bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of memory impairment in the general population: screening by questionnaire and telephone compared to subsequent face‐to‐face assessment
Authors: van Uffelen Jannique G. Z. , Chin A Paw Marijke J. M. , Klein Martin , van Mechelen Willem , Hopman‐Rock Marijke
Published: October 2006

Background

Development of efficient methods for identifying subjects with Mild Cognitive Impairment (MCI) from the general population is warranted, because these subjects represent an important group for (epidemiological) research purposes.

Objectives

(1) To describe a two‐step population screening for identifying adults with MCI from the general population for research purposes, by questionnaire and telephone; (2) to compare screening by telephone (method 1) to a subsequent face‐to‐face assessment (method 2).

Methods

In method 1, subjects with memory complaints were identified from the general population (n = 5491) by a postal questionnaire. Subsequently, cognitive status and memory were assessed in a telephone interview using the Telephone Interview for Cognitive Status and the Ten Word Learning Test. Next, subjects with MCI according to method 1 were subjected to a face‐to‐face assessment for method 2, in which cognitive status and memory were assessed using the Mini Mental State Examination (MMSE) and the Auditory Verbal Learning Test (AVLT).

Results

Two hundred and twenty‐seven subjects completed both the telephone interview and the face‐to‐face assessment. Ninety‐three subjects (41%) had MCI according to both methods. Seven subjects (3%) failed to meet MCI criteria according to method two because of an MMSE score <24; 127 subjects (56%) failed because of normal AVLT scores.

Conclusion

(1) The two‐step population screening was able to detect a considerable number of MCI‐subjects in the general population; (2) agreement between both methods was moderate. Therefore, the method of recruiting subjects for (epidemiological) studies has to be taken into consideration when interpreting results of these studies. Copyright © 2006 John Wiley & Sons, Ltd.
Usefulness of Beck Depression Inventory (BDI) in the Korean elderly population
Authors: Jo Sangmee Ahn , Park Moon Ho , Jo Inho , Ryu Seung‐Ho , Han Changsu
Published: October 2006

Objectives

This study aimed to evaluate the diagnostic validity of the Beck Depression Inventory (BDI) in the elderly and to suggest an optimal cut‐off score in order to screen major depressive disorder.

Methods

The BDI and an elderly health questionnaire were administered to 2729 subjects over the age of 60 chosen by stratified random sampling in a Ansan City, South Korea. The BDI and geriatric depression scale (GDS) were examined at about a two‐year interval. A reliability and validity test, a factor analysis and an ROC curve analysis were performed.

Results

Eighty‐four subject had depression and 2645 subjects were rated as normal. The BDI showed significant positive internal consistency (r = 0.88) and test–retest reliability (r = 0.60). Convergent validity with GDS was significantly positive (r = 0.59), and an exploratory factor analysis revealed four factors. We suggest a score of 16 as the optimal cut‐off point for the BDI when screening for major depression.

Conclusion

The results of this study showed that the Korean version of the BDI is appropriate for screening for depression and 16 is the optimal cut‐off score for the Korean elderly. Screening of elderly depression with BDI in the community would be valuable when comparing with younger adults and with their former BDI data which were taken when they were young. Copyright © 2006 John Wiley & Sons, Ltd.
Depressive symptoms in the very old living alone: prevalence, incidence and risk factors
Authors: Wilson Kenneth , Mottram Patricia , Sixsmith Andrew
Published: October 2006

Background

Living alone is one of many risk factors associated with depression. This project is nested within the ENABLE‐AGE project designed to explore the relationship between housing environment and health in the very old living alone in their own homes.

Aim

Our aim is to describe the prevalence, incidence and associated risk factors of clinically significant depressive symptoms in this population with particular emphasis on the role of the home environment.

Method

We conducted a one year follow up of 376 subjects aged between 80 and 90 years old. Data collected included variables concerned with housing, social circumstances, physical health and psychological well being.

Results

A prevalence rate of 21% and an annual incidence of 12.4% (Geriatric Depression Score of five or more) were found. Risk factors associated with prevalence depression include not living close to friends and family ((OR 2.540, CI; 1.442, 4.466), poor satisfaction with living accommodation (OR; 0.840, CI; 0.735, 0.961) and poor satisfaction with finances (OR; 0.841, CI; 0.735, 0.961). Subsequent development of clinically significant depressive symptoms was associated with base line increased scores in depression (OR; 1.68, CI; 1.206, 2.341).

Conclusions

These results are consistent with findings in the general population of similar age with the exception of considerably higher prevalence and incidence rates. However, we were unable to demonstrate that housing related variables were significant risk factors in terms of incidence cases.

Clinical Implications

Older people living alone are particularly vulnerable to depression and may benefit from targeted screening and development of appropriate care pathways. Copyright © 2006 John Wiley & Sons, Ltd.
The effect of perceived forgetfulness on quality of life in older adults; a qualitative review
Authors: Mol Martine , Carpay Margot , Ramakers Inez , Rozendaal Nico , Verhey Frans , Jolles Jelle
Published: October 2006

Background

Approximately 50% of older individuals perceive themselves as being forgetful.

Objective

The objective of this review is to get an overview of previous research on the relation between perceived forgetfulness (in the absence of objective memory deficit) and quality of life in older individuals. Findings in previous research might be a starting point for further research and possible future interventions.

Methods

Scientific papers that investigated the relation between subjective memory complaints and quality of life were searched. Two independent raters scored the articles on their methodology. The methodological quality was taken into account when conclusions were drawn.

