bluuebunny/crossref_metadata_2025 huggingface dataset:
Alpers syndrome with mitochondrial DNA depletion
Authors: Rahman S. , Taanman J.‐W. , Harding B. N.
Published: March 2003

Background and aim:  Alpers syndrome or progressive neuronal degeneration of childhood with liver disease is a rare and probably heterogeneous familial disorder of unknown aetiology. We investigated mitochondrial DNA (mtDNA) levels in three cases with Alpers syndrome.

Methods:  Three unrelated patients presented with status epilepticus and liver dysfunction between 6 months and 3 years of age. The clinical course was severely progressive and death occurred 7 days to 2 years after initial presentation. Neuropathology was performed in cases 1 and 3 and confirmed a diagnosis of Alpers syndrome. Total genomic DNA extracted from frozen skeletal muscle, liver, heart and kidney was subjected to quantitative Southern blot analysis using two probes (one for mtDNA and the other for the nuclear‐encoded 18S ribosomal DNA) and comparison with age‐matched controls.

Results:  Case 1 had 25% residual mtDNA levels in liver, 33% in skeletal muscle, 55% in cardiac muscle and normal levels in kidney. Case 2 had 19% residual mtDNA levels in liver and 42% in skeletal muscle. Case 3 had normal mtDNA levels in skeletal muscle, the only tissue available for study.

Discussion:  We conclude that Alpers syndrome may be associated with depleted levels of mtDNA. The underlying genetic defect is likely to involve mtDNA maintenance. Quantitative determination of residual mtDNA levels should be performed in all cases where there is a suspicion of Alpers syndrome.
Neuronal heterotopia in a Lagotto Romagnolo dog
Authors: Rusbridge C. , Wilkins P.
Published: March 2003

The Lagotto Romagnola is an ancient Italian dog breed originally used for retrieving ducks. Nowadays, it has the distinction of being the only breed recognized as a specialized truffle hunter. One of the first litters bred in England had locomotor difficulties. The most severely affected puppy was sacrificed and the brain examined. The dog had inferior prognathia and a brachycephalic skull, not typical for the breed. Although the brain was grossly unremarkable, histology showed a neuronal migration disorder characterized by heterotopia of the cortex, cerebellum and pons. This may represent a developmental delay as affected dogs can improve with time. A genetic abnormality is suspected.
Amyloid angiopathy in a brain biopsy of a suspected haemorrhagic tumour: case report
Authors: Bodi I. , Achawal S. V. , Sharr M. M. , Lantos P. L.
Published: March 2003

Introduction:  Amyloid angiopathy (AA), most frequently associated with Alzheimer's disease, may lead to lobar intracerebral haemorrhages. Although AA is common in the elderly population, it is rarely diagnosed in brain biopsy. We report a case of AA with Alzheimer's type changes detected by brain biopsy.

Material and methods:  A 75‐year‐old female presented with intermittent delusions and confusion for 2 months and mild memory impairment on examination. Computed tomography and magnetic resonance imaging scans revealed an old blood clot in the right frontal lobe and raised the possibility of a tumour. At operation, an organized blood clot with a partly cystic wall was removed.

Results:  Intra‐operative smear showed an infarct with foamy macrophages without evidence of tumour. Paraffin material revealed a haemorrhagic infarct with thickened leptomeningeal blood vessels being positive for Congo red and amyloid‐β (Aβ). Scattered neuritic plaques and neurofibrillary tangles were also detected by Aβ and tau. Retrospective examination of the smear preparation showed metachromatically stained thickened blood vessels consistent with AA.

Conclusions:  This case of AA presented with a haemorrhage mimicking a tumour. AA was present even in the smear preparation as diagnosed retrospectively. The possibility of AA should be born in mind in atypical haemorrhagic lesions, particularly in elderly patients.
Immunohistochemical characterization and quantification of Marinesco bodies in Alzheimer's and Parkinson's diseases
Authors: Vollans A. K. , Shukla C. , Bridges L. R.
Published: March 2003

Introduction:  Marinesco bodies (MBs) were described 100 years ago but, unlike the intranuclear inclusions in the triplet repeat diseases, have received little attention in the literature. Our aim was to see whether they are disease associated or purely age related.

Materials and methods:  We examined 15 cases each of Alzheimer's disease, Parkinson's disease and age‐matched control brains. Paraffin sections of midbrain were cut in thicknesses of 5 µm, and immunostained with α‐synuclein and ubiquitin (Novocastra) and tau, β‐amyloid and PrP (Dako). Staining was enhanced with Envision (Dako). A blue‐grey chromagen (Vector SG, Vector) was chosen to provide contrast with the brown pigment of the substantia nigra neurons.

Results:  MBs were immunopositive for ubiquitin but not for α‐synuclein, tau, β‐amyloid and PrP. Within affected neurons, MB were fewer in Parkinson's disease than in Alzheimer's disease and ‘normals’ (medians 1.48, 1.98 and 2.00 respectively; P < 0.01). Within normals, the size of MB‐affected neurons was significantly less than that of MB‐unaffected neurons (median areas 605 and 969 µm2 respectively; P < 0.01). MB relative to cell size were smaller in Parkinson's disease than Alzheimer's disease and controls (medians 0.86, 1.07 and 1.12% respectively; P < 0.01).

