bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of advanced glycation end‐product (AGE) levels in nervous tissue proteins of diabetic Lewis rats following islet transplants is related to different durations of poor metabolic control
Authors: Sensi Maurizio , Morano Susanna , Morelli Stefania , Castaldo Paola , Sagratella Elisabetta , De Rossi Maria Grazia , Andreani Domenico , Caltabiano Vera , Vetri Mario , Purrello Francesco , Di Mario Umberto
Published: December 2004

Advanced glycation end‐products (AGEs) are irreversible compounds which, by abnormally accumulating over proteins as a consequence of diabetic hyperglycaemia, can damage tissues and thus contribute to the pathogenesis of diabetic complications. This study was performed to evaluate whether restoration of euglycaemia by islet transplantation modifies AGE accumulation in central and peripheral nervous tissue proteins and, as a comparison, in proteins from a non‐nervous tissue. Two groups of streptozotocin diabetic inbred Lewis rats with 4 (T1) or 8 (T2) months disease duration were grafted into the liver via the portal vein with 1200–1500 islets freshly isolated from normal Lewis rats. Transplanted rats, age‐matched control and diabetic rats studied in parallel, were followed for a further 4‐month period. At study conclusion, glycaemia, glycated haemoglobin and body weight were measured in all animals, and an oral glucose tolerance test (OGTT) performed in transplanted rats. AGE levels in cerebral cortex, spinal cord, sciatic nerve proteins and tail tendon collagen were measured by enzyme‐linked immunosorbent assay (ELISA). Transplanted animal OGTTs were within normal limits, as were glycaemia and glycated haemoglobin. Diabetic animal AGEs were significantly higher than those of control animals. Protein AGE values were reduced in many transplanted animals compared to diabetic animals, reaching statistical significance in spinal cord (P < 0.05), sciatic nerve (P < 0.02) and tail tendon collagen (P < 0.05) of T1 animals. Thus, return to euglycaemia following islet transplantation after 4 months of diabetes with poor metabolic control reduces AGE accumulation rate in the protein fractions of the mixed and purely peripheral nervous tissues (spinal cord and sciatic nerve, respectively). However, after a double duration of bad metabolic control, a statistically significant AGE reduction has not been achieved in any of the tissues, suggesting the importance of an early therapeutic intervention to prevent the possibly pathological accumulation of AGEs in nervous and other proteins.
MuSC, a novel member of the immunoglobulin superfamily, is expressed in neurons of a subset of cranial sensory ganglia in the mouse embryo
Authors: Sekine‐Aizawa Yoko , Omori Akira , Fujita Shinobu C.
Published: December 2004

In contrast to the spinal sensory ganglia which reiterate a basic organizational and functional unit, each cranial ganglion mediates a distinct sensory modality and exhibits a characteristic pattern of peripheral and central neuronal connectivity. Molecules responsible for establishment and maintenance of the cranial ganglion‐specific networks are not known. Our hamster monoclonal antibody 802C11 strongly stained neurons and their processes of the VIIIth cranial ganglion (hearing and equilibrium), but not of the Vth cranial (somatosensory) or spinal ganglia in the mouse embryo. The cellular staining pattern of positive neurons suggested that the antigen was associated with the cell membrane, and biochemical analyses of the antigen from adult mouse brain showed the antigen to be a glycosylated intrinsic membrane protein of ≈100 kDa. The antigen was purified, and based on the partial amino acid sequences, its entire cDNA was cloned. A bacterially expressed polypeptide encoded by the cDNA was recognized by the antibody. The deduced amino acid sequence revealed that the antigen belongs to the immunoglobulin superfamily with a significant homology (73.5% identity) to chicken SC1 protein. Chicken SC1 has been shown to be a cell–cell adhesion molecule in vitro with a proposed role in neurite extension of spinal motor neurons. These results suggest that our murine SC1‐related protein (MuSC) is involved in the pathfinding and/or fasciculation of specific cranial sensory nerve fibres.
Electrophysiological and neurochemical study of the rat geniculo‐cortical pathway. Evidence for glutamatergic neurotransmission
Authors: Sáez J. A. , Palomares J. M. , Vives F. , Domínguez I. , Villegas I. , Montes R. , Price D. J. , Ferrer J. M. R.
Published: December 2004

The projection from the dorsal lateral geniculate nucleus to the primary visual cortex of the rat was studied electrophysiologically. Electrical stimulation of the dorsal lateral geniculate nucleus and the optic tract produced three types of responses on neurons of area 17: excitation followed by inhibition, excitation and inhibition. These results extend and confirm, in adult rats, previous studies done in rat geniculate‐visual cortex cocultures preparations in vitro. The role of glutamate in the neurotransmission of the rat geniculo‐cortical pathway was also investigated. In a first set of experiments, the effects of kynurenate, an antagonist of glutamate receptors, on visual cortex neurons with a monosynaptic excitatory response to dorsal lateral geniculate nucleus stimulation were studied. Microiontophoresis of kynurenate in area 17 neurons selectively suppressed the excitatory response to dorsal lateral geniculate nucleus and optic tract stimulation. In a second set of experiments, the effects of electrical stimulation of the dorsal lateral geniculate nucleus and the optic tract on the release of amino acids in the rat visual cortex in vivo were studied. Using the push–pull method, we perfused a discrete region of the visual cortex with artificial cerebrospinal fluid (CSF), and the amino acid content of the perfusates was analysed by high performance liquid chromatography (HPLC). Stimulation of either the dorsal lateral geniculate nucleus or the optic tract significantly increased glutamate release in area 17. The rest of the amino acids studied did not show significant changes. The results provide evidence for the participation of glutamate in the neurotransmission of the geniculo‐cortical pathway in the rat.
Neuroactive steroids induce GABAA receptor‐mediated depolarizing postsynaptic potentials in hippocampal CA1 pyramidal cells of the rat
Authors: Burg M. , Heinemann U. , Schmitz D.
Published: December 2004

