bluuebunny/crossref_metadata_2025 huggingface dataset:
ABO Blood Group Genotype and Plasma von Willebrand Factor in Normal Individuals
Authors: Shima Masayuki , Fujimura Yoshihiro , Nishiyama Takayuki , Tsujiuchi Tomomi , Narita Nobuhiro , Matsui Taei , Titani Koiti , Katayama Masahiko , Yamamoto Fumi‐ichiro , Yoshioka Akira
Published: March 2009

von Willebrand factor (vWF) is a multimeric plasma protein with ABO (H) blood group sugar chains. We investigated a total of 330 plasmas from normal individuals having various ABO genotypes, with special reference to vWF antigen and its platelet glycoprotein‐Ib‐related biological activities, termed ristocetin cofactor (RCof) and botrocetin cofactor (BCof). RCof reflects the biological activity of higher vWF multimers, while BCof reflects that of vWF of multimers of all sizes. Plasmas from normal individuals carrying one O gene (genotypes AO and BO) had slightly, but proportionally lower levels of vWF antigen, RCof, and BCof than those carrying no O gene (genotypes AA, AB, and BB). Normal plasmas from individuals carrying two O genes (genotype 00) showed much lower values for these parameters than the other plasmas, as previously reported. However, multimeric analysis of plasma vWF antigen revealed no differences among the different genotypes.
Lewis Histo‐Blood Group System and Associated Secretory Phenotypes
Authors: Henry Stephen , Oriol Rafael , Samuelsson Bo
Published: March 2009

This review summarises present knowledge of the chemistry, immunology, genetics and clinical significance of antibodies in the Lewis and secretor histoblood group systems. Although red cell serology has laid the foundations for these systems, more recent advances have been made by studying Lewis and related glycoconjugates with monoclonal antibodies, determining structures by mass spectrometry and NMR spectroscopy, identifying enzymes and their specificities, and identifying the genes by molecular biology. The expression of Lewis system antigens is dependent on Lewis and secretor loci. Fucosyltransferases coded by genes at these loci compete and interact with each other and with other transferases to determine an individual's Lewis and secretor phenotype. Exocrine epithelial cells, mostly of endodermal origin, synthesise the Lewis antigens which, as plasma glycolipids, are secondarily acquired by cells of the peripheral circulation. Phenotyping red cells is often regarded as a simple way of determining the Lewis and sometimes the secretor status of an individual; however, the red cell phenotype is influenced by many factors and may not necessarily reflect someone's Lewis and secretor genotypes. Two main red cell Lewis groups are usually found, Lewis negative and Lewis positive. In Lewis‐negative individuals, the secretor genotype does not affect the Lewis phenotype, but in Lewis‐positive individuals, the non‐secretor genotype generates the Le(a+b–) phenotype, the secretor genotype causes the Le(a–b+) phenotype, and the partial secretor genotype gives rise to the Le(a+b+) phenotype.
Prestorage Leukocyte Depletion with In‐Line Filtration of Whole Blood in Comparison with Blood Component Leukocyte Depletion
Authors: Riggert J. , Simson G. , Dittmann J. , Köhler M.
Published: March 2009

In‐line filtration of blood components appears to be an effective method to reduce white‐cell‐induced adverse reactions. We have investigated whether whole blood filtration (WBF), prior to component preparation, is comparable with filtration of already prepared blood components (CF), i.e. the red cell concentrate (RCC) and fresh plasma. Conventionally prepared nonfiltered blood components served as a control. No significant differences for most parameters investigated were found between leukodepleted RCCs and plasma units prepared by CF or WBF. All filtered RCCs and plasma units (CF and WBF) had white blood cell contaminations <1′105 per unit. Platelets were reduced in all filtered components: 95% in plasma and 99% in RCCs. Fresh‐frozen plasma (FFP) prepared by CF and WBF had normal amounts of factors V, VIII, von Willebrand factor and thrombin‐antithrombin‐III complexes, whereas platelet factor 4 (PF‐4) was slightly increased in FFP prepared by WBF. RCCs and plasma units prepared from filtered whole blood (n = 20) had a significantly greater volume (RCC: 288±19 ml; plasma: 274±20 ml) than conventionally prepared (n = 20) and filtered products (RCC: 257±19 ml, plasma: 259±19 ml). For early filtration of blood components, WBF prior to component preparation seems to offer an interesting technique for obtaining a leukocyte‐depleted RCC and FFP.
A Rapid and Simple ABO Genotype Screening Method Using a Novel B/O2 versus A/O2 Discriminating Nucleotide Substitution at the ABO Locus
Authors: L. Olsson Martin , Chester M. Alan
Published: March 2009

An ABO genotype screening method discriminating the common alleles A1, A2, B, O1 and O2 at the ABO locus was made possible by the discovery of a novel nucleotide substitution (G1096A) present only in B and O2 alleles. A rapid and reliable single‐tube approach using multiplex PCR with four primers amplifying exons 6 and 7 of the ABO genes followed by simultaneous addition of two restriction enzymes was developed and validated in a population of 150 Swedish blood donors. This technique is the most cost‐efficient and informative ABO genotyping method reported to date.
The Beta Chain of the GPIIb Molecule on Ruminant Leukocytes and Platelets Is Not Labelled by the Sulfo‐NHS‐Biotin Method
Authors: Pintado C. O. , Moreno Angela , Barbancho M. , Pérez de la Lastra J. M. , Llanes D.
Published: March 2009

