bluuebunny/crossref_metadata_2025 huggingface dataset:
DYNAMIC CHARACTERISTICS OF SnO2 GAS SENSOR FOR LPG DETECTION
Authors: LIU JINHUAI , MENG FANLI , HUANG XINGJIU , HUANG JIARUI
Published: May 2005

A new approach for rapid detection of hazardous gas like domestic liquefied petroleum gas (LPG) using a single SnO 2 gas sensor based on dynamic measurement was studied. The working principles of static and dynamic measurements were compared and experimental and analytical profiles of the dynamic measurement was also investigated. Experimental results showed that hazardous gas such as LPG had obvious properties by using dynamic measurement. The qualitative analysis was also studied by means of fast Fourier transform (FFT), and power spectrum showed that different properties appeared on different concentrations of LPG.
3D EUCLIDEAN RECONSTRUCTION FROM THE VARIABLE INTRINSIC PARAMETERS OF CAMERA
Authors: WU YOUFU , SHEN JUN
Published: May 2005

For 3D Eucledean reconstruction, the challenging problem is that only the hypothesis of intrinsic parameters can be used to retrieve the camera parameters without additional information. In this paper, we propose a method to find out the camera's variable intrinsic parameters using the scene invariable conics (SIC). The experiment results are presented and analysed, which show good performance of this proposed method.
NUTRITIONAL CONTROL OF GENE EXPRESSION: How Mammalian Cells Respond to Amino Acid Limitation
Authors: Kilberg M.S. , Pan Y.-X. , Chen H. , Leung-Pineda V.
Published: May 2005

▪ Abstract  The amino acid response (AAR) pathway in mammalian cells is designed to detect and respond to amino acid deficiency. Limiting any essential amino acid initiates this signaling cascade, which leads to increased translation of a “master regulator,” activating transcription factor (ATF) 4, and ultimately, to regulation of many steps along the pathway of DNA to RNA to protein. These regulated events include chromatin remodeling, RNA splicing, nuclear RNA export, mRNA stabilization, and translational control. Proteins that are increased in their expression as targets of the AAR pathway include membrane transporters, transcription factors from the basic region/leucine zipper (bZIP) superfamily, growth factors, and metabolic enzymes. Significant progress has been achieved in understanding the molecular mechanisms by which amino acids control the synthesis and turnover of mRNA and protein. Beyond gaining additional knowledge of these important regulatory pathways, further characterization of how these processes contribute to the pathology of various disease states represents an interesting aspect of future research in molecular nutrition.
ANNUAL LIPID CYCLES IN HIBERNATORS: Integration of Physiology and Behavior
Authors: John Dark
Published: May 2005

▪ Abstract  Mammalian hibernation is a temporary suspension of euthermia allowing endotherms to undergo reversible hypothermia and generate a marked savings in energy expenditure. In most fat-storing hibernator species, seasonal changes in food intake, triacylglycerol deposition, metabolism, and reproductive development are controlled by a circannual clock. In ground-dwelling sciurid rodents (ground squirrels and marmots), for example, energy intake increases during a summer body mass gain phase, and toward the end of this phase metabolic rate also begins to decrease, resulting in a profound increase in lipid deposition as fat. Increased activity of lipogenic hormones and enzymes correspond with this increase. The hibernation mass loss phase begins after the body mass peak in the fall and ends in spring. During this phase, stored lipids are slowly utilized in a programmed manner by undergoing deep torpor or hibernation during which the hypothalamic setpoint for body temperature is typically reduced to just above 0°C. Throughout the hibernation season, bouts of deep torpor are punctuated by periodic arousals in which brown adipose tissue thermogenesis plays a critical role. Lipid oxidation nearly exclusively fuels deep torpor and most of the rewarming process. The fatty acid composition of stored lipids can affect the depth and duration of deep torpor, and saturated fatty acids may be preferentially used during hibernation, whereas polyunsaturated fatty acids may be preferentially retained. Female and underweight male hibernators terminate hibernation in spring when aboveground food becomes available; in contrast, heavier males with sufficient lipid reserves spontaneously terminate hibernation several weeks before females and independent of food availability. Mating occurs shortly after emergence from hibernation, and the lipid cycle begins again with the completion of reproduction. Lipid deposition and mobilization, temperature regulation, reproduction, and circannual timing are intimately interdependent. The unique manner in which they are controlled during the annual cycle, especially lipid reserves, makes hibernators valuable and promising models for research into the mechanisms underlying these processes in all mammals.
Immediate Changes in Anticipatory Activity of Caudate Neurons Associated With Reversal of Position-Reward Contingency
Authors: Watanabe Katsumi , Hikosaka Okihide
Published: May 2005

The primate caudate nucleus plays a crucial role in transforming cognitive/motivational information into eye movement signals. A subset of caudate projection neurons fire before a visual target's onset. This anticipatory activity is sensitive to position-reward contingencies and correlates with saccade latency, which is shorter toward a rewarded position. We recorded single-unit activity of caudate projection neurons to examine the dynamics of change in anticipatory activity immediately after switches of the position-reward contingency. Two monkeys performed a visually guided saccade task where only one position was associated with reward. The position-reward mapping remained constant within a block, but was reversed frequently between blocks without any indication to the monkey. Therefore the switch could be detected only by unexpected reward delivery or unexpected lack of reward. After the switch, both saccade latency and anticipatory activity showed reliable changes already in the second trial, whether or not the first trial was rewarded. However, anticipatory activity in the second trial was generally higher if the first trial was rewarded, and the measured saccade latencies could be better explained by the difference in anticipatory activity between the two caudate nuclei. We suggest that anticipatory activity of caudate neurons reflects the reversal set of reward-position contingency.
Orientation Tuning, But Not Direction Selectivity, Is Invariant to Temporal Frequency in Primary Visual Cortex
Authors: Moore Bartlett D. , Alitto Henry J. , Usrey W. Martin
Published: May 2005

