bluuebunny/crossref_metadata_2025_split huggingface dataset:
A site‐specific mutation of tyrosine hydroxylase reduces feedback inhibition by dopamine in genetically modified cells grafted in parkinsonian rats
Authors: Chang J. W. , Lee W. Y. , Milstien S. , Kang U. J. 
Published: March 2003

AbstractAromatic l‐amino acid decarboxylase (AADC) is necessary for conversion of l‐DOPA to dopamine. Therefore, AADC gene therapy has been proposed to enhance pharmacological or gene therapies delivering l‐DOPA. However, addition of AADC to the grafts of genetically modified cells expressing tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1), which produce l‐DOPA in parkinsonian rats, resulted in decreased production of l‐DOPA and dopamine owing to feedback inhibition of TH by dopamine. End‐product feedback inhibition has been shown to be mediated by the regulatory domain of TH, and site‐specific mutation of serine 40 makes TH less susceptible to dopamine inhibition. Therefore, we investigated the efficacy of using TH with serine 40 mutated to leucine (mTH) in an ex vivo gene‐therapy paradigm. Primary fibroblasts (PF) from Fischer 344 rats were transduced with retrovirus to express mTH or wild‐type rat TH cDNA (wtTH). Both cell types were also transduced with GCH1 to provide the obligate TH cofactor, tetrahydrobiopterin. PF transfected with AADC were used as coculture and cografting partners. TH activities and l‐DOPA production in culture were comparable between PFwtTHGC and PFmTHGC cells. In cocultures with PFAADC cells, PFmTHGC cells showed significant reduction in the inhibitory effect of dopamine compared with PFwtTHGC cells. In vivo microdialysis measurement showed that cografting PFAADC cells with PFmTHGC cells resulted in smaller decreases in l‐DOPA and no reduction in dopamine levels compared with cografts of PFAADC cells with PFwtTHGC cells, which decreased both l‐DOPA and dopamine levels. Maintenance of dopamine levels with lower levels of l‐DOPA would result in more focused local delivery of dopamine and less potential side‐effects arising from l‐DOPA diffusion into other structures. These data support the hypothesis that mutation of serine 40 attenuates TH end‐product inhibition in vivo and illustrates the importance of careful consideration of biochemical pathways and interactions between multiple genes in gene therapy.
Changes in activity and expression of phosphofructokinase in different rat brain regions after basal forebrain cholinergic lesion
Authors: Zeitschel Ulrike , Schliebs Reinhard , Roßner Steffen , Bigl Volker , Eschrich Klaus , Bigl Marina 
Published: March 2003

AbstractSelective lesion of rat basal forebrain by the cholinergic immunotoxin 192IgG‐saporin was used as an animal model to address the question of whether the changes in cortical glucose metabolism observed in patients with Alzheimer's disease may be related to impaired cholinergic transmission. At different times after creating the immunolesion, the isoenzyme pattern and steady‐state mRNA levels of the key glycolytic enzyme phosphofructokinase were determined in cortex, hippocampus, basal forebrain and nucleus caudatus. The loss of cholinergic input was accompanied by a persistent decrease in choline acetytransferase and acetylcholine esterase activities in the cortical target areas similar to the cholinergic malfunction seen in Alzheimer's dementia. The basal forebrain lesion induced by the immunotoxin resulted in a transient increase in phosphofructokinase activity peaking on day 7 after inducing the lesion in cortical areas. In parallel, an increased steady‐state level of phosphofructokinase mRNA was determined by RT/real‐time PCR and in situ hybridization. In contrast, analysis by western blotting and quantitative PCR revealed no changes in the phosphofructokinase isoenzyme pattern after immunolesion. It is concluded that common metabolic mechanisms may underlie the degenerative and repair processes in denervated rat brain and in the diseased Alzheimer's brain.
Proteomic analysis of CA1 and CA3 regions of rat hippocampus and differential susceptibility to intermittent hypoxia
Authors: Gozal Evelyne , Gozal David , Pierce William M. , Thongboonkerd Visith , Scherzer Janice A. , R. Sachleben Leroy , Brittian Kenneth R. , Guo Shang‐Z. , Cai Jian , Klein Jon B. 
Published: March 2003

