bluuebunny/crossref_metadata_2025 huggingface dataset:
Protection from autoimmune diabetes by adjuvant therapy non‐obese diabetic mouse: The role of interleukin‐4 and interleukin‐10
Authors: Calcinaro Filippo , Gambelunghe Giovanni , Lafferty Kevin J
Published: May 2007

Insulin‐dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by the destruction of insulin‐producing β‐cells in the pancreatic islets. A single administration of CFA prevents clinical hyperglycaemia in non‐obese diabetic (NOD) mice. We have previously shown that CFA administration does not eliminate insulitis in the pancreas of the treated animals, but diverts the disease process from a destructive to a non‐destructive pathway. We provide evidence that this phenomenon may be under cytokine control. Neutralizing monoclonal antibodies against IL‐4 and IL‐10 were injected, singularly or in combination, into CFA‐treated NOD mice. Antibody treatment did not lead to the development of overt diabetes; however, a marked impairment of glucose tolerance was shown in about one half of the mice treated with a combination of the two antibodies at the end of the study. This functional abnormality correlated with the histological loss of pancreatic islet tissue. These studies suggest a role for IL‐4 and IL‐10 in CFA‐induced protection from diabetes in the NOD mouse. They also suggest that, in this animal model, the nature of the autoimmune response to islet tissue (either destructive or non‐destructive) may reflect the relative proportion of Th1‐ and Th2‐type cytokines produced in the lesions.
Cloning and analysis of the human complement factor H gene promoter
Authors: Ward Helena M , Higgs Naomi H , Blackmore Timothy K , Sadlon Tania A , Gordon David L
Published: May 2007

The 5′ flanking region of human factor H was cloned using nested polymerase chain reaction (PCR) and the promoter finder method. A total of 1.2 kb has been sequenced and a number of putative regulatory elements identified including glucocorticoid response elements. cAMP responsive element, HTF‐1, and acute phase signal sequences. A 717 b.p. fragment was cloned into a CAT reporter vector and transfected into HeLa cells. A series of truncations from the 5′ end of this fragment were also cloned into the CAT vector. Analysis of CAT activity of the cell lysates showed that the region from ‐699 to +18 is likely to contain promoter elements for the factor H gene as it was able to drive transcription of the CAT gene.
Inhibition of Toxoplasma gondii replication in IFN‐γ‐activated human intestinal epithelial cells
Authors: Dimier Isabelle H , Bout Daniel T
Published: May 2007

Toxoplasma gondii is an obligate intracellular parasite which is responsible for severe disease after congenital infection and in immunocompromised patients, for which there is no effective therapy. In acquired toxoplasmosis, T. gondii first invade enterocytes and are disseminated throughout the body. Treatment of the adherent human intestinal cell line CaCO2 with recombinant human IFN‐γ inhibited the replication of T. gondii. Growth of the parasite was measured in vitro by [3H]‐uracil incorporation assays 18 h after infection. This assay showed that when cells were pretreated with IFN‐γ concentrations ranging from 2.5 to 5000 U/mL, a high degree of inhibition of T. gondii replication could be observed, with the effect being dose dependent. This could be of relevance as a first line of defence against human Toxoplasma infection. Inhibition is due to a different mechanism from that existing in mouse macrophages and human fibroblasts: L‐arginine‐dependent production of reactive nitrogen intermediates, reactive oxygen intermediates synthesis or production of indoleamine 2,3 dioxygenase were not responsible for inhibition of T. gondii proliferation.
cDNA cloning of porcine interleukin‐2 receptor‐α gene
Authors: Kokuho Takehiro , Uchimura Akihiko , Inumaru Shigeki
Published: May 2007

Porcine interIeukin‐2 receptor‐a subunit (IL‐2Rα) cDNA was cloned from the cDNA library of Con A‐stimulated PBMC. The coding sequence of porcine IL‐2Rα, including the signal peptide sequence, is 813 b.p. in length. The identities of the sequence when it was compared with ovine, murine, feline and human Sequences were 72.2, 62.4, 69.8 and 68.9% at nucleotide level and 58.9, 44.6, 54.6 and 55.6% at amino acid level, respectively. Then, the coding sequence of porcine IL‐2Ra was subcloned into the COS expression vector, pcDNA3.1/Zeo(+), and transfected into COS‐7 cells. The expressed protein was specifically reactive to the mAb, 231‐3B2, which seemed to be specific for porcine IL‐2Rα. This result reciprocally confirmed that the mAb, 231‐3B2, recognizes porcine IL‐2Rα on a molecular basis.
Dependence of the adaptive immune response on innate immunity: Some questions answered but new paradoxes emerge
Authors: Parish Christopher R , O'Neill Erin R
Published: May 2007

