bluuebunny/crossref_metadata_2025 huggingface dataset:
Coping with post‐traumatic stress: young, middle‐aged and elderly comparisons
Authors: Chung Man Cheung , Werrett Julie , Easthope Yvette , Farmer Steven
Published: March 2004

Objectives

Debate persists about whether people of different ages react similarly to traumatic events, and whether elderly people are more vulnerable to such events, or better able to cope with them. The first aim of this paper was to shed light on this debate by comparing the post‐traumatic responses of young, middle‐aged and elderly community residents who had been exposed to technological disasters. The second aim was to differentiate between these three age groups in terms of coping strategies.

Methods

One hundred and forty‐eight community residents, who were exposed to two technological disasters, participated in the study. They were assessed using the Impact of Event Scale (IES), the General Health Questionnaire (GHQ‐28) and the Ways of Coping Checklists (WOC).

Results

The results showed that in terms of IES, GHQ and WOC scores, no significant differences were found across the three age groups. However, main effects were found according to type of disaster and intensity of exposure to disaster. One significant interaction effect was that residents exposed to the aircraft crash used significantly more confrontive coping than those exposed to the train collision, in all three age groups. Correlation coefficients results showed that for all three age groups, on the whole, the more they experienced intrusive thoughts and avoidance behaviour, the more they experienced general health problems.

Conclusions

Following exposure to technological disasters, young, middle‐aged and elderly community residents could display similar post‐traumatic responses and employ similar coping strategies, which contradicts the vulnerability hypothesis and the inoculation hypothesis. Copyright © 2004 John Wiley & Sons, Ltd.
Agitated behaviours among the institutionalized elderly with dementia: validation of the Korean version of the Cohen‐Mansfield Agitation Inventory
Authors: Suh Guk‐Hee
Published: March 2004

Objectives

To analyze the factor structure, the criterion validity, the internal consistency, inter–rater reliability and test–retest reliability of the Korean version of Cohen‐Mansfield Agitation Inventory, to provide data on the frequency and distribution of agitated behaviours, and to compare patterns of agitated behaviours among the institutionalized elderly with Alzheimer's disease (AD) or Vascular dementia (VaD).

Methods

The Korean version of the Cohen‐Mansfield Agitation Inventory (CMAI‐K) was administered to a total of 257 elderly with AD or VaD in a nursing home in Seoul, Korea. Three kinds of reliability and criterion validity were tested. Factor analysis using principal component analysis with the varimax rotation was performed. To identify different patterns of agitated behaviours, multiple logistic regression analysis was used.

Results

This study demonstrated satisfactory reliability and validity for the CMAI‐K as an instrument measuring agitation in Korean dementia sufferers in nursing homes. Eighty‐three percent of the subjects manifested one or more agitated behaviours at least once a week. Factor analysis yielded four subtypes of agitation: physically aggressive behaviours, physically nonaggressive behaviours, verbally agitated behaviours, and hiding/hoarding behaviours.

Conclusion

These results indicate that the CMAI‐K is a reliable and valid instrument to measure agitated behaviours in Korean elderly with AD or VaD. These results validate and expand previous research on the agitation in dementia, and guide in the development of interventions. Copyright © 2004 John Wiley & Sons, Ltd.
Profile of mental disorders among the elderly United Arab Emirates population: sociodemographic correlates
Authors: Ghubash Rafia , El‐Rufaie Omer , Zoubeidi Taoufik , Al‐Shboul Qasim M. , Sabri Sufyan M.
Published: March 2004

Objectives

To investigate the prevalence, nature and sociodemographic correlates of mental disorders among the elderly United Arab Emirates (UAE) population.

Study subjects and sample

UAE nationals aged 60 years or more, were recruited from within a random sample of households representing the UAE national population, irrespective of the age of individuals in each household.

Research Instruments

(i) Geriatric Mental State Interview (GMS‐A3): an Arabic version, using the AGECAT for analysis; (ii) A short questionnaire for relevant sociodemographic data.

Procedure

Purposely trained, Arabic speaking interviewers visited the targeted sample households to interview study subjects at their homes.

Results

The total number of screened subjects was 610: 166 (27.2%) in Al‐Ain; 286 (46.9%) in Dubai and 158 (25.9%) in Ras Al‐Khaimah. There were 347 (56.9%) male subjects and 263 (43.1%) female subjects. The mean age of the interviewed subjects was 68.6 (SD 8.3). The commonest diagnostic entities at the AGECAT syndrome case level were depression (20.2%), anxiety (5.6%), hypochondriasis (4.4%) and organic, mostly cognitive impairment with or without dementia (3.6%). Organic syndrome caseness, as an independent entity, showed significant correlation only to older age, while the rest of the mental disorders showed significant correlation with female gender, insufficient income and being single, separated, divorced or widowed.

Conclusion

The GMS‐AGECAT package proved to be a useful tool for psychiatric assessment among the elderly in this Arabian culture. The prevalence rates of mental disorders among the elderly UAE population were, more or less, within the same range reported by other comparable worldwide studies. Copyright © 2004 John Wiley & Sons, Ltd.
Emotional reactions of lay persons to someone with Alzheimer's disease
Authors: Werner Perla , Davidson Michael
Published: March 2004

Background

Information about the nature of public reactions to people with Alzheimer's disease (AD) can help reduce stigmatization associated with the disease.

Objective

The aim of this study was to examine emotional reactions to persons with AD, and its correlates.

