bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma homocysteine and cognitive function in elderly patients with diabetes mellitus
Authors: Araki Atsushi , Ito Hideki , Hosoi Takayuki , Orimo Hajime 
Published: July 2003

Background:  The purpose of the present paper was to investigate a possible contribution of plasma homocysteine to cognitive impairment. To this end the relationship between plasma homocysteine levels and cognitive performance test results were investigated in elderly patients with diabetes.Methods:  A total of 144 elderly patients (39 men and 105 women) with diabetes mellitus, who were free of clinical stroke, were studied. Plasma levels of homocysteine, folate, vitamin B12, vitamin B6, and the C677T polymorphism of methylene tetrahydrofolate reductase were determined. Cognitive function was assessed with the Wechsler Adult Intelligence Scale, Revised (digit symbol substitution, backward digit span, similarities, picture arrangement), Stroop test, Benton Visual Retention Test, and Mini‐Mental State Examination (MMSE).Results:  In elderly women with diabetes, elevated homocysteine levels in the plasma were significantly associated with impairment of cognitive performance assessed with the MMSE, digit symbol substitution test, similarities, Stroop test, and Benton visual retention test, but not the backward digit span test. Multiple logistic regression analyses revealed that the associations between the log‐transformed plasma homocysteine level and low scores of the MMSE and digit symbol substitution test remained significant after adjustment for age, education, hemoglobin (Hb)A1c, systolic blood pressures, insulin treatment, serum levels of folate, vitamin B12, and vitamin B6, and the presence of asymptomatic cerebral infarction on brain magnetic resonance images.Conclusions:  Elevated plasma homocysteine level was independently associated with cognitive impairment in elderly diabetic women. Because the cause of the association between homocysteine and cognitive impairment remains unclear, future intervention studies are necessary to examine whether reducing plasma homocysteine levels prevents cognitive decline in elderly patients with diabetes mellitus.
Association of tumor necrosis factor receptor 1 gene polymorphism with bone mineral density
Authors: Hoshino Shinjiro , Hosoi Takayuki , Shiraki Masataka , Orimo Hajime , Ouchi Yasuyoshi , Inoue Satoshi 
Published: July 2003

Background:  Estrogen deficiency in postmenopausal women causes an increased production of proinflammatory cytokines such as interleukin (IL)‐1, IL‐6, and tumor necrosis factor (TNF)‐α. These cytokines are associated with an increase of bone turnover and an acceleration of bone loss. Tumor necrosis factor‐α is known to promote osteoclastogenesis via TNFR1, one of the tumor necrosis factor receptors (TNFR). Therefore, the purpose of the present report was to investigate the association of TNFR1 gene polymorphism with bone mineral density (BMD) in postmenopausal Japanese women.Methods:  The question of whether a polymorphism of the TNFR1 gene would correlate with osteoporosis in 320 unrelated healthy postmenopausal women in Japan, was investigated. A single nucleotide polymorphism (SNP) located at Pro12 (CCA to CCG) in exon 1 of TNFR1 was utilized.Results:  The subjects were categorized into three genotypes: AA, AG, and GG. The frequency of each genotype was 72.2%, 23.8%, and 4.0%, respectively. The association of this polymorphism with BMD of the lumbar spine and total body, and several bone metabolic markers was then examined. Concerning the TNFR1 gene, the AA group had significantly low total body BMD, compared with the AG + GG group (Z score; 0.285 vs 0.568; P = 0.03), although BMD of the lumbar spine was not statistically different.Conclusion:  These results suggest an association between this SNP of the TNFR1 gene and BMD, and an involvement of TNFR1 in postmenopausal osteoporosis among Japanese.
What determines the life satisfaction of the elderly? Comparative study of residential care home and community in Japan
Authors: Ho Han Kwee , Matsubayashi Kozo , Wada Taizo , Kimura Miyuki , Yano Shoki , Otsuka Kuniaki , Fujisawa Michiko , Kita Toru , Saijoh Kiyofumi 
Published: July 2003