Recently a new model of vertebrate immunity has been gaining popularity. In this new model it is hypothesized that activation of innate immunity is a prerequisite for an adaptive immune response to an antigen. Following activation the innate system induces key costimulator molecules on APC, which are essential for antigen‐driven clonal expansion of T and B cells. The model largely explains the need for adjuvants in the induction of adaptive immunity, provides a possible mechanism for the immune system to perceive the biological nature of a pathogen and thereby produce the most effective immune response, and transfers much of the onus of self‐non‐self discrimination from the adaptive to the innate immune system. In the present article we highlight two paradoxes raised by the new model. First, by linking adaptive immunity to innate recognition the immune system is unable to take full advantage of the genetic diversity of T and B cell antigen receptors. Thus, the abihty of the immune system to combat a pathogen is totally dependent on the efficiency of recognition by the innate system and, therefore, the germ‐line mutation rate of the genes involved in the innate response. Second, if signals from the innate system induce costimulatory molecules on APC, then one would expect the accidental clonal expansion of many autoreactive T and B cells. We suggest that one means of resolving the first paradox is to propose that the major reason for the evolution of adaptive immunity was to provide, via immunological memory, resistance to reinfection, rather than simply to combat the primary infection by the pathogen. In the case of autoreactivity we suggest that autodestruction is prevented by immune responses being tightly regulated at the effector T cell level. Finally, we argue that the two paradoxes, rather than undermining the new model of immunity, highlight our lack of understanding of key elements of the vertebrate immune system.
Anti‐ovine VCAM‐1 monoclonal antibodies inhibit adhesion and proliferation between sheep endothelial and mononuclear cells in vitro
Authors: Grooby Warwick L , Krishnan Ravi , Russ Graeme R
Published: May 2007

This paper reports the production and characterization of three monoclonal antibodies (mAb) recognizing ovine vascular cell adhesion molecule‐1 (VCAM‐1). The mAb were raised against sheep umbilical vein endothelial cells (ShUVEC) and flow cytometric analysis demonstrated that one mAb, QE4G9, was crossreactive with human VCAM‐I expressed on Chinese hamster ovary cell transfectants. Protein modulation studies on ShUVEC and immunoperoxidase staining of inflamed renal tissue further indicated the reactivity of the other two ovine mAb. QE1E3 and QE2G4, with ovine VCAM‐1. The flow cytometric profile of the three mAb on stimulated ShUVEC was identical to that observed with the cross‐reactive anti‐human VCAM‐1 mAb, HAE2‐1. Peak expression occurred between 6–12 h after stimulation, followed by a slight decrease to a plateau extending beyond 48 h. In functional assays, all mAb inhibited adhesion of PMA‐activated sheep PBMC to stimulated ShUVEC. In addition, QE4G9 inhibited proliferation of sheep PBMC in the mixed lymphocyteendothelial cell reaction (MLER) by 56%. The results demonstrate that the three anti‐ovine VCAM‐1 mAb recognize functional epitopes on sheep vascular endothelial cells. These mAb will be valuable tools in the investigation of VCAM‐1 expression in various pathophysiological conditions using sheep models, and in the study of VCAM‐1‐mediated leucocyte‐endothelial cell interactions, both in vitro and in vivo.
Cellular responses and Mycobacterium bovis BCG growth inhibition by bovine lymphocytes
Authors: Carpenter Elizabeth , Fray Linley , Gormley Eamonn
Published: May 2007

Cellular responses of a group of cattle immunized subcutaneously with a low dose of Mycobacterium bovis bacille Calmette‐Guérin vaccine (BCG) were measured in vitro and compared with non‐immunized control animals. PBMC taken from immunized animals proliferated and produced IFN‐y in the presence of M. bovis BCG culture filtrate proteins. The addition of PBMC from immunized animals to M. bovis BCG‐infected autologous macrophages also resulted in secretion of IFN‐γ. In contrast, the responses of PBMC from control animals were comparatively low over the period of study. In experiments to study the interaction of non‐adherent lymphocytes with infected macrophages, M. bovis BCG growth was inhibited in cultures containing autologous PBMC from immunized and non‐immunized control animals. The degree of inhibition was related to lymphocyte concentration but did not correlate with IFN‐γ production. Treatment of macrophages with recombinant IFN‐y prior to, or postintection did not alter the intracellular growth kinetics of mycobacferia. It appears, therefore, that although M. bovis BCG immunization of cattle stimulates the generation of a T cell‐mediated immune response to M. bovis BCG, the cattle may already possess a high level of innate resistance to M. bovis BCG that requires the presence of lymphocytes.
The association of the subunits of component C3 of hagfish complement is unstable and leads to novel degradation during electrophoresis
Authors: Fujii Tamotsu , Kunisada Satomi
Published: May 2007

An opsonic molecule that is designated the third component of hagfish complement (HC3), and a fragment of HC3 known as HC3b have recently been identified in the hagfish, Eptatretus burgeri. These proteins were purified from plasma and generated a set of several bands and/or smears during SDS‐PAGE under standard, non‐reducing conditions. Two‐dimensional electrophoretic analysis of the proteins under non‐reducing and reducing conditions revealed the breakdown of polypeptides at the site of a thioester bond and the concomitant partial release of a split product, depending on the weak covalent or non‐covalent association of polypeptide chains, in a large fraction of molecules of HC3 during SDS‐PAGE. Moreover, the heterogeneity of HC3b can be ascribed to the different configurations of subunits. A similar phenomenon was not observed in the case of lamprey C3, even though breakdown of polypeptides at a thioester bond did occur in some molecules.
The development of antibody responses in the infant
Authors: Zola Heddy
Published: May 2007

The human infant is a major subject of immunization to prevent infectious disease. A better understanding of immune responses in human infants could lead to more effective immunization. Analysis of individual mechanisms is a prerequisite to understanding the whole response. We have examined the mutation and selection of immunoglobulin genes, mechanisms required for the maturation of antibody affinity. Mutations were rare in cord blood and were not detected in peripheral blood of infants under 10 days of age. Mutations were detected in most blood samples from infants aged 10 days to 2 months but the number of mutations was generally low compared with adults and there was limited evidence of selection. The ability to make and select mutated Ig increased over the 2‐8 months period, but did not reach adult levels. Neonates differ from adults in the expression of several components of the immune system that may take part in affinity maturation, including cytokine receptors, antigen receptor and co‐stimulator molecules. Thus, the mechanisms required to make high‐affinity antibody develop gradually during the first year of life. Possible evolutionary reasons for this are discussed.
Iotrochota revisited: a new sponge and review of species from the western tropical Atlantic (Poecilosclerida:Iotrochotidae)
Authors: Rützler Klaus , Maldonado Manuel , Piantoni Carla , Riesgo Ana
Published: May 2007

