bluuebunny/crossref_metadata_2025 huggingface dataset:
Chimaeric cultures of human marrow stroma and murine leukaemia cells: evidence for abnormalities in the haemopoietic microenvironment in myeloid malignancies and other infiltrating marrow disorders
Authors: DUHRSEN ULRICH , KNIELING GABRIELE , BEECKEN WOLF , NEUMANN STEFAN , HOSSFELD DIETER KURT
Published: March 2008

Summary. PGM‐1 is a transplantable C3H/HeJ leukaemia which is not viable in unstimulated in vitro culture, differentiates into mature granulocytes and macrophages in response to soluble cytokines, and undergoes self‐renewing cell divisions in coculture with selected human bone marrow stromal cell lines. When PGM‐1 cells were cultured on pre‐established adherent layers from primary human marrow samples, their fate depended on the source of the human marrow. Adherent layers from healthy marrow donors or patients with reactive marrow alterations had no or very little capacity to maintain PGM‐1 cells in an immature colony‐forming state. However, in coculture with adherent layers from patients with myeloid leukaemia or, to a lesser extent, lymphoblastic leukaemia or marrow‐infiltrating lymphoma the colony‐forming potential was retained. There was no correlation between the remission status of the patient and the PGM‐1 activity of the adherent layer. Consistent morphological differences between active and inactive stromal layers were not observed.

The PGM‐1 coculture system enables the detection of a hitherto undescribed regulatory abnormality in bone marrow malignancies. Whether the PGM‐1 supporting activity is mediated through differences in the production of a cytokine with close homology to complement factor Bb which has recently been shown to induce self‐renewal in immature PGM‐1 cells, requires further investigation.
IL‐3 is produced by normal stroma in leng‐term bone marrow cultures
Authors: GIBSON F. M. , SCOPES J. , DALY S. , RIZZO S. , BALL S. E. , GORDON‐SMITH E. C.
Published: March 2008

Summary. Interleukin‐3 (IL‐3) has been shown to have significant effects on haemopoiesis in vitro, but early investigations of normal human long‐term bone marrow cultures (LTBMC) have failed to demonstrate LL‐3 production by stromal cells, either by Northern blotting for mRNA, or assaying for bioactivity in culture supernatants. One recent report, using reverse transcription‐polymerase chain reaction (RT‐PCR), demonstrated IL‐3 expression in only one of eight cultures.

We have developed a sensitive bioassay for the detection of IL‐3 production from normal stroma in LTBMC. LTBMC were grown until confluent, irradiated, and stroma harvested by trypsinization to yield single‐cell suspensions. These cells were then cocultured with target bone marrow mononuclear cells (BMMC), or CD344 cells in clonogenic assays, either in the presence or absence of anti‐IL‐3 neutralizing antibodies. We have demonstrated IL‐3 production in 32β4 cases. In addition, by separating stroma from target cells using cell culture inserts, we have shown that direct stroma:stem cell contact is not necessary for colony growth, suggesting that LL‐3 diffuses into the supernatant. However, when supernatants from LTBMC were assayed by enzyme‐linked immunoassay (ELISA), no IL‐3 was detected. This suggests that IL‐3 is probably produced at low levels and has a short‐range interaction.

Stroma production of IL‐3 was confirmed by the detection by RT‐PCR of IL‐3 mRNA in 3β cases. The simultaneous detection of CD2 mRNA demonstrated that T cells are part of the bone marrow stroma. It is therefore possible and probably likely that these cells are the source of IL‐3.
Detection of β‐thalassaemia mutations using DNA heteroduplex generator molecules
Authors: SAVAGE DAVID A. , WOOD NIGEL A. P. , BIDWELL JEFFREY L. , FITCHES ALISON , OLD JOHN M. , HUI KAM M.
Published: March 2008

Summary. In this report we describe a rapid polymerase chain reaction (PCR) based method for the detection of β‐thalassaemia (β‐thal) mutations. This method is based on the visualization of unique DNA heteroduplex banding patterns, following non‐denaturing poly aery lamide gel electrophoresis, resulting from hybridization between mutant PCR products and synthetic DNA heteroduplex generator molecules. Using the Singaporean population, which consists of Chinese, Malay and Asian Indian ethnic groups, as a model, we have constructed and evaluated three DNA heteroduplex generator molecules for the detection of the common β‐thalassaemia mutations found in this population. The results show that these three molecules are capable of detecting approximately 95% of the mutations found in the Singaporean population. We propose that this technology may be applied as an alternative screening strategy for β‐thalassaemia mutations because it is technically simple, flexible, cost‐effective, and requires only minimal laboratory resources.
Diverse expression of cytosolic phospholipase A2, 5‐lipoxygenase and prostaglandin H synthase 2 in acute pre‐B‐lymphocytic leukaemia cells
Authors: FELTENMARK STINA , RUNARSSON GHDMUNDUR , LARSSON PONTUS , JAKOBSSON PER‐JOHAN , BJORKHOLM MAGNUS , CLAESSON HANS‐ERIK
Published: March 2008

