bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of calcitonin gene‐related peptide (CGRP) on motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the isolated perfused porcine antrum
Authors: Rasmussen T. N. , Schmidt P. , Poulsen S. S. , Holst J. J.
Published: March 2003

We studied the effect of porcine CGRP (pCGRP) in concentrations from 10–10 to 10–8 mol L–1 on the motility and on the release of substance P, neurokinin A, somatostatin and gastrin in the antrum using the isolated perfused porcine antrum as experimental model. In addition, we studied the localization of CGRP by immunohistochemistry in the porcine antrum. CGRP‐immunoreactive nerve fibres were found mainly in the submucous layer and in the external muscle coat, where they were seen in all layers, and in the ganglia of the myenteric nervous plexus. The frequency of contraction was significantly and dose‐dependently increased from a basal level of 11.8 ± 0.5 contractions per 5 min to 24.4 ± 3.6 contractions per 5 min at pCGRP 10–8 mol L–1. At this dose, the release of substance P and neurokinin A was significantly increased to 470 ± 149% and 217 ± 26%, respectively, compared to basal release. The effect of pCGRP was unaffected by the addition of the nonpeptide antagonists for the NK‐1 (CP‐99994) and NK‐2 receptors (SR48968), both at 10–6 mol L–1, whereas atropine (10–6 mol L–1) completely abolished the motor effect of pCGRP. The release of somatostatin was significantly increased by 154 ± 15% in response to CGRP at 10–8 mol L–1. The release of gastrin was unaffected by pCGRP. In conclusion, pCGRP increases contractile activity in the porcine antrum, an effect that involves cholinergic mechanisms but is independent of the release of substance P and neurokinin A. in addition, pCGRP increases the release of somatostatin but has no effect on gastrin release in the isolated perfused porcine antrum.
The tripeptide feG reduces endotoxin‐provoked perturbation of intestinal motility and inflammation
Authors: Mathison R. , Lo P. , Tan D. , Scott B. , Davison J. S.
Published: March 2003

Lipopolysaccharide (LPS)‐induced intestinal endotoxaemia perturbs motility and causes activation and influx of inflammatory cells into the muscle tissue. Because rat submandibular gland peptide T (SGP‐T; Thr‐Asp‐Ile‐Phe‐Glu‐Gly‐Gly), its carboxyl‐terminal fragment tripeptide, FEG (Phe‐Glu‐Gly) and its D‐isomeric analogue, feG, modulate intestinal anaphylactic reactions, we examined whether these peptides also modulate LPS‐induced intestinal endotoxaemia in conscious rats. The disruption of the fasting pattern of intestinal MMCs (migrating motor complexes), induced by intravenous LPS (20 μg kg−1) injection, was prevented by all three peptides. The extravasation of leucocytes into the peritoneal cavity and increased expression of the activation marker CD18 on mesenteric tissue leucocytes (18 h after intraperitoneal injection of LPS) were reduced by orally administered feG, which also significantly decreased the number of intestinal tissue leucocytes expressing the integrin CD18. We conclude that feG attenuates both the immediate (intestinal motility) and late (∼ 18 h) inflammatory reactions provoked by endotoxaemia.
Effects of motilin on human interdigestive gastrointestinal and gallbladder motility, and involvement of 5HT3 receptors
Authors: LUIKING Y. C. , AKKERMANS L. M. A. , PEETERS T. L. , CNOSSEN P. J. , NIEUWENHUIJS V. B. , VANBERGE ‐HENEGOUWEN G. P.
Published: March 2003

A plasma motilin peak and a partial gallbladder emptying precede the antral phase III of the migrating motor complex (MMC). To clarify the causal relationship between these factors, we aimed to study the role of motilin in interdigestive gastrointestinal and gallbladder motility simultaneously. In addition, involvement of 5HT3 receptors in the action of motilin was studied. Eight fasting, healthy male volunteers received 13Leu‐motilin or 0.9% NaCl i.v. for 30 min, in randomized order on two separate occasions, from 30 min after phase III. Seven of the eight subjects also received the 5HT3 receptor antagonist ondansetron in addition to motilin, on a third occasion. Antroduodenal motility, gallbladder volumes and plasma motilin were measured. The interval between the start of infusion and phase III was 95.0 (57.6–155.7) min for saline, 28.7 (21.0–33.2) min for motilin, and 39.3 (30.7–100.5) min for motilin + ondansetron (P < 0.05). Gallbladder volume decreased by one‐third from 10 min after both motilin and motilin + ondansetron infusion (P < 0.05), and returned to baseline with duodenal passage of phase III. In two of the seven subjects phase III was absent after motilin + ondansetron, although gallbladder volume decreased and only refilled during a later spontaneous phase III. We conclude that motilin induces both partial gallbladder emptying and antral phase III. Indeed, although gallbladder emptying clearly precedes antral phase III, ondansetron only prevented phase III in some cases and had no effect on gallbladder emptying. Passage of phase III in the duodenum makes an important contribution to gallbladder refilling.
gThe Dorothy Russell Memorial Lecture* The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms
Authors: McIntosh  , Saatman  , Raghupathi  , Graham  , Smith  , Lee  , Trojanowski
Published: March 2003