The systematics of tropical and subtropical western Atlantic species of Iotrochota is re-examined in light of the discovery of an undescribed species. Iotrochota birotulata (Higgin), the type species, is found to have more characters than previously recognised and is redefined with emphasis on a skeleton of spongin fibres containing stout, curved styles and strongyles (category I) and an interstitial spiculation consisting mainly of longer, slender and straight styles (II). Iotrochota bistylata Boury-Esnault is confirmed as a synonym of the above. The new species, named I. arenosa, sp. nov., differs in external morphology, strong mucus development, incorporation of sand and interstitial spicules that are mainly long, straight strongyles. Iotrochota atra (Whitfield), thought to be a synonym of I. birotulata, is recognised as a separate species occurring exclusively in the Bahamas and is found to be a senior synonym of I. imminuta Pulitzer-Finali; it is morphologically very similar to I. birotulata, but lacks birotulae and has a strongly reduced skeleton of megascleres (mostly one category of delicate strongyles). Iotrochota agglomerata Lehnert & van Soest is recognised as the fourth distinct species for its unusual colour (orange), thinly encrusting habit and special spiculation (styles with tylostylote modifications).
Ira Mellman: from endosomes to industry
Authors: Wells William A.
Published: May 2007

Disease-related research requires a different kind of teamwork, says Ira Mellman. He hopes to find that team at his new home at Genentech.
Dynamic recruitment of phospholipase Cγ at transiently immobilized GPI-anchored receptor clusters induces IP3–Ca2+ signaling: single-molecule tracking study 2
Authors: Suzuki Kenichi G.N. , Fujiwara Takahiro K. , Edidin Michael , Kusumi Akihiro
Published: May 2007

Clusters of CD59, a glycosylphosphatidylinositol-anchored receptor (GPI-AR), with physiological sizes of approximately six CD59 molecules, recruit Gαi2 and Lyn via protein–protein and raft interactions. Lyn is activated probably by the Gαi2 binding in the same CD59 cluster, inducing the CD59 cluster's binding to F-actin, resulting in its immobilization, termed stimulation-induced temporary arrest of lateral diffusion (STALL; with a 0.57-s lifetime, occurring approximately every 2 s). Simultaneous single-molecule tracking of GFP-PLCγ2 and CD59 clusters revealed that PLCγ2 molecules are transiently (median = 0.25 s) recruited from the cytoplasm exclusively at the CD59 clusters undergoing STALL, producing the IP3–Ca2+ signal. Therefore, we propose that the CD59 cluster in STALL may be a key, albeit transient, platform for transducing the extracellular GPI-AR signal to the intracellular IP3–Ca2+ signal, via PLCγ2 recruitment. The prolonged, analogue, bulk IP3–Ca2+ signal, which lasts for more than several minutes, is likely generated by the sum of the short-lived, digital-like IP3 bursts, each created by the transient recruitment of PLCγ2 molecules to STALLed CD59.
BimS-induced apoptosis requires mitochondrial localization but not interaction with anti-apoptotic Bcl-2 proteins
Authors: Weber Arnim , Paschen Stefan A. , Heger Klaus , Wilfling Florian , Frankenberg Tobias , Bauerschmitt Heike , Seiffert Barbara M. , Kirschnek Susanne , Wagner Hermann , Häcker Georg
Published: May 2007

Release of apoptogenic proteins such as cytochrome c from mitochondria is regulated by pro- and anti-apoptotic Bcl-2 family proteins, with pro-apoptotic BH3-only proteins activating Bax and Bak. Current models assume that apoptosis induction occurs via the binding and inactivation of anti-apoptotic Bcl-2 proteins by BH3-only proteins or by direct binding to Bax. Here, we analyze apoptosis induction by the BH3-only protein BimS. Regulated expression of BimS in epithelial cells was followed by its rapid mitochondrial translocation and mitochondrial membrane insertion in the absence of detectable binding to anti-apoptotic Bcl-2 proteins. This caused mitochondrial recruitment and activation of Bax and apoptosis. Mutational analysis of BimS showed that mitochondrial targeting, but not binding to Bcl-2 or Mcl-1, was required for apoptosis induction. In yeast, BimS enhanced the killing activity of Bax in the absence of anti-apoptotic Bcl-2 proteins. Thus, cell death induction by a BH3-only protein can occur through a process that is independent of anti-apoptotic Bcl-2 proteins but requires mitochondrial targeting.
Intranucleolar sites of ribosome biogenesis defined by the localization of early binding ribosomal proteins
Authors: Krüger Tim , Zentgraf Hanswalter , Scheer Ulrich
Published: May 2007

