bluuebunny/crossref_metadata_2025 huggingface dataset:
Infrequency of colonization with Oxalobacter formigenes in inflammatory bowel disease: Possible role in renal stone formation
Authors: KUMAR RITU , GHOSHAL UDAY C , SINGH GUNJANA , MITTAL RAMA D
Published: December 2004

Background and Aim:  Calcium oxalate renal stones (RS) and hyperoxaluria are common in patients with inflammatory bowel disease (IBD). The absence of intestinal oxalate degrading bacteria, Oxalobacter formigenes, may cause hyperoxaluria in IBD. The aim of the present study was to examine: (i) the colonization of O. formigenes in patients with IBD and controls and to correlate its presence with urinary oxalate excretion; and (ii) urinary analytes contributing to RS in IBD.

Methods:  Stool samples were studied for O. formigenes using polymerase chain reaction and Southern blotting in patients with IBD (n = 48: ulcerative colitis, 37; Crohn's disease, 11), RS (n = 87) and healthy subjects that were used as controls (n = 48). Levels of urinary oxalate, citrate, calcium, magnesium, creatinine and uric acid were estimated spectrophotometrically in each patient and in 13 controls for 24 h.

Results:  Five of the 48 (10.4%) patients with IBD had RS. Five of the 48 (10.4%) patients with IBD, 25 of the 87 (29%) with RS and 27 of the 48 (56%) controls were colonized with O. formigenes (P < 0.001 for RS vs controls and P = 0.01 for RS vs IBD). Patients without O. formigenes had higher urinary oxalate than those with it (IBD, median 0.48 [range 0.11–2.09]vs 0.43 [range 0.16–1.10] mmol/24 h, P = NS; RS, median 0.59 mmol/24 h, range 0.14–1.90 vs 0.44 mmol/24 h, range 0.23–0.97; P = 0.008, Mann–Whitney U‐test). Median excretion of oxalate was higher in IBD and RS than in controls (0.47 [0.11–2.09], 0.56 [0.14–1.9] and 0.41 [0.21–0.62] mmol/24 h; P < 0.01), respectively. Median calcium was also higher in IBD and RS than in controls (6.50 [1.38–21.00], 6.78 [1.55–20.30] and 4.99 [1.47–9.60] mmol/24 h; P < 0.05, Kruskal–Wallis H‐test), respectively. Median urinary magnesium was higher in IBD than in RS and controls (4.57 [1.50–12.30], 3.60 [0.90–6.35] and 2.49 [0.74–4.80]; P < 0.001, Kruskal–Wallis H‐test), respectively. Urinary citrate excretion was comparable in IBD, RS and controls.

Conclusions:  Patients with IBD and RS rarely have O. formigenes in their stools as compared with controls; this may contribute to hyperoxaluria in IBD. Hyperoxaluria and hypercalciuria may contribute to RS in patients with IBD. Hypermagnesuria in patients with IBD may protect them from RS.
What is the direct cost of treatment of acute primary angle closure glaucoma? The Singapore model
Authors: Wang Jenn‐Chyuan , Chew Paul TK
Published: December 2004

Aim: To estimate the cost of management of acute primary angle closure glaucoma in Singapore.

Methods: In this cost analysis using retrospective data, the authors performed a MEDLINE search of published papers on acute primary angle closure glaucoma (APACG) in Singapore. Using information from published data, clinical management pathways were constructed and clinical outcomes identified. For each management path, costs of medical treatment, hospitalization, clinic charges, investigations, laser treatment and surgery were identified and accounted over a 5‐year treatment period, using year 2002 rates.

Results: Given that, in Singapore, APACG affects 12.2 per 100 000 per year (95% confidence interval [CI], 10.5–13.9) in those aged 30 and older, each annual cohort would need to pay US$261 741.78 (95%CI: US$225 310.90–298 265.10) or US$287 560.26 (95%CI: US$247 274.04–330 624.84), if inclusive of cataract surgery, over 5 years after the episode of APACG. In this period, individuals would have to commit between US$879.45 and US$2576.39, depending on the complexity of disease and accompanying cataract surgery.

Conclusion: Acute primary angle closure glaucoma produces a substantial financial burden on society as well as on the individuals.
Preventive effect of lacrimal occlusion on topical timolol‐induced bronchoconstriction in asthmatics
Authors: Hepsen Ibrahim F , Yıldırım Zeki , Yılmaz Harun , Kotuk Mahir
Published: December 2004

Aim: To evaluate the potential preventive role of lacrimal occlusion on the topical timolol‐induced bronchoconstriction in asthmatics.

Methods: This was a prospective and single‐masked study. Fourteen volunteer subjects with asthma were included. Collagen plugs were inserted into both canaliculi on one side to inhibit lacrimal drainage. The effect of lacrimal occlusion on lung function tests was measured before and 60 min after the instillation of a timolol drop in unplugged and plugged eyes. The spirometric measurements include forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, and mid expiratory flow‐rate (FEF25‐75).

Results: The timolol (0.5%) drop administration into the eye caused a significant decrease in pulmonary functions in patients with asthma in whom the lacrimal punctae had not been occluded by collagen plug. P values were 0.008 for FVC and 0.001 for FEV1 and FEF25‐75. The occlusion of the lacrimal duct by intracanalicular plugs significantly reduced this decrease in pulmonary function. P values were 0.6 for FVC, 0.8 for FEV1, and 0.5 for FEF25‐75. The lacrimal occlusion did not affect heart rate and blood pressures. Three subjects complained of epiphora.