Intracellular recordings were performed in area CA1 pyramidal cells of rat hippocampal slices to determine the effects of certain steroids on inhibitory postsynaptic potentials/currents (IPSP/Cs) mediated by GABAA receptors. Following application of the steroids 5α‐pregnan‐3α,21‐diol‐20‐one (5α‐THDOC), alphaxalone and 5β‐pregnan‐3α‐ol‐20‐one (pregnanolone) hyperpolarizing PSPs developed into biphasic responses consisting of an early hyperpolarizing and a late depolarizing PSP sequence. Steroid‐induced depolarizing PSPs could be elicited in the presence of antagonists to non‐NMDA, NMDA, and GABAB receptors, indicating that these receptor types do not contribute significantly to the initiation of these responses. Depolarizing PSPs were completely blocked by both GABAA receptor antagonists bicuculline and t‐butylbicyclophosphorothionat (TBPS) providing evidence for their mediation by GABAA receptors. The reversal potential of steroid‐induced late inward PSCs, measured in single‐electrode voltage clamp, was −29.9 ± 5.3 mV, whereas the early outward current, which corresponded to the early hyperpolarizing component of PSPs, reversed at −68.2 ± 1.5 mV. Depolarizing PSPs and late inward PSCs were sensitive to reduction of extracellular [HCO3–] and block of carbonic anhydrase by application of acetazolamide. The results suggest that certain neuroactive steroids can induce GABAA receptor‐mediated depolarizing PSPs, which are dependent on HCO3–.
Survival motor neuron (SMN) protein in rat is expressed as different molecular forms and is developmentally regulated
Authors: Bella Vincenzo La , Cisterni Claire , Salaün Danièle , Pettmann Brigitte
Published: December 2004

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by a progressive degeneration of motoneurons in spinal cord and brainstem. The telomeric copy of a duplicated gene termed survival motor neuron (smn), which maps to chromosome 5q13, has been found to be deleted in most patients. The encoded gene product is a novel protein which recently has been shown to accumulate in specific nuclear organelles (gemini of coiled bodies, GEMS), and to play a part in the formation of the spliceosome complex. We have cloned and sequenced the rat smn cDNA. Antibodies generated against an N‐terminus peptide recognized a main protein of 32 kDa in immunoblots of rat embryonic tissue extracts. Minor bands of 35 kDa, 45 kDa and, in perinatal muscle, of 24 kDa were also specifically detected, indicating that SMN is expressed as different molecular forms. Subcellular fractionation indicated that the 32 kDa form is mainly soluble, while the 35 kDa and 45 kDa products segregate to the microsomal–mitochondrial fraction. SMN protein is highly regulated during development: expression is high in embryonic tissues (central nervous system, muscle, lung and liver), and then progressively decreases to very low levels in most tissues of the adult. The demonstration of different molecular forms of SMN along with its developmental regulation may help to understand the contribution of this protein in the appearance of SMA phenotype.
Expression of the GABAA receptor γ4‐subunit gene: anatomical distribution of the corresponding mRNA in the domestic chick forebrain and the effect of imprinting training
Authors: Harvey Robert J. , McCabe Brian J. , Solomonia Revaz O. , Horn Gabriel , Darlison Mark G.
Published: December 2004

The learning process of imprinting involves morphological, electrophysiological and biochemical changes in a region of the chick (Gallus gallus domesticus) forebrain known as the intermediate and medial part of the hyperstriatum ventrale (IMHV). The alterations include increases in the mean length of postsynaptic density profiles of axospinous synapses and the number of N‐methyl‐d‐aspartate (NMDA) receptor binding sites, and changes in spontaneous and evoked electrical activity. Recent immunocytochemical and behavioural studies have suggested that inhibitory GABAergic neurotransmission plays a role in learning. In this context, it has previously been reported that a novel avian γ‐aminobutyric acid (GABA) type A (GABAA) receptor gene, encoding the γ4 subunit, is highly expressed in the hyperstriatum ventrale. In this study, we have used in situ hybridization to map, in detail, the expression of the γ4‐subunit gene in the chick brain, and to assess the effect of imprinting training on the level of the corresponding transcript. Our results reveal that the γ4‐subunit mRNA has a restricted distribution, and demonstrate a highly significant, time‐dependent effect of training on its steady‐state level. At 10 h but not at 5 h after training there is a decrease (25–32%) in the amount of this transcript in parts of the medial hyperstriatum ventrale, including the IMHV. A decrease (28–39%) is also seen in certain visual and auditory pathway areas but no effect was observed in other forebrain regions such as the hyperstriatum intercalatus superior (HIS). These results suggest that imprinting training leads to a time‐dependent down‐regulation of GABAergic transmission, and raise the possibility that this down‐regulation plays a role in learning.
Rapid modulation of cortical proprioceptive activity induced by transient cutaneous deafferentation: neurophysiological evidence of short‐term plasticity across different somatosensory modalities in humans
Authors: Tinazzi Michele , Rosso Tiziana , Zanette Giampietro , Fiaschi Antonio , Aglioti Salvatore M.
Published: December 2004