Considerable efforts are being undertaken to elucidate the processes of ribosome biogenesis. Although various preribosomal RNP complexes have been isolated and molecularly characterized, the order of ribosomal protein (r-protein) addition to the emerging ribosome subunits is largely unknown. Furthermore, the correlation between the ribosome assembly pathway and the structural organization of the dedicated ribosome factory, the nucleolus, is not well established. We have analyzed the nucleolar localization of several early binding r-proteins in human cells, applying various methods, including live-cell imaging and electron microscopy. We have located all examined r-proteins (S4, S6, S7, S9, S14, and L4) in the granular component (GC), which is the nucleolar region where later pre-ribosomal RNA (rRNA) processing steps take place. These results imply that early binding r-proteins do not assemble with nascent pre-rRNA transcripts in the dense fibrillar component (DFC), as is generally believed, and provide a link between r-protein assembly and the emergence of distinct granules at the DFC–GC interface.
Interspecific competition between Sphagnum mosses at different water tables
Authors: ROBROEK B. J. M. , LIMPENS J. , BREEUWER A. , CRUSHELL P. H. , SCHOUTEN M. G. C.
Published: May 2007

Effects of climate change may affect the Sphagnum species composition in bogs, and ultimately the functioning of the whole ecosystem. We investigated the effect of different water tables on the competition between six Sphagnum species in the glasshouse. The amount of precipitation (234 mm year−1) and precipitation frequency (every 2 weeks) were kept low to encourage water‐table effects. Relevant species combinations and monocultures were grown at different water tables for a 16‐month period. We studied changes in cover, height increment and capitulum water content (WCcap) in order to understand competitive responses.

Species naturally occurring further above the water table generally showed higher competitive strength than species naturally occurring closer to the water table. Surprisingly, this effect was irrespective of the water table, indicating a minor role for capillary water transport. Cover change seemed to be related to differences in length growth, but not to water table or WCcap.

The WCcap of species within a mixture did not differ, but was lower than the WCcap of the individual species growing in monoculture, indicating differences in ability to supply water to the capitula between mono‐ and mixed cultures. Subcapitulum bulk densities between mono‐ and mixed cultures did not differ, or were even lower in monocultures, but did differ between species within mixed cultures.

Our results indicate that structural heterogeneity of the peat in mixed cultures has a negative effect on WCcap of both species. Furthermore, we show that sustained periods of drought cause species that naturally occur further above the water table to oust species that naturally occur closer to the water table, even if the water table remains high. Ultimately, the Sphagnum vegetation in raised bogs may shift from hollow to hummock species, evening out the natural microtopography of raised bogs.
New method for evaluation of tongue‐coating status
Authors: SHIMIZU T. , UEDA T. , SAKURAI K.
Published: May 2007

Summary  The purpose of this study was to determine the viability of Tongue Coating Index, which is a new method for evaluating tongue‐coating status. To determine the reliability and reproducibility of our new evaluation criteria (Score 0: Tongue coating not visible; Score 1: Tongue coating thin, papillae of tongue visible; Score 2: Tongue coating very thick, papillae of tongue not visible), 10 observers evaluated 20 photographs of tongues. Each tongue surface was divided into nine sections. Observers evaluated each section according to our new criteria and each score for tongue‐coating status was recorded in the pertinent section of the Tongue Coating Record form. They repeated the same evaluation 2 weeks after the first evaluation. The relationship between the scores obtained and number of oral microorganisms was investigated in 50 edentulous patients. Tongue coating was collected from the tongue surface after evaluation of tongue‐coating status. The total number of anaerobic bacteria and the number of Candida species were counted from the specimens collected. Interobserver agreement and intraobserver agreement were 0·66 and 0·80 by Cohen's kappa, respectively. No significant difference was observed in the number of Candida species among the three scores. The number of total anaerobic bacteria, however, was significantly different among the scores (P < 0·05). Therefore, we conclude that our method for evaluating tongue‐coating status offers new criteria that are superior in reliability and reproducibility, and that also reflect the total number of anaerobic bacteria present on the dorsum of the tongue.
Relationship between number of natural teeth in older Japanese people and health related functioning
Authors: MORITA I. , NAKAGAKI H. , KATO K. , MURAKAMI T. , TSUBOI S. , HAYASHIZAKI J. , SHEIHAM A.
Published: May 2007

Summary  The objective was to assess the relationship between number of functional occluding natural pairs of teeth and health related functioning in older free living Japanese people using the SF‐20. The participants were 107 elderly people aged 80 years. Health related functioning was measured with the SF‐20. The numbers of functional occluding natural pairs of teeth (OPs) were calculated and scored as follows: 1, for each pair of anterior teeth and premolars in occlusion. Molar functional natural occluding pairs were scored 2 for each occluding pair. The number of functional occluding pairs was assessed separately as anterior natural occluding pairs (AOPs) and posterior occluding pairs (POPs). There were significant differences in the role functioning subscale of SF‐20 between those who were edentulous and those with one to nine natural teeth and 10 or more natural teeth (P = 0·030). Those with one to six AOPs had significantly higher role functioning than the zero AOPs group (P = 0·042). Those with 1–12 POPs also had significantly higher role functioning scores than the zero natural POPs group (P = 0·007). However, there were no significant relationships between number of natural teeth, OPs or AOPs, and POPs on the one hand, and all other subscales of SF‐20 on the other hand. The community‐dwelling 80‐year‐old Japanese people in this study had overall good health related functioning. The number of functional occluding pairs of natural teeth, especially POPs, was related with the role functioning subscale of SF‐20 but had no significant relationships to the other dimensions of SF‐20.
Influence of the shape core on custom cast dowel and core removal by ultrasonic energy
Authors: QUEIROZ E. C. , MENEZES M. S. , BIFFI J. C. G. , SOARES C. J.
Published: May 2007