Conclusions: Lacrimal occlusion with intracanalicular collagen plugs may almost completely prevent the bronchoconstriction caused by topical timolol in asthmatics by inhibiting or decreasing systemic absorption of the medication.
Optimal discrimination of an Abyssinian cat recessive retinal degeneration: a short electroretinogram protocol is more efficient than a long one
Authors: Vaegan  , Narfström Kristina
Published: December 2004

Aim: To determine the diagnostic efficiency of scores in a long protocol electroretinogram (ERG) for Abyssinian cat slow recessive rod/cone dystrophy.

Methods: Kittens (n = 22) were bred from homozygous, affected and heterozygous normals. Ophthalmoscopy was regularly performed and disease signs noted. Cats (age ≥ 8 months, 40 sessions, 1–3 repeats) were dark‐adapted overnight, anaesthetized and simultaneous binocular ERG recorded using a long protocol. Conventional a‐ and b‐amplitudes and peak implicit times were measured and b/a ratios calculated, initially only for ERG to the maximum photopic and scotopic stimulus. Principal components factor analysis was applied to various subsets of these scores plus age at testing.

Results: Six cats with ophthalmoscopic change were classed as affected. Three cats, one tested three times, were suspect. The rest were considered normal. The first analysis, of 80 eyes and 37 parameters, showed that the first factor was the only effective one. Using it, the groups overlapped 5%, scotopic amplitudes and b/a ratios loaded higher than peak times, the eyes were very similar, and age and photopic b/a ratios loaded poorly. The groups were discriminable with all the data. A second analysis, with eyes averaged and the 20 measures loading over 0.5 on the first factor, showed better group separation on factor 1 alone. An iterative search with varying data sets found that factor 1 was optimal, with eight ERG measures to the three brightest scotopic and one brightest photopic response. It produced a large absolute separation and classified the suspects consistently. With b/a ratios on these four ERG also included, 12 parameters gave better separation.

Conclusion: Twelve scores on four ERG separate affected from normal cats with a wide gap and consistently classify suspects. It may work for earlier ages. Additional data probably adds noise. This combination of optimal scores needs confirmation in new data.
‘Ancient’ schwannoma of the orbit
Authors: Moloney Gregory , Brewer Janice , O'Donnell Brett A
Published: December 2004

A 65‐year‐old woman presented with a 3 month history of right eye discomfort and protrusion. Examination revealed right proptosis with hypoglobus and diplopia in extremes of upgaze. Computed tomographic scanning revealed a large extraconal mass in the superotemporal orbit. The mass was excised through an extended superior skin crease incision. Histopathology revealed a benign tumour of Schwann cell origin showing advanced cystic degeneration, the so‐called ‘ancient schwannoma’. The authors could find only two previously reported cases of such tumours arising in the orbit.
Clinical Case Notes
Authors: Kert Gilda , Clement Colin I , O'Donnell Brett A
Published: December 2004

A rare case of an orbital lymphoid tumour within an extraocular muscle is presented. The tumour displayed features of a progressive indolent systemic lymphoma. There was no response to a trial of chemotherapy and so local radiotherapy was instituted. At follow up 2 months later there was no evidence of disease.
Analysis of New Zealand's research productivity in ophthalmology and vision science: 1993–2002
Authors: Pon Jo‐Anne MC , Carroll Stuart C , McGhee Charles NJ
Published: December 2004

Aim: To assess New Zealand's research productivity in the area of ophthalmology and vision science over the decade 1993–2002.

Methods: New Zealand‐based researchers involved in ophthalmology or vision science research, including ophthalmologists, optometrists and vision scientists were identified via professional colleges, universities and electronic databases. Peer‐reviewed publications by these authors were identified by both searching electronic databases (MEDLINE/Pubmed) and personal communication with individual researchers.

Results: Eighty‐five New Zealand‐based researchers involved in ophthalmology or vision science research published 446 articles in 84 scientific journals during the 10‐year period. The cohort consisted of 59 ophthalmologists and 26 other researchers based in a diverse range of ophthalmology, optometry and university departments. Significant collaboration was observed between groups within New Zealand and with international institutions. Comparing ophthalmologists and ‘other’ researchers, ophthalmologists produced 69% of all ophthalmology and vision science research publications and those classified as ‘active ophthalmologist researchers’ published an average of 11 (range 5–55) papers each during this decade, compared to eight (range 5–25) for the group ‘other active researchers’. This was also reflected in the high productivity rate by ophthalmologists of 277 publications per 1000. Publications were identified in a wide range of journals with the majority in top 20‐ranked ophthalmology journals. The trend over the decade highlighted an increase in number of scientific publications, from 43 per annum in 1993, to 68 per annum in 2002.