Glycoprotein (Gp)IIb/IIIa molecules have been immunoprecipitated from platelets and leukocytes of cattle, goat, horse, human, sheep and swine using specific monoclonal antibodies. The sulfo‐NHS‐biotin (sulfosuccinimidobiotin) method used to label the proteins has been found unsuitable for labelling the β chain of the ruminant GPIIb/IIIa molecule. The β chain was present on ruminant leukocytes and platelets when immunoprecipitates were silver stained.
Blood Transfusion in Sickle Cell Disease
Authors: Davies Sally C. , Olatunji P.O.
Published: March 2009

Blood transfusion is used as a life‐saving and prophylactic treatment in sickle cell disease. Despite the many complications associated with its use, few randomised controlled trials and careful research studies have been performed to fully define its role. This subjects is, therefore, discussed in the context of the current literature and authors' experience.
Establishment of a T‐Cell Line from Lymphocytes Presumably Implicated in Posttransfusion Graft‐versus‐Host Disease
Authors: Nishimura Motoko , Uchida Shigeharu , Mitsunaga Shigeki , Tokunaga Katsushi , Mitomi Yoshitada , Tadokoro Kenji , Juji Takeo
Published: March 2009

Posttransfusion graft‐versus‐host disease (PTGVHD) is known to develop in immunocompetent patients exhibiting clinical symptoms such as erythroderma, fever, liver dysfunction, diarrhea and pancytopenia. It is speculated that transfused blood donors' lymphocytes might recognize the recipients' HLAs as alloantigens. The thus stimulated lymphocytes might proliferate, expand and finally attack the host's immune system or tissues. However, details regarding these expanded donor cells such as: (1) whether they represent one clone or more, (2) the composition of lymphocyte subsets, and (3) the target HLA antigens of recipients, are not clear, since T‐cell lines derived from PTGVHD patients have not yet been obtained. The aim of this study is to characterize T‐cells responsible for PTGVHD and to identify their target molecules. For that purpose, we attempted to establish T‐cell lines derived from a PTGVHD patient. We show that the established T‐cell line, proven to be derived from donor lymphocytes, showed a CD4+ phenotype and had cytotoxic activities. Furthermore, we describe that the target of the cytotoxic T‐cell line (CTL) is an HLA‐DRBl*0405‐related molecule of the patient.
Evidence that the Gya, Hy and JoaAntigens Belong to the Dombrock Blood Group System
Authors: Banks J.A. , Hemming N. , Poole J.
Published: March 2009

Ten red cell samples lacking the high incidence Gyaantigen were found to have the previously undescribed Do(a‐b‐) phenotype. Fifteen Hy‐ red cell samples were Do(a‐b+) with weak expression of Doband 6 Jo(a‐) red cell samples were Do(a+) with weak expression of Doa. Five of the 6 Jo(a‐) samples had extremely weak expression of Dob. The sixth Jo(a‐) was Do(b‐). Immune precipitates were prepared from radio‐iodinated antigen‐positive red cells with anti‐Gya, ‐Hy, ‐Doaand Dob. Immunoblotting of these immune precipitates with affinity‐purified anti‐Gyaand anti‐Dobunder non‐reducing conditions revealed similar broadly migrating bands of Mr 48,700–59,750, suggesting that the Doaand Dobantigens are carried on the same glycoprotein as Gyaand Hy. The phenotypically associated high incidence Joaantigen has previously been shown to reside on the Gya/ Hy glycoprotein. Enzyme‐treated and chemically modified red cells tested with anti‐Doa, ‐Dob, ‐Gya, ‐Hy and ‐Joagave the same pattern of reactivity. We propose that Gya, Hy and Joabecome part of the Dombrock blood group system and that, henceforth, the Gya/Hy‐active glycoprotein be renamed the Dombrock‐active glycoprotein. The Gy(a‐) Hy‐ Jo(a‐) phenotype constitutes the ‘null’ phenotype within the Dombrock system.
Audit and Education in Transfusion Medicine
Authors: Toy Pearl T.C.Y.
Published: March 2009

Because transfusions carry risks to the patient and because inappropriate transfusions are costly, interest in audits and effective education in transfusion medicine has increased over the last decade. Audits identify areas of practice that can be improved by follow‐up education of the physicians who prescribe the transfusions. Successful educational approaches to follow‐up on problems identified by audit include 30‐min one‐on‐one meetings with surgeons, traditional scheduled teaching conferences, daily clinical rounds on transfused patients, prospective review of blood transfusions and installation of transfusion practice algorithms in the operating room. Other than identifying inappropriate transfusions, audit and education have also been used successfully to improve bedside blood administration practices, decrease unnecessary crossmatches and reduce outdating of donor blood. Multi‐institutional audits play a useful benchmarking role. In summary, audit followed by targeted education can improve practices in transfusion medicine.
A Second Nonsecretor Allele of the Blood Group α(1,2)Fucosyl‐transferase Gene (FUT2)
Authors: Henry Stephen , Mollicone Rosella , Lowe John B. , Samuelsson Bo , Larson Göran
Published: March 2009

While screening Le(a+b+) Polynesian DN A samples for a candidate Sew allele, a point mutation (C571→T) resulting in a new stop codon (Arg191→stop) in the α(1,2)fucosyltransferase gene (FUT2) was identified. This point mutation resulted in the gaining of a new restriction enzyme cleavage site (DdeI), which allowed restriction enzyme cleavage screening of 40 selected Polynesians and 42 random Caucasians. The nonsecretor phenotype in two of the three nonsecretor Polynesians analyzed was due to homozygosity for the ‘new’ mutation, whereas the third Polynesian nonsecretor (with Caucasian ancestors) was due to homozygosity of the ‘old’ (Trp143→stop) mutation. The nonsecretor phenotype in all Caucasians analyzed was a consequence of homozygosity for the ‘old’ mutation. Both the new and the old nonsecretor mutations were identified in the heterozygous state in some secretor‐positive Polynesians, while only the old mutation was found in the heterozygous state in Caucasians of the same phenotype.
Why Prescribe Highly Purified Factor VIII and IX Concentrates?
Authors: Berntorp Erik
Published: March 2009