Summary. Several lines of evidence suggest that phospho‐lipases A2, leukotrienes and prostaglandins play a role in the proliferation of haemopoietic cells. The expression of genes involved in the biosynthesis of leukotrienes and prostaglandins was investigated in peripheral B lymphoblasts, isolated from eight patients with acute pre‐B‐lymphocytic leukaemia (pre B‐ALL). RT‐PCR analysis demonstrated that four of the investigated pre‐B‐ALL clones expressed the gene coding for cytosolic phospholipase A2 (cPLA2), but not the gene coding for 5‐lipoxygenase. In contrast, the remaining four pre‐B‐ALL clones expressed 5‐lipoxygenase but not cPLA2, suggesting that the transcriptional regulation of these two genes are different and that their cellular functions are not linked to each other. The capacity of pre B‐ALL cells to produce LTB4 and to express the 5‐lipoxygenase protein, correlated with the expression of 5‐lipoxygenase mRNA. All pre‐B‐ALL clones expressed genes coding for 5‐lipoxygenase activating protein (FLAP), leukotriene A4 hydrolase and prostaglandin (PG)H synthase 1. Seven of the eight pre B‐ALL clones expressed PGH synthase 2. In comparison, normal tonsillar B cells did not express cPLA2 or PGH synthase 2.
Persistence of RARa‐PML fusion mRNA detected by reverse transcriptase polymerase chain reaction in patients in long‐term remission of acute promyelocytic leukaemia
Authors: TOBAL KHALID , SAUNDERS MELANIE J. , GREY MARK R. , LIU YIN JOHN A.
Published: March 2008

Summary. Acute promyelocytic leukaemia (APL) is characterized by t(15;17), which results in the formation of two chimaeric genes, PML‐RARa and RARa‐PML. PML‐RARa transcripts have been detected in all cases of APL whilst those of RARQ‐PML have been detected in only about 67% of cases. We have used reverse transcriptase polymerase chain reaction (RT‐PCR) to detect both fusion transcripts serially in 18 patients in remission of APL after chemotherapy and bone marrow transplantation. All patients were negative for PML‐RARa, whereas in six patients (remission 3‐9 years) RARa‐PML was consistently detected. Only one patient at remission showed the 5’breakpoint RARa‐PML, with the rest showing the 3’breakpoint 144 bp RARa‐PML. The level of sensitivity for detecting RARa‐PML was some 10‐fold higher than that for PML‐RARa.

Serial negative tests for PML‐RARa have been correlated with durable remissions, suggesting possible eradication of residual leukaemia in APL. Our results, however, show persistence of t(15;17) cells expressing RARa‐PML fusion mRNA in patients in long‐term remission of APL. They indicate that patients considered clinically‘cured’of APL still have molecular evidence of minimal residual disease and also provide further insight into the biology of acute myeloid leukaemia.
Cytogenetic study in multiple myeloma at diagnosis: comparison of two techniques
Authors: SMADJA NICOLE VERONIQUE , LOUVET CHRISTOPHE , ISNARD FRANCOISE , DUTEL JEAN‐LOUIS , GRANGE MARIE‐JOSE , VARETTE CHARLES , KRULIK MARCEL
Published: March 2008

Summary. Cytogenetic studies in multiple myeloma (MM) have been disappointing due to the low mitotic index of plasma cells. Recently the detection of clonal chromosomal abnormalities at diagnosis seemed to be improved by addition of cytokines (IL‐6 and GM‐CSF) in the culture medium. We performed two parallel total bone marrow cells culture types in 33 stage I, II and III multiple myeloma patients at diagnosis: 3d without any cytokine, and 4‐7 days stimulated with IL‐6 and GM‐CSF. No clonal chromosomal abnormality was detected in the 12 stage I and II patients either in 3 d or in 4‐7 d culture. In stage III patients, abnormalities were observed in 18/21 (85‐7%) and in 8/18 (44‐4%) in the 3 d culture and the 4‐7 d stimulated cultures respectively. Our results suggest that in stage III multiple myeloma at diagnosis, 3 d culture without cytokine may be the better technique to detect clonal chromosomal abnormalities, and, before using cytokines as a reference condition, this 3 d unstimulated culture should be considered.
Trisomy 8 in acute promyelocytic leukaemia: an interphase study by fluorescence in situ hybridization
Authors: KWONG Y. L. , WONG K. F. , CHAN T. K.
Published: March 2008

Summary. Acute promyelocytic leukaemia (APL) is characterized by t(15;17)(q24;q21). Trisomy 8 is the commonest accompanying karyotypic aberration. We investigated 14 APL patients for trisomy 8 using fluorescence in situ hybridization (FISH). Conventional cytogenetic analysis showed trisomy 8 in two of nine successfully karyotyped cases. With FISH, a possible third case showing a subclone (1‐2‐5%) with trisomy 8 was found. The trisomy 8 clone size defined by karyotyping and FISH was concordant in one case and discordant in another, in which trisomy 8 was found in 100% of metaphases but only in 48% of leukaemic prbmyelocytes by FISH. Therefore trisomy 8 was mosaic in all the cases, suggesting that it had arisen from clonal evolution. AU‐trans‐retinoic acid successfully induced morphologic remission in both cases with trisomy 8.
Predicting the severity of haemolytic disease of the newborn: an assessment of the clinical usefulness of the chemiluminescence test
Authors: NOBLE A. L. , POOLE G. D. , ANDERSON N. , LUCAS G. F. , HADLEY A. G.
Published: March 2008

Summary. The ability of the chemiluminescence test (CLT) to predict the severity of haemolytic disease of the newborn (HDN) was determined in 80 alloimmunized pregnant women who delivered antigen‐positive babies. In 54 cases of alloimmunization to D, results from the CLT showed better correlation with fetal outcome than anti‐D concentration measured by AutoAnalyzer (r = 0.70 and 0.36 respectively). Results from the CLT permitted a threshold level of antibody activity (30%) below which 15/20 babies were unaffected or had mild disease, and only one required transfusion therapy in utero. CUT results above 30% were associated with moderate or severe disease in all cases.

