bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of an o‐raffinose cross‐linked haemoglobin product on oesophageal and lower oesophageal sphincter motor function
Authors: Xue  , Paterson  , Valdez  , Miller  , Christoff  , Wong  , Diamant  
Published: March 2003

The present experiments evaluate the effects on oesophageal motility of an o‐raffinose cross‐linked haemoglobin‐based oxygen carrier (HBOC) purified from outdated donated human blood cells (HemolinkTM), with attention to dose–response (0.6–2.4 g kg–1), oxygenation status and low molecular weight components (4.4–36.4% 64 kDa or less). In ketamine‐anaesthetized cats, lower oesophageal sphincter (LES) function and oesophageal peristalsis were monitored 0.5 h before, during and up to 3.5 h after HBOC infusion, and in some cats at 24 h. (1) All products significantly inhibited LES relaxation and increased peristaltic velocity in the distal smooth muscle oesophagus, without consistently altering resting LES pressure. (2) Effects on peristaltic velocity reached a maximum at the smallest dose, whereas the effects on LES relaxation had a maximum effect at 1.2 g kg–1. (3) Effects were not significantly altered by the haemoglobin oxygenation status or presence of low molecular weight components. (4) Repetitive oesophageal contractions occurred.In the cat, an o‐raffinose cross‐linked human haemoglobin product produces changes in oesophageal body and LES function, which are independent of the HBOC oxygenation status and composition of the low molecular weight components tested. Changes may persist for at least 24 h. These motility changes are likely due to scavenging of nitric oxide by the haemoglobin.
Gastrointestinal perception: pathophysiological implications
Authors: Azpiroz F. 
Published: March 2003

Abstract

Physiological gut stimuli during the digestive process are not normally perceived. However, gut stimuli activate a variety of afferent pathways and in some circumstances may induce conscious sensations. Experimental evidence gathered during the past decade suggests that patients with functional gut disorders and unexplained abdominal symptoms may have a sensory dysfunction of the gut, so that physiological stimuli would induce symptoms. Assessment of visceral sensitivity is still poorly developed, but in analogy to somatosensory testing, differential stimulation of visceral afferents may be achieved by a combination of stimulation techniques, which may help to characterize sensory dysfunctions. Visceral afferent input is modulated by a series of mechanisms at different levels of the brain gut axis, and conceivably, a dysfunction of these regulatory mechanisms could cause hyperalgesia. The sensory dysfunction in functional patients seems associated to altered reflex activity, and both mechanisms may interact to produce the symptoms. Evidence of a gut sensory–reflex dysfunction as a common pathophysiological mechanism in different functional gastrointestinal disorders, would suggest that they are different forms of the same process, and that the clinical manifestations depend on the specific pathways affected.
The effect of cholecystectomy on duodenojejunal motility in humans
Authors: Le Blanc‐Louvry I. , Denis P. , DucrottÉ P. 
Published: March 2003

Abstract

We hypothesized that certain gastrointestinal symptoms following cholecystectomy could be explained by motor disturbances. To test this hypothesis, we compared pre‐ and post‐operative motor patterns between symptomatic and asymptomatic patients after surgery to evaluate whether some motor changes could be induced by gallbladder removal and associated with symptoms. Twenty‐three patients were prospectively evaluated before and 3 months after cholecystectomy. After surgery, 17 patients were asymptomatic and six were symptomatic. Duodenojejunal manometric recordings were performed for 3 h during fasting, then 3 h after a 750‐kcal meal. Patient motor results were compared to those obtained in the duodenojejunum of 20 healthy controls. After surgery, only a few modifications in duodenojejunal motility were observed compared to the preoperative period. Motor changes related to cholecystectomy were increase in phase III amplitude and the absence of progressive decrease of the duodenojejunal motor response after the meal. After surgery, symptomatic patients had a lower postprandial duodenal motility index after the meal than asymptomatic patients (P < 0.03) and more frequent propagated clusters of contractions (PCCs) (P < 0.02). Preoperative motor patterns associated with postoperative symptoms were postprandial only and included a low duodenal motility index (P < 0.03), and a higher number of PCCs (P < 0.02). Removal of the gallbladder has a limited effect on duodenojejunal motility. Few motor differences existed between symptomatic and asymptomatic patients after surgery. However, a low duodenal motor response to a meal and PCCs were often associated with symptoms.
Capsaicin‐sensitive extrinsic afferents are involved in acid‐induced activation of distinct myenteric neurons in the rat stomach
Authors: Schicho R. , Schemann M. , Pabst M. A. , Holzer P. , Lippe I. TH. 
Published: March 2003

