bluuebunny/crossref_metadata_2025 huggingface dataset:
Normal Development of the Gut‐Associated Lymphoid Tissue Except Peyer's Patch in MyD88‐Deficient Mice
Authors: Iiyama R. , Kanai T. , Uraushihara K. , Ishikura T. , Makita S. , Totsuka T. , Yamazaki M. , Nakamura T. , Miyata T. , Yoshida H. , Takeuchi O. , Hoshino K. , Takeda K. , Ishikawa H. , Akira S. , Watanabe M.
Published: November 2003

MyD88 is a key adaptor molecule for signalling via Toll‐like receptors (TLRs) and the response to gut commensal microbes. To investigate the role of TLRs/MyD88 pathway in the development of the gut‐associated lymphoid tissue (GALT), we examined the development of Peyer's patches (PPs) and cryptopatch (CP), and also one of effector compartment, intraepithelial lymphocyte (IEL) in MyD88–/–, TLR2–/– and TLR4–/– mice. In MyD88–/– mice, the organogenesis of PPs was not disturbed. However, PPs in 2‐week‐old MyD88–/– mice were significantly smaller than those in MyD88+/– mice. Also, in 2‐week‐old TLR4–/–, but not TLR2–/– mice, PPs did not develop rapidly. The development of PPs in MyD88–/– and TLR4–/– mice was completely recovered in 10 weeks. PP cells from MyD88–/– mice showed significant decrease in proliferation when stimulated with lipopolysaccharide. The development of CP and IEL was also normal in 10‐week‐old MyD88–/– mice. These results suggest that the TLRs/MyD88 pathway might be involved in the development of PPs only at early postnatal stage, and TLRs/MyD88‐independent signalling is critically involved in the development of GALT in adult mice.
Semiquantitative Evaluation of mRNAs for the Membranous Form of Immunoglobulin Heavy Chain is Useful for Investigating the Etiology in CVID
Authors: Terada T. , Kaneko H. , Fukao T. , Teramoto T. , Asano T. , Li A. L. , Kasahara K. , Kondo N.
Published: November 2003

Common variable immunodeficiency (CVID) is a primary antibody deficiency syndrome characterized by defective B‐cell maturation and antibody formation resulting in low serum antibody levels of all immunoglobulin (Ig) isotypes. To investigate the pathogenesis of CVID, we developed a set of competitive polymerase chain reaction for membrane‐bound Ig heavy chain (mHC) mRNAs for IgM, IgG and IgA. Data on three children with CVID in group A of Bryant's classification were analysed. All the three mHC mRNA levels in Patient 1 were almost same as those in healthy controls. In Patient 2, mHC mRNA for IgM was detected at a level similar to that in controls, but mHC mRNAs for IgG and IgA heavy chains were not detected. In Patient 3, all the three mHC mRNAs were undetectable. Our data suggest that a different molecular basis exists in these patients with CVID even though all belong to group A of Bryant's classification. Use of our method facilitates a better understanding of molecular events in CVID patients and may be useful for precise classifications of CVID.
A revisit of sickle cell disease, sickle cell trait, and the extra transverse digital crease on the fingers
Authors: Ogunbiyi Adebola O. , George Adekunle O. , Daramola Olaniyi O. M.
Published: November 2003

Background  Alteration in the location and number of palmar creases has been found in association with certain disorders. The extra transverse digital crease (ETDC) has been reported in sickle cell disease. This study was carried out to determine the importance of ETDC as a diagnostic tool for sickle cell disease amongst Nigerians.

Methods  Medical students and student nurses with available hemoglobin electrophoresis records were studied. Their palms were examined for the presence of ETDC.

Results  An ETDC was present in 80 of 178 (44.9%) cases with genotype AA, 26 of 68 (38.2%) cases with sickle cell trait (AS, 65; AC, 3), and 10 of 22 (45.4%) cases with sickle cell disease (SS).

Conclusions  The results from our study show that the ETDC is not a diagnostic sign of sickle cell disease in Nigerians.
Evaluation of clinical types of cutaneous lichen planus in anti‐hepatitis C virus seronegative and seropositive Nigerian patients
Authors: Daramola Olaniyi O. M. , Ogunbiyi Adebola O. , George Adekunle O.
Published: November 2003

Background  The presentation of oral lichen planus in anti‐hepatitis C virus (HCV) seropositive and seronegative patients was previously evaluated, and the keratotic form of oral lichen planus was found to be more prevalent in anti‐HCV seropositive patients. This study evaluated the presentation of cutaneous lichen planus in anti‐HCV seropositive and seronegative Nigerians.

Methods  Fifty‐seven Nigerians with cutaneous lichen planus were carefully examined to determine the form of lichen planus present. All were screened for the presence of anti‐HCV by second‐generation enzyme‐linked immunosorbent assay (ELISA) and grouped as anti‐HCV seropositive or anti‐HCV seronegative patients.

Results  Nine patients were anti‐HCV positive. Seven of these seropositive patients had hypertrophic lichen planus.