The activity of neurons in primary visual cortex is influenced by the orientation, contrast, and temporal frequency of a visual stimulus. This raises the question of how these stimulus properties interact to shape neuronal responses. While past studies have shown that the bandwidth of orientation tuning is invariant to stimulus contrast, the influence of temporal frequency on orientation-tuning bandwidth is unknown. Here, we investigate the influence of temporal frequency on orientation tuning and direction selectivity in area 17 of ferret visual cortex. For both simple cells and complex cells, measures of orientation-tuning bandwidth (half-width at half-maximum response) are ∼20–25° across a wide range of temporal frequencies. Thus cortical neurons display temporal-frequency invariant orientation tuning. In contrast, direction selectivity is typically reduced, and occasionally reverses, at nonpreferred temporal frequencies. These results show that the mechanisms contributing to the generation of orientation tuning and direction selectivity are differentially affected by the temporal frequency of a visual stimulus and support the notion that stability of orientation tuning is an important aspect of visual processing.
Dissociation of Sensorimotor Deficits After Rostral Versus Caudal Lesions in the Primary Motor Cortex Hand Representation
Authors: Friel Kathleen M. , Barbay Scott , Frost Shawn B. , Plautz Erik J. , Hutchinson Douglas M. , Stowe Ann M. , Dancause Numa , Zoubina Elena V. , Quaney Barbara M. , Nudo Randolph J.
Published: May 2005

Primary motor cortex (M1) has traditionally been considered a motor structure. Although neurophysiologic studies have demonstrated that M1 is also influenced by somatosensory inputs (cutaneous and proprioceptive), the behavioral significance of these inputs has yet to be fully defined in primates. The present study describes differential sensory-related deficits after small ischemic lesions in either the rostral or caudal subregion of the M1 hand area in a nonhuman primate. Squirrel monkeys retrieved food pellets out of different sized wells drilled into a Plexiglas board. Before the lesion, monkeys retrieved pellets by directing the hand to the well, inserting fingers directly into it, and extracting the pellet. After a lesion to the rostral portion of M1, monkeys frequently failed to direct the hand accurately to the well. Instead, fingers contacted the surface of the board outside the well before entering the well. These aiming errors are consistent with both the large amount of proximal motor outputs and the predominant proprioceptive inputs of rostral M1. Overall, these aiming errors are suggestive of dysfunctional processing of proprioceptive information or the failure to integrate proprioceptive information with motor commands. In contrast, after a lesion to the caudal portion of M1, monkeys frequently examined their palm visually for the presence of the pellet after an attempted retrieval. These errors are consistent with both the large amount of distal motor outputs and the predominant cutaneous inputs of caudal M1. Thus these errors are suggestive of a deficit in processing of cutaneous information or the failure to integrate cutaneous information with motor commands. Rostral and caudal M1 lesions result in different deficits in sensory-dependent motor control that appear to correlate with broad segregation of motor outputs and previously described sensory inputs of M1.
Signature patterns of gene expression in mouse atherosclerosis and their correlation to human coronary disease
Authors: Tabibiazar Raymond , Wagner Roger A. , Ashley Euan A. , King Jennifer Y. , Ferrara Rossella , Spin Joshua M. , Sanan David A. , Narasimhan Balasubramanian , Tibshirani Robert , Tsao Philip S. , Efron Bradley , Quertermous Thomas
Published: May 2005

The propensity for developing atherosclerosis is dependent on underlying genetic risk and varies as a function of age and exposure to environmental risk factors. Employing three mouse models with different disease susceptibility, two diets, and a longitudinal experimental design, it was possible to manipulate each of these factors to focus analysis on genes most likely to have a specific disease-related function. To identify differences in longitudinal gene expression patterns of atherosclerosis, we have developed and employed a statistical algorithm that relies on generalized regression and permutation analysis. Comprehensive annotation of the array with ontology and pathway terms has allowed rigorous identification of molecular and biological processes that underlie disease pathophysiology. The repertoire of atherosclerosis-related immunomodulatory genes has been extended, and additional fundamental pathways have been identified. This highly disease-specific group of mouse genes was combined with an extensive human coronary artery data set to identify a shared group of genes differentially regulated among atherosclerotic tissues from different species and different vascular beds. A small core subset of these differentially regulated genes was sufficient to accurately classify various stages of the disease in mouse. The same gene subset was also found to accurately classify human coronary lesion severity. In addition, this classifier gene set was able to distinguish with high accuracy atherectomy specimens from native coronary artery disease vs. those collected from in-stent restenosis lesions, thus identifying molecular differences between these two processes. These studies significantly focus efforts aimed at identifying central gene regulatory pathways that mediate atherosclerotic disease, and the identification of classification gene sets offers unique insights into potential diagnostic and therapeutic strategies in atherosclerotic disease.
Linkage and association analyses of the UCP3 gene with obesity phenotypes in Caucasian families
Authors: Liu Yong-Jun , Liu Peng-Yuan , Long Jirong , Lu Yan , Elze Leo , Recker Robert R. , Deng Hong-Wen
Published: May 2005