Summary  The aim of this study was to assess the influence of the shape of custom cast dowel and cores on their removal by the use of ultrasound technique. Twenty‐four single‐rooted bovine teeth were prepared and had cast dowel fixed with zinc phosphate cement. The teeth were randomly divided into two groups: group I‐ received custom cast dowel and cores made without the coronal portion anatomy, simulating removal this portion with a bur, and group II‐ received cores that reproduced the coronal anatomy. Both were treated with an ultrasound device in two three‐minute cycles (US). The force necessary for dowel removal was determined using a mechanical test machine. In the second stage of the study, the custom cast dowel and cores were again cemented and no ultrasound vibration was used on them (C). Data were submitted to the two‐way anova (2 × 2) and Tukey test (P < 0·05), resulting in decreased tensile strength values (Kgf): GIC (49·85 ± 11·10); GIIC (48·22 ± 11·09); GIIUS (32·36 ± 6·21) and GIUS (8·0 ± 7·52). It was concluded that the shape of the core without the anatomic coronal portion facilitated removal of intra‐radicular retention only when associated with the use of ultrasound.
Trichuris suis excretory/secretory antigen‐specific antibodies in serum from single‐inoculated pigs
Authors: KRINGEL H. , ROEPSTORFF A.
Published: May 2007

The humoral immune response induced by Trichuris infections has mostly been described in mouse models and in infected humans, but as the immunomodulatory effect of Trichuris suis, the swine whipworm, becomes increasingly documented, the need for understanding the response induced by this specific parasite species grows. In the present study we describe changes in serum IgG1, IgG2, IgA and IgM antibodies specific to adult T. suis excretory/secretory (E/S) antigens in the time course of a primary infection in swine. The average levels of specific IgG1, IgG2 and IgM peaked at 9 weeks post‐inoculation and then declined within a few weeks of worm expulsion. The IgA level rose earlier and remained elevated after worm expulsion. The protective role of Trichuris‐specific antibodies is uncertain, but some of them presumably reflect the presence of worms in the intestine. Further development of this analysis could have diagnostic value in swine and humans infected with T. suis for experimental or therapeutic purposes.
Atypical cutaneous leishmaniasis cases display elevated antigen‐induced interleukin‐10
Authors: RODRIGUEZ B. , BEATTY R. , BELLI A. , BARRETO A. , PALACIOS X. , MARIN F. , HARRIS E.
Published: May 2007

In humans, Leishmania chagasi parasites can produce subclinical infections, atypical cutaneous leishmaniasis (ACL) and visceral leshmaniasis that is potentially fatal if not treated in a timely fashion. L. chagasi parasites that cause both ACL and visceral disease appear to be genetically similar, which suggests that host factors such as the immune response play an important role in controlling infection. We evaluated the immunologic response in ACL using peripheral blood mononuclear cells (PBMCs) of 37 subjects divided into three groups: (i) active ACL cases, (ii) asymptomatic cases and (iii) persons with no history of Leishmania infection. The supernatants of stimulated PBMCs were analysed for production of IL‐10, IFN‐γ and IL‐2. Robust production of IL‐10 in response to Leishmania stimulation was observed in active ACL cases, compared to low levels in asymptomatic cases and negative controls. Serum IgE levels, measured by ELISA, were not significantly different among the three groups. In addition, ACL cases displayed depressed levels of all cytokines in response to mitogen. Thus, this first characterization of the immune response in ACL suggests a role for IL‐10 as well as partial immunosuppression.
A longitudinal study of immune responses to Plasmodium falciparum sexual stage antigens in Tanzanian adults
Authors: BOUSEMA J. T. , DRAKELEY C. J. , KIHONDA J. , HENDRIKS J. C. M. , AKIM N. I. J. , ROEFFEN W. , SAUERWEIN R. W.
Published: May 2007

Next to children, adults form a substantial part of the infectious reservoir that is responsible for the spread of malaria. In this longitudinal study, we determined sexual stage immune responses to Plasmodium falciparum and infectiousness to mosquitoes in adults from an area with intense malaria transmission. A cohort of 43 Tanzanian adults was followed for 18 months. Parasitological data were collected monthly; serum once every three months. Antibody prevalences were determined for sexual stage antigens Pfs230 and Pfs48/45 and circumsporozoite protein (NANP5)(n = 199). Functional transmission reducing activity (TRA) was assessed by standard membrane feeding assay (SMFA; n = 85). Cumulative parasite prevalence was 67·4% (29/43) for asexual stages and 34·9% (15/43) for gametocytes. Enrolment antibody prevalence was 95·3% (41/43) for NANP5, 18·9% (7/37) for Pfs230 and 7% (3/43) for Pfs48/45 epitope 3. TRA > 50% reduction was seen in 48·2% (41/85) and TRA > 90% reduction in 4·7% (4/85) of the samples. Our findings of low and inconsistent sexual stage immune responses are likely to be the result of a low exposure to gametocytes in this older age group. This may in turn be caused by effective asexual stage immunity. We conclude that the infectivity of older individuals is less likely to be affected by sexual stage immunity.
Vaccination of goats with recombinant galectin antigen induces partial protection against Haemonchus contortus infection
Authors: YANMING S. , RUOFENG Y. , MULEKE C. I. , GUANGWEI Z. , LIXIN X. , XIANGRUI L.
Published: May 2007