Results from the AutoAnalyzer proved a less reliable predictor of disease severity; three women with anti‐D levels >20iu/ml delivered unaffected babies, and two women with anti‐D levels <10iu/ml delivered babies who had required transfusion in utero. The clinical usefulness of the CLT derives from the possibility of avoiding invasive monitoring procedures in women with high levels of anti‐D which is relatively non‐functional.
Changes in erythroid progenitor cell and accessory cell compartments in patients with myelodysplastic syndromes during treatment with all‐trans retinoic acid and haemopoietic growth factors
Authors: Maurer A. B. , Ganser A. , Seipelt G. , Ottmann O. G. , Mentzel U. , Geissler G. R. , Hoelzer D.
Published: March 2008

Differentiation induction therapy is used in myelodysplastic syndromes (MDS) to improve maturation defects and to restore impaired function of malignant cells. To this end, 18 patients with MDS received either a combination therapy consisting in study 1 of all‐trans retinoic acid (ATRA) and granulocyte‐colony stimulating factor (G‐CSF), or in study 2 of a combination with ATRA, G‐CSF, erythropoletin (Epo) and tocopherol. The ANC increased in 19/20 patients in both studies, whereas an increase in haemoglobin concentration, platelet counts or reduction of transfusion requirement was seen in only 8/20 patients, correlating strongly with good BFU‐E growth (P < 0.001). To assess the role of accessory cells in the modulation of the haemopoietic response to treatment, we analysed the capacity of peripheral blood monocytes to secrete cytokines (IL‐1β, IL‐6, IL‐8, TNFα). Secretion of all cytokines was significantly reduced before therapy when compared with healthy controls, but increased during therapy, reaching normal levels for IL‐8. These data indicate that a combination therapy with ATRA and cytokines improves impaired cytokine secretion from monocytes and induces a multilineage clinical response in a subgroup of MDS patients characterized by an almost intact erythroid compartment. In contrast, induction of TNFα might be responsible for treatment failure.
Unexpected high incidence of intracranial subdural haematoma during intensive chemotherapy for acute myeloid leukaemia with a monoblastic component
Authors: Jourdan E. , Dombret H. , Glaisner S. , Micléa J. M. , Castaigne S. , Degos L.
Published: March 2008

We report a high incidence of subacute, chronic and sometimes occult intracranial subdural haematoma (SDH) occurring during intensive chemotherapy for acute myeloid leukaemia (AML) with a monoblastic component. Between March 1990 and January 1993, 86 AML patients from our institution were randomized in the multicentric French AML 90 trial. Eight patients (9%) presented a grade > 2 haemorrhagic event, which was intracranial SDH in five of them. All these five SDH patients had hyperleucocytic AML4 or AML5 and had experienced at least one lumbar puncture (LP) before SDH diagnosis (with intrathecal chemotherapy in four cases). SDH diagnosis was assessed on a brain computed tomography scan which was performed 1‐9 d after initial SDH symptoms (mainly mild headaches considered a result of prior LP). All these five patients recovered from this severe event after a specified therapy.

SDH does not appear to be an uncommon complication of AML4 and AML 5 therapy. Its incidence might be underreported because of poor symptomatology. Lumbar punctures, known to cause exceptional SDH in nonleukaemic patients, might trigger these haemorrhagic events, eventually in combination with other predisposing factors such a haemostasis disorders or leukaemic CNS infiltration.
Interferon response in chronic myeloid leukaemia correlates with ABL/BCR expression: a preliminary study
Authors: Yin Jian‐Lin , Williams Bronwyn G. , Arthur Chris K. , MA David D. F.
Published: March 2008

α‐Interferon (IFN) has been used to induce cytogenetic remission in chronic myeloid leukaemia (CML), but there are few indicators to predict IFN response. The role of the chimaeric BCR/ABL gene in the malignant process is undisputed. There are, however, conflicting views as to whether the breakpoint site within the BCR gene, and the type of mRNA produced determine disease prognosis and progression. The function and clinical significance of the newly discovered ABL/BCR mRNA has not been investigated for a correlation with CML prognosis or response to therapy. We have used a two‐step reverse transcriptase polymerase chain reaction (RT‐PCR) to detect the transcripts of the chimaeric genes BCR/ABL, ABL/BCR, as well as the normal ABL and BCR genes in 24 CML patients treated with IFN.

Because of the variable expression of the four transcripts at presentation, a correlation between gene expression, prognosis and clinical progression was examined. No correlation between prognosis and gene expression was seen. Also, no correlation was found between expression of BCR, ABL or BCR/ABL mRNA and response to treatment with IFN. However. 7/10 ABL/BCR mRNA positive patients achieved a major cytogenetic response to IFN; but of the 13 ABL/BCR mRNA negative patients, only two achieved a major cytogenetic response (P=0‐013). Further studies are required to confirm these findings.
Flow cytometric determination of pre‐transfusion red cell volume in fetuses and neonates requiring transfusion based on RhD+ dilution by transfused D‐ red cells
Authors: Wynn R. , Dixon S. , Al‐Ismail S. A. , Jones J. G. , Fisher J. , Hoy T. , Dawson A. , Wardrop C. A. J.
Published: March 2008

We report a case of feto‐maternal haemorrhage and describe a new flow‐cytometric method of determining a fetus's or infant's pre‐transfusion red cell volume (RCV). We validate this method against an established technique, employing fetal haemoglobin (HbF) dilution, for determining the RCV in fetuses and neonates requiring intravascular transfusion. We discuss advantages and other potential applications of this new method.
Detection of chromosome 11 alterations in blood and bone marrow by interphase cytogenetics in mantle cell lymphoma
Authors: Zucca Emanuele , Soldati Gianni , Schlegelberger Brigitte , Booth Mark J. , Weber‐Matthiesen Klaus , Cavalli Franco , Cotter Finbarr E.
Published: March 2008