Conclusions:  Differences exist between number and size of Marinesco bodies and affected neurons in neurodegeneration and normal ageing, but there is no clear evidence of a disease association.
Sudden and unexpected death in epilepsy: neuropathological findings and HSP‐70 immunohistochemistry
Authors: Thom M. , Seetah S. , Scaravilli F.
Published: March 2003

Patients with epilepsy can die suddenly and unexpectedly with no cause of the death being ascertained at postmortem (SUDEP). The majority of SUDEP cases are not witnessed but there is strong evidence that it is a seizure‐related event. The risk factors and mechanisms of SUDEP are under study. In our series of 41 SUDEP cases between the years 1992 and 2001, the mean age at death was 42 years; the majority of deaths were unwitnessed, with 15 patients found dead in bed. In six patients, seizures were reported in the previous 24 h. Neuropathological findings included old cerebral cortical contusions (eight), cerebellar atrophy (17) and, in 15 cases, a potential epileptogenic pathology was identified, such as hippocampal sclerosis or cortical malformation. We investigated the presence of HSP‐70 protein expression in SUDEP in the hippocampus and temporal lobe as a potential indicator of a recent cerebral insult. Our control groups were non‐SUDEP sudden deaths and non‐SUDEP epilepsy deaths. Immunopositive neurons were identified in hippocampal subfields or neocortex in SUDEP cases as evidence of acute neuronal damage. Positive neurons were also demonstrated in some control groups, however, and the distribution of immunopositivity was compared.
Oxidative DNA damage in the spinal cord in multiple sclerosis
Authors: Abedin K. J. , Papadopoulos D. , Dexter D. T. , Reynolds R.
Published: March 2003

Introduction:  Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by multifocal demyelination and axonal loss. In addition to the role of the immune response in targeting oligodendrocytes and myelin in MS lesions, the extensive inflammatory infiltration is likely to lead to free radical production and oxidative damage to both oligodendrocytes/myelin and neurons. In this study we investigated the extent of free radical damage to DNA in postmortem MS spinal cord.

Materials and methods:  Serial 10 µm tissue sections were cut from 26 fixed and cryoprotected spinal cord blocks from 11 MS cases (age 64 ± 4 years, pmd 13 ± 2 h) and two controls (age 70 ± 9 years, pmd 22 ± 4 h). Lesions were characterized using H&E and LFB‐PAS histology and HLA‐DR immunohistochemistry. DNA oxidative damage was detected using a monoclonal antibody against 8‐hydroxy‐2′‐deoxyguanosine (8OHdG; supplied by Dr S Toyokuni, Kyoto), the most abundant modified DNA base.

Results:  Quantitative analysis revealed a 150% increase in 8OHdG+ cells relative to normal appearing WM and a 400% increase relative to control WM. A positive correlation was found between the level of macrophage infiltration (HLA‐DR+) and 8OHdG‐expressing cells.

Discussion:  These results suggest a role for oxidative damage to DNA due to free radicals in the evolution of the MS lesion.
High frequency of a 30‐bp deletion of Epstein–Barr virus latent membrane protein 1 gene in primary HIV non‐Hodgkin's brain lymphomas
Authors: Vallat‐Decouvelaere A.‐V. , Bretel M.‐A. , Vassias I. , Laplanche J.‐L. , Polivka M. , Wassef M. , Brunet M. , Thiebaut J.‐B. , Gosselin B. , Morinet F. , Mikol J.
Published: March 2003

A characteristic 30‐base pair (bp) deletion (del) in the 3′ end of the Epstein–Barr virus (EBV) latent membrane protein 1 (LMP1) gene, coding for the C‐terminal NF‐kappaB activation domain, has been identified in various lymphoproliferative disorders and nasopharyngeal carcinomas. In the single report to date of human immunodeficiency virus primary brain lymphomas (HIV‐PBLs), del‐LMP1 was noted in seven cases out of nine. The present study was designed to identify this deletion in a series of 31 diffuse large B‐cell HIV‐PBLs, with the aim of determining its possible oncogenic action. The presence of EBV was confirmed by EBER mRNA in situ hybridization. After genomic extraction from frozen tissue, two 20‐base oligonucleotide primers flanking the site of the 30‐bp deletion were used. DNA sequencing of the polymerase chain reaction (PCR) products confirmed an identical segment spanning 30‐bp and 69‐bp, frequently associated with mutational hotspots in 19 cases (61%). A role for del‐LMP1 in the oncogenic potential of EBV in systemic proliferations is a matter of debate. Its high incidence suggests that the oncogenic mechanism of LMP1 in the brain might differ significantly from that in systemic lymphoid proliferations, and might be enhanced by HIV infection.
Racial differences in birthweight for gestational age and infant mortality in extremely‐low‐risk US populations
Authors: Alexander  , Kogan  , Himes  , Mor  , Goldenberg
Published: March 2003

Using national data, we develop and contrast the birthweight percentiles for gestational age by infants of extremely‐low‐risk (ELR) White and African‐American women and examine racial differences in the proportion of small‐for‐gestational‐age (SGA) births. We then scrutinise racial variations in infant mortality rates of the infants of ELR women. We further compare the infant mortality rates of infants at or below the 10th percentile of birthweight for gestational age of each race group to determine whether infants with similar restricted fetal growth have comparable risks of subsequent mortality. Single live births, 34–42 weeks’ gestation, to White and African‐American US‐resident mothers were selected from the 1990–91 US Linked Live Birth–Infant Death File (n = 4 360 829). Extremely‐low‐risk mothers were defined as: married, aged 20–34 years, 13+ years of education, multiparae, with average parity for age, adequate prenatal care, vaginal delivery, and no reports of medical risk factors, tobacco use or alcohol use during pregnancy.