Conclusions: Despite a relatively small and geographically isolated population, New Zealand ophthalmology and vision science research is highly active and collaborative, with significantly increased research productivity during the period 1993–2002. The present study is the first to document these trends and provides strong evidence to justify continued support for ophthalmology and vision science research in New Zealand.
Origin of acetylcholinesterase in the neuromuscular junction formed in the in vitro innervated human muscle
Authors: Jevsek Marko , Mars Tomaz , Mis Katarina , Grubic Zoran
Published: December 2004

Synaptic basal lamina is interposed between the pre‐ and postsynaptic membrane of the neuromuscular junction (NMJ). This position permits deposition of basal lamina‐bound NMJ components of both neuronal and muscle fibre origin. One such molecule is acetylcholinesterase (AChE). The origin of NMJ AChE has been investigated previously as the answer would elucidate the relative contributions of muscle fibers and motor neurons to NMJ formation. However, in the experimental models used in prior investigations either the neuronal or muscular components of the NMJs were removed, or the NMJs were poorly differentiated. Therefore, the question of AChE origin in the intact and functional NMJ remains open. Here, we have approached this question using an in vitro model in which motor neurons, growing from embryonic rat spinal cord explants, form well differentiated NMJs with cultured human myotubes. By immunocytochemical staining with species‐specific anti‐AChE antibodies, we are able to differentiate between human (muscular) and rat (neuronal) AChE at the NMJ. We observed strong signal at the NMJ after staining with human AChE antibodies, which suggests a significant muscular AChE contribution. However, a weaker, but still clearly recognizable signal is observed after staining with rat AChE antibodies, suggesting a smaller fraction of AChE was derived from motor neurons. This is the first report demonstrating that both motor neuron and myotube contribute synaptic AChE under conditions where they interact with each other in the formation of an intact and functional NMJ.
Autoinhibition of transmitter release from PC12 cells and sympathetic neurons through a P2Y12 receptor‐mediated inhibition of voltage‐gated Ca2+ channels
Authors: Lechner Stefan G. , Dorostkar Mario M. , Mayer Martina , Edelbauer Hannah , Pankevych Halyna , Boehm Stefan
Published: December 2004

Although feedback inhibition of noradrenaline release by coreleased nucleotides is a well known phenomenon, it remained unclear which P2 receptor subtypes and associated signalling cascades may be involved. In the rat pheochromocytoma cell line PC12, 2‐methylthio‐ADP reduced noradrenaline release triggered by K+ depolarization more potently than ADP and ATP, whereas UDP or UTP failed to do so. The inhibition by ADP was abolished by pertussis toxin and antagonized by reactive blue 2, 2‐methylthio‐AMP, and AR‐C69931MX, but not by suramin. AR‐C69931MX acted as a competitive antagonist with an apparent affinity of 2 nm, but did not alter noradrenaline release, when PC12 cells were continuously superfused. However, when the superfusion was halted during K+ depolarization, release was significantly reduced and this inhibition was attenuated by AR‐C69931MX, thus revealing ongoing autoinhibition. Rises in cellular cyclic AMP did not alter depolarization‐evoked release nor its reduction by ADP, even though the nucleotide did inhibit cyclic AMP accumulation. ADP and the direct Ca2+ channel blocker Cd2+ inhibited voltage‐activated Ca2+ currents, but not ATP‐induced currents, and both agents reduced K+‐evoked, but not ATP‐evoked, release. Hence, if voltage‐gated Ca2+ channels do not contribute to stimulation‐evoked release, ADP fails to exert its inhibitory action. In primary cultures of rat sympathetic neurons, ADP also reduced Ca2+ currents and K+‐evoked noradrenaline release, and AR‐C69931MX acted again as competitive antagonist with an apparent affinity of 3 nm. These results show that P2Y12 receptors mediate an autoinhibition of transmitter release from PC12 cells and sympathetic neurons through an inhibition of voltage‐gated Ca2+ channels.
Human immunodeficiency virus type 1 glycoprotein gp120 reduces the levels of brain‐derived neurotrophic factor in vivo: potential implication for neuronal cell death
Authors: Nosheny Rachel L. , Bachis Alessia , Acquas Elio , Mocchetti Italo
Published: December 2004

Neuronal loss has been observed in post mortem brains of patients with human immunodeficiency virus type 1 (HIV‐1). Experimental evidence has implicated HIV‐1‐derived envelope glycoprotein 120 (gp120) in the neuronal cell death observed in these patients. However, the intrinsic mechanisms by which gp120 causes neurotoxicity are still unknown. We have recently shown that the neurotoxic effect of gp120 in vitro is reduced by brain‐derived neurotrophic factor (BDNF). We therefore tested the hypothesis that low levels of BDNF render neurons more sensitive to gp120. Gp120 was injected acutely into the striatum of BDNF heterozygous mice and wild‐type littermates. BDNF heterozygous mice exhibited more apoptotic neurons in the striatum than wild‐type mice, suggesting that BDNF is neuroprotective also in vivo. Because several neurodegenerative disorders are characterized by lack of trophic support, we tested the hypothesis that gp120 may cause apoptosis by reducing BDNF expression. Gp120 was injected acutely in the rat striatum and BDNF levels determined by a two‐site immunoassay at various times after the injection. Gp120 elicited a dramatic decrease in BDNF protein levels by 24 h. Reduced BDNF levels were still present at 4 days. Cellular localization of BDNF immunoreactivity revealed that gp120 decreases BDNF immunoreactivity mainly in neuronal processes. This effect of gp120 precedes the peak of caspase‐3 activation and neuronal cell death. We propose that one of the mechanisms whereby gp120 causes neurotoxicity is a reduction of the neurotrophic factor environment crucial for cell survival.
Is there a role of visual cortex in spatial hearing?
Authors: Zimmer Ulrike , Lewald Jörg , Erb Michael , Grodd Wolfgang , Karnath Hans‐Otto
Published: December 2004