Uncoupling protein 3 (UCP3) uncouples ATP production from mitochondrial respiration, thereby dissipating energy as heat and affecting the efficiency of energy metabolism. Genetic variations in the UCP3 gene have been conceived to affect body weight in the general population. In this study, using the quantitative transmission disequilibrium test (QTDT), we assessed linkage and association between the UCP3 gene and obesity phenotypes in a large sample of 1,873 subjects from 405 United States Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percent fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry. We first selected five single nucleotide polymorphisms (SNPs) and then analyzed three highly polymorphic ones, namely, −55 C/T (promoter), Tyr99Tyr (exon 3), and Tyr210Tyr (exon 5), in the total sample. Significant linkage disequilibria (0.392 ≤ D′ ≤ 0.940, P < 0.0001) were observed between pairs of SNPs. In single-locus analyses, we found statistically significant association ( P = 0.034) and linkage ( P = 0.031) between −55 C/T and BMI. This polymorphism explains 2.29% of BMI variation, and subjects carrying the T allele had an average of 3.5% lower BMI than those without it ( P = 0.003). In haplotype analyses, we also observed evidence of linkage ( P = 0.002) and association ( P = 0.035) with BMI. In summary, our results suggest that UCP3 gene polymorphisms may contribute to BMI variation in this Caucasian population.
Genetic modifiers interact withCpefatto affect body weight, adiposity, and hyperglycemia
Authors: Collin Gayle B. , Maddatu Terry P. , Sen Śaunak , Naggert Jürgen K.
Published: May 2005

Obesity and Type II diabetes are complex diseases in the human population. The existence of a large number of contributing loci and gene-gene as well as gene-environment interactions make it difficult to identify the disease genes underlying these complex traits. In mouse models of obesity and Type II diabetes such as the murine fat mutation, genetic crosses can be used to dissect the genetic complexity influencing the observed phenotypes. The underlying defect in the fat mutant is a Ser202Pro change in carboxypeptidase E (CPE), an enzyme responsible for the final proteolytic processing step of prohormone intermediates. On the HRS/J (HRS) inbred strain background, mice homozygous for the fat mutation exhibit early onset hyperinsulinemia followed by postpubertal moderate obesity without hyperglycemia. In contrast, on the C57BLKS/J (BKS) genetic background, fat/fat mice become severely obese, hyperinsulinemic, and hyperglycemic. Therefore, in the Cpefatgenetic model, the fat mutation is necessary but not sufficient for the development of obesity, Type II diabetes, and related metabolic disorders. To dissect the susceptibility loci responsible for modifying obesity- and diabetes-associated traits, we characterized, both genetically and phenotypically, fat/fat male progeny from a large intercross between BKS. HRS- fat/fat and HRS- +/+ mice. Four major loci were mapped, including a locus for body weight (body weight 1) on chromosome 14; a locus for hyperglycemia (fat-induced diabetes 1) on chromosome 19; a locus for hyperglycemia, hyperinsulinemia, and hypercholesterolemia (fat-induced diabetes 2) on chromosome 5; and a locus for adiposity and body weight (fat-induced adiposity 1) on chromosome 11. The identification of these interacting genetic determinants for obesity and Type II diabetes may allow better definition of the obesity/diabetes-related hormone signaling pathways and ultimately may provide new insights into the pathogenesis of these complex diseases.
Time Course of Dehydrating Effects of Isosorbide on Experimentally Induced Endolymphatic Hydrops in Guinea Pigs
Authors: Kakigi Akinobu , Takeda Setsuko , Takeda Taizo , Sawada Shoichi , Azuma Hiroshi , Higashiyama Kasumi , Yamakawa Kazuhiro , Takeuchi Shunji
Published: May 2005

Osmotic diuretics are therapeutic agents used to reduce endolymphatic hydrops. However, glycerol-induced change in endolymph volume is followed by a rebound phenomenon. In this study, we investigated the rebound phenomenon occurring with isosorbide, an osmotic diuretic used as a therapeutic agent for Ménière’s disease in Japan. Forty guinea pigs underwent surgical obliteration of the endolymphatic sac. Thirty received isosorbide orally 1 month after surgery. These animals were sacrificed 3, 6, or 12 h after isosorbide intake. The remaining 10 animals served as controls. Quantitative assessment of changes in the endolymphatic space was performed light-microscopically. Isosorbide reduced cochlear endolymph volume, with a peak reduction 6 h after intake. Thereafter, no prominent rebound phenomenon was noted. Clinically, since isosorbide is orally administered every 8 h, rebound phenomenon need not be considered in the treatment with isosorbide.
Quantitative DNA Measurement in Oropharyngeal Squamous Cell Carcinoma and Surrounding Mucosa
Authors: Preuss S.F. , Brieger J. , Essig E.K. , Stenzel M.J. , Mann W.J.
Published: May 2005

Objective: The appearance of local recurrences, distant metastases and second primary tumors limit the survival rate of patients with head and neck squamous cell carcinomas. The presence of genetic alterations at the resection margins is an indicator of inadequate excision and a predictor of local failure. Design: To receive insight into the genetic abnormalities in the mucosa surrounding oropharyngeal cancers, we performed a quantitative DNA measurement in the primary tumor and the surrounding areas. Results: We found a high level of DNA irregularity in primary tumors. The DNA irregularity decreased in specimens taken at a distance of 1 and 2 cm from the tumor margin. Conclusions: The genetically altered field is thought to determine the risk for recurrence of a second tumor. We therefore believe that the genetic analysis of tissue surrounding the tumor could become a feasible diagnostic procedure to determine the individual risk for local recurrence or second primary tumors.
Surgical Outcomes of Cerebellar Tumors in Children
Authors: Akay Kamil Melih , Izci Yusuf , Baysefer Alper , Atabey Cem , Kısmet Erol , Timurkaynak Erdener
Published: May 2005