Single cell recording in non‐human primates shows plastic changes of cortical somatic representations across different types of somatic inputs originating from the same peripheral territory. In humans, muscle afferents from first dorsal interosseus are supplied by the ulnar nerve while the cutaneous territory overlying this muscle is supplied by the radial nerve. This peculiar anatomical nervous distribution allowed us to devise an experimental model which provided a unique opportunity to assess, in humans with a non‐invasive technique, the functional relationships between cutaneous and muscle afferent inputs originating from the same peripheral territory. We recorded spinal, brainstem and cortical somatosensory potentials evoked by stimulation of muscle afferents of the right first dorsal interosseus before, during and after anaesthetic block of the sensitive branch of the ipsilateral radial nerve. Amplitude of parietal N20 and P27 and frontal N30 somatosensory evoked potential components showed an increase of amplitudes with more profound anaesthesia. Amplitudes returned to pre‐anaesthetic values several minutes after anaesthesia. By contrast, spinal N13 and brainstem P14 potentials did not change throughout the experiment. Results show, for the first time in humans, that a transient cutaneous deafferentation may induce rapid modulation of cortical activity evoked by stimulation of muscle afferents originating in the anaesthetic territory.
Glutamate activates NF‐κB through calpain in neurons
Authors: Schölzke Marion N. , Potrovita Ioana , Subramaniam Srinivasa , Prinz Simone , Schwaninger Markus
Published: December 2004

Glutamate induces gene transcription in numerous physiological and pathological conditions. Among the glutamate‐responsive transcription factors, NF‐κB has been mainly implicated in neuronal survival and death. Recent data also suggest a role of NF‐κB in neural development and memory formation. In non‐neuronal cells, degradation of the inhibitor IκBα represents a key step in NF‐κB activation. However, little is known of how glutamate activates NF‐κB in neurons. To investigate the signalling cascade involved we used primary murine cerebellar granule cells. Glutamate induced a rapid reduction of IκBα levels and nuclear translocation of the NF‐κB subunit p65. The glutamate‐induced reduction of IκBα levels was blocked by the N‐methyl‐d‐aspartate inhibitor MK801. Specific inhibitors of the proteasome, caspase 3, and the phosphoinositide 3‐kinase had no effect on glutamate‐induced IκBα degradation. However, inhibition of the glutamate‐activated Ca2+‐dependent protease calpain by calpeptin completely blocked IκBα degradation and reduced the nuclear translocation of p65. Calpeptin also partially blocked glutamate‐induced cell death. Our data indicate that the Ca2+‐dependent protease calpain is involved in the NF‐κB activation in neurons in response to N‐methyl‐d‐aspartate receptor occupancy by glutamate. NF‐κB activation by calpain may mediate the long‐term effects of glutamate on neuron survival or memory formation.
Kv3 voltage‐gated potassium channels regulate neurotransmitter release from mouse motor nerve terminals
Authors: Brooke Ruth E. , Moores Thomas S. , Morris Neil P. , Parson Simon H. , Deuchars Jim
Published: December 2004

Voltage‐gated potassium (Kv) channels are critical to regulation of neurotransmitter release throughout the nervous system but the roles and identity of the subtypes involved remain unclear. Here we show that Kv3 channels regulate transmitter release at the mouse neuromuscular junction (NMJ). Light‐ and electron‐microscopic immunohistochemistry revealed Kv3.3 and Kv3.4 subunits within all motor nerve terminals of muscles examined [transversus abdominus, lumbrical and flexor digitorum brevis (FDB)]. To determine the roles of these Kv3 subunits, intracellular recordings were made of end‐plate potentials (EPPs) in FDB muscle fibres evoked by electrical stimulation of tibial nerve. Tetraethylammonium (TEA) applied at low concentrations (0.05–0.5 mm), which blocks only a few known potassium channels including Kv3 channels, did not affect muscle fibre resting potential but significantly increased the amplitude of all EPPs tested. Significantly, this effect of TEA was still observed in the presence of the large‐conductance calcium‐activated potassium channel blockers iberiotoxin (25–150 nm) and Penitrem A (100 nm), suggesting a selective action on Kv3 subunits. Consistent with this, 15‐µm 4‐aminopyridine, which blocks Kv3 but not large‐conductance calcium‐activated potassium channels, enhanced evoked EPP amplitude. Unexpectedly, blood‐depressing substance‐I, a toxin selective for Kv3.4 subunits, had no effect at 0.05–1 µm. The combined presynaptic localization of Kv3 subunits and pharmacological enhancement of EPP amplitude indicate that Kv3 channels regulate neurotransmitter release from presynaptic terminals at the NMJ.
Shifting baselines and the decline of pelagic sharks in the Gulf of Mexico
Authors: Baum Julia K. , Myers Ransom A.
Published: December 2004