The integration of auditory and visual spatial information is an important prerequisite for accurate orientation in the environment. However, while visual spatial information is based on retinal coordinates, the auditory system receives information on sound location in relation to the head. Thus, any deviation of the eyes from a central position results in a divergence between the retinal visual and the head‐centred auditory coordinates. It has been suggested that this divergence is compensated for by a neural coordinate transformation, using a signal of eye‐in‐head position. Using functional magnetic resonance imaging, we investigated which cortical areas of the human brain participate in such auditory–visual coordinate transformations. Sounds were produced with different interaural level differences, leading to left, right or central intracranial percepts, while subjects directed their gaze to visual targets presented to the left, to the right or straight ahead. When gaze was to the left or right, we found the primary visual cortex (V1/V2) activated in both hemispheres. The occipital activation did not occur with sound lateralization per se, but was found exclusively in combination with eccentric eye positions. This result suggests a relation of neural processing in the visual cortex and the transformation of auditory spatial coordinates responsible for maintaining the perceptual alignment of audition and vision with changes in gaze direction.
Transient Ca2+‐permeable AMPA receptors in postnatal rat primary auditory neurons
Authors: Eybalin Michel , Caicedo Alejandro , Renard Nicole , Ruel Jérôme , Puel Jean‐Luc
Published: December 2004

Fast excitatory transmission in the nervous system is mostly mediated by α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) receptors whose subunit composition governs physiological characteristics such as ligand affinity and ion conductance properties. Here, we report that AMPA receptors at inner hair cell (IHC) synapses lack the GluR2 subunit and are transiently Ca2+‐permeable before hearing onset as evidenced using agonist‐induced Co2+ accumulation, Western blots and GluR2 confocal microscopy in the rat cochlea. AMPA (100 µm) induced Co2+ accumulation in primary auditory neurons until postnatal day (PND) 10. This accumulation was concentration‐dependent, strengthened by cyclothiazide (50 µm) and blocked by GYKI 52466 (80 µm) and Joro spider toxin (1 µm). It was unaffected by D‐AP5 (50 µm), and it could not be elicited by 56 mm K+ or 1 mm NMDA + 10 µm glycine. Western blots showed that GluR1 immunoreactivity, present in homogenates of immature cochleas, had disappeared by PND12. GluR2 immunoreactivity was not detected until PND10 and GluR3 and GluR4 immunoreactivities were detected at all the ages examined. Confocal microscopy confirmed that the GluR2 immunofluorescence was not located postsynatically to IHCs before PND10. In conclusion, AMPA receptors on maturing primary auditory neurons differ from those on adult neurons. They are probably composed of GluR1, GluR3 and GluR4 subunits and have a high Ca2+ permeability. The postsynaptic expression of GluR2 subunits may be continuously regulated by the presynaptic activity allowing for variations in the Ca2+ permeability and physiological properties of the receptor.
Estrogen attenuates antinociception produced by stimulation of Kölliker–Fuse nucleus in the rat
Authors: Nag S. , Mokha S. S.
Published: December 2004

This is the first demonstration of sex‐related differences in the α2‐adrenoceptor‐mediated antinociceptive effects produced by stimulation of an endogenous noradrenergic pathway. Electrical or chemical (substance P) stimulation of Kölliker–Fuse nucleus (KF, A7) is known to produce antinociception mediated by α2‐adrenoceptors in the spinal cord. KF stimulation has also been shown to inhibit the responses of nociceptive neurons in the dorsal horn of the medulla and the spinal cord. We investigated whether KF stimulation produces sex‐specific modulation of trigeminal nociception. The N‐methyl‐d‐aspartic acid (NMDA)‐induced nociceptive behavior was employed as an index of nociception. Microinjection of NMDA (2 nmol/10 µL) in the trigeminal region produced nociceptive scratching behavior that was confined to the orofacial region. Male and ovariectomized (OVX) Sprague–Dawley rats were implanted with a guide cannula dorsal to the KF nucleus and a PE‐10 cannula in the trigeminal region dorsal to obex. Nociceptive testing was conducted after 5–7 days of recovery. A group of ovariectomized rats (OVX+E) was treated with estradiol benzoate 48 h prior to nociceptive testing. There were no significant differences in the number of NMDA‐induced scratches or duration between the male, OVX and OVX+E groups. Microinjection of substance P (3.7 pmol/0.5 µL) in the KF significantly reduced the number of NMDA‐induced scratches and their duration in male and OVX groups; these were restored to control levels by yohimbine (30 µg/15 µL), an α2‐adrenoceptor antagonist. However, KF stimulation failed to inhibit the NMDA‐induced scratching behavior in the OVX+E group. We conclude that stimulation of KF produces estrogen‐dependent modulation of nociception.
Entorhinal cortex contributes to object‐in‐place scene memory
Authors: Charles David P. , Browning Philip G. F. , Gaffan David
Published: December 2004

Four rhesus monkeys (Macaca mulatta) were trained preoperatively in a test of object‐in‐place scene memory. They were presented daily with lists of unique computer‐generated scenes each containing a spatial array of multiple individual objects. Within each scene, objects to be discriminated appeared in the foreground, each occupying a unique location, and monkeys were required to correctly discriminate the rewarded object to receive a food reward. Once this preoperative criterion was attained, the monkeys received bilateral entorhinal cortex ablation performed as either one or two surgical operations with a period of testing following each. Postoperatively, they were significantly impaired in learning new object‐in‐place scene problems. These results show that the entorhinal cortex, like anatomically related structures including the perirhinal cortex and the fornix, contributes to object‐in‐place scene learning.
The clock in the dorsal suprachiasmatic nucleus runs faster than that in the ventral
Authors: Noguchi Takako , Watanabe Kazuto , Ogura Akihiko , Yamaoka Sadao
Published: December 2004