The aftermath of the HIV catastrophe and hepatitis virus transmission to hemophiliacs has been characterized by continuous efforts to improve the purity of factor VIII and factor IX concentrates, increasing sophistication of the virucidal methods used, and the introduction of recombinant factor VIII. The cost of hemophilia care is substantial and there is a large price difference between products depending on their purity; generally, the purer the concentrate, the higher the price. The use of expensive highly purified concentrates may be questioned if these products are not superior in terms of safety, efficacy or convenience. The properties of concentrates used in hemophilia care are discussed in this review, as are their safety and side effects. The available data do not clearly reveal any clinical difference between factor VIII concentrates, although the highly purified products may be of theoretical benefit. With regard to factor IX, purified products do not seem to carry any risk of the well‐known thromboembolic complications which occur in certain situations after treatment with prothrombin complex concentrates.
Evaluation of Platelet Function Using the in vitro Bleeding Time and Corrected Count Increment of Transfused Platelets: Comparison between Platelet Concentrates Derived from Pooled Buffy Coates and Apheresis
Authors: Eriksson L. , Kristensen J. , Olsson K. , Bring J. , Högman C. F.
Published: March 2009

The functional capacity of transfused platelets was evaluated with in vitro bleeding time (IVBT) and corrected count increment (CCI) in order to compare platelet concentrates (PCs) derived from pooled buffy coats (BC‐PCs) with PCs collected by apheresis (A‐PCs). The suspension medium in the BC‐PCs was 30% CPD plasma and 70% of an additive solution (containing sodium and potassium chloride, sodium citrate and phosphate, mannitol), and in the A‐PCs the medium was 100% CPD plasma. IVBT was evaluated using a Thrombostat 4000/2. BC‐PC and A‐PC were transfused 57 and 41 times, respectively to 36 patients with chemotherapy‐induced thrombocytopenia. PCs transfused within 2 days of donation were considered fresh, and those transfused within 3–5 days were considered stored. IVBT was determined before, as well as 10–30 min and 24 h after transfusion; CCI was determined 10–30 min and 24 h after transfusion. The median pretransfusion IVBT value was 486 s. It was measurable in 21 of 98 (21%) of the transfusions, i.e. below the cutoff limit of 486 s. Ten to 30 min after transfusion, the IVBT showed a measurable reduction in 90% of the transfusions with fresh BC‐PCs, 92% of those with fresh A‐PCs, 63% of those with stored BC‐PCs and 79% of those with stored A‐PCs. After 24 h, the corresponding values were 63% for fresh BC‐PCs, 50% for fresh A‐PCs, 26% for stored BC‐PCs and 38% for stored A‐PCs. The median value of CCI 10–30 min after transfusion was 20 for fresh BC‐PCs, 17 for fresh A‐PCs, 16 for stored BC‐PCs and 14 for stored A‐PCs. The difference in IVBT between fresh and stored BC‐PCs was significant (p = 0. 032), unlike that between fresh and stored A‐PC. After 24 h the corresponding values were 7 for fresh BC‐PCs, 4 for fresh A‐PCs, 4 for stored BC‐PCs and 3 for stored A‐PCs. When all transfusions with fresh PCs (BC‐PCs+A‐PCs) were compared with all transfusions with stored PCs, a statistical difference was demonstrated in both CCI (p = 0.027) and IVBT (p = 0.043). Spearman's rank correlation coefficient (rs) was ‐0.41 between CCI and IVBT486 s 10–30 min after transfusion, and 4.55 between the posttransfusion plateled count and IVBT, indicating a relatively poor correlation between CCI and IVBT, and a slightly better correlation between platelet count and IVBT. In conclusion, BC‐PCs showed a slightly higher CCI and a better response in IVBT than A‐PCs. No statistical difference was demonstrated between BC‐PCs and A‐PCs transfused within 2 days after donation, with respect to function and recovery in vivo. BC‐PCs stored for 3 days or more showed about the same CCI and IVBT as stored A‐PC but significantly lower CCI and higher IVBT than fresh BC‐PCs. This may indicate that the preparation and/or storage conditions were not optimal. IVBT seems to be a useful possibility to test the in vivo behavior of transfused platelets.
Inheritance of Abnormal Glycophorin C of the Gerbich and Yussef Type in a French Family
Authors: Loirat M.J. , Pineau‐Vincent F. , Schiffer C. , Muller J. Y. , Blanchard D.
Published: March 2009

The discovery of a natural Gerbich antigen (anti‐Ge2) in the serum of a propositus prompted us to study his red blood cells (RBCs) by using monoclonal antibodies (mAbs) directed against glycophorin (GP) C and GPD. An mAb directed against the Ge4 antigen (mAb NaM10‐7G11) agglutinated both untreated and trypsin‐treated cells, demonstrating the expression of a trypsin‐resistant GPC (namely, GPC of the Gerbich type: GPCGe). Surprisingly, an anti‐Ge3 antibody (mAb NaM19‐3C4) agglutinated untreated cells, showing that they also express the Ge3 antigen that may be carried by normal GPC and CPD or by the abnormal GPC of the Yussef (Yus) type (GPCYus). Immunoblotting analysis performed with an mAb directed against the C‐terminal portion of GPC showed that the propositus' RBCs do not contain normal GPC and GPD but both GPCGe and GPCYus. Analysis of RBCs from the family demonstrated that, like the propositus, 2 of the 3 sisters had inherited both the GYPCGe and the GYPCYus alleles from the parents, who carried either the GYPCGe or the GYPC Yus allele. The third sister had inherited the normal GYPC alleles from her parents, whereas the child of the propositus had inherited the GYPCGe allele. Interestingly, natural anti‐Ge2 antibodies were identified in the serum of 2 of the 3 Ge‐negative individuals.
DNA Sequencing and Screening for Point Mutations in the Human Lewis (FUT3) Gene Enables Molecular Genotyping of the Human Lewis Blood Group System
Authors: Elmgren Anders , Börjeson Cecilia , Svensson Lola , Rydberg Lennart , Larson Göran
Published: March 2009