Methods

A total of 150 Jewish Israeli adults (mean age=59.9) were interviewed face‐to‐face regarding their emotional reactions to people with AD using a vignette methodology.

Results

Only a third of the participants gave the correct label. The person described in the vignette elicited more positive than negative emotions. Gender and perceived threat were the most important factors associated with emotional reactions.

Conclusions

Findings suggest the need to expand the efforts to increase the recognition of AD by lay persons, and to address the negative emotions of several risk groups, such as male adults and those with greater concern about developing the disease. Copyright © 2004 John Wiley & Sons, Ltd.
Stated and actual altruistic willingness to pay for insecticide‐treated nets in Nigeria: validity of open‐ended and binary with follow‐up questions
Authors: Onwujekwe Obinna , Uzochukwu Benjamin
Published: March 2004

Objectives: To determine whether the binary with follow‐up (BWFU) or open‐ended (OPED) contingent valuation question format would yield better valid estimates of altruistic willingness to pay (WTP) and examine the feasibility of using intra‐community altruistic contributions to procure insecticide‐treated nets (ITNs) for the poor in Nigeria.

Methods: Structured questionnaires were used to elicit stated altruistic WTP from a random sub‐sample of respondents that had either the OPED or BWFU used to elicit WTP in Southeast Nigeria. One month after the survey the respondents were asked to redeem their WTP pledges. Construct validity was determined using econometric analyses, while phi correlation coefficient was used to determine criterion validity.

Findings: More than 57% of the respondents were hypothetically willing to pay for altruism in both BWFU and OPED groups. Altruistic WTP was positively related to respondents' WTP for own nets (p<0.01) and nets for other household members (p<0.05) in both groups. A total of 27.0% and 33.1% of the respondents with positive hypothetical WTP in the BWFU and OPED actually contributed. Phi correlation coefficient was 0.23 (95%CI 0.20–0.29) in BWFU and 0.49 (95%CI 0.44–0.54) in OPED. The money realised was used to buy some ITNs, which were presented to poor people selected by community leaders.

Conclusion: The OPED elicited better valid estimates of altruistic WTP than BWFU. The potential for more capable people to contribute for the poor in ITNs programmes actually exist and malaria control programmes should explore altruistic contributions as a means to increase net coverage. Copyright © 2004 John Wiley & Sons, Ltd.
Why cost‐effectiveness should trump (clinical) effectiveness: the ethical economics of the South West quadrant
Authors: Dowie Jack
Published: March 2004

In many health decision making situations there is a requirement that the effectiveness of interventions, usually their ‘clinical’ effectiveness, be established, as well as their cost‐effectiveness. Often indeed this is effectively a prior requirement for their cost‐effectiveness being investigated. If, however, one accepts the ethical argument for using a threshold incremental cost‐effectiveness ratio (ICER) for interventions that are more effective but more costly (i.e. fall in the NE quadrant of the cost‐effectiveness plane), one should apply the same decision rule in the SW quadrant, where the intervention is less effective but less costly. This implication is present in most standard treatments of cost‐effectiveness analysis, including recent stochastic versions, and had gone relatively unquestioned within the discipline until the recent suggestion that the ICER threshold might be ‘kinked’. A kinked threshold would, O'Brien et al. argue, better reflect the asymmetrical individual preferences found in empirical studies of consumer's willingness to pay and willingness to accept and justify different decision rules in the NE and SW quadrants. We reject the validity of such asymmetric preferences in the context of public health care decisions and consider and counter the two main ‘ethical’ objections that probably underlie the asymmetry in this case – the objection to ‘taking away’ and the objection to being required to undergo treatment that is less effective than no treatment at all. Copyright © 2004 John Wiley & Sons, Ltd.
Co‐payments for prescription drugs and the demand for doctor visits – Evidence from a natural experiment
Authors: Winkelmann Rainer
Published: March 2004

The German health care reform of 1997 provides a natural experiment for evaluating the price sensitivity of demand for physicians' services. As a part of the reform, co‐payments for prescription drugs were increased step up to 200%. However, certain groups of people were exempted from the increase, providing a natural control group against which the changed demand for physicians' services of the treated, those subject to increased co‐payments, can be assessed. The differences‐in‐differences estimates indicate that increased co‐payments reduced the number of doctor visits by about 10% on an average. Copyright © 2004 John Wiley & Sons, Ltd.
The wage effects of obesity: a longitudinal study
Authors: Baum Charles L. , Ford William F.
Published: March 2004

We use National Longitudinal Survey of Youth (NLSY) data to examine the effects of obesity on wages by gender. Sample means indicate that both men and women experience a persistent obesity wage penalty over the first two decades of their careers. We then control for a standard set of socioeconomic and familial variables but find that standard covariates do not explain why obese workers experience persistent wage penalties. This suggests that other variables – including job discrimination, health‐related factors and/or obese workers' behavior patterns – may be the channels through which obesity adversely affects wages. The study closes with a discussion of the public policy implications suggested by these findings. Copyright © 2004 John Wiley & Sons, Ltd.
Cost efficiency in primary care contracting: a stochastic frontier cost function approach
Authors: Puig‐Junoy Jaume , Ortún Vicente
Published: March 2004