The t(11;14)(q13;q32) translocation is a consistent chromosome change in mantle cell lymphomas. This study investigates the application of fluorescent in situ hybridization (FISH) with chromosome painting probes for interphase cytogenetic analysis in patients with mantle cell lymphomas. Chromosome 11 paints have been able to show splitting of the chromosome signal consistent with the t(11; 14) translocation in interphase cells from bone marrow and blood of patients with mantle cell lymphomas. These include some in clinical remission. The chromosome probes conjugated with fluorescent molecules are hybridized with patient's DNA allowing the easy detection of chromosome 11 abnormalities with fluorescent‐light microscopes. Interphase FISH has a higher sensitivity and is quicker than standard metaphase cytogenetics. This may be beneficial in rapid detection of chromosome 11 abnormalities, assisting in the diagnosis of mantle cell lymphomas. In addition, detection of a clonal population of cells is possible.
The high frequency of the — 6G → A factor IX promoter mutation is the result both of a founder effect and recurrent mutation at a CpG dinucleotide
Authors: Morgan G. E. , Figueiredo M. S. , Winship P. R. , Baker R. , Bolton‐Maggs P. H. B. , Brownlee G. G.
Published: March 2008

We report a new Liverpool family with a mild haemophilia B Leyden phenotype caused by a — 6G → A mutation in a CpG dinucleotide in the promoter of the clotting factor IX gene. This mutation had previously been identified in three other U.K. pedigrees and six others worldwide. To investigate whether these mutations were of independent origin, the haplotype was determined for eight polymorphic loci, within or immediately adjacent to the factor IX gene, for nine of the 10 existing patients. Six probands had identical haplotypes, including all four U.K. probands, suggesting that they arose from a common founder. The other three probands differed in haplotype from the common haplotype, and from each other. suggesting that they were independent mutations at this CpG dinucleotide.
In vivo folic acid supplementation partially corrects in vitro methotrexate toxicity in patients with Down syndrome
Authors: Peeters Marie A. , Rethore Marie‐Odile , Lejeune Jérocme
Published: March 2008

Patients with Down syndrome have been found to have characteristic in vivo and in vitro methotrexate toxicity. The in vitro methotrexate toxicity characteristic of Down syndrome can be diminished by the in vivo administration of supplemental high doses of folic acid. A possible explanation for the increased sensitivity to methotrexate which has been documented in patients with Down syndrome may be due to imbalances in nucleotide pools which result from a gene dosage effect and to greater methylation demands. Supplemental folic acid may be beneficial by virtue of a down‐regulation of excess gene activity and may also provide needed monocarbons.
Problems of resistance development in arthropod pests of agricultural crops in Russia
Authors: Sukhoruchenko G. I. , Dolzhenko V. I.
Published: March 2008

This paper presents the results of long‐term monitoring of insecticide resistance in populations of agricultural pests in Russia. Over the last 45 years, resistance developments were recorded for 36 arthropod pest species in 11 agricultural crops and pastures in relation to nearly all commonly used plant protection products. Development of group, cross and multiple resistance has been revealed in populations of many economically important pests. Toxicological and phenotypical (for Colorado potato beetle) methods have been devised to monitor the development of pesticide resistance. Based on experience over the last century, systems aimed at preventing the development of pest resistance to insecticides and acaricides are elaborated. These systems are based on resistance monitoring and using plant protection measures which minimize the toxic pressure on agroecosystems.
Pests of the palm (Palmae sp.) and date palm (Phoenix dactylifera) determined in Turkey and evaluation of red palm weevil (Rhynchophorus ferrugineus Olivier) (Coleoptera:Curculionidae)
Authors: Bozbuga R. , Hazir Adalet
Published: March 2008

This paper covers the palm (Palmae sp.) and date palm (Phoenix dactylifera) pests which were determined by studies conducted in Turkey between 1941 and 2006. In total 15 species have been found to date: 1 belonging to Coccidae, 9 to Diaspididae, 1 to Margarodidae and 2 to Pseudococcidae families of the order Homoptera and 1 species to Scarabaeidae and 1 to Curculionidae families of the order Coleoptera. Among these pests, red palm weevil (Rhynchophorus ferrugineus Olivier) has caused a great deal of damage in recent years.
Fungi associated with root rot and collapse of melon in Italy
Authors: Chilosi G. , Reda R. , Aleandri M. P. , Camele I. , Altieri L. , Montuschi C. , Languasco L. , Rossi V. , Agosteo G. E. , Macrì C. , Carlucci A. , Lops F. , Mucci M. , Raimondo M. L. , Frisullo S.
Published: March 2008