Background:  Increasing lifespan has forced elderly persons and researchers alike to look at life and aging in a new way: at adding life to years rather than years to life. With increasing lifestyle choices for the elderly, the present study was undertaken to determine and compare the factors associated with life satisfaction in elderly living in a residential care home and in the community in Japan.Methods:  This was a cross‐sectional, self‐reported, questionnaire‐based study. Elderly persons from the residential care home in Kyoto City (n = 261, mean age ± SD = 79.6 ± 6.6 years, male : female = 1 : 3.1) and from the town of Urausu, Hokkaido (n = 733, mean age ± SD = 74.8 ± 6.8 years, male : female = 1 : 1.3), participated in the study. This represented 95.3% and 89.5% of all eligible elderly ≥ 65 years in the home and town, respectively. Activities of daily living, higher functions, medical and social history, geriatric depression scale and quality of life were studied. Using multiple logistic regression models, factors associated with high satisfaction of life were identified.Results:  In community‐dwelling elderly, relationship with friends, as opposed to relationship with family for elderly in residential care home, were factors related to life satisfaction.Conclusions:  This study demonstrates the relative importance of social factors versus medical and functional factors as determinants of life of elderly. We have also shown how these factors differ for elderly living in different environments. Understanding these different as well as common determinants of life satisfaction from a whole array of diverse ones allows us to make effective strategy to improve the quality of life of elderly living in different conditions.
Four‐year prospective study of the influence of elevated serum lipoprotein (a) concentration on ischemic heart disease and cerebral infarction in elderly patients with type‐2 diabetes
Authors: Suzuki Tatsuya , Oba Kenzo , Igari Yoshimasa , Matsumura Noriaki , Inuzuka Yuki , Kigawa Yoshiaki , Ajiro Yumiko , Okazaki Kyoji , Nakano Hiroshi , Metori Shohei 
Published: July 2003

Background:  The purpose of the present paper was to elucidate the influence of an elevated serum lipoprotein (a) (Lp(a)) concentration on the incidence of ischemic heart disease (IHD) and perforating artery occlusion‐type cerebral infarction (CI) in elderly patients with type‐2 diabetes.Methods:  The serum Lp(a) levels in type‐2 diabetic subjects aged ≥60 years (n = 158; 81 male, 77 female) were measured. At the commencement of the study, subjects were allocated on the basis of past history of CI to a CI– or CI+ group, and on the basis of past history of angina pectoris or myocardial infarction to an IHD– or IHD+ group. They were followed up prospectively for 4 years and the incidences of IHD and CI were monitored. Diagnoses of CI were confirmed by computed tomography (CT), and of myocardial infarction by electrocardiography and blood chemistry. Serum Lp(a) levels of ≥ 20 mg/dL were considered elevated, and < 20 mg/dL as normal. Kaplan–Meier survival analysis (log–rank test) was used to assess the time to event rate stratified by an Lp(a) cut‐off of 20 mg/dL. The predictive value for CI or IHD events was assessed by multiple logistic regression analysis.Results:  The probability of IHD events was significantly higher in the elevated Lp(a) group than in the normal Lp(a) group without a history of IHD (P < 0.001; log–rank test), but was similar in the two subgroups of subjects with a history of IHD. No significant difference was seen between the elevated Lp(a) and normal Lp(a) groups in the probability of CI events, with or without a history of CI. On multiple logistic regression analysis, Lp(a), hyperlipidemia and a history of IHD were significant predictors of IHD, whereas hypertension, hyperlipidemia and a history of CI were significant predictors of CI.Conclusion:  These results indicate that an elevated serum Lp(a) concentration is an independent risk factor for IHD, but not for perforating artery occlusion‐type CI, in elderly patients with type‐2 diabetes.
Gene expression in dopamine and GABA systems in an animal model of schizophrenia: effects of antipsychotic drugs
Authors: Lipska Barbara K. , Lerman Daniel N. , Khaing Zin Z. , Weickert Cynthia Shannon , Weinberger Daniel R. 
Published: July 2003