The mechanisms underlying secondary or delayed cell death following traumatic brain injury (TBI) are poorly understood. Recent evidence from experimental models of TBI suggest that diffuse and widespread neuronal damage and loss is progressive and prolonged for months to years after the initial insult in selectively vulnerable regions of the cortex, hippocampus, thalamus, striatum, and subcortical nuclei. The development of new neuropathological and molecular techniques has generated new insights into the cellular and molecular sequelae of brain trauma. This paper will review the literature suggesting that alterations in intracellular calcium with resulting changes in gene expression, activation of reactive oxygen species (ROS), activation of intracellular proteases (calpains), expression of neurotrophic factors, and activation of cell death genes (apoptosis) may play a role in mediating delayed cell death after trauma. Recent data suggesting that TBI should be considered as both an inflammatory and/or a neurodegenerative disease is also presented. Further research concerning the complex molecular and neuropathological cascades following brain trauma should be conducted, as novel therapeutic strategies continue to be developed.
Antisense epidermal growth factor receptor RNA transfection in human malignant glioma cells leads to inhibition of proliferation and induction of differentiation
Authors: Tian  , Lam  , Chen  , Pang  , To  , Di‐Tomaso  , Ng
Published: March 2003

The epidermal growth factor receptor (EGFR) is a proto‐oncogene that is frequently observed with alterations in late stage gliomas, suggesting an important role of this gene in glial tumorigenesis and progression. In this study we evaluated an antisense EGFR approach as an alternative therapeutic modality for glioblastomas. We transfected U‐87MG cells with an antisense EGFR construct and obtained several clones stably expressing lower or undetectable levels of EGFR protein. These clones were found to have impaired proliferation as well as a reduced transforming potential to grow in soft agarose. The number of cells positive for the cell cycle‐specific nuclear antigen Ki‐67 was also significantly decreased (P<0.05) in antisense EGFR‐transfected clones compared with parental or empty vector‐transfected cells. Flow cytometric analysis revealed that the proportion of cells in G0 /G1 phases of the cell cycle in the antisense clones increased by up to 31% compared with control cells, whereas the proportion of cells in S phase decreased by up to 58%. In addition, the antisense EGFR‐transfected cells showed higher expression of glial fibrillary acidic protein and a more differentiated form, with smaller cell bodies possessing fine tapering cell processes. These results suggest that EGFR plays a major role in modulating cell growth and differentiation in glioblastoma cells. Our experimental model of antisense EGFR provides a basis for future development of antisense EGFR oligodeoxynucleotides in treatment of glioblastomas.
Apoptosis of myofibres and satellite cells: exercise‐induced damage in skeletal muscle of the mouse
Authors: Podhorska‐Okolow  , Sandri  , Zampieri  , Brun  , Rossini  , Carraro
Published: March 2003

Apoptosis is well accepted as a type of cell death occurring in the development of mammalian muscles, but the death of adult myofibres in neuromuscular disorders and exercise‐induced muscle damage is usually explained in terms of muscle necrosis. The current view that apoptosis precedes necrosis in death of dystrophin‐deficient muscle fibres of mdx mouse has been well substantiated. Moreover, apoptotic myonuclei have been reported to increase in mdx mice 2 days after spontaneous exercise. To investigate the contribution of apoptosis to exercise‐induced damage of normal muscle fibre a time‐course analysis has been performed in adult C57BL/6 mice. Groups of five mice were sacrificed immediately after the end of the exercise, and after a rest period of 6 or 96 h. The amount of apoptosis in leg muscles was assessed by electron microscopy, by the terminal deoxynucleotidyl transferase assay and by electrophoretic detection of fragmented DNA; the expression of Bcl‐2, Bax, Fas, ICE, p53 and ubiquitin was examined by immunohistochemistry and Western blot. Absent in muscles of normal dentary’ mice, apoptotic myonuclei peak in muscles of normal mice after a night of spontaneous wheel‐ running (4%±3.5, immediately and 2.5%±1.8 after 6 h rest, P<0.05 vs non‐runner mice); they then decrease but are present 4 days later (0.8%±1.5). Satellite cells are also involved in the apoptotic process. Myofibre content of Bcl‐2 decreases whereas Bax, Fas, ICE and ubiquitin modify their pattern of expression in correlation with the changes in apoptotic myonuclei. Apoptosis of endothelial cells is present after the night of wheel‐running and with a twofold increase 4 days later (1.5±2.3 and 4.8±4.4 P<0.05, respectively). Satellite cells are also involved in the apoptotic process. Thus, spontaneous running in unaccustomed mice increases the number of apoptotic nuclei in adult muscle fibres and in endothelial cells. It remains to be established whether muscle apoptosis is restricted to the repair mechanisms, as often suggested in many pathologic processes, or it is also part of pathogenesis of muscle damage. Regardless of whether these results are extended to human dystrophies, the clinical implications in terms of secondary pathogenetic mechanisms and muscle training are obvious.
The amyloid precursor protein of Alzheimer’s disease and the Aβ peptide
Authors: Storey  , Cappai
Published: March 2003