Conclusion  Hypertrophic lichen planus in Nigerians is more prevalent with HCV infection.
Solitary embolic cutaneous aspergillosis in the immunocompromised patient with acute myelogenous leukemia – a propos another case caused by Aspergillus flavus
Authors: Krunic Aleksandar L. , Medenica Maria , Busbey Shail
Published: November 2003

A 68‐year‐old male with acute myelogenous leukemia was admitted for consolidation chemotherapy. The in‐hospital course was complicated by neutropenia, fever and nodular pulmonary opacities suggestive of multifocal pneumonia. The patient subsequently developed a single, solitary necrotic crusted nodule on the right cheek. Skin biopsy demonstrated embolic vascular invasion with septate hyphae, dichotomous branching and minimal inflammation. Tissue culture revealed Aspergillus flavus. Despite systemic antifungal therapy with amphotericin B and granulocyte transfusions, the patient developed respiratory failure and died of disseminated aspergillosis, sepsis and renal failure. The clinical presentation of disseminated infection with Aspergillus flavus as a solitary embolic cutaneous lesion is extremely rare. We have reviewed other cases described in the literature and suggest this pattern of cutaneous involvement as more typical of disseminated infection with Aspergillus flavus.
Casanova and venereology
Authors: Vincent Barrazza
Published: November 2003

In 1750 Casanova met Henriette de Bourbon‐Conti, Duchess of Chartres, in Paris. She was suffering from a disfiguring syphilis. He prescribed an unusual treatment and noticed a transient improvement. But skin disorders rapidly recurred. A few years later the young aristocrat died.
Clinical and economic impact of Apligraf® for the treatment of nonhealing venous leg ulcers
Authors: Fivenson David , Scherschun Lubomira
Published: November 2003

Background  Controlled studies have shown that Apligraf® (Organogenesis Inc., Canton, USA) is more economical and more effective at healing venous leg ulcers (VLUs) than compression therapy alone. However, the clinical and economic impact of Apligraf on healing VLUs in clinical practice has not been fully examined.

Methods  A medical chart review was conducted of patients who were treated with Apligraf for one or more nonhealing VLUs over a 2‐year period at the Henry Ford Hospital. Following Apligraf treatment, patients were followed for up to 9 months. Primary clinical outcome measures were mean change in baseline ulcer size (cm2) per week and percent reduction in baseline ulcer size at final study visit. Economic evaluation of Apligraf treatment was based on VLU‐related medical care costs (US$) in relation to ulcer size (cm2) changes before and after Apligraf therapy.

Results  Thirteen patients with 21 chronic VLUs were treated with Apligraf. All had at least one comorbidity, most commonly hypertension (38%). Twelve patients were known to have had a prior history of VLU. At baseline, mean ulcer duration was 23.9 months and median ulcer size was 13.5 cm2; for the 6 months preceding Apligraf treatment, in which patients received conventional compression therapy, mean ulcer size increased +0.72 cm2 per week. During the Apligraf post‐treatment study period, mean ulcer size decreased by −2.37 cm2 per week. At final clinic visit, ulcers exhibited an average 60.5% reduction in baseline size; 21 ulcers (n = 13) showed 75% or greater reduction in size, compared with baseline. Economic data were available for five patients; among these individuals ulcer‐related medical costs per unit change in ulcer size were lower following Apligraf treatment relative to such costs with conventional compression therapy applied during the Apligraf pretreatment period.

Conclusions  In a clinical practice setting, Apligraf is more effective and more economical at healing VLUs than conventional therapy alone.
Mucoepidermoid carcinoma (adenosquamous carcinoma) treated with Mohs micrographic surgery
Authors: Nouri Keyvan , Trent Jennifer T. , Lowell Brooke , Vaitla Rama , Jimenez Gloria P.
Published: November 2003

Background  Mucoepidermoid carcinoma (MEC), sometimes referred to as adenosquamous carcinoma (ASC), is a common malignant tumor of the salivary glands that can also develop from the esophagus, lacrimal passages, lung, upper respiratory tract, pancreas, prostate and thyroid. Rarely, MEC will present primarily in the skin.

Case  We present a case of primary MEC of the lower eyelid treated successfully with Mohs micrographic surgery.

Results  Mohs micrographic surgery was performed because of the highly aggressive and unpredictable nature of this tumor. The tumor was completely excised using Mohs with negative margins achieved in three stages. The patient has been disease free for 3 years since the surgery.

Conclusion  We offer Mohs as an option for treating MEC.
Atrophying tinea versicolor: A clinical and histological study of 12 patients
Authors: Crowson A. N. , Magro C. M.
Published: November 2003

Background  We describe 12 patients with an atrophying dermatitis in whom the biopsy findings were compatible with tinea versicolor.

Design  We encountered 12 skin biopsies from 12 patients in whom a clinically atrophying dermatosis was associated with light microscopic (LM) evidence of atrophy and epidermal colonization by Pityrosporum sp. Formalin‐fixed, paraffin‐embedded tissue sections were cut at 5 microns and stained with H&E, alcian blue‐PAS and PAS‐diastase preparations.

Results  Five men and seven women aged 17–73 years in whom lesions characterized as atrophic plaques, patches or macules prompted clinical differential diagnoses including parapsoriasis or mycosis fungoides (MF), anetoderma, lupus erythematosus, and steroid atrophy. A LM examination showed epidermal colonization with pityrosporum hyphae and spores accompanied by variable epidermal and dermal atrophy characterized by rete‐ridge effacement, subepidermal fibroplasia, pigment incontinence and elastolysis.

