bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural mechanisms involved in the delay of gastric emptying of liquid elicited by acute blood volume expansion in awake rats
Authors: GONDIM F. DE A. A. , OLIVEIRA  , GRAÇA  , GONDIM  , ALENCAR  , DANTAS  , SANTOS  , ROLA
Published: March 2003

We have previously reported that acute blood volume expansion in awake rats delays the gastric emptying of a liquid meal, using the phenol red method. In this study we attempted to investigate the neural mechanisms involved in this phenomenon. Blood volume expansion, due to Ringer‐bicarbonate infusion up to a volume equivalent to 5% of body weight, decreased the gastric emptying of a liquid meal by half (38.2 ± 1.8 vs 18.7 ± 3.2%, P < 0.05). The blood volume expansion effect on gastric emptying of liquid was prevented by separate pretreatments, consisting of subdiaphragmatic vagotomy or i.v. injection of hexamethonium (20 mg kg−1) or yohimbine (3 mg kg−1). Intravenous injection of atropine (0.5 mg kg−1), guanethidine (10 mg kg−1), L‐NAME (3 mg kg−1), prazosin (1 mg kg−1) or propranolol (2 mg kg−1) did not prevent the blood volume expansion effect on gastric emptying. Bilateral adrenalectomy or coeliac ganglionectomy were also ineffective. The results indicate that blood volume expansion decreases gastric emptying of liquid through vagal‐dependent pathways, sensitive to hexamethonium and yohimbine. Evidence for the participation of the peripheral sympathetic nervous system was not found.
Evidence for functional NK1‐tachykinin receptors on motor neurones supplying the circular muscle of guinea‐pig small and large intestine
Authors: Bian  , Bertrand  , Furness  , Bornstein
Published: March 2003

The guinea‐pig intestine was investigated to determine which neurones are excited via NK1 receptors. The specific NK1 receptor agonists [Sar9, Met(O2)11]‐SP and septide contracted the circular muscle of all regions via a tetrodotoxin (TTX)‐insensitive mechanism. In the proximal colon, they also evoked a TTX‐sensitive relaxation; in the distal colon, the contractions were larger when nerve impulses were blocked with TTX, indicating that the agonists excited inhibitory motor neurones. In the duodenum and ileum, TTX reduced agonist‐evoked contractions indicating that excitatory motor neurones were activated. In the presence of indomethacin, TTX enhanced contractions of ileal circular muscle evoked by these agonists suggesting that NK1 receptors were on inhibitory motor neurones. Blockade of nitric oxide synthase (NOS) enhanced NK1 receptor agonist evoked contractions of duodenal circular muscle, indicating that the agonists excite inhibitory motor neurones in duodenum. Neurones immunoreactive for NK1 receptors were studied in the duodenum and distal colon. As reported previously for the ileum,1 some neurones were immunoreactive for NOS and had Dogiel type I morphology; features characteristic of inhibitory motor neurones. In conclusion, there are functional NK1 receptors on excitatory and inhibitory motor neurones in the guinea‐pig small intestine and on inhibitory motor neurones in the colon.
Effect of the selective serotonin reuptake inhibitor sertraline on gastric sensitivity and compliance in healthy humans1
Authors: Ladabaum U , Glidden D
Published: March 2003

Abstract
 Visceral hypersensitivity may contribute to symptoms in functional dyspepsia. Selective serotonin reuptake inhibitors (SSRIs) may be beneficial in functional gastrointestinal disorders. The aim of this study was to determine whether the SSRI sertraline affects gastric sensitivity and compliance in healthy humans. Ten healthy humans completed a 6‐week randomized, double‐blind, crossover trial of sertraline (50 mg day−1) vs. placebo. After each 2‐week treatment, fullness, pain and nausea were rated at increasing gastric barostat distending pressures. Sensation thresholds above minimal distending pressure (MDP) were determined with a tracking method. Somatic sensory testing was performed by hand immersion in ice water. No differences were found between sertraline and placebo for symptoms as a function of distending pressure (fullness, P = 0.72; pain, P = 0.79; nausea, P = 0.41), gastric compliance (P = 0.15), median and interquartile range thresholds for first sensation [4.1 (3.5–5.7) vs. 6.2 (3.3–10.0) mmHg above MDP, P = 0.19] and pain [15.2 (8.3–21.0) vs. 15.3 (10.3–19.8) mmHg above MDP, P = 0.85], and median tolerance times for hand ice water immersion [27 (19–99) vs. 29 (20–180) s, P = 0.73]. In conclusion, sertraline had no effect on gastric sensitivity or compliance, or somatic pain tolerance in healthy humans. Studies are needed to assess the effects of SSRIs on visceral sensation and clinical symptoms in patients with functional dyspepsia.
Subdiaphragmatic vagal afferent innervation in activation of an opioidergic antinociceptive system in response to colorectal distension in rats
Authors: Gschossmann J. M. , Mayer E. A. , Miller J. C. , Raybould H. E.
Published: March 2003