Alzheimer’s disease is characterized by the accumulation of beta amyloid peptides in plaques and vessel walls and by the intraneuronal accumulation of paired helical filaments composed of hyperphosphorylated tau. In this review, we concentrate on the biology of amyloid precursor protein, and on the central role of amyloid in the pathogenesis of Alzheimer’s disease. Amyloid precursor protein (APP) is part of a super‐family of transmembrane and secreted proteins. It appears to have a number of roles, including regulation of haemostasis and mediation of neuroprotection. APP also has potentially important metal and heparin‐binding properties, and the current challenge is to synthesize all these varied activities into a coherent view of its function. Cleavage of amyloid precursor protein by β‐and γ‐secretases results in the generation of the Aβ (βA4) peptide, whereas α‐secretase cleaves within the Aβ sequence and prevents formation from APP. Recent findings indicate that the site of γ‐secretase cleavage is critical to the development of amyloid deposits; Aβ1–42 is much more amyloidogenic than Aβ1–40 . Aβ1–42 formation is favoured by mutations in the two presenilin genes (PS1 and PS2), and by the commonest amyloid precursor protein mutations. Transgenic mouse models of Alzheimer’s disease incorporating various mutations in the presenilin gene now exist, and have shown amyloid accumulation and cognitive impairment. Neurofibrillary tangles have not been reproduced in these models, however. While aggregated Aβ is neurotoxic, perhaps via an oxidative mechanism, the relationship between such toxicity and neurofibrillary tangle formation remains a subject of ongoing research.
The expression of myelin protein mRNAs during remyelination of lysolecithin‐induced demyelination
Authors: Woodruff  , Franklin
Published: March 2003

To gain insights into the mechanisms of myelin repair in the CNS and to establish the extent to which this process resembles myelination in development we have examined the patterns of expression of transcripts of the major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP) during remyelination of lysolecithin‐induced demyelination in the adult rat spinal cord. Injection of 1 μl 1% lysolecithin into the dorsal funiculus caused a dramatic decrease in levels of MBP exon 1 and MBP exon 2‐containing transcripts and PLP/DM20 transcripts. Between 10 and 21 days post‐lesion induction there was a gradual increase in levels of expression of all transcripts, which had returned to levels associated with normally myelinated spinal cord white matter at 21 days. These increases in levels of expression corresponded to the appearance of remyelinated axons, detected on toluidine blue‐stained resin sections. Foci of high levels of expression occurred in regions of the lesion in which new myelin sheath formation was occurring, although the level of expression throughout the lesion never exceeded levels associated with myelin sheath maintenance in normal white matter due to the asynchronous pattern of remyelination. The changes in levels of expression of MBP exon 2 closely followed those of MBP exon 1. Our results indicate that (i) myelin protein gene expression associated with myelinogenesis during remyelination follows a similar pattern to that of myelinogenesis during development and that (ii) in rat models of demyelination changes of expression of MBP exon 1 and exon 2‐containing transcripts are of equal value, an observation relevant to quantifying the effects of putative remyelination‐enhancing strategies using the lysolecithin model.
Evidence of blood–brain barrier dysfunction in human cerebral malaria
Authors: Brown  , Hien  , Day  , Mai  , Chuong  , Chau  , Loc  , Phu  , Bethell  , Farrar  , Gatter  , White  , Turner
Published: March 2003

Patients infected with the malaria parasite Plasmodium falciparum may develop a diffuse reversible encephalopathy, termed cerebral malaria. It is unclear how the intraerythrocytic parasite, which sequesters in the cerebral microvasculature but does not enter the brain parenchyma, induces this neurological syndrome.

 Adhesion of parasitized red blood cells in the brain microvasculature is mediated by specific receptors on the host endothelium, including intercellular adhesion molecule (ICAM)‐1, CD36 and CD31. Leucocyte binding to cerebral endothelial cells in culture induces intracellular signalling via ICAM‐1. The hypothesis that parasitized red blood cells binding to receptors on cerebral endothelial cells causes changes in the integrity of the blood–brain barrier was tested.

 Immunohistochemistry was used to examine the blood–brain barrier in human cerebral malaria, with antibodies to macrophage and endothelial activation markers, intercellular junction proteins, and plasma proteins. The distribution of the cell junction proteins occludin, vinculin and ZO‐1 were altered in cerebral malaria cases compared to controls. While fibrinogen was the only plasma protein detected in the perivascular space, there was widespread perivascular macrophage activation, suggesting that these cells had been exposed to plasma proteins.

 It was concluded that functional changes to the blood–brain barrier occur in cerebral malaria, possibly as a result of the binding of parasitized red blood cells to cerebral endothelial cells. These changes require further examination in vitro.
Immunocytochemical study of the dorsal and median raphe nuclei in patients with Alzheimer’s disease prospectively assessed for behavioural changes
Authors: Chen C. P. L. ‐H. , Eastwood S. L. , Hope T. , McDonald B. , Francis P. T. , Esiri M. M.
Published: March 2003

The dorsal and median raphe nuclei were examined with immunocytochemistry to display the 5‐HT neurones in 16 cases of post‐mortem‐proven Alzheimer’s disease (AD) and 12 age and sex‐matched controls. The AD cases had been prospectively assessed during life for expression of behavioural changes as well as for cognitive decline. A significant (P < 0.001) 41% reduction in density of dorsal raphe neurones was found along with a significant (P < 0.02) 29% reduction in density of median raphe neurones in AD. There were significantly more neurofibrillary tangles in both dorsal and median raphe nuclei in AD than in controls (P < 0.001). There was no correlation between reduction in neurone density in these nuclei and behavioural change, cognitive decline, neurofibrillary tangle counts in these nuclei or plaque and tangle pathology in frontal and temporal cortex. It was concluded from these findings that the raphe nuclei are significantly affected by the pathology of AD and that plasticity in the 5‐HT system is the probable reason for the lack of correlation of reduced 5‐HT neurone density and clinical disease parameters.
Monocyte infiltration is highly associated with loss of the tight junction protein zonula occludens in HIV‐1‐associated dementia
Authors: Boven L. A. , Middel J. , Verhoef J. , De Groot C. J. A. , Nottet H. S. L. M.
Published: March 2003

