bluuebunny/crossref_metadata_2025 huggingface dataset:
Infusion of Alpha-2-Adrenergic Agents into the Paraventricular and Arcuate Nuclei of the Hypothalamus in the Siberian Hamster: Opposing Effects on Basal Prolactin
Authors: Dodge James C. , Badura Lori L.
Published: April 2003

Although the α2-adrenergic receptor subtype has been shown to have a significant influence on circulating levels of prolactin (PRL), its exact role remains unclear. A multitude of studies have demonstrated that blockade of the α2-receptor can either elevate or decrease circulating levels of PRL. α2-Receptor-mediated control of both stimulatory and inhibitory arms of the PRL regulatory system may explain this discrepancy. Activation of the α2-receptor has been shown to inhibit the activity of its target cell, and therefore antagonism of the α2-receptor within a stimulatory component (e.g., paraventricular nucleus (PVN) of the hypothalamus) would theoretically have the opposite effect that it would have within an inhibitory component (arcuate nucleus of the hypothalamus). Thus, the purpose of this study was to investigate the functional role of the α2-adrenergic receptor in modulating circulating levels of PRL both at the level of the PVN and arcuate using reverse microdialysis of α2-adrenergic agents coupled with serial blood sampling in the male Siberian hamster. Male hamsters were fitted with a jugular cannula for serial blood sampling, and an indwelling microdialysis probe for intrahypothalamic drug administration between 08:00 and 10:00 h. Blood samples were collected every hour for 5 h (12:00–17:00 h). During the third sampling period, atipamezole (α2-antagonist) or medetomidine (α2-agonist) at one of three doses were infused into the PVN or the arcuate to assess effects on basal PRL. At the level of the PVN, infusion of atipamezole initiated an increase in basal PRL in a dose-dependent fashion, whereas infusion of medetomidine induced a significant decline in basal PRL in a dose-dependent fashion. In the arcuate, only the highest dose of atipamezole had an effect on PRL, and this was in the opposite direction from that seen in the PVN. Infusion of medetomidine did not have a significant effect on basal PRL levels; however, a trend toward a significant elevation was observed for the highest dose. These results suggest that the α2-receptor subtype may have opposite effects on circulating levels of PRL within the PVN and arcuate regions, and may explain why antagonism of the α2-receptor has been shown to initiate both surges and declines in basal levels of PRL.
Estradiol Stimulates Gene Expression of Norepinephrine Biosynthetic Enzymes in Rat Locus coeruleus
Authors: Serova Lidia , Rivkin Mark , Nakashima Akira , Sabban Esther L.
Published: April 2003

Gender-specific differences in susceptibility to a number of disorders related to catecholaminergic systems, including depression and hypertension, have been postulated to be mediated, at least in part, by estrogens. In this study, we examined if estrogens may regulate gene expression of norepinephrine biosynthetic enzymes. Administration of five injections of 15 or 40 µg/kg estradiol benzoate to ovariectomized (OVX) female rats elicited a dose-dependent elevation in mRNA levels of tyrosine hydroxylase (TH) in locus coeruleus, to as great as 3-fold over control. Dopamine β-hydroxylase (DBH) mRNA levels were also similarly increased. To examine the mechanism, PC12 cells were cotransfected with luciferase reporter constructs under control of DBH or TH promoters [pDBH/Luc(–2,236/+21) or pTH/Luc(–272/+27 or –773/+27)] with an expression vector for estradiol receptor α. The cells were treated with 17β-estradiol (E2) for 12–36 h. E2 triggered a several fold increase in luciferase activity under control of the DBH promoter in a dose-dependent fashion. Omission of estrogen receptor α or addition of the estrogen receptor antagonist ICI 182,780 prevented the DBH promoter-driven increase in luciferase. When E2 was given with 0.2 mM CPT-cAMP, reporter activity with pDBH/Luc(–2,236/+21) was increased greater than with either treatment alone. In contrast, addition of E2 to cells transfected with pTH/Luc(–272/+27) elicited no change in basal luciferase activity nor in the response to 0.2 mM CPT-cAMP. These findings are the first to reveal that estrogen can stimulate DBH gene expression. Differing mechanisms may underlie the regulation of TH and DBH gene expression by estrogens.
Clinical Significance of Vascular Endothelial Growth Factor C Expression and Angiogenesis at the Deepest Invasive Site of Advanced Colorectal Carcinoma
Authors: Furudoi Akira , Tanaka Shinji , Haruma Ken , Kitadai Yasuhiko , Yoshihara Masaharu , Chayama Kazuaki , Shimamoto Fumio
Published: April 2003

Aim: Vascular endothelial growth factor C (VEGF-C) is known to be associated with the development of the lymphatic vascular system. The aim of this study was to elucidate the clinical significance of VEGF-C expression and microvessel density (MVD) at the deepest invasive site in advanced colorectal carcinoma (CRC). Methods: 152 patients who had undergone surgical resection for advanced CRC entered this study. VEGF-C expression was examined immunohistochemically with anti-VEGF-C polyclonal antibody C-20. Tumor MVD was determined immunohistochemically with anti-CD34 antibody. VEGF-C expression was defined as positive if distinct staining of the cytoplasm was observed in at least 10% of tumor cells at the deepest invasive site, central portion and superficial part of the tumor. MVD was estimated by averaging the count of three ×400 fields in the most vascular area at the deepest invasive site. Results: VEGF-C expression was detected in 71 of 152 lesions (46.7%) at the deepest invasive site. VEGF-C expression correlated significantly with poorer histologic grade, depth of invasion, lymphatic invasion, lymph node metastasis, venous invasion, liver metastasis and Duke’s stage. At the central portion and superficial part, there were no significant differences between VEGF-C expression and clinicopathological findings. VEGF-C expression at the deepest invasive site also correlated significantly with MVD. In cases with curative surgery, patients with VEGF-C expression at the deepest invasive site had a significantly poorer prognosis than those without VEGF-C expression. Furthermore, prognosis for patients with both VEGF-C expression and high MVD at the deepest invasive site was significantly poorer than that of patients without VEGF-C expression and with low MVD. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF-C expression were significant risk factors. Conclusions: VEGF-C expression at the deepest site of tumor invasion can be a useful predictor of poor prognosis in advanced CRC and show a close relation to angiogenesis.
Inhibition of Lens Epithelial Cell Migration by an Acrylic Intraocular Lens in vitro
Authors: Kurosaka Daijiro , Obasawa Minoru , Kurosaka Hiroyo , Nakamura Kunihiko
Published: April 2003

We developed a new in vitro system to evaluate the effect of intraocular lenses (IOLs) on the migration of lens epithelial cells (LECs) and determined how acrylic and other IOLs influence LEC migration using this model. In an in vitro system, porcine LECs were cultured in a cell culture chamber insert, containing a collagen membrane, for 10 days with no IOL or with various types of IOLs. Migration of LECs beneath each IOL optic was observed with an inverted-phase microscope. The cell-free areas under the IOL optic, where the LECs had not migrated, were measured. Without IOL, LECs completely covered the collagen membrane within 5 days after plating (5.0 ± 0.0 days). Complete coverage was slowed by a silicone IOL (6.7 ± 1.2 days, p = 0.0305). LECs cultured with acrylic or with round- or sharp-edged polymethylmethacrylate (PMMA) IOLs did not completely cover the area. Ten days after initiating cultures, the cell-free areas under IOLs with sharp edges (acrylic, 41.1 ± 8.0%; sharp-edged PMMA, 60.9 ± 39.0%) were significantly larger than under IOLs with round edges (silicone, 0.0 ± 0.0%; round-edged PMMA, 1.5 ± 1.2%). A sharp edge may act as a barrier to LEC migration. Moreover, LEC migration under the acrylic IOL slowed after the LECs had crossed the barrier of the optic edge, perhaps due to acrylic adhesive properties. Only a few LECs reached the collagen membrane beneath the central 3 mm of the acrylic IOL. This new in vitro model was useful in evaluating the effect of various IOLs on LEC migration. Acrylic IOLs inhibited LEC migration by not only a sharp edge but also other factors, such as adhesive properties.
Mucin-Like Glycoprotein Associated with Photoreceptor Cells in the Postnatal Developing Rat Retina
Authors: Uehara Fumiyuki , Ohba Norio , Ozawa Masayuki
Published: April 2003

Purpose: To examine the developmental expression of mucin-like glycoprotein associated with photoreceptor cells (MLGAPC), and to confirm that MLGAPC with a relative mass of 120 and 135 kD correspond to the cone and rod types, respectively. Methods: We isolated the cDNA of the core protein of rat MLGAPC, prepared an anti-rat MLGAPC core protein antibody and then examined the expression of the MLGAPC core protein in postnatal developing rat retinas by means of Western blotting and immunohistochemistry. Results: On postnatal early days when cone photoreceptor cells were thought to be developing, MLGAPC was detected as a single band of 120 kD and was found to be positive in the apical portion of the neuroblastic layer. After postnatal day 7, when rod photoreceptor cells were developing, MLGAPC was detected as a minor band of 120 kD and an additional major band of 135 kD and was present throughout the differentiated photoreceptor and outer plexiform layers. Conclusions: The present findings revealed the developmental expression of MLGAPC and confirmed that MLGAPC of 120 and of 135 kD correspond to the cone and rod types, respectively. This demonstration is advantageous for studying the physiological roles of MLGAPC in the photoreceptor and outer plexiform layers, since the cone- and rod-associated glycoproteins should be investigated separately.
Multifocal Electroretinogram with a Multiflash Stimulation Technique in Open-Angle Glaucoma
Authors: Palmowski A.M. , Allgayer R. , Heinemann-Vernaleken B. , Ruprecht K.W.
Published: April 2003

Purpose: To analyze a multiflash multifocal electroretinogram in 20 patients with open-angle glaucoma (OAG). Methods: The stimulation sequence consisted of a binary m-sequence (Lmax 200 cd/m2, Lmin <1 cd/m2). Each m-sequence stimulus was followed by three global flashes (luminance: 400 cd/m2) at an interval of 26 ms. Results: The presence of a response to the three global flashes indicated an adaptive effect of the response to the preceding m-sequence stimulus. In the nasal retinal response average the relative amplitude contribution of the response to the second global flash in relation to the other two global flash responses was outside the range of normal (10th–90th percentile) in 10 of 20 OAG patients. Conclusions: The changes in the relative contribution of the response to the second global flash seem indicative of impaired adaptive effects presumably due to inner retinal damage.
Long-Term Results of Functional Hemispherectomy for Intractable Seizures
Authors: Tan Qifu , Sun Kangjian , Pan Yunxi , Sun Kehua , Hua Changchun , Qiao Liang
Published: April 2003

Objective: From May 1989 to April 1997, functional hemispherectomy was performed in 8 cases of intractable seizures. We retrospectively analyzed our experience to evaluate the seizure control and complications of this surgical technique. Methods: Following Dr. Rasmussen’s model of functional hemispherectomy or performing a modification of this operation, we removed the sensorimotor cortex and temporal lobe associated with disconnection of the remaining portions of the frontal lobe and parieto-occipital lobe. Results: All the patients were followed up for 3–11 years (mean 6.7 years). Satisfactory seizure control was obtained in all the cases. Life quality improved and patients worked or studied well after the operations. No cases of superficial cerebral hemosiderosis were found. Conclusion: Modified functional hemispherectomy may allow the patients to lead more independent lives by leading to a cessation or reduced frequency of seizures.
Multimodality Program Involving Stereotactic Surgery in Brain Tumor Management
Authors: Gildenberg Philip L. , Woo Shiao Y.
Published: April 2003

Stereotactic and image guided surgery is becoming increasingly important in the management of brain tumors. Although there are several stereotactic modalities that have been reported to be of value, it is the combination of techniques in a multimodality approach that seems to show the most promise. Both frame-based and frameless guidance may facilitate glioma resection, allowing the optimal amount of resection while permitting avoidance of surrounding eloquent areas. Not only does this optimize resection, but leaving a minimal amount of gross tumor may provide a better bed for intracavitary chemotherapy. Deep tumors may be localized and approached through a small channel. Surgical exposure may be minimized to protect uninvolved areas of the brain. There is increasing evidence that patients operated with imaging guidance have a more benign course and more rapid discharge, perhaps with a lower incidence of adverse neurological sequelae. Stereotactic conformal radiotherapy allows a higher tumor dose while sparing uninvolved brain from radiation more efficiently than conventional radiation. Residual tumor may be treated with a boost of stereotactic radiotherapy. Stereotactic instillation of radioisotope may be used to treat cystic tumors. Stereotactic insertion of cannulae or radioisotope seeds permits efficient brachytherapy. Stereotactic surgery has moved beyond a subspeciality, so that every neurosurgeon might benefit from using stereotactic techniques in brain tumor management.
The Role of an Androgen Receptor Polymorphism in the Clinical Outcome of Patients with Metastatic Prostate Cancer
Authors: Cude Kelly J. , Montgomery Jeffrey S. , Price Douglas K. , Dixon Shannon C. , Kincaid Randall L. , Kovacs Karl F. , Venzon David J. , Liewehr David J. , Johnson Margaret E. , Reed Eddie , Figg William D.
Published: April 2003

The androgen receptor plays a major role in the development and function of normal and malignant prostate cells. Due to the relationship of the androgen receptor and prostatic growth, it has been proposed that polymorphisms within the androgen receptor may play a role in an individual’s susceptibility to developing prostate cancer. An inverse relationship has been established between a highly polymorphic trinucleotide repeat located in the first exon of the androgen receptor and the transactivaton function of the receptor. Serum samples were collected from 131 patients with histologically confirmed adenocarcinoma of the prostate, DNA was isolated, and the polymorphic CAG repeat was amplified by PCR and sequenced. The CAG repeat lengths were then compared with age at diagnosis, age at time of study, baseline log10 PSA, Gleason score, time from diagnosis to initiation of hormonal therapy, time to progression after androgen ablation, and overall survival time. No correlation was found between CAG length and time to progression or overall survival time, but a significant correlation was found between Gleason score and CAG length suggesting that shorter CAG lengths may predict a higher histological grade of prostate cancer.
Acute Effects of Serotonin on Rat Bladder Contractility
Authors: Kim Hyung Jee , Lee Gilho , Kim Dong Hee , Lee Suk Jae , Yoon Duck Ki , Cho Jae Heung
Published: April 2003

Introduction: The purpose of this study is to investigate in vitro the effects of serotonin on the rat detrusor. In particular, it examines which drugs inhibit the serotonin-induced detrusor contractions. Materials and Methods: Isometric tension changes of isolated rat bladder muscle strips were recorded in an organ bath using a force transducer. Acute effects of serotonin (0.0001–0.01 mM) on resting tension were assessed. Electrical field stimulation (EFS); bethanechol (0.0001–0.01 mM); ATP (1–3 mM)- or KCl (63.5–254 mM)-induced contractions using an application in an organ bath were compared with serotonin-induced contractions. In order to examine the action mechanism of serotonin-induced stimulation, EFS-, bethanechol-, ATP- or KCl-induced contraction on serotonin treatment (0.001 mM) was assessed and serotonin (0.001–0.1 mM) was cumulatively added to the organ bath following preincubation with propranolol, ketanserin, tropisetron, propiverine, sodium nitroprusside or doxazosin. Results: The serotonin-induced response has two phases: an initial transient contraction and a prolonged tonic phase. Serotonin produced a reversible and dose-dependent contraction of the detrusor strips. Responses to bethanechol significantly increased with a concentration of 0.001 mM serotonin (p < 0.05). There was no effect on the responses to ATP, KCl, or EFS on 0.001 mM serotonin. The 5-HT2 receptor is mainly responsible for serotonin-induced contractions of the detrusor (p < 0.05), while the 5-HT1 receptor is partially responsible. Doxazosin and propiverine each significantly suppressed the response to serotonin, while sodium nitroprusside and tropisetron each had no effect (p < 0.05). Conclusions: Because the 5-HT2 antagonist blocked the effect of serotonin-induced bladder contractions and the stimulation of the adrenoreceptors, the 5-HT2 antagonist seems to improve lower urinary tract symptoms.
Are Clinical Characteristics of Familial Benign Prostatic Hyperplasia Different than in Sporadic Cases?
Authors: Tan M. Özgür , Diker Yusuf , Uygur M. Cemil , Karabıyık İlhan , Erol Demokan
Published: April 2003

Objective: Familial benign prostatic hyperplasia (BPH) is a recently popularised entity with yet uncertain clinical and pathological features. In the present study we investigated whether there was any difference between clinical characteristics of familial and sporadic BPH in a series of 148 surgically treated BPH patients. Materials and Methods: A retrospective analysis was performed in 148 patients subjected to transvesical or transurethral prostatectomy to determine the clinical features of familial BPH. Patients were categorised as having familial BPH when 3 or more (including the patient) first-degree family members gave a history of BPH. Accordingly 23 cases who fit this criterion were accepted as having familial BPH and the rest of the cases were taken as the control group. The two groups were compared with respect to age, International Prostate Symptom Score (IPSS), quality of life score, prostate specific antigen (PSA), maximum urinary flow rate and the weight of the surgical prostate specimen. Results: The mean age, IPSS, quality of life score, total PSA, maximum urinary flow rate and the weight of the surgical prostate specimen were found as 65.13 ± 5.51 years, 23.13 ± 4.82, 4.78 ± 0.95, 6.0 ± 4.1 ng/ml, 6.9 ± 2.7 ml/s and 62.96 ± 38.76 g, respectively, in the familial BPH group whereas the same parameters were measured as 68.13 ± 7.68 years, 24.74 ± 3.73, 4.52 ± 0.85, 5.93 ± 4.75 ng/ml, 4.6 ± 1.71 ml/s and 70.87 ± 53.21 g, respectively. No significant difference was present between familial and sporadic BPH cases in any of the studied parameters. Conclusion: The clinical features of familial BPH did not differ significantly from those of sporadic BPH.
Comparative Study of Peptides Isolated from Class I Antigen Groove of Urological Specimens
Authors: Torabi-Pour N. , Nouri A.M.E. , Saffie R. , Oliver R.T.D.
Published: April 2003

Backgound: The major histocompatibility (MHC) class I antigens act as associative molecules for interaction amongst immuno-competent cells. The grooves of class I antigens are normally loaded with self peptides of between 8 and 11 amino acids. However, when the cells transform to malignant state they may carry peptide(s) of non-self origin within these grooves. Using immuno-bead purification followed by high-performance liquid chromatography (HPLC), this study attempted to isolate peptides from class I antigens of various biological specimens Results: The combination of immuno-bead purification (BP) and HPLC was reliable for peptide isolation. Class I antigens and associated peptides could be isolated from normal peripheral blood leukocyte (PBL). Under the same conditions, the PBL yielded almost twice as much peptide as that of tumour cell lines. The HPLC profile of peptides (range of 8–10 amino acid residues) isolated from a bladder and a cervical tumour cell line showed unique features. In the case of the bladder line there were at least 22 peptides. In addition, the class I-associated peptides could also be isolated from kidney tumour fragments of three individuals. In each the isolated peptides showed a unique HPLC peak profile with some similarities as well as differences. Conclusions: These data indicated a variation in the nature of peptides isolated from different specimens. The approach showed the feasibility of preparing peptide(s) from a relatively small number of cells. The data also showed that peptide isolation could also be carried out from tumour tissue biopsies paving the way for the future of peptide vaccination in cancer patients following the identification of putative tumour-specific replicate(s).
A Study of Menses-Related Changes to the Larynx in Singers with Voice Abuse
Authors: Chernobelsky S.I.
Published: April 2003

Fifteen vocally abusive and 15 healthy female classical singers were examined before and outside menses by means of laryngoscopy, laryngostroboscopy and electroglottography. Investigation before menses revealed more extensive alteration of the larynx in vocally abusive singers than in healthy ones. Subsequent investigation, after the inappropriate use of their voice had been eliminated, indicated decreased changes to the larynx. It was concluded that premenstrual hyperchanges were a result of combined abuse- and menses-related influence on the larynx, and that laryngeal examination before menstruation could be a useful test for the presence of physiologically correct singing.
Changes during Long-Term Management of Locked-In Syndrome: A Case Report
Authors: Pickl Gonda B.
Published: April 2003

This paper describes various approaches of treatment to a male client suffering from the locked-in syndrome following closed head injury. During the course of therapy, which started more than 5 years after onset and lasted for as much as 11 years, the client progressed from the so-called classical to the incomplete locked-in state. The different approaches as well as the outcomes are presented in detail, followed by a discussion about interdisciplinary issues, duration of treatment and the impact of a patient’s personality on the course and goals of the treatment as well as on the mode of communication.
The Relationship between End Tidal Carbon Dioxide and Arterial Carbon Dioxide during Controlled Hypotensive Anaesthesia
Authors: Ali Syed Shujat , Dubikaitis Alexander , Al Qattan Abdul Raheem
Published: April 2003

Objectives: To prospectively assess the magnitude of changes in the arterial-to-end tidal carbon dioxide gradient [P(a-ET)CO2] as well as in the ratio of physiological dead space to tidal volume (Vdphys/Vt) during controlled hypotensive anaesthesia, and to evaluate whether or not ventilatory requirements remain unaltered during this procedure. Subjects and Methods: Twelve adult patients with American Society of Anesthesiologists’ physical status I and II undergoing middle ear surgery were selected. A standard anaesthetic procedure was followed for all cases, using thiopental sodium, succinylcholine, fentanyl, atracurium and 60% N2O in 40% oxygen supplemented with isoflurane. Mean arterial blood pressure (MAP) was reduced to 60 ± 5 mm Hg in all patients using a sodium nitroprusside infusion. The end tidal (ET) CO2, PaCO2, MAP, peak airway pressure, plateau pressure and expiratory minute volume were recorded during a period of normal arterial blood pressure (time 1) and during hypotension (time 2). Results: A significant decrease in PaCO2 (7%) and ETCO2 (17%) from time 1 to time 2 (p < 0.01) was noted, as was a significant increase in P(a-ET)CO2 (48%) and in the Vdphys/Vt ratio (41.17%) (p < 0.01) during the same period. Conclusion: The decrease in ETCO2 does not reflect the changes in PaCO2. The larger decrease in ETCO2 is mainly due to the increase in the Vdphys/Vt ratio. During anaesthesia, once normocapnia is achieved with normal arterial blood pressure, there is hardly any need to change the ventilation after initiation of controlled hypotension.
Hemoglobin Electrophoresis and Hemoglobinopathies in Kuwait
Authors: Marouf R. , D’souza T.M. , Adekile A.D.
Published: April 2003

Objectives: To analyze the results of hemoglobin electrophoresis (HE) in the routine laboratory of a tertiary hospital in Kuwait and to review the common types of hemoglobinopathies prevalent in the country. Methods: This was a prospective study of HE performed on 2,386 samples in Mubarak Al-Kabeer Hospital, which serves more than 30% of the population of Kuwait, from June 1997 to May 1998. Results: Of the 2,386 HE tests, only 561 (23.5%) had abnormal hemoglobin genotypes. The most commonly identified hemoglobinopathies were β-thalassemia minor (14%), sickle cell trait (6%), sickle cell anemia (0.9%), Sβ⁰thal (0.8%) and Sβ+thal (0.8%). Two rare hemoglobin variants, Hb DPunjab and Hb E, were encountered. Conclusion: HE yielded only 23.5% abnormal results, thus indicating the need to streamline requests for the test. The test should be limited to patients with hematological and clinical features suggestive of hemoglobinopathies or to individuals with a positive family history.
The Cyclic Alternating Pattern Decreases as a Consequence of Total Sleep Deprivation and Correlates with EEG Arousals
Authors: De Gennaro Luigi , Ferrara Michele , Spadini Valentina , Curcio Giuseppe , Cristiani Riccardo , Bertini Mario
Published: April 2003

The aim of this study was to assess the sensitivity of the cyclic alternating pattern (CAP) parameters to the increased need for recuperation that follows one night of sleep deprivation. Nine normal male subjects were recorded for 3 nights [adaptation, baseline (BSL) and recovery (REC)]. BSL and REC nights were separated by a 40-hour sleep deprivation. Recovery after sleep deprivation was characterized by a decrease in stage 1, stage 2 and sleep latency, and an increase in slow wave sleep (SWS) and the sleep efficiency index, while rapid eye movement (REM) and non-REM (NREM) time did not differ as compared to BSL sleep. CAP parameters were significantly affected by sleep deprivation, and the main results were the following: (1) the CAP rate (time spent in CAP phases/NREM time) significantly decreased from 38.85 to 31.47%, and (2) within phase A subtypes, there was a significant decrease in A3 subtypes (from 38.11 to 19.57). Furthermore, the number of arousals scored according to American Sleep Disorders Association rules strongly correlated with A3 subtypes during both the BSL (r = 0.79) and REC nights (r = 0.95). These results indicate that recuperative processes after sleep deprivation are also associated with a lesser arousal instability as defined by the reduction of the CAP rate, which is strongly correlated with EEG arousals.
Changes in Brain Complexity during Valproate Treatment in Patients with Partial Epilepsy
Authors: Kim Jae-Moon , Jung Ki-Young , Choi Chung-Mi
Published: April 2003

Objective: The effect of valproate (VPA) on human electroencephalography (EEG) was studied using nonlinear dynamics analysis to investigate changes in brain complexity. Methods: We propose a spatial linear mode complexity (SLMC) measure to quantify the complexity of spatial linear modes in multichannel EEGs. Nine patients with complex partial seizures who had not previously been exposed to antiepileptic drugs (AEDs) were included in this study. Eighteen-channel EEG data were collected before and after VPA therapy. Changes in brain complexity were examined using the proposed SLMC measure, which reflects brain complexity. Fifteen normal, healthy subjects were included as a control group. To compare SLMC with spectral analysis, we performed spectral analysis within the conventional frequency bands. Results: Spectral analysis showed that the patient group had decreased relative power of the alpha2 band in the T7, P3, O1 and C4 leads before VPA treatment and an increased relative theta power in the O1 lead relative to the control group. However, no significant changes occurred in any lead at any frequency band after VPA treatment. The mean SLMC value was significantly lower in the patient group before treatment than in the control group (p = 0.026). The average SLMC value for all patients increased after treatment and neared that of the control group, although statistical significance was not attained (p = 0.074). Conclusions: These results suggest that epilepsy patients have interictal abnormalities that are demonstrated by reduced brain complexity, and that VPA partially reverses this trend. Nonlinear analysis of EEG data may be useful in evaluating the effect of AEDs.
Rumpshaker Behaves like Juvenile-Lethal Plp Mutations When Combined with Shiverer in Double Mutant Mice
Authors: Billings-Gagliardi Susan , Nunnari John J. , Wolf Merrill K.
Published: April 2003

The phenotypes of double mutant mice whose genomes are homozygous for an Mbp (myelin basic protein) mutation and hemizygous for a juvenile-lethal Plp (proteolipid protein) mutation were compared in earlier studies. The results suggested that the shiverer Mpb mutation might have some unexplained ability to partially rescue oligodendrocytes (OLs) from the ‘death sentence’ that is imposed by the Plp mutations. Conversely, they also indicated that the juvenile-lethal Plp mutations may normalize shiverer OL morphology by reducing the numbers of microprocesses. The Plp mutation rumpshaker produces a mild hypomyelination without reduction in OL numbers and a normal lifespan. This report describes double mutant mice combining two Mbp mutations with rumpshaker, utilizing a common B6C3F1 hybrid-based genetic background. Initial studies on B6C3F1 rumpshaker optic nerve and spinal cord white matter showed unanticipated signs of OL death, with morphologic criteria suggestive of an apoptotic mechanism. In shiverer*rumpshaker double mutant mice, this small class of dying cells could not be identified. White matter morphology was similar to that of mice expressing only the shiverer mutation, except that OL microprocesses were far less abundant. This evidence suggests that, despite their distinctive phenotypic differences, rumpshaker may share more characteristics with the juvenile-lethal Plp mutations than has previously been recognized.
Neuregulin-Induced Association of Sos Ras Exchange Protein with HER2(erbB2)/HER3(erbB3) Receptor Complexes in Schwann Cells through a Specific Grb2-HER2(erbB2) Interaction
Authors: Goodearl Andrew , Viehover Andrea , Vartanian Timothy
Published: April 2003

Neuregulins are members of the epidermal growth factor family of related ligands that exert pleotropic effects during development on the Schwann cell lineage. The receptor complex activated by neuregulin in Schwann cells consists of HER2 (erbB2) and HER3 (erbB3). The intracellular signaling events that follow activation of the HER2/HER3 receptor complex in primary cells, and in particular in Schwann cells, are poorly understood. We have found that neuregulin induces the rapid association of the guanine nucleotide exchange factor SOS with the HER2/HER3 receptor complex. The association of SOS with the HER2/HER3 receptor complex is preceded by the rapid association of Grb2 with the HER2/HER3 receptor complex. Far Western analysis indicates that Grb2 and SOS bind exclusively to HER2 in the HER2/HER3 receptor complex.
Stimulation of the Epidermal Growth Factor Receptor Induces Glial-Specific Protein Expression in the Human DAOY Neuroectodermal Cell Line
Authors: Shen Yu-Min , Meltzer Hal , Saljooque Farid , Sang U Hoi
Published: April 2003

Central nervous system (CNS) stem cells require epidermal growth factor (EGF) to survive and express glial-specific proteins (GSPs) under its influence. EGF and its receptor (EGF-R) therefore are involved in gliogenesis. We hypothesize that EGF selectively modulates GSP expression in pluripotential CNS cells and this effect is dependent on the degree of EGF-R activation (i.e., the amount of both EGF and the EGF-R present). In order to explore this, we investigated the effects of EGF on the expression of glial- and neuronal-specific proteins in the pluripotential human neuroectodermal cell line, DAOY. DAOY clones expressing different EGF-R levels were treated with EGF. The expression of glial fibrillary acid protein (GFAP), glutamine synthetase (GS) and neuron-specific enolase (NSE) were measured by ELISA. In a clone with low EGF-R levels (clone DAOY-YS-15), EGF selectively stimulated GSPs. In cells which express twice the EGF-R level, EGF (10–8 M) stimulated both glial and neuronal proteins nonspecifically. In cells with higher EGF-R numbers, EGF suppressed both glial and neuronal proteins. These effects were not due to the negligible growth influences of EGF on the cells. In clone DAOY- YS-15, selective GSP expression was observed as early as 2 days after exposure to EGF (10–9 M). In these cells, GFAP induction was also shown at the transcriptional level using a quantitative reverse transcriptase-polymerase chain reaction. This suggests one mechanism for EGF action. Our findings are therefore consistent with the hypothesis that the selective induction of GSPs in pluripotent cells is dependent on the EGF-R level and the degree of EGF-R activation.
Postnatal Expression of α-Synuclein Protein in the Rodent Substantia nigra and Striatum
Authors: Jakowec M.W. , Donaldson D.M. , Barba J. , Petzinger G.M.
Published: April 2003

A primary goal of our research is to elucidate the mechanisms involved in neuroplasticity of the basal ganglia in both development and in response to injury. One means to this aim is through the analysis of the ontological profile of proteins in the basal ganglia and to correlate their pattern of expression with morphological development. One protein thought to be important in neuroplasticity is α-synuclein. The purpose of this study was to characterize and compare the pattern of expression of α-synuclein protein using immunocytochemistry in the substantia nigra and striatum of the rodent in early postnatal and adult life. Our results demonstrate that there is a high level of expression of α-synuclein protein within cell bodies of the substantia nigra pars compacta in the 1st week of postnatal life that decreases both in intensity and number of immunoreactive cells between postnatal days 7 and 14. This is in contrast to the substantia nigra pars reticulata where α-synuclein protein expression in the neuropil increases after postnatal day 7. In the striatum, expression in early postnatal life is distributed in a mosaic-like fashion and becomes more diffuse after postnatal day 14. Our results support the findings of others that expression of α-synuclein is developmentally regulated and suggest that α-synuclein may play an important role in establishing the function of the basal ganglia. Understanding the role of α-synuclein in the normal basal ganglia may provide insights into the molecular mechanisms involved in neuroplasticity in response to injury.
Target Cells Promote the Development and Functional Maturation of Neurons Derived from a Sympathetic Precursor Cell Line
Authors: Bharmal Saleem , Slonimsky John D. , Mead Jonathan N. , Sampson Catherine P.B. , Tolkovsky Aviva M. , Yang Bo , Bargman Renee , Birren Susan J.
Published: April 2003

The role of target interactions in the development and functional maturation of peripheral neurons was investigated using an immortalized sympathetic precursor cell line. bMAH cells underwent neuronal differentiation in response to neurotrophic factors, but maintained an immature neuronal phenotype characterized by small cell bodies and continued cell division. Co-culture with cardiac myocytes, a target of sympathetic innervation, promoted the appearance of large-diameter postmitotic bMAH neurons. Analysis of bMAH maturation in the presence and absence of co-cultured myocytes indicated that myocyte-derived factors promoted the survival of maturing bMAH neurons prior to their acquisition of nerve growth factor dependence. Myocyte interactions also promoted the functional maturation of bMAH neurons, leading to an increase in the localization of synaptic vesicle proteins into neuritic varicosities and the acquisition of sympathetic-like intrinsic electrical properties. Like primary sympathetic neurons, mature bMAH neurons formed functional connections to cardiac myocytes as measured by evoked postsynaptic responses in connected myocytes. The effects of myocyte co-culture on developing bMAH neurons could be mimicked by myocyte conditioned medium, indicating that cardiac myocytes produce soluble factors that promote the appearance of mature neurons. These experiments indicate that targets of innervation play a role in directing the development and final maturation of peripheral neurons.
Transdifferentiation of Pigmented Epithelial Cells: A Source of Retinal Stem Cells?
Authors: Fischer Andy J. , Reh Thomas A.
Published: April 2003

In urodeles, larval anurans, embryonic chicks and rodents, the retinal pigmented epithelium (RPE) is capable of transdifferentiation and generating new neurons. Recent evidence suggests that pigmented cells in the ciliary body of the adult rodent eye are capable of producing new neurons in vitro. Here we provide data to suggest that the pigmented epithelium at the retinal margin of postnatal chickens is similar to that found in the embryonic retina. Pigmented cells at the retinal margin expressed mitf and pax6, transcription factors that are transiently expressed by the developing RPE. Furthermore, these pigment cells at the retinal margin express high levels of proliferating cell nuclear antigen and accumulate bromodeoxyuridine, indicating that they continue to proliferate long after embryonic stages of development. Exogenous fibroblast growth factor-2 (FGF2) or insulin alone did not affect the proliferation of these cells, while FGF2 plus insulin induced their proliferation and loss of pigmentation. We propose that the pigmented cells at the retinal margin of the postnatal chicken are similar to those found in the embryonic eye, and these cells could be a source of neural regeneration under appropriate conditions.
Unraveling Oligodendrocyte Origin and Function by Cell-Specific Transgenesis
Authors: Belachew Shibeshih , Yuan Xiaoqing , Gallo Vittorio
Published: April 2003

Besides the role of mature oligodendrocytes in myelin synthesis during the development of the central nervous system (CNS), the oligodendrocyte lineage also encompasses the largest pool of postnatal proliferating progenitors whose behavior in vivo remains broadly elusive in health and disease. We describe here transgenic models that allow us to track the functions and origins of such cells by using proteolipid protein and 2′,3′-cyclic nucleotide 3′-phosphodiesterase (CNP) gene promoters to direct oligodendroglial expression of different reporters, in particular the green fluorescent protein (GFP). We emphasize that the CNP-GFP mouse, which targets the entire oligodendroglial lineage from embryonic life to adulthood, provides an outstanding tool to study the in vivo properties of oligodendrocyte progenitor cells in normal and damaged CNS.
Glial-Defined Boundaries in Xenopus CNS
Authors: Yoshida Mika
Published: April 2003

Regional specificity, which arises early during central nervous system (CNS) development, reflects the generation of boundary regions that define the domains of distinct neural cell types and the guidance of axonal growth. The boundaries between discrete CNS domains often appear to be established by specialized glial cells. Boundary glia have been implicated in supporting neurite extension by providing mechanical and chemical barriers during development and regeneration. The present study demonstrates biochemical and morphological differences in boundary glial cells in the hindbrain and spinal cord of developing Xenopus laevis. DMγ, a membrane protein of the proteolipid protein family, is localized to radial glial processes in hindbrain boundary regions. By contrast, DMβ, a neuronal protein that bears significant homology to DMγ in primary sequence and that promotes neurite outgrowth, is expressed in hindbrain axonal pathways. In addition, the expression of two intermediate filament proteins, glial fibrillary acidic protein and vimentin, are progressively restricted to glial cells in the rhombomere center and boundary regions, respectively. Those two intermediate filament proteins show distinct expression domains in the spinal cord as well. The present study suggests that a glial surface protein, DMγ, may act as a boundary molecule in developing Xenopus hindbrain and that a distinct subpopulation of glial cells may define functional domains within the CNS.
Dopamine Induces Phenotypic Differentiation or Apoptosis in a Dose-Dependent Fashion: Involvement of the Dopamine Transporter and p53
Authors: Porat Shai , Premkumar Arumugam , Simantov Rabi
Published: April 2003

The effect of dopamine on the growth, phenotypes (morphological and biochemical) and programmed cell death (apoptosis) of the human neuronal NMB cell line was examined. Exposure to 20–50 µM of dopamine decreased cell growth, induced an apparent differentiated cell morphology and increased 3H-dopamine uptake. At higher concentrations (100–300 µM) dopamine was neurotoxic and induced apoptosis, as reported previously. The observed effects of both low and high doses of dopamine were blocked by cocaine, which suggested involvement of dopamine transporters. Indeed, several experiments demonstrated the relationship between dopamine uptake of cells and their vulnerability to the toxic effect of dopamine. High concentrations of dopamine, which induced apoptosis, also increased p53 levels, detected by RT-PCR analysis and immunoblotting, whereas lower dopamine concentrations, which induced a differentiated phenotype, did not increase p53 immunoblotting. Dibutyryl-cAMP and dimethyl sulfoxide, which induced differentiation but not apoptosis of the NMB cells, did not increase p53 expression. These findings provide an insight into the role of dopamine, dopamine transporters and p53 in the differentiation and apoptosis of dopaminergic neurons, which will further our understanding of neuronal development and neurodegenerative diseases.
Testosterone Regulates Terminal Schwann Cell Number and Junctional Size during Developmental Synapse Elimination
Authors: Jordan Cynthia L. , Williams Terrance J.
Published: April 2003

Previous work has shown that exposure to exogenous testosterone during synapse elimination permanently stabilizes synapses that would normally be lost in the androgen-sensitive levator ani (LA) muscle, indicating that testosterone is a potent stabilizing factor for developing LA synapses. Terminal Schwann cells (TSCs), which cap the neuromuscular junction, have also been implicated in the control of synaptic stability and may play a decisive role in the selective stabilization of synapses during synapse elimination. In this study, we begin to investigate the possible role of TSCs in the effect of testosterone on synapse elimination by determining whether testosterone influences their number. As the number of TSCs generally correlates with the size of endplates, we also measured endplate size. Male rats were castrated or sham gonadectomized at postnatal day (P) 7 and given capsules containing either testosterone or nothing. Three weeks later (P27–28), LA neuromuscular junctions (NMJs) were stained using immune and nonimmune markers. As expected, testosterone treatment during synapse elimination maintained synapses that would ordinarily be eliminated. In addition, we find that the size of LA endplates and the number of TSCs per LA junction were also increased by the testosterone treatment. However, testosterone significantly increased the number of TSCs on both singly and multiply innervated fibers, indicating that the effect of testosterone on the number of TSCs is not specific to its effect on synapse maintenance. Rather the testosterone-induced increase in the number of TSCs appears related to the size of LA NMJs, a relationship that has precedence.
The Value of Rotatory Tests in Vestibular Testing
Authors: Gentine André , Eber Anne-Marie
Published: April 2003

The aim of this paper is to evaluate the usefulness of rotatory tests in the diagnosis of otoneurological disorders. Material and Method: The charts of 203 consecutive outpatients investigated at the Vestibular Pathology Unit of the University Hospital of Strasbourg were reviewed, to analyze the clinical history, the results of the physical examination, the pure tone audiogram, the spontaneous nystagmus evaluated with nystagmography, the caloric test, the Conraux damped pendular swing rotatory test and the index of nystagmus inhibition by visual fixation. Results: 28 patients were suffering from benign positional paroxysmal vertigo, 84 had a normal caloric test, 17 a bilateral vestibular weakness, 73 a unilateral vestibular weakness (UVW) with directional preponderance (DP) of the nystagmus in 9, 22 a DP of the nystagmus without any UVW, 49 an horizontal unisense nystagmus, 15 had a vertical nystagmus and 9 a multisense nystagmus. The rotatory test was normal in 92 patients and asymmetric in 111. The index of nystagmus inhibition by visual fixation was abnormal in 18 patients. Discussion: The rotatory test is the best test to establish vestibular compensation: 31 patients were compensated, 33 uncompensated while only 17 patients had a unilateral horizontal spontaneous nystagmus. DP of the nystagmus at the rotatory test directed toward the UVW was present in the case of vestibular hydrops (11 patients). 40 patients had an asymmetric rotatory test although the caloric test was normal. These patients will improve with vestibular rehabilitation.
Molecular genetic delineation of 2q37.3 deletion in autism and osteodystrophy: report of a case and of new markers for deletion screening by PCR
Authors: Smith M. , Escamilla J.R. , Filipek P. , Bocian M.E. , Modahl C. , Flodman P. , Spence M.A.
Published: April 2003

We recently studied a patient who meets criteria for autistic disorder and has a 2q37 deletion. Molecular cytogenetic studies were carried out using DNA isolated from 22 different 2q37 mapped BACs to more precisely define the extent of the chromosome deletion. We also analyzed 2q37 mapped polymorphic markers. In addition DNA sequences of BACs in the deletion region were scanned to identify microsatellite repeats. We describe four new polymorphic microsatellite repeat markers in the 2q37.3 region. These markers enabled us to determine the parental origin of the deletion in our patient. DNA from 8–13 unrelated individuals was used to determine heterozygosity estimates for these markers. We review four genes deleted in our patient – genes whose known functions and sites of expression in the brain and/or bone make them candidates for involvement in autism and/or the osteodystrophy observed in patients with 2q37.3 deletions.