The principal aim of this paper is to estimate a stochastic frontier cost function and an inefficiency effects model in the analysis of the primary health‐care services purchased by the public authority and supplied by 180 providers in 1996 in Catalonia. The evidence from our sample does not support the premise that contracting out has helped improve purchasing cost efficiency in primary care. Inefficient purchasing cost was observed in the component of this purchasing cost explicitly included in the contract between purchaser and provider. There were no observable incentives for the contracted‐out primary health‐care teams to minimise prescription costs, which were not explicitly included in the contracting system. Copyright © 2004 John Wiley & Sons, Ltd.
Deriving welfare measures from discrete choice experiments: a response to Ryan and Santos Silva
Authors: Lancsar Emily , Savage Elizabeth
Published: March 2004

In this response we start by highlighting the key area of agreement between the commentaries and our original paper: if there is uncertainty regarding which alternative will be chosen, in a DCE or in the real world, then the compensating variation as modified for discrete data by Small and Rosen is the appropriate method of deriving welfare measures from DCEs. Both commentators point out circumstances in which the method traditionally used in the health economics arena may be consistent with the compensating variation. We show that these circumstances require a number of potentially unrealistic and ad hoc assumptions, and argue that using the traditional method could produce erroneous welfare estimates if these assumptions fail to hold in practice. We show that the compensating variation method can accommodate each of the special cases raised by the commentators and therefore is the more general and appropriate approach to deriving welfare measures from DCEs. We also respond to issues raised regarding the estimation of DCEs in general and our application to asthma medication in particular. Copyright © 2004 John Wiley & Sons, Ltd.
Primary mucosal desmoplastic melanoma of the head and neck
Authors: Prasad Manju L. , Patel Snehal G. , Busam Klaus J
Published: March 2004

Background.

Desmoplastic variants of melanoma rarely affect the mucosa.

Method.

The clinicopathologic features and p53 status of seven primary mucosal desmoplastic melanomas of the oral and nasal cavity were studied.

Results.

The patients included six men and one woman (median age, 61 years; range, 23–74 years). Desmoplastic melanoma involved the lip in two, alveolus in three, buccal mucosa in one, and nasal vestibule in one patient. Four tumors infiltrated up to lamina propria, and three infiltrated bone and/or cartilage. All were amelanotic spindle cell tumors, five were neurotropic, and two were vasoinvasive. Aberrant p53 expression was seen in six tumors. All tumors recurred locally, and distant metastasis developed in three. Six patients died with disease (survival, 1–41 years; median, 8 years), and one patient was free of disease (survival 20 years).

Conclusions.

Primary mucosal desmoplastic melanomas are clinically characterized by local recurrence and may lead to distant metastasis and death even after several years. Alterations in p53 expression are frequently associated with desmoplastic melanoma. © 2003 Wiley Periodicals, Inc. Head Neck 26: 373–377, 2004
Swallowing dysfunction after chemoradiation for advanced squamous cell carcinoma of the head and neck
Authors: Kotz Tamar , Costello Rosemary , Li Yi , Posner Marshall Roy
Published: March 2004

Background.

Swallowing dysfunction is a common side effect of chemoradiation.

Methods.

Twelve patients with stage III or IV squamous cell carcinoma of the head and neck were enrolled. Videofluorographic swallowing studies were performed before initiation of chemoradiation to provide baseline swallowing function data. Postchemoradiation videofluorographic swallowing studies were performed from 1 to 14 weeks after the completion of treatment (mean, 8 weeks).

Results.

Changes in swallowing physiology after treatment included decreased base of tongue to posterior pharyngeal wall contact (p = .0010) and reduced pharyngeal contraction (p = .0313), resulting in impaired bolus transport through the pharynx. In addition, decreased laryngeal elevation (p = .0039), decreased laryngeal vestibule closure (p = .0078), and laryngeal penetration (p = .0078) were present. Bolus volume did not have a significant effect on swallowing ability. Aspiration was observed in four patients.

Conclusions.

Organ preservation treatment impairs movement of structures essential for normal swallowing. Prophylactic swallowing exercises may benefit these patients. © 2004 Wiley Periodicals, Inc. Head Neck 26: 365–372, 2004
Kupffer cells alter organic anion transport through multidrug resistance protein 2 in the post-cold ischemic rat liver
Authors: Kudo Atsushi , Kashiwagi Satoshi , Kajimura Mayumi , Yoshimura Yasunori , Uchida Koji , Arii Shigeki , Suematsu Makoto
Published: March 2004

Although Kupffer cells (KCs) may play a crucial role in post-cold ischemic hepatocellular injury, their role in nonnecrotic graft dysfunction remains unknown. This study examined reveal the role of KC in post-cold ischemic liver grafts. Rat livers treated with or without liposome-encapsulated dichloromethylene diphosphonate, a KC-depleting reagent, were stored in University of Wisconsin (UW) solution at 4°C for 8 to 24 hours and reperfused while monitoring biliary output and constituents. The ability of hepatocytes to excrete bile was assessed through laser-confocal microfluorography in situ. Cold ischemia-reperfused grafts decreased their bile output significantly at 8 hours without any notable cell injury. This event coincided with impaired excretion of glutathione and bilirubin-IXα (BR-IXα), suggesting delayed transport of these organic anions. We examined whether intracellular relocalization of multidrug resistance protein-2 (Mrp2) occurred. Kinetic analyses for biliary excretion of carboxyfluorescein, a fluoroprobe excreted through this transporter, revealed significant delay of dye excretion from hepatocytes into bile canaliculi. The KC-depleting treatment significantly attenuated this decline in biliary anion transport mediated through Mrp2 in the 8-hour cold ischemic grafts via redistribution of Mrp2 from the cytoplasm to the canalicular membrane. Furthermore, thromboxane A2 (TXA2) synthase in KC appeared involved as blocking this enzyme improved 5-carboxyfluorescein excretion while cytoplasmic internalization of Mrp2 disappeared in the KC-depleting grafts. In conclusion, KC activation is an important determinant of nonnecrotic hepatocellular dysfunction, jeopardizing homeostasis of the detoxification capacity and organic anion metabolism of the post-cold ischemic grafts. (Hepatology 2004;39;1099-1109.)
Identification of discriminators of hepatoma by gene expression profiling using a minimal dataset approach
Authors: Neo Soek Ying , Leow Chon Kar , Vega Vinsensius B. , Long Philip M. , Islam Amirul F.M. , Lai Paul B.S. , Liu Edison T. , Ren Ee Chee
Published: March 2004