Abstract
 In a number of different experimental paradigms of somatic pain, there is evidence for a vagally mediated antinociceptive system. This pathway probably involves opioid mechanisms. However, whether this pathway is activated in visceral pain or if it involves subdiaphragmatic vagal afferents is unclear. The aim of the present study was to determine whether subdiaphragmatic vagal afferents mediate antinociception in response to a visceral stimulus and whether this involves an opioid pathway. Colorectal distension was performed in fasted, conscious male Sprague–Dawley rats using a balloon catheter connected to an electronic distension device. The number of abdominal contractions (visceromotor response) in response to a tonic colorectal distension (60 mmHg for 10 min) was recorded. Experiments were performed in sham or subdiaphragmatically vagotomized, perineural vehicle‐ or capsaicin‐treated rats (to functionally denervate vagal afferents) before and after administration of naloxone (25 mg kg−1bodyweight intraperitoneally). Vagotomy, capsaicin and naloxone pretreatments all significantly enhanced the visceromotor response to colorectal distension. The effect of naloxone in capsaicin‐treated rats did not appear to be additive. These results suggest that activation of subdiaphragmatic afferents, which can be blocked by capsaicin, may play a role in opioid‐dependent antinociceptive pathways activated by a noxious visceral stimulus.
Distinct patterns of oesophageal shortening during primary peristalsis, secondary peristalsis and transient lower oesophageal sphincter relaxation
Authors: Shi G. , Pandolfino J. E. , Joehl R. J. , Brasseur J. G. , Kahrilas P. J.
Published: March 2003

Abstract
 This study characterized oesophageal shortening during secondary peristalsis and transient lower oesophageal sphincter relaxation (TLOSR) in an attempt to determine its contribution to the opening mechanism. Eight healthy subjects (four males, 26 ± 1 years) had metal clips affixed at 0, +3, and +8 cm relative to the squamocolumnar junction (SCJ), defining two distal oesophageal segments. Axial clip movement was assessed with concurrent videofluoroscopy and manometry during primary peristalsis, secondary peristalsis and TLOSR. Clip‐defined oesophageal segment length change was measured at 0.5‐s intervals. The magnitude of the most distal segment shortening was least with TLOSR, greatest with primary peristalsis and intermediate with secondary peristalsis. Conversely, maximal overall oesophageal shortening during TLOSR, evidenced by SCJ movement, was similar to that during primary peristalsis. In 3/12 TLOSRs, the moment of LOS opening and gas reflux was optimally imaged; SCJ excursion was 0.3 ± 0.1 cm prior to LOS opening and 1.4 ± 0.7 cm immediately after gas reflux. The segmental pattern of oesophageal shortening was distinct during primary peristalsis, secondary peristalsis and TLOSR. During TLOSR, significant elevation of the SCJ occurred only after LOS opening, suggesting that this was a consequence of oesophageal distension induced by gas reflux rather than a component of the opening mechanism.
HIV‐associated brain pathology: a comparative international study
Authors: Davies J. , Everall I. P. , Weich S. , Glass J. , Sharer L. R. , Cho E. S. , Bell J. E. , Majtenyi C. , Gray F. , Scaravilli F. , Lantos P. L.
Published: March 2003

J. Davies, I. P. Everall, S. Weich, J. Glass, L. R. Sharer, E. S. Cho, J. E. Bell, C. Majtenyi, F. Gray, F. Scaravilli and P. L. Lantos (1998) Neuropathology and Applied Neurobiology24, 118–124

HIV‐associated brain pathology: a comparative international study

Little is known about the frequency and variation of HIV‐associated brain pathology in different geographical centres. To assess whether there is an association between the frequency of disease and demographic factors we examined the neuropathological findings in four European and two American cities. The cities included London, Edinburgh, Paris, Budapest, Baltimore and Newark. Information was collected on a total of 1144 cases. HIV encephalitis was the most common observation in all the centres, although its frequency varied between them (P < 0.01). Furthermore, there were significant differences (P < 0.001) between the various categories of exposure and the frequency of HIV encephalitis in Edinburgh and other centres. The occurrence of toxoplasmosis, progressive multifocal leukoencephalolpathy (PML) and cryptococcal infection also differed between the various centres (P < 0.01). None of the findings was attributable to age, sex, or ethnic origin, but the introduction of anti‐retroviral treatment, such as Zidovudine, may have been important. Overall, this study highlights geographical variability and the potential importance for group of exposure and anti‐retroviral medication as factors affecting the development of various HIV‐associated brain lesions.
Distribution of interleukin‐1‐immunoreactive microglia in cerebral cortical layers: implications for neuritic plaque formation in Alzheimer’s disease
Authors: Sheng  , Griffin  , Royston  , Mrak
Published: March 2003

Activated microglia overexpressing interleukin‐1 (IL‐1) are prominent neuropathological features of Alzheimer’s disease. We used computerized image analysis to determine the number of IL‐1α‐immunoreactive (IL‐1α+ ) microglia in cytoarchitectonic layers of parahippocampal gyrus (Brodmann’s area 28) of Alzheimer and control patients. For cortical layers I and II, the numbers of IL‐1α+ microglia were similar in Alzheimer and control patients. For layers III–VI, the numbers of IL‐1α+ microglia were higher than that seen in layers I–II for both Alzheimer and control patients. Moreover, for layers III–VI, the number of IL‐1α+ microglia in Alzheimer patients was significantly greater than that in control patients (relative Alzheimer values of threefold for layer III–V and twofold for layer VI; P<0.05 in each case). The cortical laminar distribution of IL‐1α+ microglia in Alzheimer patients correlated with the cortical laminar distribution of β‐amyloid precursor protein‐immunoreactive (β‐APP+ ) neuritic plaques found in Alzheimer patients (r=0.99, P<0.005). Moreover, the cortical laminar distribution of IL‐1α+ microglia in control patients also correlated with the cortical laminar distribution of β‐APP+ neuritic plaques found in Alzheimer patients (r=0.91, P<0.05). These correlations suggest that pre‐existing laminar distribution patterns of IL‐1α+ microglia (i.e. that seen in control patients) are important in determining the observed laminar distribution of β‐APP+ neuritic plaques in Alzheimer patients. These findings provide further support for our hypothesis that IL‐1 is a key driving force in neuritic plaque formation in Alzheimer’s disease.
Spinal cord pathology and viral burden in homosexuals and drug users with AIDS
Authors: Shepherd  , Brettle  , Liberski  , Aguzzi  , Ironside  , Simmonds  , Bell
Published: March 2003