Results

The literature search resulted in 682 articles, of which five studies met the inclusion criteria. Although the five studies differed in their methodology, the findings of the methodologically adequate studies show a relation between memory complaints and a diminished quality of life in the elderly.

Conclusions

The negative impact that subjective memory complaints can have on quality of life makes it important to acknowledge forgetfulness as a serious issue in the life of older individuals. However, more research is needed to explore the relationship between subjective memory complaints and quality of life, also with regard to the influence of depression and objective memory performance. Copyright © 2006 John Wiley & Sons, Ltd.
The challenge of measuring quality of care at health centre level in Africa: the example of Tsholotsho health district in Matabeleland North, Zimbabwe
Authors: Van Eygen Luk , Van Lerberghe Veerle , Blaise Pierre , Woelk Godfrey , Criel Bart
Published: October 2006

This study is on the evaluation of quality of health care within first line health services in rural Zimbabwe. It took place between 2001 and 2002, and consisted of a cross‐sectional survey designed to compare the quality of health care on offer at a newly created health centre with that provided by the district hospital's outpatient department. The hypothesis to be tested was that the health centre offered better quality of care. A comprehensive quality of care evaluation framework was designed. The concept of patient enablement was incorporated into the study's assessment of health care delivery outcomes. The results did not provide conclusive evidence that the care offered at the health centre was better than the care on offer at the hospital OPD. The reasons for these unexpected findings are discussed in depth. They are related to the limited understanding amongst local health workers of the organisational changes introduced by the District Health Executive (DHE), together with a (European) cultural bias in the quality of care model under test. An important lesson of this study is that the notion of enablement, notwithstanding the need to put into context the tools used to measure it, was considered by the DHE as relevant in the organisation and evaluation of health care. Copyright © 2006 John Wiley & Sons, Ltd.
The risk of pancreatic cancer in patients with gastric or duodenal ulcer disease
Authors: Luo Juhua , Nordenvall Caroline , Nyrén Olof , Adami Hans‐Olov , Permert Johan , Ye Weimin
Published: October 2006

Although Helicobacter pylori (H. pylori) seropositivity is linked to an excess risk of pancreatic cancer, the biologic mechanism is unknown. Gastric ulcer is primarily associated with corpus colonization of H. pylori, atrophic gastritis and formation of N‐nitrosamines. Duodenal ulcer is a marker of antral colonization, hyperacidity and uninhibited secretin release. We estimated relative risks for pancreatic cancer among patients with gastric or duodenal ulcer, based on a register‐based retrospective cohort study with 88,338 patients hospitalized for gastric ulcer and 70,516 patients for duodenal ulcer recorded in the Swedish Inpatient Register between 1965 and 2003. Following operation, the 14,887 patients who underwent gastric resection and 8,205 with vagotomy were analyzed separately. Multiple record‐linkages allowed complete follow‐up and identification of all incident cases of pancreatic cancer until December 31, 2003. Standardized incidence ratios (SIRs) estimated relative risks. During years 3–38 of follow‐up, we observed a 20% excess risk (95% confidence interval [CI] 10–40%) for pancreatic cancer among unoperated gastric ulcer patients. The excess increased to 50% (95% CI 10–110%) 15 years after first hospitalization (p for trend = 0.03). SIR was 2.1 (95% CI 1.4–3.1) 20 years after gastric resection. Unoperated duodenal ulcer was not associated with pancreatic cancer risk, nor was vagotomy. Our results lend indirect support to the nitrosamine hypothesis, but not to the hyperacidity hypothesis in the etiology of pancreatic cancer. © 2006 Wiley‐Liss, Inc.
Expression of the mitotic checkpoint gene MAD2L2 has prognostic significance in colon cancer
Authors: Rimkus Caroline , Friederichs Jan , Rosenberg Robert , Holzmann Bernhard , Siewert Jörg‐Rüdiger , Janssen Klaus‐Peter
Published: October 2006

Aneuploidy and genetic instability are a hallmark of colorectal cancer and other solid tumors, and they are thought to enhance tumor progression. The gene MAD2L2 (mitotic arrest deficient 2‐like 2) encodes the spindle checkpoint protein MAD2L2 (or MAD2B), a key component of a surveillance system that delays anaphase until all chromosomes are correctly oriented. Defects in this mitotic checkpoint are known to contribute to genetic instability, i.e., numerical and structural aberrations of chromosomes. We have previously identified MAD2L2 as significantly upregulated in locally restricted colorectal tumors by gene expression profiling. So far, MAD2L2 has not been reported to play a major role in human cancer in contrast to its homologue MAD2. To address this question, 118 histologically confirmed colorectal lesions were analyzed by quantitative real‐time PCR for expression of MAD2L2, and compared to normal colon tissue from 11 patients. Twenty‐five out of 118 tumor samples (21%) showed MAD2L2 overexpression of 3‐fold or more compared to normal colon, and the fraction of overexpressing tumors increased with tumor stage. Correspondingly, protein levels of MAD2L2 were found to be significantly upregulated in tumors as compared to matched normal tissue. Tumors with upregulated MAD2L2 expression had significantly higher numbers of aberrant mitotic figures (anaphase bridges), an indication of chromosomal instability. Elevated expression of MAD2L2 was significantly correlated with reduced patient survival. By multivariate analysis, MAD2L2 expression was retained as an independent prognostic parameter for patient survival. Thus, our results demonstrate that overexpression of MAD2L2 correlates with bad prognosis in colorectal cancer. © 2006 Wiley‐Liss, Inc.
Cell death induced by N‐(4‐hydroxyphenyl)retinamide in human epidermal keratinocytes is modulated by TGF‐β and diminishes during the progression of squamous cell carcinoma
Authors: Davies Maria , Paterson Ian C. , Ganapathy Anu , Prime Stephen S.
Published: October 2006