The severity of hepatocellular carcinoma (HCC) and the lack of good diagnostic markers and treatment strategies have rendered the disease a major challenge. Previous microarray analyses of HCC were restricted to the selected tissue sample sets without validation on an independent series of tissue samples. We describe an approach to the identification of a composite discriminator cassette by intersecting different microarray datasets. We studied the global transcriptional profiles of matched HCC tumor and nontumor liver samples from 37 patients using cDNA (cDNA) microarrays. Application of nonparametric Wilcoxon statistical analyses (P < 1 × 10−6) and the criteria of 1.5-fold differential gene expression change resulted in the identification of 218 genes, including BMI-1, ERBB3, and those involved in the ubiquitin-proteasome pathway. Elevated ERBB2 and epidermal growth factor receptor (EGFR) expression levels were detected in ERBB3-expressing tumors, suggesting the presence of ERBB3 cognate partners. Comparison of our dataset with an earlier study of approximately 150 tissue sets identified multiple overlapping discriminator markers, suggesting good concordance of data despite differences in patient populations and technology platforms. These overlapping discriminator markers could distinguish HCC tumor from nontumor liver samples with reasonable precision and the features were unlikely to appear by chance, as measured by Monte Carlo simulations. More significantly, validation of the discriminator cassettes on an independent set of 58 liver biopsy specimens yielded greater than 93% prediction accuracy. In conclusion, these data indicate the robustness of expression profiling in marker discovery using limited patient tissue specimens as well as identify novel genes that are highly likely to be excellent markers for HCC diagnosis and treatment. Supplementary material for this article can be found on the Hepatology website (http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (Hepatology 2004;39:944-953.)
Integration of woodchuck hepatitis and N-myc rearrangement determine size and histologic grade of hepatic tumors
Authors: Jacob James R. , Sterczer Agnes , Toshkov Ilia A. , Yeager Amy E. , Korba Brent E. , Cote Paul J. , Buendia Marie-Annick , Gerin John L. , Tennant Bud C.
Published: March 2004

Integrations of woodchuck hepatitis virus (WHV) DNA and rearrangements of the N-myc 2 gene have been detected frequently in hepatocellular carcinoma (HCC) of Eastern woodchucks (Marmota monax) chronically infected with WHV. Fifty-five hepatocellular neoplasms and matched nontumor hepatic tissue specimens obtained postmortem from 13 chronic WHV carriers were analyzed and the frequency of WHV DNA integrations and of N-myc rearrangements compared in tumors of different size and histologic grade. Four small tumor nodules were classified histologically as adenomas and integrated sequences of WHV DNA were detected in two of the four tumor nodules. In one of the two nodules, there was evidence of N-myc rearrangement. Fifty-one neoplasms were classified as HCC. Seven were grade 1 HCCs. WHV DNA integrations were demonstrated in 43% but none had N-myc rearrangements. Twenty grade 2 HCCs had WHV DNA integrations in 80% and in 38% N-myc rearrangements were present. Twenty-four grade 3 HCCs had integrations of WHV DNA in 79% and N-myc rearrangements in 74%. In two other grade 3 HCCs, rearrangements of N-myc were detected in the absence of WHV DNA integrations. The 12 largest tumors in the series all were grade 2 or 3 HCCs, and in 83%, both WHV DNA integrations and N-myc rearrangements were demonstrated. In conclusion, molecular changes observed in this study suggest a progression of genetic alterations providing either a significant proliferative stimulation and/or a growth advantage in hepatocarcinogenesis of woodchucks with chronic WHV infection. (Hepatology 2004;39:1008-1016.)
Nonalcoholic fatty liver disease among patients with hypothalamic and pituitary dysfunction
Authors: Adams Leon A. , Feldstein Ariel , Lindor Keith D. , Angulo Paul
Published: March 2004