Unless treated with effective antiretroviral therapy many AIDS patients develop a characteristic vacuolar myelopathy of the spinal cord associated with moderate clinical disability. Opinion is divided as to whether vacuolar myelopathy is causally linked to HIV myelitis. To investigate this further, spinal cord pathology was assessed in 41 drug users, 33 homosexual men and 16 other patients, all with AIDS. Previous work has shown that HIV encephalitis is more common in Edinburgh drug users than in homosexual men. In the present study HIV myelitis (10% overall) was more common in drug users (17%) than in homosexual men (3%) (P=0.05), whereas the incidence of opportunistic infections (7% v. 9%) and lymphomas (2% v. 6%) was comparable in the two groups, but with a slight trend in the reverse direction, reflecting similar findings in the brain. However, moderate or severe vacuolar myelopathy was equally represented in both groups (20% of drug users and 21% of homosexual men). The HIV proviral load, assessed by polymerase chain reaction in frozen samples of thoracic spinal cord in 37 cases, correlated closely with the presence of giant cells and/or with immunocytochemical evidence of productive HIV infection. In 13 cases, the proviral load was measured in cervical, thoracic and lumbar samples and proved to be uniformly high or low in individual cases. This study provides no evidence for direct involvement of HIV, cytomegalovirus, papovavirus or human foamy virus in the pathogenesis of vacuolar myelopathy.
Immunohistochemical expression of Trk receptor proteins in focal cortical dysplasia with intractable epilepsy
Authors: Nishio  , Morioka  , Hamada  , Hisada  , Fukui
Published: March 2003

Focal cortical dysplasia (FCD), which is often associated with intractable epilepsy, is a form of abnormal structure of the cerebral cortex caused by a disorder of normal neocortical development. In such cerebral lesions obtained from four patients (two male, two female; average age 32.3 years at operation), the immunohistochemical expression of Trk receptors, which interact with neurotrophins and result in both growth and maturational changes in neuronal cells, was investigated in relation to the possible histogenesis of these lesions. In all cases, a derangement of the cortical laminar structure, dysplastic cytomegalic neurones, and large round balloon cells were the characteristic histological features. Immunohistochemically, the TrkA expression was localized in large dysplastic cytomegalic neurones, and TrkB expression was observed in large dysplastic and relatively small neuronal cells within the affected cortex. Although the exact roles of neurotrophins and their receptors in the pathogenesis of FCD remain uncertain, its development might be governed by such neurotrophic influences, and thus possibly prevent the death of abnormal neuronal cells. In addition, Trk receptors in FCDs may also play a role in establishing in the intrinsic epileptogenicity of FCDs.
CADASIL: hereditary disease of arteries causing brain infarcts and dementia
Authors: Kalimo  , Viitanen  , Amberla  , Juvonen  , Marttila  , Pöyhönen  , Rinne  , Savontaus  , Tuisku  , Winblad
Published: March 2003

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) begins with migraine with aura in approximately one‐third of the patients. More severe symptoms of recurrent strokes usually appear at 30–50 years of age. However, well before the first stroke, CADASIL may be diagnosed on the basis of characteristic hyperintensities in T2‐weighted magnetic resonance images. Multiple lacunar infarcts located mainly in the basal ganglia and frontal white matter lead to a cognitive decline and finally to dementia. These infarcts result from a thickening and fibrosis of the walls of the small and medium‐sized penetrating arteries with consequent obliteration and/or thrombosis. Although the symptoms are almost exclusively neurological, the arteriopathy is generalized. Thus, basophilic, periodic acid–Schiff‐positive and, in electron microscopy, osmiophilic material accumulates between degenerating smooth muscle cells. This occurs even in dermal arteries, which renders skin a useful target for diagnostic biopsy. Presently, no specific therapy is available. CADASIL is caused by missense point mutations in the Notch3 gene, which encodes a transmembrane receptor protein. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular, N‐terminal domain of the molecule, which most probably results in conformational alteration. The function of Notch3 in adults and the pathogenesis of CADASIL are still unknown.
Establishment and characterization of a human cell line from paediatric cerebellar glioblastoma multiforme
Authors: Di Tomaso E. , Pang J. C. S. , Ng H. K. , Lam P. Y. P. , Tian X. X. , Suen K. W. , Hui A. B. Y. , Hjelm N. M.
Published: March 2003

Permanent glioma cell lines are invaluable tools in understanding the biology of glioblastomas. The present study reports the establishment of a clonal human cell line, GBM6840, derived from a biopsy of paediatric cerebellar glioblastoma multiforme. GBM6840 had a doubling time of 32 h and grew as a monolayer of large round cells that retained immunopositivity for glial fibrillary acidic protein and vimentin. Karyotypic analysis revealed a modal chromosome number of 68 and polysomies of chromosomes 3, 5 and 20, as well as the presence of 3–4 marker chromosomes. GBM6840 also showed anchorage‐independent growth in soft agar and tumour formation in nude mice. The p16(CDKN2A) gene was transcriptionally silenced by hypermethylation, consistent with the lack of protein expression observed in the original tumour and cultured cells. Western blot analysis revealed normal protein expression of pRb and CDK4. It appears that p16 is the major component altered in the cell cycle pathway and may confer these cells unrestrained proliferation potential. Neither EGFR gene amplification nor over‐expression of the protein was detected in the cultured cells. Over‐expression of the p53 protein was observed in the majority of cells, despite undetectable mutation (exons 5–8) in the gene. One allele of the PTEN gene was found to be mutated during in vitro cultivation. Telomerase activity was demonstrated in the cultured cells but not in the original tumour, supporting the hypothesis that telomerase is required for the in vitro immortalization process.
Caspase‐cleaved actin (fractin) immunolabelling of Hirano bodies
Authors: Rossiter J. P. , Anderson L. L. , Yang F. , Cole G. M.
Published: March 2003