AbstractThe CA1 and CA3 regions of the hippocampus markedly differ in their susceptibility to hypoxia in general, and more particularly to the intermittent hypoxia that characterizes sleep apnea. Proteomic approaches were used to identify proteins differentially expressed in the CA1 and CA3 regions of the rat hippocampus and to assess changes in protein expression following a 6‐h exposure to intermittent hypoxia (IH). Ninety‐nine proteins were identified, and 15 were differentially expressed in the CA1 and the CA3 regions. Following IH, 32 proteins in the CA1 region and only 7 proteins in the more resistant CA3 area were up‐regulated. Hypoxia‐regulated proteins in the CA1 region included structural proteins, proteins related to apoptosis, primarily chaperone proteins, and proteins involved in cellular metabolic pathways. We conclude that IH‐mediated CA1 injury results from complex interactions between pathways involving increased metabolism, induction of stress‐induced proteins and apoptosis, and, ultimately, disruption of structural proteins and cell integrity. These findings provide initial insights into mechanisms underlying differences in susceptibility to hypoxia in neural tissue, and may allow for future delineation of interventional strategies aiming to enhance neuronal adaptation to IH.
A novel in vivo post‐translational modification of p53 by PARP‐1 in MPTP‐induced parkinsonism
Authors: Mandir Allen S. , Simbulan‐Rosenthal Cynthia M. , Poitras Marc F. , Lumpkin John R. , Dawson Valina L. , Smulson Mark E. , Dawson Ted M. 
Published: March 2003

AbstractSporadic Parkinson's disease (PD) affects primarily dopaminergic neurons of the substantia nigra pars compacta. There is evidence of necrotic and apoptotic neuronal death in PD, but the mechanisms behind selected dopaminergic neuronal death remain unknown. The tumor suppressor protein p53 functions to selectively destroy stressed or abnormal cells during life and development by means of necrosis and apoptosis. Activation of p53 leads to death in a variety of cells including neurons. p53 is a target of the nuclear enzyme Poly(ADP‐ribose)polymerase (PARP), and PARP is activated following DNA damage that occurs following 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced neurotoxicity. MPTP is the favored in vivo model of PD, and reproduces the pathophysiology, anatomy and biochemistry of PD. p53 protein normally exhibits a fleeting half‐life, and regulation of p53 stability and activation is achieved mainly by post‐translational modification. We find that p53 is heavily poly(ADP‐ribosyl)ated by PARP‐1 following MPTP intoxication. This post‐translational modification serves to stabilize p53 and alters its transactivation of downstream genes. These influences of PARP‐1 on p53 may underlie the mechanisms of MPTP‐induced parkinsonism and other models of neuronal death.
Corticosterone acutely prolonged N‐methyl‐d‐aspartate receptor‐mediated Ca2+ elevation in cultured rat hippocampal neurons
Authors: Takahashi Taiki , Kimoto Tetsuya , Tanabe Nobuaki , Hattori Taka‐aki , Yasumatsu Nobuaki , Kawato Suguru 
Published: March 2003

AbstractThis work reports the first demonstration that corticosterone (CORT) has a rapid and transient effect on NMDA receptor‐mediated Ca2+ signaling in cultured rat hippocampal neurons. Using single cell Ca2+ imaging, CORT and agonists of glucocorticoid receptors were observed to modulate the NMDA receptor‐mediated Ca2+ signals in a completely different fashion from pregnenolone sulfate. In the absence of steroids, 100 µm NMDA induced a transient Ca2+ signal that lasted for 30–70 s in 86.1% of the neurons prepared from postnatal rats (3–5 days old). After pre‐treatment with 0.1–100 µm CORT for 10–20 min, NMDA induced extremely prolonged Ca2+ elevation. This prolonged Ca2+ elevation was terminated by the application of MK‐801 and followed by washing out of CORT. The proportion of CORT‐modulated neurons within the NMDA‐responsive cells increased from 25.1 to 95.5% when the concentration of CORT was raised from 0.1 to 50 µm. Substitution of BSA‐conjugated CORT produced essentially the same results. When hippocampal neurons were preincubated with 10 µm cortisol and 1 µm dexamethasone for 20 min, a very prolonged Ca2+ elevation was also observed upon NMDA stimulation. The CORT‐prolonged Ca2+ elevation caused a long‐lasting depolarization of the mitochondrial membrane, as observed with rhodamine 123. In contrast, incubation with 100 µm pregnenolone sulfate did not considerably alter the time duration of NMDA‐induced transient Ca2+ elevation, but caused a significant increase in the peak amplitude of Ca2+ elevation in hippocampal neurons. These results imply that high levels of CORT induce a rapid and non‐genomic prolongation of NMDA receptor‐mediated Ca2+ elevation, probably via putative membrane surface receptors for CORT in the hippocampal neurons.
Distinct effects of methamphetamine and cocaine on preprodynorphin messenger RNA in rat striatal patch and matrix
Authors: Adams David H. , Hanson Glen R. , Keefe Kristen A. 
Published: March 2003