Conclusions  Atrophying cutaneous lesions comprise part of the clinical spectrum of tinea versicolor for which we propose the term ‘atrophying tinea versicolor’. The pathogenetic basis is unclear but could be the sequela of delayed type hypersensitivity and the release by T‐helper lymphocytes of leukotrienes which perturb collagen metabolism and/or keratinocyte growth. Lesions may be mistaken clinically for MF or other atrophying dermatoses.
Engagement of visual fixation suppresses sensory responsiveness and multisensory integration in the primate superior colliculus
Authors: Bell A. H. , Corneil B. D. , Munoz D. P. , Meredith M. A.
Published: November 2003

Neurons in the intermediate and deep layers of the superior colliculus (SC) often exhibit sensory‐related activity in addition to discharging for saccadic eye movements. These two patterns of activity can combine so that modifications of the sensory response can lead to changes in orienting behaviour. Can behavioural factors, however, influence sensory activity? In this study of rhesus monkeys, we isolate one behavioural factor, the state of visual fixation, and examine its influences on sensory processing and multisensory integration in the primate SC. Two interleaved fixation conditions were used: a FIX condition requiring exogenous fixation of a visible fixation point; and a FIX‐BLINK condition, requiring endogenous fixation in the absence of a visible fixation point. Neurons of the SC were influenced by fixation state, exhibiting both lower levels of sensory activity and reduced multisensory interactions when fixation was exogenously engaged on a visible fixation point. These results are consistent with active visual fixation suppressing responses to extraneous stimuli, and thus demonstrate that sensory processing and multisensory responses in the SC are not dependent solely on the physical properties of the sensory environment, but are also dynamically influenced by the behavioural state of the animal.
Dynamics of Ca2+ and Na+ in the dendrites of mouse cerebellar Purkinje cells evoked by parallel fibre stimulation
Authors: Kuruma Akinori , Inoue Takafumi , Mikoshiba Katsuhiko
Published: November 2003

Ca2+ and Na+ play important roles in neurons, such as in synaptic plasticity. Their concentrations in neurons change dynamically in response to synaptic inputs, but their kinetics have not been compared directly. Here, we show the mechanisms and dynamics of Ca2+ and Na+ transients by simultaneous monitoring in Purkinje cell dendrites in mouse cerebellar slices. High frequency parallel fibre stimulation (50 Hz, 3–50‐times) depolarized Purkinje cells, and Ca2+ transients were observed at the anatomically expected sites. The magnitude of the Ca2+ transients increased linearly with increasing numbers of parallel fibre inputs. With 50 stimuli, Ca2+ transients lasted for seconds, and the peak [Ca2+] reached ∼100 µm, which was much higher than that reported previously, although it was still confined to a part of the dendrite. In contrast, Na+ transients were sustained for tens of seconds and diffused away from the stimulated site. Pharmacological interventions revealed that Na+ influx through α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) receptors and Ca2+ influx through P‐type Ca channels were essential players, that AMPA receptors did not operate as a Ca2+ influx pathway and that Ca2+ release from intracellular stores through inositol trisphosphate receptors or ryanodine receptors did not contribute greatly to the large Ca2+ transients.
Synaptic and non‐synaptic mechanisms of amygdala recruitment into temporolimbic epileptiform activities
Authors: Klueva Julia , Munsch Thomas , Albrecht Doris , Pape Hans‐Christian
Published: November 2003

Lateral amygdala (LA) activity during synchronized‐epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple‐site extra‐ and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4‐aminopyridine (50 µm) induced epileptiform discharges in all regions under study. Slow interictal‐like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal‐like activity. Disconnection of the amygdala resulted in de‐synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal‐like activity was intracellularly reflected in LA projection neurons as γ‐aminobutyric acid (GABA)A/B receptor‐mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal‐like activity in all areas under study. We conclude that interictal‐like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons.
Modulation of neuronal activity by the endogenous pentapeptide QYNAD
Authors: Meuth Sven G. , Budde Thomas , Duyar Hüseyin , Landgraf Peter , Broicher Tilman , Elbs Martin , Brock Roland , Weller Michael , Weissert Robert , Wiendl Heinz
Published: November 2003

Inflammation and demyelination both contribute to the neurological deficits characteristic of multiple sclerosis. Neurological dysfunctions are attributable to inflammatory demyelination and, in addition, to soluble factors such as nitric oxide, cytokines and antibodies. QYNAD, an endogenous pentapeptide identified in the cerebrospinal fluid of patients with demyelinating disorders, has been proposed to promote axonal dysfunction by blocking sodium channels. The present study aimed at characterizing the properties of QYNAD in acutely isolated thalamic neurons in vitro. QYNAD, but not a scrambled peptide (NYDQA), blocked sodium channels in neurons by shifting the steady‐state inactivation to more negative potentials. Blocking properties followed a dose–response curve with a maximum effect at 10 µm. A fluorescently labelled QYNAD analogue with retained biological activity specifically stained thalamic neurons, positive for type II sodium channels, thus demonstrating the specificity of QYNAD binding. Our study confirms and extends previous observations describing QYNAD as a potent sodium channel‐blocking agent. These data as well as our preliminary observations in in vivo experiments in an animal model of inflammatory CNS demyelination warrant further in vivo studies in order to clarify the exact pathogenetic role of QYNAD in inflammatory neurological diseases.
Correlated stage‐ and subfield‐associated hippocampal gene expression patterns in experimental and human temporal lobe epilepsy
Authors: Becker Albert J. , Chen Jian , Zien Alexander , Sochivko Dmitry , Normann Sabine , Schramm Johannes , Elger Christian E. , Wiestler Otmar D. , Blümcke Ingmar
Published: November 2003