Historical abundances of many large marine vertebrates were tremendously greater than today. However, while pelagic sharks are known to have declined rapidly in the northwest Atlantic in recent years, there, as elsewhere, little is known about the former natural abundances of these species. Here, we compare initial (1950s) and recent (late‐1990s) standardized catch rates of pelagic sharks in the Gulf of Mexico, the area where methods of exploitation between these two periods were most comparable. We estimate that oceanic whitetip and silky sharks, formerly the most commonly caught shark species, have declined by over 99 and 90%, respectively. That the former prevalence of oceanic whitetip sharks in this ecosystem is unrecognized today is clear evidence of shifting baselines. Our analysis provides the missing baseline for pelagic sharks in the Gulf of Mexico that is needed for the rational management and restoration of these species.
Haldane rules: costs of outbreeding at production of daughters in sand lizards
Authors: Olsson Mats , Ujvari Beata , Madsen Thomas , Uller Tobias , Wapstra Erik
Published: December 2004

Haldane's rule is one of the most widely applicable paradigms in evolutionary biology, stating that in species crossings, the heterogametic sex will suffer more severely in terms of sterility and inviability. We address this in a within‐species outbreeding situation by assessing the risk of producing inviable offspring depending on the sex ratio of the clutch produced in between‐population crossings in the laboratory. In crossings between male and female sand lizards (Lacerta agilis) from two different sampling regions, one in Sweden, one in central Europe, risk of gametic incompatibility is unaffected by outbreeding, but offspring from between‐population crossings show 300% higher malformation frequency and 10% lower hatching success. The risk of having inviable offspring increases with the production of daughters, i.e. the hemizygous sex in this species (ZW). Such sex‐specific genetic costs of offspring production need to be incorporated into life history ecology, e.g. sex allocation theory.
‘As Earth's testimonies tell’: wilderness conservation in a changing world
Authors: Gillson Lindsey , Willis Katherine J.
Published: December 2004

Too often, wilderness conservation ignores a temporal perspective greater than the past 50 years, yet a long‐term perspective (centuries to millennia) reveals the dynamic nature of many ecosystems. Analysis of fossil pollen, charcoal and stable isotopes, combined with historical analyses and archaeology can reveal how ongoing interactions between climatic change, human activities and other disturbances have shaped today's landscapes over thousands of years. This interdisciplinary approach can inform wilderness conservation and also contribute to interpreting current trends and predicting how ecosystems might respond to future climate change. In this paper, we review literature that reveals how increasing collaboration among palaeoecologists, archaeologists, historians, anthropologists and ecologists is improving understanding of ecological complexity. Drawing on case studies from forested and non‐forested ecosystems in Europe, the Americas, Africa and Australia, we discuss how this integrated approach can inform wilderness conservation and ecosystem management.
Genome mosaicism is conserved but not unique in Pseudomonas aeruginosa isolates from the airways of young children with cystic fibrosis
Authors: Ernst Robert K. , D′Argenio David A. , Ichikawa Jeffrey K. , Bangera M. Gita , Selgrade Sara , Burns Jane L. , Hiatt Peter , McCoy Karen , Brittnacher Mitchell , Kas Arnold , Spencer David H. , Olson Maynard V. , Ramsey Bonnie W. , Lory Stephen , Miller Samuel I.
Published: December 2004

Pseudomonas aeruginosa strains from the chronic lung infections of cystic fibrosis (CF) patients are phenotypically and genotypically diverse. Using strain PAO1 whole genome DNA microarrays, we assessed the genomic variation in P. aeruginosa strains isolated from young children with CF (6 months to 8 years of age) as well as from the environment. Eighty‐nine to 97% of the PAO1 open reading frames were detected in 20 strains by microarray analysis, while subsets of 38 gene islands were absent or divergent. No specific pattern of genome mosaicism defined strains associated with CF. Many mosaic regions were distinguished by their low G + C content; their inclusion of phage related or pyocin genes; or by their linkage to a vgr gene or a tRNA gene. Microarray and phenotypic analysis of sequential isolates from individual patients revealed two deletions of greater than 100 kbp formed during evolution in the lung. The gene loss in these sequential isolates raises the possibility that acquisition of pyomelanin production and loss of pyoverdin uptake each may be of adaptive significance. Further characterization of P. aeruginosa diversity within the airways of individual CF patients may reveal common adaptations, perhaps mediated by gene loss, that suggest new opportunities for therapy.
Early steps in microbial colonization processes at deep‐sea hydrothermal vents
Authors: Alain Karine , Zbinden Magali , Le Bris Nadine , Lesongeur Françoise , Quérellou Joël , Gaill Françoise , Cambon‐Bonavita Marie‐Anne
Published: December 2004

A pluri‐disciplinary in situ colonization experiment was performed to study early stages of colonization in deep‐sea vent Alvinella spp. worm habitats. Four colonization devices were deployed onto Alvinella spp. colonies of different chimneys of the East‐Pacific Rise (EPR 13°N), for two different periods: a short (less than a week) and a longer one (3 weeks). Video imagery and monitoring of the thermal and physico‐chemical conditions were performed during the colonization experiments. Numerous microorganisms bearing specialized adhesion‐appendages and/or high amounts of polymeric extracellular matrix were observed on devices, which may efficiently contribute to the colonization of new surfaces. The microbial cohorts preceding and accompanying Alvinella spp. settlement were identified. In all cases, Archaea could not be detected and the microbial mats were essentially composed of e‐Proteobacteria. Within this group, one phylotype (AlviH2) was found to dominate the libraries of three colonization devices. Dominance of e‐Proteobacteria in the libraries may reflect the wide physiological variety encountered within this group or an adaptability of these microorganisms towards their changing environment. Bacteria affiliated to the Cytophaga‐Flavobacterium‐Bacteroides group or to the e‐Proteobacteria, that grow either chemo‐organoheterotrophically by fermentation or chemolithoautotrophically with H2 as an electron donor and S°/S2O32– or NO3– as a terminal electron acceptor, were isolated from one of the microbial mat formed in 20 days.
Efficacy and safety comparative evaluation of orlistat and sibutramine treatment in hypertensive obese patients
Authors: Derosa G. , Cicero A. F. G. , Murdolo G. , Piccinni M. N. , Fogari E. , Bertone G. , Ciccarelli L. , Fogari R.
Published: December 2004