Hirano bodies are eosinophilic rod‐like inclusions that are found predominantly in neuronal processes in the hippocampal CA1 sector with increasing age and are particularly numerous in Alzheimer’s disease. They contain a variety of cytoskeletal epitopes, especially actin and actin‐binding proteins. Actin cleavage by cysteinyl aspartate‐specific proteases (caspases) is a feature of apoptosis. Cleavage at aspartate 244 generates N‐terminal 32 kDa and C‐terminal 15 kDa actin fragments. This has led to the development of a rabbit polyclonal antibody specific for caspase‐cleaved actin, directed to the last five C‐terminal amino acids of the 32 kDa fragment of actin (‘fractin’). Fractin immunohistochemistry was performed on hippocampal sections from Alzheimer’s disease and control cases containing numerous Hirano bodies, in addition to immunolabelling with CM1 antiserum which recognizes activated caspase‐3. The Hirano bodies showed strong diffuse fractin immunoreactivity. They did not label with CM1 antiserum, perhaps reflecting too low a level of activated caspase‐3 for immunodetection, or involvement of a different member of the caspase family. The finding of fractin immunoreactivity of Hirano bodies suggests that caspase‐like cleavage of actin may play a role in their formation and further supports caspase‐like activity in neuronal processes, distinct from that associated with acute perikaryal apoptosis.
Motor neuronal death in sporadic amyotrophic lateral sclerosis (ALS) is not apoptotic. A comparative study of ALS and chronic aluminium chloride neurotoxicity in New Zealand white rabbits
Authors: He B. P. , Strong M. J.
Published: March 2003

Whether diseased motor neurones in sporadic amyotrophic lateral sclerosis (ALS) die via apoptosis is unknown. Because this relates primarily to difficulties in utilizing post‐mortem tissue from end‐stage disease, motor neurone degeneration in ALS spinal cord was compared with that of a model of a chronic motor neurone degeneration. Degenerating motor neurones in ALS, identified by ubiquitin immunoreactivity, did not demonstrate the morphological characteristics of apoptosis and were not c‐Jun immunoreactive or TUNEL positive. A temporal analysis of spinal motor neurone death in the chronic AlCl3 neurotoxicity model of motor neurone degeneration was also undertaken. AlCl3 was administered intracisternally every 4 weeks and, at intervals of 51, 107, 156 and 267 days, evidence of apoptosis was sought by morphology, TUNEL hybridization or DNA laddering. Double‐labelling immunostudies were also performed with antibodies to either c‐Jun, ubiquitin or high molecular weight neurofilament (NFH) with TUNEL hybridization. Although significant neurone loss was evident, apoptosis was not found. These studies demonstrate a lack of apoptosis in ALS spinal motor neurones and suggest that this observation does not relate to the utilization of post‐mortem tissue in which apoptotic neurones may have been lost.
Accelerated ageing changes in the choroid plexus of a case with multiple mitochondrial DNA deletions
Authors: Cottrell D. A. , Ince P. G. , Wardell T. M. , Turnbull D. M. , Johnson M. A.
Published: March 2003

Mitochondrial abnormalities, in particular the accumulation of mitochondrial DNA mutations, have been proposed as a potential cause of normal ageing. One group of patients with mtDNA disorders have a nuclear DNA defect which accelerates the chronological accumulation of mitochondrial DNA mutations. These patients provide an ideal means of investigating whether accelerated mitochondrial DNA defects can cause accelerated ageing pathology. The choroid plexus demonstrates a robust accumulation of pathological changes, in the form of Biondi bodies, with normal ageing. We have therefore examined the choroid plexus of a case with multiple mitochondrial DNA deletions for evidence of accelerated ageing and compared it with two cases with point mutation mitochondrial DNA disorders and several age‐matched and elderly controls with and without clinical and neuropathological evidence of neurodegenerative disease. We also demonstrate that the choroid plexus of the mitochondrial DNA cases contain cells with levels of mitochondrial DNA mutation sufficient to cause a biochemical deficiency in the oxidative phosphorylation pathway. As previously reported, both cases with point mutation mitochondrial DNA disorders exhibit a characteristic oncocytic type transformation of the choroidal epithelial cells. However, in the case with multiple mitochondrial DNA deletions we demonstrate pathological changes in choroid plexus that are strongly suggestive of accelerated ageing. We believe that this finding supports the theory that the accumulation of mitochondrial DNA mutations can lead to pathological changes typical of ageing cells.
Human medulloblastomas lack point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene
Authors: Kraus J. A. , Oster C. , Sörensen N. , Berthold F. , Schlegel U. , Tonn J. C. , Wiestler O. D. , Pietsch T.
Published: March 2003