Epileptic activity evokes profound alterations of hippocampal organization and function. Genomic responses may reflect immediate consequences of excitatory stimulation as well as sustained molecular processes related to neuronal plasticity and structural remodeling. Using oligonucleotide microarrays with 8799 sequences, we determined subregional gene expression profiles in rats subjected to pilocarpine‐induced epilepsy (U34A arrays, Affymetrix, Santa Clara, CA, USA;P < 0.05, twofold change,n = 3 per stage). Patterns of gene expression corresponded to distinct stages of epilepsy development. The highest number of differentially expressed genes (dentate gyrus, approx. 400 genes and CA1, approx. 700 genes) was observed 3 days after status epilepticus. The majority of up‐regulated genes was associated with mechanisms of cellular stress and injury – 14 days after status epilepticus, numerous transcription factors and genes linked to cytoskeletal and synaptic reorganization were differentially expressed and, in the stage of chronic spontaneous seizures, distinct changes were observed in the transcription of genes involved in various neurotransmission pathways and between animals with low vs. high seizure frequency. A number of genes (n = 18) differentially expressed during the chronic epileptic stage showed corresponding expression patterns in hippocampal subfields of patients with pharmacoresistant temporal lobe epilepsy (n = 5 temporal lobe epilepsy patients; U133A microarrays, Affymetrix; covering 22 284 human sequences). These data provide novel insights into the molecular mechanisms of epileptogenesis and seizure‐associated cellular and structural remodeling of the hippocampus.
Pain processing within the primary somatosensory cortex in humans
Authors: Inui Koji , Wang Xiaohong , Qiu Yunhai , Nguyen Binh Thi , Ojima Shiro , Tamura Yohei , Nakata Hiroki , Wasaka Toshiaki , Tran Tuan Diep , Kakigi Ryusuke
Published: November 2003

To investigate the processing of noxious stimuli within the primary somatosensory cortex (SI), we recorded magnetoencephalography following noxious epidermal electrical stimulation (ES) and innocuous transcutaneous electrical stimulation (TS) applied to the dorsum of the left hand. TS activated two sources sequentially within SI: one in the posterior bank of the central sulcus and another in the crown of the postcentral gyrus, corresponding to Brodmann's areas 3b and 1, respectively. Activities from area 3b consisted of 20‐ and 30‐ms responses. Activities from area 1 consisted of three components peaking at 26, 36 and 49 ms. ES activated one source within SI whose location and orientation were similar to those of the TS‐activated area 1 source. Activities from this source consisted of three components peaking at 88, 98 and 109 ms, later by 60 ms than the corresponding TS responses. ES and TS subsequently activated a similar region in the upper bank of the sylvian fissure, corresponding to the secondary somatosensory cortex (SII). The onset latency of the SII activity following ES (109 ms) was later by 29 ms than that of the first SI response (80 ms). Likewise, the onset latency of SII activity following TS (52 ms) was later by 35 ms than that of area 1 of SI (17 ms). Therefore, our results showed that the processing of noxious and innocuous stimuli is similar with respect to the source locations and activation timings within SI and SII except that there were no detectable activations within area 3b following noxious stimulation.
Single olfactory sensory neurons simultaneously integrate the components of an odour mixture
Authors: Duchamp‐Viret Patricia , Duchamp André , Chaput Michel A.
Published: November 2003

Most odours are complex mixtures. However, the capacities of olfactory sensory neurons (OSNs) to process complex odour stimuli have never been explored in air‐breathing vertebrates. To face this issue, the present study compares the electrical responses of single OSNs to two odour molecules, delivered singly and mixed together, in rats in vivo. This work is the first aimed at demonstrating that single OSNs simultaneously integrate several chemical signals and which, furthermore, attempts to describe such processes for the whole concentration range over which single OSNs can work. The results stress that complex interactions occur between components in odour mixtures and that OSN responses to such mixtures are not simply predictable from the responses to their components. Three types of interactions are described. They are termed suppression, hypoadditivity and synergy, in accord with psychophysical terminology. This allows us to draw links between peripheral odour reception and central odour coding. Indeed, events occurring in single OSNs may account for the dominating or even the masking effects of odour molecules in complex mixtures, i.e. for the prevailing action of a minor component in the final qualitative perception of a mixture. We conclude that our observations with binary mixtures anticipate the complexity of processes which may rise at the level of a single OSN in physiological conditions. Following this hypothesis, a natural odour would induce a multi‐chemical integration at the level of single OSNs which may result in refining their individual odour‐coding properties, leading them to play a crucial role in the final performance of the olfactory system.
Seizures preferentially stimulate proliferation of radial glia‐like astrocytes in the adult dentate gyrus: functional and immunocytochemical analysis
Authors: Hüttmann Kerstin , Sadgrove Matthew , Wallraff Anke , Hinterkeuser Stefan , Kirchhoff Frank , Steinhäuser Christian , Gray William P.
Published: November 2003