Patients with hypopituitarism develop a phenotype similar to metabolic syndrome with central obesity and diabetes. Similarly, patients with hypothalamic damage may develop central obesity, insulin resistance, and hyperphagia. We sought to examine the clinical associations between hypopituitarism, hypothalamic dysfunction, and nonalcoholic fatty liver disease (NAFLD). A case series of patients seen at our institution with diagnoses of hypopituitarism, hypothalamic obesity, or craniopharyngioma and NAFLD was undertaken. Clinical, laboratory, and liver biopsy features were reviewed. Twenty-one patients were identified. NAFLD was diagnosed 6.4 ± 7.5 years (median 3 years) after the diagnosis of hypothalamic/pituitary dysfunction. Mean gain in body mass index (BMI) between diagnoses of hypothalamic/pituitary disease and NAFLD was 11.3 ± 8.9 kg/m2 at an average yearly rate of 2.2 ± 2.2 kg/m2. The majority of patients developed elevated glucose levels and dyslipidemia by time of diagnosis of NAFLD. Of the 10 patients biopsied, six were cirrhotic, two had nonalcoholic steatohepatitis (NASH) with fibrosis, and two had simple steatosis. Long-term follow-up of 66 ± 33 months (range 12-120) was available for 18 patients. Two required liver transplantation. Six patients died, two from liver related causes. In conclusion, patients with hypothalamic and/or pituitary disease are at risk of excessive weight gain, impaired glucose tolerance, and dyslipidemia with subsequent development of NAFLD. This group has a high prevalence of cirrhosis placing them at risk for liver-related death. The novel evidence that hypothalamic/pituitary dysfunction may be accompanied by progressive NAFLD has important implications for the work-up and management of patients with hypothalamic/pituitary disease. (Hepatology 2004;39:909-914.)
Celecoxib-induced apoptosis in rat cholangiocarcinoma cells mediated by Akt inactivation and Bax translocation
Authors: Zhang Zichen , Lai Guan-Hua , Sirica Alphonse E.
Published: March 2004

Recently, we demonstrated that the cyclooxygenase-2 (COX-2) inhibitor celecoxib acts to significantly suppress the growth of rat C611B cholangiocarcinoma (ChC) cells in vitro. To establish a molecular mechanism for this growth suppression, we investigated the effects of celecoxib on apoptotic signaling pathways in cultured rat C611B ChC cells. Celecoxib and another COX-2 inhibitor, rofecoxib, at 5 μM were almost equally effective in inhibiting prostaglandin E2 (PGE2) production by these cells, but at this low concentration, neither inhibitor suppressed growth or induced apoptosis. Celecoxib at 50 μM induced prominent apoptosis in these cells, whereas rofecoxib at 50 μM was without effect in either suppressing growth or inducing apoptosis. Celecoxib (50 μM) did not alter Bcl-2, Bcl-xL, or COX-2 protein levels, nor did it inhibit p42/44 mitogen-activated protein kinase (MAPK) phosphorylation; however, it significantly suppressed serine/threonine kinase Akt/PKB (Akt) phosphorylation and kinase activity in cultured C611B cells. This effect, in turn, directly correlated with Bax translocation to mitochondria, cytochrome c release into cytosol, activation of caspase-9 and caspase-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Addition of 25 μM PGE2 to C611B cell cultures blocked the apoptotic actions of celecoxib. Rofecoxib (50 μM) was without effect in suppressing Akt phosphorylation and caspase-3 activation. In vivo, celecoxib partially suppressed tumorigenic growth of C611B ChC cells. In conclusion, our results indicate that celecoxib preferentially acts in vitro to induce apoptosis in ChC cells through a mechanism involving Akt inactivation, Bax translocation, and cytochrome c release. Our in vivo results further suggest celecoxib might have potential therapeutic or chemopreventive value against ChC. (Hepatology 2004;39:1028-1037.)
Expression of Notch-1 and its ligand Jagged-1 in rat liver during liver regeneration
Authors: Köhler Christoph , Bell Aaron W. , Bowen William C. , Monga Satdarshan P. , Fleig Wolfgang , Michalopoulos George K.
Published: March 2004

The Notch/Jagged signaling pathway is important for cellular differentiation and proliferation. Its dysfunction is associated with human pathologies in several tissues including liver. Point mutations in Jagged-1 gene are the cause for Alagille syndrome, associated with paucity of intrahepatic bile ducts. To determine the putative role of the trans-membrane receptor Notch and its ligand Jagged-1 in liver regeneration, we investigated the expression of Notch and Jagged-1 in rat liver following 2/3 partial hepatectomy. Immunohistochemical staining of normal rat liver showed that Notch was expressed in hepatocytes, bile duct cells and endothelial cells, whereas Jagged-1 was expressed in bile duct cells and hepatocytes. Both Notch-1 and Jagged-1 proteins were upregulated in hepatocytes after partial hepatectomy up to day 4. After partial hepatectomy, nuclear translocation of the intracellular cytoplasmic domain of Notch (NICD) increased and peaked within 15 minutes, indicating the activation of Notch. Expression of the Notch-dependent target gene (HES-1) expression increased within 30-60 minutes. Addition of recombinant Jagged-1 protein to primary cultures of hepatocytes stimulated hepatocyte DNA synthesis. Furthermore, injection of silencing RNA for Notch and Jagged-1 to livers 2 days before partial hepatectomy significantly suppressed proliferation of hepatocytes at days 2 to 4 of the regenerative response. In conclusion, Notch/Jagged signaling pathway is activated during liver regeneration and is potentially contributing to signals affecting cell growth and differentiation. Supplementary material for this article can be found on the Hepatology website (
http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html
). (Hepatology 2004;39:1056-1065.)
Common pathway in the medial temporal lobe for storage and recovery of words as revealed by event‐related functional MRI
Authors: Daselaar Sander M. , Veltman Dick J. , Witter Menno P.
Published: March 2004