It has been demonstrated that the chemopreventive agent N‐(4‐hydroxyphenyl)retinamide (4‐HPR) induces apoptotic cell death, but recent data has suggested that late stage/recurrent tumours lose their response to 4‐HPR‐induced cell death by mechanisms that are unknown. Our study investigated the ability of 4‐HPR to induce cell death in keratinocyte cell lines that represent different stages of carcinogenesis and the role of TGF‐β signalling in the induction of cell death by 4‐HPR. We show that treatment of the immortalised keratinocyte cell line HaCaT with 10−5 M 4‐HPR induced cell death by apoptosis and caused an accumulation of cells in the G0/G1 phase of the cell cycle. Using a genetically related series of human skin keratinocytes derived from HaCaT that reflect tumour progression and metastasis in vivo, we demonstrate that 4‐HPR‐induced cell death and apoptosis is attenuated in the more aggressive tumour cell lines but that a reduced level of response is retained. Response to TGF‐β‐induced growth inhibition was also reduced in the more aggressive cell lines. Treatment of HaCaT cells with 4‐HPR induced TGF‐β2 expression and an increase in the amount of active TGF‐β in the culture medium. The inhibition of TGF‐β signalling attenuated 4‐HPR‐induced apoptosis and both TGF‐β1 and TGF‐β2 potentiated 4‐HPR‐induced apoptosis and enhanced 4‐HPR‐induced growth inhibition. Our results demonstrate that loss of response to 4‐HPR correlates with a loss of response to the growth inhibitory effects of TGF‐β and that adjuvant therapies that upregulate TGF‐β may enhance the chemopreventive effects of 4‐HPR. © 2006 Wiley‐Liss, Inc.
Possible role of calcium in the cardiovascular effects of prolonged administration of gamma‐hch (lindane) in rats
Authors: Anand M. , Meera P. , Kumar R. , Gupta G. S. D. , Tripathi O. , Srimal R. C.
Published: October 2006

Gamma‐HCH (lindane) administered for long durations is reported to cause toxic cardiovascular effects. Present study was carried out to assess the changes in cardiovascular activity and cellular calcium homeostatic mechanisms in rats administered 3 mg kg−1 day−1 of gamma‐HCH p.o. for 6 weeks. The changes in electrocardiogram were marked by a decrease in R–R interval and the amplitude of the P wave by 53% and 50%, respectively. The amplitude of R and T waves was increased by 65% and 58%, respectively. Calcium‐45 influx was increased in atrial trabeculae (33%) and in papillary muscle (10%). The plasma calcium concentration was increased (32%) and Ca, K‐ATPase activity in heart was decreased (50%). It is suggested on the basis of these findings that cellular calcium homeostatic mechanisms are involved in the cardiovascular effects of gamma‐HCH administered chronically in rats.
Inhalation exposure to jp‐8 jet fuel alters pulmonary function and substance p levels in fischer 344 rats
Authors: Pfaff John , Parton Kathleen , Clark Lantz R. , Chen Huizhong , Hays Allison M. , Witten Mark L.
Published: October 2006

In a simulated military flightline exposure protocol, Fischer 344 rats (F344) were used to investigate the pulmonary effects of JP‐8 jet fuel inhalation. Exposures were nose only and for 1 h daily. Groups were exposed for 7 days (7D) or 28 days (28D). Each exposure group had a matched longitudinal control group (LC7 and LC28). Exposure concentrations of 520 mg m−3 caused an increase in dynamic compliance after 7 days of exposure, but compliance changes were not seen with continued exposure (28D, 495 mg m−3). Pulmonary resistance was increased in both 7‐ and 28‐day JP‐8‐exposed groups. Changes in pulmonary function were accompanied by a decrease in substance P concentrations from the bronchoalveolar lavage fluid (BALF). No significant change was observed in BALF levels of 6‐keto‐PGF1α, the stable metabolite of prostacyclin, which is a marker of endothelial cell function. The JP‐8‐exposed rats gained significantly less weight during the study period than the LC7 and LC28 groups, and the lungs of the 7D group were heavier by wet lung/body weight ratio (WtL/WtB). Alveolar clearance of technetium‐labelled diethylenetriamine pentaacetate ([99mTc]DTPA) was increased in jet fuel‐exposed groups. Light microscopy showed no pathological evidence of lung injury. Recovery from the early pulmonary effects of JP‐8 inhalation occurred with continued exposure, as seen by recovery of pulmonary compliance and WtL/WtB.
Comparative developmental toxicity of butyltin trichloride, dibutyltin dichloride and tributyltin chloride in rats
Authors: Ema Makoto , Kurosaka Reiko , Amano Hiro , Ogawa Yoshiyuki
Published: October 2006