AbstractWe used in situ hybridization histochemistry to assess expression of dopamine receptors (D1R, D2R and D3R), neurotensin, proenkephalin and glutamate decarboxylase‐67 (GAD67) in the prefrontal cortex, striatum, and/or nucleus accumbens in adult rats with neonatal ventral hippocampal (VH) lesions and in control animals after acute and chronic treatment with antipsychotic drugs clozapine and haloperidol. We also acquired these measures in a separate cohort of treatment‐naïve sham and neonatally VH‐lesioned rats used as an animal model of schizophrenia. Our results indicate that the neonatal VH lesion did not alter expression of D1R, D3R, neurotensin or proenkephalin expression in any brain region examined. However, D2R mRNA expression was down‐regulated in the striatum, GAD67 mRNA was down‐regulated in the prefrontal cortex and prodynorphin mRNA was up‐regulated in the striatum of the VH‐lesioned rats as compared with sham controls. Antipsychotic drugs did not alter expression of D1R, D2R or D3R receptor mRNAs but elevated neurotensin and proenkephalin expression in both groups of rats; patterns of changes were dependent on the duration of treatment and brain area examined. GAD67 mRNA was up‐regulated by chronic antispychotics in the nucleus accumbens and the striatum and by chronic haloperidol in the prefrontal cortex in both sham and lesioned rats. These results indicate that the developmental VH lesion changed the striatal expression of D2R and prodynorphin and robustly compromised prefrontal GAD67 expression but did not modify drug‐induced expression of any genes examined in this study.
Endogenous rhythm generation in the pre‐Bötzinger complex and ionic currents: modelling and in vitro studies
Authors: Rybak Ilya A. , Shevtsova Natalia A. , St‐John Walter M. , Paton Julian F. R. , Pierrefiche Olivier 
Published: July 2003

AbstractThe pre‐Bötzinger complex is a small region in the mammalian brainstem involved in generation of the respiratory rhythm. As shown in vitro, this region, under certain conditions, can generate endogenous rhythmic bursting activity. Our investigation focused on the conditions that may induce this bursting behaviour. A computational model of a population of pacemaker neurons in the pre‐Bötzinger complex was developed and analysed. Each neuron was modelled in the Hodgkin–Huxley style and included persistent sodium and delayed‐rectifier potassium currents. We found that the firing behaviour of the model strongly depended on the expression of these currents. Specifically, bursting in the model could be induced by a suppression of delayed‐rectifier potassium current (either directly or via an increase in extracellular potassium concentration, [K+]o) or by an augmentation of persistent sodium current. To test our modelling predictions, we recorded endogenous population activity of the pre‐Bötzinger complex and activity of the hypoglossal (XII) nerve from in vitro transverse brainstem slices (700 µm) of neonatal rats (P0–P4). Rhythmic activity was absent at 3 mm[K+]o but could be triggered by either the elevation of [K+]o to 5–7 mm or application of potassium current blockers (4‐AP, 50–200 µm, or TEA, 2 or 4 mm), or by blocking aerobic metabolism with NaCN (2 mm). This rhythmic activity could be abolished by the persistent sodium current blocker riluzole (25 or 50 µm). These findings are discussed in the context of the role of endogenous bursting activity in the respiratory rhythm generation in vivo vs. in vitro and during normal breathing in vivo vs. gasping.
Connexin43 is not expressed in principal cells of mouse cortex and hippocampus
Authors: Theis Martin , Söhl Goran , Speidel Dina , Kühn Ralf , Willecke Klaus 
Published: July 2003

AbstractPrevious immunofluorescence analyses in mice and rats showed a mainly astrocytic expression of the gap junction protein connexin43 (Cx43) in brain. However, in situ hybridization of murine brain sections suggested strong expression of Cx43 mRNA in hippocampal and cortical pyramidal neurons and Purkinje cells. These findings contrast with recent immunoelectron microscopic studies that excluded prominent Cx43 protein expression in neurons. Both contrasting results could be explained by post‐transcriptional control mechanisms. Here we demonstrate by conditional replacement of the Cx43 coding region by a lacZ reporter gene, mimicking transcriptional activity of the Cx43 gene, that Cx43 is not expressed in principal cells of murine brain. This histochemical approach used is not prone to cross‐reactivity of mRNA probes or antibodies. Furthermore, we show that in situ hybridization signals, suggested to be specific for Cx43 in mouse neurons, are retained even when the Cx43 coding DNA in neurons is removed by cre‐mediated deletion. Our results confirm the previous findings of a mainly astrocytic expression of Cx43 in adult mouse brain and underscore the importance of connexin‐deficient mice as controls for in situ hybridization studies. We found no evidence for post‐transcriptional control of the Cx43 gene in principal neurons. Thus, the synchronized activity of neuronal networks cannot depend on Cx43 containing gap junctions in these cells.
Binding characteristics of [3H]14‐methoxymetopon, a high affinity µ‐opioid receptor agonist
Authors: Spetea Mariana , Tóth Fanni , Schütz Johannes , Ötvös Ferenc , Tóth Géza , Benyhe Sandor , Borsodi Anna , Schmidhammer Helmut 
Published: July 2003