AbstractWe and others previously reported that equimolar doses of methamphetamine and cocaine differentially increase preprodynorphin mRNA in striatum: methamphetamine causes a patchy increase, whereas cocaine produces a more homogenous one. The current study directly examined whether this effect reflects differential induction in the patch–matrix division of striatum, as identified by µ opioid receptor immunohistochemistry. In addition, we determined whether doses of cocaine (30 mg/kg) and methamphetamine (2 mg/kg) that produced equivalent increases in extracellular dopamine differentially affected preprodynorphin mRNA expression in striatum of male, Sprague–Dawley rats. In both experiments, methamphetamine and cocaine differentially affected preprodynorphin mRNA in striatum after 3 h. The high, equimolar dose of methamphetamine selectively increased preprodynorphin mRNA in the patch division of rostral striatum, whereas cocaine increased preprodynorphin mRNA throughout patch and matrix divisions of striatum. In contrast, a dose of methamphetamine (2.0 mg/kg) that caused an increase in extracellular dopamine similar to that produced by 30 mg/kg cocaine did not significantly affect preprodynorphin mRNA in any region of striatum. These data provide further evidence that cocaine and amphetamines exert distinct effects on the patch–matrix division of striatum and suggest further that the post‐synaptic consequences of elevated extracellular dopamine produced by methamphetamine and cocaine are distinct.
Inhibition of NADH oxidation by chloramphenicol in the freely moving rat measured by picosecond time‐resolved emission spectroscopy
Authors: Mottin Stéphane , Laporte Pierre , Cespuglio Raymond 
Published: March 2003

AbstractOwing to the lack of methods capable to monitor the energetic processes taking place within small brain regions (i.e. nucleus raphe dorsalis, nRD), the neurotoxicity of various categories of substances, including antibiotics and psycho‐active drugs, still remains difficult to evaluate. Using an in vivo picosecond optical spectroscopy imaging method, we report that chloramphenicol (CAP), besides its well‐known ability to inhibit the mitochondria protein synthesis, also influences the NADH/NAD+ redox processes of the respiratory chain. At a 200‐mg/kg dose, CAP indeed produces a marked increase in the fluorescent signal of the nRD which, according to clear evidence, is likely to be related to the NADH concentration. This effect also implies an efficient inhibition of complex I of the respiratory chain by CAP. It refers to the mechanism through which the adverse effects of the antibiotic may take place. It could explain why paradoxical sleep, a state needing aerobic energy to occur, is suppressed after CAP administration. The present approach constitutes the first attempt to determine by fluorescence methods the effects of substances on deep brain structures of the freely moving animal. It points out that in vivo ultrafast optical methods are innovative and adequate tools for combined neurochemical and behavioural approaches.
MsGC‐II, a receptor guanylyl cyclase isolated from the CNS of Manduca sexta that is inhibited by calcium
Authors: Morton David B. , Nighorn Alan 
Published: March 2003

AbstractWe describe the cloning of a receptor guanylyl cyclase, MsGC‐II, from the CNS of the insect Manduca sexta. Sequence comparisons with other receptor guanylyl cyclases show that MsGC‐II is most similar to a predicted guanylyl cyclase in the Drosophila genome and to vertebrate retinal guanylyl cyclases. When expressed in COS‐7 cells, MsGC‐II exhibited a low level of basal activity that was nearly abolished in the presence of 10 µm calcium. Incubation with either a mammalian guanylyl cyclase‐activating protein or Drosophila frequenin resulted in only mild stimulation of activity, whereas incubation of COS‐7 cells expressing MsGC‐II with a variety of Manduca tissue extracts failed to stimulate enzyme activity above basal levels. Analysis of the tissue distribution of MsGC‐II revealed that it is nervous system specific. In the adult, MsGC‐II is present in neurons in the optic lobes, antennal lobes and cellular cortex, but it is most highly expressed in subsets of intrinsic mushroom body neurons. Thus, MsGC‐II appears to be a neural‐specific receptor guanylyl cyclase whose activity may be regulated either directly or indirectly by calcium.
Possible regulation by N‐methyl‐d‐aspartate receptors of proliferative progenitor cells expressed in adult mouse hippocampal dentate gyrus
Authors: Kitayama Tomoya , Yoneyama Masanori , Yoneda Yukio 
Published: March 2003