Lesion studies have provided compelling evidence that episodic memory is dependent on the integrity of the medial temporal lobe (MTL). This role of the MTL in episodic memory has been supported by several neuroimaging studies during both episodic encoding and retrieval. After two meta‐analyses of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies, we investigated a possible dissociation within the MTL memory system in relation to encoding and retrieval processes. Based on previous reports that specifically related the function of the MTL in episodic memory to successful encoding and actual recovery of information, we applied event‐related fMRI to compare successful encoding of words (ES) directly with successful recognition of those same words (RS). Our results did not indicate a clear dissociation between encoding and retrieval activations in the MTL. Instead, a region in the left MTL, covering the parahippocampal cortex and hippocampal formation, which was activated during ES almost completely overlapped with the area that was activated during RS. An additional region in the left anterior MTL, including the entorhinal cortex, was found to be activated exclusively during ES. Research has indicated that a large percentage of cells in this region are particularly sensitive to the relative novelty of stimuli. Our results, therefore, suggest that the parahippocampal/hippocampal region is involved in the formation and subsequent reactivation of memory traces, whereas the activity observed in the entorhinal cortex may reflect elementary memory processes related to novelty detection. © 2003 Wiley‐Liss, Inc.
Impaired place navigation in place and matching‐to‐place swimming pool tasks follows both retrosplenial cortex lesions and cingulum bundle lesions in rats
Authors: Harker K. Troy , Whishaw Ian Q.
Published: March 2004

The retrosplenial (RS) cortex (area 29) and the adjacent cingulum bundle (CG) are components of neural circuits that include the hippocampus. Given the evidence suggesting that the hippocampus plays a central role in spatial navigation, several lines of investigation have examined the possible contributions of these structures to spatial navigation. The combined and/or separate contributions of these structures have been difficult to establish because their close proximity usually results in combined injury after lesions and because there have been conflicting results related to lesion type and the strain of rat subjects. The purpose of the present study was to compare the effects of selective CG damage with selective RS damage in Long‐Evans rats, a domestic rat strain that displays superior spatial skills, and by using spatial behavior assessment procedures that are sensitive to CG damage. Rats with cytotoxic N‐methyl‐D‐aspartate (NMDA) RS lesions or surgical CG transection were tested on two spatial tasks in the Morris water task; a place learning task, sensitive to nonspatial and spatial behavior, and a matching‐to‐place task, sensitive to spatial behavior. Both the RS and CG groups were impaired on most measures relative to the control group on both the place task and the matching‐to‐place task. The results are discussed in relation to the anatomical organization of CG and RG projections to the hippocampus and with respect to their possible separate/conjoint contributions to spatial behavior. © 2004 Wiley‐Liss, Inc.
Immunolocalization of metabotropic glutamate receptor 1α (mGluR1α) in distinct classes of interneuron in the CA1 region of the rat hippocampus
Authors: Ferraguti Francesco , Cobden Philip , Pollard Marie , Cope David , Shigemoto Ryuichi , Watanabe Masahiko , Somogyi Peter
Published: March 2004

In the hippocampal CA1 region, metabotropic glutamate subtype 1 (mGluR1) receptors have been implicated in a variety of physiological responses to glutamate, which include modulation of synaptic transmission and plasticity, as well as neuronal excitability and synchronization. The mGluR1α isoform is characteristically expressed only by nonprincipal cells, and it is particularly enriched in somatostatin (SS)‐containing interneurons in stratum oriens‐alveus. Anatomical and physiological data have indicated the presence of mGluR1α in several distinct classes of interneurons with their somata located also in strata pyramidale, radiatum, and lacunosum moleculare. Each different interneuron subtype, as defined by functionally relevant criteria, including input/output characteristics and expression of selective molecular markers, subserves distinct functions in local hippocampal circuits. We have investigated which of the different CA1 interneuron classes express mGluR1α by immunofluorescent labeling, combining antibodies to mGluR1α, calcium‐binding proteins, and neuropeptides, and by intracellular labeling in vitro. Several types of interneuron that are immunopositive for mGluR1α each targeted different domains of pyramidal cells and included (1) O‐LM interneurons, found to coexpress both SS and parvalbumin (PV); (2) interneurons with target selectivity for other interneurons, expressing vasoactive intestinal polypeptide (VIP) and/or the calcium‐binding protein calretinin; (3) pro‐cholecystokinin‐immunopositive interneurons probably non‐basket and dendrite‐targeting; and (4) an as‐yet unidentified SS‐immunoreactive but PV‐immunonegative interneuron class, possibly corresponding to oriens‐bistratified cells. Estimation of the relative proportion of mGluR1α‐positive interneurons showed 43%, 46%, and 30% co‐labeling with SS, VIP, or PV, respectively. The identification of the specific subclasses of CA1 interneurons expressing mGluR1α provides the network basis for assessing the contribution of this receptor to the excitability of the hippocampus. © 2004 Wiley‐Liss, Inc.
Spatial reference memory in GluR‐A‐deficient mice using a novel hippocampal‐dependent paddling pool escape task
Authors: Schmitt W.B. , Deacon R.M.J. , Reisel D. , Sprengel R. , Seeburg P.H. , Rawlins J.N.P. , Bannerman D.M.
Published: March 2004