   Marked racial variation in birthweight percentiles by gestational age was evident. Compared with ELR White mothers, the risk of an SGA infant was 2.64 times greater for ELR African‐American mothers and the risk of infant mortality was 1.61 times greater. For the ELR group, the infant mortality rates of African‐American and White infants at or below the 10th percentile of birthweight for gestational age of their respective maternal race group were essentially identical after controlling for gestational age. In conclusion, race differences in fetal growth patterns remained after controlling for risk status. Efforts to remove racial disparities in infant mortality will need to develop aetiological pathways that can explain why African‐Americans have relatively higher rates of preterm birth and higher infant mortality rates among term and non‐SGA infants.
The efficacy of the non‐stress test in preventing fetal death in post‐term pregnancy
Authors: Li Tong , Rhoads George G. , Demissie Kitaw , Smulian John
Published: March 2003

We conducted a case–control study to examine the efficacy of non‐stress testing in preventing fetal death in post‐term pregnancy. The analysis was based on data from the 1988 National Maternal and Infant Health Survey, which was a nationally representative sample of live births, fetal deaths and infant deaths that occurred in 1988. Information on whether a woman had non‐stress testing was obtained from a questionnaire sent to prenatal care providers and hospitals. Cases were post‐term women (with 42 weeks or more gestation) who had fetal deaths. Three post‐term controls, who had live births and who delivered at the same time or later than the cases, were randomly chosen and individually matched to each case by maternal race. The proportion of women who had one or more non‐stress tests during pregnancy was compared between cases and controls. Non‐stress testing was used in 30.9% of the 126 cases and in 28.5% of the 375 controls. The race‐adjusted odds ratio for exposure to non‐stress test was 1.12 [95% CI 0.72, 1.75]. After controlling for other important confounding variables the odds ratio was 1.05 [95% CI 0.57, 1.91]. These results do not support the efficacy of non‐stress testing in post‐term pregnancies. A more detailed evaluation of this widely used screening procedure is needed.
The epidemiology of infantile hypertrophic pyloric stenosis in Greater Glasgow area, 1980–96
Authors: Sule Sa'adatu T. , Stone David H. , Gilmour Harper
Published: March 2003

The annual incidence of infantile hypertrophic pyloric stenosis (IHPS) in Greater Glasgow area from 1980 to 1996 was calculated. An increasing incidence was observed between 1980 and 1988 but not thereafter. There is a suggestion that environmental factors may play a role in the aetiology of this condition.
An epidemiological study of childhood disability in Jeddah, Saudi Arabia
Authors: Shawky Sherine , Abalkhail Bahaa , Soliman Nadia
Published: March 2003

Childhood disability is a major health problem that is pronounced in developing countries. The objectives of this study were to identify the maternal risk factors present in our society and their impact on acquiring a disabled child. Data were collected from the six governmental rehabilitation institutes and a sample of normal non‐disabled school children in Jeddah City. Information on sociodemographic factors and maternal risk factors was collected by in‐person interview and copied from the children’s institute records. Logistic regression models were fitted to calculate the adjusted odds ratios in order to demonstrate the impact for the various maternal risk factors on having a disabled child. Our results have shown that certain modifiable maternal risk factors affecting child health still exist in our community, such as early and late‐age marriage and childbearing, as well as low education, unemployment, multiparity and consanguineous marriages. All these risks were shown to put the mother at higher risk of having an auditory disabled child. Also, older‐age childbearing (≥30 years), low education level and multiparity were the maternal risk factors identified that influenced the risk of visual disability in children. Similar maternal risk factors, in addition to unemployment, were more observed among mothers of mentally disabled children. A huge effort is required to discourage the potential risk factors in our community that influence child health.
The effect of the change in air temperature on the number of newborns in Vienna 1984–99
Authors: Waldhoer Thomas , Klein Matthias , Haidinger Gerald
Published: March 2003

The number of daily births depends on a wide range of sociodemographic, temporal as well as many other mostly unknown factors, resulting in non‐random patterns. We tested the hypothesis of the influence of the change in air temperature on the daily number of all newborns in Vienna (n = 254 797) in the period 1984–99
(n = 5843 days). We found a significant association of sudden changes in temperature with the daily number of births. The observed effect is responsible for up to 0.27% of the explained variation in the regression model.
Epidemiology of neonatal group B streptococcal disease in The Netherlands 1997–98
Authors: Trijbels‐Smeulders Monique , Gerards Leo J. , M. Pieternel C. , Jong Pasker‐de , Lingen Richard A. van , Adriaanse Albert H. , Jonge Guus A. de , Kollée Louis A. A.
Published: March 2003