Cerebellar tumors in childhood are generally associated with a favorable outcome if they are managed appropriately. 27 cases of pediatric cerebellar tumors, operated over a 7-year period, are presented. Histopathological diagnoses were as follows: pilocytic astrocytoma (48.2%); medulloblastoma (22.2%); ependymoma (18.5%); fibrillary astrocytoma grade III (3.7%); cystic oligodendroglioma (3.7%), and hemangioblastoma (3.7%). Microscopic gross total resection was achieved in 16 (59.3%) of 27 cases. The total removal of pediatric cerebellar tumors without neurological deficit is possible with appropriate microsurgical techniques excluding brain stem invasion. The follow-up periods must be shorter if brain stem invasion exists. Radiotherapy and chemotherapy are the adjuvant therapies according to the pathological diagnosis and the patient’s age.
Coexistence of Rapidly Resolving Acute Subdural Hematoma and Delayed Traumatic Intracerebral Hemorrhage
Authors: Erol Fatih S. , Kaplan Metin , Topsakal Cahide , Ozveren M. Faik , Tiftikci Murat T.
Published: May 2005

Rapid resolution of acute subdural hematoma is rare. Delayed traumatic intracerebral hematomas following medical or surgical treatment of increased intracranial pressure have also been reported. Coexistence of a quickly resolving acute subdural hematoma and a delayed traumatic intracerebral hemorrhage has not been reported before. A 13-month-old boy was admitted to our emergency department after a car accident. On CT, a thin acute subdural hematoma on the right frontotemporal region and a small epidural hematoma on the left frontal region could be seen. On 24-hour follow-up CT, the right subdural hematoma was found to be less dense but larger than it had been before. At 36 h after hospitalization, CT showed that the right acute subdural hematoma had completely disappeared; however, a delayed traumatic intracerebral hematoma on the left occipital region was identified. We think that the mechanism involved in the development of a delayed intracerebral hematoma in our case was similar to the one causing delayed traumatic intracerebral hematoma after treatment for increased intracranial pressure.
Epidural Hematoma as a Complication of Endoscopic Biopsy and Shunt Placement in a Patient Harboring a Third Ventricle Tumor
Authors: Hamlat Abderrahmane , Heckly Anne , Doumbouya Namane , Seigneuret Eric , Brassier Gilles
Published: May 2005

Although some complications have been reported when using endoscopic techniques, epidural hematoma (EDH) has rarely been caused. The authors report a case of EDH complicating a concomitant endoscopic biopsy procedure with ventricular shunt placement in a young, 14-year-old boy harboring a third ventricle tumor with a hydrocephalus. Few cases have been reported; however, the authors warn that there is a risk that EDH may develop following an endoscopic procedure and shunt placement.
Intracranial Pressure Monitoring in Patients with Fulminant Hepatic Failure Treated with Plasma Exchange and Continuous Hemodiafiltration
Authors: Nakanishi Kazuya , Hirasawa Hiroyuki , Oda Shigeto , Shiga Hidetoshi , Matsuda Kennichi , Nakamura Masataka , Hirano Takeshi , Hirayama Yoh , Moriguchi Takeshi , Watanabe Eizo , Nitta Masakazu
Published: May 2005

Background/Aims: To study the influence of our artificial liver support (ALS) on intracranial pressure (ICP) and to evaluate the significance of ICP monitoring in fulminant hepatic failure (FHF) patients treated with ALS. Methods:ICP was measured in 13 consecutive FHF patients treated with ALS. Maximum value in ICP every day was employed as ICPmax of the day. We analyzed the correlation: (a) between ICPmax and consciousness level; (b) between ICP and colloid osmotic pressure (COP), and (c) between ICP and PaCO2. Results: ICP in 11 patients of 13 was controlled <20 mm Hg through our ALS. A significant positive correlation between ICPmax and consciousness level was found (p < 0.01). Although there was a significantly negative correlation between ICP and COP (p < 0.001), there was no correlation between ICP and PaCO2. Conclusions:We conclude that our ALS does not have any adverse effects on ICP and that ICP monitoring is one of the inevitable monitorings in the management of FHF.
Mixed Bacterial Infection Model of Sepsis in Rabbits and Its Application to Evaluate Superantigen-Adsorbing Device
Authors: Fukuyama Mayumi , Miwa Keishi , Shibayama Naoko , Ogura Shinji , Nishiyama Takashi , Maekawa Nobuhiro
Published: May 2005

Background: Superantigens are suspected to be the potent and lethal pathogens of gram-positive sepsis, and a new therapy that targeted to superantigens are required. Methods: A mixed infection model was developed in rabbits by the cecal ligation and puncture associated with the intraperitoneal injection of Staphylococcus aureus, which produces toxic shock syndrome toxin 1 (TSST-1). Animals were also hemoperfused with a superantigen-adsorbing device (SAAD), or a control column. Results: The model animals revealed multiple organ failure and died 6–12 h after the injection of S. aureus. The plasma levels of TSST-1, but not of lipopolysaccharide (LPS), significantly (p < 0.01) and inversely correlated with mean arterial pressure (r = -0.63). Plasma TSST-1 level was significantly reduced and shock-onset time was significantly retarded in the SAAD treated group, although the survival time was not significantly affected. Conclusions: The animal model developed could serve as a model for sepsis. It is suggested that there is the potential application of SAAD in treating superantigen-related sepsis.
Association of the –159C/T Polymorphism of the Endotoxin Receptor (CD14) with Carotid Artery Disease and Cardiovascular Mortality in Dialysis Patients
Authors: Losito Attilio , Kalidas Kamini , Santoni Stefania , Errico Rosa , Jeffery Steve
Published: May 2005