AbstractThe highly potent µ‐opioid receptor agonist 14‐methoxymetopon (4,5α‐epoxy‐3‐hydroxy‐14β‐methoxy‐5β,17‐dimethylmorphinan‐6‐one) was prepared in tritium labelled form by a catalytic dehalogenation method resulting in a specific radioactivity of 15.9 Ci/mmol. Opioid binding characteristics of [3H]14‐methoxymetopon were determined using radioligand binding assay in rat brain membranes. [3H]14‐Methoxymetopon specifically labelled a single class of opioid sites with affinity in low subnanomolar range (Ki = 0.43 nm) and maximal number of binding sites of 314 fmol/mg protein. Binding of [3H]14‐methoxymetopon was inhibited by ligands selective for the µ‐opioid receptor with high potency, while selective κ‐opioids and δ‐opioids were weaker inhibitors. 14‐Methoxymetopon increased guanosine‐5′‐O‐(3‐[35S]thio)‐triphosphate ([35S]GTPγS) binding with an EC50 of 70.9 nm, thus, providing evidence for the agonist character of this ligand. The increase of [35S]GTPγS binding was inhibited by naloxone and selective µ‐opioid antagonists, indicating a µ‐opioid receptor‐mediated action. [3H]14‐Methoxymetopon is one of the few nonpeptide µ‐opioid receptor agonists available in radiolabelled form up to now. Due to its high affinity and selectivity, high stability and extremely low nonspecific binding (<10%), this radioligand would be an important and useful tool in probing µ‐opioid receptor mechanisms, as well as to promote a further understanding of the opioid system at the cellular and molecular level.
Distribution of central sensory axons in transgenic mice overexpressing nerve growth factor and lacking functional p75 neurotrophin receptor expression
Authors: Hannila Sari S. , Kawaja Michael D. 
Published: July 2003

AbstractThis study examined the roles of nerve growth factor (NGF) and the p75 neurotrophin receptor (p75NTR) in the growth of dorsal root ganglion (DRG) central processes in the dorsal horn. Two genetically modified mouse strains were used: transgenic mice that overexpress NGF in the CNS under the control of the glial fibrillary acidic protein promoter, and p75NTR exon III null mutant mice that express a hypomorphic form of this receptor. In both NGF transgenic and nontransgenic mice with hypomorphic expression of p75NTR, there is a significant loss of DRG neurons compared to mice with normal p75NTR expression. This reduction in neuron number has been shown to underlie a corresponding decrease in peripheral nociceptive sensory innervation. Within the CNS, however, nociceptive innervation of the dorsal horn appears to be unaffected by hypomorphic expression of p75NTR. Comparisons of calcitonin gene‐related peptide immunoreactivity in the dorsal horn revealed that the area occupied by DRG central processes was not significantly different between p75NTR hypomorphic mice and wild‐type siblings, or between NGF transgenic mice with either hypomorphic or normal expression of p75NTR. We propose that DRG central processes arborize extensively in both NGF‐transgenic and nontransgenic p75NTR hypomorphic mice in order to compensate for the loss of DRG neurons and restore dorsal horn innervation to normal levels. We also present evidence suggesting that NGF plays only a minor role in the growth of DRG central processes.
Dopamine and adenosine mediate substance P‐induced depression of evoked IPSCs in the rat nucleus accumbens in vitro
Authors: Kombian Samuel B. , Ananthalakshmi Kethireddy V. V. , Parvathy Subramanian S. , Matowe Wandikayi C. 
Published: July 2003