Group B streptococcal (GBS) infection is still an important cause of morbidity and mortality in newborn infants. In The Netherlands, there are no published data on the incidence of neonatal GBS infection. We collected data of all infants with GBS disease during the first 3 months of life, as reported to the Dutch Paediatric Surveillance Unit (DPSU) during a period of 2 years (1997–98). Neonates with early‐onset GBS disease (both sepsis and probable sepsis) were included for further analysis. The level of completeness of the DPSU data was determined by capture–recapture techniques. The incidence of early‐onset GBS disease in The Netherlands in 1997–98, as calculated from the DPSU data, was 0.9 per 1000 live births. After correction for under‐reporting, the incidence was estimated to be 1.9 per 1000 live births. The case fatality rate of early‐onset GBS disease was only 5%. Despite the decrease in the mortality rate during the last decades, it remains a serious condition with potential irreversible brain damage. Therefore, formal guidelines for the prevention of neonatal early‐onset GBS disease in The Netherlands were introduced in 1999. The data collected in this study may serve as baseline data for evaluation of the effect of these guidelines.
In vivo expression of cytokine mRNA in rats infected with Schistosoma mansoni
Authors: CÊTRE CATHERINE , COCUDE CÉCILE , PIERROT CHRISTINE , GODIN CLAUDE , CAPRON ANDRÉ , CAPRON MONIQUE , KHALIFE JAMAL
Published: March 2003

As an animal model, rat schistosomiasis mansoni has provided considerable knowledge of immune mechanisms involved in the expulsion of worms and in a subsequent development of immunity to reinfection. Although it is clear that ADCC mechanisms participate in immunity to reinfection; the nature of the cytokines involved in immunity is unknown. To analyse the pattern of cytokines involved, the mRNA levels of different cytokines were assessed by RT‐PCR as they occur within tissues during the course of infection. In spleens from infected rats, a significant elevation in IL‐2 and IL‐5 mRNA was observed during the early phase of infection (day 7). Analysis of pulmonary cytokine responses showed a dramatic increase in IL‐4 and IL‐5 on day 7. This was accompanied with a low but significant increase in IL‐2 (day 11) and IL‐12 (day 7) in the absence of augmented IFN‐γ expression. The cytokine expression patterns of draining lymph nodes (LN) from infected rats showed a significant increase of IL‐2, IL‐4 and IL‐5 on day 21. Analysis of IL‐10 expression showed exclusively a significant increase in LN on day 11. IFN‐γ mRNA was not detected in any tissue sample. Thus, rats develop a predominately Th2‐type cytokine response during a primary infection which may be involved at least in part, in the expression of immunity against Schistosoma mansoni infection.
Interleukin‐12 suppresses filaria‐induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness
Authors: MEHLOTRA RAJEEV K. , HALL LAURIE R. , HIGGINS ALAN W. , DRESHAJ ISMAIL A. , HAXHIU MUSA A. , KAZURA JAMES W. , PEARLMAN ERIC
Published: March 2003

Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial‐specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL‐12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL‐12 modulated the T helper (Th) response in the lungs from Th2‐ to Th1‐like, with elevated IFN‐γ, and decreased IL‐4 and IL‐5 production. Consistent with this shift in cytokine response, antigen‐specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL‐12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL‐12 suppressed airway hyperresponsiveness compared with saline‐injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL‐12 down‐regulates filaria‐induced lung immunopathology.
Heligmosomoides polygyrus immunomodulatory factor (IMF), targets T‐lymphocytes
Authors: TELFORD  , WHEELER  , PPLEBY  , BOWEN  , PRITCHARD
Published: March 2003

Experiments were performed to investigate the immunological site of action of an immunomodulatory factor (IMF), isolated from the gastrointestinal nematode Heligmosomoides polygyrus. IMF inhibited antibody production in murine and human ‘T‐helper (Th‐2) driven’ immunoassays. The effects were mediated via T lymphocytes as T cell‐depleted cultures failed to respond to IMF, a result confirmed by prepulsing discrete cell subsets with the immunomodulant. Although the molecular nature and mode of action of IMF has yet to be determined, it would appear to be a relatively small non‐proteinaceous molecule. From this data, we suggest that H. polygyrus secretes a systemically‐active IMF from the intestinal lumen, to down‐regulate Th‐2 cell development in order to promote its survival in a potentially immunologically hostile environment.
Characterization of variable immunodominant antigens of Cowdria ruminantium by ELISA and immunoblots
Authors: PEREZ JEAN‐MARIE , MARTINEZ DOMINIQUE , SHEIKBOUDOU CHRISTIAN , JONGEJAN FRANS , BENSAID ALBERT
Published: March 2003

Cross‐immunization experiments have revealed a significant antigenic diversity of the isolate of Cowdria ruminantium which needs to be characterized for the development of vaccines. We identified polymorphic immunodominant antigens by ELISA and immunoblot. Using serum from a goat immune to the Gardel stock of Cowdria (isolated in Guadeloupe) adsorbed on antigen of the Senegal stock of this pathogen, distinct serogroups were revealed by ELISA among six isolates from different geographical origins. Furthermore, a goat serum directed against the Senegal stock and adsorbed on Gardel antigens was shown to be specific for the Senegal stock, thus confirming the existence of serotypes in Cowdria. The Major Antigenic Protein 1 (MAP1) of Cowdria was shown to have variable antigenic determinants. Also in a group of variable proteins ranging from 23 to 29 kDa, one antigen of 26–27 kDa had a determinant specific for the Gardel isolate. These polymorphic antigens may be relevant components of Cowdria ruminantium for a vaccine as the sera revealing these antigens originated from a goat surviving a lethal challenge. However, the presence of T‐cell epitopes and the ability of these antigens to confer protection to ruminants remain to be investigated. The production of a rabbit antiserum against this group of polypeptides will be of great use for their purification and for the screening of expression libraries.
Cytokine and chemokine secretion by human peripheral blood cells in response to viable Echinococcus multilocularis metacestode vesicles
Authors: Dreweck Caroline M. , Soboslay  , Schulz‐Key  , Gottstein  , Kern
Published: March 2003