In mammals, circadian rhythms are driven by a pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The pacemaker is composed of an ensemble of multiple, single‐cell oscillators in the SCN. We measured arginine–vasopressin (AVP) release in organotypic SCN slices. The SCN slice culture showed circadian oscillation of AVP release with a period length (± SEM) of 23.84 ± 00.03 h. This period is very similar to the one we previously reported in dispersed SCN cultures and is also close to that of behavioural rhythms. When the ventral part was removed by a surgical cut across the slice in the horizontal plane, however, the period became shorter (23.22 ± 00.08 h). On the other hand, the removal of the dorsal part did not affect period length. These results suggest that the oscillators in ventral and dorsal cells contribute differently to period length and that the dorsal oscillators are entrained by the ventral ones to form a single integrated oscillator.
Possible role of phosphatidylinositol 4,5, bisphosphate in luteinizing hormone releasing hormone‐mediated M‐current inhibition in bullfrog sympathetic neurons
Authors: Ford Christopher P. , Stemkowski Patrick L. , Smith Peter A.
Published: December 2004

Luteinizing hormone releasing hormone (LHRH) is a physiological modulator of neuronal excitability in bullfrog sympathetic ganglia (BFSG). Actions of LHRH involve suppression of the noninactivating, voltage‐dependent M‐type K+ channel conductance (gM). We found, using whole‐cell recordings from these neurons, that LHRH‐induced suppression of gM was attenuated by the phospholipase C (PLC) inhibitor U73122 (10 µm) but not by the inactive isomer U73343 (10 µm). Buffering internal Ca2+ to 117 nm with intracellular 20 mm BAPTA + 8 mm Ca2+ or to < 10 nm with intracellular 20 mm BAPTA + 0.4 mm Ca2+ did not attenuate LHRH‐induced gM suppression. Suppression of gM by LHRH was not antagonized by the inositol 1,4,5 trisphosphate (InsP3) receptor antagonist heparin (∼ 300 µm). Preventing phosphatidylinositol‐4,5‐bisphosphate (PIP2) synthesis by blocking phosphatidylinositol‐4‐kinase with wortmannin (10 µm) or with the nonhydrolysable ATP analogue AMP‐PNP (3 mm) prolonged recovery of LHRH‐induced gM suppression. This effect was not produced by blocking phosphatidyl inositol‐3‐kinase with LY294002 (10 µm). Rundown of gM was attenuated when cells were dialysed with 240 µm di‐octanoyl PIP2 or 240 µm di‐octanoyl phosphatidylinositol‐3,4,5‐trisphosphate (PIP3) but not with 240 µm di‐octanoyl phosphatidylcholine. LHRH‐induced gM suppression was competitively antagonized by dialysis with 240 µm di‐octanoyl PIP2, but not with di‐octanoyl phosphatidylcholine. These results would be expected if LHRH‐induced gM suppression reflects a PLC‐mediated decrease in plasma membrane PIP2 levels.
Feedback control of Purkinje cell activity by the cerebello‐olivary pathway
Authors: Bengtsson F. , Svensson P. , Hesslow G.
Published: December 2004

The pathway from the deep cerebellar nuclei to the inferior olive, the source of the climbing fibre input to the cerebellum, inhibits olivary transmission. As climbing fibre activity can depress the background firing of the Purkinje cells, it was suggested that nucleo‐olivary (N–O) inhibition is a negative feedback mechanism for regulating Purkinje cell excitability. This suggestion was investigated, in a set‐up with decerebrate ferrets, both by blocking and by stimulating cerebellar output while recording Purkinje cell activity. Blocking the N–O pathway was followed by an increased climbing fibre activity and a dramatic reduction in simple spike firing. Stimulation of the N–O fibres depressed climbing fibre responses and caused an increase in simple spike firing. These results are taken as support for the feedback hypothesis.
Myelination triggers local loss of axonal CNR/protocadherinα family protein expression
Authors: Morishita Hirofumi , Kawaguchi Masahumi , Murata Yoji , Seiwa Chika , Hamada Shun , Asou Hiroaki , Yagi Takeshi
Published: December 2004

The cadherin‐related neuronal receptor (CNR)/protocadherin (Pcdh) α family is one of the diverse protocadherin families expressed in developing axons. We observed a strong axonal expression of these proteins at late embryonic and early postnatal stages corresponding to regions where fibers had not yet been myelinated. We therefore followed the postnatal localization of CNR/Pcdhα protein in major axonal tracts, such as the internal capsule, lateral olfactory tract, and optic nerve, and found that its axonal localization was dramatically lost in parallel with the increased expression of myelin markers. Moreover, the hypomyelinated optic nerve tracts of the myelin‐deficient Shiverer mouse exhibited elevated levels of CNR/Pcdhα expression. These axonal expression patterns of CNR/Pcdhα in wild‐type and Shiverer mice were similar to those of growth associated protein 43 (GAP‐43) and L1, both of which are associated with axonal maturation. Thus, myelination may be a trigger for the local loss of axonal CNR/Pcdhα protein, and this process may be important in the maturation of neural circuits.
5‐HT2A and α1b‐adrenergic receptors entirely mediate dopamine release, locomotor response and behavioural sensitization to opiates and psychostimulants
Authors: Auclair Agnès , Drouin Candice , Cotecchia Susanna , Glowinski Jacques , Tassin Jean‐Pol
Published: December 2004