Medulloblastomas (MBs) are malignant primitive neuroectodermal tumours (PNETs) of the cerebellum occurring predominantly in childhood. The association of monosomy of chromosome 22 with MB is controversial. Atypical teratoid/rhabdoid tumours (AT/RTs) of the brain share clinical and histological features with MBs and supratentorial PNETs (sPNETs). In particular, AT/RTs can be misdiagnosed as MBs and sPNETs because AT/RTs frequently contain areas of primitive neuroepithelial cells similar to PNETs. Recently, mutations of the tumour suppressor gene hSNF5/INI1, located on 22q11.23, have been described in AT/RTs, MBs and sPNETs, with conflicting data on the prevalence of hSNF5/INI1 mutations in the latter entities. Therefore, we screened MBs for point mutations and homozygous deletions of the hSNF5/INI1 tumour suppressor gene. In 90 MBs, no mutations of the hSNF5/INI1 gene were identified. Thus, our study virtually rules out hSNF5/INI1 as a tumour suppressor gene involved in the pathogenesis of medulloblastoma.
The threat to primates and other mammals from the bushmeat trade in Africa, and how this threat could be diminished
Authors: Jones-Bowen Evan , Pendry Stephanie
Published: March 2003

The threat that the bushmeat trade presents to primates and other taxa was assessed from the literature, including data from markets, village hunting studies and logging concessions in Central and West Africa. In many cases the numbers of both common and protected species of primate being killed throughout the region are thought to be unsustainable. This is also the case for other taxa involved in the bushmeat trade, which crosses geographic, cultural and economic boundaries. A suite of measures must be considered to mitigate the effects of this trade, and these measures will have to recognize the local, regional and national socio-economic importance of the trade if they are to result in long-term conservation success.
Risks of induction of labour in uncomplicated term pregnancies
Authors: Boulvain  , Marcoux  , Bureau  , Fortier  , Fraser
Published: March 2003

Our objective was to evaluate the risks of maternal and perinatal morbidity associated with induction of labour in uncomplicated term pregnancies. We conducted a retrospective cohort study including 7430 women, not referred from another institution, with a single baby in vertex presentation, and delivering between 38 and 40 weeks of pregnancy. Among these women, 3546 were excluded for prelabour pregnancy complications. Relative risks (RR), adjusted for parity, were computed to compare 3353 women who went into labour spontaneously with 531 women whose labour was induced. Induction of labour was found to be associated with a higher risk of caesarean section [RR = 2.4, 95% CI 1.8, 3.4]. Use of non‐epidural [RR = 1.5, 95% CI 1.2, 1.8] and of epidural analgesia [RR = 1.4, 95% CI 1.1, 1.7] was more frequent after labour induction. Resuscitation [RR = 1.2, 95% CI 1.0, 1.5], admission to the intensive care unit [RR = 1.6, 95% CI 1.0, 2.4] and phototherapy [RR = 1.3, 95% CI 1.0, 1.6] were more frequent after induction of labour. Results were similar when controlling simultaneously for parity, maternal age, gestational age, year of delivery, birthweight and the physician in charge of delivery in a logistic regression analysis. The results of this study suggests that induction of labour is associated with a higher risk of caesarean section and of some perinatal adverse outcomes. Induction of labour should be reserved for cases where maternal and perinatal benefits outweigh the risk of these complications.
Risk factors for low birthweight in north‐east Brazil: the role of caesarean section
Authors: Silva Antônio A.M. , Lamy‐Filho Fernando , Alves Maria T.S.S.B. , Coimbra Liberata C. , Bettiol Heloisa , Barbieri Marco A.
Published: March 2003

Caesarean section (CS) delivery is associated with low birthweight (LBW) in south‐east Brazil. A hospital‐based study was conducted on singleton infants from mothers residing in São Luís, to assess if an association between CS and LBW was found in the northern part of the country, where the CS rate is lower than in the south‐east. A standardised questionnaire was administered to a sample of 2541 mothers in 10 hospitals, representing 94% of all deliveries, from March 1997 to February 1998. In a logistic model, type of delivery was the independent variable, the other variables were treated as confounders, and interaction terms were added between type of delivery and all other factors. LBW was associated with low maternal height, maternal smoking, primiparity, previous LBW, public insurance, preterm birth and CS. The CS rate was 33.7%. The risk of CS was higher for primiparous and married mothers, those with high level of schooling and attended by the same physician during prenatal and delivery care, deliveries held in private hospitals, daylight hours or evenings, and for those mothers who had adequate prenatal care. Because it appears unlikely that only medical reasons are operative, it is a possibility that CS could cause LBW, reflecting abusive indications for elective CS.
Prevalence of cigarette smoking in pregnant women participating in the special supplemental nutrition programme for Women, Infants and Children (WIC) in Minneapolis and Saint Paul, Minnesota, USA
Authors: Ross Julie A. , Swensen Andrine R. , Murphy Sharon E.
Published: March 2003

Several adverse birth outcomes are associated with cigarette smoking. It is important to determine the prevalence of cigarette smoking among pregnant low‐income women and to evaluate their smoking cessation patterns in order to target appropriate interventions. Ethnically diverse pregnant women aged 15–45 years were recruited from Minneapolis or Saint Paul Women, Infants, and Children (WIC) clinics before their third trimester. Serum cotinine levels were assayed for 98 women and compared with self‐report. The women were unaware that their smoking status would be validated. Twenty‐one (21%) women had a positive serum cotinine value (≥3 ng/mL); 16 (76%) admitted smoking within the previous 24 h before interview and five denied smoking. Of the five, four had cotinine levels that could suggest passive smoke exposure. Thirty‐seven women (38%) admitted cigarette smoking during the pregnancy but before knowing that they were pregnant; 18 (49%) of these denied current smoking at the interview and also presented with negative cotinine levels. These data suggest that some participants in WIC make a concerted effort to quit smoking when they find out they are pregnant, and are generally truthful when reporting their smoking habits during pregnancy.
Maternal second‐trimester serum ferritin concentrations and subsequent risk of preterm delivery
Authors: Xiao Rong , Sorensen Tanya K. , Frederick Ihunnaya O. , El‐Bastawissi Amira , King Irena B. , Leisenring Wendy M. , Williams Michelle A.
Published: March 2003