Background: Atherosclerosis is a major problem in end-stage renal disease (ESRD) patients treated by hemodialysis and the prevalence of carotid artery disease is much higher in this group than in the general population. Repeated exposure to cytokine-inducing material, derived from dialysate, may induce a chronic inflammatory state, that could contribute to the atherosclerotic process. Endotoxin is mainly cleared from plasma by the sCD14, the soluble form of the endotoxin receptor CD14. The levels of sCD14 are associated with a polymorphism, –159 C/T, of the CD14 gene. Methods and Results: We determined the genotype for the –159 C/T polymorphism in 158 haemodialysis patients and 168 healthy controls. In patients we investigated the association between the CD14 polymorphism and carotid artery disease. With a prospective follow-up study we assessed whether the CD14 polymorphism shows any relationship with cardiovascular mortality. The polymorphic frequency was comparable between patients and controls. In patients, we found a significant difference in the prevalence of carotid artery disease between groups divided by genotype: CC 87.0%, CT 71.7%, TT 48.9% (p = 0.0093). In dialysis patients with hypertension the CC polymorphism was associated with an increased cardiovascular mortality. Conclusions: These results demonstrate an association between the –159 C/T polymorphism of the CD14 gene and carotid artery disease in dialysis patients. We hypothesize that the low plasma clearance of endotoxin associated with the CC genotype facilitates the atherogenic action of endotoxin-derived cytokines in haemodialysis patients.
Hydrofluoric Acid Burns
Authors: Kim Kea-Jeung , Park Yong-Tae , Yoo Jae-Hak , Park Tae-Ho
Published: May 2005

Hydrofluoric acid (HFA) burns have been occurring with ever-increasing frequency due to the wide use of HFA in industrial fields, such as electronics and semiconductor industries. HFA is one of the strongest inorganic acids and is capable of producing extremely serious and progressively destructive skin burns, with potential serious systemic effects and even death. It is therefore of great importance that clinicians understand the unique characteristics of such burns and the fundamentals of their treatment. Herein we aim to present the clinical features of HFA burns, histopathological studies using guinea pigs and several therapeutic methodologies along with 4 cases of HFA burns we experienced, showing the importance of early initial treatment.
Cellular Oxidative Processes in Relation to Renal Disease
Authors: Wardle E. Nigel
Published: May 2005

This article summarizes the biochemical processes that produce reactive oxygen species (ROS) and other mediators that account for ‘oxidative stress’. Formation of ROS in signal transduction cascades is illustrated from studies of kidney cell systems. The pathophysiological implications for the nephrologist are then reviewed.
Neuronal and Nonneuronal Quantitative BACE Immunocytochemical Expression in the Entorhinohippocampal and Frontal Regions in Alzheimer’s Disease
Authors: Leuba Geneviève , Wernli Gwenaëlle , Vernay André , Kraftsik Rudolf , Mohajeri M. Hasan , Saini Krishan D.
Published: May 2005

In this study, we quantitatively investigated the expression of β-site amyloid precursor protein cleaving enzyme (BACE) in the entorhinohippocampal and frontal cortex of Alzheimer’s disease (AD) and old control subjects. The semiquantitative estimation indicated that the intensity of BACE overall immunoreactivity did not differ significantly between AD and controls, but that a significantly stronger staining was observed in the hippocampal regions CA3–4 compared to other regions in both AD patients and controls. The quantitative estimation confirmed that the number of BACE-positive neuronal profiles was not significantly decreased in AD. However, some degeneration of BACE-positive profiles was attested by the colocalization of neurons expressing BACE and exhibiting neurofibrillary tangles (NFT), as well as by a decrease in the surface area of BACE-positive profiles. In addition, BACE immunocytochemical expression was observed in and around senile plaques (SP), as well as in reactive astrocytes. BACE-immunoreactive astrocytes were localized in the vicinity or close to the plaques and their number was significantly increased in AD entorhinal cortex. The higher amount of β-amyloid SP and NFT in AD was not correlated with an increase in BACE immunoreactivity. Taken together, these data accent that AD progression does not require an increased neuronal BACE protein level, but suggest an active role of BACE in immunoreactive astrocytes. Moreover, the strong expression in controls and regions less vulnerable to AD puts forward the probable existence of alternate BACE functions.
Diminished Production of Proinflammatory Cytokines in Patients with Alzheimer’s Disease
Authors: Richartz E. , Batra A. , Simon P. , Wormstall H. , Bartels M. , Buchkremer G. , Schott K.
Published: May 2005