Butyltin trichloride (BT), dibutyltin dichloride (DBT) and tributyltin chloride (TBT) were compared for their developmental toxicity including teratogenic potential following administration during the susceptible period for the teratogenesis of DBT. Pregnant rats were given either BT at a dose of 1000, 1500 or 2000 mg kg−1, DBT at a dose of 10 or 15 mg kg−1 or TBT at a dose of 40 or 80 mg kg−1 by gastric intubation on days 7 and 8 of pregnancy. Although maternal toxicity occurred, as evidenced by a significantly increased maternal lethality at 1500 and 2000 mg kg−1 and decreased maternal weight gain at 1000 and 1500 mg kg−1, no significant increase in the incidences of postimplantation loss and malformed fetuses were observed after treatment with BT. Treatment with DBT resulted in a significantly lower maternal weight gain, lower fetal weight and higher postimplantation embryolethality. A significantly and markedly increased incidence of fetuses with malformations, such as exencephaly, cleft jaw, cleft lip, ankyloglossia, club foot, deformity of the vertebral column in the cervical and thoracic regions and of the ribs and ano‐ or microphthalmia, was observed in both groups treated with DBT. While treatment with TBT at 40 and 80 mg kg−1 caused a significantly decreased maternal weight gain and increased postimplantation embryolethality, no significantly increased incidence of malformed fetuses occurred. It could be concluded that BT, DBT and TBT are different in the susceptibility and spectrum of developmental toxicity.
Genotoxicity and twenty‐eight‐day subchronic toxicity studies on tertiary amyl methyl ether
Authors: Daughtrey Wayne C. , Bird Michael G.
Published: October 2006

Tertiary amyl methyl ether (TAME) is an oxygenate with a potential role as a component in reformulated gasolines. The genotoxic potential of TAME was assessed in an Ames assay and a mouse micronucleus assay. The Ames assay was carried out using five standard salmonella strains and doses ranging from 100 to 10000 μg per plate. Tertiary amyl methyl ether was not mutagenic in any of the strains, either with or without metabolic activation. In the micronucleus assay, mice were given a single intraperitoneal injection of TAME at doses of 0.15, 0.375 or 0.75 g kg−1. Bone marrow samples were collected and evaluated for micronucleus formation at 24, 48 and 72 h after dosing. No elevation in micronucleus frequency was observed at any dose or at any of the collection times. Thus, TAME was not clastogenic to mouse bone marrow under the conditions of this study. Preliminary test data indicated that the acute oral LD50 for TAME in Sprague‐Dawley rats was ca. 2.1 g kg−1. In the 28‐day subchronic study, Sprague‐Dawley rats of both sexes were dosed orally with vehicle, 0.125, 0.5 or 1.0 g kg−1 day−1 TAME in corn oil at a dose volume of 2 ml/kg−1. Dosing continued 7 days a week for a period of 28 days. Deaths of two out of 10 animals in the high‐dose group (1 g kg−1 day−1) appeared to be compound related. Food consumption and body weights were reduced in the high‐dose male group relative to controls; otherwise, clinical observations were minimal. Dose‐related increases in adrenal and kidney weights were observed but no histopathological changes were evident in any of the tissues examined. It is concluded that while some evidence of toxicity was observed at the highest dose, TAME is of low oral toxicity following repeated dosing. The no‐observed‐effect level (NOEL) for this study was 0.125 g kg−1 day−1 and the no‐observed‐adverse‐effect level (NOAEL) was 0.5 g kg−1 day−1.
Effect of prenatal and postnatal exposure to lead on kidney function in male and female rats
Authors: Vyskocil A. , Cizkova M. , Tejnorova I.
Published: October 2006

The effect of 5 months' exposure to 0.5% lead acetate in drinking water on the kidney function of developing rats was studied. In both sexes, lead exposure produced a significant elevation of the kidney weight and after 3 months' treatment both male and female rats showed signs of tubular impairment. In male rats increased β2‐microglobulin and lactate dehydrogenase excretion was observed. Lysozyme was increased after 5 months of exposure. No changes were observed in total proteins and albumin excretion. Female rats showed a significantly increased excretion of β2‐microglobulin from 3 months onwards, while lactate dehydrogenase increased only at the end of 3 months and total proteins after 5 months of exposure. No changes were observed in lysozyme and albumin excretion. Thus, the results suggest that lead exposure produces changes in the renal tubular function of developing rat. There is no sex difference in the nephrotoxicity of lead. Comparison with our previous studies suggests that exposure to lead starting at weaning is more renotoxic than exposure starting 2 months later. However, prenatal exposure might also have been a contributory factor.
Nephrotoxicity of ifosfamide in rats
Authors: Springate James E. , van Liew Judith B.
Published: October 2006

Renal proximal tubule cell injury is an important side effect of the chemotherapeutic agent ifosfamide in humans. We investigated the effect of this medication on kidney function in rats. Animals received either 40 or 80 mg kg−1 ifosfamide intraperitoneally daily for 3 days every 3 weeks for a total of four treatment courses. Ifosfamide‐treated rats had significantly lower body weight and hematocrit than sterile water‐treated control rats. Animals receiving 40 mg kg−1 ifosfamide developed isolated phosphaturia after their fourth and final treatment course. Rats receiving 80 mg kg−1 ifosfamide had low‐grade glucosuria, phosphaturia and proteinuria throughout the study. Urine flow rate, creatinine clearance, urinary sodium and potassium excretion and kidney glutathione and malondialdehyde content were not affected by ifosfamide at either dose. These findings indicate that ifosfamide produces abnormalities in rat renal function resembling subclinical Fanconi syndrome.
Effect of dosing vehicle on the toxicity and metabolism of unsaturated aliphatic nitriles
Authors: Farooqui Mohammed Y. H. , Ybarra Benjamin , Piper John , Tamez Angel
Published: October 2006