Addictive properties of drugs of misuse are generally considered to be mediated by an increased release of dopamine (DA) in the ventral striatum. However, recent experiments indicated an implication of α1b‐adrenergic receptors in behavioural responses to psychostimulants and opiates. We show now that DA release induced in the ventral striatum by morphine (20 mg/kg) is completely blocked by prazosin (1 mg/kg), an α1‐adrenergic antagonist. However, morphine‐induced increases in DA release in the ventral striatum were found to be similar in mice deleted for the α1b‐adrenergic receptor (α1b‐AR KO) and in wild‐type (WT) mice, suggesting the presence of a compensatory mechanism. This acute morphine‐evoked DA release was completely blocked in α1b‐AR KO mice by SR46349B (1 mg/kg), a 5‐HT2A antagonist. SR46349B also completely blocked, in α1b‐AR KO mice, the locomotor response and the development of behavioural sensitization to morphine (20 mg/kg) and d‐amphetamine (2 mg/kg). Accordingly, the concomitant blockade of 5‐HT2A and α1b‐adrenergic receptors in WT mice entirely blocked acute locomotor responses but also the development of behavioural sensitization to morphine, d‐amphetamine or cocaine (10 mg/kg). We observed, nevertheless, that inhibitory effects of each antagonist on locomotor responses to morphine or d‐amphetamine were more than additive (160%) in naïve WT mice but not in those sensitized to either drug. Because of these latter data and the possible compensation by 5‐HT2A receptors for the genetic deletion of α1b‐adrenergic receptors, we postulate the existence of a functional link between these receptors, which vanishes during the development of behavioural sensitization.
Long‐term sensorineural hearing loss induces functional changes in the rat auditory nerve
Authors: Shepherd Robert K. , Roberts Lloyd A. , Paolini Antonio G.
Published: December 2004

Loss of cochlear hair cells in the rat initiates degenerative change within the primary auditory neurons (ANs) of the cochlea. These degenerative changes include loss of peripheral processes, demyelination and ultimately cell death. This pathology will affect the biophysical processes involved in action potential generation and propagation to an electrical stimulus via a cochlear implant. We measured the response properties of ANs, with particular reference to their refractory behaviour, in normal, short‐ (9 weeks) and long‐term (> 52 weeks) deafened rats. AN loss was moderate in the short‐term and severe in the long‐term deafened animals. AN activity was elicited using a brief electrical stimulus delivered via a bipolar electrode array implanted into the cochlea. The general response properties of ANs recorded from deafened cochleae were similar to those observed in normal cochleae, i.e. a monotonic increase in the probability of firing and a decrease in response latency and temporal jitter with increasing stimulus intensity. However, the absolute refractory period was significantly prolonged in animals deaf for > 12 months (P = 0.0026). Deafened animals also exhibited a highly significant increase in threshold compared with normal controls (P < 0.001). These functional changes have implications for recipients of cochlear implants and potential therapies directed toward halting or reversing AN pathology.
Attitudes and confidence towards computers and books as learning tools: a cross‐sectional study of student cohorts
Authors: Garland Kate , Noyes Jan
Published: December 2004

Students today comprise a very diverse group, and this will be reflected in their attitudes towards learning. This study set out to examine four different cohorts of UK students during the same time period. Contrary to expectations, it was found that attitudes towards books and computers, as measured by separate but matched scales, were equal, even though experience of the two media varied considerably. A key predictor for computer attitude was found to be confidence for learning from computers rather than general computer confidence. Further, attitudes and confidence towards books and computers as learning tools varied significantly across the four cohorts.
How to structure online discussions for meaningful discourse: a case study
Authors: Gilbert Patricia K. , Dabbagh Nada
Published: December 2004

This study examined the impact of structuredness of asynchronous online discussion protocols and evaluation rubrics on meaningful discourse. Transcripts of twelve online discussions involving 87 participants from four sections of a graduate course entitled Instructional Technology Foundations and Learning Theory were analysed across four semesters. Protocols and evaluation rubrics guiding online discussions in this course ranged from minimal structure or loosely defined protocols in the first section, to high sructure or well defined and comprehensive protocols and evaluation criteria in the fourth section. The analyses revealed that some elements of structure had a significant impact on meaningful discourse. Particularly, guidelines that assisted the facilitation and evaluation of online discussions increased the cognitive quality of student postings promoting a deeper and more meaningful understanding of course content.
Identification of learning styles online by observing learners’ browsing behaviour through a neural network
Authors: Lo Jia‐Jiunn , Shu Pai‐Chuan
Published: December 2004

Identification of individual learning style is important when developing adaptive educational hypermedia systems. Current systems ask learners to complete questionnaires to identify their learning styles, which might not be appropriate in some contexts. The goal of this research is to identify the learner's learning style by simply observing his/her browsing behaviour without asking the learner to answer any questions or filling out any form. It is implemented through a multi‐layer feed forward neural network (MLFF). Browsing behaviour, in this research, includes three factors, the use of embedded support devices (ESDs), the selection of link types, and the navigation between visited/unvisited nodes. The experiment results showed the proposed model performed well in identifying learning styles. Link type is the dominant factor and Time shift may not be a major factor in the identification of learning styles. Because of the fast execution property of neural networks and identification of learning styles online, it is possible to incorporate learning styles into online adaptive educational web‐based systems.
PHILIP HEFNER AND THE MODERNIST/POSTMODERNIST DIVIDE
Authors: Stone Jerome A.
Published: December 2004

