bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of duodenal fat, protein or mixed‐nutrient infusions on epigastric sensations during sustained gastric distension in healthy humans
Authors: FEINLE C. , CHRISTEN M. , GRUNDY D. , FAAS H. , MEIER O. , OTTO B. , FRIED M.
Published: March 2003

Duodenal fat modulates sensory and motor responses to gastric distension and raises plasma cholecystokinin compared with glucose. The effects of protein (also releasing cholecystokinin), or mixed nutrients (with a balanced macronutrient composition), on gastrointestinal sensations in relation to gastric relaxation and plasma cholecystokinin concentrations are not known. The aim of this study was therefore to compare the effects of duodenal infusion of fat, protein or mixed nutrients during sustained gastric distension (mimicking the intragastric presence of food) on these parameters. In 10 healthy subjects, gastric distension to fullness was maintained for 90 min, while gastric volume, sensations and plasma cholecystokinin were monitored during duodenal infusion of isotonic saline or nutrients (2 kcal min−1). During saline infusion, all parameters remained unchanged for 90 min. Initially, only lipid increased plasma cholecystokinin, gastric volume and scores for sensations. Cholecystokinin and gastric volume responses to protein and mixed nutrients were delayed and not associated with significant changes in sensations. In conclusion, the intensity of gastrointestinal sensations is related to, but not entirely explained by, the magnitude in intragastric volume and plasma cholecystokinin changes. Our results offer new insights into the role of dietary nutrient composition in gastrointestinal sensations, and may have implications for the dietary management of digestive symptoms.
Distinct regional expression of SNARE proteins in the feline oesophagus
Authors: Ji J. , Lau H. , Sheu L. , Diamant N. E. , Gaisano H. Y.
Published: March 2003

Abstract
 Soluble N‐ethylmaleimide‐sensitive factors attachment protein receptors (SNAREs), initially found to mediate membrane fusion, have now been shown to also bind and regulate a number of membrane ion channels in neurones and neuroendocrine cells. We recently reported that the SNARE protein SNAP‐25 regulates Ca2+‐ activated (KCa) and delays rectifier K+channels (KV) in oesophageal smooth muscle cells. This raised the possibility that cognate and other SNARE proteins could also be present in the oesophageal smooth muscle cell to regulate these and other functions. Circular muscle tissue sections and single freshly isolated muscle cells from the oesophageal body circular and longitudinal layers, and from lower oesophageal sphincter clasp and sling regions were studied. The subcellular location of SNAP‐23, SNAP‐25, syntaxins 1 to 4, and vesicle‐associated membrane protein (VAMP)‐2 were explored using a laser scanning confocal imaging system. Feline oesophageal smooth muscle of all regions examined demonstrated the presence of SNAP‐23, SNAP‐25, syntaxins 1 to 4, and VAMP‐2 on the plasma membrane. The intensity of these syntaxins and SNAP‐25/‐23 proteins varied between the different muscle groups of the oesophagus. In some regions, some SNARE proteins were also noted in the muscle cell cytoplasm. No differential expression was found for VAMP‐2. The differential expression of SNAP‐25 and its regulation of K+channels indicate the important role of SNAP‐25 in regulating the distinct membrane excitability and contractility along the smooth muscle of the oesophagus. This is further contributed by its interactions with the cognate syntaxins, which are also differentially expressed in the muscle groups of the oesophageal body and lower oesophageal sphincter (LOS). These SNARE proteins probably have other functions in the smooth muscle cell, such as regulating vesicular transport processes.
Effect of lipopolysaccharide on rabbit small intestine muscle contractilityin vitro: role of prostaglandins
Authors: Rebollar E. , Arruebo M. P. , Plaza M. A. , Murillo M. D.
Published: March 2003

AbstractThe purpose of this study was to investigate the effect of lipopolysaccharide (LPS) on spontaneous contractions and acetylcholine (ACh) induced contractions of rabbit intestinal segments in vitro, with two different protocols: intestinal segments isolated from LPS‐treated rabbits and intestinal segments incubated with LPS. The frequency of spontaneous movements decreased significantly in LPS‐treated rabbits at 2 μg kg−1in the duodenum and 20 μg kg−1in the duodenum, jejunum and ileum. LPS (0.2 μg kg−1) reduced significantly the ACh contractions (10−6mol L−1) in the duodenum (61%), jejunum (48%) and ileum (21%). Indomethacin (1, 5 and 10 mg kg−1) administered 15 min before LPS (0.2 μg kg−1) antagonized the LPS effects on the ACh‐induced contractions. Prostaglandin (PG)E2(8 μg kg−1) inhibited significantly the frequency of spontaneous contractions in the ileum and reduced the ACh‐induced contractions in the three segments, mimicking the LPS effects. The amplitude and frequency of contractions in rabbit intestinal segments previously incubated with LPS (0.03, 0.3, 3 and 30 μg mL−1) were not modified with respect to the control. The ACh‐induced contractions (10−4 mol L−1) were significantly reduced after 90 min of incubation with LPS. The inhibition of LPS (0.3 μg mL−1) was 43% in the duodenum, 35% in the jejunum and 17% in the ileum. Indomethacin added before LPS blocked the effect of LPS on the ACh‐induced contractions in the duodenum, jejunum and ileum. These results show that LPS decreases intestinal contractility in rabbits and suggest that PGs are implicated in these actions.
Prion encephalopathy with insertion of octapeptide repeats: the number of repeats determines the type of cerebellar deposits
Authors: Vital C. , Gray F. , Vital A. , Parchi P. , Capellari S. , Petersen R. B. , Ferrer X. , Jarnier D. , Julien J. , Gambetti P.
Published: March 2003