AbstractAn immunohistochemical technique was employed to analyze mechanisms underlying modulation by N‐methyl‐d‐aspartate (NMDA) receptors of proliferation of neural progenitor cells in adult mouse brain. The systemic administration of NMDA at 100 mg/kg resulted in marked expression of c‐Fos, Fra‐2 and c‐Jun proteins in the granule cell layers of the dentate gyrus in murine hippocampus 2 h later, followed by a significant reduction of the incorporation of 5‐bromo‐2′‐deoxyuridine (BrdU) in a manner sensitive to the antagonist dizocilpine 2 days after administration. The administration of NMDA also suppressed constitutive expression of both nestin and proliferating cell nuclear antigen (PCNA) in the dentate granule cells 2 days later, without markedly affecting cell viability for up to 8 weeks after administration. In the subventricular zone and olfactory bulb, however, NMDA failed to affect either the incorporation of BrdU or the expression of nestin and PCNA. The NR1 subunit was highly expressed in the dentate gyrus in addition to the stratum oriens in the hippocampus, but not in the subventricular zone and olfactory bulb. These results suggest that NMDA receptors may play a role crucial for maintenance of the integrity and function of proliferative neural progenitor cells through expression of the nuclear transcription factor activator protein‐1 in granule cells of the dentate gyrus in adult mouse brain.
Factors associated with the self‐care of home‐dwelling elderly
Authors: Backman Kaisa , Hentinen Maija 
Published: March 2003

Factors associated with the self‐care of home‐dwelling elderly The purpose of this study was to examine how functional capacity, activities of daily living (ADL), instrumental activities of daily living (IADL), life satisfaction and self‐esteem are related to the self‐care behaviour styles of home‐dwelling elderly persons. Data were collected by qualitative interviews (self‐care) and structured interviews (functional capacity, life satisfaction and self‐esteem) from home‐dwelling elderly persons (n=40) aged 75 or more. The persons were living in a medium‐sized city in northern Finland. The qualitative data were analysed using deductive content analysis. The classification frame consisted of a theoretical classification developed in an earlier study. The categories were quantified and the relationship between the variables analysed by cross‐tabulation. The persons whose self‐care behaviour style was responsible, formally guided or independent carried out their daily activities without assistance from others, while those who showed abandoned self‐care did not manage their daily activities without help. Life satisfaction was the highest among the formally guided persons and self‐esteem among the responsible ones. Poor life satisfaction and self‐esteem correlated with abandoned self‐care behaviour.
The general health in women suffering from gynaecological disorders is improved by means of hysterectomy
Authors: Rannestad Toril , Eikeland Ole‐Johan , Helland Harald , Qvarnström Ulla 
Published: March 2003

The general health in women suffering from gynaecological disorders is improved by means of hysterectomy Gynaecological disorders can have adverse effects on women’s general health, and for a substantial number of these women hysterectomy is performed. This study aims to evaluate the long‐term impact of hysterectomy on this outcome variable. The patient‐group was tested pre‐operatively and 6 and 12 months after hysterectomy. The control‐group was tested once. This study shows that the general health in women suffering from gynaecological disorders is significantly lower compared with that of the control‐group (p < 0.00). Both 6 and 12 months after the hysterectomy, however, the patient‐group has reached the same level of their general health as the control‐group. Twenty‐eight per cent of their potentiality for improved health has been obtained. For those women with poorest health both pre‐ and postoperatively, other factors than the hysterectomy have had a negative impact on their general health and lives. The results from this study suggest that hysterectomy is associated with a positive long‐term impact on women’s general health.
Do occupational therapy and physiotherapy students care about research? A survey of perceptions and attitudes to research
Authors: Kamwendo Kitty , Törnquist Kristina 
Published: March 2003