We studied the relationship between maternal second‐trimester serum ferritin concentrations and preterm delivery. The 312 preterm delivery cases, studied in aggregate and in subgroups [spontaneous preterm labour, preterm premature rupture of membranes, medically induced preterm delivery, moderate preterm delivery (gestational age at delivery 34–36 weeks) and very preterm delivery (gestational age at delivery <34 weeks)] were compared with 424 randomly selected women who delivered at term. Maternal ferritin concentrations, measured in serum collected at 17 weeks gestation on average, was determined using a two‐site chemiluminometric immunoassay. Using multiple logistic regression, we derived maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals [CI]. Elevation in maternal second‐trimester ferritin was weakly associated with the risk of preterm delivery overall. After adjusting for possible confounding by maternal age, race/ethnicity, parity, Medicaid payment status and smoking during the index pregnancy, the OR for extreme quartiles (>64.5 vs. <26.0 ng/mL) of ferritin was 1.3 [95% CI 0.8, 2.1]. Stratified analyses indicated that elevated maternal serum ferritin was associated with an increased risk of preterm premature rupture of membranes (OR = 2.1; 95% CI 1.1, 4.1), but not with spontaneous preterm labour (OR = 0.9; 95% CI 0.4, 1.7) or medically induced preterm delivery (OR = 1.1; 95% CI 0.6, 2.0). The relationship between elevated maternal second‐trimester serum ferritin concentrations and preterm delivery was strongest for spontaneous very preterm deliveries (<34 weeks gestation). Women with ferritin concentrations in the highest decile (>96 ng/mL) experienced a 2.7‐fold increased risk of delivering before 34 completed weeks, compared with women with concentrations <26.0 ng/mL. These results are consistent with some previous reports, and further underline the potential for heterogeneity in the aetiology of preterm delivery.
Relevance of circulating antigen detection to follow‐up experimental and human cystic hydatid infections
Authors: Ferragut G , Ljungström I , Nieto A
Published: March 2003

We analysed specific antibody (Ab) and circulating antigen (CAg) profiles along experimental mouse infection using as control a group of mice immunized with intact but dead parasites. Results from this experiment showed an early major CAg peak followed by a larger Ab peak which partially overlaps with other minor CAg peaks. These results suggest that CAg may be a marker of early mouse infection. In order to study the relevance of these findings in humans we similarly analysed by ELISA 148 sera provided by retrospective post‐surgical follow‐up of 19 patients. Available records showed that 14 patients developed new cysts one to ten years after surgery while no new disease was observed in the other five. Some of the former patients showed CAg as early as two months after surgery while no CAg was observed in the other five patients at any time. In addition, a collection of 38 sera obtained before surgery were similarly tested and five of them showed only CAg, while 18 showed only Ab and 12 sera showed Ab&CAg. These results in humans are consistent with the findings in the mouse experimental model and suggest that CAg may be an early marker of hydatid infection, thus being relevant for post‐surgical follow‐up.
A hookworm allergen which strongly resembles calreticulin
Authors: Pritchard  , Brown Alan , Kasper Grit , Mcelroy Paul , Loukas Alex , Hewitt Colin , Berry Colin , Füllkrug Ralf , Beck Ewald
Published: March 2003

Immmoglobulin E‐rich plasma from patients from Papua New Guinea infected with Necator americanus has been used to probe an adult N. americanus cDNA library for the presence of hookworm allergens. Using this approach, one hookworm allergen has been identified as calreticulin, which was subsequently expressed in Escherichia coli. Little serological cross reactivity was seen between the recombinant calreticulins of this hookworm and its host. Prospective roles for hookworm calreticulin in the host‐parasite relationship are discussed in depth.
The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro
Authors: Balmer Paul , Phillips Helen M. , Maestre Amanda E. , McMonagle Fiona A. , Phillips Stephen R.
Published: March 2003

Protective immune mechanisms to the asexual erythrocytic stages of the malaria parasite Plasmodium chabaudi AS strain include antibody‐independent mechanisms. Nitric oxide (NO) is produced during the infection and indirect evidence suggests that it can contribute to the antiparasitic mechanisms. We examined the effect of an NO producer, S‐nitroso‐acetyl‐penicillamine (SNAP), on the growth and survival in vitro of P. chabaudi AS, P. berghei and P. falciparum. Growth of the parasites was monitored by the uptake of tritiated hypoxanthine and, in the case of P. falciparum,by morphological examination in stained blood smears.
dl‐penicillamine and sodium nitrite, as controls, had no inhibitory activity at the concentrations used. The results showed that at SNAP concentrations of approximately 182 μm and above NO was cytotoxic to P. falciparum but, at lower concentrations, there was a cytostatic effect and some parasites resumed growth and division after NO production had ceased. Rings were less susceptible to NO effects than later stages in the asexual cycle. The antimalarial activity of NO from SNAP also extended to the rodent parasites but, under the experimental conditions used, they were less sensitive than the human species. In the cultures of P. chabaudi,increasing the numbers of noninfected erythrocytes present did not diminish the antimalarial activity of SNAP, suggesting that here at least haemoglobin was not scavenging NO significantly.
Differential immunoglobulin E and cytokine responses in BALB/c and C57Bl/6 mice during repeated infections with blood‐stage Plasmodium chabaudi malaria
Authors: Helmby Helena , Troye‐Blomberg Marita
Published: March 2003