C. Vital, F. Gray, A. Vital, P. Parchi, S. Capellari, R. B. Petersen, X. Ferrer, D. Jarnier, J. Julien and P. Gambetti (1998) Neuropathology and Applied Neurobiology24, 125–130

Prion encephalopathy with insertion of octapeptide repeats: the number of repeats determines the type of cerebellar deposits

We studied modifications of the molecular layer of the cerebellum in three patients with octapeptide repeat insertion (OPRI). Two brothers carrying a six‐OPRI showed only spongiosis in haematoxylin & eosin preparations (H&E), whereas immunocytochemical examination (ICC) with an antiprion protein (PrP) antibody revealed numerous elongated PrP deposits. The third patient from a family with an eight‐OPRI had numerous plaques visible in H&E preparations and had been diagnosed as Gerstmann‐Straüssler–Scheinker syndrome. So far, 15 other cases from seven families and three individual cases with OPRI have undergone neuropathological examination. Characteristic PrP deposits were seen in six other cases, two isolated cases with a four‐ and a seven‐OPRI, whereas four cases with a six‐OPRI came from three different families. Such deposits have never been reported in other cases of prion encephalopathy, without OPRI. Genuine plaques were observed in five out of the 15 other patients. Interestingly, four had an eight‐OPRI and one a nine‐OPRI. Cases with OPRI are prone to develop different PrP deposits: those only visible on ICC are not to be confused with genuine plaques visible in H&E preparations. Elongated PrP deposits are present in cases with a four‐ to seven‐OPRI, whereas plaques are present when there is an eight‐ or a nine‐OPRI. All these cases should be termed prion encephalopathy with OPRI.
Infantile HIV encephalopathy associated with cerebral and cerebellar telangiectases
Authors: Luzar  , Popovi  , Cerar
Published: March 2003

We describe a paediatric case of HIV encephalopathy associated with cerebral and cerebellar telangiectases. Although immunohistochemistry failed to show HIV in the walls of dilated blood vessels, or in their vicinity, brain capillary telangiectases might be an additional complication indirectly related to paediatric HIV infection.
Clinicopathological correlation of cell proliferation, apoptosis and p53 in cerebellar pilocytic astrocytomas
Authors: Haapasalo  , Sallinen  , Sallinen  , Helén  , Jääskeläinen  , Salmi  , Paetau  , Paljärvi  , Visakorpi  , Kalimo
Published: March 2003

We have analysed 78 cerebellar pilocytic astrocytomas to assess whether histopathology, cell proliferation, apoptosis rate, p53 immunoreactivity, or flow cytometry could predict their long‐term behaviour. Classic pilocytic/microcystic pattern was seen in 62 patients and 16 patients had mixed pattern with an additional non‐pilocytic glial component. The overall 5‐year survival was 93%, complete resection providing 100% survival. The four patients who died during the follow‐up were more than 14 years of age, their primary operation had been incomplete and three of them were mixed variants. In 15 cases the tumour recurred giving a recurrence‐free 5‐year survival of 77%. The proliferation indices were low: Ki‐67MIB‐1 (median 2.0%), PCNA (1.2%) and S‐phase fraction (4.4%). The Ki‐67MIB‐1‐labelling index was significantly higher in young patients, but did not differ between the classic and mixed variants. Twenty‐two per cent of the tumours were aneuploid with a significantly higher S‐phase fraction than in diploid tumours. p53 seems to act as ardian of the genome’ in pilocytic astrocytomas, because aberrant/increased expression of p53 and aneuploidy associated with enhanced apoptosis. Only patient age (P=0.01), radicality of the primary operation (P=0.0001) and histology (classic vs mixed, P=0.008) significantly correlated with survival. The poorer prognosis of the mixed variant suggests that this may represent a distinct entity. Although none of the novel parameters significantly predicted recurrence or survival, they indicate substantial biological variation among cerebellar pilocytic astrocytomas.
Upregulation of microglia in drug users with and without pre‐symptomatic HIV infection
Authors: Tomlinson  , Simmonds  , Busuttil  , Chiswick  , Bell
Published: March 2003

It is generally thought that infection of the central nervous system (CNS) by HIV‐1 can occur early, even around the time of seroconversion, and evidence from animal studies supports this. However, the mode and timing of viral entry remain poorly understood since there have been comparatively few studies of the early neuropathology of HIV infection. In this study, samples of frontal and temporal lobes, and basal ganglia, were selected from 12 HIV‐positive drug users who had been infected for 4–130 months before death, 10 HIV‐negative drug users and 10 non‐drug using controls, all age and sex matched. Routine and immunocytochemical staining showed that leptomeningeal and perivascular lymphocytic infiltrate was upregulated in HIV‐infected cases compared with the two control groups, and choroid plexitis was confined to the HIV‐positive subjects, suggesting an association with viral infection. In contrast, CD68‐positive microglia were enhanced in both HIV‐ positive and HIV‐negative drug users, considerably above the baseline seen in normal controls. However, there was no statistical difference between the three groups in relation to astrocytes. Screening and competitive polymerase chain reaction (PCR) undertaken on multiple samples including brain tissue, choroid plexus and leptomeninges from four of the HIV‐positive subjects and one control case showed that the pro‐viral burden was never more than 13 copies/μg DNA and was negative in multiple samples from one HIV‐positive case and one control case. All the basal ganglia samples were PCR‐negative. This study has not revealed any t spots’ of viral load in brain tissue, choroid plexus or meninges, either early or late in the course of pre‐symptomatic HIV infection. Drug use alone is associated with significant upregulation of microglia and this may predispose to HIV infection of the nervous system in drug users.
Dendritic and synaptic alterations of hippocampal pyramidal neurones in scrapie‐infected mice
Authors: Belichenko P. V. , Brown D. , Jeffrey M. , Fraser J. R.
Published: March 2003