The human Lewis gene encodes an α(1,3/1,4)‐fucosyltransferase responsible for synthesis of the Lea and Leb antigens. To define the molecular background for non‐functional Lewis genes we have sequenced PCR‐amplified DNA fragments from two Le(a‐b‐) individuals. One was homozygously mutated at nucleotides 202 (T→C) and 314 (C→T), altering Trp68 to Arg and Thrl05 to Met, and the other was homozygously mutated at nucleotides 59 (T→G) and 1067 (T→A), altering Leu20 to Arg and Ile356 to Lys. Using PCR we screened for these and additionally one other mutation atnucleotide 508 (G→A) among 40 Caucasians. Of 15 Le(a‐b‐) individuals, 7 typed as le59/1067 le202/314, 4 as le202/314le202/314 and 1 as le59/10671e59/1067. Of 21 Le(a‐b+) and 4 Le(a+b‐), 17 typed as LeLeand 7 as Lele202/314. A pedigree study of 8 Lewis‐positive individuals showed that the mutations at nucleotides 202 and 314 were located on the same allele.
Selection of Monoclonal Antibodies for the Identification of D Variants: Ability to Detect Weak D and to Split epD2, epD5 and epD6/7
Authors: Jones Jefl , Filbey Derek
Published: March 2009

Red cells from known D variant donors were tested with 41 monoclonal anti‐D reagents, 26 IgG and 15 IgM, with the view to selecting a panel to aid the identification of unusual D types. These antibodies gave reaction patterns which allowed the identification of most of the known D category cells, recognizing epD2, epD5, epD6/7, epD8 and epD9, but were unable to distinguish category III from normal D‐positive cells. Reactivity with HMi, HMii, DFR, DBT and RoHar cells split epD2, epD5 and epD6/7 into two, three and eight groups, respectively. A panel comprising 15 monoclonal anti‐D, 11 IgG and four IgM, was selected as representative of the antibodies tested. Reactivity of monoclonal anti‐D was dependent on antibody concentration and antibody avidity. An antibody concentration of at least 12 pg/ml was required for optimum reactivity of the two monoclonal antibodies tested. A simple calculation of division of the titre by the antibody concentration provided a relatively simple means of establishing the reactivity performance of the antibody and correlated well with ability to detect weak D (Du) cells. A characteristic variable reduction in reaction strength with all the IgG anti‐D was observed with weak D cells. The IgM antibodies, except the high avidity RUM‐1, T3D2T6, D9A4 and BS226, performed poorly in detecting weak D. The majority of the IgM antibodies tested reacted with RoHarr cells, while only one IgG antibody was positive.
The Impact of Neocyte Transfusion in the Management of Thalassaemia
Authors: Spanos Theodore , Ladis Vassilis , Palamidou Fany , Papassotiriou Ioannis , Banagi Anastasia , Premetis Evangelos , Kattamis Christos
Published: March 2009

Transfusional iron overload leading to cardiopathy and other severe complications continues to be a major problem in chronically transfused homozygous β‐thalassaemia patients. It is well known that young red cells (neocytes) survive longer after transfusion and therefore may contribute to the extension of the intervals between transfusions. We evaluated the impact of neocytes in the total annual blood requirements and consequently the transfusional iron load in 18 thalassaemia patients. A two‐period study comparing transfusions of standard red cells versus neocytes in the same group of patients was performed. Neocytes were harvested by density separation using the Neocel®System. The method of preparation was simple with relatively low costs and required no special equipment. There was a significant difference (p <0.005) in PK and MCV values of the neocyte and older red cell (gerocyte) fractions indicating that a good separation of the two populations was achieved. All patients had a reduction in blood requirements during the neocyte period. The total annually transfused red blood cells and concomitant iron blood load were significantly reduced (p <0.001) by 20.2±9.1%. However, the response was variable. Seven of the 18 patients had a large reduction in blood consumption (24.8–34.8%), 9 others ranged between 10.7 and 21.6%, and in 2 the reduction was less than 10%. This reduction in blood requirements and in the transfused iron may change the chelation index resulting in more efficient iron chelation therapy and perhaps reduce the cost of the haemochromatosis therapy on a long‐term basis. We conclude that the use of neocyte therapy using this system can benefit the majority of chronically transfused patients by reducing transfusional iron overload and related complications and may lead to a much better quality of life.
Psychiatry, mental health nurses, and invisible power: Exploring a perturbed relationship within contemporary mental health care
Authors: Cutcliffe John , Happell Brenda
Published: March 2009