Repeated blood‐stage Plasmodium chabaudi chabaudi AS challenge infections in BALB/c and C57Bl/6 mice result in increased serum immunoglobulin (Ig) E levels and splenic cytokine production. The genetic background of the host influences both the cytokine response as well as the development of IgE antibodies. BALB/c mice showed high interleukin (IL)‐4 secretion from splenocytes after in‐vitro stimulation with malaria antigen after repeated P. chabaudi challenges and this was closely followed by higher levels of total IgE. Despite slightly elevated serum IgE levels, splenocytes from C57Bl/6 mice did not secrete any detectable IL‐4 but produced interferon (IFN)‐γ in response to malaria antigen‐stimulation in vitro. These data suggest that induction of IgE antibodies during murine malaria infection is genetically regulated.
Juvenile Fasciola hepatica are resistant to killing in vitro by free radicals compared with larvae of Schistosoma mansoni
Authors: Piedrafita David , Spithill Terry W. , Dalton John P. , Brindley Paul J. , Sandeman Mark R. , Wood Paul R. , Parsons Jim C.
Published: March 2003

Free radicals have previously been shown to kill the immature stages of the trematode, Schistosoma mansoni but their effect on newly excysted juvenile (NEJ) flukes of Fasciola hepatica has not been established. Using acetaldehyde and xanthine oxidase to chemically generate reactive oxygen intermediates (ROI), up to 61% of NEJ were killed but only when exposed to high levels of ROI. At low concentrations of acetaldehyde and xanthine oxidase as sources of reactive oxygen intermediates, only 6–29% of NEJ were killed compared with 70–92% of schistosomula. Incubation with lipopolysaccharide (LPS)‐stimulated rat peritoneal lavage cells (PLCs) killed only 7–15% of NEJ whereas 78–87% of schistosomula were killed under the same conditions by a mechanism dependent on the production of reactive nitrogen intermediates. Relative to immature and adult parasites, NEJ expressed 2.5–20‐fold lower levels of superoxide dismutase and glutathione S‐transferase but no catalase activity was detected. Incubation of NEJ with inhibitors of peroxidases and glutathione metabolism increased the mean killing of NEJ by LPS‐stimulated rat PLCs to 40–75%. These results demonstrate that, in comparison to schistosomula of S. mansoni, NEJ of F. hepatica are relatively resistant to killing by free radicals and this resistance could, in part, be due to the activity of oxidant scavenger enzymes of NEJ.
Protective mechanisms against the intestinal nematode Strongyloides venezuelensis in Schistosoma japonicum‐infected mice
Authors: Maruyama Haruhiko , Osada Yoshio , Yoshida Ayako , Futakuchi Mitsuru , Kawaguchi Hitoshi , Zhang Renli , Fu Jun , Shirai Tomoyuki , Kojima Somei , Ohta Nobuo
Published: March 2003

Mice infected with Schistosoma japonicum were resistant to the intestinal nematode, Strongyloides venezuelensis. The numbers of adult S. venezuelensis recovered from mice were significantly decreased when infections were given from 6 weeks after S. japonicum infection. Larval recovery from the lungs showed that significant numbers of subcutaneously inoculated S. venezuelensis larvae were eliminated by 3 days in S. japonicum‐infected mice (P < 0.0001), while histology revealed that this was associated with massive eosinophilic infiltration in the lungs. In addition, adult S. venezuelensis worms implanted in the duodenum of S. japonicum‐infected mice could not establish in the intestine. This failure was associated with mucosal mastocytosis. Activation of eosinophils and intestinal mast cells was correlated with elevated expression of mRNA for interleukin (IL)‐3, IL‐4, and IL‐5 in S. japonicum‐infected mice. Sera from S. japonicum‐infected mice recognized S. venezuelensis larva antigens as strongly as those from S. venezuelensis‐infected mice, although transfer of sera from S. japonicum‐infected mice to normal recipient mice did not protect them from S. venezuelensis challenge infection. It was concluded that the mechanisms for larval killing and adult worm expulsion of S. venezuelensis in S. japonicum‐infected mice were identical to those seen in infections with S. venezuelensis only.
Protective immunity in human Bancroftian filariasis: inverse relationship between antibodies to microfilarial sheath and circulating filarial antigens
Authors: Ravindran B. , Satapathy A.K. , Sahoo P.K. , Babu Geddam J.J.
Published: March 2003

The existence and the nature of protective immunity in human filariasis continues to be a subject of intense debate. While there is no broad consensus on functional immunity against larval and adult stage parasites, anti‐microfilarial immunity has been demonstrated to be mediated by antibodies to the microfilarial sheath. In the present study, circulating filarial antigens (CFA), a marker of active filarial infection in human Bancroftian filariasis, was found to be inversely associated with antibodies to microfilarial sheath in a cohort of 411 subjects representing all categories of filariasis across the clinical spectrum of the disease. Approximately 80% of humans of all age groups (5–65 years) were found to have either CFA or anti‐sheath antibodies. The inverse relationship observed between these two parameters was found to be independent of the clinical manifestation; both symptomatic and asymptomatic cases were found to display similar inverse association between CFA and anti‐sheath antibodies. The prevalence of anti‐sheath antibodies in the paediatric group was found to be very high as compared to adults; 78% of children below the age of 10 years tested positive for anti‐sheath antibodies although the mf rate and CFA rate were only 4.5% and 22.7%, respectively, in this age group, indicating that developing larvae or juvenile adult stage parasites could have been the source of antigenic stimulus for induction of antibodies to the microfilarial sheath.
Involvement of complement and fibronectin in eosinophil‐mediated damage to Nippostrongylus brasiliensis larvae
Authors: Shin Eun‐Hee , Osada Y. , Sagara H. , Takatsu K. , Kojima S.
Published: March 2003