Neurone damage and eventual loss may underlie the clinical signs of disease in the transmissible spongiform encephalopathies (TSEs). Although neurone death appears to be through apoptosis, the trigger for this form of cell death in the TSEs is not known. Using two different murine scrapie models, hippocampal pyramidal cells were studied through microinjection of fluorescent dye, and synaptic integrity, using p38‐immunoreactivity (p38‐IR), both visualized using confocal laser scanning microscopy. Intradendritic distensions and dendritic spine loss were found to co‐localize to areas of vacuolar and prion protein pathology in the hippocampus of mice infected with ME7 or 87 V scrapie. A significant reduction in p38‐IR was found concomitantly in the hippocampus in ME7 scrapie mice. These results indicate that both pre‐ and post‐synaptic sites are altered by scrapie infection; this would disrupt neuronal circuitry and may initiate apoptotic cell death, giving rise to the neurological disturbances manifested in clinical TSE cases.
Cases of Alzheimer's disease due to deletion of exon 9 of the presenilin‐1 gene show an unusual but characteristic β‐amyloid pathology known as ‘cotton wool’ plaques
Authors: Mann D. M. A. , Takeuchi A. , Sato S. , Cairns N. J. , Lantos P. L. , Rossor M. N. , Haltia M. , Kalimo H. , Iwatsubo T.
Published: March 2003

The pattern of deposition of amyloid β protein (Aβ) was investigated, using the monoclonal antibodies BA27 and BC05 detecting the C‐terminal species Aβ40 and Aβ42(43), in six cases of Alzheimer's disease (AD) due to deletions in exon 9 of PS‐1 gene. These cases are characterized histologically by the presence of very large rounded plaques within the frontal cortex, known as ‘cotton wool’ plaques, composed of both Aβ40 and Aβ42(43) that are relatively free from neuritic changes and glial cell components, and usually devoid of a compact amyloid core. In the cerebellum the plaques are almost entirely of a compact type, again composed of Aβ40 and Aβ42(43), with only few diffuse Aβ42(43) containing plaques. The area fraction of Aβ40, and the ratio between Aβ40 and Aβ42(43), in frontal cortex was significantly higher than that seen in other cases of AD due to different PS‐1 mutations, or in cases of sporadic AD, all of similar APO E genotype. The area fractions of Aβ42(43), however, did not significantly differ between these three groups. The unusual nature of the Aβ deposition in these cases may reflect the uniqueness of the mutation, which results in a failure to constitutively cleave the PS‐1 holoprotein into its active form, and the effect this might have on APP trafficking and catabolism.
The glioma‐associated gangliosides 3′‐isoLM1, GD3 and GM2 show selective area expression in human glioblastoma xenografts in nude rat brains
Authors: Hedberg K. M. , Mahesparan R. , Read T.‐A. , Tysnes B. B. , Thorsen F. , Visted T. , Bjerkvig R. , Fredman P.
Published: March 2003

This work describes the in vivo expression and distribution of glioma‐associated gangliosides (GD3, GM2, 3′‐isoLM1) in a novel human brain tumour nude rat xenograft model. In this model, the tumours, which are established directly from human glioblastoma biopsies, show extensive infiltrative growth within the rat brain. This model therefore provides an opportunity to study ganglioside expression not only within the macroscopic tumour, but also in brain areas with tumour cell infiltration. The ganglioside expression was studied by confocal microscopy of immunostained brain sections using antiganglioside monoclonal antibodies. Xenografts from four human glioblastoma multiformes were established in rats and the brains removed after 3–4 months. Ganglioside GD3 was expressed in the tumour parenchyma while ganglioside 3′‐isoLM1 was more abundantly expressed in the periphery of the tumour associated with areas of tumour cell invasion. GM2 expression was only seen in one tumour, where it was located within the main tumour mass. Double staining with a pan antihuman monoclonal antibody (3B4) and the antiganglioside monoclonal antibodies confirmed that the ganglioside expression was associated with tumour cells. This work supports the concept of different biological roles for individual gangliosides and indicates that antibodies or ligands directed against GD3 and 3′‐isoLM1 might be complementary when applied in the treatment of human glioblastomas.
Rabies viral antigen in extracranial organs:  a post‐mortem study
Authors: Jogai S. , Radotra B. D. , Banerjee A. K.
Published: March 2003

