bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modafinil affects mood, but not cognitive function, in healthy young volunteers
Authors: Randall Delia C. , Shneerson John M. , Plaha Komal K. , File Sandra E. 
Published: March 2003

AbstractModafinil is a selective wakefulness‐promoting agent with beneficial effects in narcolepsy and conditions of sleep deprivation. In a double‐blind study we examined its effects in 30 healthy, non sleep‐deprived students (19 men and 11 women, aged 19–23 years), who were randomly allocated to placebo, 100 or 200 mg modafinil and 3 h later completed 100 mm visual analogue scales relating to mood and bodily symptoms, before and after an extensive battery of cognitive tests (pen and paper and CANTAB). There were no significant differences between the three treatment groups on any of the cognitive tests used in this study. There was a significant post‐treatment change in the factor measuring ‘somatic anxiety’ and in individual ratings of ‘shaking’, ‘palpitations’, ‘dizziness’, ‘restlessness’, ‘muscular tension’, ‘physical tiredness’ and ‘irritability’, which was mainly due to significantly higher ratings of somatic anxiety in the 100 mg group compared with the other two groups. Further changes in mood were revealed after the stress of cognitive testing, with the 100 mg group showing greater increases in the ‘psychological anxiety’ and the ‘aggressive mood’ factors (as measured from the Bond and Lader scales). Copyright © 2002 John Wiley & Sons, Ltd.
Differences in the behavioral and psychological symptoms between Alzheimer's disease and vascular dementia: are the different pharmacologic treatment strategies justifiable?
Authors: Kim Jae‐Min , Lyons Declan , Shin Il‐Seon , Yoon Jin‐Sang 
Published: March 2003

AbstractBackgroundThis study aimed (1) to compare the behavioral and psychological symptoms of dementia (BPSD) between patients with Alzheimer's disease (AD) and vascular dementia (VaD); (2) to investigate the differences in the correlates of BPSD between them; and (3) to suggest potential different pharmacological strategies in treating BPSD of either etiology.MethodsIn a study group of 135 patients with dementia (99 AD, 36 VaD), information on age, gender, education, age at onset and duration of dementia was collected. The severity of dementia was measured by the following assessment scales: Korean version of Mini‐Mental State Examination (MMSE‐K) for cognitive function; Blessed Dementia Scale (BDS) for functional activities of daily living (ADL); Barthel Index (BI) for physical ADL; and Brief Psychiatric Rating Scale (BPRS), Hamilton Depression Scale (HAM‐D) and Hamilton Anxiety Scale (HAM‐A) for BPSD. The independent variables between the patients with AD and VaD were compared, and then the correlations of BPSD with other variables were estimated.ResultsHAM‐D and HAM‐A scores were higher in patients with VaD than in those with AD, while other variables demonstrated no statistical differences. BPRS score correlated with scores on MMSE‐K, BDS and BI in AD, but only with BDS in VaD. The HAM‐D score correlated with scores on BDS and BI in AD, but only with BDS in VaD. The HAM‐A score was correlated with score on BDS in AD not in VaD.ConclusionsBPSD were more severe in the patients with VaD. However, BPSD correlated more prominently with cognitive or ADL impairments in patients with AD. Different treatment approaches to BPSD may be required according to the clinical differentiation of dementia type. Copyright © 2002 John Wiley & Sons, Ltd.
Mismatch negativity is not correlated with neuroendocrine indicators of catecholaminergic activity in healthy subjects
Authors: Hansenne M. , Pinto E. , Scantamburlo G. , Couvreur A. , Reggers J. , Fuchs S. , Pitchot W. , Ansseau M. 
Published: March 2003