In human alveolar echinococcosis, asexually proliferating metacestodes of Echinococcus multilocularis progressively infiltrate host tissues and cause serious pathology to the affected organs. This study employed an in vitro culture of E. multilocularis and examined the production of cytokines and chemokines by peripheral blood cells from echinococcosis patients in response to viable proliferating E. multilocularis metacestode vesicles (Em‐vesicles). A significant interleukin‐8 (IL‐8) and monocyte chemoattractant protein‐1 (MCP‐1) production was elicited in echinococcosis patients when their cells were cocultured with viable Em‐vesicles and autologous immune sera. Furthermore, in echinococcosis patients, substantial amounts of cytokines were detected; and the levels of IL‐12 and IL‐13 found in patients correlated with the actual state of clinical disease. These observations suggest that viable E.multilocularis vesicles will induce significant cellular production of cytokines and chemokines in patients, and that such immune mediators may activate and enhance antibody‐dependent cellular effector mechanims against proliferating metacestodes of E.multilocularis.
Experimental Ascaris suum infection in the pig: protective memory response after three immunizations and effect of intestinal adult worm population
Authors: Jungersen Gregers , Eriksen Lis , Roepstorff Allan , Lind Peter , Meeusen Els N.T. , Rasmussen Tina , Nansen Peter
Published: March 2003

The protective immune response to larval migration in pigs, with or without adult intestinal worm populations, 10 weeks after 3 weekly Ascaris suum inoculations, was studied in 45 pigs. Controlled adult worm populations were achieved by oral transfer of 10 adult worms to previously immunized pigs after anthelmintic drenching. A significant reduction in larval recovery from lungs on day 7, and small intestine on day 14, was observed in immunized pigs compared with previously uninfected control pigs after challenge inoculation. The strong anamnestic response to larval migration was characterized by blood eosinophilia and specific immune responses measured by peripheral blood enzyme‐linked immunospot and immunosorbent assays using larval excretory‐secretory products and adult body fluid as well as Western blotting with a panel of stage‐specific A. suum antigens. Immune detection of a previously unreported 10 kDa band, specific to the L2 larval stage and egg hatch fluid, emerged in all pigs after challenge, while the major adult body fluid constituent, ABA‐1, remained unrecognized. No significant effect of an intestinal adult worm burden on the larval recovery after a challenge inoculation or on the immune response before or after challenge inoculation could be detected. These results indicate that a significant protective memory immune response to A. suum challenge inoculation can be induced in pigs, and that this protective immunity is not significantly modulated by the presence of adult parasites in the gut.
Infection of mice by a Toxoplasma gondii isolate from an AIDS patient: virulence and activation of hosts' immune responses are independent of parasite genotype
Authors: Haque Sakhina , Hanna Stephane , Gharbi Severine , Franck Jacqueline , Dumon Henri , Haque Azizul
Published: March 2003

Virulence of a Toxoplasma gondii isolate from an AIDS patient (designated as PTN) was compared with that of PLK, a variant of P‐strain. Virulence was assessed in term of host survival upon inoculation in different strains of mice. All C57BL/6 mice died of acute toxoplasmosis by 7–10 days following intraperitoneal infection with 1 × 105 tachyzoites of PTN and 40% of BALB/c died on day 23 of infection, whereas 100% CBA/J infected with the same dose of PTN survived, as did outbred Swiss Webster mice. All C57BL/6, BALB/c, CBA/J, or Swiss Webster died of acute toxoplasmosis by 3–9 days postinfection upon inoculation with same dose of tachyzoites of the PLK strain. Further studies in CBA/J mice demonstrated that mice infected with PTN elicited a significantly higher lymphoproliferative response to crosslinked anti‐CD3 mAb or Con A than PLK infected mice, and augmented production of TNFα, lower levels of nitrite and a higher number of NK cells. Genetical analysis indicated that both PLK and PTN strains of T. gondii are from type ll. Interestingly, being of the same genotype, the later showed less virulence upon inoculation in mice and had greater capacity to activate host immune system than the PLK strain.
CD36 folding revealed by conformational epitope expression is essential for cytoadherence of Plasmodium falciparum‐infected red blood cells
Authors: Gruarin Paola , De Monte Lucia , Alessio Massimo
Published: March 2003