In human immunodeficiency virus (HIV)‐1‐associated dementia (HAD), consequences of interactions between infiltrating monocytes and brain endothelial cells are not yet fully understood. This study investigated whether the blood–brain barrier is affected in brain tissue of patients suffering from HAD and whether it was possible to find a correlation with the presence or absence of monocytic cells, which have been suggested to play a major role in HAD. Immunohistochemical analysis for zonula occludens 1, a tight junction protein, and CD68, a macrophage marker, revealed that loss of tight junction immunoreactivity was highly correlated with monocyte infiltration and with HAD. This suggests that the presence of perivascular macrophages cells is associated with breakdown of the blood–brain barrier thereby facilitating infiltration of more monocytic cells hence enhancing disease progression.
The ethics of reusing archived tissue for research
Authors: Ashcroft R.
Published: March 2003

Pathologists have been establishing archives of human organs and tissue for research use for many years now. Controversy has arisen recently over these collections, particularly with regard to the right of patients or relatives to consent to removal and retention of tissue, genetic research using stored tissue samples, and commercial exploitation of tissue collections and genetic material. This paper discusses the ethics of reusing existing archives of tissue. New archives are established under much more stringent conditions than in the past. What rules should apply to existing archives? Guidelines to regulate such use are useful, but face serious difficulties in balancing the variety of public and private interests relating to tissue banking. Consent cannot be obtained retrospectively, but public trust can be established by open acknowledgement of the evolution of ethical standards and strict adherence to current best practice. Guidelines and standards vary from country to country, but ethical principles should not. The implications of this view for pathologists worldwide are discussed.
Deafferentation‐induced abnormal neurofilament phosphorylation in red nucleus neurones
Authors: Torack R. M. , Miller J. W. , Roth K. A.
Published: March 2003

Hippocampal deafferentation has been proposed as a pathogenetic mechanism for neurofibrillary tangle (NFT) formation in human mesolimbocortical dementia. We previously developed a rodent model of hippocampal deafferentation involving bilateral destructive lesions of the ventrotegmental area (VTA), septum of the medial forebrain and entorhinal cortex combined with pharmacological inhibition of serotonin 5‐HT2 and dopamine D1 receptors. Unexpectedly, we observed an alteration in phosphorylated neurofilament protein immunoreactivity and argyrophilia in magnocellular neurones of the red nucleus. Here, we determined the neuroanatomical, pharmacological and temporal requirements for this effect on red nucleus neurones. We found that abnormal phosphorylation and argyrophilia were critically dependent on bilateral destruction of the VTA and antagonism of 5‐HT2 receptors. Although extensive neurofilament hyperphosphorylation and argyrophilia were observed in red nucleus magnocellular neurones within nine days of treatment, no NFTs were formed and these effects were transitory. Resolution of these cytoskeletal abnormalities was accompanied by increased expression of the calcium binding protein, parvalbumin, suggesting that alterations in intraneuronal calcium levels may modify the deafferentation response.
Cerebrospinal fluid outflow resistance in sheep: impact of blocking cerebrospinal fluid transport through the cribriform plate
Authors: Silver I. , Kim C. , Mollanji R. , Johnston M.
Published: March 2003

Recent studies in sheep suggest that a significant proportion of global cerebrospinal fluid (CSF) drainage (50% or greater) occurs through the cribriform plate into nasal mucosal lymphatics. If this is true, obstructing CSF clearance through the cribriform plate should have an impact on the ability of the intracranial pressure regulating systems to compensate for volume infusions. To test this concept, bolus infusions of artificial CSF were administered into one lateral ventricle in sheep and the intracranial pressure monitored from the contralateral side. Peak intracranial pressures (ICP) were measured and CSF outflow resistances were calculated from the pressure patterns observed in response to bolus infusions administered before and after the cribriform plate was sealed in the same animal. To obstruct the cribriform plate, a portion of nasal bone was removed to expose the nasal mucosa. The olfactory mucosa, a portion of the nasal mucosa and all soft tissue on the extracranial surface of the cribriform plate were scraped away with a curette and the bone surface sealed with bone wax. Obstruction of CSF transport through the cribriform plate increased the peak ICP after infusion (P = 0.016) and augmented the time required for ICP to return to baseline. CSF outflow resistance was elevated approximately 2.7 times (P = 0.006). When the cribriform plate was left intact (sham surgery), no significant changes in peak ICP or CSF outflow resistance were observed. We conclude that the cribriform plate represents an important site for CSF clearance. Obstruction of this pathway reduces volumetric CSF transport significantly.
Classifying the medulloblastoma: insights from morphology and molecular genetics
Authors: Ellison D.
Published: March 2003