Aim:  The aim of our study was to comparatively evaluate the efficacy and safety of orlistat and sibutramine treatment in obese hypertensive patients, with a specific attention to cardiovascular effects and to side effects because of this treatment.

Methods:  Patients were enrolled, evaluated and followed at three Italian Centres of Internal Medicine. We evaluated 115 obese and hypertensive patients. (55 males and 60 females; 26 males and 29 females, aged 50 ± 4 with orlistat; 28 males and 30 females, aged 51 ± 5 with sibutramine). All patients took antihypertensive therapy for at least 6 months before the study. We administered orlistat or sibutramine in a randomized, controlled, double‐blind clinical study. We evaluated anthropometric variables, blood pressure and heart rate (HR) during 12 months of this treatment.

Results:  A total of 113 completed the 4 weeks with controlled energy diet and were randomized to double‐blind treatment with orlistat (n = 55) or sibutramine (n = 58). Significant body mass index (BMI) improvement was present after 6 (p < 0.05), 9 (p < 0.02), and 12 (p < 0.01) months in both groups, and body weight (BW) improvement was obtained after 9 (p < 0.05) and 12 (p < 0.02) months in both groups. Significant waist circumference (WC), hip circumference (HC) and waist/hip ratio (W/H ratio) improvement was observed after 12 months (p < 0.05, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05) was present in orlistat group after 12 months. Lipid profile [total cholesterol (TC), low‐density lipoprotein‐cholesterol (LDL‐C) and triglycerides] reduction (p < 0.05, respectively) was observed in orlistat group and triglyceride reduction (p < 0.05) in sibutramine group after 12 months. No significant change was observed in sibutramine group during the study. No significant HR variation was obtained during the study in both groups. Of the 109 patients who completed the study, 48.1% of patients in the orlistat group and 17.5% of patients in the sibutramine group had side effects (p < 0.05 vs. orlistat group). Side‐effect profiles were different in the two treatment groups. All orlistat side effects were gastrointestinal events. Sibutramine caused an increase in blood pressure (both SBP and DBP) in two patients, but it has been controlled by antihypertensive treatment. The vitamin changes were small and all mean vitamin and β‐carotene values stayed within reference ranges. No patients required vitamin supplementation.

Conclusions:  Both orlistat and sibutramine are effective on anthropometric variables during the 12‐month treatment; in our sample, orlistat has been associated to a mild reduction in blood pressure, while sibutramine assumption has not be associated to any cardiovascular effect and was generically better tolerated than orlistat.
Incidence of insulin resistance in obese subjects in a rural Japanese population: The Tanno and Sobetsu study
Authors: Ohnishi H. , Saitoh S. , Takagi S. , Ohata J. , Takeuchi H. , Isobe T. , Katoh N. , Chiba Y. , Fujiwara T. , Akasaka H. , Shimamoto K.
Published: December 2004

Objectives:  Although it is well known that obesity is closely related to insulin resistance, the incidence of the development of insulin resistance in people with obesity is not known. In this study, we investigated the incidence of insulin resistance in citizens of two rural communities in Japan.

Subjects and methods:  The subjects were 102 men and 126 women over the age of 30 years selected from 1035 citizens who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, in 1991 and 1998. Those who were on medication for hypertension, diabetes, hyperlipidaemia, coronary heart disease and cerebral vessel disease were excluded. The simple index to determine insulin resistance [i.e. homeostasis model assessment (HOMA‐R) ≥ 1.73] was used, and subjects who were determined to be positive for insulin resistance according to this index in 1991 were also excluded in order to determine the incidence of insulin resistance in subjects who had no abnormalities other than obesity. The systolic blood pressure (SBP), diastolic blood pressure, body mass index (BMI), triglyceride level, high‐density lipoprotein level, blood sugar level, serum insulin value and HOMA‐R were measured in all subjects in 1991 and in 1998. Moreover, the subjects were divided into two groups according to BMI, a normal group consisting of subjects with BMI < 25 and an obesity group consisting of subjects with BMI ≥ 25. We also compared the incidences of insulin resistance in normal and obesity groups of subjects who were newly determined to be positive for insulin resistance on the basis of data obtained from medical examinations conducted in 1998.

Results:  The incidence of insulin resistance was significantly higher in the obesity group than in the normal group (25.0 vs. 4.5%). The results of logistic regression analysis showed that obesity was closely related to insulin resistance and that the relative risk of development of insulin resistance adjusted for age, sex, SBP, FPG and HDL was 3.193 (95% CI 1.085–9.401).

