bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurotrophins: possible role in affective disorders
Authors: Sandler M 
Published: September 2002

AbstractVarious monoamine hypotheses of affective disorders have been unable to provide a complete explanation for the observed clinical findings. Recently Duman et al. (1997) have produced a molecular and cellular theory of depression which seems to be a worthy successor to these hypotheses. Whereas the earlier theories were unable to explain the time lag between antidepressant drug administration and lightening of affect, Duman's group pinpoints intracellular mechanisms, in the right time frame, which decrease or increase the generation of neurotrophic factors necessary for the survival of certain neurons, particularly in the hippocampus. This new concept may lead to novel therapeutic approaches. Copyright © 2001 John Wiley & Sons, Ltd.
The immunoregulatory effects of antidepressants
Authors: Maes Michael 
Published: September 2002

AbstractThere is some evidence that major depression is accompanied by activation of the inflammatory‐response system (IRS). It has been hypothesized that increased production of proinflammatory cytokines may play a role in the etiology of major depression. If increased production of proinflammatory cytokines is at all involved in the etiology of depression, one would expect antidepressive treatments to have negative immunoregulatory effects. This paper reviews the effects of antidepressants, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), heterocyclic antidepressants (HCAs), serotonin‐noradrenaline reuptake inhibitors (SNRIs), lithium,l‐5‐hydroxytroptophan (L‐5‐HTP), reversible inhibitors of MAO‐A (RIMA) on the production of proinflammatory cytokines, e.g. interferon‐γ (IFNγ), and negative immunoregulatory cytokines and agents, e.g. interleukin‐10 (IL‐10). In depressed patients, prolonged treatment with antidepressants and mood stabilizers normalizes signs of activation of the IRS, such as increased serum IL‐6 and acute phase protein concentrations. In vitro, it has been shown that various types of antidepressive drugs, including TCAs (imipramine; clomipramine); SSRIs (citalopram, fluoxetine, sertraline); lithium; SNRIs (venlafaxine); HCAs (trazodone); RIMAs (moclobemide) and L‐5‐HTP significantly suppress the ratio of IFNγ/IL‐10 production by peripheral blood immunocytes. These antidepressant drugs appear to have a common effect on the IRS, i.e. in vitro they increase the production of IL‐10 by peripheral blood leukocytes. Thus, the results suggest that antidepressants have negative immunoregulatory effects. It may be speculated that antidepressants exert some of their antidepressant effects through their negative immunoregulatory capacities. Copyright © 2001 John Wiley & