bluuebunny/crossref_metadata_2025 huggingface dataset:
The Relationship between Plaque pH and Glycemic Index of Various Breads
Authors: Lingström P. , Liljeberg H. , Björck I. , Birkhed D.
Published: April 2003

Plaque pH was studied during 60 min in situ in 10 subjects after eating various breads. The pH response was then compared to glycemic index (GI; calculated from the incremental blood glucose area) obtained from our earlier investigations. The following four products were tested: (1) barley kernel bread (BKB), (2) BKB, sourdough–fermented (BKBS), (3) white wheat bread (WWB), and (4) syrup–sweetened wheat–rye bread (SWRB). BKB was also tested with more intensive chewing and SWRB with the addition of fat. A 5% sucrose solution served as a control. The pH drops with all the breads were considerably smaller than with the sucrose solution during the first 15 min. From 30 min and onwards the breads gave similar, or even lower (SWRB) pH than sucrose. There was a great difference in pH response among the four breads, with the most pronounced pH fall for SWRB, followed by WWB (based on the AUC values). Intensive chewing of BKB increased, while the addition of fat to SWRB reduced the pH fall, in both cases by about 0.2 pH units. A high correlation (r = 0.94) between plaque pH and GI was found, i.e. the more pronounced the pH drop in plaque, the higher the GI in blood. Therefore, both from a cariogenic and from a metabolic point of view, breads with a low GI should be recommended.
In vitro Evaluation of Five Alternative Methods of Carious Dentine Excavation
Authors: Banerjee A. , Kidd E.A.M. , Watson T.F.
Published: April 2003

This in vitro, split–tooth study aimed to evaluate the efficiency (time taken) and effectiveness (quantity of dentine removed) of four techniques of carious dentine excavation (bur, air–abrasion, sono–abrasion and Carisolv™ gel) compared to conventional hand excavation. Eighty freshly extracted human molars were assigned to four experimental groups (n = 20), sectioned longitudinally through occlusal lesions and pre–excavation colour photomicrographs obtained. Using the natural autofluorescence of carious dentine (detected using confocal laser scanning microscopy) as an objective and reproducible guide, carious dentine removal was assessed in each half of the split tooth sample, comparing hand excavation to the test method. The time taken to reach a cavity floor that was hard to a dental probe was noted and final colour photomicrographs were taken. From the results, it was concluded that bur excavation was quickest but overprepared cavities relative to the autofluorescent signature, whereas Carisolv excavation was slowest but removed adequate quantities of tissue. Sono–abrasion tended to underprepare whereas air–abrasion was more comparable to hand excavation in both the time and amounts of dentine removed. Conventional hand excavation appeared to offer the best combination of efficiency and effectiveness for carious dentine excavation within the parameters used in this study.
Reproducibility of Quantitative Measurement of White Enamel Demineralisation by Image Analysis
Authors: Willmot D.R. , Benson P.E. , Pender N. , Brook A.H.
Published: April 2003

The reproducibility of measuring artificial enamel white spot lesions from captured photographic images using computerised image analysis was assessed. Enamel lesions were induced on the buccal surface of 22 human teeth over periods of 3, 7 and 14 days. Standardised photographs were taken from above and below the occlusal plane. These were repeated after 2 weeks. The photographs were converted into TIFF images and mean grey scale levels of the areas of etched enamel were measured using computerised image analysis. Assessment of repeat readings of the same slide showed good reproducibility for photographs taken below the occlusal plane. The limits of agreement showed reasonable agreement between readings carried out on two slides of the same tooth. Capturing TIFF images via 35–mm film and measuring grey scale levels by computerised image analysis is a useful method of quantitative study of early enamel demineralisation. This may be developed for application in the clinical setting.
Reproducibility in the Assessment of Caries Lesion Behaviour: A Comparison between Conventional Film and Subtraction Radiography
Authors: Wenzel A. , Anthonisen P.N. , Juul M.B.
Published: April 2003

The purpose of this study was to compare reproducibility in the assessment of caries lesion behaviour in digital subtraction images and conventional radiographs. Ninety–seven pairs of conventional film bite–wings were included. The radiographs had been taken with a Kwik–Bite filmholder without further standardisation. The selection criterion was that at least one surface imaged in a bite–wing pair should show progresssion of a caries lesion from the first exposure to the second. The time interval between the bite–wings was 1–2 years. The radiographs were scanned into a personal computer and the two images from the same patient subtracted. Seven observers scored the subtraction images and the conventional films. The scale was based on no change/ change in surface appearance scored in the following categories: 0 = no change; 1 = development of a new caries lesion in enamel; 2 = development of caries lesion in enamel and dentine/progression of an existing enamel lesion into dentine/progression of a dentinal lesion further into dentine; 3 = development of secondary caries; 4 = new filling/change of filling/extension of filling. Cohen’s κ coefficients were calculated for intra– and inter–observer agreement for the two radiographic methods separately. The κ value served as the statistical sampling unit for testing differences between the two methods (Wilcoxon’s test for ranked pairs). The average intra–observer κ value was 0.875 (range 0.775–0.958) for the subtraction images and 0.758 (range 0.560–0.890) for the conventional radiographs. The difference was statistically significant (p<0.05). For inter–observer agreement, the κ values were lower than for intra–observer agreement. The average value was 0.678 (range 0.485–0.754) for the subtraction images and 0.701 (range 0.497–0.817) for the conventional radiographs (p>0.1). This study suggests a new way of comparing reproducibility in terms of κ values between diagnostic methods in clinical studies where accuracy cannot be evaluated. The subtraction method may be useful in the assessment of caries lesion behaviour in the clinic.
A Raman Spectroscopic Investigation of Dentin and Enamel Structures Modified by Lactic Acid
Authors: Tramini Paul , Pélissier Bruno , Valcarcel Jean , Bonnet Bernard , Maury Luc
Published: April 2003

Confocal Raman microspectrometry allows a thorough molecular analysis of mineralised dental tissues. The output information is provided in the form of curves representing the intensity of the signal according to the frequency, and its mathematical exploitation permits all sorts of comparative and quantitative analyses. By this process, we investigated the in vitro action of lactic acid on enamel and dentin from human permanent teeth. Modifications due to the acidic attack essentially concern phosphate grouping PO43–, which represents the mineral phase in enamel and dentin (hydroxyapatite): on Raman spectra, changes in intensity of the PO43– band are linked to the type of dentin, to its anatomical location, and to the age of the subject. The variability of the dentinal chemical structure was confirmed by a quantitative statistical analysis, revealing a significant spectral difference between coronal and root dentin.
Studies Concerning the Glucosyltransferase of Streptococcus sanguis
Authors: Vacca Smith Anne M. , Ng-Evans Linda , Wunder David , Bowen William H.
Published: April 2003

We have shown in previous studies that the glucosyltransferase (Gtf) enzymes of Streptococcus mutans have distinct properties when adsorbed to a surface. In the present study, we compared the activity of Gtf from Streptococcus sanguis, designated GtfSs, in solution and on the surface of saliva–coated hydroxyapatite (sHA) beads, and determined the ability of its product glucan to support the adherence of oral microorganisms. Gtf from S. sanguis 804 NCTC 10904 was purified from culture supernatant fluids by means of hydroxyapatite chromatography. Enzyme and the substrate were prepared in buffers at pH values from 3.5 to 7.5. Maximum activity of GtfSs occurred between pH 5.5 and pH 6.5, whether in solution or adsorbed onto a surface. The solubilized and insolubilized enzymes showed highest activity at 40°C; activity was reduced by 50(±2)% at 20 and 30°C. The enzyme did not form glucans in either phase at 10 or 60°C. The Km, determined from Lineweaver–Burk plots, for the enzyme in solution was 4.3(±0.4) mmol/l sucrose, and the Km for the enzyme on sHA beads was 5.0(±1.0) mmol/l sucrose. The ability of the GtfSs glucan synthesized on the surface of sHA beads to support the adherence of oral bacteria was investigated. 3H–thymidine–labeled bacteria (S. mutans GS–5, S. sobrinus 6715, S. sobrinus 6716, S. sanguis 10904, Actinomyces viscosus OMZ105E, A. viscosus 2085, and A. viscosus 2086) were incubated with sHA beads coated with GtfSs glucan. S. mutans GS–5 displayed the highest level of binding numerically. These results show that the GtfSs of S. sanguis is active on sHA beads, that the pH optimum for activity on a surface differs slightly from that in solution, and that its product glucan can support the adherence of oral microorganisms.
Polychlorinated Biphenyls Cause Developmental Enamel Defects in Children
Authors: Jan J. , Vrbič V.
Published: April 2003

The aim of this study was to evaluate the effects of long–term exposure to polychlorinated biphenyls (PCBs) on developing dental enamel. 202 8– to 14–year–old children who were pre– and post–natally exposed to PCBs in the contaminated region of Bela Krajina, Slovenia, were studied. 202 controls from Bršljin were matched for age and sex. Risk assessment was based on the concentrations of toxic PCB congeners in the diet. Levels of PCBs in dentine were used to validate exposure. PCB levels were analysed by high–resolution gas chromatography. The prevalence of developmental defects of enamel was assessed using the FDI Index. Developmental defects of enamel in permanent teeth were found in 71.3% of exposed children, compared to 49.5% in the control group. The enamel was abnormal in 21.9% of the permanent index teeth of exposed children and in 12.7% of the control children. The difference was statistically significant (χ2 = 84.18; p = 0.0019), mostly on account of demarcated opacities and hypoplasia. The extent of the defects was also greater in the exposed group (χ2 = 61.3; p = 0.0001). No significant correlations were found between PCB exposure and developmental defects in deciduous teeth. In conclusion, our results showed that long–term exposure to PCBs may cause developmental defects of enamel.
Early Embryonic Coats: Morphology, Function, Practical Applications
Authors: Herrler A. , Beier H.M.
Published: April 2003

Mammalian egg and embryo coats are primarily represented by the zona pellucida which, however, undergoes biochemical and structural changes during fertilization and embryo development. It serves several functions, from ovulation until shortly before implantation. Initially the zona pellucida induces sperm-oocyte interaction, acrosome reaction and prevents polyspermy. Later, it prevents disaggregation of the noncompacted blastomeres and the premature attachment to the oviductal and endometrial surface. Additionally, it protects the embryo against toxins and xenobiotics, as well as bacteria, viruses and phagocytes. As the embryo is covered by the zona pellucida until immediately before implantation, all signals of embryo-maternal signalling have to pass the zona and are detectable within it. Logically we may define the zona pellucida as a mailbox of the embryo-maternal signalling, especial for investigating these messages. Oviductal, uterine and embryonic proteins are incorporated into the zona pellucida as embryonic development goes on and change the zona’s morphological and biochemical properties. Whether a protein is able to penetrate the zona, whether it accumulates within the zona or whether it is rejected by the zona depends on its biochemical properties. Three specific proteins have been detected within the embryonic coats (IGFBP3, HB-EGF, P19). New insights into the physiology of the zona pellucida might present new achievements in the in vitro culture of embryos, and present new aspects as to how to prevent zona hardening. Furthermore, knowledge of the zona proteins enables the development of immunocontraceptive vaccines. Consequently, the zona pellucida is not only significant with regard to fertilization, but also during early embryonic development. Investigations of the zona pellucida will yield new insights into early embryo-maternal signalling which in turn may lead to improvements in classic IVF and new approaches to in vitro culture.
Imaging Techniques in the Evaluation of Adenocarcinoma of the Pancreas
Authors: Brand Randall E. , Matamoros Aurelio
Published: April 2003

Adenocarcinoma of the pancreas is a highly malignant neoplasm that presents late and carries a dismal prognosis. Despite technical advances, the various imaging modalities used to evaluate and stage a pancreatic adenocarcinoma have not had a significant impact on survival rates. This article describes the various imaging modalities used to image and stage an adenocarcinoma of the pancreas and reviews their relative accuracy and limitations in diagnosing and staging this carcinoma. We conclude that for appropriate staging of adenocarcinoma of the pancreas, the combination of a computed axial tomography scan and an endoscopic ultrasound represents an efficient and cost-effective approach.
Complications and Lessons Learned from 10 Years of Expandable Gastrointestinal Prostheses
Authors: Kozarek Richard
Published: April 2003

Initially inserted percutaneously for malignant biliary stenoses, expandable gastrointestinal prostheses have evolved as primary treatment for malignant dysphagia and as an alternative to plastic prostheses for some types of obstructive jaundice. They are also in their infancy as a means to palliate unresectable obstructions of the gastric outlet, small bowel, and colorectum. Despite a decade of development, problems persist and include: maldeployment; inadequate expansion; ingrowth; overgrowth; erosion, and migration. This article outlines some of the problems noted and opportunities to improve this still-evolving technology.
Pathology Report in Colon Cancer: What Is Prognostically Important?
Authors: Compton Carolyn C.
Published: April 2003

Surgical resection is the primary treatment modality for colorectal cancer, and the most powerful tool for assessing prognosis following surgery is pathologic analysis of the resection specimen. Although the parameters that determine the pathologic stage are the strongest predictors of postoperative outcome, a number of additional pathologic features have prognostic significance that is independent of stage. These include: histologic grade; small vessel (lymphatic or venular) invasion; extramural venous invasion; perineural invasion; tumor border configuration; host lymphoid response to tumor, and the status of surgical margins. For specimens in which the radial (circumferential) margin is applicable, surgical clearance around the tumor is also of import. It is self-evident that, compared to data derived from additional assays, prognostic information that can be derived directly from standard histologic sections of a tumor is of the greatest cost-benefit to the patient. In the current era of cost containment, it is essential that surgical pathologists evaluate and report the pathologic features that are of prognostic and/or predictive significance in every case of colorectal cancer and, in turn, that the import of these be understood by the treating physicians.
Determinants of Global Clinical Change Assessment in Patients with Early Alzheimer’s Disease
Authors: Claus Jules J. , Teunisse Saskia , Walstra Gerard J.M. , van Gool Willem A.
Published: April 2003

Global clinical impression (GCI) of change is assumed to integrate aspects of both cognitive and noncognitive functioning. We evaluated 140 consecutive patients with probable (n = 90) and possible (n = 50) early Alzheimer’s disease at baseline and after 6 months with measurements of global cognitive function (CAMCOG), behavior, activities of daily living, and burden of the caregiver. After 6 months, both the clinician (GCI-clin) and the caregiver (GCI-care) rated clinical change on a 3-point scale (worse, no change, improved). Data were analyzed with multiple polychotomous logistic regression, adjusted for age and sex. Change in global cognitive function and GCI-care were significantly and independently related to GCI-clin, while changes in activities of daily living and in behavior were significantly and independently associated with GCI-care. The findings suggest a double dissociation. Change in cognition appears to be the major determinant of the clinician’s global impression but not change in behavioral and functional parameters, while global impression of the caregiver is primarily based on change in behavioral and functional measures but not on change in cognition.
Predicting Survival in Patients with Early Alzheimer’s Disease
Authors: Claus Jules J. , van Gool Willem A. , Teunisse Saskia , Walstra Gerard J.M. , Kwa Vincent I.H. , Hijdra Albert , Verbeeten Jr. Bernard , Koelman J. Hans T.M. , Bour Lo J. , Ongerboer De Visser Bram W.
Published: April 2003

We investigated whether an index based on clinical features, electroencephalogram and computed tomography is useful to predict survival in early Alzheimer’s disease. One hundred and sixty-three consecutively referred patients to an outpatient memory clinic and first diagnosed with Alzheimer’s disease (105 ‘probable’ and 58 ‘possible’, NINCDS-ADRDA criteria) were studied and outcome measure was death. Cox proportional hazards regression analysis and Kaplan-Meier survival curves were used to investigate relations between baseline parameters and survival. Eighty-four patients (51.5%) died during the follow-up period that extended to 5.8 years, with a median duration of survival after entry of 4.3 years. Baseline factors that were statistically significant and independently related to increased risk of mortality were high age, male sex, poor cognitive function as measured with the CAMCOG, low alpha and beta power on electroencephalogram, and temporoparietal atrophy on computed tomography scan. These results were independent of the diagnosis probable or possible Alzheimer’s disease. Based on the coefficients from the regression equation, we computed a survival index for each patient and we constructed three groups according to tertiles of this index. After 5.2 years of follow-up, survival curves showed a low mortality group with 81.7% patients alive (median survival at least 5.7 years), an intermediate mortality group with 35.9% patients alive (median survival 3.8 years), and a high mortality group with no patients alive (median survival 2.3 years). Log rank tests were statistically significant for comparisons between all three groups. We conclude that an overall index combining demographic, cognitive, electroencephalogram and computed tomography features is a strong predictor of survival in early Alzheimer’s disease.
Behavioral Syndromes in Alzheimer’s Disease: Description and Correlates
Authors: Frisoni GiovanniB. , Rozzini Luca , Gozzetti Alessandra , Binetti Giuliano , Zanetti Orazio , Bianchetti Angelo , Trabucchi Marco , Cummings JeffreyL.
Published: April 2003

Introduction: Behavioral disturbances in patients with Alzheimer’s disease (AD) are ill-defined conditions. We hypothesize that the many behavioral disturbances hitherto described and studied might be grouped into few syndromes with separate determinants and correlates. Patients and Methods: 162 consecutive patients with probable AD admitted to a dementia unit were assessed by the UCLA Neuropsychiatric Inventory (NPI). Results: Factor analysis was carried out on NPI subscales, leading to three syndromes: ‘mood’, ‘psychotic’ and ‘frontal’. Patients with the ‘psychotic’ syndrome were older, had older age at dementia onset, had poorer cognition, were more often males, and had faster rate of dementia progression. Patients with the ‘frontal’ syndrome had higher education, longer disease duration, and slower rate of progression. Discussion: Some combinations of behavioral disturbances occur more frequently together and might represent separate behavioral syndromes. Different clinical correlates of the syndromes suggest separate etiologies.
Impairment of Neocortical Metabolism Predicts Progression in Alzheimer’s Disease
Authors: Herholz K. , Nordberg A. , Salmon E. , Perani D. , Kessler J. , Mielke R. , Halber M. , Jelic V. , Almkvist O. , Collette F. , Alberoni M. , Kennedy A. , Hasselbalch S. , Fazio F. , Heiss W.-D.
Published: April 2003

Progression rates of Alzheimer’s disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment.
Dementia and Antiphospholipid Antibodies
Authors: Mosek A. , Yust I. , Treves T.A. , Vardinon N. , Korczyn A.D. , Chapman J.
Published: April 2003

Antiphospholipid antibodies (aPLAb) may cause both focal ischemic and diffuse brain damage and may be associated with dementia. We have examined the relationship of aPLAb to dementia in the elderly. Blood samples were obtained from 87 consecutive patients with dementia (74 ± 11 years old) and 69 controls (78 ± 9 years old), residents of an old age home who were not overtly demented. Levels of aPLAb were measured by a standardized ELISA, utilizing cardiolipin as antigen, and we considered levels above 20 IgG antiphospholipid units (GPLU) as significantly elevated. We found that 5 of the 87 demented patients (6%), but none of the 69 controls, had significantly elevated aPLAb levels (p = 0.03, one-tailed Fisher’s exact test). All the patients with high aPLAb levels were diagnosed clinically as having dementia of the Alzheimer type, except for 1 who had mixed dementia, and none had features of an immune-mediated disease. Thus, a small but significant number of patients with dementia have high levels of aPLAb. The role of the aPLAb in these patients, with apparently diffuse brain disease, is currently unknown.
Lipoprotein(a) Phenotypes in Patients with Vascular Dementia
Authors: Urakami K. , Wada-Isoe K. , Wakutani Y. , Ikeda K. , Ji Y. , Yamagata K. , Kowa H. , Okada A. , Adachi Y. , Nakashima K.
Published: April 2003

We tried to examine if there is a particular distribution pattern of lipoprotein(a) [Lp(a)] phenotypes specific for patients with vascular dementia (VD). Fourteen cases of VD (9 males and 5 females), 18 cases of dementia of the Alzheimer type (DAT)(7 males and 11 females), 29 cases of cerebrovascular disease (CVD) in the chronic phase (18 males and 11 females) and 47 healthy individuals as controls (25 males and 22 females) were examined for serum Lp(a). Serum concentrations and phenotypes of Lp(a) were assessed by ELISA and a test kit for the Lp(a) phenotype, respectively. Serum concentrations of Lp(a) were significantly higher in patients with VD (p < 0.05) as well as patients with CVD (p < 0.01) compared with those in healthy individuals. Serum concentrations of Lp(a) did not significantly differ between patients with DAT and healthy individuals. The incidences of Lp(a) phenotypes containing relatively low-molecular-weight apolipoprotein(a) isoforms were significantly higher in patients with CVD in the chronic phase (p < 0.05) or those with VD (p < 0.01) compared with those in healthy individuals. Distribution patterns of Lp(a) phenotypes did not differ between patients with DAT and healthy individuals. Thus, high serum levels of Lp(a) could be considered a clinical hallmark to distinguish VD from DAT. Abnormally high serum levels of Lp(a) in patients with CVD and VD seemed to be due to specific increases in low-molecular-weight apolipoprotein(a) isoforms in Lp(a).
Dopamine and N-Methyl-D- Aspartate Receptor Interactions in the Neostriatum
Authors: Cepeda Carlos , Levine Michael S.
Published: April 2003

This review examines dopamine (DA) and glutamate receptor interactions in the neostriatum (NS) primarily from a neurophysiological perspective. Historically, a clear understanding of the function of DA in the NS has been difficult because it was considered a classical neurotransmitter with either excitatory or inhibitory actions and because many of the data were obtained by use of varying methodologies. When DA is considered a neuromodulator whose role is to alter how NS cells respond to glutamatergic inputs, many of its actions can be accounted for and predicted with great accuracy within a model of receptor subtype. In this model, DA via activation of D1 receptors potentiates responses mediated by activation of N-methyl-D-aspartate (NMDA) receptors. DA via activation of D2 receptors attenuates responses mediated by activation of non-NMDA receptors. Outcomes of combinations of NMDA and D2 and non-NMDA and D1 receptors are not as predictable. The mechanisms underlying the D1-NMDA receptor interactions appear to involve alterations in cell excitability mediated by activation of Ca2+ conductances and/or phosphorylation of NMDA receptors. Less is known about mechanisms underlying the D2-non-NMDA receptor interaction. The functional implications of this model in setting membrane potentials, signal-to-noise ratio, plasticity and excitotoxicity are discussed.
Relationship between Dye Coupling and Spontaneous Activity in Developing Ferret Visual Cortex
Authors: Kandler Karl , Katz Lawrence C.
Published: April 2003

Neuronal coupling by gap junctions is common during early development of the brain. Coupling is thought to create functional cell assemblies which may be involved in the functional specification of brain areas and the formation of synaptic circuits. In the present study we used slices from the visual cortex of postnatal ferrets to investigate the temporal relationship of gap junction coupling and formation of functional synapses. Individual neurons were filled with the gap-junction-permeable dye biotin ethylenediamine while spontaneous synaptic currents were recorded using whole-cell patch clamp recording techniques. We found that dye coupling increased during the first 2 postnatal weeks resulting at a peak around P14, after which coupling steadily decreased until adult levels were reached in animals older than P30. Spontaneous synaptic activity increased 30-fold between birth and maturity (from 10.8 ± 2.4 to 318 ± 54 events/min). The sharpest rise in synaptic activity, an over 5-fold increase, occurred between P15 and P19, shortly after the invasion of thalamocortical fibers.
Effect of Sympathetic Innervation on Isoproterenol-Induced Cystatin S Gene Expression in Rat Submandibular Glands during Early Development
Authors: Chaparro Orlando , Yu Wan-hua Amy , Shaw Phyllis A.
Published: April 2003

The rat submandibular gland is innervated by both sympathetic and parasympathetic branches of the autonomic nervous system which, in turn, regulate the secretory function of the gland. Parasympathetic innervation of rat submandibular glands is present at birth; in contrast, sympathetic innervation reaches the glands by postnatal day 5. Isoproterenol (IPR), a β-adrenoreceptor agonist, induces hypertrophic and hyperplastic enlargement of rat salivary glands, and induces the expression of a number of genes, including cystatin S (Cys S), a member of family 2 of the cysteine proteinase inhibitor superfamily. Cys S gene expression is tissue specific, cell type specific, occurs temporally during normal development and is not observed in adult animals unless stimulated by IPR. In addition, sympathectomy of adult rat submandibular glands reduced IPR-induced expression of the Cys S gene. This paper reports experiments analyzing the participation of the sympathetic branch of the autonomic nervous system in IPR-induced expression of the cystatin S gene during early development of the submandibular gland. The rat Cys S gene could be induced by IPR by day 3, and the level of Cys S mRNA remained constant until 8 days at which time a dramatic IPR induction of Cys S mRNA was observed. This statistically significant increase in Cys S mRNA at 8 days was diminished, but not completely suppressed, upon sympathectomy of 1-day-old animals. These data indicate that an intact sympathetic innervation is not a requisite for IPR-induced Cys S gene expression in developing submandibular glands; however, sympathetic innervation is required for the full IPR response of the Cys S gene in developing submandibular glands. The developmental experiments presented in this paper indicate that factor(s) coming from the sympathetic nervous system participate in IPR-induced expression of the Cys S gene in rat submandibular glands.
Molecular Components of Striatal Plasticity: The Various Routes of Cyclic AMP Pathways
Authors: Rajadhyaksha Anjali , Leveque Jean-Christophe , Macías Wendy , Barczak Amy , Konradi Christine
Published: April 2003

Neuroplasticity serves an important role for normal striatal function and in disease states. One route to neuroplasticity involves activation of the transcription factor cyclic 3′,5′-adenosine monophosphate (cyclic AMP) response element binding protein (CREB) by phosphorylation of the amino acid 133Ser. Dopamine and glutamate, the two predominant neurotransmitters in the striatum, induce CREB phosphorylation in primary cultures of rat striatum through cyclic AMP and Ca2+ pathways. Here we present the role of N-methyl-D-aspartate receptors and Ca2+ in cyclic AMP-mediated CREB phosphorylation.
A Role for N-Methyl-D-Aspartate Receptors in the Regulation of Synaptogenesis and Expression of the Polysialylated Form of the Neural Cell Adhesion Molecule in the Developing Striatum
Authors: Butler Amy K. , Uryu Kunihiro , Chesselet Marie-Françoise
Published: April 2003

Striatal development proceeds during a protracted postnatal period in rats. In the dorsolateral striatum, the number of asymmetric synapses, formed mostly by glutamatergic afferents innervating the dendritic spines of medium-sized striatal neurons, increases during the 3rd postnatal week and then rapidly declines before reaching adult levels. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which is widely expressed along neuronal membranes early in development, becomes progressively localized to synapses, and is no longer detectable in remaining synapses after synaptic pruning has occurred. Administration of MK-801, an antagonist of N-methyl-D-aspartate receptors, on day 20, either peripherally or locally into the striatum, decreases asymmetric synapse number by 30% and totally abolishes immunolabelling for PSA-NCAM in the dorsolateral striatum.
Comparison of Lactate and Glucose Metabolism in Cultured Neocortical Neurons and Astrocytes Using 13C-NMR Spectroscopy
Authors: Waagepetersen H.S. , Bakken I.J. , Larsson O.M. , Sonnewald U. , Schousboe A.
Published: April 2003

In cerebral cortical neurons, synthesis of the tricarboxylic acid (TCA) cycle-derived amino acids, glutamate and aspartate as well as the neurotransmitter of these neurons, γ-aminobutyrate (GABA), was studied incubating the cells in media containing 0.5 mM [U-13C]glucose in the absence or presence of glutamine (0.5 mM). Lyophilized cell extracts were analyzed by 13C nuclear magnetic resonance (NMR) spectroscopy and HPLC. The present findings were compared to results previously obtained using 1.0 mM [U-13C]lactate as the labeled substrate for the neurons. Regardless of the amino acids studied, incubation periods of 1 and 4 h resulted in identical amounts of 13C incorporated. Furthermore, the metabolism of lactate was studied under analogous conditions in cultured cerebral cortical astrocytes. The incorporation of 13C from lactate into glutamate was much lower in the astrocytes than in the neurons. In cerebral cortical neurons the total amount of 13C in GABA, glutamate and aspartate was independent of the labeled substrate. The enrichment in glutamate and aspartate was, however, higher in neurons incubated with lactate. Thus, lactate appears to be equivalent to glucose with regard to its access to the TCA cycle and subsequent labeling of glutamate, aspartate and GABA. It should be noted, however, that incubation with lactate in place of glucose led to lower cellular contents of glutamate and aspartate. The presence of glutamine affected the metabolism of glucose and lactate differently, suggesting that the metabolism of these substrates may be compartmentalized.
Glucose and Lactate Metabolism in C6 Glioma Cells: Evidence for the Preferential Utilization of Lactate for Cell Oxidative Metabolism
Authors: Bouzier A.-K. , Voisin P. , Goodwin R. , Canioni P. , Merle M.
Published: April 2003

13C and 1H nuclear magnetic resonance spectroscopy (NMR) was used to investigate the metabolism of L-lactate and D-glucose in C6 glioma cells. The 13C enrichment of cell metabolites was examined after a 4-h incubation in media containing 5.5 mM glucose and 11 mM lactate, each metabolite being alternatively labelled with either [1-13C]D-glucose or [3-13C]L-lactate. The results indicated that exogenous lactate was the major substrate for oxidative metabolism. They were consistent with the concept of the existence of 2 pools of both lactate and pyruvate, of which 1 pool was closely connected with exogenous lactate and oxidative metabolism, and the other pool was closely related to glycolysis and disconnected from oxidative metabolism. The molecular basis of this behaviour could be related to different locations for the lactate dehydrogenase isoenzymes, as suggested by their immunohistochemical labelling.
Brain Anaerobic Lactate Production: A Suicide Note or a Survival Kit?
Authors: Schurr Avital , Rigor Benjamin M.
Published: April 2003

Aerobic energy metabolism utilizes glucose and oxygen to satisfy all the energy needs of the adult brain. Anaerobically, the brain switches to the significantly less efficient glycolytic pathway for its most basic energy requirements. Anaerobic glycolysis provides the adult brain with a limited amount of energy and time to maintain ion homoeostasis and other essential processes before several events occur that lead to brain cell damage and death. Recent evidence that lactate, produced mainly in glial cells during a period of oxygen deprivation, becomes the only utilizable and thus obligatory substrate for aerobic energy metabolism upon reoxygenation is summarized here. This evidence also supports the hypothesis that a lactate shuttle exists between glia and neurons, and emphasizes its importance in the post-ischemic survival of neurons.
In vivo Investigation of Glutamate–Glutamine Metabolism in Hyperammonemic Monkey Brain Using 13C-Magnetic Resonance Spectroscopy
Authors: Tsukada Y. , Kanamatsu T. , Watanabe H. , Okamoto K.
Published: April 2003

To investigate the metabolism of glutamate and glutamine in living monkey brain, a system of in vivo 13C magnetic resonance spectroscopy (MRS) using 1H-decoupled 13C spectroscopy combined with monitoring temperature changes in the brain by MR phase mapping was developed. Serial 13C-NMR spectra of the amino acids glutamate and glutamine were acquired non-invasively over 4 h from anesthetized monkey brain after the intravenous administration of [1-13C]glucose (0.5–1.0 g/kg). In the acute hyperammonemic state induced by the administration of ammonium acetate (77 mg/kg bolus), it was observed that 13C incorporation into glutamine-4 was clearly accelerated, without changes of 13C incorporation into glutamate-4. During hyperammonemia, it was shown directly by [2-13C]glucose administration that the anaplerotic pathway for the TCA cycle was also augmented, contributing to the formation of glutamine in the astroglia.
Immunoultrastructural Expression of ICAM-1 and PECAM-1 Occurs Prior to Structural Maturity of the Murine Blood-Brain Barrier
Authors: Lossinsky Albert S. , Wisniewski Henryk M.
Published: April 2003

This study investigated the time of expression of two endothelial cell adhesion molecules, ICAM-1/CD54 and PECAM-1/CD31 in the developing postpartum mouse blood-brain barrier (BBB). Immunoultrastructural studies demonstrated that both adhesion molecules are initially expressed primarily on the luminal endothelial cell surfaces at birth or shortly thereafter, they increase in an intensity at approximately 1 week postpartum and then decrease to a weak labeling of the luminal endothelial cell surfaces at 2 weeks after birth. In the adult animals, little or no adhesion molecule labeling was expressed on blood vessels. Our results present immunocytochemical evidence that upregulation of ICAM-1 and PECAM-1 occurs prior to structural maturity of the BBB. Moreover, these data support a notion that these adhesion molecules play an important role for angiogenesis in the developing murine BBB.
Origin of Renewed Spinal Ganglia during Tail Regeneration in Urodeles
Authors: Koussoulakos Stauros , Margaritis Loukas H. , Anton Hermann-Josef
Published: April 2003

The source of the cells which form the spinal ganglia within the regenerating urodele tail is not yet indisputably known. Classical and modern experimental approaches trace the spinal cord as the most probable source. The aim of the present study was to further investigate this item by conventional histology, counting of mitotic figures, and estimating the labeling index. The main results can be summarized as follows: (a) The regenerated part of the tail contained only two bilaterally asymmetrical pairs of ganglia, with respect to the rostrocaudal (anterior-posterior) axis. (b) The anterior ganglia were slightly differentiated and appropriately localized; therefore, analysis was performed mainly in the posterior, still developing ganglia. (c) An anatomical continuation between the ventrolateral side of the regenerated spinal cord and the laterally forming spinal ganglion was noticed. There was some indication that many cells migrated out from the spinal cord towards the spinal ganglion, through the ventral root. (d) The mitotic and the labeling index along the regenerated spinal cord exhibited individual peaks near the level of each developing ganglion. The last two observations corroborate and reinforce the prevailing view that the progenitors of the spinal ganglion cells which are formed in the regenerating tail are of spinal cord origin.
Levels of Amino Acid Neurotransmitters during Mouse Cerebellar Neurogenesis and in Histotypic Cerebellar Cultures
Authors: Miranda-Contreras L. , Benítez-Diaz P.R. , Mendoza-Briceño R.V. , Delgado-Saez M.C. , Palacios-Prü E.L.
Published: April 2003

The variation in the levels of excitatory (glutamate and aspartate) and inhibitory (GABA, glycine and taurine) neurotransmitters during neurogenesis in mouse cerebellum, from embryonic day (E) 15 until the young adult stage, was analyzed by high-pressure liquid chromatography. Between E15 and E21, high contents of GABA, glutamate and aspartate were detected, with the GABA levels approximately 2- to 3-fold higher than those of glutamate and aspartate. After birth, the levels of GABA remained high during the first 2 postnatal weeks and then reached a plateau comparable to adult values by the third week. The levels of glutamate and aspartate increased gradually from birth to the young adult stage, showing peak values at postnatal days (P) 3 and P11. Glycine and taurine were present at relatively low concentrations during the prenatal period, then rose significantly by about 4-fold after birth; their levels decreased by the end of the first postnatal week but increased gradually thereafter until reaching adult values by the third week. To determine the endogenous neurotransmitter production in the cerebellar cortex, primary histotypic cerebellar cultures prepared at P10 were analyzed and the in vitro transmitter contents were compared with the adult in situ values. The cultures showed about the same levels of glutamate and aspartate; however, their concentrations were lower by half than in vivo, suggesting that both play an equally important role in the excitatory neurotransmission of the cerebellar cortex internal circuitry pathways and that in mature cerebellum, about 50% of the excitatory synaptic inputs derive from the afferent climbing and mossy fibers. The in vitro GABA and glycine contents were comparable with the in vivo levels, whereas the taurine concentrations were about 5-fold lower in vitro than in vivo. These findings indicate that most of the GABA and glycine transmitters are produced intrinsically while a high proportion of taurine in the cerebellum comes from extracerebellar afferents. This study provides data on the changing levels of the amino acid neurotransmitters in developing mouse cerebellum and the relative proportions of neurotransmitter contents that are produced by intrinsic neurons in contrast to those derived from extrinsic afferent fibers.
Electrophysiological Responses in vivo of Hippocampal CA1 Pyramidal Neurons in an Animal Model of Neuronal Migration Disorders
Authors: Smith Bret N. , Choi Byung-Ju , Roper Steven N. , Dudek F. Edward
Published: April 2003

Cortical dysgenesis arising from neuronal migration disorders is closely associated with intractable epilepsy in humans. We used extracellular field potential and conventional intracellular recordings from the dorsal hippocampus of intact adult rats to determine if the excitability of CA1 pyramidal cells was enhanced in rats with experimentally induced hippocampal dysplasia. Electrical stimulation of afferent fibers resulted in more robust population responses in the CA1 region of irradiated rats versus controls. Synaptic inhibition of pyramidal cells was also reduced in these animals. These results suggest that the excitability of the CA1 region in rats with hippocampal dysplasia is greater than in control animals.
Age and Etiology as Predictors of Language Outcome following Hemispherectomy
Authors: Curtiss Susan , de Bode Stella
Published: April 2003

We report on the effects of etiology and age on the linguistic outcomes in a large pediatric hemispherectomy population. Four populations were considered separately: cortical dysplasia (multilobar involvement), Rasmussen’s encephalitis, infarction as a primary etiology and, fourth, children who failed to develop language, regardless of etiology. We argue against the ‘the-earlier-the-better’ hypothesis and propose our own hypothesis that weds maturational factors to etiological factors to predict language outcomes following pervasive brain insult. The implications of our ‘critical impact point’ hypothesis are discussed.
Evidence for Regulation of Myelin Protein Synthesis by Contact between Adjacent Schwann Cell Plasma Membranes
Authors: Sasagasako Naokazu , Ohno Masaharu , Quarles Richard H.
Published: April 2003

The spontaneously immortalized S16 Schwann cell line expresses higher levels of myelin-associated glycoprotein (MAG) and PO glycoprotein and their messenger RNAs when grown at high density than at low density [Sasagasako et al: J Neurochem 1996;66:1432–1439]. This up-regulation of myelin protein expression at high density is not associated with decreased cellular proliferation and may be caused by direct cell-to-cell contact. To investigate the hypothesis that increased mRNA levels for myelin proteins are caused by contact between Schwann cells, sparse S16 cell cultures were treated for 48 h with plasma-membrane-enriched fractions isolated from dense S16 cells. The treatment had no effect on the proliferation of the cells, but MAG and PO mRNAs were elevated 2- and 1.3-fold, respectively, in comparison to untreated cells. These effects on levels of myelin protein mRNAs were eliminated by pretreatment of the membrane fraction with heat or trypsin and were not caused by plasma membrane fractions from NIH 3T3 cells. These data support the hypothesis that homotypic contact between Schwann cells up-regulates expression of myelin proteins and suggest the possibility of autotypic contact-mediated regulation of myelinogenesis by adjacent spiraled membranes of individual Schwann cells.
Mechanisms of Progenitor Maturation Are Conserved in the Striatum and Cortex
Authors: Burrows Robert C. , Lillien Laura , Levitt Pat
Published: April 2003

We recently reported that developmental changes in the expression of epidermal growth factor receptors (EGFRs) by cortical progenitor cells regulate their fate and migration. Higher levels of EGFRs are expressed by later embryonic progenitor cells and are required for several responses to EGF family ligands, including astrocyte differentiation and migration. Progenitor cells in the ganglionic eminence (GE), the forerunner of the striatum, also exhibit a developmental increase in EGFR expression. The striatum differs from the cortex in several respects, including cytoarchitecture, the timing of changes in EGFRs, and the level of transforming growth factor-α (TGFα) expression. To determine whether signaling mediated by EGFRs in GE progenitors regulates their fate and migration as observed in cortex, we used a retrovirus to increase EGFR expression in embryonic GE progenitor cells prematurely. As in cortex, premature elevation of EGFRs promoted the departure of GE progenitors from the ventricular zone and their differentiation into astrocytes. Settling patterns of infected cells in the striatum, however, differed from the patterns observed in cortex. In addition, the extent of premature astrocyte differentiation reached similar levels in striatal cells, even in the presence of greater endogenous TGFα. These findings suggest that additional factors play an important role in modulating EGFR-mediated changes in cell fate. Together with previous studies in cortex, these observations in the striatum indicate that a conserved mechanism involving developmental changes in EGFR expression regulates cell fate and the timing of migration.
Chick Homeobox Gene cDlx Expression Demarcates the Forebrain Anlage, Indicating the Onset of Forebrain Regional Specification at Gastrulation
Authors: Borghjid Saihan , Siddiqui M.A.Q.
Published: April 2003

Here we describe the isolation and characterization of a chick homeobox-containing gene, cDlx, which shows greater than 85% homology to the homeodomain of other vertebrate Distal-less genes. Northern blot analysis and in situ hybridization studies reveal that cDlx expression is developmentally regulated and is tissue specific. In particular, the developmental expression pattern is characterized by an early appearance of cDlx transcript in the prospective forebrain region of gastrulating embryos. During neurulation, cDlx is consistently expressed in a spatially restricted domain in the presumptive ventral forebrain region of the neural plate that will give rise to the hypothalamus and the adenohypophysis. Our data support the notion that members of the Dlx gene family are part of a homeobox gene code in forebrain pattern formation and suggest that regional specification of the forebrain occurs at much earlier stages than previously thought. The homeobox gene cDlx may thus play a role in defining forebrain regional identity as early as gastrulation.