors but is down‐regulated in post‐mitotic neurons. We report that REST expression is modified, in a time‐dependent manner, in SH‐SY5Y neuroblastoma cells exposed to insulin‐like growth factor I (IGF‐I), a polypeptide hormone affecting various aspects of neuronal induction and maturation. REST is increased in cells treated with IGF‐I for 2 days and then declines in 5‐day‐treated cells concomitant with a progressive neurite extension. To investigate any role played by REST in neurodifferentiation by IGF‐I, we employed an antisense oligonucleotide (AS‐ODN) complementary to REST mRNA. In AS‐ODN‐treated cells, the effects elicited by IGF‐I on cell proliferation are not influenced whereas a marked decrease of REST significantly increases neurite elongation without any gross perturbation of neurogenesis. Synapsin I and βIII‐tubulin gene promoters contain an RE‐1 motif and their transcription is repressed by REST; both of them are increased in cells exposed to IGF‐I for 5 days and further elevated by AS‐ODN treatment. A parallel increase of growth cone‐associated protein 43, a protein chosen as a neuronal marker not directly regulated by REST, is also observed. Therefore, REST is elevated during early steps of neural induction by IGF‐I and could contribute to down‐regulate genes not yet required by the differentiation program while it declines later for the acquisition of neural phenotypes. These results suggest a model in which differentiating neuroblastoma cells determine their extent of neurite outgrowth on the basis of REST disappearance.
Repeated administration of the monoamine reuptake inhibitor BTS 74 398 induces ipsilateral circling in the 6‐hydroxydopamine lesioned rat without sensitizing motor behaviours
Authors: Lane E. L. , Cheetham S. C. , Jenner P.
Published: January 2005

BTS 74 398 (1‐[1‐(3,4‐dichlorophenyl)cyclobutyl]−2‐(3‐diaminethylaminopropylthio)ethanone monocitrate) is a monoamine reuptake inhibitor that reverses motor deficits in MPTP‐treated (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) common marmosets without provoking established dyskinesia. However, it is not known whether BTS 74 398 primes the basal ganglia for dyskinesia induction. In this study, the ability of BTS 74 398 to sensitize 6‐hydroxydopamine (6‐OHDA)‐lesioned rats for the production of abnormal motor behaviours and the induction of striatal ΔFosB were determined in comparison with l‐3,4‐dihydroxyphenylalanine methyl ester (l‐dopa). Acute administration of BTS 74 398 induced a dose‐dependent ipsilateral circling response in unilaterally 6‐OHDA‐lesioned rats whereas l‐dopa produced dose‐dependent contraversive rotation. The ipsilateral circling response to BTS 74 398 did not alter during 21 days of administration. In contrast, l‐dopa treatment for 21 days caused a marked increase in rotational response. Repeated administration of both l‐dopa and BTS 74 398 increased general motor activity and stereotypic behaviour. In l‐dopa‐treated rats, orolingual, locomotive, forelimb and axial abnormal movements developed whereas BTS 74 398 produced only locomotion with a side bias but no other abnormal movements. Sensitization of circling responses and the development of abnormal movements in 6‐OHDA‐lesioned rats have been associated with the potential of dopaminergic drugs to induce dyskinesia. Furthermore, striatal ΔFosB immunoreactivity, shown to correlate with dyskinesia induction, was increased by l‐dopa but was unaffected by repeated BTS 74 398 administration. The lack of such changes following repeated BTS 74 398 treatment suggests that it may be an effective antiparkinsonian therapy that is unlikely to produce involuntary movements.
Differential progression of proprioceptive and visual information processing deficits in Parkinson's disease
Authors: Keijsers N. L. W. , Admiraal M. A. , Cools A. R. , Bloem B. R. , Gielen C. C. A. M.
Published: January 2005