Interpersonal relationships, although considered to be the cornerstone of therapeutic engagement, are replete with issues of power; yet, the concept of ‘invisible power’ within such formal mental health care relationships is seldom explored and/or critiqued in the literature. This paper involves an examination of power in the interpersonal relationship between the mental health nurse and the consumer. Issues of power are emphasized by drawing on examples from clinical experiences, each of which is then deconstructed as an analytical means to uncover the different layers of power. This examination highlights the existence of both obscure and seldomly acknowledged invisible manifestations of power that are inherent in psychiatry and interpersonal mental health nursing. It also identifies that there is an orthodoxy of formal mental health care that perhaps is best described as ‘biopsychiatry’ (or ‘traditional psychiatry’). Within this are numerous serious speech acts and these provide the power for mental health practitioners to act in particular ways, to exercise control. The authors challenge this convention as the only viable discourse: a potentially viable alternative to the current of formal mental health care does exist and, most importantly, this alternative is less tied to the use of invisible power.
Long‐term homelessness in men with a psychosis: Limitation of services
Authors: Burns Adam , Robins Alan , Hodge Mark , Holmes Alex
Published: March 2009

A proportion of persistently homeless men with psychosis are unable to function in the community, despite intensive outreach. The present study aimed to (i) develop a method to measure the number of homeless clients with a psychosis who are unable to maintain basic levels of function, despite the application of intensive community treatment; and (ii) determine if the proportion of these men had increased in an Australian inner urban setting over a 5‐year period. Criteria were developed and validated to define this group. A review of records of clients engaged in homeless settings was conducted in order to compare the proportion of men with these features in 2000 and 2005. In 2005, 23% met the criterion of long‐term homelessness with poor function, despite intensive outreach, as compared with 17% in 2000 (P = 0.62). The 2005 cohort was more likely to have attempted intensive community psychiatric treatment (P = 0.04). We conclude that a proportion of homeless men with a psychosis in Australia do not achieve basic function, despite access to intensive outreach. The proportion of these men did not change between 2000 and 2005. These men require additional specialized services, including access to long‐term supported housing.
A putative role for cell cycle‐related proteins in microtubule‐based neuroplasticity
Authors: Schmetsdorf Stefanie , Arnold Erik , Holzer Max , Arendt Thomas , Gärtner Ulrich
Published: March 2009

Cyclins and cyclin‐dependent kinases (Cdks) are the main components that control the orderly progression through cell cycle. In the mature nervous system, terminally differentiated neurons are permanently withdrawn from cell cycle, as mitotic quiescence is essential for the functional stability of the complexly wired neuronal system. Recently, we characterized the expression and colocalization of cyclins and Cdks in terminally differentiated pyramidal neurons. The functional impact of the expression of cell cycle‐related proteins in differentiated neurons, however, has not been elucidated yet. In the present study, we show by immunoelectron microscopy and immunobiochemical methods an association of cyclins and Cdks with the microtubule network. Cyclins D, E, A and B as well as Cdks 1, 2 and 4 were also found to be associated with the microtubule‐associated protein tau. Cyclin/Cdk complexes, in addition, exhibit kinase activity towards tau. In vitro, downregulation of cyclins and Cdks by a siRNA approach and by pharmacological inhibition promotes neurite extension. Taken together, these results indicate that the expression of cell cycle‐related proteins in terminal differentiated neurons is associated with physiological functions beyond cell cycle control that might be involved in microtubule‐based mechanisms of neuroplasticity.
17β‐estradiol and enriched environment accelerate cognitive recovery after focal brain ischemia
Authors: Söderström Ingegerd , Strand Magnus , Ingridsson Anna‐Cajsa , Nasic Salmir , Olsson Tommy
Published: March 2009

Cognitive impairments, including spatial memory and learning deficiencies, are common after ischemic stroke. Estrogen substitution improves cognitive functions in post‐menopausal women and ovariectomized rodents, partially through induction of neuroplasticity in the hippocampal formation. Post‐ischemic housing of male rats in an enriched environment (EE) improves functional outcome, without changing infarct volume. We hypothesized that 17β‐estradiol combined with an EE would accelerate cognitive recovery after focal brain ischemia in ovariectomized rats and that recovery would be related to altered expression of nerve growth factor‐induced gene (NGFI)‐A in the hippocampus. 17β‐estradiol or placebo pellets were implanted 6 h after transient middle cerebral artery occlusion. Two days later, rats were placed in an EE or a deprived environment (DE) for 6 weeks. At 5 weeks after middle cerebral artery occlusion, 17β‐estradiol‐treated rats housed in an EE showed improvements in cognitive function (i.e. shorter latency and path in the Morris water maze task) compared with placebo‐treated animals housed in an EE. Furthermore, beneficial effects on latency and path were observed when comparing EE‐housed vs. DE‐housed 17β‐estradiol‐treated rats. When comparing 17β‐estradiol‐treated EE‐housed rats vs. placebo‐treated DE‐housed rats, pronounced effects on latency and path were observed. Infarct volumes did not differ between groups. 17β‐estradiol‐treated EE‐housed rats had significantly higher NGFI‐A mRNA expression bilaterally in the cornu ammonis 1 region and in the ipsilateral dentate gyrus of the hippocampus, compared with placebo‐treated EE‐housed rats. In conclusion, 17β‐estradiol treatment combined with an EE improved recovery of cognitive function after experimental brain ischemia, putatively through the upregulation of NGFI‐A in hippocampal subregions.
Rapid plasticity at inhibitory and excitatory synapses in the hippocampus induced by ictal epileptiform discharges
Authors: Lopantsev Valeri , Both Martin , Draguhn Andreas
Published: March 2009