CD36 is a membrane glycoprotein and a putative scavenger receptor expressed by several cell types. In capillary endothelial cells, it mediates the adherence of erythrocytes infected with Plasmodium falciparum. The CD36 sequence contains two hydrophobic domains located at the amino‐and carboxyl‐termini of the protein, but the topology of this protein and the functional significance of these domains are still not clearly defined. We generated soluble CD36–IgG chimeric molecules by fusion of the extracellular domains of CD36 with human immunoglobulin domains. The construct containing the N‐terminal hydrophobic domain of CD36 was completely retained intracellularly as membrane‐associated molecule, suggesting that the N‐terminal hydrophobic domain of the CD36 is a real transmembrane domain and that CD36 has hairpin topology. A small amount of the CD36–IgG chimeric construct lacking both transmembrane domains escaped retention, was correctly processed, and accumulated in the extracellular medium as a soluble molecule. This CD36–IgG construct failed to bind Plasmodium falciparum‐infected erythrocytes. Using monoclonal antibodies specific for either conformational or structural epitopes, we demonstrate that failure of this CD36–IgG construct to bind infected erythrocytes was due to incorrect folding of the soluble chimeric molecule.
Cerebral malaria and immunogenetics
Authors: Mazier Dominique , Nitcheu Josiane , Idrissa‐Boubou Mariama
Published: March 2003

Cerebral malaria depends largely on the capacity of Plasmodium falciparum infected red blood cells to adhere to the endothelia of microvessels, leading to their occlusion. The most important players include receptors expressed on the surface of the endothelial cell and known to interact with the parasite, cytokines modulating the expression of these adhesion molecules and nitric oxide (NO). Platelets, monocytes and lymphocytes have the ability to adhere to these endothelial receptors and to one another, leading to a more complex situation and an increase in the degree of vessel occlusion. The polymorphism of all these molecules, implicated either in adhesion, in modulation of this adhesion or activation of the expression of diverse endothelial mediators should be an important field of study. Polymorphism of five of these molecules has been explored so far: ICAM‐1, TNF‐α, IL‐1‐β, inducible NOS and complement receptor‐1 (CR‐1). To these studies can be added those concerning mannose binding protein (MBP), a protein playing a role in innate immunity, and the class‐I antigen HLA‐B53. To date, the only clear cut result concerns TNF‐α. With the other polymorphisms, either no association is found (IL‐1RA, CR‐1, MBP), or the results are geographically heterogeneous (ICAM‐1, HLA‐B53), or contradictory (iNOS2). Most often, the candidate gene approach has been followed, as part of case control studies. One of the main problems in this approach is the difficulty of establishing the control cohort. This difficulty disappears in family studies, which include their own controls. So far, the only results based on complex segregation analysis have been focused on parasite multiplication and not on cerebral malaria.
Cutaneous interleukin‐7 transgenic mice display a propitious environment to Schistosoma mansoni infection
Authors: Roye Olivier , Delacre Myriam , Williams Ifor R. , Auriault Claude , Wolowczuk Isabelle
Published: March 2003

Interleukin (IL)‐7 is produced early in Schistosoma mansoni infected human and murine skin and was recently shown to favour parasite development. In the present work, we investigated the participation of keratinocyte‐derived IL‐7 in this process. Keratinocytes are the predominant cellular constituents of the epidermis and the first tissue encountered by the parasite when it infects the vertebrate host. We therefore infected IL‐7 cutaneous transgenic mice and compared several parasitological and immunological parameters to those of infected littermate controls. In transgenic mice, an increased number of total adult worms was observed while egg number and female fecundity remained unchanged. Additionally, transgenic animals displayed a more intensive hepatic fibrosis. In parallel, infected IL‐7 transgenic animals showed a dominant Th2‐type humoral response towards egg antigens. The results presented here confirm and reinforce the key role play by IL‐7 in S. mansoni –vertebrate host interplay, beginning with keratinocyte‐derived IL‐7.
Vaccination with neutrophil inhibitory factor reduces the fecundity of the hookworm Ancylostoma ceylanicum
Authors: Ali F. , Brown A. , Stanssens P. , Timothy L.M. , Soule H.R. , Pritchard D.I.
Published: March 2003

Neutrophil inhibitory factor (NIF), a protein isolated from hookworms of the genus Ancylostoma, inhibits CD11b/18‐dependent leucocyte function, binding to the I domain of CD11b. Historically, NIF was serendipitously isolated from whole worm extracts during a search for novel antihaemostatic agents, and little is known of its source or biological significance to the parasite. NIF has also been identified as a possible hookworm vaccine candidate. Ancylostomaceylanicum recombinant NIF, expressed in its active form in Pichia pastoris, was purified and its functional activity confirmed using neutrophil adhesion assays and confirmatory immunoassay. Recombinant NIF was subsequently used in vaccination trials in the A. ceylanicum‐hamster model system for human hookworm infection. Vaccinated and challenged animals were not protected in terms of worm burden or haematocrit values, despite the presence of high levels of specific antibody against NIF. However, adult worms resident in vaccinated animals showed a significant reduction in fecundity (85·8% by day 21 postinfection), indicating a degree of protection against subsequent transmission by vaccination. These data indicate that targeted vaccination with recombinant subunit material, derived from a known and effective immune suppressant secreted by the parasite, may offer partial protection against the transmission of hookworm infection. Furthermore, we can also report that a biological activity characteristic of NIF is detectable in the secretions of A.ceylanicum using two complementary bioassays. Complete neutralization of this secreted activity by vaccination in combination with other vaccine candidates may result in improved protection against A. ceylanicum infection.
Effect of nitric oxide synthase inhibition on Schistosoma japonicum egg‐induced granuloma formation in the mouse liver
Authors: Hirata Mizuki , Hirata Kazuho , Kage Masayoshi , Zhang Mei , Hara Tatsuru , Fukuma Toshihide
Published: March 2003