Genetically modified mice lacking the L‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor subunit, GluR‐A (GluR1), and deficient in hippocampal CA3‐CA1 long‐term potentiation (LTP), were assessed on a novel, hippocampal‐dependent spatial reference memory, paddling pool escape task. The mice were required to use the extramaze cues around the laboratory to find a hidden escape tube that was in a constant location at one of 12 possible positions around the perimeter of the paddling pool, in order to escape from shallow water. The knockout mice performed well on this task. They displayed a small initial impairment (in terms of both escape latencies and choice errors), but they were soon as efficient as the wild‐type mice in escaping from the water. This was further demonstrated by performance during a 20‐s probe trial in which the exit tube was blocked. Both groups of mice spent most of the time searching in the quadrant of the pool in which the exit tube had previously been located. In a subsequent experiment, entirely normal spatial acquisition was observed in the knockout mice when the paddling pool was moved to a novel spatial environment. The GluR‐A−/− mice were also unimpaired in a further reversal phase in which the correct exit location was moved by 180° around the perimeter wall. These results are consistent with previous watermaze studies, providing further demonstration of intact hippocampus‐dependent spatial reference memory in GluR‐A knockout mice. They contrast strikingly with the profound deficits in hippocampus‐dependent, short‐term, flexible spatial working memory observed in these knockout mice. This study also demonstrates a novel behavioral task for assessing spatial memory in genetically modified mice. This task shares the behavioral profile of the well‐established watermaze paradigm, but may have advantages for the study of genetically modified mice. © 2004 Wiley‐Liss, Inc.
Properties of horizontal axo‐axonic cells in stratum oriens of the hippocampal CA1 area of rats in vitro
Authors: Ganter Paul , Szücs Peter , Paulsen Ole , Somogyi Peter
Published: March 2004

Local‐circuit γ‐aminobutyric acid (GABA)ergic interneurons constitute a diverse population of cells, which remain poorly defined into functionally distinct subclasses. Traditionally, dendritic and axonal arbors have been used to describe cell classes. In the present report, we characterize a set of hippocampal interneurons, horizontal axo‐axonic cells, located in stratum oriens. They displayed the pattern of axonal arborization characteristic of axo‐axonic cells with radially aligned rows of boutons making synapses exclusively on axon initial segments of pyramidal cells, as shown by electron microscopy. However, in contrast to previously described axo‐axonic cells, which have radial dendrites spanning all layers, the dendrites of the horizontal axo‐axonic cells were restricted to stratum oriens and ran parallel with the layers for several hundred micrometers. Single action potentials elicited by depolarizing current steps in these cells were often followed by a fast‐ and medium‐duration afterhyperpolarization, distinguishing them from fast‐spiking interneurons. In two out of four cells, trains of action potentials showed prominent early spike frequency adaptation and a characteristic “accommodative hump.” Excitatory postsynaptic potentials (EPSPs) could be evoked by stimuli delivered to stratum oriens. Paired recordings unequivocally confirmed direct synaptic inputs from CA1 pyramidal cells. The kinetics of the EPSPs were fast (rise time 1.7 ± 0.6 ms, mean ±SD, n = 3; decay time constant 19.3 ± 2.4 ms). They showed paired‐pulse depression with inter‐stimulus intervals of 10–50 ms. One pair showed a reciprocal connection establishing a direct feedback loop. The axo‐axonic cell‐evoked inhibitory postsynaptic potentials (IPSPs) were reliable (failure rate ∼10%). Our data show that the laminar distribution of the dendrites of axo‐axonic cells can vary, suggesting distinct synaptic inputs. However, this remains to be shown directly, and we cannot exclude the possibility that all axo‐axonic cells may gather similar synaptic input, leaving them as one distinct class of interneuron. © 2004 Wiley‐Liss, Inc.
Expression of long‐term potentiation in aged rats involves perforated synapses but dendritic spine branching results from high‐frequency stimulation alone
Authors: Dhanrajan Tiruchinapalli M. , Lynch Marina A. , Kelly Aine , Popov Victor I. , Rusakov Dmitri A. , Stewart Michael G.
Published: March 2004

Evidence for morphological substrates of long‐term changes in synaptic efficacy is controversial, partly because it is difficult to employ an unambiguous control. We have used a high‐frequency stimulation protocol in vivo to induce long‐term potentiation (LTP) in the hippocampal dentate gyrus of aged (22‐month‐old) rats and have found a clear distinction between animals that sustain LTP and those that fail to sustain it. The “failure group” was used as a specific/“like‐with‐like” control for morphological changes associated with the expression of LTP per se. Quantitative optical and electron microscopy was used to analyze large populations of dendritic spines and excitatory perforant path synapses; LTP was found to be associated with an increase in numbers of segmented (perforated) postsynaptic densities in spine synapses. In contrast, an increase in the number of branched spines appears to result from high‐frequency stimulation alone. These data shed light on the current controversy about the expression mechanism of LTP. © 2004 Wiley‐Liss, Inc.
Endogenous 5‐HT inhibits firing activity of hippocampal CA1 pyramidal neurons during conditioned fear stress‐induced freezing behavior through stimulating 5‐HT1A receptors
Authors: Tada Koji , Kasamo Kimihiro , Suzuki Tadashi , Matsuzaki Yamato , Kojima Takuya
Published: March 2004