Indirect evidence suggests that patients with Parkinson's disease (PD) have deficits not only in motor performance, but also in the processing of sensory information. We investigated the role of sensory information processing in PD patients with a broad range of disease severities and in a group of age‐matched controls. Subjects were tested in two conditions: pointing to a remembered visual target in complete darkness (DARK) and in the presence of an illuminated frame with a light attached to the index finger (FRAME). Differences in pointing errors in these two conditions reflect the effect of visual feedback on pointing. PD patients showed significantly larger constant and variable errors than controls in the DARK and FRAME condition. The difference of the variable error in the FRAME and DARK condition decreased as a function of the severity of PD. This indicates that any deficits in the processing of proprioceptive information occur already at very mild symptoms of PD, and that deficits in the use of visual feedback develop progressively in later stages of the disease. These results provide a tool for early diagnosis of PD and shed new light on the functional role of the brain structures that are affected in PD.
Neocortex is the major target of sedative concentrations of volatile anaesthetics: strong depression of firing rates and increase of GABAA receptor‐mediated inhibition
Authors: Hentschke Harald , Schwarz Cornelius , Antkowiak Bernd
Published: January 2005

General anaesthetics cause sedation, amnesia and hypnosis. Although these clinically desired actions are indicative of an impairment of neocortical information processing, it is widely held that they are to a large part mediated by subcortical neural networks. Anaesthetic action on brain stem, basal forebrain and thalamus, all of which are known to modulate cortical excitability, would thus ultimately converge on neocortex, perturbing and reducing action potential activity therein. However, as neocortex harbours molecular targets of anaesthetics in high densities, notably GABAA receptors, neocortex itself should be very sensitive to anaesthetics. Here, we performed experiments to reveal the extent to which neocortex proper is a relevant target of the low concentrations of volatile anaesthetics causing sedation and hypnosis. We compared the effects of isoflurane, enflurane and halothane on spontaneous action potential activity of rat neocortical neurons in vivo and in isolated cortical networks in vitro, i.e. in the presence and absence of subcortical arousal systems. We observed that the anaesthetics decreased spontaneous firing of neurons via intracortical mechanisms; concentrations inducing hypnosis in humans reduced discharge rates both in vivo and in vitro to the same extent, approximately 50%. This decrease in neuronal activity was paralleled by a significant enhancement of neocortical GABAA receptor‐mediated inhibition. These findings challenge the notion of predominantly subcortical effects of volatile anaesthetics and suggest that intracortical targets, among them neocortical GABAA receptors, mediate the sedative and hypnotic properties of volatile anaesthetics.
Genetic ablation of the mammillary bodies in the Foxb1 mutant mouse leads to selective deficit of spatial working memory
Authors: Radyushkin Konstantin , Anokhin Konstantin , Meyer Barbara I. , Jiang Qiuhong , Alvarez‐Bolado Gonzalo , Gruss Peter
Published: January 2005

Mammillary bodies and the mammillothalamic tract are parts of a classic neural circuitry that has been implicated in severe memory disturbances accompanying Korsakoff's syndrome. However, the specific role of mammillary bodies in memory functions remains controversial, often being considered as just an extension of the hippocampal memory system. To study this issue we used mutant mice with a targeted mutation in the transcription factor gene Foxb1. These mice suffer perinatal degeneration of the medial and most of the lateral mammillary nuclei, as well as of the mammillothalamic bundle. Foxb1 mutant mice showed no deficits in such hippocampal‐dependent tasks as contextual fear conditioning and social transmission of food preference. They were also not impaired in the spatial reference memory test in the radial arm maze. However, Foxb1 mutants showed deficits in the task for spatial navigation within the Barnes maze. Furthermore, they showed impairments in spatial working memory tasks such as the spontaneous alternation and the working memory test in the radial arm maze. Thus, our behavioural analysis of Foxb1 mutants suggests that the medial mammillary nuclei and mammillothalamic tract play a role in a specific subset of spatial tasks, which require combined use of both spatial and working memory functions. Therefore, the mammillary bodies and the mammillothalamic tract may form an important route through which the working memory circuitry receives spatial information from the hippocampus.