Kainate‐induced seizures increase hippocampal neurogenesis. Glial fibrillary acidic protein‐positive astrocytes with radial processes in the dentate gyrus share many of the characteristics of radial glia and appear to act as precursor cells for adult dentate neurogenesis. Using the chemoconvulsant kainate and transgenic mice with human glial‐fibrillary acidic protein (hGFAP) promoter‐controlled enhanced green fluorescent protein (EGFP) expression, we examined the proliferation, morphology and electrophysiological properties of astrocytes in the neurogenic subgranular zone of the dentate gyrus in control animals and upon the induction of seizure‐induced cell proliferation, three days post‐kainate. EGFP‐positive cells with and without radial processes could easily be distinguished. Kainate treatment caused a significant increase in the total number of proliferating EGFP‐positive cells, particularly a tenfold elevation in the number of proliferating radial glia‐like astrocytes, and also caused a preferential shift in the dividing cell population towards cells expressing EGFP. Immunohistochemical analysis revealed a surprisingly low proportion of cells coexpressing the astroglial marker S100β and EGFP. Kainate increased the number of EGFP‐positive, S100β‐positive and S100β‐positive–EGFP‐positive astrocytes in the subgranular zone. We also report a subset of faintly EGFP‐positive cells expressing markers of early neuronal differentiation. Patch‐clamp analysis revealed the presence of three functionally different populations of EGFP‐positive cells in both kainate and control tissue. We conclude that there is an early increase in proliferating radial glia‐like astrocytes in the dentate after kainate‐induced seizures, consistent with a recruitment of precursors for seizure‐induced neurogenesis.
Sensorimotor memory and grip force control: does grip force anticipate a self‐produced weight change when drinking with a straw from a cup?
Authors: Nowak Dennis A. , Hermsdörfer Joachim
Published: November 2003

We examined whether self‐generated weight changes are anticipated by adequate grip force adjustments when repeatedly lifting an instrumented manipulandum. Subjects lifted a cup filled with 500 mL of water prior to and following drinking two portions of water with a straw without touching it. One half of the subjects drank from and lifted an uncovered cup receiving constant visual information about its filling level and the other half of the subjects drank from a covered cup without such visual feedback. During the lifts immediately following the drinking procedures, grip force scaling was erroneously programmed for the heavier weight of the preceding lift as was obvious from an inadequately high rate of grip force development. Vision had only a minor influence on the rate of grip force increase. The influence of vision on the scaling of peak grip force was more pronounced. More accurate force scaling was obtained with an increasing number of lifts performed under each weight condition, indicating an ongoing force adjustment process probably based on sensory feedback. We conclude that self‐generation of a change in the weight of an object to be lifted is not, in itself, sufficient to elicit a predictive grip force output. Rather, accurate feedback information associated with the self‐generated weight change is essential to update internal models related to the mechanical object properties. This assumption was confirmed in pilot experiments; when subjects lifted the cup after having poured water from it, they accurately scaled their fingertip force to the self‐produced weight change. Here, direct sensory feedback from the grasping fingers could signal the weight change and update internal models while pouring water from the cup. Our data support the hypothesis that the sensorimotor system planning and processing predictive fingertip force can operate independently of higher‐level cognitive and perceptual systems.
Glial cell line‐derived neurotrophic factor increases calcitonin gene‐related peptide immunoreactivity in sensory and motoneurons in vivo
Authors: Ramer Matt S. , Bradbury Elizabeth J. , Michael Gregory J. , Lever Isobel J. , McMahon Stephen B.
Published: November 2003

Calcitonin gene‐related peptide (CGRP) is expressed at high levels in roughly 50% of spinal sensory neurons and plays a role in peripheral vasodilation as well as nociceptive signalling in the spinal cord. Spinal motoneurons express low levels of CGRP; motoneuronal CGRP is thought to be involved in end‐plate plasticity and to have trophic effects on target muscle cells. As both sensory and motoneurons express receptors for glial cell line‐derived neurotrophic factor (GDNF) we sought to determine whether CGRP was regulated by GDNF. Rats were treated intrathecally for 1–3 weeks with recombinant human GDNF or nerve growth factor (NGF) (12 µg/day) and dorsal root ganglia and spinal cords were stained for CGRP. The GDNF treatment not only increased CGRP immunoreactivity in both sensory and motoneurons but also resulted in hypertrophy of both populations. By combined in situ hybridization and immunohistochemistry we found that, in the dorsal root ganglia, CGRP was up‐regulated specifically in neurons expressing GDNF but not NGF receptors following GDNF treatment. Despite the increase in CGRP in GDNF‐treated rats, there was no increase in thermal or mechanical pain sensitivity, while NGF‐treated animals showed significant decreases in pain thresholds. In motoneurons, GDNF increased the overall intensity of CGRP immunoreactivity but did not increase the number of immunopositive cells. As GDNF has been shown to promote the regeneration of both sensory and motor axons, and as CGRP appears to be involved in motoneuronal plasticity, we reason that at least some of the regenerative effects of GDNF are mediated through CGRP up‐regulation.
Specific γ‐hydroxybutyrate‐binding sites but loss of pharmacological effects of γ‐hydroxybutyrate in GABAB(1)‐deficient mice
Authors: Kaupmann Klemens , Cryan John F. , Wellendorph Petrine , Mombereau Cedric , Sansig Gilles , Klebs Klaus , Schmutz Markus , Froestl Wolfgang , Van Der Putten Herman , Mosbacher Johannes , Bräuner‐Osborne Hans , Waldmeier Peter , Bettler Bernhard
Published: November 2003