Conclusions:  The incidence of insulin resistance was significantly higher in the obesity group than in the normal group in this study, suggesting that improvement in obesity is important for prevention of the occurrence of type 2 diabetes or atherosclerotic disease based on insulin resistance.
Progression to clinically diagnosed and treated diabetes from impaired glucose tolerance and impaired fasting glycaemia
Authors: Qiao Q. , Lindström J. , Valle T. T. , Tuomilehto J.
Published: December 2004

Aims  To evaluate the risk of diabetes in subjects with impaired fasting glycemia (IFG) as compared with impaired glucose tolerance (IGT) and normal glucose tolerance.

Methods  Men (1223) and women (1370) aged 45–64 years and free of diabetes at baseline were followed‐up for 10 years, with 26 737 person years accumulated. The incident diabetic cases were identified through the national Drug Register and the Hospital Discharge Register.

Results  During the 10 years of follow‐up, 53 (4.3%) men and 47 (3.4%) women developed diabetes. IFG alone defined 22 (15.5/1000 person years) diabetic cases, which was higher than for subjects with normal fasting glucose. Subjects with isolated IGT identified an additional 34 cases (155% more) which could not be defined by IFG alone. The area under the ROC curve was larger for 2‐h glucose (0.77, 95% CI 0.72–0.82) than for fasting glucose (0.65, 0.58–0.71). The multivariate adjusted Cox hazard ratio was higher for isolated IGT (3.9, 95% CI 2.4–6.2) than for isolated IFG (2.3, 0.9–5.7) as compared with subjects with neither IFG nor IGT.

Conclusion  Both IFG and IGT are risk predictors for diabetes, but IGT defines a much larger target population for prevention.
Isolation of enterovirus strains from children with preclinical Type 1 diabetes
Authors: Salminen K. K. , Vuorinen T. , Oikarinen S. , Helminen M. , Simell S. , Knip M. , Ilonen J. , Simell O. , Hyöty H.
Published: December 2004

Aims  To develop methods for isolation of enterovirus strains from subjects with preclinical Type 1 diabetes and evaluate if their presence in stools is associated with beta‐cell damage.

Methods  The study subjects were participants of the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP). The prospectively followed birth cohort comprised 12 children who turned positive for diabetes‐associated autoantibodies during the follow‐up (case children) and 53 controls matched for date of birth, sex and HLA‐DQB1 alleles. Altogether, 878 stool samples were analysed for the presence of enterovirus RNA by RT‐PCR followed by virus isolation and partial sequencing of viral genome. Enterovirus antibodies and RNA were simultaneously analysed from serum.

Results  Eleven enterovirus infections were diagnosed in case children and 42 infections in control children by the presence of viral RNA in stools. The proportion of children who were repeatedly enterovirus RNA‐positive stools was higher among case than control children (42% vs. 11% of children; P = 0.02). Combined serum (antibody and RT‐PCR) and stool analyses indicated at least one enterovirus infection in 83% of the case children before the appearance of autoantibodies, while only 42% of the control children had infection by the same age (P = 0.006). Twelve enterovirus strains were isolated from case children and 38 strains from control children.

Conclusions  This protocol makes it possible to isolate a large number of enterovirus strains from prediabetic subjects. The findings suggest that enterovirus infections may be associated with the beta‐cell damaging process.

Diabet. Med. 21, 156–164 (2004)
Carotid haemodynamic parameters as risk factors for cerebral infarction in Type 2 diabetic patients
Authors: Nakatou T. , Nakata K. , Nakamura A. , Itoshima T.
Published: December 2004

Aims  The purpose of this study was to investigate the usefulness of carotid haemodynamic parameters, i.e. the resistive index (RI) and the pulsatility index (PI), in estimating the risk of cerebral infarction in Type 2 diabetic patients.

Methods  Three hundred and eighty‐two Type 2 diabetic patients (223 men and 159 women; mean age 61 years, range 40–88; 40 had a history of cerebral infarction) and 110 control subjects were analysed in a cross‐sectional study. All subjects underwent ultrasonography of the common carotid artery, with determination of intima‐media thickness (IMT), RI, and PI. A SMART (Second Manifestations of ARTerial Disease) atherosclerosis risk score was determined for all diabetic patients.

Results  The mean values for IMT, RI, and PI were increased in diabetic patients compared with control subjects, and they were significantly elevated in patients with previous cerebral infarction compared with patients without cerebral infarction. (IMT 0.88 ± 0.22 vs. 0.77 ± 0.19, P < 0.005; RI 0.77 ± 0.07 vs. 0.75 ± 0.06, P < 0.05; PI 1.88 ± 0.36 vs. 1.71 ± 0.36, P < 0.01) Significant but weak correlations were found between SMART risk scores and IMT, RI and PI (IMT r = 0.390, P < 0.0001; RI r = 0.346, P < 0.0001; PI r = 0.393, P < 0.0001). The multiple logistic model showed that both the IMT [odds ratio (OR) 6.50, 95% confidence interval (CI) 3.42, 12.34] and the PI (OR 4.16, 95% CI 2.36, 7.34) were independent risk factors for cerebral infarction. The subjects who had an IMT of > 1.0 and a PI > 2.00 had a greater risk of developing a cerebral infarction than did the subjects who had an IMT of < 1.0 and a PI < 2.00 (OR 6.21, 95% CI 2.26, 17.05).