Significant advances in the treatment of the medulloblastoma (MB) have been made in the last 30 years, reducing mortality by 2‐fold. Further improvements in the cure rate require an increased understanding of the biology of MBs, and this will translate into refinements in their classification. Scrutiny of the cytological variation found among MBs has recently led to the concept of the anaplastic MB, which overlaps the large‐cell variant and appears to share its poor prognosis. In contrast, the MB with extensive nodularity, a distinctive nodular/desmoplastic variant occurring in infants, has a better outcome than most MBs in these young patients. Building on cytogenetic studies that have drawn attention to abnormalities on chromosome 17 in over a third of MBs, research shows non‐random losses on chromosomes 8, 9, 10, 11 and 16, and gains on chromosomes 1, 7 and 9. Overexpression of ErbB2 receptors and losses on chromosome 17p have been proposed as independent indicators of aggressive behaviour, while high TrkC receptor expression indicates a favourable outcome. There is a strong association between anaplastic/large‐cell tumours and MYC amplification, which has previously been linked with aggressive disease, but associations between abnormalities on chromosome 17 and anaplastic/large‐cell MBs and between abnormalities in the shh/PTCH pathway and the desmoplastic variant are more controversial. Classification of the MB histopathologically and according to profiles of molecular abnormalities will help both to rationalize approaches to therapy, increasing the cure rate and reducing long‐term side‐effects, and to suggest novel treatments.
Familial British dementia (FBD): a cerebral amyloidosis with systemic amyloid deposition
Authors: Holton J. L. , Ghiso J. , Lashley T. , Ganguly M. , Strand K. , Rostagno A. , Plant G. , Frangione B. , Revesz T.
Published: March 2003

Introduction:  FBD is an autosomal dominant disease with neuropathological similarities to Alzheimer's disease (AD) as it is characterized by amyloid angiopathy, parenchymal amyloid plaque deposition and neurofibrillary degeneration. FBD is associated with a stop codon mutation in the BRI2 gene encoding a type II transmembrane protein, BriPP. Mutation results in an extended precursor protein, ABriPP, from which a C‐terminal 34 amino acid peptide (ABri) is generated by furin‐like proteolytic cleavage and deposited as amyloid and preamyloid in the central nervous system. Despite the morphological parallels with AD the sequences of the amyloidogenic peptides, ABri in FBD and Aβ in AD, are completely different. We examined systemic tissues in FBD for ABri deposition.

Materials and methods:  Immunohistochemistry using an ABri‐specific antibody, Ab338, counterstained with Thioflavin S and Ab338 immuno‐electron microscopy identified ABri deposits and determined whether these were amyloid or preamyloid in nature.

Results:  Amyloid bearing blood vessels stained positively for ABri in myocardium, uterus, bladder, spleen, pancreas, lung and skeletal muscle. ABri was also identified in either amyloid or preamyloid conformation in the parenchyma of myocardium, adrenal, pancreas and skeletal muscle.

Conclusion:  This study demonstrates that FBD is the first described cerebral amyloidosis with neurofibrillary pathology and dementia to be accompanied by systemic amyloid deposition.
A quantitative analysis of cellular prion protein (PrPc) expression in Alzheimer's disease (AD), diffuse Lewy body disease (DLBD) and in normal brain
Authors: Pontikis C. , Hudson L. , Lantos P. L. , Rezaie P.
Published: March 2003

Introduction:  Cellular prion protein (PrPc) is a normal glycosyl phosphatidylinositol‐anchored protein expressed on a wide variety of cell types. Within the CNS, low levels of PrPc are particularly associated with neurons in normal healthy individuals. In contrast, a more pronounced expression of this protein may occur in certain neurodegenerative disorders (Esiri et al. Neuropath Appl Neurobiol 2000; 26: 273; Voigtlander et al. Acta Neuropathol 2001; 101: 417). Overexpression of PrPc has itself been reported to demonstrate neuropathology in transgenic mice (Westaway et al. Cell 1994; 76: 117). The present study investigated whether prion protein is up‐regulated in two well‐characterized neurodegenerative disorders: Alzheimer's disease (AD) and diffuse Lewy body disease (DLBD).

Material and methods:  Frozen material (frontal and occipital cortex) from cases with AD (n = 10), DLBD (n = 10) and neuropathologically normal brain (n = 10) were obtained from the MRC Brain Bank (Institute of Psychiatry, London), serially sectioned at 15–20 µm and immunoreacted in entire batches with four antisera to detect PrPc (3f4, sp40, 12f10 and F89/160.1.5) using the DAKO ABC method and DAB as chromogen. Sections from a case with Creutzfeldt‐Jakob disease served as positive controls. Negative controls included preincubating test sections with proteinase K/guanidinium thiocyanate/formic acid, omitting primary antibody or incubation with nonspecific IgG. Immunoreactivity within selected brain regions was analysed using OPTIMAS image analysis software (OPTIMAS Corp., USA) on duplicate sections, and data processed as percentage immunoreactivity per defined field, based on a constant threshold (von Eitzen et al. JNEN 1998; 57: 246). The distribution of PrPc was further tested for correlation with glial reactivity (GFAP, PGM‐1).

Results:  PrPc expression was mainly localized to the grey matter and was higher in occipital than frontal cortex. PrPc did not colocalize with glial reactivity. Instead, expression within the grey matter appeared to associate with neurons. Expression did not vary significantly between DLBD and controls. However, regional variations in PrPc expression were noted in AD. Epitope specificity of antibodies was also important in detecting PrPc, and may relate to selective regional glycosylation patterns of this protein.