This study examines the activity of hippocampal CA1 pyramidal neurons during conditioned fear stress (CFS)‐induced freezing behavior in unanesthetized, unrestrained rats. The firing frequency of hippocampal CA1 pyramidal neurons was significantly decreased when conditioned rats exhibited freezing behavior. Firing frequency returned to the baseline after freezing behavior disappeared. The selective 5‐hydroxytryptamine (5‐HT)1A antagonists, N‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]ethyl]‐N‐(2‐pyridinyl)cyclohexanecarboxamide (WAY‐100635), and N‐tert‐butyl‐3‐[4‐(2‐methoxyphenyl)piperazine‐1‐yl]‐2‐phenylpropamide (WAY‐100135) and 5‐HT depletion with parachlorophenylalanine (PCPA) completely abolished the decrease in firing frequency during CFS‐induced freezing behavior. These results suggested that endogenous 5‐HT inhibited the firing activity of hippocampal CA1 pyramidal neurons during CFS‐induced freezing behavior mainly through stimulating 5‐HT1A receptors. © 2004 Wiley‐Liss, Inc.
Hippocampal prosaposin changes during stress: A glucocorticoid‐independent event
Authors: Scaccianoce Sergio , Mattei Vincenzo , Del Bianco Paola , Gizzi Chiara , Sorice Maurizio , Hiraiwa Masao , Misasi Roberta
Published: March 2004

Several studies indicate that stress can produce remarkable effects on neurotrophic factors. In this regard, hippocampus is the most interesting structure of the brain because of its broad involvement in behavioral and neuroendocrine phenomena. In the present study, we investigated the effect of stress on hippocampal prosaposin, which is known to act as a neurotrophic and neuroprotective factor. Rats subjected to restraint stress (120 min) had a significant and transient reduction of hippocampal, but not hypothalamic, prosaposin full‐length protein. Indeed, when this stressful stimulus was applied daily for 3 days, no differences were detected in comparison with naive rats. To investigate the role of glucocorticoids in the stress‐induced decrease in hippocampal prosaposin, adrenalectomized and corticosterone‐treated rats were studied. The results indicate that adrenalectomized rats behave as intact animals. This finding indicates that the absence of endogenous corticosterone does not prevent a decrease in hippocampal prosaposin. When an increase of corticosterone was achieved through exogenous administration, hippocampal prosaposin concentrations were unchanged in comparison with vehicle‐injected (sesame oil) rats. These results led to the conclusion that stress, not via an increase of glucocorticoid hormone, transiently reduces hippocampal prosaposin levels. This phenomenon is followed by rapid recovery of the neurotrophin level, even when the stress stimulus persists. © 2004 Wiley‐Liss, Inc.
Muscarinic signaling is required for spike‐pairing induction of long‐term potentiation at rat Schaffer collateral‐CA1 synapses
Authors: Adams Scott V. , Winterer Jochen , Müller Wolfgang
Published: March 2004

Cholinergic input from the basal forebrain and septum to the hippocampus is well known to be critical in learning and memory. Muscarinic induction of theta‐frequency oscillations may synchronize pre‐ and postsynaptic firing and thereby enhance plasticity in the hippocampus. Previous studies have demonstrated that muscarinic activation facilitates long‐term potentiation (LTP) induced with tetanus in vitro. In the present study, we tested the role of muscarinic receptor activity in the induction of LTP beyond effects on spike timing by using a spike‐pairing (SP) method at Schaffer collateral‐CA1 synapses in rat hippocampal slices. Pairings of pre‐ and postsynaptic action potentials (APs) have been shown to induce LTP when the presynaptic AP precedes the postsynaptic AP by 5–15 ms, but contribution of muscarinic co‐activation has not been ruled out. We demonstrate that the mAChR antagonist atropine abolishes LTP induction by SP. Surprisingly, prolonged exposure to the mAChR agonist carbachol inhibits LTP induction by SP, perhaps because of receptor desensitization. These results demonstrate an essential role of cholinergic signaling in this form of hippocampal plasticity. © 2004 Wiley‐Liss, Inc.
Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress
Authors: Kole Maarten H.P. , Czéh Boldizsár , Fuchs Eberhard
Published: March 2004

The experience of chronic stress induces a reversible regression of hippocampal CA3 apical neuron dendrites. Although such postsynaptic membrane reduction will obviously diminish the possibility of synaptic input, the consequences for the functional membrane properties of these cells are not well understood. We tested the hypothesis that chronic stress affects the input‐output characteristics and excitability of CA3 pyramidal cells. Somatic whole‐cell current‐clamp recording with parallel intracellular biocytin labeling was performed on CA3 neurons from in vitro hippocampal slices from male tree shrews, which were collected after 28 days of psychosocial stress exposure and compared to recordings obtained from control animals. Post hoc morphometric analysis of biocytin‐labeled CA3 cells revealed branch regression, by fewer dendritic crossings and length, limited to a distance of ∼280–340 μm from the soma only. The results from whole‐cell recording indicate that chronic stress surprisingly reduced the apparent membrane time constant and input resistance 20–25%, accompanied by increased amplitude of the hyperpolarization‐induced voltage “sag.” All active membrane properties, including depolarization‐induced action potential kinetics, complex spiking patterns, and afterhyperpolarization voltages, were indistinguishable from control recordings. Although linear association analysis confirmed that differences in geometry, such as apical length or branch number, were correlated to functional variability in properties of the AP current and voltage threshold, these changes were too marginal to be reflected in the group differences. However, the individual adrenal hormone status was associated significantly with the selective changes in subthreshold excitability. Taken together, the data provide evidence that despite long‐term stress induces morphological changes, upregulates cortisol release and shifts the intrinsic membrane properties, the efficacy of somatic excitability of CA3 pyramidal neurons is largely preserved. © 2004 Wiley‐Liss, Inc.