Conclusions  The results of this cross‐sectional study showed that the measurement of haemodynamic parameters was useful, together with IMT, in estimating the risk of previous cerebral infarction in Type 2 diabetic patients. The predictive value of these parameters in identifying the risk of future cerebral infarction must await the results of future prospective studies.
Treatment of symptomatic diabetic polyneuropathy with the antioxidant α‐lipoic acid: a meta‐analysis
Authors: Ziegler D. , Nowak H. , Kempler P. , Vargha P. , Low P. A.
Published: December 2004

Aims  To determine the efficacy and safety of 600 mg of α‐lipoic acid given intravenously over 3 weeks in diabetic patients with symptomatic polyneuropathy.

Methods  We searched the database of VIATRIS GmbH, Frankfurt, Germany, for clinical trials of α‐lipoic acid according to the following prerequisites: randomized, double‐masked, placebo‐controlled, parallel‐group trial using α‐lipoic acid infusions of 600 mg i.v. per day for 3 weeks, except for weekends, in diabetic patients with positive sensory symptoms of polyneuropathy which were scored by the Total Symptom Score (TSS) in the feet on a daily basis. Four trials (ALADIN I, ALADIN III, SYDNEY, NATHAN II) comprised n = 1258 patients (α‐lipoic acid n = 716; placebo n = 542) met these eligibility criteria and were included in a meta‐analysis based on the intention‐to‐treat principle. Primary analysis involved a comparison of the differences in TSS from baseline to the end of i.v. Treatment between the groups treated with α‐lipoic acid or placebo. Secondary analyses included daily changes in TSS, responder rates (≥ 50% improvement in TSS), individual TSS components, Neuropathy Impairment Score (NIS), NIS of the lower limbs (NIS‐LL), individual NIS‐LL components, and the rates of adverse events.

Results  After 3 weeks the relative difference in favour of α‐lipoic acid vs. placebo was 24.1% (13.5, 33.4) (geometric mean with 95% confidence interval) for TSS and 16.0% (5.7, 25.2) for NIS‐LL. The responder rates were 52.7% in patients treated with α‐lipoic acid and 36.9% in those on placebo (P < 0.05). On a daily basis there was a continuous increase in the magnitude of TSS improvement in favour of α‐lipoic acid vs. placebo which was noted first after 8 days of treatment. Among the individual components of the TSS, pain, burning, and numbness decreased in favour of α‐lipoic acid compared with placebo, while among the NIS‐LL components pin‐prick and touch‐pressure sensation as well as ankle reflexes were improved in favour of α‐lipoic acid after 3 weeks. The rates of adverse events did not differ between the groups.

Conclusions  The results of this meta‐analysis provide evidence that treatment with α‐lipoic acid (600 mg/day i.v.) over 3 weeks is safe and significantly improves both positive neuropathic symptoms and neuropathic deficits to a clinically meaningful degree in diabetic patients with symptomatic polyneuropathy.

Diabet. Med. 21, 114–121 (2004)
Evidence for a Type 1 diabetes‐specific mechanism for the insulin gene‐associated IDDM2 locus rather than a general influence on autoimmunity
Authors: Tait K. F. , Collins J. E. , Heward J. M. , Eaves I. , Snook H. , Franklyn J. A. , Barnett A. H. , Todd J. A. , Maranian M. , Compston A. , Sawcer S. , Gough S. C. L.
Published: December 2004

Aims  The Type 1 diabetes susceptibility locus, IDDM2, has been mapped to a variable number of tandem repeats (VNTR) region 5′ upstream of the insulin (INS) and insulin‐like growth factor (IGF2) genes on chromosome 11p15. The function of the VNTR is uncertain; however, it may influence the thymic expression of the insulin gene and affect the development of immune self‐tolerance. The aim of this study was to investigate whether the INS VNTR region is a Type 1 diabetes‐specific locus or acting as a general autoimmunity gene.

Methods  We genotyped the INS‐IGF2 VNTR [using the surrogate INS−23 HphI single nucleotide polymorphism (SNP)] in 823 Graves’ disease (GD)/multiple sclerosis (MS) families, 1433 GD/MS patients and 837 healthy control subjects.

Results  We found no evidence of excess transmission of the allele associated with Type 1 diabetes to individuals affected by GD or MS within the families. Analysis of the case–control dataset showed no genotypic or allelic difference between the two populations.

Conclusions  These data suggest that the INS‐IGF2 VNTR is acting as a Type 1 diabetes‐specific susceptibility gene rather than as an influence on general autoimmunity.
Is visual reference necessary? Contributions of facial versus vocal cues in 12‐month‐olds’ social referencing behavior
Authors: Vaish Amrisha , Striano Tricia
Published: December 2004

To examine the influences of facial versus vocal cues on infants’ behavior in a potentially threatening situation, 12‐month‐olds on a visual cliff received positive facial‐only, vocal‐only, or both facial and vocal cues from mothers. Infants’ crossing times and looks to mother were assessed. Infants crossed the cliff faster with multimodal and vocal than with facial cues, and looked more to mother in the Face Plus Voice compared to the Voice Only condition. The findings suggest that vocal cues, even without a visual reference, are more potent than facial cues in guiding infants’ behavior. The discussion focuses on the meaning of infants’ looks and the role of voice in development of social cognition.
Tuned to the signal: the privileged status of speech for young infants
Authors: Vouloumanos Athena , Werker Janet F.
Published: December 2004