AbstractThe identification of the brain structures and neurotransmitters responsible for the generation and/or modulation of the mismatch negativity (MMN) may contribute to a clearer understanding of its functional significance, and may have clinical implications. In this context, some findings suggest that the scalp‐recorded MMN reflects activity from multiple neuronal ensembles within or in the immediate vicinity of the primary auditory cortex and with possible contribution from the frontal cortex. However, few data are available concerning the influence of neurotransmitter systems on the MMN. In this study, the relationship between both noradrenergic and dopaminergic systems and the MMN were investigated in 34 healthy volunteers. Noradrenergic and dopaminergic activities were assessed with the apomorphine and clonidine challenge tests. The results showed no significant relationship between either growth hormone (GH) responses to apomorphine or clonidine and the MMN amplitude or latency. Therefore, this study does not demonstrate the implication of dopaminergic and noradrenergic activities as assessed by GH response to apomorphine and clonidine for the generation and/or the modulation of the MMN. However, given the complexity of the central neurotransmitter systems, these results cannot be considered as definitive evidence against a relationship between dopaminergic and noradrenergic activity and the MMN. Copyright © 2002 John Wiley & Sons, Ltd.
Drug therapy of frontotemporal dementia
Authors: Allain Hervé , Bentué‐Ferrer Danièle , Tribut Olivier , Mérienne Marc , Belliard Serge 
Published: March 2003

AbstractFrontal lobe dementia, or more generally frontotemporal dementia (FTD), includes several clinical entities and, although highly prevalent, lacks any codified therapeutic strategy. The present review is an attempt to depict the main neurochemical correlates of FTD and, as a consequence, to propose the most sound targets for symptomatic drugs. Large scale double‐blind controlled clinical trials should be carried out to test any hypothesis: serotonergic agents, glutamate neurotransmission enhancers, monoamine oxidase inhibitors. The recent discovery of tau gene mutations in FTD with Parkinsonism linked to chromosome 17 has reinforced the direct role attributed to abnormal tau proteins (hyperphosphorylation) and thus raised the possibility to target specifically these processes by drugs (aetiopathogenic compounds). Copyright © 2003 John Wiley & Sons, Ltd.
Zotepine in Huntington's disease
Authors: Bonelli Raphael M. , Niederwieser Gerald , Lahousen Theresa , Hofmann Peter 
Published: March 2003

AbstractThe authors report a patient with Huntington's disease (HD) presenting with severe chorea. The motor scale of the unified HD rating scale (UHDRS‐I) revealed 81 points. Motor function clearly improved with zotepine, until she reached an UHDRS‐I of 34 points on day 7 of treatment. The patient was stable for at least 12 weeks. The improvement includes all seven categories of the UHDRS‐I, especially chorea, gait and oral function. This is the first description of zotepine in HD. Our findings suggest that zotepine is useful in the treatment of HD chorea. Controlled trials of its use in HD would be welcome. Copyright © 2003 John Wiley & Sons, Ltd.
Assessing subjective sleep reports in the first‐degree relatives of antidepressant‐treated depressed outpatients
Authors: Mayers Andrew G. , van Hooff Johanna C. , Baldwin David S. 
Published: March 2003

AbstractThis study sought to investigate whether first‐degree relatives of depressed patients report, and react to, sleep perceptions in the same way as the depressed group. Our previous research suggested that depressed individuals may experience greater sleep ‘distress’ than healthy individuals; we wished to explore whether this was also apparent in their nearest relatives. A sample was recruited of 18 antidepressant‐treated patients with a current DSM‐IV diagnosis of major depressive disorder, 18 healthy controls, and a group of 10 first‐degree relatives for each study group. In accordance with previous findings, poorer sleep perceptions corresponded with poorer life‐quality and mood perceptions, and depressed individuals reported poorer sleep perceptions and poorer life‐quality/mood perceptions than controls. Additionally, there was evidence of similar sleep reporting between depressed patients and their relatives, and for a difference between these relatives and other non‐depressed groups. There was a non‐significant trend for depressed patients, and their relatives, to report total sleep time in the same manner as each other, and differently to other non‐depressed groups. Reports of poor sleep may be associated with reports of poor mood in depression, but in non‐depressed individuals the association may be with a feeling of weariness. Copyright © 2003 John Wiley & Sons, Ltd.
Novel stimulatory role for insulin‐like growth factor binding protein‐2 in prostate cancer cells
Authors: Moore Michael G. , Wetterau Lawrence A. , Francis Malik J. , Peehl Donna M. , Cohen Pinchas 
Published: March 2003