Rabies is a communicable disease and a significant health hazard. Histopathological confirmation of the diagnosis depends on the demonstration of Negri bodies – characteristic intracytoplasmic inclusions. In cases where these are not seen, immunohistochemistry serves as a useful adjunct. After its establishment in the central nervous system, the rabies virus is known to reach peripheral organs by a centrifugal spread. The present study was undertaken with the aim of demonstrating rabies viral antigen (RVAg) in the extracranial organs. Eleven confirmed cases of rabies were analysed and RVAg was found in the adrenal glands, heart, gastrointestinal tract and pancreas, confirming the centrifugal spread of the virus. The detection of RVAg in the extracranial sites may serve as a useful tool in the ante‐mortem diagnosis by subjecting the extracranial tissue to biopsy and subsequent immunohistochemistry.
The impact of consanguinity and inbreeding on perinatal mortality in Karachi, Pakistan
Authors: Hussain
Published: March 2003

Close consanguineous unions continue to be extremely common in much of West Asia, including Pakistan. However, the impact of inbreeding on offspring mortality, particularly perinatal mortality, remains poorly documented. This paper attempts to measure the mortality risks associated with consanguinity and inbreeding while controlling for the effects of other potential confounders. The study sample comprises a multi‐ethnic population residing in selected squatter settlements of Karachi. The adjusted odds ratio for perinatal mortality in the offspring of women married to their first cousins was 2.0 [95% CI 1.5, 2.6]. When parental inbreeding was also taken into account, the adjusted odds ratio for perinatal mortality increased further. Analysis of a subsample of data limited to pregnancies to women aged 35 years or above (at the time of the survey) showed that, despite adjustment for important biological and socio‐demographic factors, both consanguinity and inbreeding remained important predictors of perinatal mortality in the offspring. Implications of the present study for further research are highlighted.
Risk of stillbirth from medications, illnesses and medical procedures
Authors: Pastore  , Hertz‐Picciotto  , Beaumont
Published: March 2003

Associations between stillbirth and 14 medical exposures during pregnancy were examined using deliveries in 1984 in 10 California counties. Cases (n = 332) were stillbirths and infant deaths within 24 h of birth. Randomly selected live births served as controls (n = 357) and were frequency matched by maternal age and county. Using questionnaire and vital statistics data, logistic regression and proportional hazards modelling were performed with adjustment for potential confounders. The most prevalent exposures were ultrasound (65% of cases, 58% of controls) and acetaminophen (45% of cases, 54% of controls). Prescription pain medication, when taken in the first 2 gestational months, was strongly associated with stillbirths due to congenital anomalies (odds ratio = 7.5, 95% confidence interval [CI] 2.3, 24.1). First and second trimester use of prescription pain or migraine medication was positively associated with all stillbirths (rate ratio [RR] range 1.3–1.6). Fertility drugs were positively associated with stillbirths in total and stillbirths due to complications of the placenta, cord and membranes (RR = 1.8, 95% CI 0.8, 4.1; and RR = 2.5, 95% CI 0.9, 7.2 respectively). No associations were found for aspirin, amniocentesis, diagnostic X‐rays or fever, consistent with previous studies. This report is among the few studies of specific causes of stillbirth and medical exposures by gestational time window.
The Dutch ‘Folic Acid Campaign’–have the goals been achieved?
Authors: Van Der Pal‐de Bruin  , De Walle  , Jeeninga  , De Rover  , Cornel  , De Jong‐van den Berg  , Schouten  , Brand  , Buitendijk
Published: March 2003

Periconceptional folic acid use considerably reduces the risk of neural tube defects. The aim of this study was to measure the effect of the national and the local ‘Folic Acid Campaign’ on periconceptional folic acid use. Before (1995 survey) and 1 year after the campaign (1996 survey), the awareness and use of folic acid was measured among pregnant women in four regions of the Netherlands. To this end, pregnant women who visited the midwife, general practitioner or obstetrician for the first or second prenatal visit were asked to complete a questionnaire. The results showed that use of folic acid for any period around conception increased from 25.1% in 1995 to 53.5% in 1996. Appropriate use (4 weeks before until 8 weeks after conception) increased from 4.8% in 1995 to 21.0% in 1996. No additional effect of the local Folic Acid Campaign was found (adjusted odds ratio = 1.0; 95% confidence interval = 0.7, 1.4). It was possible to conclude that folic acid use at the recommended time increased considerably as a result of the national and the local Folic Acid Campaign, but the target (use in 46% of women wishing to conceive) was not achieved. New health education programmes are needed to increase further its use at the appropriate times.
Reliability of demographic, smoking and occupational data provided by mothers vs. fathers in a childhood cancer study
Authors: McKean‐Cowdin R. , Preston‐Martin S. , Pogoda J.M. , Mueller B.A. , Holly E.A.
Published: March 2003

A large case–control study of children was used to test mothers’ reporting of information on fathers’ background, lifestyle and occupational factors. For a subset (104) of 1341 enrolled families, both parents were interviewed about fathers’ characteristics. Reliability of reporting was determined for fathers’ race, education, smoking status, non‐recent job history and use of occupational agents. The ability of mothers to report fathers’ race, education and smoking status was high (kappa > 0.70). Mothers were generally able to report jobs held by the fathers in the 5 years preceding the birth of the child, but reliability was higher for jobs held for longer (kappa typically above 0.70), rather than shorter periods (kappa above 0.40). The finding that mothers’ reporting on fathers’ background, lifestyle and non‐recent job history was reliable is encouraging, because many studies on childhood health rely exclusively on information from interviews with mothers. However, mothers were not reliably able to describe exposure to specific occupational agents.
Adult survival after prenatal exposure to the Dutch famine 1944–45
Authors: Roseboom T. J. , Meulen J. H. P. van der , Osmond C. , Barker D. J. P. , Ravelli A. C. J. , Bleker O. P.
Published: March 2003