Do occupational therapy and physiotherapy students care about research? A survey of perceptions and attitudes to research In this cross‐sectional study, we have used a questionnaire to study perceptions and attitudes to research‐related activities of Swedish occupational therapy and physiotherapy first (T1) and final term (T6) students. Two hundred and eleven students from programmes employing either problem‐based learning (PBL) or traditional education methods participated. The results showed that students had a positive attitude towards research, particularly for the activity ‘read research literature to update knowledge’ and ‘apply research findings to improve practice’. When T1 were compared with T6 students, the ability to perform research‐related activities was rated significantly higher by T6 students regardless of educational methods. A comparison of PBL and the traditional educational method resulted in moderate but significant differences. The PBL students had a more positive attitude towards research and to a greater extent intended to engage in research activities in the future. The results give hope for a positive future development of the occupational therapy and physiotherapy professions and a PBL education method may be more conducive to the shaping of a research consumer than a traditional method, although more research is needed to substantiate these claims.
Patient reported quality of care before vs. after the implementation of a diagnosis related groups (DRG) classification and payment system in one Swedish county
Authors: Ljunggren Birgitta , Sjödén Per‐Olow 
Published: March 2003

Patient reported quality of care before vs. after the implementation of a diagnosis related groups (DRG) classification and payment system in one Swedish county The purpose was to evaluate the effects of a diagnosis related groups (DRG)‐intervention on the quality of care as perceived by patients at two surgical clinics in the County Council of Gävleborg, Sweden. The study was planned as a nonequivalent control groups design, but external factors turned it into a prospective longitudinal design. Changes in patient experiences of received care were evaluated for the period 1992–1996. Of the 40 included consecutive patients per year from each hospital, > 85% completed the questionnaire. The selection of patients was defined by diagnoses and surgical treatments, and by geographical area. The results demonstrated a decrease of the quality of care as seen from the patient perspective, especially with respect to treatment by staff. Previously stated DRG goals were partially fulfilled and the DRG‐intervention was gradually implemented. Other presumed causal variables were: other reforms, restrained resources, quality assurance activities, organizational and structural changes within the county council. Further studies of the effects of health care reforms would yield more distinct conclusions, provided it would be possible to evaluate interventions prior to full‐scale implementation.
Nurses' experiences of abusive/non‐abusive caring for demented patients in acute care settings
Authors: Eriksson Catharina , Saveman Britt‐Inger 
Published: March 2003

Nurses' experiences of abusive/non‐abusive caring for demented patients in acute care settingsNurses caring for patients with dementia in acute care settings often lack specialized education in geriatric nursing. The acute care settings do not have an environment made for dementia care. The staff often had a high workload, which makes the situation stressful and the nurses who take care of these patients might end up in difficult situations. The aim of this study was to describe nurses' experiences of difficulties related to caring for patients with dementia in acute care settings. Interviews were performed with 12 nurses. Qualitative thematic content analyses were carried out in several steps. The results show that the nurses experienced various difficulties in meeting patients with dementia in acute care settings. This gave rise to for example frustration. Most commonly reported was lack of time to treat these patients satisfactorily. The difficulties were mostly related to the often disorderly conduct of these patients, the ethical problems that appeared in the care of these patients, and the medical care organization. The problematic situations described sometimes led to abuse and neglect of these patients.
Assessment of pain, depression, and anxiety by visual analogue scale in Japanese women with rheumatoid arthritis
Authors: Tamiya Nanako , Araki Shunichi , Ohi Gen , Inagaki Katsuhiko , Urano Naoko , Hirano Wataru , Daltroy Lawren Hugh 
Published: March 2003

Assessment of pain, depression, and anxiety by visual analogue scale in Japanese women with rheumatoid arthritis Visual analogue scales (VAS) of depression and anxiety were compared with standard full‐length measures of these variables and with VAS of pain (VAS Pain). This was a good way to develop a practical methodology for the routine assessment of pain and affect in rheumatoid arthritis (RA) patients. The reliability of VAS Pain was studied by test–retest. The validity of VAS Pain in our sample was proved by correlations with the results of other tests. We also investigated the relationship between VAS Pain and C‐reactive protein (CRP).In 145 female RA patients, VAS of depression and anxiety were significantly correlated with full‐length measures of these variables, and accounted for the majority of the explained variance in VAS Pain, while the full‐length standard measures contributed little more.In conclusion, VAS measurements of pain and affect were comprehensible, easily filled‐out, and reliable in a sample of Japanese women with RA, and could capture some aspect of affective distress unique to RA patients.