AbstractThe insulin‐like growth factor (IGF) axis is a complex system composed of 2 mitogenic ligands, IGF‐I and ‐II, 2 receptors, IGF‐1R and IGF‐2R, and 6 binding proteins, IGFBP‐1 to ‐6. The IGFBPs exert their actions through their regulation of IGF bioavailability for IGF receptors. In addition, some IGFBPs have also been found to have direct cellular actions independent of IGFs. IGFBP‐2 is a major IGFBP in the prostate and in seminal fluid. IGFBP‐2 levels, which are elevated in many malignancies, are markedly increased in prostate cancer, and show a positive correlation with prostate specific antigen (PSA) and prostate tumor aggressiveness. We investigated the potential role of IGFBP‐2 in the pathogenesis of prostate cancer by evaluating its ability to stimulate growth and the expression and activity of the nuclear enzyme, telomerase. We found IGFBP‐2 to have a modest suppressive effect on the growth of primary cultures of normal prostate epithelial cells and a potent IGF‐antagonistic effect in these cells, similar to previous reports on the inhibitory nature of this molecule. Surprisingly, IGFBP‐2 had a potent stimulatory effect on growth of LAPC‐4 prostate cancer cells, an effect that was more pronounced in the absence of androgens. IGFBP‐2 growth stimulation of LAPC‐4 cells was completely blocked by MAP‐kinase inhibitors and partially blocked by PI3‐kinase inhibitors. IGFBP‐2 stimulation of LAPC‐4 cell growth seen in serum‐free conditions was lost in the presence of 10% FBS. IGFBP‐2 also had a growth stimulatory effect on DU 145 prostate cancer cells. IGFBP‐2 significantly stimulated telomerase activity in LAPC‐4 cells in the absence of androgens. In addition, IGFBP‐2 significantly stimulated hTERT expression and telomerase activity in DU 145 cells. Thus, we demonstrated an inhibitory effect of IGFBP‐2 on non‐malignant prostate cells, but showed it to be stimulatory for prostate cancer cells in a MAP‐kinase and androgen‐modulated process. In conclusion, IGFBP‐2 may play a role in the progression, but not in the initiation of the prostate cancer disease process, suggesting the existence of a molecular switch transitioning IGFBP‐2 from a growth inhibitor to a pro‐carcinogenic molecule. © 2003 Wiley‐Liss, Inc.
n‐3 polyunsaturated fatty acid intake and cancer risk in Italy and Switzerland
Authors: Tavani Alessandra , Pelucchi Claudio , Parpinel Maria , Negri Eva , Franceschi Silvia , Levi Fabio , La Vecchia Carlo 
Published: March 2003

AbstractData from a series of case‐control studies, conducted in Italy and Switzerland between 1991 and 2001, have been analyzed to evaluate the role of n‐3 polyunsaturated fatty acid (PUFA) intake in the etiology of cancer of oral cavity and pharynx (736 cases, 1,772 controls), esophagus (395 cases, 1,066 controls), large bowel (1,394 colon, 886 rectum, 4,765 controls), breast (2,900 cases, 3,122 controls) and ovary (1,031 cases, 2,411 controls). Controls were patients admitted to hospital for acute, non‐neoplastic conditions, unrelated to modifications in diet. The multivariate odds ratios (OR) for the highest quintile of n‐3 PUFAs compared to the lowest one were 0.5 for oral and pharyngeal cancer, 0.5 for oesophageal cancer, 0.7 for colon cancer, 0.8 for rectal and breast cancer and 0.6 for ovarian cancer; the estimates and the trends in risk were significant for all cancer sites, excluding rectal and breast cancer. The estimates for an increase in n‐3 PUFAs of 1 g/week were 0.70 for oral and pharyngeal cancer, 0.71 for oesophageal, 0.88 for colon, 0.91 for rectal, 0.90 for breast and 0.85 for ovarian cancer. All the estimates were statistically significant, excluding that for rectal cancer, and consistent across strata of age and gender. These results suggest that n‐3 PUFAs decrease the risk of several cancers. © 2003 Wiley‐Liss, Inc.
Lung cancer rates convergence in young men and women in the United States: Analysis by birth cohort and histologic type
Authors: Jemal Ahmedin , Travis William D. , Tarone Robert E. , Travis Lois , Devesa Susan S. 
Published: March 2003