Early life events may affect adult survival. We studied the effect of prenatal exposure to the Dutch famine 1944–45 on survival among 2254 people born in Amsterdam. Mortality up to age 50 was highest among those born before the famine (15.2%) and among those exposed to famine in late gestation (14.6%). It was lower among those exposed in mid‐ (11.2%) or early gestation (11.5%), and was lowest among those conceived after the famine (7.2%). These differences were caused by effects on mortality in the first year after birth and were mainly related to nutrition and infections. There was no effect of exposure to famine on mortality after the age of 18. The hazard ratio was 1.4 [0.8, 2.3] for those born before the famine, 1.1 [0.5, 2.3] for those exposed in late gestation, 0.8 [0.3, 1.8] for those exposed in mid‐gestation and 1.1 [0.5, 2.5] in those exposed in early gestation compared with those conceived after the famine. We could not demonstrate effects of prenatal exposure to famine on cause‐specific mortality after the age of 18. Because prenatal exposure to famine is linked to cardiovascular risk factors and disease, increased cardiovascular mortality in the future may be expected.
Implications of cleaning gestational age data
Authors: Parker Jennifer D. , Schoendorf Kenneth C.
Published: March 2003

Gestational age is an important birth characteristic examined in epidemiological studies. Though there are well‐documented problems with the reporting of gestational age on birth certificates, schemes for addressing this issue have not been systematically evaluated. With singleton births from the 1995–97 US linked birth/infant death files, we compared a handful of perinatal outcome estimates derived from the resulting analytical files using two published methods often used to manage inconsistent gestational age data. The first method (Alexander et al., 1996), provides cut‐points for implausible birthweight–gestational age combinations and excludes infants with birthweights outside a plausible range. The second (Zhang and Bowes, 1995), provides different cut‐points for implausible birthweight–gestational age combinations and then substitutes the clinical gestational age estimate for the original value, if available, reducing the number of births at the affected gestational age, but excluding fewer births from the resulting analytical files. The Alexander method excluded 0.4% of our study population and the Zhang method reassigned and excluded 1.0% and 0.2%, respectively; however, over 20% of birth records with gestational age 28–30 weeks were modified by either method. Using either method, more high‐risk than low‐risk and more black than white births were excluded. These differential exclusions affected corresponding perinatal outcome estimates and relative risks between maternal risk groups for preterm delivery, gestation‐specific infant mortality and birthweight; overall infant mortality rates were not affected. Systematic comparisons between results of different studies will need to consider the data modifications used, the populations affected, and the outcomes assessed when drawing conclusions.
Epidemiological features of uterine rupture in West Africa (MOMA Study)
Authors: Joud Dahada Ould El , Prual Alain , Vangeenderhuysen Charles , Bouvier‐Colle Marie‐Hélène , Group The MOMA
Published: March 2003

Summary

The aim of the study was (1) to assess the incidence of uterine rupture in West Africa; (2) to identify its risk factors there; (3) to assess their predictiveness. The study (MOMA study) was prospective and population based. Data on a large cohort of pregnant women were collected. Univariable and multivariable analysis was used including stepwise logistic regression. We identified 25 cases of clinically symptomatic uterine rupture in a population of 20 326 pregnant women giving an incidence rate of 1.2 uterine ruptures per 1000 deliveries. Five variables were significantly associated with uterine rupture (in both the univariable and multivariable analyses): uterine scars, malpresentation, limping, cephalopelvic disproportion and high parity (≥7). In conclusion, the incidence of uterine rupture is high in West Africa, even in large cities where essential obstetric care is available and despite the low prevalence of uterine scars. A uterine scar multiplies the risk of uterine rupture by 11. Uterine rupture cannot be predicted from currently known risk factors, including uterine scars. The high case fatality rate (33.3%) and the associated perinatal mortality (52%) bear witness to the absence or inadequacy of health facilities in providing essential obstetric care and to the poor quality of maternal health care, even in major cities.
Deprivation and stillbirth risk in rural and urban areas
Authors: Dickinson Heather O. , Hutton Jane L. , Greaves Lynda H. , Dummer Trevor J. B. , Parker Louise
Published: March 2003

The objective of the study was to investigate whether stillbirth risk was higher, and the effect of deprivation on inequality in stillbirth risk more marked, in rural than in urban areas. We carried out a cohort study of all 280 757 singleton births to mothers domiciled in Cumbria, north‐west England, 1950–92. After allowing for individual social class and community deprivation, the risk of stillbirth was lower outside urban centres both during 1950–65 (OR = 0.91, 95% CI 0.84, 1.00) and during 1966–92 (OR = 0.82, 95% CI 0.73, 0.92). In earlier years, unsupported mothers in rural areas and mothers living in remote areas were particularly at risk. Urban/rural differences in risk were not explained by individual social class, community deprivation or overcrowding and have persisted over a 40‐year time period.
A district‐based analysis of stillbirth and infant mortality rates in Italy: 1989–93
Authors: Lauria Laura , De Stavola Bianca L.
Published: March 2003