AbstractThe major projection cells of the nucleus accumbens (NAc) are under a strong inhibitory influence from GABAergic afferents and depend on afferent excitation to produce their output. We have earlier reported that substance P (SP), a peptide which is colocalized with GABA in these neurons, depresses excitatory synaptic transmission in this nucleus (Kombian, S.B., Ananthalakshmi, K.V.V., Parvathy, S.S. & Matowe, W.C. (2003) J. Neurophysiol., 89, 728–738). In order to better understand the role of this peptide in the synaptic physiology of the NAc, it is important to determine its effects on inhibitory synaptic responses. Using whole‐cell recording in rat forebrain slices, we show here that SP also depresses evoked inhibitory postsynaptic currents (IPSCs) in the NAc via intermediate neuromodulators. SP caused a partially reversible, dose‐dependent decrease in evoked IPSC amplitude. This effect was present without measurable changes in the holding current, input resistance of recorded cells or decay rate (τ) of IPSCs. It was mimicked by a neurokinin‐1 (NK1) receptor‐selective agonist, [Sar9, Met (O2)11]‐SP, and blocked by an NK1 receptor‐selective antagonist, L 732 138. The SP‐induced IPSC depression was prevented by SCH23390, a dopamine D1‐like receptor antagonist and by 8‐cyclopentyltheophylline, an adenosine A1 receptor blocker. Furthermore, the SP effect was also markedly attenuated by exogenous adenosine, dipyridamole, rolipram and barium. These data show that SP, acting on NK1 receptors, depresses inhibitory synaptic transmission indirectly by enhancing extracellular dopamine and adenosine levels. SP therefore acts in the NAc to modulate both excitatory and inhibitory afferent inputs using the same mechanism(s).
Dissociation between top‐down attentional control and the time course of visual attention as measured by attentional dwell time in patients with mild cognitive impairment
Authors: Perry Richard J. , Hodges John R. 
Published: July 2003

AbstractStudies of the time course of visual attention have identified a temporary functional blindness to the second of sequentially presented stimuli in that the attentional cost of attending to one visual stimulus may lead to impairments in identifying a second stimulus presented within 500 ms of the first. This phenomenon is known as the attentional blink or attentional dwell time. The neural correlates of the attentional blink and its relationship to mechanisms that control attention are unknown. To examine this relationship we tested healthy controls and subjects in the preclinical stage of Alzheimer's disease, known as mild cognitive impairment (MCI), on a paradigm which affords quantification of both the attentional blink and the top‐down control of attention. When subjects were asked to identify both a number and a letter that were rapidly and sequentially presented on a visual display, the detrimental effect that identifying the first stimulus had on the ability to identify the second served as a measure of the attentional blink. When asked to identify only one of the two stimuli, the ability to ignore the first stimulus was a function of their top‐down attentional control. The MCI subjects demonstrated a normal attentional dwell time but in contrast they showed impaired top‐down attentional control within the same paradigm. This dissociation suggests that these two aspects of visual attention are subserved by different neural systems. The possible neural correlates of these two attentional functions are discussed.
The effect of urocortin on ingestive behaviours and brain Fos immunoreactivity in mice
Authors: Sinnayah P. , Blair‐West J. R. , McBurnie M. I. , McKinley M. J. , Oldfield B. J. , Rivier J. , Vale W. W. , Walker L. L. , Weisinger R. S. , Denton D. A. 
Published: July 2003

AbstractThe influence of urocortin (UCN) on ingestive behaviours and brain neural activity, as measured immunohistochemically by the presence of Fos protein, was determined in mice. Rat UCN was administered by continuous intracerebroventricular (ICV) or subcutaneous (SC) infusion. ICV infusion of UCN (100 ng/h, 14 days) transiently reduced daily food and water intakes (days 1–4) but body weight was reduced from day 2 into the post‐infusion period. Sodium intake was reduced from day 3 to the end of infusion. SC infusion of UCN caused similar but smaller reductions in food and water intakes and body weight, without change in sodium intake. In separate experiments, Fos immunoreactivity was increased in several brain nuclei known to be involved in the control of body fluid and energy homeostasis, e.g. central nucleus of the amygdala, median preoptic nucleus, bed nucleus of the stria terminalis and arcuate nucleus. Increased Fos expression was similar for ICV and SC infusions when measured on days 2–3 or 6–7 of infusion. In conclusion, increases of brain activity by UCN may be associated with stimulation of adrenocorticotrophic hormone release and sympathetic nervous activity, but increases may also indicate suppression of ingestive behaviours by stimulating central inhibitory mechanisms located in areas known to control body fluid and energy homeostasis.