Conclusion:  This study indicates that changes in expression of PrPc occur in certain neurodegenerative disorders such as AD. Whether this is secondary to the disease or contributes towards pathology remains to be investigated.
Tracking the movements of translocated elephants in Malaysia using satellite telemetry
Authors: Stüwe Michael , Abdul Jasmi B. , Nor Burhanuddin Mohd. , Wemmer Christen M.
Published: March 2003

Malaysia incurs damage worth millions of dollars annually from elephants feeding in plantations. In response, the Malaysian Wildlife Department has translocated over 392 elephants from plantations into protected areas since 1974. Dense rain forest and steep terrain at the release sites have made it near impossible to follow the movements of the released elephants and evaluate the success of the programme. In October 1995, a translocated female elephant was fitted with a satellite transmitter to determine its post-release movements. By August 1996, the female had moved within a range of 7000 sq km. The movements were erratic initially and covered a large area. They were followed by a shift in location twice, each time covering successively smaller areas. Attempts to locate and follow the female on the ground revealed no evidence that she travelled in a group. A second, male, elephant was equipped with a satellite transmitter in February 1996 and by August 1996, it had moved within a range of 350 sq km. An attempt to locate and follow the male on the ground provided evidence that he was in a group of at least three individuals. The difference in the behaviour of the two elephants, released at exactly the same location, is striking, but additional elephants need to be followed to increase sample size and allow a scientific explanation of the findings.
Impact of wildfires on the megafauna of Emas National Park, central Brazil
Authors: Silveira Leandro , Henrique Flávio , Rodrigues G. , de Almeida Jácomo Anah Tereza , Filho José Alexandre F. Diniz
Published: March 2003

This study evaluates the impact of two wildfires, in 1994 and 1995, on the large mammal fauna of Emas National Park, central Brazil. The 1994 fire burned 100 per cent of the park's grassland and after the fire, in a c. 2000-ha survey area, the authors found 16 giant anteaters Myrmecophaga tridactyla, two giant armadillos Priodontes maximus and one tapir Tapirus terrestris that had died in the fire. The 1995 fire burned 15 per cent of the park's grassland and no dead animals were found in a 220-ha survey area. The authors discuss the possible long-term ecological consequences of wildfires on the large mammal fauna of Emas, with a special focus on the giant anteater population, which is particularly susceptible to fires. They recommend a fire management programme, which would include controlled burns on a rotational basis in different sections of the park. The programme would also improve the availability of food for herbivores and control the spread of alien grass species.
Trade in Asian elephant ivory in Sri Lanka
Authors: Santiapillai Charles , Silva Ajith , Karyawasam Champika , Esufali Shameema , Jayaniththi Salila , Basnayake Mano , Unantenne Vasantha , Wijeyamohan S.
Published: March 2003

ElephantsElephas maximushave declined in range and number in the wild in Sri Lanka, fromc. 12,000 at the turn of the nineteenth century toc. 4000 today. While in the distant past the decline in elephant numbers was due largely to indiscriminate killing by sportsmen and trophy hunters, today elephants are being killed primarily because they interfere with agriculture. Human-elephant conflicts have increased substantially in the recent past and ivory poaching has become a byproduct of such conflicts. Elephant tusks have been used traditionally in the ivory-carving industry in Sri Lanka since the time of the ancient kings. Until the turn of the century, very little ivory was imported from Africa because there was a plentiful supply of tuskers locally available. Sri Lankan ivory carvers started to use African ivory in 1910. Today ivory and fake-ivory products are sold openly to tourists in some 86 shops in the island. Before the listing of the African elephant in Appendix I of the Convention on International Trade in Endangered Species (CITES), the value of raw ivory in Sri Lanka used to be $US228–285 per kg. After the listing, the price fell to $US72 per kg, reflecting a drastic drop in the demand for ivory from tourists. Many ivory carvers have switched to other jobs or are using substitutes (such as bone and horn) to produce fake-ivory carvings. Only about 7.5 per cent of bulls in Sri Lanka are tuskers and they are under poaching pressure outside protected areas. Given the rarity of tuskers in Sri Lanka, promotion of trade in ivory products, even locally, may pose a serious threat to their long-term survival in the wild.
Arabian oryx reintroduction in Oman: successes and setbacks
Authors: Spalton J. A. , Lawerence M. W. , Brend S. A.
Published: March 2003

The return of the Arabian oryxOryx leucoryxto Oman symbolized the success of a new approach to species conservation and established reintroduction as a conservation tool. Ten years after the species had been exterminated in the wild by poaching, the first 10 founder oryx, descendants of the ′World Herd′, were reintroduced to the desert in central Oman in January 1982. A second release followed in 1984 and the population grew slowly through a 3-year drought that was broken by rain in June 1986. Further years of good rainfall and more founders meant that by April 1990 there were over 100 oryx in the wild, independent of supplementary feed and water, and using a range of over 11,000 sq km. At that time a new monitoring programme was implemented that allowed the transition from individual- to population-based monitoring and management. The population continued to grow and by October 1995 numbered approximately 280 in the wild (of which 22 were surviving founders) and used over 16,000 sq km of the Arabian Oryx Sanctuary. However, in February 1996 poaching resumed and oryx were captured for sale as live animals outside the country. Despite the poaching the population continued to increase and by October 1996 was estimated to be just over 400. However, poaching intensified and continued through late 1996 and 1997. By September 1998 it had reduced the wild population to an estimated 138 animals, of which just 28 were females. The wild population was no longer considered viable and action was taken to rescue some of the remaining animals from the wild to form a captive herd.
Preliminary notes on the conservation status of Baird's tapir Tapirus bairdii in north-eastern Honduras
Authors: Flesher Kevin
Published: March 2003