Melon represents the most widespread cucurbit in Italy. In recent years melon has been subjected to significant losses in yield and quality due to an increasing number of soil‐borne fungal diseases. The collapse of melon, caused by a complex of fungal pathogens, including Monosporascus cannonballus, Acremonium cucurbitacearum, Plectosporium tabacinum and Rhizopycnis vagum, represents one of most destructive diseases worldwide. The purpose of this study was to determine the occurrence of collapse throughout melon‐producing areas in Italy in recent years, to verify the identification of isolates collected, and to test their pathogenicity on melon and other cucurbits. Several fungi were isolated from symptomatic roots of melons in the Italian production areas. The identification was supported by PCR with a species‐specific primer and DNA sequence data. RFLP and sequence analyses showed the existence of a substantial homogeneity among Italian M. cannonballus isolates. Given the self‐incompatibility of these isolates it is impossible to ascertain vegetative compatibility groups (VGC) and consequently genetic relatedness cannot be studied. The frequency of isolation of fungal species varied with geographic locations, M. cannonballus being present mainly in Central Italy, while A. cucurbitacearum and P. tabacinum were most common in Apulia. In pathogenicity tests under greenhouse conditions M. cannonballus, A. cucurbitacearum and P. tabacinum caused collapse symptoms and root rots, whereas R. vagum was found to be a weak pathogen.
First year growth and survival of common carp in two glacial lakes
Authors: PHELPS Q. E. , GRAEB B. D. S. , WILLIS D. W.
Published: March 2008

Abstract  Cohorts of common carp, Cyprinus carpio Linnaeus, were monitored from hatch through the next spring in two South Dakota, USA lakes to identify factors affecting year‐class strength. Hatching occurred over 37‐ and 47‐day periods in the two lakes. Common carp that hatched earlier achieved greater total lengths at the end of the first growing season (Brant Lake: r = −0.84, d.f. = 77, P < 0.001; Campbell Lake: r = −0.87, d.f. = 78, P < 0.001). Mean daily growth rates were approximately 1.0 mm day−1 and similar between lakes. Total length was positively related to daily growth rate in the two lakes, indicating that members of the cohort that grew faster achieved greater total lengths by time of capture. Hatch date was inversely related to daily growth (fish hatched earlier grew faster) in one lake (r = −0.44, d.f. = 77, P < 0.001) but not the other (r = −0.04, d.f. = 78, P = 0.678), suggesting that length at the end of the growing season can be affected by length of growing season and growth rate. Overwinter survival of age‐0 fish appeared to be size dependent because age‐1 common carp length–frequency distributions from both lakes comprised only of the larger cohort members present the previous autumn.
Pre‐stocking acclimatisation of brown troutSalmo trutta: effects on growth and capture in a fast‐flowing river
Authors: BAER J. , BRINKER A.
Published: March 2008

Abstract A field experiment was carried out over two consecutive years in a fast‐flowing river to evaluate the effects of a 5‐day acclimation period on the subsequent growth and capture of stocked juvenile brown trout,Salmo truttaL. Post‐stocking growth of both acclimated and non‐acclimated fish remained very poor for at least 44 to 50 days. After this slow start, all fish grew significantly but acclimated trout performed 40.1% better than non‐acclimated individuals. However, the better growth did not lead to higher capture rates. Capture success post‐stocking was low, regardless of acclimation. Flooding, combined with low fitness of the stocked fish in the first weeks was considered the main reason for the unsatisfactory stocking success. It was concluded that in‐stream acclimation aids rapid adaptation of stocked trout and thus imparts some growth advantages, although this does not necessarily result in higher yields.
Body mass index in adults with intellectual disability: distribution, associations and service implications: a population‐based prevalence study
Authors: Bhaumik S. , Watson J. M. , Thorp C. F. , Tyrer F. , McGrother C. W.
Published: March 2008

Background  Previous studies of weight problems in adults with intellectual disability (ID) have generally been small or selective and given conflicting results. The objectives of our large‐scale study were to identify inequalities in weight problems between adults with ID and the general adult population, and to investigate factors associated with obesity and underweight within the ID population.

Methods  We undertook a population‐based prevalence study of 1119 adults with ID aged 20 and over on the Leicestershire Learning Disability Register who participated in a programme of universal health checks and home interviews with their carers. We performed a cross‐sectional analysis of the register data and compared the observed and expected prevalences of body mass index categories in the ID and general populations using indirect standardisation for age. We used logistic regression to evaluate the association of a range of probable demographic, physical, mental and skills attributes with obesity and underweight.

Results  In those aged 25 and over, the standardised morbidity ratio (SMR) for obesity was 0.80 (95% CI 0.64–1.00) in men and 1.48 (95% CI 1.23–1.77) in women. The SMR for underweight was 8.44 (95% CI 6.52–10.82) in men and 2.35 (95% CI 1.72–3.19) in women. Among those aged 20 and over, crude prevalences were 20.7% for obesity, 28.0% for overweight, 32.7% for normal weight and 18.6% for underweight. Obesity was associated with living independently/with family, ability to feed/drink unaided, being female, hypertension, Down syndrome and the absence of cerebral palsy. Underweight was associated with younger age, absence of Down syndrome and not taking medication.

Conclusion  Obesity in women and underweight in both men and women was more common in adults with ID than in the general population after controlling for differences in the age distributions between the two populations. The associated factors suggest opportunities for targeting high‐risk groups within the ID population for lifestyle and behaviour modification.
Teaching picture‐to‐object relations in picture‐based requesting by children with autism: a comparison between error prevention and error correction teaching procedures
Authors: Carr D. , Felce J.
Published: March 2008

Background  Children who have a combination of language and developmental disabilities with autism often experience major difficulties in learning relations between objects and their graphic representations. Therefore, they would benefit from teaching procedures that minimize their difficulties in acquiring these relations. This study compared two teaching procedures, an error prevention procedure and an error correction procedure, for teaching relations between objects and pictures.

Method  Participants were two groups of children with autism, aged between 3 and 7 years. In the context of picture‐to‐object requesting, one group was taught using an error correction method and the other group with an error prevention method. The measures for each child were accuracy of correspondences between taught picture and object pairs and accuracy of delayed correspondences in learning outcome tests with all combinations of object and picture pairs presented to them throughout the study.