Despite a substantial decline in stillbirth and infant mortality rates in Italy during the last century, there are still large differences between the north and south of the country. This paper analyses the geographical distribution of these rates in the period 1989–93 in terms of biological and social indicators with the aim of identifying possible sources for these differentials. Numbers of stillbirths, infant deaths and deliveries were available in an aggregate form by categories of biological and social factors for each of the 95 Italian administrative districts (‘province’) operative at the time. Substantial differences in stillbirth (SB) and infant mortality (IM) rates were found across geographical areas, with the lower rates found in the richer and more industrialised north and the higher ones in the more deprived south. Negative binomial regression models were used to study the geographical variations in these rates in terms of biological and social factors. The latter showed strong and significant effects on both SB and IM rates, even after controlling for biological factors. The effects of the biological factors, birthweight and maternal parity in particular, however, were found to differ across geographical areas. Further studies to investigate whether these results may be explained by differentials in health care should be considered.
Characterization ofNeospora caninumiscom antigens using monoclonal antibodies
Authors: BJÖRKMAN  , HEMPHILL
Published: March 2003

Neospora caninumis a cyst‐forming coccidian parasite which in cattle can cause abortion and birth of feeble calves. For the serological diagnosis of neosporosis, antibodies directed to the parasite can be demonstrated by ELISA, utilizingN. caninumproteins incorporated into iscoms (immunostimulating complexes) as antigen. Electrophoretic and immunoblotting studies had earlier revealed thatN. caninumiscoms contained a restricted number of proteins compared with soluble parasite extracts, but the cellular origin of the incorporated proteins has not yet been determined. In the present study, monoclonal antibodies were raised againstN. caninumiscoms. Six of these, named Ncmab‐4, 7, 10, 13, 17 and 24, were used to characterize theN. caninumiscom antigen. The nature of the reactive epitopes and their localization withinN. caninumtachyzoites were determined by means of immunological methods, including immunoblot, IFAT and immunogold electron microscopy. The apparent molecular weights of the dominant iscom antigens were found to be 18, 30, 32, 41 and 61 kDa. While the 61 kDa antigen was located intracellularly, the others were found on the parasite surface as well as within distinct intracellular compartments.
Setting in motion the immune mechanisms underlying genetically determined resistance and susceptibility to infection with Leishmania major
Authors: LAUNOIS PASCAL , CONCEIC¸AO‐SILVA FATIMA , HIMMERLICH HAYO , PARRA‐LOPEZ CARLOS , TACCHINI‐COTTIER FABIENNE , LOUIS JACQUES A.
Published: March 2003

The murine model of infection with Leishmania major has allowed the demonstration of a causal relationship between, on the one hand, genetically determined resistance to infection and the development of a Th1 CD4+ cell response, and on the other hand, genetically determined susceptibility and Th2 cell maturation. Using this murine model of infection, the role of cytokines in directing the functional differentiation pathway of CD4+ T cell precursors, has been demonstrated in vivo. Thus, IL‐12 and IFN‐γ have been shown to favour Th1 cell development and IL‐4 is crucial for the differentiation of Th2 responses. Maturation of a Th2 response in susceptible BALB/c mice following infection with L. major is triggered by the IL‐4 produced during the first two days after parasite inoculation. This IL‐4 rapidly renders parasite specific CD4+ T cells precursors unresponsive to IL‐12. A restricted population of CD4+ T cells expressing the Vβ4Vα8 TCR heterodimer and recognizing a single epitope on the LACK (Leishmania Activated C‐Kinase) antigen of L. major is responsible for this rapid production of IL‐4, instructing subsequent differentiation towards the Th2 phenotype of CD4+ T cells specific for several parasite antigens.
Proteolytic activity of cysteine protease in excretory–secretory product of Paragonimus westermani newly excysted metacercariae pivotally regulates IL‐8 production of human eosinophils
Authors: Shin Myeong Heon , Lee Soo Young
Published: March 2003

This study investigated the effect of the excretory–secretory product (ESP) of Paragonimus westermani newly excysted metacercariae (PwNEM) on IL‐8 production of human mature eosinophils. Treatment of eosinophils with lower concentrations (0.3 and 1 μg/ml) of the ESP significantly (P < 0.01) induced IL‐8 production, whereas treament of cells with higher concentrations (3 and 10 μg/ml) did not. This effect of the ESP was concentration‐dependent. Interestingly, the amount of IL‐8 production released into the culture supernatants was inversely correlated with the rate of eosinophil survival. When eosinophils were cultured with the same concentrations of the ESP for 24 h, the ESP resulted in eosinophil death in a dose‐dependent manner. To investigate whether high proteolytic activity of proteases in the ESP could cause little production of IL‐8, 10 μg/ml of ESP was pretreated with heat at 100 °C for 10 min or 56 °C for 30 min to reduce its proteolytic activity. IL‐8 production of eosinophils incubated with heat‐treated ESP was markedly increased comparable to that of cells treated with the lowest concentration used in this study. These findings suggest that the protease in the ESP of PwNEM pivotally regulates IL‐8 production by controlling of eosinophil survival, depending on the amount of ESP released in vivo. Thus, the cysteine protease in the ESP of PwNEM could provide a novel role to control recruitment of inflammatory cells in larval‐infected lesions in human paragonimiasis.
Modulation of the cellular immune response by a carbohydrate rich fraction from Echinococcus granulosus protoscoleces in infected or immunized Balb/c mice
Authors: Dematteis Sylvia , Pirotto Fiorella , Marqués J. , Nieto Alberto , Örn Anders , Baz Adriana
Published: March 2003