The efficacy of vaccination against Haemonchus contortus infection with two recombinant proteins, rHco‐gal‐m and rHco‐gal‐f, was studied in 9–10‐month‐old goats. Vaccination with 100 µg protein reduced faecal egg output and worm burdens by 37·25% and 41·1%, respectively. Corresponding reductions with 200 µg protein were 48·03% and 46·19%. Vaccinated groups had significantly higher IgG levels than the negative and positive controls. Significant negative correlations were detected between IgG level, mucosal homogenate IgA concentration, haemoglobin and abomasal worm burden at necropsy. By contrast a positive correlation was found between the percentage of B cells, monocytes and abomasal worm burden. These findings suggested that vaccination with a combination of recombinant rHco‐gal‐m/f proteins had a role in protecting goats against H. contortus infection.
AIDS dementia and HIV‐1 replication
Authors: Takahashi Hidehiro , Kurata Takeshi , Nagashima Kazuo
Published: May 2007

Of those infected with human immunodeficiency virus type 1 (HIV‐1), approximately 50% develop neurological complications. At postmortem examination, approximately 50% of those infected with HIV‐1 have histological evidence of AIDS encephalitis. Pathologically, this disorder is characterized by multifocal gliosis and parenchymal infiltrates of multinucleated giant cells and macrophages. Many of the macrophages comprising these infiltrates, contain HIV‐1 protein, viral transcripts, and mature virions. In addition, these histological changes are not associated with secondary opportunistic pathogens, so it is believed that HIV encephalitis represents a primary lentiviral disease manifestation and the target for HIV‐1 in the brain is thought to be the macrophages. Recently, macrophage‐tropic primary HIV‐1 isolates have been found to use receptors for CC chemokine, CKR‐5 and CKR‐3 as a co‐receptor for virus entry. Genetic analysis proved that CKR‐5 plays an important role in disease progression or virus infection. Furthermore, some ligand‐derivatives for these receptors are expected as a drug for treatment. Certainly, the elucidation of entry mechanisms has led to renewed enthusiasm in AIDS research. Besides, to develop research and understand this disease, a small animal model is necessary. However, simple transfection of human genes into animal cells does not establish an HIV‐1 infection. Mechanisms that inhibit HIV‐1 replication in non‐primate cells remain to be determined. Therefore, focus is given to post‐entry mechanisms of HIV‐1 replication, which is expected to play a key role HIV‐1 to infect non‐primate cells.
Expression of amyloid precursor protein mRNA in vascular smooth muscle cells of the human brain
Authors: Takahashi Reisuke Heavy , Sawa Hirofumi , Takada Akio , Kitabatake Akira , Nagashima Kazuo
Published: May 2007

Amyloid deposition in the cerebral vessels is the hallmark of cerebral amyloid angiopathy (CAA). In order to establish which type of cell produces amyloid, we performed Northern blot analysis and in situ hybridization studies on human meningeal arteries. Northern blotting showed that amyloid precursor protein (APP) mRNA was expressed not only in the cerebral cortex, but also in the meninges. An antisense RNA probe that hybridizes with APP transcripts was used for in situ hybridization. This analytic modality revealed APP messages in the tunica media of the meningeal arteries and arterioles. The presence of smooth muscle cells in these vessels was verified immunohistochemically on consecutive serial sections. These observations indicate that APP is produced by vascular smooth muscle cells.
Membranous cytoplasmic bodies in a patient with amyotrophic lateral sclerosis with short clinical duration
Authors: Kihira Tameko , Wakayama Ikuro , Tada Jyoji , Namikawa Tadashi , Yoshida Sohei , Yase Yoshiro
Published: May 2007

Recently membranous cytoplasmic bodies (MCB) were observed in spinal anterior horn neurons in two patients with sporadic amyotrophic lateral sclerosis (ALS). Membranous cytoplasmic bodies are considered to be lysosomal in nature, therefore the abnormalities in the lysosomal system in ALS were emphasized in the report. We also observed abundant MCB in the lumbar anterior horn neurons in a sporadic ALS patient with short clinical duration. The neurons with MCB were densely packed with 10 nm neurofilaments, ribosome‐like granules, lipofuscin granules and other intracytoplasmic organelles without any distinctive inclusions. They appeared to show simple atrophy or chromatolysis upon light microscopy. By comparison, the ubiquitin reactive inclusion‐laden neurons showed fewer MCB. We speculate that in some ALS cases with short clinical duration the degenerative neurons have some abnormalities or overload of the lysosomal proteolytic systems leading to development of MCB.
The microvasculature of the spinal cord in the human adult
Authors: Zhang Ze‐An , Nonaka Hiroko , Hatori Tsutomu
Published: May 2007

The microvasculature of the human spinal cord have been studied with scanning electron microscopy (SEM) on the corrosion casts of blood vessels, and light microscopy on the transparent after intra‐arterial injection of Indian ink and vascular staining specimens.

On the surface of the cord, the density of the pial venous plexus was higher than the pial arterial plexus. The anterior spinal artery and vein gave off central arteries and veins, which ran posteriorly within the anterior median fissure. The number of the central arteries and veins per centimeter in length is highest in the lumbosacral cord, followed by the cervical and then the thoracic cord. In this study, the central arteries and veins were classified into types; type 1 dominated the arterial system and type 2 the venous system. The central arteries and veins sent long branches both rostrally and caudally along the axis of spinal cord. The order of their length was as follows: thoracic, cervical, lumbar and sacral cord. These blood vessels overlapped each other. The peripheral arteries terminated in the periphery of the gray matter while the peripheral veins originated within the different depth of the gray matter. The posterior spinal artery supplied the posterior horn and the substantia gelatinosa. The posteromedial veins arose in the deep posterior horns and posterior funiculus, and were occasionally connected with the anterior spinal vein within the cord. Overlapped zone which was supplied by both the central and peripheral vascular system was seen within the cord, and its extent was variable at different levels. The overlapped zone of the venous supply was broader than the arterial one. The peripheral veins appeared to drain blood not only from the white matter but also from the gray matter. The distribution of the capillary networks in the gray matter was slightly denser and showed more horizontal arrangement in the lumbosacral cord, and more sparse and longitudinal in the cervicothoracic cord. The distribution of the capillary networks in the white matter was parallel to nerve fibers which run longitudinal in the whole cord.