Nitric oxide (NO) plays diverse roles in a variety of pathological processes. We investigated the role of NO in Schistosoma japonicum egg‐induced granuloma formation in a mouse hepatic model. Immunohistological analysis revealed that there is the most intense and extensive inducible nitric oxide (iNOS) expression 2 weeks after egg implantation, and thereafter it decreased considerably with time. Treatment with nitric oxide synthase inhibitors, NIL (lN6‐ (iminoethyl)‐lysine) or Nω‐nitro‐l‐arginine methyl ester (l‐NAME), resulted in two different types of unusual granulomas at 2 weeks. One type showed suppressed fibrosis, while another showed foreign body‐type multinuclear cell formation which frequently appeared particularly when 50 µg/ml NIL was given. At 3 weeks following treatment, fibrotic granulomas with scanty peripheral cellularity was obvious. However, there were no apparent changes after this period (at 4 weeks). Cytokine analysis in NIL‐treated mice showed a significant increase of IL‐4 and IL‐13 production at 2 weeks. These findings indicated that nitric oxide contributes to granuloma development during the early stages, probably through the regulation of Th2 cytokine production.
Increased immunoglobulin secretion by B lymphocytes from Trypanosoma cruzi infected mice after B lymphocytes–natural killer cell interaction
Authors: De Arruda Hinds Luciana B. , Alexandre‐Moreira Magna Suzana , Decoté‐Ricardo Débora , Nunes Marize P. , Peçanha Ligia M.T.
Published: March 2003

In the present study, we investigated whether natural killer (NK) cells modulate immunoglobulin (Ig) secretion by B cells from Trypanosoma cruzi‐infected mice. B cells from infected mice increased IgM and IgG2a secretion in the presence of a NK cell line, and this response was cell contact‐dependent. Stimulation of splenic B cells with polyinosinic‐polycytidylic acid, a NK cell activator, also increased Ig secretion by B cells from infected mice. B cells from infected mice expressed higher levels of the B7·2 molecule. Our results suggest that NK cells may be involved in the control of the abnormal B cell activation observed during T. cruzi infection.
Defect of protective immunity to Schistosoma mansoni infection in Mongolian gerbils involves limited recruitment of dendritic cells in the vaccinated skin
Authors: Sato H. , Kamiya H.
Published: March 2003

In Mongolian gerbils, Meriones unguiculatus, the attenuated Schistosoma mansoni vaccine, is known to induce marginal or no resistance to a homologous infection. To clarify the base of defective acquisition of the resistance, we have focused on the induction phase of protective immunity to S. mansoni, i.e. cellular responses in the skin and skin‐draining lymph nodes (SLN). Percutaneous exposure to normal or ultraviolet (18mJ/cm2)‐attenuated cercariae induced comparable increases in SLN leucocyte counts, in contrast to other attenuated schistosome vaccine models in rodents where attenuated parasites induce more notable increases in SLN leucocyte counts than normal ones. Using serial sections, it was demonstrated that greater numbers of attenuated larvae remained for a longer period in the exposed skin than normal ones. Correlated with cellular responses in the SLN, attenuated and normal schistosomes elicited a comparable degree of response of epidermal Langerhans' cells/putative dermal dendritic cells that were visualized by immunohistochemistry using a monoclonal antibody to a gerbil major histocompatibility complex class II molecule (HUSM‐M.g.30). It is speculated that in Mongolian gerbils limited recruitment of dendritic cells around attenuated S. mansoni larvae, at least partially, contribute to defective induction of protective immunity by the attenuated vaccine.
Physiological age‐grading and ovarian physiology of Prostephanus truncatus
Authors: SCHOLZ D. , BORGEMEISTER C. , MARKHAM R. H. , POEHLING H.‐M.
Published: March 2003

Abstract. The reproductive tracts of male and female Prostephanus truncatus (Horn) (Coleoptera: Bostrichidae) were described for beetles between emergence and 30 days old in order to determine age‐grading criteria. Seminal vesicles were bigger among non‐mated males than among mated males due to accumulation of sperm; no age‐specific differences were found for male P. truncatus. Ovaries (germarium size, number of follicles and follicle size) were similarly developed for females between 5 and 30 days old and did not differ between mated and non‐mated females. Starved females were found to resorb follicles. Yellow body formation was strongly dependent on age, and was used as an age‐grading criterion for female P. truncatus.

Females flying off maize cobs and caught with pheromone traps were of varying physiological age and mated, and their ovarian development was suspended. All migrating females were mated, indicating that lone females may act as colonizers, independently of males. The applicability of migration theories to P. truncatus and adaptive inter‐reproductive dispersal as part of its life history strategy are discussed.
Does dispersal affect the reproductive physiology of the sweet potato whitefly,Bemisia tabaci?
Authors: Veenstra Klaas H. , Byrne David N.
Published: March 2003

Abstract.The reproductive physiology of sweet potato whiteflies,Bemisia tabaci(Gennadius) (Homoptera: Aleyrodidae), was examined after their dispersal from cotton fields. Of particular interest was the synthesis of vitellogenins and the production of mature eggs. Whiteflies that dispersed out of fields, and were flying at ≈ 0.1 m above the soil surface, exhibited a reproductive physiology that was not significantly different from whiteflies that remained in cotton fields. However,B. tabacicaught at 2.1 m above the ground matured eggs at a significantly lower rate. It appears these latter whiteflies exhibit a physiology that indicates a reallocation of nutrient and energy resources in support of movement.
Electrophysiological and behavioural identification of host kairomones as olfactory cues for Culicoides impunctatus and C. nubeculosus
Authors: Bhasin A. , (luntz) A. J. Mordue , Mordue W.
Published: March 2003