Abstract Philip Hefner is part of neither the dominant Western paradigm nor the usual postmodernist reaction against it. He belongs within an Anglo‐American viewpoint that also is within neither the dominant Western nor the postmodernist paradigm. Herein I sketch the differences between these paradigms. I elaborate Hefner's theology of the created co‐creator to show where Hefner constrasts with them and then contrast his ideas with those of two contemporary theologians who fit into the second paradigm, George Lindbeck and Mark C. Taylor.
AN EVOLUTIONARY CRITIQUE OF THE CREATED CO‐CREATOR CONCEPT
Authors: Irons William
Published: December 2004

Abstract The created co‐creator theology states that human beings have the purpose of creating the most wholesome future possible for our species and the global ecosystem. I evaluate the human aspect of this theology by asking whether it is possible for human beings to do this. Do we have sufficient knowledge? Can we be motivated to do what is necessary to create a wholesome future for ourselves and our planet? We do not at present have sufficient knowledge, but there is reason to believe that with further scientific research we will be able to acquire it. The more difficult question is whether we can be motivated to cooperate on the scale necessary to fulfill this purpose. Evolutionary theories of human sociality, altruism, and cooperation are reviewed. I conclude that it is possible for human beings to fulfill the purpose defined for us by the created cocreator concept, but doing this will not be easy.
CREATED CO‐CREATOR AND THE PRACTICE OF MEDICINE
Authors: Pederson Ann
Published: December 2004

AbstractThere is a crisis of interpretation experienced by those making critical‐care decisions and creating health‐care policies and by the patients and families who make life‐and‐death decisions. For example, at both the beginning and end of life, new technologies are changing the way we define life and death. We can prolong life or hasten death in ways that we could not earlier have imagined. This crisis of interpretation demands new ways of thinking and doing. My task is to explicate how the created co‐creator can be used as a springboard to help link theological concepts with feminist concerns about two issues: interpreting the culture and practice of medicine in a new way, and explicating the ambiguity of decision making when considering issues of life and death.
RETHINKING THE IMAGE OF GOD
Authors: Case‐Winters Anna
Published: December 2004

AbstractThe present ecological crisis imposes a rethinking of the relation between the human being and the rest of nature. Traditional theological articulations of this relation have proven problematic where they foster separatism and anthropocentrism, which give a false report on the relation and have a negative impact on thinking and acting in relation to nature. One place to begin rethinking is through an exploration of the affirmation that the human being is “made in the image of God,”imago dei.Some ways of construing the theological meaning of this designation are more helpful than others. Science has recognized the extent to which the human being is not only dependent upon but even emergent from nature. We are made of the same “stuff” that makes up the rest of the universe. Wearenature. The place of the human being is much more modest, recent, and precarious than usually acknowledged in theological reflection. New ways of interpreting our role within nature must evolve out of this new understanding. Philip Hefner has proposed that we think of the human being as created co‐creator. His is a distinctive and promising contribution. This essay responds with both affirmations and friendly questions.
Early calpain‐mediated proteolysis following AMPA receptor activation compromises neuronal survival in cultured hippocampal neurons
Authors: Araújo Inês M. , Verdasca Maria J. , Leal Ermelindo C. , Bahr Ben A. , Ambrósio António F. , Carvalho Arsélio P. , Carvalho Caetana M.
Published: December 2004

In this work, we investigated the involvement of calpains in the neurotoxicity induced by short‐term exposure to kainate (KA) in non‐desensitizing conditions of AMPA receptor activation (cyclothiazide present, CTZ), in cultured rat hippocampal neurons. The calpain inhibitor MDL28170 had a protective effect in cultures treated with KA plus CTZ (p < 0.01), preventing the decrease in MTT reduction caused by exposure to KA (p < 0.001). Caspase inhibition by ZVAD‐fmk was not neuroprotective against the toxic effect of KA. At 1 h after treatment, we could already observe significantly increased calpain activity, which was prevented by MDL 28170 and NBQX. Western blot analysis of calpain substrates, GluR1, neuronal nitric oxide synthase (nNOS) and nonerythroid spectrin (fodrin), showed a time‐dependent and MDL 28170‐sensitive proteolysis of these proteins. This effect was due to calpains, but not caspases, since ZVAD‐fmk was ineffective in preventing proteolytic events. Breakdown products of fodrin (BDPs) were detected as early as 15 min after exposure to KA. Overall, these results show early activation of calpains following activation of AMPA receptors as well as compromise of neuronal survival, likely due to proteolytic events that affect proteins involved in neuronal signaling.
Expression profiling upon Nex1/MATH‐2‐mediated neuritogenesis in PC12 cells and its implication in regeneration
Authors: Uittenbogaard Martine , Chiaramello Anne
Published: December 2004

The expression of Nex1 peaks during brain development when neurite outgrowth and synaptogenesis are highly active. We previously showed that Nex1 is a critical effector of the nerve growth factor (NGF) pathway and its overexpression results in spontaneous neuritogenesis. Furthermore, the PC12‐Nex1 cells exhibit accelerated neurite extension upon NGF exposure, and have the capacity to regenerate neurites in the absence of NGF. In this study, we identify the repertoire of genes targeted by Nex1 to unravel the molecular mechanisms by which Nex1 promotes differentiation and regeneration. Our transcriptional analysis reveals that Nex1 modulates a wide spectrum of genes with diverse functions, many of them being key downstream regulators of the NGF pathway, and critical to neuritogenesis, such as microtubules, microtubule‐associated proteins (MAPs) and intermediate filaments. We also provide the first evidence that a basic helix‐loop‐helix (bHLH) protein stimulates the expression of the cyclin‐dependent kinase (CDK) inhibitors belonging to the INK4 family, which plays a role in promoting cell‐cycle arrest. Finally, we show a dramatic synergistic effect between Nex1 and cAMP, resulting in an impressive regeneration of an elaborate and dense neurite network. Thus, Nex1 has endowed the PC12‐Nex1 cells with a distinct combination of gene products that takes part in the complex regulation of neuritogenesis and regeneration.
Intracellularly generated amyloid‐β peptide counteracts the antiapoptotic function of its precursor protein and primes proapoptotic pathways for activation by other insults in neuroblastoma cells
Authors: Esposito Luke , Gan Li , Yu Gui‐Qiu , Essrich Christian , Mucke Lennart
Published: December 2004