Epileptic seizures can induce pathological processes of plasticity in the brain that tend to promote the generation of further seizures. However, the immediate impact of epileptic seizures on cellular excitability remains poorly understood. In order to unravel such early mechanisms of epilepsy‐induced plasticity, we studied synaptic transmission before and shortly after three ictal discharges induced by transient elevation of extracellular K+ in mouse hippocampal slices. Discharges were initiated in the CA3 region and propagated via the Schaffer collaterals into CA1 where they were associated with sustained membrane depolarization and bursts of action potentials in CA1 pyramidal cells. Subsequently, discharges were followed by long‐term potentiation (LTP) of Schaffer collateral‐evoked field excitatory post‐synaptic potentials (EPSPs) in the CA1. The ability to generate epileptiform activity in response to repetitive stimulation was enhanced during LTP. Changes in both inhibitory and excitatory synaptic transmission contributed to LTP in CA1 pyramidal cells. Discharges reduced γ‐aminobutyric acid‐A receptor‐mediated hyperpolarizing inhibitory post‐synaptic potentials by shifting their reversal potentials in a positive direction. At the same time, the amplitudes of Schaffer collateral‐evoked RS‐α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor‐mediated EPSPs and action potential‐independent miniature EPSPs were enhanced. However, N‐methyl‐d‐aspartate receptor‐mediated EPSPs remained unchanged. Paired‐pulse stimulation revealed a reduced probability of glutamate release. Together, these changes in synaptic transmission produce a sustained increase in hippocampal excitability. We conclude that a few seizure‐like ictal episodes are sufficient to cause fast and lasting changes in the excitation/inhibition balance in hippocampal networks, and therefore may contribute to early phases of progressive epileptogenesis.
Examination of intravenous and intra‐CSF protein delivery for treatment of neurological disease
Authors: Hemsley Kim M. , Luck Amanda J. , Crawley Allison C. , Hassiotis Sofia , Beard Helen , King Barbara , Rozek Tomas , Rozaklis Tina , Fuller Maria , Hopwood John J.
Published: March 2009

Mucopolysaccharidosis type IIIA is a neurodegenerative lysosomal storage disorder characterized by progressive loss of learned skills, sleep disturbance and behavioural problems. Absent or greatly reduced activity of sulphamidase, a lysosomal protein, results in intracellular accumulation of heparan sulphate. Subsequent neuroinflammation and neurodegeneration typify this and many other lysosomal storage disorders. We propose that intra‐cerebrospinal fluid protein delivery represents a potential therapeutic avenue for treatment of this and other neurodegenerative conditions; however, technical restraints restrict examination of its use prior to adulthood in mice. We have used a naturally‐occurring Mucopolysaccharidosis type IIIA mouse model to determine the effectiveness of combining intravenous protein replacement (1 mg/kg) from birth to 6 weeks of age with intra‐cerebrospinal fluid sulphamidase delivery (100 μg, fortnightly from 6 weeks) on behaviour, the level of heparan sulphate‐oligosaccharide storage and other neuropathology. Mice receiving combination treatment exhibited similar clinical improvement and reduction in heparan sulphate storage to those only receiving intra‐cerebrospinal fluid enzyme. Reductions in micro‐ and astrogliosis and delayed development of ubiquitin‐positive lesions were seen in both groups. A third group of intravenous‐only treated mice did not exhibit clinical or neuropathological improvements. Intra‐cerebrospinal fluid injection of sulphamidase effectively, but dose‐dependently, treats neurological pathology in Mucopolysaccharidosis type IIIA, even when treatment begins in mice with established disease.
Oculomotor control in children with fetal alcohol spectrum disorders assessed using a mobile eye‐tracking laboratory
Authors: Green C. R. , Mihic A. M. , Brien D. C. , Armstrong I. T. , Nikkel S. M. , Stade B. C. , Rasmussen C. , Munoz D. P. , Reynolds J. N.
Published: March 2009

Prenatal exposure to alcohol can result in a spectrum of adverse developmental outcomes, collectively termed fetal alcohol spectrum disorders (FASDs). This study evaluated deficits in sensory, motor and cognitive processing in children with FASD that can be identified using eye movement testing. Our study group was composed of 89 children aged 8–15 years with a diagnosis within the FASD spectrum [i.e. fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), and alcohol‐related neurodevelopmental disorder (ARND)], and 92 controls. Subjects looked either towards (prosaccade) or away from (antisaccade) a peripheral target that appeared on a computer monitor, and eye movements were recorded with a mobile, video‐based eye tracker. We hypothesized that: (i) differences in the magnitude of deficits in eye movement control exist across the three diagnostic subgroups; and (ii) children with FASD display a developmental delay in oculomotor control. Children with FASD had increased saccadic reaction times (SRTs), increased intra‐subject variability in SRTs, and increased direction errors in both the prosaccade and antisaccade tasks. Although development was associated with improvements across tasks, children with FASD failed to achieve age‐matched control levels of performance at any of the ages tested. Moreover, children with ARND had faster SRTs and made fewer direction errors in the antisaccade task than children with pFAS or FAS, although all subgroups were different from controls. Our results demonstrate that eye tracking can be used as an objective measure of brain injury in FASD, revealing behavioral deficits in all three diagnostic subgroups independent of facial dysmorphology.
Tolerance to non‐opioid analgesics in PAG involves unresponsiveness of medullary pain‐modulating neurons in male rats
Authors: Tortorici Victor , Aponte Yexica , Acevedo Humberto , Nogueira Lourdes , Vanegas Horacio
Published: March 2009