Cerebral inflammation as well as systemic immunological alterations have been reported in Alzheimer’s disease (AD). We examined the production of the proinflammatory cytokines interleukin-6, interleukin-12, interferon-γ, and tumor necrosis factor-α in whole blood cell cultures of AD patients and age-matched controls. The production of all measured cytokines after mitogen stimulation is significantly decreased in the AD group compared to controls. The results reflect an attenuated secretory activity of monocytes/macrophages, but also of T-helper cells. The data sustain the assumption that a systemic, possibly age-related alteration of immune mechanisms may play a pathogenetic role in the development of AD.
Low-Density Lipoprotein Cholesterol: Association with Mortality and Hospitalization in Hemodialysis Patients
Authors: Chiang Chih-Kang , Ho Tai-I , Hsu Shih-Ping , Peng Yu-Sen , Pai Mei-Fen , Yang Shao-Yu , Hung Kuan-Yu , Tsai Tun-Jun
Published: May 2005

Background/Aims: Hypocholesterolemia is a common finding in hospitalized elderly people, critically ill surgical patients, septic patients and end-stage renal disease patients. The different effect of lipid subfractions on patients with end-stage renal disease has never been demonstrated. We aim to study the effect of lipid subfractions on hospitalization and mortality in maintenance hemodialysis (MHD) patients. Methods: Lipid subfractions, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured in 210 patients with MHD in a single dialysis center. Patients were stratified into three groups based on the tertiles of lipid levels, and differences in patient characteristics and survival were evaluated. Results: Of a total of 22 deceased patients in our MHD cohort, infection-related mortality (50%) was higher than cardiovascular-related mortality (18.2%). Significant differences (p < 0.05) in the duration and frequency of hospitalization and in mortality events were observed when patients were divided into different subgroups according to the tertiles of baseline TC and LDL-C levels. Patients with lower LDL had significantly lower levels of albumin, TC and TG. The LDL-C tertiles were similar in terms of age, hypertension, diabetes, biochemical results, hematocrit, adequacy of hemodialysis and normalized protein catabolism rate. Both TC and LDL-C predicted survival (p < 0.001), but not TG and HDL-C in the Kaplan-Meier model. The Cox proportional hazard model demonstrated that baseline serum LDL-C was the best lipid subfraction in predicting all-cause death with an adjusted hazard ratio (95% confidence interval) for each 10 mg/dl of 0.752 (0.631–0.898; p = 0.002). Conclusions: We firstly demonstrated that lipid subfractions, including TC and LDL-C, predict poor outcomes in a MHD cohort with high infection-related mortality.
Plasma Interleukin-18 Levels in Chronic Renal Failure and Continuous Ambulatory Peritoneal Dialysis
Authors: Chiang Chih-Kang , Hsu Shih-Ping , Pai Mei-Fen , Peng Yu-Sen , Ho Tai-I , Liu Shing-Hwa , Hung Kuan-Yu , Tsai Tun-Jun , Hsieh Bor-Shen
Published: May 2005

Background/Aims: Based on associations of interleukin (IL)-18 with chronic inflammation, we investigated IL-18, IL-6, and tumor necrosis factor-α (TNF-α) in patients with chronic renal failure (CRF) and patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: Plasma was evaluated by ELISA methodology in 15 healthy controls, 27 CRF and 15 CAPD patients. Results: Plasma IL-18 levels in CRF (572.5 ± 41.9 pg/ml) or CAPD (479.2 ± 47.4 pg/ml) were significantly higher than normal (263.6 ± 20.0 pg/ml), but there was no difference in IL-18 between CRF and CAPD patients. The IL-18 concentration negatively correlated with creatinine clearance (Ccr). However, the duration of dialysis, normalized protein nitrogen appearance, weekly Ccr, and Kt/Vurea were not correlated with plasma IL-18 in CAPD. The plasma IL-18 concentration was positively correlated with TNF-α but not with IL-6 in renal failure patients with or without CAPD. Conclusion: Uremia is the principal origin of increased plasma IL-18 in these patients. Increased IL-18 levels may be associated with Th1 differentiation and elevated TNF-α.
Myelinogenesis in the Brachial and Lumbosacral Enlargements of the Spinal Cord of the Opossum Monodelphis domestica
Authors: Lamoureux Stéphanie , Gingras Jacinthe , Cabana Thérèse
Published: May 2005

Using immunohistochemistry in light microscopy, the myelin basic protein and proteolipid protein were localized on sections of the spinal cord enlargements of opossums, Monodelphis domestica, to determine the timecourse of myelinogenesis therein and compare it with other events of motor systems development. Additional tissue not processed for immunohistochemistry was prepared for transmission electron microscopy. No immunolabeling for either protein occurred on spinal sections from the newborn opossum, but in electron microscopy occasional fibers surrounded by loose, irregular membranous rings were seen on the outskirts of the ventral horn. Immunolabeling was detected first in the brachial enlargement during the second week, presumably on motoneuronal, vestibular and reticular axons. The areas of the dorsal columns, other spino-encephalic, reticulospinal and propriospinal projections became labeled in the third week, and the area of rubrospinal axons at 4 weeks. In the brachial gray matter, immunolabeling appeared along ventrodorsal and lateromedial gradients from the fourth to seventh weeks. Labeling developed similarly in the white and gray matter of the lumbosacral enlargement, but 3–5 days later than at brachial levels. Labeling intensity in the white and gray matter increased until at least 4 months, but remained light in laminae I–III. Thus, myelinogenesis in the spinal cord enlargements of the opossum is protracted and follows general rostrocaudal, ventrodorsal and lateromedial sequences. It occurs later than synaptogenesis at comparable levels of the cord, but earlier than myelinogenesis in the corresponding ventral and dorsal roots. Spinal myelinogenesis correlates with the development of sensorimotor reflexes, weight support and quadrupedal locomotion.
The Organization of the Inner Retina in a Pure-Rod Deep-Sea Fish
Authors: Hirt Bernhard , Wagner Hans-Joachim
Published: May 2005