By using IL‐5 transgenic mice, it has been shown that eosinophils might play a key role in elimination of larval stages of nematode infections. The present study was carried out to clarify molecular mechanisms involved in the eosinophil‐mediated killing of Nippostrongylus brasiliensis larvae. The larvicidal activity was observed in the presence of normal serum in vitro. Electron microscopic observations revealed firm attachment of eosinophils to the cuticular surface of larvae, which was damaged by electron‐dense materials released from eosinophils. The larvicidal activity was abrogated by heat‐ or zymosan‐treatment of the serum, whereas depletion of IgG or IgM from the serum did not interfere with eosinophil adhesion and killing. Moreover, pretreatment of eosinophils with monoclonal antibodies against CD11b or VLA‐4 inhibited the eosinophil‐mediated killing of larvae. Immunofluorescent staining demonstrated the deposition of C3c and plasma fibronectin on the cuticle of the larvae. These results indicate that interactions between CD11b and VLA‐4 and their respective counter‐ligands deposited on the cuticle are essential in eosinophil‐mediated adhesion and damage to larvae of N. brasiliensis.
The Schistosoma mansoni egg‐derived r38 peptide‐induced Th1 response affects the synchronous pulmonary but not the asynchronous hepatic granuloma growth
Authors: Chen Yiguang , Boros Dov L.
Published: March 2003

The p38 peptide derived from Schistosoma mansoni egg‐antigens (SEA) is a preferential inducer of the Th1 response. In the present study, we investigated whether induction of a p38‐specific Th1 or Th2 response can influence granuloma development in infected or sensitized mice. Mice sensitized with SEA/IL‐12 3 weeks after infection but before worm oviposition commenced developed Th1 cytokine responses and had significantly reduced hepatic granuloma size. Similar immunization with p38/IL‐12 induced a strong peptide‐specific Th1, mixed SEA‐specific Th1/Th2 responses without effect on hepatic granuloma development. Presentation of p38 with alum or alum/IL‐12 mixture enhanced Th2 cytokine responses and hepatic granuloma sizes. In the synchronized pulmonary model, sensitization of naïve mice with p38/IL‐12 induced a strong Th1 cytokine production to p38 and SEA, led to a moderate increase in granuloma growth at days 4 and 8 following egg injection and actually promoted the resolution of the lesion by day 16. Sensitization with p38 in alum induced Th2 cytokine production and generated the largest granulomas whereas the p38/alum/IL‐12 sensitized group showed intermediate results in cytokine production and granuloma growth. Thus, in infected mice, the p38 induced strong Th1 response was insufficient to cross‐regulate the evolving Th2 environment that generated large granulomas.
Regional immune responses with stage‐specific antigen recognition profiles develop in lymph nodes of pigs following Ascaris suum larval migration
Authors: Jungersen Gregers , Eriksen Lis , Nansen Peter , Lind Peter , Rasmussen Tina , Meeusen Els N.T.
Published: March 2003

The early life‐cycle of the pig round worm, Ascaris suum, involves well‐defined larval development in the liver, lungs and finally the small intestine. Distinct regional immune responses to larval antigens of A. suum were observed in the draining lymph nodes of immunized and challenged pigs during larval migration. This was reflected in a transient enlargement of the stimulated lymph nodes, due to increases in numbers of B cells and CD4 T cells, and the production of A. suum‐specific antibody by antibody secreting cell (ASC) cultures. Larval antigen recognition pattern of antibodies in serum, bile and draining lymph node ASC culture supernatant (ASC‐probes) was examined by immunoblotting. This revealed distinct organ‐specific recognition patterns of larval‐specific antigens by the draining lymph nodes at different times after challenge. In particular, an early larval 42 kDa antigen was recognized specifically by ASC‐probes of the liver lymph nodes at 7 but not 14 days postchallenge (pc) which was not detected in other lymph nodes, serum or bile of the same pig. Similarly, a late larval antigen of 34 kDa was uniquely detected by lung and jejunal ASC‐probes at 14 days pc. These observations demonstrate how development of distinct regional immune responses in tissues with different antigen stimulation can be monitored with ASC‐probes and flow cytometry.
Cellular immune responses of filaria (Litomosoides sigmodontis) infected BALB/c mice detected on the level of cytokine transcription
Authors: Taubert Anja , Zahner Horst
Published: March 2003

Cellular immune responses of BALB/c mice infected with 80 or 160 L3 of Litomosoides sigmodontis were studied over a period of 200 days postinfection (p.i.) by stimulating spleen cells with specific microfilariae and adult antigens and Concanavalin A (Con A). Effects were determined as the level of transcription of cytokine genes [interleukin (IL)‐2, interferon (IFN)‐γ, IL‐4, IL‐5, IL‐10, IL‐13] employing a semiquantitative reverse transcriptase‐polymerase chain reaction technique. Con A stimulation resulted in generally enhanced transcription levels in infected animals. Exposure to filarial antigens stimulated T cells of infected animals dependent on time p.i. There was a general strong response in the early prepatency (24 days p.i.), a temporary almost complete downregulation of cytokine gene transcription except IL‐10 towards the end of prepatency (45 days p.i.), and subsequently strong reactions particularly concerning IFN‐γ and IL‐13 during patency and postpatency. The dose of infection as well as the mode of antigenic stimulation had generally only small effects on the cytokine gene transcription: following the same type of kinetics, infection with 160 L3 as well as the use of microfilarial antigen generally induced lower levels of cytokine gene transcription compared with infection with 80 L3 and stimulation with female antigen, respectively.