Results  The group receiving the error prevention‐based teaching made significantly fewer errors during the teaching phases and in their learning outcome test for correspondences between all combinations of pictures and objects.

Conclusions  The error prevention teaching procedure would seem to provide a more efficient and ecologically valid method than the error correction procedure for teaching relations between objects and their graphic‐based referents. Improvements in the methodology were suggested for providing a stronger basis for comparison between error correction and error prevention teaching methods.
Attention deficits in tuberous sclerosis complex (TSC): rethinking the pathways to the endstate
Authors: De Vries P. J. , Watson P.
Published: March 2008

Background Tuberous sclerosis complex (TSC) is a genetic disorder associated with a range of neurocognitive manifestations, including neuropsychological attention deficits most notably in dual tasking/divided attention. These dual‐task deficits have so far been interpreted as evidence of a vulnerable ‘cognitive module’ in TSC. Here, we suggest that this interpretation represents an ‘adult neuropsychological’ perspective, and argue that a developmental approach would be more appropriate to examine attention deficits in TSC.

Method We examined the pathway to ‘endstate’ dual‐task deficits in twenty 6–16 year olds with TSC utilising the Test of Everyday Attention for Children (TEA‐Ch). We predicted that the pattern of attentional deficits in TSC would support a ‘conditional’ model where the establishment of a later‐maturing skill was dependent on the functional maturation of an earlier expected skill.

Results Attentional profiles showed statistical support for a conditional model. Only one child showed a deterministic pattern while one showed a hybrid pattern, attributed to the admixture of a surgically acquired lesion and a neurodevelopmental disorder.

Conclusion This preliminary study suggests that the developmental cascade in TSC may be arrested at various stages of neuropsychological development, thus leading to different developmental trajectories towards similar ‘endstate’ profiles.
Perspectives on pain and intellectual disability
Authors: Symons F. J. , Shinde S. K. , Gilles E.
Published: March 2008

Historically, individuals with intellectual disability (ID) have been excluded from pain research and assumed to be insensitive or indifferent to pain. The weight of the evidence suggests that individuals with ID have been subject to practices and procedures with little regard for their ability to experience or express pain. A number of issues central to improving understanding of pain in ID will be introduced and current research related to the definition of pain and its social context, underlying sensory and metabolic systems and factors influencing judgments about the ability to experience pain will be reviewed. Accumulating evidence from interdisciplinary research designed to improve assessment, understand individual differences, and evaluate bias and beliefs about pain suggests that new perspectives are emerging and beginning to shape an innovative frontier of research that will ultimately pay tremendous dividends for improving the quality of life of individuals with ID.
Quantitative assessment of inflammatory cytokine gene expression in chronic adult periodontitis
Authors: Roberts F. A. , Hockett R. D. , Bucy R. P. , Michalek S. M.
Published: March 2008

Adult periodontitis is a chronic destructive disease characterized by an interaction between gram‐negative bacteria and the host inflammatory response. Microbial substances such as lipopolysaccharide can activate host cells, e.g., macrophages, fibroblasts and keratinocytes, to secrete proinflammatory cytokines including tumor necrosis factor a and interleukin 1β (IL‐1β). This study examined the hypothesis that periodontitis tissue contains increased levels of cytokines that promote osseous and connective tissue destruction. To test this hypothesis, diseased and healthy gingival biopsies were examined for differences in the expression of cytokine mRNA for the pro‐inflammatory cytokines tumor necrosis factor α and IL‐1β and the anti‐inflammatory cytokine IL‐1ra using quantitative reverse transcriptase polymerase chain reaction and in situ hybridization methods. The levels of tumor necrosis factor α and IL‐1ra mRNA were shown to be significantly higher in diseased than healthy tissues. Additionally, a significantly correlated expression of IL‐1β and IL‐1ra mRNA was seen in all tissue examined. Analysis of tissue sections by immunohistochemical and in situ hybridization techniques revealed a mononuclear cell infiltrate that consisted of a higher average number of cells staining positive for tumor necrosis factor α mRNA, CD14, and CD3 in the diseased than healthy tissues. Although both diseased and healthy tissues expressed IL‐1β and IL‐1ra mRNA in the epithelium, the diseased tissue biopsies expressed more IL‐1β and IL‐1ra mRNA in the connective tissue. These results implicate the potential involvement of both the pro‐and anti‐inflammatory cytokines in the regulation of the chronic inflammatory disease adult periodontitis.
Absence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia pneumoniae in human subgingival plaque
Authors: Tran T. , Flynn M. J. , Chen C. , Slots J.
Published: March 2008

Little is known about the presence of common medical pathogens in the human oral cavity. Using a 16S rRNA‐based PCR identification method, this study determined the occurrence of Porphyromonas asaccharolytica, Bacteroides fragilis and Chlamydia pneumoniae in subgingival plaque from 50 adults with advanced periodontitis. Each patient contributed samples from 3 deep periodontal pockets collected by paper points. The PCR primers were for P. asaccharolytica 5′‐CTC TAG CTA GAG TGT ACT GG‐3′ and 5′‐ATA GGG TTT ATA GAT TAG CTC TCT‐3′, for B. fragilis 5′‐AAT GAT TCC GCA TGG TTT CAT TA‐3′ and 5′‐GCG GTG ATT GCT CAC TGA CA‐3′, and for C. pneumoniae 5′‐TGA CAA CTG TAG AAA TAC AGC‐3′ and 5′‐CGC CTC TCT CCT ATA AAT‐3′. The primers yielded a single amplicon with the respective reference strains and produced no amplicon with colonies of 25 groups of oral organisms. None of the three test species were detected in any of the 50 pooled subgingival samples tested. P. asaccharolytica, B. fragilis and C. pneumoniae do not seem to be part of the periodontopathic microbiota in humans.
The chemistry behind redox regulation with a focus on sulphur redox systems
Authors: Jacob Claus , Anwar Awais
Published: March 2008