Abstract Challenge of the rat gastric mucosa with 0.5 mol L−1 HCl activates nitrergic neurons in the myenteric plexus as visualized by c‐Fos immunohistochemistry. In the present study, we characterized the activated neurons more extensively by their chemical coding and investigated whether a neural pathway that involves capsaicin‐sensitive extrinsic afferents and/or cholinergic neurons transmitting via nicotinic receptors contributes to the activation of myenteric neurons. In multiple labelling experiments, c‐Fos was examined for co‐localization with nitric oxide synthase (NOS), vasoactive intestinal peptide (VIP), neuropeptide Y (NPY), enkephalin (ENK), gastrin‐releasing peptide (GRP), substance P (SP), calbindin D‐28k (CALB) and neurofilament 145 (NF 145). All c‐Fos‐positive neurons were immunoreactive for NOS, VIP, NPY and NF 145, but not for SP, ENK, GRP and CALB. Nerve fibres co‐expressing NOS, VIP and NPY were predominantly found in the external muscle layer and in the muscularis mucosae but rarely in the mucosa. Pre‐treatment with capsaicin or hexamethonium or a combination of both pre‐treatments reduced HCl‐induced c‐Fos expression by 54, 66 and 63%, respectively. Acid challenge of the stomach, therefore, leads to activation of presumably inhibitory motor neurons responsible for muscle relaxation. Activation of these neurons is partly mediated by capsaicin‐sensitive afferents and involves ganglionic transmission via nicotinic receptors.
The role of microglial activation in the resolution of CNS lesions
Authors: Willis C. L. , Lynch N. J. , Schwaeble W. J. , Ray D. E. 
Published: March 2003

We are developing a rat model to investigate the relationship between cell death, the inflammatory response and blood–brain barrier function. A single dose of S‐α‐chlorohydrin induces early astrocyte swelling and loss (6–18 h), followed by neuronal death (36–48 h) and barrier dysfunction (24 h‐6 d) with no primary immune involvement. Using in situ hybridization we looked for increased expression of C1q; the first component of the classical complement pathway and a sensitive marker of microglial activation previously shown to be up regulated within 1 h of a global ischaemic insult (Schwaeble et al. J Immunol 2000; 164: 5446). Our results suggest that microglial activation is a comparatively late event commencing at 36 h and appears to be prompted by neuronal rather than astrocytic death, while barrier function is restored in parallel with removal of cell debris and extravasated protein. It appears that microglial activation may not be causing barrier breakdown but instead promoting rapid resolution of the lesion by limiting the inflammatory response. We are currently investigating the time course of pro‐ and anti‐inflammatory marker expression and its role in lesion resolution.
Towards a molecular definition of microglia
Authors: Moran L. B. , Thykjaer T. , Orntoft T. F. , Graeber M. B. 
Published: March 2003

Introduction:  Microglia account for at least 10% of all glial cells in the CNS. Morphologically they are unique, forming highly ramified and perpendicularly branching cell processes. In response to pathological stimuli, microglia show considerable plasticity and may assume a macrophage phenotype. Here we report transcriptome data on normal rat microglial cells in vitro.Material and methods:  Microglial cultures of high purity (>95%) were prepared from newborn rat brains. RNA was used for comparative expression profiling on two different Affymetrix GeneChips, the rat neurobiology U34 microarray, and the more comprehensive U34A chip.Results:  Analysis of the expression data was performed using GeneSpring. Only genes exhibiting expression values >2 signal/control ratio were included. Microglia were found to express 8% (107) of the genes on the neurobiology array and 14% (1203) of the genes on the U34A chip, respectively. Among the expressed ‘functional motifs’, groups of immunomodulatory molecules including interleukin (1,18), complement and MIF featured prominently in agreement with the view that microglia represent an intrinsic immune network in the CNS. However, novel products of microglia, e.g. embigin, were also found.Conclusions:  We provide a tentative molecular definition of microglia.
Loss of chromosome 10, retinoblastoma and deleted‐in‐colon‐carcinoma (DCC) proteins in glioblastomas
Authors: Hilton D. A. , Love S. , Penny M. , Pobereskin L. 
Published: March 2003