γ‐Hydroxybutyrate (GHB), a metabolite of γ‐aminobutyric acid (GABA), is proposed to function as a neurotransmitter or neuromodulator. γ‐Hydroxybutyrate and its prodrug, γ‐butyrolactone (GBL), recently received increased public attention as they emerged as popular drugs of abuse. The actions of GHB/GBL are believed to be mediated by GABAB and/or specific GHB receptors, the latter corresponding to high‐affinity [3H]GHB‐binding sites coupled to G‐proteins. To investigate the contribution of GABAB receptors to GHB actions we studied the effects of GHB in GABAB(1)−/− mice, which lack functional GABAB receptors. Autoradiography reveals a similar spatial distribution of [3H]GHB‐binding sites in brains of GABAB(1)−/− and wild‐type mice. The maximal number of binding sites and the KD values for the putative GHB antagonist [3H]6,7,8,9‐tetrahydro‐5‐hydroxy‐5H‐benzocyclohept‐6‐ylidene acetic acid (NCS‐382) appear unchanged in GABAB(1)−/− compared with wild‐type mice, demonstrating that GHB‐ are distinct from GABAB‐binding sites. In the presence of the GABAB receptor positive modulator 2,6‐di‐tert‐butyl‐4‐(3‐hydroxy‐2,2‐dimethyl‐propyl)‐phenol GHB induced functional GTPγ[35S] responses in brain membrane preparations from wild‐type but not GABAB(1)−/− mice. The GTPγ[35S] responses in wild‐type mice were blocked by the GABAB antagonist [3‐[[1‐(S)‐(3,4dichlorophenyl)ethyl]amino]‐2‐(S)‐hydroxy‐propyl]‐cyclohexylmethyl phosphinic acid hydrochloride (CGP54626) but not by NCS‐382. Altogether, these findings suggest that the GHB‐induced GTPγ[35S] responses are mediated by GABAB receptors. Following GHB or GBL application, GABAB(1)−/− mice showed neither the hypolocomotion, hypothermia, increase in striatal dopamine synthesis nor electroencephalogram delta‐wave induction seen in wild‐type mice. It, therefore, appears that all studied GHB effects are GABAB receptor dependent. The molecular nature and the signalling properties of the specific [3H]GHB‐binding sites remain elusive.
Inhibitory effect of mouse neocortex layer I on the underlying cellular network
Authors: Shlosberg Dan , Patrick Saundra L. , Buskila Yossi , Amitai Yael
Published: November 2003

The mammalian cortical layer I is a convergence site for axons of sub‐ and intracortical origin, and the apical dendritic tufts of pyramidal neurons. A prominent feature of layer I is an extensive plexus of inhibitory axons, which originate from stellate cells in all cortical laminae. The role of this inhibitory projection in the activity of cortical networks has yet to be determined. We investigated the degree to which inhibitory inputs within layer I affect the activity of the underlying cellular network. Field potentials (FPs) were recorded in layer II/III. Focal application of the GABAA blocker picrotoxin in layer I above the recording pipette or the removal of layer I resulted in larger FP amplitudes for stimulations at control‐equal intensities. When inhibition was partially blocked, the removal of layer I caused a significant reduction in the threshold stimulus intensity required for generating epileptiform events, and a rise in the propagation velocity of these events. Immunocytochemistry for chemical markers of interneurons proved that the inhibitory input to layer I is predominantly somatostatin immunoreactive (SM‐ir), such that layer I contains approximately one‐third of all SM‐ir axons in the cortex. Calretinin‐immunoreactive axons were also present in layer I at a lower density. We conclude that the impact of layer I on the cortical cellular network includes a significant inhibitory component. This inhibition confers a moderate restraining influence, and its removal increases the excitability of cortical circuits, but not sufficiently to induce epileptic phenomena.
Tracking mouse visual pathways with WGA transgene
Authors: Hanno Yoko , Nakahira Masakiyo , Jishage Kou‐ichi , Noda Tetsuo , Yoshihara Yoshihiro
Published: November 2003