The effect of dosing vehicle on toxicity and metabolism of unsaturated aliphatic nitriles was investigated in male Sprague–Dawley rats. Five unsaturated aliphatic nitriles—acrylonitrile, methacrylonitrile, allylnitrile, crotononitrile and fumaronitrile—were prepared in five different dosing vehicles—saline, corn oil, safflower oil, mineral oil, olive oil and Tween‐20. Groups of six male rats were given 0.5 LD50 doses of the nitriles by gavage and they were observed for 12 h for cholinomimetic and central nervous system effects. Cyanide and glutathione levels were determined in blood and various organs at 1, 3 and 6 h after nitrile administration and thiocyanate levels were determined at 6 h after nitrite administration. The results indicate that all the vehicles studied potentiated the toxicity of all the nitriles compared to nitriles administered in saline and significantly increased their metabolism to cyanide and thiocyanate and nitrile‐induced depletion of glutathione in rats. This behavior of vehicles illustrates the difficulty of identifying suitable vehicles for administration of lipophilic compounds in toxicology studies.
Fluoride accumulation and toxicity in laboratory populations of wild small mammals and white mice
Authors: Boulton Iain C. , Cooke John A. , Johnson Michael S.
Published: October 2006

A laboratory experiment was conducted to compare the toxicological response and metabolism of inorganic fluoride by three species of wild mammals and laboratory white mice (Mus musculus L.). The experimental populations of the wild species—the short‐tailed field vole (Microtus agrestis L.), the bank vole (Clethrionomys glareolus L.) and the wood mouse (Apodemus sylvaticus L.)—were laboratory reared from wild stock, and all test animals were exposed to 0, 40 or 80 μg F ml−1 in their drinking water for up to 84 days. The 40 and 80 μg F ml−1 treatments induced premature mortalities in M. agrestis and C. glareolus only. Differential intakes, absorption and retention of fluoride were evident between M. musculus and M. agrestis, the two species subject to cage studies of fluoride metabolism budgets. Interspecific variation in accumulation of fluoride with time was also evident between all four species as regards the femur, molars and incisors. Severe dental lesions were apparent in species surviving the 80 μg ml−1 treatment for 84 days. Overall, however, there were few clear differences in inherent species sensitivity to fluoride, the interspecific variation in metabolism and accumulation rates being attributable mainly to variation in intake.
Hematological profile of the euthymic hairless guinea pig following sulfur mustard vesicant exposure
Authors: Gold Mark B. , Scharf Bruce A.
Published: October 2006

Sulfur mustard (HD) is a potent vesicating agent of military importance, with known radiomimetic properties. The euthymic hairless guinea pig (EHGP) (Cavia porcellus) is emerging as the animal model of choice for cutaneous HD study. With elucidation of the systemic effects, we may better utilize this animal for all HD toxicity work. To this end, studies were conducted to determine the definitive median lethal dose (MLD) of subcutaneously applied sulfur mustard (HD) in the EHGP, and to correlate the induced hematological changes. Eight groups of two animals each were dosed at 0.3 log intervals from an extrapolated expected dose, deriving a tentative mean around which five groups of six animals each were dosed at 0.1 log intervals, resulting in a definitive MLD of 48.17 mg kg−1. Sulfur mustard was then administered to seven groups of six animals each at a dose of 30 mg kg−1 and hematology performed. Significant leukocyte count suppression was found to occur on days 4, 5 and 6, following a leukocyte elevation on day 1 after exposure. Serum potassium levels were found to be elevated all 7 days after HD exposure. Establishing the MLD for subcutaneously applied HD and the pattern of induced leukocyte suppression allows for more definitive evaluation of successful toxicity counter‐measures.
Zinc and the cytoskeleton in the neuronal modulation of transcription factor NFAT
Authors: Mackenzie Gerardo G. , Oteiza Patricia I.
Published: October 2006

Transcription factor NFAT is crucial in the development of the nervous system due to its role in neuronal plasticity and survival. In this study we characterized the role of zinc and the cytoskeleton in the modulation of NFAT in neuronal cells. The incubation of cells in zinc deficient media led to NFAT activation that was inhibited by the calcium chelator BAPTA and the antioxidants (±)‐α‐lipoic acid and N‐acetyl cysteine, suggesting the involvement of calcium and oxidants in the initial steps of NFAT activation associated with zinc deficiency. At a second step of regulation, a decrease in cellular zinc led to an impaired transport of the active NFAT from the cytosol into the nucleus due to alterations in tubulin polymerization secondary to a decrease in neuronal zinc. Furthermore, disruption of the cytoskeleton structure by cold and chemical agents (colchicine (Col), vinblastine (VB), cytochalasin D (Cyt)) also inhibited NFAT transport into the nucleus. The altered nuclear transport caused a decrease in NFAT‐dependent gene expression. This study demonstrates for the first time that zinc can modulate transcription factor NFAT in neuronal cells, and that microtubules are involved in NFAT nuclear translocation, crucial event in the regulation of NFAT transcriptional activity. J. Cell. Physiol. 210: 246–256, 2007. © 2006 Wiley‐Liss, Inc.
The organic osmolytes betaine and proline are transported by a shared system in early preimplantation mouse embryos
Authors: Idris Anas Mohamed‐Kheir , Hammer Mary‐Anne , Lever Michael , Stanton Jo‐Ann L. , Baltz Jay M.
Published: October 2006