Introduction:  Glioblastomas have a median survival of 9–12 months. However, some patients die within a few weeks of diagnosis and others may survive for 2 years or more. To try to predict survival more accurately, we have evaluated a number of morphological, immunohistochemical and molecular markers in a retrospective series of glioblastomas.Material and methods:  Paraffin sections from 107 consecutive glioblastomas diagnosed between 1993 and 1997 were included in the study. All cases were reviewed and the presence of calcification or oligodendroglioma‐like areas noted. Sections were immunostained with commercial antibodies to retinoblastoma and DCC proteins and subjected to in situ hybridization with probes to chromosomes 12 and 10.Results:  Loss of retinoblastoma and DCC protein expression was seen in 20% and 71% of glioblastomas respectively. Loss of retinoblastoma protein expression correlated with poor outcome (P = 0.045). 64% of glioblastomas showed loss of chromosome 10 but this did not have a significant association with survival. The five tumours with oligodendroglioma‐like areas had a median survival of 70 weeks, compared with 27 weeks for those without (P = 0.014).Conclusion:  In this study, age, loss of retinoblastoma protein and a lack of oligodendroglioma‐like areas were predictors of significantly shorter survival in glioblastomas.
The expression of the EGF receptor family and their ligands in human medulloblastomas
Authors: Collins V. P. , Ichimura K. , Liu L. 
Published: March 2003

Introduction:  Little is known about the molecular processes behind the development of medulloblastomas. While many chromosomal abnormalities have been more or less consistently observed, only a few cellular pathways have been identified as being targeted. These include the Hedgehog/patched signalling pathway (involving PTCH, PTCH2, SSH and SMOH) and the Wnt signalling pathway (involving APC, and β‐catenin). Amplification of N‐myc is associated with a bad prognosis.Material and methods:  We examined the expression of the Epidermal Growth Factor Receptor family and nine of their ligands in a series of 48 medulloblastomas and supratentorial primitive neuroectodermal tumours (PNETs) by quantitative RT‐PCR, Western blot and immunocytochemistry.Results:  The most striking finding was the high levels of expression of erbB4 transcript – in some cases greater that 250 times that found in normal cerebellum. ErbB4 transcript levels greater than 10 times that of cerebellum were seen in 73% of the series. ErbB2 and erbB3 transcript levels exceeding 10 times that of cerebellum were seen in 35% of cases. Only two cases had overexpression of EGFR/erbB1 at these levels. Ligands (Epiregulin/Betacellulin/NDF_/NDF_1/NDF_2) for erbB4 were coexpressed in 74% (26/35) of the cases with high erbB4 expression. Only one case showed no expression of erbB4 and its ligands.Conclusions:  The findings suggest that various forms of autocrine, paracrine, and juxtacrine stimulation through these receptors may contribute to the malignant phenotype of medulloblastomas.
Correlation of single photon emission computed tomography with pathology and seizure outcome in children undergoing epilepsy surgery
Authors: Cross J. H. , Hartley L. , Harkness W. , Harding B. , Neville B. , Gordon I. 
Published: March 2003

Introduction:  Single photon emission computed tomography (SPECT) imaging regional cerebral blood flow (rCBF) can help localize the seizure focus in partial epilepsies during presurgical evaluation. Few studies have explored the possible relationship between preoperative SPECT and underlying pathology, or any relationship to postsurgical outcome.Study group:  Thirty‐five children with medically intractable epilepsy undergoing resective surgery between the ages of 11 months and 18 years had presurgical ictal and interictal rCBF and post surgery follow up of 3–6 years.Results:  Pathological examination revealed 13 to have hippocampal sclerosis (HS): of these 11 had relatively low interictal rCBF perfusion on the side of seizure onset, and eight had hyperfusion ictally. Eight children had morphological evidence of cortical dysplasia: all had a localizing ictal rCBF concordant with the area resected whereas only six demonstrated localized reduction in perfusion on interictal rCBF. All three patients with Rasmussens encephalitis had informative rCBF scans, concordant with the seizure focus. However, infarct, tumours and nonspecific pathology demonstrated poor localization of the seizure focus. No SPECT parameter correlated independently with outcome, although overall the HS group had the best outcome, particularly those with localizing ictal SPECT.Comment:  Ictal SPECT appears predictive of underlying cortical dysplasia. Although in this small group of HS in children, ictal SPECT added little to interictal SPECT for seizure localization, it may be useful in the prediction of outcome. SPECT adds little to the evaluation of children being considered for hemispherectomy over and above the abnormalities detectable on MRI scan.
Alpers syndrome with mitochondrial DNA depletion
Authors: Rahman S. , Taanman J.‐W. , Harding B. N. 
Published: March 2003