Infection of Balb/c mice with Echinococcus granulosus protoscoleces constitutes the model for secondary hydatid infection. The immune response of Balb/c mice infected with E. granulosus is characterized by secretion of antibodies specific for carbohydrate epitopes and production of type‐2 cytokines. A role for glycoconjugates in the induction of type‐2 responses has been suggested in other host–parasite systems. Although glycoconjugates are immunogenic in E. granulosus infection, the role of these molecules in the establishment of the type‐2 response has never been analysed. In this study, a carbohydrate rich fraction (E4+) from E. granulosus protoscoleces was obtained using the monoclonal antibody E492/G1 specific for the moiety Galα(1,4)Gal which is widely represented in protoscoleces and other E. granulosus antigenic preparations. The results showed that E4+ was immunogenic in Balb/c mice evoking an antibody response mainly directed against carbohydrate epitopes. In addition, splenocytes from E4+‐immunized mice showed suppressed proliferative responses to Con A and E4+ induced IL‐10 secretion by E4+‐primed and naive splenocytes. The fraction E4+ also was immunogenic in infected mice during early infection. In this case also, splenocytes from infected mice as well as peritoneal cells from infected or naive mice, when stimulated in vitro with E4+, secreted IL‐10. Collectively, these results suggest that E4+ may be involved in immunosuppression phenomena and, by stimulating IL‐10 secretion, may contribute to the induction and sustaining of the type‐2 cytokine response established in early experimental infection.
Cytokine responses to mitogen and Schistosoma haematobium antigens are different in children with distinct infection histories
Authors: Scott Janet T. , Turner C.michael R. , Mutapi Francisca , Woolhouse Mark E.J. , Ndhlovu Patricia D. , Hagan Paul
Published: March 2003

Prevalence of Schistosoma haematobium infection in children from two neighbouring villages in Zimbabwe was 77·1% and 40·3%, respectively. The age‐intensity data indicated peak intensities of infection at a lower age in the high prevalence village. This study investigated whether the difference in infection histories was reflected in a difference in cytokine profiles between children resident in these two villages. Blood samples were taken to assay for cytokine secretion 1 year after treatment for schistosomiasis. They were cultured with phytohaemagglutinin (PHA), schistosome egg antigens (SEA) or cultured without stimulant and tested for the presence of interleukin (IL)‐4, IL‐5, IL‐10, granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) and IFN‐γ. Blood samples from children from the low prevalence village were more likely to produce IL‐4 (P < 0·0001) and produced higher levels of IFN‐γ (P < 0·02) and GM‐CSF (P < 0·03) when cultured with PHA for 24 h. Residence in the high prevalence village was associated with production of IL‐10 (P < 0·006) and GM‐CSF (P < 0·04) in response to culture with SEA and IL‐5 (P < 0·02) with PHA for 48 h. The interaction between age and village was not significant for these results; however, there was a significant interaction between age and village for IL‐5 detected in blood samples cultured with PHA for 24 h (P < 0·01). These results concur with previous observations that major patterns of cytokine production can be related to immunosuppression, but also indicate an underlying pattern which reflects the importance of history of infection to the immune response.
Effects of irradiation on Plasmodium falciparum sporozoite hepatic development: implications for the design of pre‐erythrocytic malaria vaccines
Authors: Silvie O. , Semblat J. P. , Franetich J. F. , Hannoun L. , Eling W. , Mazier D.
Published: March 2003

Immunization with irradiation‐attenuated Plasmodium sporozoites confer protection against live sporozoite challenge. Protection relies primarily on cytotoxic lymphocyte activity against infected hepatocytes, and is suppressed when sporozoites are over‐irradiated. Here, we demonstrate that over‐irradiated (25–30 krad) Plasmodium falciparum sporozoites invade human hepatocytes and transform into uninucleate liver‐trophozoites with the same efficiency as non‐irradiated and irradiation‐attenuated (12–15 krad) sporozoites. Since hepatocytes infected with over‐irradiated non‐protective sporozoites are likely to express sporozoite‐derived peptide/major histocompatibility complex class I molecules on their surface, our results strongly suggest that sporozoite proteins are not the main immunogens involved in protection, and thus may not per se constitute proper malaria vaccine candidates.
Effects of starvation and oviposition activity on the reproductive physiology of the sweet potato whitefly, Bemisia tabaci
Authors: VEENSTRA KLAAS H. , BYRNE DAVID N.
Published: March 2003

Abstract. We examined the effects of starvation and oviposition on the reproductive physiology of the sweet potato whitefly, Bemisia tabaci (Gennadius) (Homoptera: Aleyrodidae). In a first set of experiments, females were starved as well as denied the opportunity to oviposit. The combined amounts of vitellogenin and vitellin per female increased by 69% when they were removed from plants for 24 h, egg load increased two‐fold in approximately 4.5 h. The lipid content, on the other hand, decreased significantly over an 8 h perod. Thus, vitellogenin synthesis and the formation of mature eggs do not seem to be limited by the lack of nutrient intake or the ability to oviposit. In a second set of experiments, females were restricted to either young leaves of melon plants (Cumis melo), that are preferred oviposition sites, or to old melon leaves, that are non‐preferred oviposition sites. At the end of the experiment, females on the old leaves contained significantly higher amounts of vitellogenins and vitellins than females confined to young leaves. These comparisons were made relative to body weight. The data also indicate that females accumulated both vitellogenins and lipids when confined to old leaves, but did not do so on young leaves. These results are consistent with the hypothesis that females of B. tabaci explicitly discriminate against older leaves for oviposition. We argue that examinations of changes in egg load or the combined vitellogenin and vitellin content that accompany oviposition can provide better insights into the oviposition behaviour of B. tabaci.
Alternative life cycles controlled by temperature and photoperiod in the oligophagous bug, Dybowskyia reticulata
Authors: NAKAMURA KEIJI , NUMATA HIDEHARU
Published: March 2003