AbstractAge‐specific rates of lung cancer have been consistently higher for men than for women in the United States, due primarily to different patterns of cigarette smoking. Gender differences in cigarette smoking have diminished in recent birth cohorts, however, especially among whites. We used U.S. population‐based incidence and mortality data and examined trends in age‐specific rates of lung cancer by birth cohort according to gender, ethnic group, and histology to evaluate the generational changes in U.S. lung cancer risk for menvs. women. All tests of statistical significance are 2‐sided (95% confidence interval [CI]). Lung cancer mortality rates have converged between men and women born after 1960, especially in whites. The male‐to‐female (M:F) mortality rate ratio for ages 35–39 years decreased from 3.0 (95% CI = 2.7–3.4) around the 1915 birth cohort to 1.1 (95% CI = 1.0–1.1) around the 1960 birth cohort among whites and from 4.0 (95% CI = 3.2–5.0) around the 1925 birth cohort to 1.5 (95% CI = 1.3–1.7) around the 1960 birth cohort among blacks. Similarly, incidence rates for white men and women converged rapidly for adenocarcinoma, small cell carcinoma, and large cell carcinoma, but less so for squamous cell carcinoma. These findings reflect the smoking patterns among white and black men and women: cigarette smoking prevalence at age 24 was essentially equal among white men and women born after 1960 but continued to be higher in black men than women. The convergence of lung cancer death rates among men and women born after 1960s supports the idea that males and females maybe equally susceptible to develop lung cancer from a given amount of cigarette smoking, rather than the hypothesis that women are more susceptible. © 2003 Wiley‐Liss, Inc.
55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with the androgen receptor
Authors: Ishiguro Hitoshi , Uemura Hiroji , Fujinami Kiyoshi , Ikeda Naoya , Ohta Shinsuke , Kubota Yoshinobu 
Published: March 2003

AbstractMost prostate cancer grows in a hormone‐dependent manner. Most patients, however, show hormone‐independent growth after several years of hormone therapy. The mechanism of hormone‐refractory prostate cancer remains unknown. It is important, therefore, to identify gene(s) related to prostate cancer that are up‐ or downregulated. We studied differences in gene expression in pairs of prostate cancer and normal prostate tissue utilizing the differential display method. Expression of the identified gene was examined by RT‐PCR and real time quantitative PCR (TaqMan‐PCR) using 26 pairs of human prostate cancer and normal tissues. We identified a specific upregulated gene encoding a 55 kDa nuclear matrix protein (nmt55) in human prostate cancer. nmt55 gene expression in human prostate cancer tissue was higher (20/26 cases) than that in normal prostate tissue. Moreover, the relationship between nmt55 and androgen receptor (AR) expression showed a positive correlation. In another experiment, transcriptional activity of the prostate specific antigen (PSA) promoter was upregulated by nmt55 in 293 cells. nmt55 showed high expression in prostate cancer compared to normal tissue and its expression showed a positive correlation with AR expression. The PSA promoter was activated by nmt55 expression. These results suggest the possibility that nmt55 expression is related to hormone‐dependency or ‐independence associated with the AR. © 2003 Wiley‐Liss, Inc.
Elevation of de novo ceramide synthesis in tumor masses and the role of microsomal dihydroceramide synthase
Authors: Koyanagi Satoru , Kuga Minoru , Soeda Shinji , Hosoda Yoshiko , Yokomatsu Tsutomu , Takechi Hiroaki , Akiyama Takeshi , Shibuya Shiroshi , Shimeno Hiroshi 
Published: March 2003

AbstractCeramide is formed through sphingomyelin hydrolysis or de novo synthesis and may play a key role in cell growth, differentiation and apoptosis. To clarify which pathway tumor cells use to form ceramide and how its formation is regulated, we determined the levels of dihydroceramide and ceramide in mice inoculated with Sarcoma 180, B16 melanoma or Lewis lung carcinoma cells. The levels in these tumor masses were very high compared to those in other healthy tissues. The high levels were significantly reduced by a single administration of the dihydroceramide synthase inhibitor fumonisin B1, but not by a sphingomyelinase inhibitor, sphingomyelin analog‐1 (SMA‐1), suggesting that the tumor cells have a very effective means of synthesizing dihydroceramide and ceramide. To investigate the characteristics of dihydroceramide synthase, we prepared microsomes from Sarcoma 180 tumor masses and healthy mouse liver cells, and compared their catalytic activities on dihydroceramide formation. A kinetic analysis using sphinganine and palmitoyl CoA as substrates revealed that the enzyme present in the tumor formed dihydroceramide 3 times more efficiently than that in healthy liver cells. Partial purification of dihydroceramide synthase from bovine liver microsomes revealed that the enzyme was present in healthy tissues as a 333 kDa form constructed of 47 kDa subunit proteins. However, gel filtration of the enzyme solubilized from the Sarcoma 180 tumor masses demonstrated that its molecular weight was 1,300 kDa. These results suggest that malignant transformation causes the cell to produce a form of dihydroceramide synthase with a larger than normal molecular mass; the increased molecular mass may account for the enzyme's increased catalytic efficiency. © 2003 Wiley‐Liss, Inc.
Quantitative detection of micrometastases in the lymph nodes of gastric cancer patients with real‐time RT‐PCR: A comparative study with immunohistochemistry
Authors: Kubota Keisuke , Nakanishi Hayao , Hiki Naoki , Shimizu Nobuyuki , Tsuji Eiichi , Yamaguchi Hirokazu , Mafune Ken‐ichi , Tange Tsuyoshi , Tatematsu Masae , Kaminishi Michio 
Published: March 2003