By use of wheat germ agglutinin (WGA) cDNA as a transgene, we have succeeded in generating a transgenic mouse line in which the visual pathways can be accurately and reproducibly visualized. The WGA transgene was expressed in the retinal rod bipolar cells under the control of mouse L7 promoter. The transgene product, WGA protein, was transferred from the bipolar cells to the amacrine cells and the ganglion cells across synapses in the retinal neural circuitry and further conveyed along the optic nerve to the visual centers such as the suprachiasmatic nucleus, the lateral geniculate nucleus, the pretectal nucleus and the superior colliculus. By crossing the WGA‐expressing transgenic mice with the retinal degeneration mutant mice, we analyzed change in the visual pathways by monitoring WGA immunoreactivity and found that the disorganization process of the visual pathways was relatively slow in spite of the rapid degeneration of the photoreceptor cells. Thus, this transgenic mouse line would provide a useful tool for analyzing phenotypic changes in the visual pathways of various mutant mice.
Hippocampal gene expression profiles in passive avoidance conditioning
Authors: D'Agata Velia , Cavallaro Sebastiano
Published: November 2003

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long‐term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory, the collective behaviours of the genes is mostly unknown. We have used genome‐scale screening by microarray analysis to examine the hippocampal expression of more than 1200 genes relevant to neurobiology during instrumental conditioning. Training rats on a step‐through passive avoidance task led to unique patterns of gene expression when compared to naïve animals or those exposed to the conditioned or the unconditioned stimulus alone. The newly identified genes afford a quantitative view of the changes which accompany conditioning at the genomic level and enable deeper insights into the molecular basis underlying learning and memory.
Ear of stimulation determines schizophrenia‐normal brain activity differences in an auditory paired‐stimuli paradigm
Authors: Clementz Brett A. , Dzau Jacqueline R. , Blumenfeld Laura D. , Matthews Scott , Kissler Johanna
Published: November 2003

Schizophrenia patients have abnormalities of auditory information processing, theoretically associated with dysfunction of neuronal excitation. Auditory paired‐stimuli (S1–S2) paradigms are used to evaluate the nature of these abnormalities. It is unknown whether patients' abnormalities during S1–S2 paradigms are attributable to specific hemispheric differences in cortical processing. The present studies used whole head magnetoencephalography and monaural or binaural versions of the paired‐stimuli paradigm to evaluate auditory processing among 38 schizophrenia and 38 normal subjects. The strengths of auditory‐evoked brain responses over time were quantified using distributed source reconstructions with L2 minimum norm constraint and realistic head models. For left ear stimuli, schizophrenia and normal groups did not differ on either left or right hemisphere activity over auditory cortex. For right ear and binaural stimuli, schizophrenia patients had less activity over left auditory cortex from 80 to 120 ms post‐stimulus but did not differ from normal on activity over right auditory cortex. Additionally, in response to monaural stimulation, schizophrenia patients had significantly less activity than normal over right temporal parietal junction from 60 to 120 ms post‐stimulus. These data are consistent with four propositions about schizophrenia: (i) right auditory cortex is functioning normally; (ii) processing of simple auditory stimuli is abnormal in left auditory cortex, probably specifically in supra‐granular layers; (iii) auditory localization abilities are deficient; and (iv) auditory cortex abnormalities are not a function of deficient hemispheric communication because they are evident early in processing as long as stimuli are delivered directly to left hemisphere.
Oestrogen regulates sympathetic neurite outgrowth by modulating brain derived neurotrophic factor synthesis and release by the rodent uterus
Authors: Krizsan‐Agbas D. , Pedchenko T. , Hasan W. , Smith P. G.
Published: November 2003

Sympathetic innervation of the adult rodent uterus undergoes cyclic remodelling. Terminal sympathetic axons degenerate when oestrogen levels rise and regenerate when oestrogen levels decline. This study examined the role of neurotrophins in oestrogen‐mediated uterine sympathetic nerve remodelling. Oestrogen injection of ovariectomized female rats did not affect uterine NT‐3 levels 24 h postinjection, and increased endometrial NGF protein, indicating that reduced NGF or NT‐3 is not responsible for the oestrogen‐induced denervation. Oestrogen also raised BDNF protein and mRNA in myometrium and endometrium. To assess whether increased BDNF affects uterine receptivity to sympathetic outgrowth, sympathetic ganglion explants were co‐cultured with myometrium. Myometrium from ovariectomized rats induced neuritogenesis in oestrogen‐free conditions, and this was abolished when BDNF was added to the medium. Neuritogenesis induced by ovariectomized myometrium was suppressed by oestrogen, and restored by a BDNF function‐blocking antibody. To determine if target BDNF synthesis is required for oestrogen to suppress sympathetic neurite outgrowth, uteri from wild‐type mice and mice homozygous or heterozygous for recombinant mutations of the BDNF gene were cultured with rat sympathetic ganglia. Neuritogenesis induced by wild‐type uteri was diminished by oestrogen. Neurite formation in the presence of homozygous BDNF mutant uteri was not affected by oestrogen, but was lower than that of wild‐type mice. Uteri from mice heterozygous for the BDNF mutation, who have reduced BDNF synthesis, showed normal neuritogenic properties, but were not affected by oestrogen. These findings suggest that oestrogen alters neuritogenic properties of the rodent uterus by regulating BDNF synthesis, which inhibits sympathetic neurite outgrowth.
Enrichment enhances the expression of sgk, a glucocorticoid‐induced gene, and facilitates spatial learning through glutamate AMPA receptor mediation
Authors: Lee Eminy H. Y. , Hsu W. L. , Ma Y. L. , Lee P. J. , Chao C. C.
Published: November 2003