The pure rod retina of a deep-sea eel species was used as a model system for the study of the differentiation of horizontal, bipolar, amacrine and ganglion cells. We wanted to test the hypothesis that the functional organization of the inner retina is less complex than in species with duplex, rod- and cone-containing retinae. We used immunocytochemistry, backfilling ganglion cells with fluorescent dextranes and microinjection of Lucifer Yellow, to visualize the micromorphology of the various cell types in a confocal microscope. The pure rod retina contains a single type of horizontal cell. The inner plexiform layer is 10–15 µm thick and shows three main sublayers. Bipolar terminals are found in all sublayers, but the majority are found in the inner sublamina b (PKC-immunoreactive cells, that in fish with duplex retinae receive a mixed rod-cone input). The neurochemical diversity of amacrine cells in terms of immunoreactivity does not differ from other teleosts; this similarity includes the pattern of dendritic stratification and ramification as revealed by microinjection. Ten different types of ganglion cells are distinguished based on the sizes of their perikaryon and dendritic field, and the stratification pattern in the inner plexiform layer. This is similar to the situation in catfish with retinae containing a single type of cone in addition to a majority of rods. In this respect, the differences between pure rod retinae and duplex retinae containing a single cone type were less obvious than hypothesized. In the deep-sea eel, the density of dendritic ramification in amacrine and ganglion cells was strongly reduced. This may be functionally related to the fact that vision in the deep sea environment relies exclusively on bioluminescence and is represented by burst-like emissions of point sources. This requires a mode of retinal signal processing that is less complex than in duplex retinae and involves a lower density of dendritic branching and synapses.
Chemopreventive Effect of Five Drugs on Renal Interstitial Fibrosis Induced by an Aristolochic Acid-Containing Chinese Herb in Rats
Authors: Zhu Shaoming , Liu Jiubo , Chen Lin , Li Yan , Yao Junxia , Jin Chaoxia , Wang Zuojun , Wang Lei , Wu Pingyong , Luo Qiang , Zhou Juan
Published: May 2005

Background/Aims: This study focuses on the chemopreventive effect of five drugs on renal interstitial fibrosis induced by an aristolochic acid-containing Chinese herb Mu-Tong. Methods: Renal interstitial fibrosis was induced in rats by administration of the Mu-Tong solution intragastrically for 6 weeks, and 36 rats were randomly divided into six groups: (1) Mu-Tong, (2) Mu-Tong + captopril, (3) Mu-Tong + losartan, (4) Mu-Tong + simvastatin, (5) Mu-Tong + spironolactone, and (6) Mu-Tong + diammonium glycyrrhizinate. Blood biochemistry and extracellular matrix were detected at weeks 0, 2, 4, and 6. At the end of week 6, kidney tissue of all groups was evaluated with special Masson staining for the degree of renal fibrosis as well as regular histopathology. Results: Mu-Tong caused progressive elevation of blood urea nitrogen, creatinine, hyaluronic acid, procollagen type III, and laminin. All five drugs suppressed elevation of blood biochemistry and extracellular matrix to some degree, but only the simvastatin group showed a significantly reduced percentage of positive Masson staining area in renal section compared to the Mu-Tong group (p < 0.05). Conclusions: Our study indicates that Mu-Tong induces a similar kidney injury with general characteristics in patients with renal interstitial fibrosis. All five different drugs have suppressive effects on Mu-Tong-induced renal function damage, and in particular, simvastatin shows a protective effect on development of Mu-Tong-induced renal interstitial fibrosis to a certain degree.
Distribution of G-Protein-Coupled Receptor (GPCR)135 Binding Sites and Receptor mRNA in the Rat Brain Suggests a Role for Relaxin-3 in Neuroendocrine and Sensory Processing
Authors: Sutton Steven W. , Bonaventure Pascal , Kuei Chester , Roland Barbara , Chen Jingcai , Nepomuceno Diane , Lovenberg Timothy W. , Liu Changlu
Published: May 2005

G-protein-coupled receptor 135 (GPCR135), a former orphan GPCR also known as SALPR, has recently been shown to be modulated by relaxin-3 (R3). In addition to GPCR135, R3 has been shown to be an agonist for GPCR142 (which is a pseudogene in the rat) and to activate LGR7, which is primarily the receptor for relaxin-1/2. The interaction of R3 with LGR7 has confounded the autoradiographic study of the GPCR135 distribution in the rat CNS due to significant expression of LGR7 in the brain. R3/I5, a chimera of the B-chain of R3 bonded to the A-chain of INSL-5, is a specific GPCR135 agonist which is highly selective for GPCR135 over LGR7. [125I]R3/I5 specifically binds to sites on rat brain sections with a pharmacology matching results from membrane preparations of recombinant GPCR135 receptors. Autoradiographic studies show the GPCR135 receptor density is most prominent in areas such as the olfactory bulb, sensory cortex, amygdala, thalamus, paraventricular nucleus, supraoptic nucleus, inferior and superior colliculus. The GPCR135 mRNA distribution generally overlaps the pattern of GPCR135 binding sites shown by autoradiography using [125I]R3/I5. The nucleus incertus, which has been implicated in the extrapituitary actions of corticotropin-releasing hormone, is the primary source of R3 in the rat central nervous system and expresses GPCR135 receptors. These binding autoradiography and in situ hybridization data suggest that GPCR135 plays an important role in the central processing of sensory signals in rats, are consistent with a putative role for R3/GPCR135 as modulators of stress responses, and confirm the identity of R3 as the central nervous system ligand for GPCR135.
Use of Computers and Software in Medical Research
Authors: Bech Jan , Kjeldsen Keld , Schmidt Thomas Andersen
Published: May 2005