Most mutations in amyloid precursor proteins (APPs) linked to early onset familial Alzheimer's disease (FAD) increase the production of amyloid‐β peptides ending at residue 42 (Aβ42), which are released from APP by β‐ and γ‐secretase cleavage. Stably transfected cells expressing wild‐type human APP (APPWT) were more resistant to apoptosis‐inducing treatments than cells expressing FAD‐mutant human APP (APPFAD). Preventing Aβ42 production with an M596I mutation (β–), which blocks β‐secretase cleavage of APP, or by treatment with a γ‐secretase inhibitor increased the resistance of APPFAD‐expressing cells to apoptosis. Exposing hAPPFAD/β– cells to exogenous Aβ42 or conditioned medium from Aβ42‐producing APPFAD cells did not diminish their resistance to apoptosis. Preventing APP from entering the distal secretory pathway, where most Aβ peptides are generated, by retaining APP in the endoplasmic reticulum (ER)/intermediate compartment (IC) increased the resistance of APPFAD‐expressing cells to apoptosis and did not alter the resistance of APPWT‐expressing cells. p53‐mediated gene transactivation after apoptosis‐inducing treatments was much stronger in APPFAD cells than in hAPPWT or hAPPFAD/β– cells. In contrast, upon induction of ER stress, cells expressing APPFAD, hAPPFAD/β–, or APPWT had comparable levels of glucose‐regulated protein‐78 mRNA, an unfolded protein response indicator. We conclude that Aβ, especially intracellular Aβ, counteracts the antiapoptotic function of its precursor protein and predisposes cells to p53‐mediated, and possibly other, proapoptotic pathways.
Apolipoprotein E isoforms and apolipoprotein AI protect from amyloid precursor protein carboxy terminal fragment‐associated cytotoxicity
Authors: Maezawa Izumi , Jin Lee‐Way , Woltjer Randall L. , Maeda Nobuyo , Martin George M. , Montine Thomas J. , Montine Kathleen S.
Published: December 2004

Inheritance of the apolipoprotein (APO) E gene ɛ4 or ɛ2 allele alters the risk of developing Alzheimer disease (AD), while increased alpha‐tocopherol (AT) intake appears to lower the risk of AD. As APOE is a major apolipoprotein in the CNS and AT in vivo is transported in lipoproteins, we tested the hypothesis that CNS lipoproteins, as modeled by relevant concentrations of high density lipoprotein (HDL), and AT would interact to suppress neurotoxicity in a cell culture model of amyloid beta (Aβ)‐ related toxicity. These cells conditionally express C99‐derived peptides, proposed to be a key step in AD pathogenesis; this expression is closely associated with subsequent cell death. We found that physiologic concentrations of lipoproteins present in the CNS protected from C99‐associated toxicity and provided evidence for two mechanisms of protection. The first was AT‐independent, APOE isoform‐dependent, and most potent for the APOE2 isoform. The second was a synergistic protection afforded by a combination of APOAI, or less so APOE, and AT. These data provide a novel explanation for the apparent AD‐protective effect of inheriting an ɛ2 APOE allele, and suggest that optimizing AT enrichment of CNS lipoproteins or devising APOAI mimetics may augment AT efficacy in treating AD.
Dopamine D3 receptor stimulation promotes the proliferation of cells derived from the post‐natal subventricular zone
Authors: Coronas V. , Bantubungi K. , Fombonne J. , Krantic S. , Schiffmann S. N. , Roger M.
Published: December 2004

In the adult mammalian brain, neural stem cells persist in the subventricular zone (SVZ) where dopamine D3 receptors are expressed. Here, we demonstrate that addition of 1 µm apomorphine increases cell numbers in post‐natal SVZ cell cultures. This effect was prevented by a co‐treatment with haloperidol, sulpiride or U‐99194A, a D3‐preferring antagonist, and mimicked by the dopamine D3 receptor selective agonist 7‐hydroxy‐dipropylaminotetralin (7‐OH‐DPAT). EC50 values were 4.04 ± 1.54 nm for apomorphine and 0.63 ± 0.13 nm for 7‐OH‐DPAT, which fits the pharmacological profile of the D3 receptor. D3 receptors were detected in SVZ cells by RT‐PCR and immunocytochemistry. D3 receptors were expressed in numerous β‐III tubulin immunopositive cells. The fraction of apoptotic nuclei remained unchanged following apomorphine treatment, thus ruling out any possible effect on cell survival. In contrast, proliferation was increased as both the proportion of nuclei incorporating bromo‐deoxyuridine and the expression of the cell division marker cyclin D1 were enhanced. These findings provide support for a regulatory role of dopamine over cellular dynamics in post‐natal SVZ.