Based on the result of present study, it was considered that the circulatory disturbances are prone to occur in the thoracic cord, and the circulatory block in the arterial system of the cord tends to cause a lesion in the gray matter, whereas the circulatory disturbances in the venous system tends to cause a lesion in the white matter.
Diagnostic imaging of spinal cord lesions
Authors: Tamaki Norihiko , Eguchi Takahiro
Published: May 2007

Magnetic resonance imaging (MRI) has greatly facilitated morphologic evaluation of spinal cord lesions. Eleven cases representative of inflammatory, demyelinating, neoplastic and vascular diseases, are presented which illustrate and summarize important abnormal features in spinal cord imaging, particularly MR findings. Recently, specialised techniques such as MR angiography, fat‐inhibiting methods, dynamic MRI and functional imaging have been developed. These methods have facilitated not only lesion diagnosis but also qualitative assessment, and are being used to analyze pathophysiology. Comprehensive diagnoses based on such modalities may be important in determining indications for surgery or defining the extent of surgery or the intensity of other treatments.
Spinal cord lesions of multiple sclerosis
Authors: Shirabe Teruo , Fushimi Shigeko , Morisada Yumi
Published: May 2007

The neuropathological findings of the spinal cord lesions of six human multiple sclerosis cases are described. The spinal cord was extensively necrotic and occasionally cystic in five remitting and relapsing cases. The lesions became more severe as the disease course prolonged and relapses increased. The spinal cords of two cases in particular, with a duration of illness of more than 5 years, were severely atrophic. In these cases, peripheral type remyelination was prominent, although central type remyelination was minimal. In contrast, in mouse spinal cords, in which experimental demyelination and remyelination were induced by ethidium bromide, the degree of central type remyelination and peripheral type remyelination was almost the same. Longitudinal sections of the transitional zone between the areas of central type remyelination and peripheral type remyelination contrained Ranvier nodes, in which central type myelin and peripheral type myelin were situated side by side around a central type axon. These transitional zones were similar to those of the normal transitional zone between the central nervous system and peripheral nervous system of the nerve roots. One chronic progressive case, despite the very long duration of illness, showed classical sharply demarcated demyelinated lesions with marked fibrillary gliosis. The spinal cord of this case was not atrophic and axons were well preserved.
Hereditary ceruloplasmin deficiency: A cerebro‐retino‐diabetic disease
Authors: Kato Takeo , Kawanami Toru , Daimon Makoto , Sasaki Hideo
Published: May 2007

Hereditary ceruloplasmin deficiency (HCD) is a recently recognized neurodegenerative disease of an autosomal recessive inheritance. This disease is caused by the defect of the ceruloplasmin gene. The initial manifestation of HCD is usually adult‐onset diabetes mellitus. Neurological symptoms occur 10 to 20 years thereafter, between 40 and 60 years of age. These include dementia, abnormal involuntary movements, and cerebellar ataxia. Retinal degeneration is also present. The cardinal pathological change is a massive iron deposition to the brain, liver and pancreas. A marked loss of neurons is observed in the caudate nucleus and putamen of the brain. The number of insulin cells is decreased in the islets of the pancreas. In the clinical settings, it seems that HCD patients may exist among the population of adult‐onset diabetic patients.
A novel autoantibody in paraneoplastic sensory‐dominant neuropathy
Authors: Arawaka Shigeki , Kato Takeo , Kurita Keiji , Daimon Makoto , Matsumoto Naoya , Sasaki Hideo
Published: May 2007

We detected a novel autoantibody in the serum and cerebrospinal fluid of a patient with sensory‐dominant neuropathy and gastric cancer. In rats, the antigen was localized in the perikarya of some small neurons and the cytoplasm of a few satellite cells in the dorsal root ganglia, and in the neuropil of the laminae I, II of the posterior horns in the spinal cord and the spinal trigeminal nuclei in the medulla oblongata. Immunoblotting revealed the molecular weight of the antigen as approximately 47 kDa. With respect to its histological localization and molecular weight, this autoantibody is different from any other reported autoantibodies including anti‐Hu, and this autoantibody seems to be responsible for the patient's sensory disturbance.
Ganglioglioma: A clinicopathological study of 10 cases
Authors: Büttner Andreas , Bavbek Bilge , Winkler Peter A. , Mehraein Parviz , Weis Serge
Published: May 2007