Sulphur metabolism in plants provides a wealth of natural products, including several chemically unusual substances, such as thiosulphinates, polysulphides and isothiocyanates. Many of these reactive sulphur species (RSS) exhibit a distinct redox behaviour in vitro, which translates into a rather interesting biological activity in vivo, such as antibiotic, fungicidal, pesticidal or anticancer activity. While the molecular basis for such activity has long remained obscure, research into sulphur‐based redox systems during the past 5–10 years has achieved a better knowledge of the in vitro properties of RSS and has led to an improved understanding of their impact on intracellular redox signalling and control pathways in living cells. It has become apparent that the redox chameleon sulphur occurs in biological systems in about 10 different oxidation states, which give rise to an extensive and complicated network of sulphur‐based redox events. Together, natural sulphur products from plants and their intracellular targets provide the basis for innovative design of novel antibiotics, fungicides, pesticides and anticancer agents.
EIN3‐like gene expression during fruit ripening of Cavendish banana (Musa acuminata cv. Grande naine)
Authors: Mbéguié‐A‐Mbéguié Didier , Hubert Olivier , Fils‐Lycaon Bernard , Chillet Marc , Baurens Franc‐Christophe
Published: March 2008

Ethylene signal transduction initiates with ethylene binding at receptor proteins and terminates in a transcription cascade involving the EIN3/EIL transcription factors. Here, we have isolated four cDNAs homologs of the Arabidopsis EIN3/EIN3‐like gene, MA‐EILs (Musa acuminata ethylene insensitive 3‐like) from banana fruit. Sequence comparison with other banana EIL gene already registered in the database led us to conclude that, at this day, at least five different genes namely MA‐EIL1, MA‐EIL2/AB266318, MA‐EIL3/AB266319, MA‐EIL4/AB266320 and AB266321 exist in banana. Phylogenetic analyses included all banana EIL genes within a same cluster consisting of rice OsEILs, a monocotyledonous plant as banana. However, MA‐EIL1, MA‐EIL2/AB266318, MA‐EIL4/AB266320 and AB266321 on one side, and MA‐EIL3/AB266319 on the other side, belong to two distant subclusters. MA‐EIL mRNAs were detected in all examined banana tissues but at lower level in peel than in pulp. According to tissues, MA‐EIL genes were differentially regulated by ripening and ethylene in mature green fruit and wounding in old and young leaves. MA‐EIL2/AB266318 was the unique ripening‐ and ethylene‐induced gene; MA‐EIL1, MA‐EIL4/Ab266320 and AB266321 genes were downregulated, while MA‐EIL3/AB266319 presented an unusual pattern of expression. Interestingly, a marked change was observed mainly in MA‐EIL1 and MA‐EIL3/Ab266319 mRNA accumulation concomitantly with changes in ethylene responsiveness of fruit. Upon wounding, the main effect was observed in MA‐EIL4/AB266320 and AB266321 mRNA levels, which presented a markedly increase in both young and old leaves, respectively. Data presented in this study suggest the importance of a transcriptionally step control in the regulation of EIL genes during banana fruit ripening.
Vein recovery from embolism occurs under negative pressure in leaves of sunflower (Helianthus annuus)
Authors: Nardini Andrea , Ramani Matteo , Gortan Emmanuelle , Salleo Sebastiano
Published: March 2008

Leaf veins undergo cavitation at water potentials (Ψleaf) commonly experienced by field‐growing plants. Theoretically, embolism reversal should not be possible until xylem pressures rise by several kilopascals of atmospheric pressure, but recent evidence suggests that embolized conduits can be refilled even when surrounded by others at substantial tension (novel refilling). The present study reports ‘novel refilling’ occurring in leaf veins of sunflower (Helianthus annuus L.) while at Ψleaf = −0.33 MPa. Sixty per cent loss of vein hydraulic conductance (Kvein) was recorded at Ψleaf < −0.65 MPa, while stem hydraulic conductance (Kstem) was unaffected even at Ψleaf = −1.1 MPa. Loss of Kvein was accompanied by stomatal closure. Water‐stressed plants (Ψleaf = −1.1 MPa) were rehydrated overnight to different target water potentials achieved by using PEG at different concentrations as irrigation medium. Kvein recovered by 50% at Ψleaf = −0.47 MPa and vein refilling was complete at Ψleaf = −0.33 MPa, i.e. well below the theoretical limit for conduit refilling (−0.05 MPa as calculated for sunflower minor veins). Mercurials supplied to detached leaves had no effect on the refilling process. Upon rehydration, recovery of Kvein was not paralleled by recovery of whole‐plant hydraulic conductance or leaf conductance to water vapour (gL), as a likely consequence of hydraulic failure of other components of the water pathway (root system or extravascular leaf compartments) and/or root‐to‐leaf chemical signalling. This is the first study providing experimental evidence for ‘novel refilling’ in a herbaceous dicot and highlighting the importance of this process in the leaf.
NTRC new ways of using NADPH in the chloroplast
Authors: Spínola María C. , Pérez‐Ruiz Juan M. , Pulido Pablo , Kirchsteiger Kerstin , Guinea Manuel , González Maricruz , Cejudo Francisco J.
Published: March 2008