Opiate analgesia can be hampered by a reduction in pharmacological effectiveness (tolerance), and this crucially depends on the periaqueductal gray matter (PAG). Non‐opioids like metamizol (dipyrone) or aspirin also induce PAG‐dependent analgesia and tolerance, but the neuronal bases of this tolerance are unknown. Metamizol is a pyrazolon derivative and cyclooxygenase inhibitor with widespread use as an analgesic in Europe and Latin America. Metamizol was microinjected into the PAG of awake male rats, and antinociception was assessed by the tail flick (TF) and hot plate (HP) tests. Microinjection twice daily for 2.5 days caused tolerance to metamizol. The rats were then anesthetized and recordings from pain‐facilitating on‐cells and pain‐inhibiting off‐cells of the rostral ventromedial medulla (RVM) were performed. PAG microinjection of morphine or metamizol depresses on‐cells, activates off‐cells and thus inhibits nociception, including TF and HP. In metamizol‐tolerant rats, however, PAG microinjection of metamizol failed to affect on‐ or off‐cells, and this is interpreted as the reason for tolerance. In metamizol‐tolerant rats morphine microinjection into PAG also failed to affect RVM neurons or nociception (cross‐tolerance). In naïve, non‐tolerant rats the antinociceptive effect of PAG‐microinjected metamizol or morphine was blocked when CTOP, a μ‐opioid antagonist, was previously microinjected into the same PAG site. These results emphasize a close relationship between opioid and non‐opioid analgesic mechanisms in the PAG and show that, like morphine, tolerance to metamizol involves a failure of on‐ and off‐cells to, respectively, disfacilitate and inhibit nociception. Cross‐tolerance between non‐opioid and opioid analgesics should be important in the clinical setting.
Light stimulation evokes two different calcium responses in Müller glial cells of the guinea pig retina
Authors: Rillich Katja , Gentsch Janina , Reichenbach Andreas , Bringmann Andreas , Weick Michael
Published: March 2009

Intracellular calcium responses are a characteristic of glial activation upon neuronal activity. In acutely isolated preparations of the guinea pig retina, Müller glial cells displayed cytosolic calcium rises in response to repetitive light stimulation. The calcium rises consisted of two components, a slowly developing immediate response that occurred simultaneously over the whole length of all Müller cell fibers and a delayed fast response that originated in the ganglion cell layer and spread as a wave through the bodies of some Müller cells toward the outer processes in the photoreceptor layer. The slow calcium response was evoked by photoreceptor‐to‐glia signaling, resulting in a glutamate transporter‐ and zinc‐mediated alteration in the membrane potential and an influx of calcium from the extracellular space. The fast calcium response was evoked by a release of calcium from intracellular stores, probably after activation of purinergic receptors. The data suggest that light stimulation of the retina causes glial activation by alterations in both the membrane potential and receptor‐mediated mechanisms. The former may be implicated in glial support of the neuronal signal transfer from photoreceptors to ganglion cells (glial forward signaling), whereas the latter may constitute a glial feedback signaling from ganglion cells to photoreceptors.
Increased vascular endothelial growth factor expression in patients with bladder pain syndrome/interstitial cystitis: its association with pain severity and glomerulations
Authors: Kiuchi Hiroshi , Tsujimura Akira , Takao Tetsuya , Yamamoto Keisuke , Nakayama Jiro , Miyagawa Yasushi , Nonomura Norio , Takeyama Masami , Okuyama Akihiko
Published: March 2009

OBJECTIVE

To determine the angiogenic profiles in the bladder of patients with bladder pain syndrome (BPS)/interstitial cystitis (IC), and to evaluate the relationship between these profiles and associated clinical features including pelvic pain and glomerulations.

PATIENTS AND METHODS

Angiogenesis and angiogenic components are important in chronic inflammatory disease. High levels of vascular endothelial growth factor (VEGF) have been shown to induce immature angiogenesis, where microvessels have insufficient coverage of pericytes, resulting in haemorrhagic vessels. Biopsy specimens from 30 patients with BPS/IC and glomerulations, and 10 control patients, were examined immunohistochemically for VEGF expression, microvessel density (MVD) and immature microvessels. Pericyte coverage of microvessels in the specimens was used as an indicator of mature microvessels, and pericytes were identified by double‐immunohistochemistry for CD34 and α‐smooth muscle actin. The microvessel pericyte coverage index (MPI) was calculated as the ratio of mature vessels to total vessels. We also assessed the relationship between these angiogenic profiles and associated clinical features including pain and glomerulations.

RESULTS

VEGF expression in the lamina propria was significantly higher in BPS/IC than in control samples (50% vs 10%, P < 0.05). Among patients with BPS/IC, VEGF expression was significantly higher in those with severe pain than in those with mild pain (78% vs 38%, P < 0.05). The MPI was significantly lower in BPS/IC than in control samples (23% vs 35%, P < 0.05), whereas MVD did not differ significantly between BPS/IC and control samples.

CONCLUSIONS

There is increased VEGF and immature vascularization in patients with BPS/IC, and VEGF expression is associated with the degree of pain described by patients. Taken together, VEGF might contribute to pain and promote the formation of immature vessels in BPS/IC, and the increased immature vascularization might have a role in glomerulations in patients with BPS/IC.
Open radical retropubic prostatectomy gives favourable surgical and functional outcomes after transurethral resection of the prostate
Authors: Palisaar Jüri R. , Wenske Sven , Sommerer Florian , Hinkel Andreas , Noldus Joachim
Published: March 2009

OBJECTIVES

To assess the peri‐ and postoperative outcome of patients treated with open radical retropubic prostatectomy (RRP) for prostate cancer and who had previously undergone transurethral resection of the prostate (TURP).