AbstractHistologic examination lacks the sensitivity to detect micrometastases in gastric cancer lymph nodes. In the present study, we applied a real‐time RT‐PCR approach to the quantitative detection of micrometastases in gastric cancer lymph nodes and compared diagnostic power with routine histology and immunohistochemistry. We studied 392 lymph nodes from 21 gastric cancer patients who underwent curative surgery. Real‐time quantitative RT‐PCR was performed on a LightCycler instrument using a hybridization probe for carcinoembryonic antigen (CEA) and cytokeratin‐20 (CK20) as marker genes. Immunohistochemistry with antibodies to wide‐keratin was also performed in the lymph nodes to compare the sensitivity and specificity. Median (average) values of CEA mRNA in lymph nodes in patients with histology+, immunohistochemistry+/histology−, immunohistochemistry−/histology− and negative control results were 4,600 (16,000), 200 (400), 0 (9.8) and 0 (0.6), respectively. There were some false‐negative results with simple CEA and CK20 real‐time RT‐PCR due to the presence of low gene‐expressing gastric cancers as revealed by CEA and CK20 immunohistochemistry. CEA in combination with CK20 (duplex) real‐time RT‐PCR partially covered this weakness. Consequently, all 71 histology+ lymph nodes were positive for duplex real‐time RT‐PCR as well as wide‐keratin immunohistochemistry. Positivity rates by histology, wide‐keratin immunohistochemistry and duplex real‐time RT‐PCR were 18.0% (71/392), 20.9% (82/392) and 25.8% (101/392), respectively. In 2 of 8 patients with pT1N0, positive lymph nodes were observed by real‐time RT‐PCR but not by immunohistochemistry. These results indicate that duplex quantitative real‐time RT‐PCR is the most sensitive method for detecting micrometastases and useful for evaluating the prognostic significance of lymph node micrometastasis in gastric cancer patients. © 2003 Wiley‐Liss, Inc.
Human malignant glioma cell lines are sensitive to low radiation doses
Authors: Beauchesne Patrick D. , Bertrand Suzanne , Branche Robert , Linke Steven P. , Revel Roland , Dore Jean‐François , Pedeux Rémy M. 
Published: March 2003

AbstractMalignant gliomas display aggressive local behavior and are not cured by existing therapy. Some cell lines that are considered radioresistant respond to low radiation doses (<1 Gy) with increased cell killing (low‐dose hypersensitivity). In our study, 4 of 5 human glioma cell lines exhibited significant X‐ray sensitivity at doses below 1 Gy. The surviving fractions (SFs) obtained at 0.7 and/or 0.8 Gy were comparable to those at 1.5 Gy. Low‐dose hypersensitivity was evident when irradiation was combined with etoposide treatment. Repeated irradiation with low doses was markedly more effective than irradiation with single, biologically equivalent doses in decreasing SFs, inhibiting xenograft tumor growth in mice. All experiments were conducted with an accelerator used in clinics, establishing that low‐dose hypersensitivity was present following megavoltage X‐irradiation. Thus, repeated low‐dose irradiation (ultrafractionation) could greatly improve the effectiveness of radiotherapy of gliomas and could allow safe treatment of patients with cumulative doses greater than 60 Gy. © 2003 Wiley‐Liss, Inc.