Despite being the primary source of energy in the biosphere, photosynthesis is a process that inevitably produces reactive oxygen species. Chloroplasts are a major source of hydrogen peroxide production in plant cells; therefore, different systems for peroxide reduction, such as ascorbate peroxidase and peroxiredoxins (Prxs), are found in this organelle. Most of the reducing power required for hydrogen peroxide reduction by these systems is provided by Fd reduced by the photosynthetic electron transport chain; hence, the function of these systems is highly dependent on light. Recently, it was described a novel plastidial enzyme, stated NTRC, formed by a thioredoxin reductase (NTR) domain at the N‐terminus and a thioredoxin (Trx) domain at the C‐terminus. NTRC is able to conjugate both NTR and Trx activities to efficiently reduce 2‐Cys Prx using NADPH as a source of reducing power. Based on these results, it was proposed that NTRC is a new pathway to transfer reducing power to the chloroplast detoxification system, allowing the use of NADPH, besides reduced Fd, for such function. In this article, the most important features of NTRC are summarized and the implications of this novel activity in the context of chloroplast protection against oxidative damage are discussed.
Microbially induced formation of ooid‐like coated grains in the Late Cretaceous methane‐seep deposits of the Nakagawa area, Hokkaido, northern Japan
Authors: Jenkins Robert Gwyn , Hikida Yoshinori , Chikaraishi Yoshito , Ohkouchi Naohiko , Tanabe Kazushige
Published: March 2008

Abstract  Ooid‐like coated grains are found in the Late Cretaceous methane‐seep deposits in the Nakagawa area, Hokkaido, Japan. The coated grains were examined using macro‐ and microscopic observations, electron‐probe microanalysis, and biomarker analysis. They are round‐ to oval‐shaped, with nuclei consisting of fractured sediment and micritic envelopes. The fractures probably occurred as a result of increasing hydrostatic pressure when the sediment was still unconsolidated or weakly consolidated. Biomarker analysis revealed that two types of molecules, crocetane and PMI, are predominant in the hydrocarbon fraction with highly negative carbon isotopic composition as low as −122‰ (vs Vienna Peedee Belemnite). These data suggest that the coated grains were formed under the influence of anaerobic oxidation of methane, near the sediment/seawater interface. The presence of such grains indicates that methane‐containing pore water reached the sea floor at that time.
Innate immunity and alcoholic liver fibrosis
Authors: Jeong Won‐Il , Gao Bin
Published: March 2008

The hepatic innate immune system consists of predominant innate immunity, which plays an important role in innate defense against infection and tumor transformation. Emerging evidence suggests that innate immunity also contributes to liver injury, repair, and fibrosis. The present review summarizes the recent findings on the role of innate immunity in liver fibrosis. In general, Kupffer cells stimulate liver fibrosis via production of reactive oxygen species and pro‐inflammatory cytokines, whereas natural killer (NK) cells inhibit liver fibrosis by directly killing activated hepatic stellate cells and production of γ‐interferon (IFN‐γ). Complement components, interferons, and Toll‐like receptors have also been shown to regulate liver fibrosis. Recent evidence also suggests that modulation of innate immunity by alcohol plays an important role in the pathogenesis of alcoholic liver fibrosis. These include alcohol amplification of the profibrotic effects of Kupffer cells and suppression of the antifibrotic effects of NK/IFN‐γ.
Individual susceptibility to alcoholic pancreatitis
Authors: Apte Minoti V , Pirola Romano C , Wilson Jeremy S
Published: March 2008

The observation that only a minority of heavy drinkers develop pancreatitis has prompted an intensive search for a trigger factor/cofactor/susceptibility factor that may precipitate a clinical attack. Putative susceptibility factors examined so far include diet, smoking, amount and type of alcohol consumed, the pattern of drinking and lipid intolerance. In addition, a range of inherited factors have been assessed including blood group antigens, human leukocyte antigen serotypes, alpha‐1‐antitrypsin phenotypes and several genotypes. The latter group comprises mutations/polymorphisms in genes related to alcohol‐metabolizing enzymes, detoxifying enzymes, pancreatic digestive enzymes, pancreatic enzyme inhibitors, cystic fibrosis and cytokines. Disappointingly, despite this concerted research effort, no clear association has been established between the above factors and alcoholic pancreatitis. Experimentally, the secretagogue cholecystokinin (CCK) has been investigated as a candidate ‘trigger’ for alcoholic pancreatitis. However, the clinical relevance of CCK as a trigger factor has to be questioned, as it is difficult to envisage a situation in humans where abnormally high levels of CCK would be released into the circulation to trigger pancreatitis in alcoholics. In contrast, bacterial endotoxemia is a candidate cofactor that does have relevance to the clinical situation. Plasma lipopolysaccharide (LPS, an endotoxin) levels are significantly higher in drinkers (either after chronic alcohol intake or a single binge) compared to non‐drinkers. We have recently shown that alcohol‐fed animals challenged with otherwise innocuous doses of LPS exhibit significant pancreatic injury. Moreover, repeated LPS exposure in alcohol‐fed rats leads to progressive injury to the gland characterized by significant pancreatic fibrosis. These studies support the concept that endotoxin may be an important factor in the initiation and progression of alcoholic pancreatitis. Scope remains for further studies examining proteins related to cellular anti‐oxidant defenses, minor cystic fibrosis (CF) mutations and trans‐heterozygosity involving a combination of mutations of different genes (such as CFTR alterations combined with SPINK1 or PRSS1 variants), as potential triggers of alcoholic pancreatitis.