The clinical, radiological, and pathological features in 10 cases of ganglioglioma are described. The clinical data were derived from the patients' medical records, including a review of the age, sex, details of the presenting symptoms, radiological imagings, surgical intervention, and the clinical outcome. Age ranged from 1 to 66 years (mean 29); there were five males and five females. The tumors were located in the fronto‐medial, bifrontal, temporal, temporo‐basal, temporo‐parieto‐occipital, and parietal lobes; the 3rd ventricle; the cervicothoracic spinal cord; and the conus medullaris. The presenting symptoms were focal seizures, headaches, hemiparesis, paraparesis, and tetraparesis. In four patients, gross total resection was achieved and in the remaining six patients only subtotal resection was possible. Tumor recurrence occurred in three patients, 1 year, 14 months, and 2 years after the first operation. The histopathologic appearance of gangliogliomas showed a broad variation of the neuronal, glial, and stromal component. Studying proliferation characteristics, labeling for Ki‐67 ranged from 0 to 13.7% (mean 4.1) and for PCNA from 0 to 32.1% (mean 20.4). Due to their favorable prognosis, early recognition and correct diagnosis are important in order to avoid progressive neurological deficits and unnecessary aggressive therapy. The application of immunohistochemistry for both neuronal (synaptophysin, NSE, NFP) and astrocytic (GFAP) cell markers, as well as proliferation markers, are recommended in the diagnostic setting for gangliogliomas. The treatment of choice is total surgical resection. The role of radio‐ and chemotherapy is still controversial.
Intraventricular administration of GABAA receptor agonist muscimol attenuates the exo‐focal change of the substantia nigra neurons following transient middle cerebral artery occlusion in rats
Authors: Yamada Kazumichi , Goto Satoshi , Yoshikawa Makoto , Okamura Akira , Nagahiro Shinji , Ushio Yukitaka
Published: May 2007

A therapeutic effect of the selective GABAA receptor agonist muscimol on the ‘exo‐focal postischemic death’ was examined in the substantia nigra pars reticulata (SNr) of rats. Continuous intraventricular infusion of muscimol (muscimol‐infusion group) or saline (control group) was initiated from 24 h after the transient middle cerebral artery occlusion for 2 h. At 3 days postischemia, in accordance to a marked depletion of GABAergic afferent fibers in the ipsilateral substantia nigra, strong immunolabelling for 72 kDa heat shock protein (HSP72) appeared in the SNr neurons of the control rats. In contrast, there was no apparent HSP72 immunoreactivity in the ipsilateral SNr in the muscimol infusion group at this stage. In addition, cell density analysis showed that neuronal cell loss in the ipsilateral SNr was effectively prevented by muscinol infusion, as compared to that in the control group, at 15 days after ischemic insult. Thus, the GABA agonist could relieve the deafferented SNr neurons from the lethal metabolic changes responsible for induction of the stress response, which may occur in the course of exo‐focal postischemic death.
Adrenoleukodystrophy with involvement of the cerebral cortex
Authors: Kakita Akiyoshi , Ishikawa Atsushi , Koike Ryoko , Tsuji Shoji , Takahashi Hitoshi
Published: May 2007

This report describes adrenoleukodystrophy (ALD) in a 54‐year‐old man of 18 years duration. Histological examination revealed widespread, severe degeneration of the cerebral white matter, which is typical of the disease. Furthermore, severe neuron loss, spongiform change and hypertrophic astrocytosis were evident in the cerebral cortex overlying the devastated convolutional white matter. This neuron loss cannot simply be explained in terms of a change secondary to the white matter lesion. An ultrastructural study of the affected cerebral cortex revealed occasional lamellar intracytoplasmic inclusions in the remaining cells with neuronal features such as lipofuscin granules and intermediate filaments with fine side arms. These inclusions were consistent with those observed in the striated macrophages and glial cells of the cerebral white matter and in the cortical cells of the adrenal gland. These pieces of evidence suggest that the cerebral cortex has the potential to be affected primarily in ALD.
Vascular dementia clinically resembling Creutzfeldt‐Jakob disease
Authors: Seno Haruo , Ishino Hiroshi , Inagaki Takuji , Iijima Masaaki , Kikumoto Osamu , Yoshinaga Junji , Matsuura Hiroo , Tachiyama Yoshiro
Published: May 2007

An autopsy case of vascular dementia, clinically resembling Creutzfeldt‐Jakob disease, is reported. A 74‐year‐old woman showed progressive dementia, transient myoclonus of the right upper arm, diffuse periodic synchronous discharges on electroencephalography, and brain atrophy on computed tomography. The duration of the illness was 17 months. Neuropathologic findings were numerous small necrotic foci in the middle and lower layers of the cerebral cortex, myelin pallor of the cerebral white matter, and fibrous thickening of the arterial and arteriolar walls in the cerebrum and cerebellum (both cortex and white matter). Vascular dementia was diagnosed. On the basis of these features, it is considered that such neuropathologic changes caused Creutzfeldt‐Jakob‐like symptoms, such as dementia and periodic synchronous discharges.
Selective enlargement of the fourth ventricle in Machado‐Joseph disease: With special reference to the neuroradiological and neuropathological correlation
Authors: Tsuchiya Kuniaki , Ikeda Kenji , Sugihara Hiroshi , Watabiki Sadakiyo , Ohbu Sadayoshi , Abe Mitsubumi , Takahashi Ryosuke , Tadokoro Mamoru , Shimada Hiroyuki
Published: May 2007

This report concerns a study of serial brain computed tomography (CT) images including neuroradiological and neuropathological correlations in three patients with Machado‐Joseph disease (MJD). The diagnosis of MJD was confirmed by neuropathological examination in two patients (Cases 1 and 2), and by molecular analysis in one (Case 3). Serial CT images of Case 1 were obtained for nine years, and of Cases 2 and 3 for three years. The results indicate that in the initial stages of MJD only enlargement of the fourth ventricle is seen and that in the advanced stages of the disease, atrophy of the cerebellar hemispheres also becomes evident. These findings are essentially in agreement with the previously described sequential neuropathological changes of the spinocerebellar pathways in MJD patients. Enlargement of the fourth ventricle in the initial stages of the disease is probably due to the involvement of the dentate nucleus with degeneration of the efferent fibers. The atrophy of the cerebellar hemispheres seen in the advanced stages of MJD is probably caused by alterations of the pontine nucleus with degeneration of the cerebellar white matter.