Betaine and proline protect preimplantation mouse embryos against increased osmolarity and decreased cell volume, implying that they may function as organic osmolytes. However, the transport system(s) that mediates their accumulation in fertilized eggs and early embryos was unknown, and previously identified mammalian organic osmolyte transporters could not account for their transport. Here, we report that there is a single saturable transport component shared by betaine and proline in 1‐cell mouse embryos. A series of inhibitors had nearly identical effects on both betaine and proline transport by this system. In addition, Ki values for reciprocal inhibition of betaine and proline transport were ∼100–300 µM, similar to Km values (∼200–300 µM) for their transport, and both had similar maximal transport rates (Vmax). The Ki values for inhibition of betaine and proline transport by dimethylglycine were similar (∼2 mM), further supporting transport of both substrates by a single transport system. Finally, betaine and proline transport each required Na+‐ and Cl−. These data were consistent with a single, Na+‐ and Cl−‐requiring, betaine/proline transport system in 1‐cell mouse embryos. While betaine was only transported by a single saturable system, we found an additional, less conspicuous proline transport route that was betaine‐insensitive, Na+‐sensitive, and inhibited by alanine, leucine, cysteine, and methionine. Furthermore, we showed that betaine, like proline, is present in the mouse oviduct and thus could serve as a physiological substrate. Finally, accumulation of both betaine and proline increased with increasing osmolarity, consistent with a possible role as organic osmolytes in early embryos. J. Cell. Physiol. 210: 266–277, 2007. © 2006 Wiley‐Liss, Inc.
Human fetal cortical and striatal neural stem cells generate region‐specific neurons in vitro and differentiate extensively to neurons after intrastriatal transplantation in neonatal rats
Authors: Kallur Therése , Darsalia Vladimer , Lindvall Olle , Kokaia Zaal
Published: October 2006

Human fetal brain is a potential source of neural stem cells (NSCs) for cell replacement therapy in neurodegenerative diseases. We explored whether NSCs isolated from cortex and striatum of human fetuses, aged 6–9 weeks post‐conception, maintain their regional identity and differentiate into specific neuron types in culture and after intrastriatal transplantation in neonatal rats. We observed no differences between cortex‐ and striatum‐derived NSCs expanded as neurospheres in proliferative capacity, growth rate, secondary sphere formation, and expression of neural markers. After 4 weeks of differentiation in vitro, cortical and striatal NSCs gave rise to similar numbers of GABAergic and VMAT2‐ and parvalbumin‐containing neurons. However, whereas cortical NSCs produced higher number of glutamatergic and tyrosine hydroxylase‐ and calretinin‐positive neurons, several‐fold more neurons expressing the striatal projection neuron marker, DARPP‐32, were observed in cultures of striatal NSCs. Human cortical and striatal NSCs survived and migrated equally well after transplantation. The two NSC types also generated similar numbers of mature NeuN‐positive neurons, which were several‐fold higher at 4 months as compared to at 1 month after grafting. At 4 months, the grafts contained cells with morphologic characteristics of neurons, astrocytes, and oligodendrocytes. Many of neurons were expressing parvalbumin. Our data show that NSCs derived from human fetal cortex and striatum exhibit region‐specific differentiation in vitro, and survive, migrate, and form mature neurons to the same extent after intrastriatal transplantation in newborn rats. © 2006 Wiley‐Liss, Inc.
Myelin deficiencies visualized in vivo: Visually evoked potentials and T2‐weighted magnetic resonance images of shiverer mutant and wild‐type mice
Authors: Martin Melanie , Hiltner Timothy D. , Wood John C. , Fraser Scott E. , Jacobs Russell E. , Readhead Carol
Published: October 2006

Visually evoked potentials (VEPs) and micromagnetic resonance imaging (μMRI) are widely used as noninvasive techniques for diagnosis of central nervous system (CNS) diseases, especially myelin diseases, such as multiple sclerosis. Here we use these techniques in tandem to validate the in vivo data in mouse models. We used the shiverer mutant mouse, which has little or no CNS myelin, as a test model. These data show that shiverer (MBPshi/MBPshi) has a VEP latency that is 30% longer than that of its wild‐type sibling. Surprisingly, the heterozygous (MBPshi/+) mouse, with apparently normal myelin, nevertheless has a 7% increase in its VEP latency vs. wild type. The μMRIs of the same animals show that myelinated white matter is hypointense compared with gray matter as a result of the shorter T2 in myelinated regions of the CNS. T2‐weighted images of wild‐type and heterozygous shiverer mice show regions of hypointensity corresponding to the major myelinated tracts, including the optic nerve and the optic tract of the CNS, whereas shiverer mice have no regions of low intensity and therefore no detectable myelinated areas. In shiverer mice, μMRI can discern hypomyelination throughout the brain, including the optic tract, and these changes correlate with longer VEP latencies. In addition, VEPs can also detect changes in the molecular make up of myelin that are not discernible with histology or μMR. These data show the potential of using μMRI in combination with VEPs to follow changes in both the quality and the quantity of myelin in vivo. These combined methods would be useful for longitudinal studies and therapy testing. © 2006 Wiley‐Liss, Inc.
Composition and bioactive factor content of cowpea (Vigna unguiculata L. Walp) raw meal and protein concentrate
Authors: Olivera‐Castillo Leticia , Pereira‐Pacheco Fabiola , Polanco‐Lugo Erik , Olvera‐Novoa Miguel , Rivas‐Burgos José , Grant George
Published: October 2006