Between April and August 1994, three steps were taken to assess the status of Baird's tapir Tapirus bairdii in north-eastern Honduras: (i) forest cover was mapped to estimate the amount of habitat available; (ii) interviews with local people were conducted to determine where the species occurs; and (iii) searches were made for tapir signs in several mountain ranges to corroborate interview information. Local reports and searches indicated that the species occurred in forests throughout the area. Using density estimates of 0.05–0.24 tapirs per sq km, there may be 520–2760 tapirs in the 10,400–11,500 sq km of contiguous rain forest that remains in north-eastern Honduras—a population large enough to have a good chance of long-term persistence. The main threat to the population is human colonization, which is destroying the forest along the rivers and major streams. This is fragmenting the tapii population into isolated units, which will be increasingly subject to the stochastic events that drive small populations to extinction. Hunting, which along with habitat destruction, is a major contributor to the rapid decline of tapir populations in areas of human colonization, does not appear to pose an immediate threat in the study area. However, population trend data are lacking and the impact of hunting on tapirs remains unassessed.
Rare plants on Mount Oku summit, Cameroon
Authors: Maisels Fiona G. , Cheek Martin , Wild Chris
Published: March 2003

The forests of the Kilum-Ijim area, around Mount Oku in West Cameroon, are the largest remaining patch of montane forest in West Africa, and the highest in altitude. This important habitat harbours endemic species of both animals and plants but is surrounded by a high density of human settlements: c. 300,000 people live within a day's walk of the forest, which covers only 200 sq km. BirdLife International and the Ministry of the Environment and Forestry, Government of Cameroon, are currently operating the Kilum-Ijim Forest Project, with the overall goal of conserving representative areas of the Cameroon montane forest biome in the long-term. The purpose of the project is toensure that the biodiversity, extent and ecological processes of the Kilum-Ijim Forest are maintained and that the forest is used sustainably by the local communities. The existence of a small Sphagnum community and associated wetland plant species was discovered in 1997 on the summit of Mount Oku, at 2900 m. This site is of extremely high conservation importance because several plant species endemic to the Kilum-Ijim area have been recorded there. In addition, it is the highest Sphagnum bog and the source of the highest stream in West Africa.
Crop-raiding elephants and conservation implications at Way Kambas National Park, Sumatra, Indonesia
Authors: Nyhus Philip J. , Tilson Ronald , Sumianto
Published: March 2003

Crop raiding by wild elephants is one of the most significant sources of park–people conflict in Sumatra, Indonesia. The distribution, impact and conservation implications of elephant crop-raiding in 13 villages that border Way Kambas National Park in southern Sumatra were studied for 18 months. The data are based on rapid village and field assessments, data logs maintained by village observers and a quantitative household survey. Elephants raided crops year-round at a mean rate of 0.53 elephants per day for the entire study area. The frequency of crop raiding was related to vegetation type along the park border, the size and presence of rivers, and the distance to the park's Elephant Training Center (ETC), which houses about 150 captive elephants. Wild elephants damaged at least 450,000 sq m of corn, rice, cassava, beans and other annual crops, and close to 900 coconut, banana and other perennial trees in the area surveyed. Elephants killed or injured 24 people over a 12-year period in villages near the park. Villagers try to reduce elephant damage by guarding fields, digging trenches between the park and their fields, and modifying their cropping patterns. Elephant–human conflict decreases the probability of support from local people for conservation efforts. We suggest methods to improve the effectiveness of existing elephant trenches, the need to consider electric fences, external support to affected villages, and compensation to villagers for any damage caused.
Importance of Furugelm Island in the Sea of Japan for wetland birds: the first record of a breeding colony of the Chinese egret Egretta eulophotes
Authors: Litvinenko Natalia M. , Shibaev Yuriy V.
Published: March 2003

A new breeding site of the globally threatened Chinese egret Egretta eulophotes was recorded on Furugelm Island in the summer of 1998. The discovery of this colony moves the breeding limit of the species more than 600 km further to the north-east in the Sea of Japan. Thirty to forty pairs of Chinese egrets were discovered on the island, which is also home to thousands of colonial seabirds as well. The egret's colony is within the Far-Eastern Marine Reserve but some of its main foraging sites lie outside the protected area and are disturbed by both tourists and hunters. More worryingly, however, the main threat to the Chinese egret's survival is a new economic development project: the Tumen River Area Development Program. We make an urgent plea for the protection of the Chinese egrets' foraging areas within the Far-Eastern Marine Reserve and recommend that a transfrontier reserve be created to enhance the protection of this important waterbird site.
Contemporary extinctions and population declines of the monarchs (Pomareaspp.) in French Polynesia, South Pacific
Authors: Thibault Jean-Claude , Meyer Jean-Yves
Published: March 2003