Background and aim:  Alpers syndrome or progressive neuronal degeneration of childhood with liver disease is a rare and probably heterogeneous familial disorder of unknown aetiology. We investigated mitochondrial DNA (mtDNA) levels in three cases with Alpers syndrome.Methods:  Three unrelated patients presented with status epilepticus and liver dysfunction between 6 months and 3 years of age. The clinical course was severely progressive and death occurred 7 days to 2 years after initial presentation. Neuropathology was performed in cases 1 and 3 and confirmed a diagnosis of Alpers syndrome. Total genomic DNA extracted from frozen skeletal muscle, liver, heart and kidney was subjected to quantitative Southern blot analysis using two probes (one for mtDNA and the other for the nuclear‐encoded 18S ribosomal DNA) and comparison with age‐matched controls.Results:  Case 1 had 25% residual mtDNA levels in liver, 33% in skeletal muscle, 55% in cardiac muscle and normal levels in kidney. Case 2 had 19% residual mtDNA levels in liver and 42% in skeletal muscle. Case 3 had normal mtDNA levels in skeletal muscle, the only tissue available for study.Discussion:  We conclude that Alpers syndrome may be associated with depleted levels of mtDNA. The underlying genetic defect is likely to involve mtDNA maintenance. Quantitative determination of residual mtDNA levels should be performed in all cases where there is a suspicion of Alpers syndrome.
Amyloid angiopathy in a brain biopsy of a suspected haemorrhagic tumour: case report
Authors: Bodi I. , Achawal S. V. , Sharr M. M. , Lantos P. L. 
Published: March 2003

Introduction:  Amyloid angiopathy (AA), most frequently associated with Alzheimer's disease, may lead to lobar intracerebral haemorrhages. Although AA is common in the elderly population, it is rarely diagnosed in brain biopsy. We report a case of AA with Alzheimer's type changes detected by brain biopsy.Material and methods:  A 75‐year‐old female presented with intermittent delusions and confusion for 2 months and mild memory impairment on examination. Computed tomography and magnetic resonance imaging scans revealed an old blood clot in the right frontal lobe and raised the possibility of a tumour. At operation, an organized blood clot with a partly cystic wall was removed.Results:  Intra‐operative smear showed an infarct with foamy macrophages without evidence of tumour. Paraffin material revealed a haemorrhagic infarct with thickened leptomeningeal blood vessels being positive for Congo red and amyloid‐β (Aβ). Scattered neuritic plaques and neurofibrillary tangles were also detected by Aβ and tau. Retrospective examination of the smear preparation showed metachromatically stained thickened blood vessels consistent with AA.Conclusions:  This case of AA presented with a haemorrhage mimicking a tumour. AA was present even in the smear preparation as diagnosed retrospectively. The possibility of AA should be born in mind in atypical haemorrhagic lesions, particularly in elderly patients.
Immunohistochemical characterization and quantification of Marinesco bodies in Alzheimer's and Parkinson's diseases
Authors: Vollans A. K. , Shukla C. , Bridges L. R. 
Published: March 2003