Abstract. Effects of temperature and photoperiod on the induction and re‐induction of adult diapause were examined in Dybowskyia reticulata (Dallas) (Heteroptera: Pentatomidae). Adults collected from the field after overwintering in early summer continued oviposition under long‐day conditions of LD 16:8 h at 20 or 25°C, while they re‐entered diapause under short‐day conditions of LD 12:12 h at 25, 27.5 or 30°C. By contrast, adults reared in the laboratory from eggs at 20 or 25°C entered diapause under both long‐day and short‐day conditions, whereas those reared at 27.5 and 30°C entered diapause only under short‐day conditions. Under quasi‐natural conditions in 1993, when summer temperature was low, most adults of the first generation entered diapause in late July. However, in the warmer summer of 1996, oviposition was recorded in many females that ecdysed into adults from July to early August. Even though the seeds of the host plants occur in a restricted period from early summer to early autumn, in warmer years D. reticulata may produce a second generation. The response to temperature with a threshold between 25 and 27.5°C in D. reticulata brings about a switch between the univoltine and bivoltine life cycles.
Antifeedant discrimination thresholds for two populations of western corn rootworm
Authors: EICHENSEER HERBERT , MULLIN CHRISTOPHER A. , CHYB SYLWESTER
Published: March 2003

Abstract.Sensitivities to β‐hydrastine, strychnine and picrotoxinin were compared between two populations of western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), differing in their susceptibility to cyclodiene insecticides. The antifeedants are antagonists of γ‐aminobutyric acid (GABA) neuroreceptors that may mediate gustation and, in the case of picrotoxinin, interact directly with the target site for cyclodiene insecticides. In combination with cucurbitacin B, a specific Diabroticite phagostimulant, cyclodiene‐resistant beetles were two‐ to four‐fold less sensitive to hydrastine and strychnine. The discrimination threshold for picrotoxinin was higher for resistant beetles; however, overall dose–response profiles were similar. Beetles were more sensitive to hydrastine and strychnine in combination with L‐alanine, a general phagostimulant of less potency than cucurbitacin B. Dose–response slopes for the alkaloid‐alanine combinations were double those of respective cucurbitacin B slopes, which indicates that phagostimulatory input from l‐alanine was more negatively affected by the alkaloidal antifeedants than the respective cucurbitacin B treatments. Picrotoxinin sensitivity was similar in mixtures with either phagostimulant. Comparison of chemosensillum responses to strychnine was inconclusive. Results are discussed in context of GABA receptor pharmacology.
Number and size of intracisternal granules in the adipokinetic hormone‐secreting cells of locusts: a phase‐dependent characteristic
Authors: Diederen J. H. B. , Verstegen M. M. A. , Oudejans R. C. H. M. , Vullings H. G. B. , Van Der Horst D. J.
Published: March 2003

Abstract.The intracisternal (= ergastoplasmic) granules in the adipokinetic hormone‐secreting cells of the glandular lobes of the corpora cardiaca in Locusta migratoria migratorioides represent accumulations of adipokinetic prohormones within cisternae of the rough endoplasmic reticulum. Solitary locusts have more and larger intracisternal granules than gregarious locusts. This coincides with the general locomotor activity and thus the energy metabolism in solitary locusts being quite different from that of gregarious locusts, which apparently has consequences for the amounts of adipokinetic hormones synthesized and/or released and, consequently, for the storage of these hormones in the intracisternal granules. These granules apparently function as supplementary stores of secretory material.
Three‐dimensional analysis of aphid landing behaviour in the laboratory and field
Authors: Storer J. Robert , Young Stephen , Hardie JiM.
Published: March 2003

The final second of the landing approach of black bean aphids,Aphis fabae,was analysed in three dimensions using video techniques. A yellow landing platform was placed upwind or downwind from aphids aggregating under a ceiling light in a laboratory wind tunnel with 10, 20, 30, 40 or 50 cm s–1wind speeds, and up‐tunnel or down‐tunnel in still air. As individual aphids flew to the platform, body orientation (assessed by direct observation) was predominantly into‐wind whether the initial flight direction to the landing platform was upwind or downwind. A greater proportion showed into‐wind body orientation as wind speed increased. Flight track parameters which differed significantly between wind speeds were the track length, linear start to finish distance, linearity index, horizontal ground speed, speed vertical to the ground, vertical turning rate, and horizontal turning rate. The position of the landing platform was important for track length, linear start to finish distance, horizontal ground speed, three‐dimensional turning rate, horizontal turning rate, vertical turning rate, and sinuosity. As wind speed increased above 30 cm s–1the ground speed became more consistent and indicated considerable variation in air speed to adjust for ground speed. For the majority of aphids there was a strong preference (88%) for into‐wind landings with initial upwind directed flight, while for downwind flights a significant number (55%) of insects reversed initial flight direction and landed into‐wind. Field recorded landings showed that 66% of aphids landed into‐wind and there was a mean bearing to the wind of 71 ± 42°, a similar finding to wind‐tunnel studies.