Do young infants treat speech as a special signal, compared with structurally similar non‐speech sounds? We presented 2‐ to 7‐month‐old infants with nonsense speech sounds and complex non‐speech analogues. The non‐speech analogues retain many of the spectral and temporal properties of the speech signal, including the pitch contour information which is known to be salient to young listeners, and thus provide a stringent test for a potential listening bias for speech. Our results show that infants as young as 2 months of age listened longer to speech sounds. This listening selectivity indicates that early‐functioning biases direct infants’ attention to speech, granting speech a special status in relation to other sounds.
Infant social attention predicts preschool social cognition
Authors: Wellman Henry M. , Phillips Ann T. , Dunphy‐Lelii Sarah , LaLonde Nicole
Published: December 2004

Recent research examining infants’ understanding of intentional action claims to be studying the early origins or precursors of children's later theories of mind. If these infant understandings are continuous with later preschool achievements, there should be empirical connections between the two. We provide initial evidence that infants’ social attention predicts later social cognition. Specifically, 14‐month‐olds’ habituation to human intentional action significantly predicts later preschool mentalistic construal of persons, as measured on a Theory of Mind Scale.
It's Theories All the Way Down: A Response to Scientific Research in Education
Authors: Gee James Paul
Published: December 2004

This article considers the six principles that the National Research Council's report Scientific Research in Education claims define an enterprise as scientific. I argue that these principles are relatively vacuous generalities because one cannot determine anything about any of them from outside specific theories of specific domains (and domains are smaller, usually considerably smaller, than disciplines). Such theories can differ greatly on how they would define the meanings of the words in the six principles. In the end, I argue that we ought to compare specific theories and their track records, caring less about what “science” is and more about using theories with good track records.
Agency in Borderland Discourses: Examining Language Use in a Community Center with Black Queer Youth
Authors: Blackburn Mollie V.
Published: December 2004

This article focuses on the ways in which a small group consisting mostly of Black queer youth makes sense of their use of language to assert agency in a world that is often heterosexist, homophobic, ageist, and racist. The author draws from the work of Gee and Anzaldúa to identify what youth call “Gaybonics,” as a Borderland Discourse that is intertwined with Ebonics. The author and youth worked together in a youth-run center for lesbian, gay, bisexual, transgender, and questioning youth to analyze the ways that these youth engaged in Gaybonics to elicit pleasure and subvert oppression, and, when their borders were violated, they shifted from this discourse to another to retaliate against hatred. When youth analyzed their use of Borderland Discourses, they came to understand the ways that they engage in such discourses to position themselves as agents and the power they can (and cannot) access by engaging in various discourses. The author asserts that youth need opportunities to explore such access to power through language, particularly in the margins, as conceptualized by hooks. Finally, the author calls for work with youth that not only supports their assertion of agency but also their efforts at activism.
The Danger of Deference: A Case of Polite Governance
Authors: Minor James T. , Tierney William G.
Published: December 2004

Over the past decade numerous arguments have been put forth that campus governance needs to be reformed to meet new challenges. Rethinking admission standards, implementing distance learning, increasing fund-raising, diversifying the faculty, and creating external partnerships are just a few issues that demand timely and informed decisions. For some individuals, these topics create decision-making contexts that stand in contradiction to the tradition of shared governance. To others, shared governance becomes an obstacle to effective decision-making rather than its vehicle. This study explores a campus where the perception is that “governance works.” The university enjoys a stable organizational history, climate, and administration that are circumscribed by what we will define as a culture of deference. The institution, however, does not appear to struggle over questions of quality such as how they might improve and what actions might create these improvements. The authors question whether a decision-making culture of deference promotes effective campus governance. The text begins with a discussion of what the authors mean by effective governance within an organization's culture and they then present data from an intensive case study of one campus. The authors conclude that cooperation and trust are foundational but insufficient indicators of good governance.
On Making Determinations of Quality in Teaching
Authors: Fenstermacher Gary D. , Richardson Virginia
Published: December 2004

This article examines the notion of quality teaching, exploring its conceptual, empirical and normative properties. We begin by analyzing the concept of teaching, separating it into its task sense (what teachers try to do) and its achievement sense (the student learning that teachers foster). The analysis suggests that any determination of quality in teaching must account for both the worthiness of the activity (good teaching) as well as the realization of intended outcomes (successful teaching). Good teaching is not the same as successful teaching, nor does one logically entail the other. For teaching to be both good and successful, it must be conjoined with factors well beyond the range of control of the classroom teacher. The analysis of the concept of teaching is then used to explore three programs of research on teaching: process-product, cognitive science, and constructivist. The article concludes with an analysis of the policy implications of this explication of quality teaching.
Integrated approach of cognitive maps and neural networks using qualitative information on the World Wide Web: the KBNMiner
Authors: Hong Taeho , Han Ingoo
Published: December 2004

Abstract: In this paper, we propose a method for integrating cognitive maps and neural networks to gain competitive advantage using qualitative information acquired from news information on the World Wide Web. We have developed the KBNMiner, which is designed to represent the knowledge of domain experts with cognitive maps, to search and retrieve news information on the Internet according to the knowledge and to apply the information to a neural network model. In addition, we investigate ways to train neural networks more effectively by separating the learning data into two groups on the basis of event information acquired from news information. To validate our proposed method, we applied 180,000 news articles to the KBNMiner. The experimental results are found to support our proposed method through tenfold cross‐validation.