Analysis was done of the composition and bioactive factor content of whole meal, processed meal and protein concentrate from a cowpea cultivar (Vigna unguiculata L. Walp var. IT86D‐719) grown in Yucatan, Mexico and of changes in these parameters after soaking and dehulling. Both meals had a high protein content (247.53 and 257 g kg−1 dry matter (DM) respectively). The protein concentrate was rich in protein (786 g kg−1 DM) and lipids (58.47 g kg−1 DM) and had an amino acid profile similar to that of the processed meal. The amino acid profiles of the meals almost covered human dietary requirements based on FAO/WHO/UNU‐suggested profiles but were deficient in sulphur amino acids. Trypsin inhibitor activity was high in both meals compared with levels found in previous studies. Trypsin inhibitor activity in the concentrate was not eliminated but was significantly reduced. Lectin activity, tannin levels, phytate levels and α‐amylase inhibitor activity were relatively low in the meals, and cyanogenic glucosides were not detected. Residual amounts of α‐amylase inhibitors, tannins and phytate were observed in the concentrate, and lectin activity was not detected. Results indicate that V. unguiculata L. Walp var. IT86D‐719 meals and protein concentrate are good potential foodstuffs in the Yucatan region. Copyright © 2006 Society of Chemical Industry
Phenolics, inflammation and nutrigenomics
Authors: Evans David A , Hirsch Julie B , Dushenkov Slavik
Published: October 2006

Nutrigenomics is the study of the effects of bioactive compounds from food on gene expression. In the last several years, an increasing body of scientific evidence has demonstrated that individual compounds, as well as complex mixtures of chemicals, derived from food alter the expression of genes in the human body. By turning on or off genes, bioactives in food alter the concentration of specific proteins directly or indirectly associated with human diseases. Several human diseases result in multiple inflammatory responses which are associated with many diseases including arthritis, cancer, cardiovascular disease, dermatitis, asthma, obesity, and others. Detailed mechanisms of action as to how food derived components play an active role in prevention of inflammation have been elucidated. Such biologically active compounds include theaflavins and catechins from tea, curcumin from turmeric, resveratrol from grapes, and lactones from chicory. While chronic diseases are very complex, an opportunity exists to regulate genes involved in inflammation by enriching our diet with the specific foods inherently rich in such compounds, enriched foods containing standardized extracts of well studied sources, or dietary supplements. Copyright © 2006 Society of Chemical Industry
Sentinel lymph node biopsy in squamous cell carcinomas of the lips and the oral cavity—A single center experience
Authors: Frerich Bernhard , Förster Marcus , Schiefke Franziska , Wittekind Christian , Hemprich Alexander , Sabri Osama
Published: October 2006

Background and Objectives

Despite the availability of initial data on sentinel lymph node biopsy (SLNB) in OSCC, its value in clinical practice remains unclear. The aim of this study is to evaluate the feasibility and potential of SLNB as a reliable staging procedure in early stage SCC of the lips and the oral mucosa.

Methods

From 2001 to 2004, 40 patients with early stage SCC of the lips and oral cavity were enrolled. The main inclusion criteria were: cN0 category by MRI and ultrasound, tumor category T1‐T2, for certain sites also T3. Patients with positive SLN underwent MRND and/or radiation. Patients with negative SLN were monitored monthly.

Results

In eight patients, the SLN were positive. Two patients with negative SLN subsequently developed nodal disease (5% false negatives). Twenty‐one patients have a follow‐up longer than 24 months. Five patients died (one from nodal disease, one from local recurrence, and three from unrelated causes). One patient developed a second primary tumor, the remaining patients are free of disease.

Conclusions

SLNB may contribute to more targeted lymph node dissection strategies. Further studies will have to ensure the safety of this procedure in comparison to selective neck dissection. J. Surg. Oncol. 2007;95:97–105. © 2007 Wiley‐Liss, Inc.
Beyond mistrust and competition—the role of social and personal bonding processes in sustaining livelihoods of rural tourism businesses: a case of the Peak District National Park
Authors: Saxena Gunjan
Published: October 2006

This paper theorises the significance of social and personal bonding processes in promoting sustainable resource‐use and equitable tourism development using research on personal and social bonding process and relationship marketing. By looking at small, rural tourism businesses in the Peak District National Park (PDNP) it discusses how in intricate ways, individual business owners/managers are utilising social and kinship ties to increase their visual presence and competitive position in contemporary markets. The paper describes the significance of social and personal bonds as the respondents discuss how their informal affiliations have enabled them to tap into additional resources and develop products embedded in locally specific conventions that are more attractive to visitors, and are also assisting them to monitor each others' progress through informal forms of regulation. Copyright © 2006 John Wiley & Sons, Ltd.
The perceived impact of risks on travel decisions
Authors: Law Rob
Published: October 2006

The recent phenomena of infectious diseases, natural disasters and terrorist attacks have imposed an unprecedented threat to the global tourism industry. This paper reports on a study that investigated the perceived probability of occurrence, magnitude of threat and efficacy of official media on major types of risks from 1304 international travellers. The study also examined the perceived usefulness of a set of measures that aims to strengthen the confidence of travellers. This paper should provide tourism practitioners and policy‐makers an updated view from the perspective of travellers, which in turn, can assist the formulation of risk management strategies, an area that has long been of interest to tourism researchers and practitioners. Copyright © 2006 John Wiley & Sons, Ltd.
Prevalence of pathological gambling in patients with Parkinson's disease
Authors: Avanzi Maurizio , Baratti Mario , Cabrini Silvia , Uber Elena , Brighetti Gianni , Bonfà Flavio
Published: October 2006

Pathological gambling (PG) is a psychiatric disorder characterized by loss of control of gambling, which has repercussions on family, personal, and professional life. Several recent studies have reported the relationship between PG and the treatment of Parkinson's disease (PD), but no prevalence study has yet been conducted to investigate this correlation. The purpose of this study was to evaluate the prevalence of PG in Italian patients with PD on dopamine replacement therapy. The prevalence of PG in a PD sample (n = 98) and in an age‐ and sex‐matched control group (n = 392) was obtained. The prevalence of PG results significantly higher (P = 0.00001) in PD patients than in control subjects (6.1% vs. 0.25%). Our results emphasize that PG in patients with idiopathic PD on dopamine replacement therapy is an emergent comorbidity, but probably at present the condition is not properly diagnosed because it is mostly unknown. © 2006 Movement Disorder Society
Employment, medical absenteeism, and disability perception in Parkinson's disease: A pilot double‐blind, randomized, placebo‐controlled study of entacapone adjunctive therapy
Authors: Korchounov Alexei , Bogomazov Gregory
Published: October 2006