PATIENTS AND METHODS

Prospectively collected data from a consecutive series of 1760 patients who had RRP between July 2003 and June 2007 at our institution were used to retrospectively match 62 cases (with previous TURP) with the same number of controls (without previous TURP). Matching variables were patient age, body mass index, prostate volume, preoperative total prostate‐specific antigen (PSA) level, Gleason score, pathological stage, and intraoperative nerve‐sparing procedure. Complete 1‐year follow‐up data were available for all patients. All collected data on surgery and perioperative complications were analysed. Functional outcome data at the 1‐year follow‐up were evaluated by applying an institutional questionnaire. Sexual function was assessed using the abbreviated International Index of Erectile Function‐5 questionnaire, and urinary control was evaluated by defining complete urinary control as no pad usage.

RESULTS

The rate of complete urinary control rate in cases and controls was similar (81% vs 82%). When nerves were spared, 60% (15/25) of patients in either group were capable of sexual intercourse. The overall positive surgical margin rate was insignificantly higher in cases (19% vs 13, P > 0.05). After 1 year of follow‐up the biochemical recurrence rate (PSA >0.04 ng/mL) did not differ significantly in patients who had RRP after TURP vs RRP alone (six of 62, 10%, vs five of 62, 8%; P = 0.77).

CONCLUSIONS

RRP for prostate cancer in patients who have had previous TURP does not result in a higher perioperative complication rate, or a worse functional outcome.
Adiponectin: from obesity to cardiovascular disease
Authors: Antoniades C. , Antonopoulos A. S. , Tousoulis D. , Stefanadis C.
Published: March 2009

Adiponectin is an adipokine whose biosynthesis is deranged in obesity and diabetes mellitus, predisposing to atherosclerosis. Evidence suggests that adiponectin has anti‐atherogenic properties by improving endothelial function and having anti‐inflammatory effects in the vascular wall. In addition, adiponectin modifies vascular intracellular redox signalling and exerts indirect antioxidant effects on human myocardium. However, its clinical role in cardiovascular disease is obscure. Adiponectin's positive prognostic value in coronary artery disease had been widely supported over the last years, but this view has been questioned recently. High adiponectin levels are paradoxically associated with poorer prognosis in heart failure syndrome. These controversial findings seem surprising as adiponectin has been viewed overall as an anti‐atherogenic molecule. Therefore, any certain conclusion about adiponectin's role in cardiovascular disease seems premature. Despite the rapidly accumulating literature on this adipokine, it is still unclear whether adiponectin is a key mediator or a bystander in cardiovascular disease. It is still uncertain whether adiponectin levels have any clinical significance for risk stratification in cardiovascular disease or they just reflect the activation of complex and opposing underlying mechanisms. Circulating adiponectin levels should be interpreted with caution, as they may have completely different prognostic value, depending on the underlying disease state.
Prevalence of obesity among children aged 6–7 years in South‐East Serbia
Authors: Stojanovic D. , Belojevic G.
Published: March 2009

A cross‐sectional study of the prevalence of obesity in urban and rural areas of South‐East Serbia was performed on 541 children (273 boys and 268 girls), aged 6–7 years. Prevalence of obesity in urban boys and girls was 6.3% and 3.8% respectively (P > 0.05). Prevalence of obesity in rural boys and girls was 1.1% and 3.3% respectively (P > 0.05). The difference in the prevalence of obesity between urban boys and rural boys was statistically significant (P < 0.05), while the difference between urban and rural girls was insignificant (P > 0.05). Urban boys consumed more sweets and fast food compared with rural boys (P < 0.05). Urban children spent more time in watching TV compared with rural children (P < 0.05).
Competition Effects of Supermarket Services
Authors: Bonanno Alessandro , Lopez Rigoberto A.
Published: March 2009

This article investigates the competition effects of supermarket services using fluid milk as a case study. A simultaneous equation model for services and price competition is estimated with scanner data from fifteen supermarket chains using two alternative measures of services, namely store size and principal components of in‐store services. Empirical results show that increasing services results in economies of scope, greater supermarket chain‐level demand, lower price elasticity of demand, and enhanced market power, leading to higher milk prices and quantity sold. We conclude that, as result of service competition, supermarkets differentiate themselves from competitors and successfully attract less price‐sensitive consumers.
Reducing the Compliance Burden of Non‐profit Organisations: Cutting Red Tape
Authors: McGregor‐Lowndes Myles , Ryan Christine
Published: March 2009

Australian governments now rely on the non‐profit sector to provide essential services. Yet, anecdotally, the compliance burden imposed by governments consumes scarce service delivery resources. This study quantifies the cost of government generated paperwork for Queensland non‐profit organisations. Fourteen non‐profits kept logs to record government paperwork over 12 months. The non‐profits also provided their experiences of government paperwork and in particular grant submission and reporting processes. The study finds that government grant paperwork forms the bulk of a non‐profits total paperwork burden with grant submissions being the most costly to complete. Costs are clearly regressive with small non‐profits bearing a significantly higher burden. Governments need to lead the way and empower the non‐profit sector by reducing this administrative burden and releasing the funds for direct service provision.
Healthy Country, Healthy People: Policy Implications of Links between Indigenous Human Health and Environmental Condition in Tropical Australia
Authors: Garnett Stephen T. , Sithole Bev , Whitehead Peter J. , Burgess C. Paul , Johnston Fay H. , Lea Tess
Published: March 2009

Investment in programs that help Indigenous people undertake work maintaining the environmental health of their country has benefits for the environment as well as the physical, mental and cultural health of the Indigenous people involved. For health these findings have direct implications for some national health policies, service provision to homelands, health promotion and Indigenous health research. There are also direct implications for environmental investment in northern Australia and the design and regulation of markets in resource entitlements. Indirectly the findings should be important for economic, employment and education policies as well as those promoting social harmony. Given the range of benefits there is a strong argument for cross‐agency investment in working on country by Indigenous people.