Introduction:  Marinesco bodies (MBs) were described 100 years ago but, unlike the intranuclear inclusions in the triplet repeat diseases, have received little attention in the literature. Our aim was to see whether they are disease associated or purely age related.Materials and methods:  We examined 15 cases each of Alzheimer's disease, Parkinson's disease and age‐matched control brains. Paraffin sections of midbrain were cut in thicknesses of 5 µm, and immunostained with α‐synuclein and ubiquitin (Novocastra) and tau, β‐amyloid and PrP (Dako). Staining was enhanced with Envision (Dako). A blue‐grey chromagen (Vector SG, Vector) was chosen to provide contrast with the brown pigment of the substantia nigra neurons.Results:  MBs were immunopositive for ubiquitin but not for α‐synuclein, tau, β‐amyloid and PrP. Within affected neurons, MB were fewer in Parkinson's disease than in Alzheimer's disease and ‘normals’ (medians 1.48, 1.98 and 2.00 respectively; P < 0.01). Within normals, the size of MB‐affected neurons was significantly less than that of MB‐unaffected neurons (median areas 605 and 969 µm2 respectively; P < 0.01). MB relative to cell size were smaller in Parkinson's disease than Alzheimer's disease and controls (medians 0.86, 1.07 and 1.12% respectively; P < 0.01).Conclusions:  Differences exist between number and size of Marinesco bodies and affected neurons in neurodegeneration and normal ageing, but there is no clear evidence of a disease association.
Oxidative DNA damage in the spinal cord in multiple sclerosis
Authors: Abedin K. J. , Papadopoulos D. , Dexter D. T. , Reynolds R. 
Published: March 2003

Introduction:  Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by multifocal demyelination and axonal loss. In addition to the role of the immune response in targeting oligodendrocytes and myelin in MS lesions, the extensive inflammatory infiltration is likely to lead to free radical production and oxidative damage to both oligodendrocytes/myelin and neurons. In this study we investigated the extent of free radical damage to DNA in postmortem MS spinal cord.Materials and methods:  Serial 10 µm tissue sections were cut from 26 fixed and cryoprotected spinal cord blocks from 11 MS cases (age 64 ± 4 years, pmd 13 ± 2 h) and two controls (age 70 ± 9 years, pmd 22 ± 4 h). Lesions were characterized using H&E and LFB‐PAS histology and HLA‐DR immunohistochemistry. DNA oxidative damage was detected using a monoclonal antibody against 8‐hydroxy‐2′‐deoxyguanosine (8OHdG; supplied by Dr S Toyokuni, Kyoto), the most abundant modified DNA base.Results:  Quantitative analysis revealed a 150% increase in 8OHdG+ cells relative to normal appearing WM and a 400% increase relative to control WM. A positive correlation was found between the level of macrophage infiltration (HLA‐DR+) and 8OHdG‐expressing cells.Discussion:  These results suggest a role for oxidative damage to DNA due to free radicals in the evolution of the MS lesion.
Racial differences in birthweight for gestational age and infant mortality in extremely‐low‐risk US populations
Authors: Alexander  , Kogan  , Himes  , Mor  , Goldenberg  
Published: March 2003

Using national data, we develop and contrast the birthweight percentiles for gestational age by infants of extremely‐low‐risk (ELR) White and African‐American women and examine racial differences in the proportion of small‐for‐gestational‐age (SGA) births. We then scrutinise racial variations in infant mortality rates of the infants of ELR women. We further compare the infant mortality rates of infants at or below the 10th percentile of birthweight for gestational age of each race group to determine whether infants with similar restricted fetal growth have comparable risks of subsequent mortality. Single live births, 34–42 weeks’ gestation, to White and African‐American US‐resident mothers were selected from the 1990–91 US Linked Live Birth–Infant Death File (n = 4 360 829). Extremely‐low‐risk mothers were defined as: married, aged 20–34 years, 13+ years of education, multiparae, with average parity for age, adequate prenatal care, vaginal delivery, and no reports of medical risk factors, tobacco use or alcohol use during pregnancy.   Marked racial variation in birthweight percentiles by gestational age was evident. Compared with ELR White mothers, the risk of an SGA infant was 2.64 times greater for ELR African‐American mothers and the risk of infant mortality was 1.61 times greater. For the ELR group, the infant mortality rates of African‐American and White infants at or below the 10th percentile of birthweight for gestational age of their respective maternal race group were essentially identical after controlling for gestational age. In conclusion, race differences in fetal growth patterns remained after controlling for risk status. Efforts to remove racial disparities in infant mortality will need to develop aetiological pathways that can explain why African‐Americans have relatively higher rates of preterm birth and higher infant mortality rates among term and non‐SGA infants.