The objective of this study was to test the impact of entacapone (ENT) addition to levodopa with a decarboxylase inhibitor (LD) in full‐time–employed patients with Parkinson's disease (PD), focusing on retirement rates, medical absenteeism, self‐perception of disability, as well as motor assessments of parkinsonism, motor fluctuations, and dyskinesias. Thirty full‐time–employed PD patients (disease onset before age 60 years) and on optimized monotherapy with LD exhibiting minor motor fluctuations or dyskinesias were entered into a 2‐year randomized double‐blind placebo‐controlled study of ENT adjunctive therapy. The outcome measures were the number of full‐time–employed patients at study end, cumulative days of medical absenteeism, patient‐completed disability assessments, diary records, and the Unified Parkinson's Disease Rating Scale–based measures of motor fluctuations and dyskinesias. LD + ENT treatment was associated with a lower retirement rate (2 [17%] of 12 vs. 6 [50%] of 12; P = 0.12), lower absenteeism rate (21.5 vs. 43.5 days; P < 0.0001), improved self‐perception of disability progression over 2 years (change score 1.0 vs. 4.5; P < 0.0001), and lower scores for both motor fluctuations and dyskinesia assessments compared to LD monotherapy. In this pilot study, LD with ENT adjunctive therapy positively influenced employment rate over 2 years; this effect was associated with reduced motor complications and patient perceptions of stabilized disability. © 2006 Movement Disorder Society
Case–control study of anxiety symptoms in hemifacial spasm
Authors: Tan Eng‐King , Fook‐Chong Stephanie , Lum Sau‐Ying
Published: October 2006

In a case–control study, we evaluated symptoms in nine different psychological domains in hemifacial spasm (HFS; using the Symptom Checklist‐90R [SCL‐90R]) and found the anxiety score to be significantly greater in HFS compared to healthy controls in both the univariate (P = 0.004) and multivariate analysis (adjusted for sex, age, marital status, and educational level; P = 0.002). Similar findings were obtained when comparison was made with an independent group of outpatient controls. Compared to outpatient controls, the HFS patients had a higher mean Hamilton Anxiety Rating Score (HAM‐A; 10.0 ± 8.0 [range, 0 to 28] vs. 5.0 ± 5.0 [range, 0 to 25]; P = 0.004), and 19.5% had HAM‐A score of 18 or above compared to 3.8% in controls (P = 0.02). Among the HFS patients, the mean anxiety score in SCL‐90R was significantly higher in those defined with mild to severe anxiety under HAM‐A compared to those without anxiety (74.0 ± 6.0 vs. 48.0 ± 13.0) (P < 0.0005). There was good correlation of the anxiety score with the HAM‐A in HFS patients (r = 0.915; P < 0.0001). HFS patients with anxiety reported significant improvement of their symptoms (mean HAM‐A score 19.0 ± 5.0 vs. 11.0 ± 6.0; P = 0.001) following appropriate management. As stress and anxiety can aggravate HFS, diagnosis and early management of anxiety symptoms can improve quality of life in these patients. © 2006 Movement Disorder Society
Identifying systematic errors in quantitative dynamic‐susceptibility contrast perfusion imaging by high‐resolution multi‐echo parallel EPI
Authors: Jochimsen Thies H. , Newbould Rexford D. , Skare Stefan T. , Clayton David B. , Albers Gregory W. , Moseley Michael E. , Bammer Roland
Published: October 2006

Several obstacles usually confound a straightforward perfusion analysis using dynamic‐susceptibility contrast‐based magnetic resonance imaging (DSC‐MRI). In this work, it became possible to eliminate some of these sources of error by combining a multiple gradient‐echo technique with parallel imaging (PI): first, the large dynamic range of tracer concentrations could be covered satisfactorily with multiple echo times (TE) which would otherwise result in overestimation of image magnitude in the presence of noise. Second, any bias from T1 relaxation could be avoided by fitting to the signal magnitude of multiple TEs. Finally, with PI, a good tradeoff can be achieved between number of echoes, brain coverage, temporal resolution and spatial resolution. The latter reduces partial voluming, which could distort calculation of the arterial input function. Having ruled out these sources of error, a 4‐fold overestimation of cerebral blood volume and flow remained, which was most likely due to the completely different relaxation mechanisms that are effective in arterial voxels compared with tissue. Hence, the uniform tissue‐independent linear dependency of relaxation rate upon tracer concentration, which is usually assumed, must be questioned. Therefore, DSC‐MRI requires knowledge of the exact dependency of transverse relaxation rate upon tracer concentration in order to calculate truly quantitative perfusion maps. Copyright © 2006 John Wiley & Sons, Ltd.
Two‐level preconditioners for serendipity finite element matrices
Authors: Hakopian Yuri R. , Harutyunyan Arsen S.
Published: October 2006

In this paper an approach to construct algebraic multilevel preconditioners for serendipity finite element matrices is presented. Two‐level preconditioners constructed in the paper allow to obtain multilevel preconditioners in serendipity case using multilevel preconditioners for linear finite element matrices. Copyright © 2006 John Wiley & Sons, Ltd.