Electroantennograms (EAGs) were recorded from wild‐caught parous, female Culicoides impunctatus (Goetghebuer) in response to components of host odour. Nine synthetic compounds were found to be electrophysiologically active, eliciting EAGs which were significantly different from solvent control. An EAG hierarchy was established, in which 1‐octen‐3‐ol elicited the highest amplitude EAGs, followed by acetone, lactic acid and butanone. The overall responses to phenolic compounds were reduced compared to the non‐phenolics.

Subsequent behavioural analyses of the effects of these compounds when tested singly revealed 1‐octen‐3‐ol, acetone and butanone to be attractive over specific stimulus doses. Exposure to supra‐optimal doses modified the insects’ behaviour; insects either ceased to respond or were repelled. Lactic acid was attractive at the lowest dose tested but was repellent at high doses. Behavioural responses to the phenolic components of host odour and lactic acid were similar, generally causing arrestment at low doses and repelling at the higher doses tested.

A comparison of EAG profiles and behavioural assays between laboratory‐reared Culicoides nubeculosus (Meigen) and C. impunctatus suggested that the same kairomones are utilized by both species, with C. nubeculosus being less sensitive than C. impunctatus. The EAG hierarchy of C. nubeculosus to the four non‐phenolics was identical to that of C. impunctatus.
Allatotropic and nervous control of corpora allata in the adult male loreyi leafworm, Mythimna loreyi (Lepidoptera: Noctuidae)
Authors: Kou Rong , Chen Shu J.
Published: March 2003

Allatotropic activity is found in methanolic extracts of the brain–suboesophageal ganglion (SOG)–corpora cardiaca (CC) complex from virgin males of Mythimna loreyi Duponchel (Lepidoptera, Noctuidae). Corpora allata (CA) from 6‐day‐old virgin males exhibit low rates of release of Juvenile Hormone (JH) acid (JHA) in vitro. Release of JHA can be activated by the addition of an extract of brain–SOG–CC complex in a dose‐dependent manner, and this allatotropic activation can be sustained consistently in the continuous presence of such extracts. Based on its trypsin sensitivity and heat stability, the allatotropic factor is most likely a peptide. The allatotropic activity is dependent on the concentration of calcium ions in the medium, with the highest activation achieved beyond 2 m
m. The results of nerve transection experiments suggest that both nervi corporis allati I (NCA I) and NCA II are involved in mediating the allatotropic control of CA in vitro. Isolated CA alone show significantly higher rates of release of JHA than the intact brain–SOG–CC–CA complex during the first 3 h of incubation, but the release of JHA reaches almost the same range in both groups by the end of the fourth hour of incubation.
The response of grass‐cutting ants to natural and synthetic versions of their alarm pheromone
Authors: Hughes W. O. H. , Howse P. E. , Vilela E. F. , Goulson D.
Published: March 2003

The responses of the grass‐cutting ants Atta bisphaerica (Forel) and Atta capiguara (Gonçalves) to the main components of their alarm pheromones were examined in simple field bioassays. Both species react most strongly to 4‐methyl‐3‐heptanone, which causes the full range of alarm behaviour and a large increase in the number of individuals near the sources. In later experiments with A. capiguara, this increase was found to be due primarily to attraction, with some arrestment also occurring. The ant response to 4‐methyl‐3‐heptanone was compared with that to crushed heads and to that with whole ants with crushed heads. The pheromone 4‐methyl‐3‐heptanone by itself stimulates the same level of attraction as crushed heads, but results in far less alarm behaviour and arrests fewer ants. Whole ants with crushed heads attract a greater number of ants than the other sources and also cause more alarm behaviour. Bodies alone attract ants, but do not result in alarm behaviour. The main component in both species is the same, supporting the view that alarm pheromones lack species specificity. However, it appears that other components may also be important either as synergists of the main compound, or by stimulating behaviours that would not be observed in its absence.
Flight capability and flight motor pattern in a sedentary South African grasshopper,Phymateus morbillosus– a comparison with migratory species
Authors: Kutsch W. , Martz H. , Gäde G.
Published: March 2003

AbstractAmong the Acridoidea, not all species are strong fliers. We have examined the possible causes for loss of flight in a species with a reduced flight system, the South African grasshopper,Phymateus morbillosus(L.). This is a sedentary species that, in the field, displays only marginal flight (in males) or no flight (in females). In a wind tunnel, however, this species can be stimulated to perform flight movements for a short time. In the present study, several morphometric parameters and aspects of the flight motor output have been examined. The data are compared with those of the migratory locust species (Locusta migratoriaL. andSchistocerca gregariaForsk.).Phymateus morbillosuscan exhibit the typical flight motor pattern for short periods of up to 1 min. Morphometric data and wing‐beat frequency inP. morbillosusare similar to that of other members of this insect group. However, female specimens ofP. morbillosusare too heavy to lift themselves for active flight. We assume that females of this species invest in the augmentation of reproduction rather than investing in the flight system.