New computers, software and updated versions of already established programs are constantly being released, and from a practical point of view it may be considered nearly impossible to remain up-to-date with this constantly evolving market. The aim of the present paper is to share our own experiences with software we found convenient to use in medical research. We give an overview over different programs and provide references to relevant websites for more information. The focus is on backup programs/devices, word processors, spreadsheets/databases, graphics pages, statistics programs, Reference Manager and antivirus programs. This review will not focus on specific computers or details in various programs, it is not intended to serve as a manual.
ACE Inhibitors for Older Patients with Heart Failure: A Review of Evidence, Practice Patterns and Challenges
Authors: Peterson Pamela N. , Masoudi Frederick A.
Published: May 2005

Heart failure is predominantly a condition of the elderly and is associated with substantial mortality, morbidity and functional limitation. In clinical trials of patients with left ventricular systolic dysfunction (LVSD), angiotensin-converting enzyme (ACE) inhibitors reduce the burden of heart failure. Clinical trials, however, have largely excluded older persons. This paper reviews the evidence for efficacy and effectiveness of ACE inhibitors, current patterns of use of these important agents and the challenges of prescribing ACE inhibitors for older patients with heart failure. The existing literature indicates that (1) despite a relative paucity of data from randomized controlled trials, observational studies suggest that the elderly with LVSD are as likely to benefit from ACE inhibitors as younger patients; (2) ACE inhibitors are underused in older persons despite guideline recommendations, and (3) the older population presents specific challenges in applying the clinical evidence supporting ACE inhibitors, including polypharmacy, cognitive impairment and other common comorbid conditions. Nevertheless, the judicious use of ACE inhibitors in eligible older patients will likely improve health outcomes.
Intensive Treatment and Stem Cell Transplantation in Chronic Myelogenous Leukemia: Long-Term Follow-Up
Authors: Simonsson Bengt , Öberg Gunnar , Björeman Mats , Björkholm Magnus , Carneskog Jan , Karlsson Karin , Gahrton Gösta , Grimfors Gunnar , Hast Robert , Karle Hans , Linder Olle , Ljungman Per , Nielsen Johan L. , Nilsson Jonas , Löfvenberg Eva , Malm Claes , Olsson Karin , Olsson-Strömberg Ulla , Paul Christer , Stenke Leif , Stentoft Jesper , Turesson Ingemar , Udén Ann-Marie , Wahlin Anders , Vilén Lars , Weis-Bjerrum Ole
Published: May 2005

In the present study we combined interferon (IFN) and hydroxyurea (HU) treatment, intensive chemotherapy and autologous stem cell transplantation (SCT) in newly diagnosed chronic myelogenous leukemia patients aged below 56 years, not eligible for allogeneic SCT. Patients who had an HLA-identical sibling donor and no contraindication went for an allogeneic SCT (related donor, RD). After diagnosis, patients not allotransplanted received HU and IFN to keep WBC and platelet counts low. After 6 months patients with Ph-positive cells still present in the bone marrow received 1–3 courses of intensive chemotherapy. Those who became Ph-negative after IFN + HU or after 1–3 chemotherapy courses underwent autologous SCT. Some patients with poor cytogenetic response were allotransplanted with an unrelated donor (URD). IFN + HU reduced the percentage of Ph-positive metaphases in 56% of patients, and 1 patient became Ph-negative. After one or two intensive cytotherapies 86 and 88% had a Ph reduction, and 34 and 40% became Ph-negative, respectively. In patients receiving a third intensive chemotherapy 92% achieved a Ph reduction and 8% became Ph-negative. The median survival after auto-SCT (n = 46) was 7.5 years. The chance of remaining Ph-negative for up to 10 years after autologous SCT was around 20%. The overall survival for allo-SCT RD (n = 91) and URD (n = 28) was almost the same, i.e. ≈60% at 10 years. The median survival for all 251 patients registered was 8 years (historical controls 3.5 years). The role of the treatment schedule presented in the imatinib era is discussed.
Mesencephalic Trigeminal Nucleus Development Is Dependent on Krox-20 Expression
Authors: De Shampa , Nguyen Anh Quan , Shuler Charles F. , Turman Jr. Jack E.
Published: May 2005

Krox-20, a C2H2-type zinc-finger transcription factor, plays an important role in rhombomere development. This study reveals that the Krox-20 null mutation impacts the development of mesencephalic trigeminal (Me5) neurons, a cell group traditionally thought to emerge from the mesencephalon. Based on cell counting studies, we show that Krox-20 null mutants have twice as many Me5 neurons relative to wildtypes at E15, but by birth have half the number of Me5 cells as wildtypes. TUNEL studies reveal a period of increased apoptosis from E17-P0 in mutants. The mutation does not result in differences in Me5 cell size, morphology, gene expression or peripheral projection patterns between genotypes, as demonstrated by retrograde tracing and Brn3a immunohistochemistry. The data suggest that Krox-20 regulates the period and extent of Me5 apoptosis, impacting the final number of Me5 neurons. The loss of Me5 in Krox-20–/– mice may highlight species-specific differences in the origin of these cells.