We have previously demonstrated that the serum and glucocorticoid‐inducible kinase (sgk) gene plays a causal role in facilitating memory performance in rats. Environment enrichment is known to facilitate spatial learning. We therefore examined the effect of enrichment on sgk expression. We also examined the role of sgk in spatial and nonspatial learning and the regulation of sgk expression by activation of different glutamate receptors. Both real‐time polymerase chain reaction and Western blot analyses revealed that enrichment training preferentially increased sgk mRNA and protein levels in the hippocampus. Transfection of sgk mutant DNA to the hippocampal CA1 area markedly impaired spatial learning, fear‐conditioning learning and novel object‐recognition learning in rats, but enrichment training effectively reversed these learning deficits. Meanwhile, S422A mutant DNA transfection prevented enrichment‐induced spatial learning facilitation. In studying glutamate receptor regulation of sgk expression, we found that blockade of N‐methyl‐d‐aspartate (NMDA) receptors in general, and the NR2B subunit in particular both effectively blocked enrichment‐induced spatial learning facilitation, but they did not block enrichment‐induced sgk expression. Upon various glutamate agonist infusions, only α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) increased sgk mRNA levels significantly in the hippocampus. Furthermore, blockade of AMPA receptors effectively blocked both enrichment‐induced spatial learning facilitation and sgk expression. These results indicate that there is a dissociation between NMDA receptor activation and sgk expression. Enrichment enhanced spatial learning through both NMDA and AMPA receptor activation, whereas enrichment‐induced sgk expression is specifically mediated through AMPA receptors. These results suggest that sgk could serve as a novel molecular mechanism, in addition to the NMDA receptor NR2B, underlying enrichment‐induced learning facilitation.
VEGF is necessary for exercise‐induced adult hippocampal neurogenesis
Authors: Fabel Klaus , Fabel Konstanze , Tam Betty , Kaufer Daniela , Baiker Armin , Simmons Natalie , Kuo Calvin J. , Palmer Theo D.
Published: November 2003

Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic–pituitary–adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running‐induced neurogenesis but had no detectable effect on baseline neurogenesis in non‐running animals. These data suggest that VEGF is an important element of a ‘somatic regulator’ of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis.
Partitioned Nature, Privileged Knowledge: Community‐based Conservation in Tanzania
Authors: Goldman Mara
Published: November 2003

Community Based Conservation (CBC) has become the catch–all solution to the social and ecological problems plaguing traditional top–down, protectionist conservation approaches. CBC has been particularly popular throughout Africa as a way to gain local support for wildlife conservation measures that have previously excluded local people and their development needs. This article shows that, despite the rhetoric of devolution and participation associated with new CBC models, conservation planning in Tanzania remains a top–down endeavour, with communities and their specialized socio–ecological knowledge delegated to the margins. In addition to the difficulties associated with the transfer of power from state to community hands, CBC also poses complex challenges to the culture or institution of conservation. Using the example of the Tarangire–Manyara ecosystem, the author shows how local knowledge and the complexities of ecological processes challenge the conventional zone–based conservation models, and argues that the insights of local Maasai knowledge claims could better reflect the ecological and social goals of the new CBC rhetoric.
Nationalizing Space: Cosmetic Federalism and the Politics of Development in Northeast India
Authors: Baruah Sanjib
Published: November 2003

Until recently Arunachal Pradesh on India's Northeast frontier was relatively insulated from the processes associated with development. State institutions were barely present during the colonial era. In 1962, however, India and China fought a border war in this area: this war, along with signs of unrest among indigenous peoples in the neighbourhood, exposed India's vulnerabilities in the region. Since then, nationalizing this frontier space by extending the institutions of the state all the way into the international border region has become the thrust of Indian policy. The region's governmental infrastructure was fundamentally redesigned to put in place what can only be described as a cosmetic federal regional order with a number of small states dependent on the central government's largess and subject to monitoring by India's Home Ministry. The new regional order has put Arunachal firmly on a developmentalist track, which has enabled India to meet its national security goals, but at a significant cost to the region.
Employment Effects of Minimum Wages: Evidence from a Quasi‐Experiment
Authors: Leigh Andrew
Published: November 2003

To estimate the impact of raising the minimum wage on employment, this article uses a natural experiment, arising from six increases in the Western Australian statutory minimum wage during the period 1994–2001. Relative to the rest of Australia, the employment to population ratio in Western Australia fell following each of the six rises, twice by a statistically significant margin. Aggregating the increases, the elasticity of labour demand with respect to the Western Australian statutory minimum wage is found to be −0.13.
The Labour Market and Inequality
Authors: Keating Michael
Published: November 2003

Newspoll reported in 2000 that by a margin of 70 to 28 per cent, Australians would prefer the gap between rich and poor to get smaller rather than have the nation's overall wealth grow as quickly as possible. This article examines the reasons for the increase in the dispersion of earnings, and changes in unemployment and workforce participation, which are central to this concern about inequality. The major finding is that the widening dispersion of earnings and changes in labour force status are principally due to changes in the structure of labour demand in favour of more skilled jobs. The article then considers what this changing job mix implies for policy directed to maintaining income inequality.