Four species of monarchs (Pomarea spp.) presently inhabit French Polynesia, one on Tahiti and three on the Marquesas Islands. Although all species populations were abundant during the nineteenth century or at the beginning of the twentieth century, their range and population numbers have recently decreased dramatically: intensive field surveys conducted between 1998 and 2000 reveal that four subspecies are now extinct from five islands in the Marquesas in the last decades. Introduction of the black rat is the major cause of extinction and decline, now amplified by new threats such as aggressive introduced birds and invasive alien plants reducing suitable habitats for breeding.
Identifing priority ecoregions for rodent conservation at the genus level
Authors: Amori Giovanni , Gippoliti Spartaco
Published: March 2003

Rodents account for 40 per cent of living mammal species. Nevertheless, despite an increased interest in biodiversity conservation and their high species richness, Rodentia are often neglected by conservationists. We attempt for the first time a world-wide evaluation of rodent conservation priorities at the genus level. Given the low popularity of the order, we considered it desirable to discuss identified priorities within the framework of established biodiversity priority areas of the world. Two families and 62 genera are recognized as threatened. Our analyses highlight the Philippines, New Guinea, Sulawesi, the Caribbean, China temperate forests and the Atlantic Forest of south-eastern Brazil as the most important (for their high number of genera) ‘threat-spots’ for rodent conservation. A few regions, mainly drylands, are singled out as important areas for rodent conservation but are not generally recognized in global biodiversity assessments. These are the remaining forests of Togo, extreme ‘western Sahel’, the Turanian and Mongolian-Manchurian steppes and the desert of the Horn of Africa. Resources for conservation must be allocated first to recognized threat spots and to those restricted-range genera which may depend on species-specific strategies for their survival.
Population status of the Alaotran gentle lemur Hapalemur griseus alaotrensis
Authors: Mutschler Thomas , Randrianarisoa A. Jeannicq , Feistner Anna T. C.
Published: March 2003

The results of a field census of Alaotran gentle lemurs Hapalemur griseus alaotrensis carried out in February and March 1999 are reported. The results are compared with a census carried out 5 years earlier in 1994. Both censuses followed the same methods and were carried out by the same team, using direct observation from canoe. Mean group encounter rates for the lemur were assessed in each location, which allowed us to calculate the relative group density in each site. Qualitative information on habitat condition (on the basis of plant diversity, vegetation height and evidence of burning) was gathered at each site. Additional information, mainly on lemur hunting, was acquired through interviews with local people. In most sites group encounter rate was at least 50 per cent lower than 5 years before. Taking into account unusually low water levels because of a drought at Lac Alaotra in 1999, we estimate that these encounter rates reflect a 30 per cent decline in the total population size over the last 5 years. The main cause of this dramatic decrease was humaninduced fire (habitat degradation) coupled with heavy hunting (poaching of lemurs for food). The importance of assessing regularly both population status and threats, and of adjusting conservation actions accordingly is emphasized.
The conservation status of Tanimbar corella and blue-streaked lory on the Tanimbar Islands, Indonesia: results of a rapid contextual survey
Authors: Jepson Paul , Brickle Nick , Chayadin Yusup
Published: March 2003

Two parrot species, Tanimbar corellaCacatua goffiniand blue-streaked loryEos reticulata, endemic to the Tanimbar Islands, Indonesia, were regularly trapped and sold into the international wild bird trade prior to 1992. Following concerns about numbers entering the trade, but with little knowledge of the remaining wild population or socio-economic role of bird trapping on the islands, international trade in both species was suspended at the 1992 CITES meeting. This paper reports on a rapid survey conducted on the islands in 1993 as a follow-up to the decision on trade. The survey attempted to determine the status of the wild populations, the distribution and activity of the human population, the interaction between Tanimbar corella and agriculture, and the structure of the local commodity-chain for wild-caught parrots. We found that: (a) both parrot species were widely distributed and present at relatively high densities across the largest island in the group, Yamdena; (b) catching of parrots is geographically limited; (c) in the case of Tanimbar corella, at least, the catching is of birds raiding crops and probably involves mainly immature and non-reproductive birds; (d) the international and domestic ban on catching was generally adhered to locally but the reasons for the ban were not widely understood, contributing to a general mistrust of conservationists that still remains. Although not advocating a lifting of the ban on trapping, we do conclude that in this case invoking the precautionary principle without proper consideration of local context may have been counterproductive to conservation goals.
An overview of the status and conservation of the red panda Ailurus fulgens in India, with reference to its global status
Authors: Choudhury Anwaruddin
Published: March 2003

The current status and distribution of the red panda Ailurus fulgens in the wild is poorly known. The subspecies fulgens is found in the Himalaya in Nepal, India, Bhutan, northern Myanmar and southwest China, and the subspecies styani occurs further to the east in south-central China. The red panda is an animal of subtropical and temperate forests, with the exception of Meghalaya in India, where it is also found in tropical forests. In the wild, red pandas take a largely vegetarian diet consisting chiefly of bamboo. The extent of occurrence of the red panda in India is about 170,000 sq km, although its area of occupancy within this may only be about 25,000 sq km. An estimate based on the lowest recorded average density and the total area of potential habitat suggests that the global population of red pandas is about 16,000–20,000. Habitat loss and poaching, in that order, are the major threats. In this paper the distribution, status and conservation problems of the red panda, especially in India, are reviewed, and appropriate conservation measures recommended, including the protection of named areas and the extension of some existing protected areas.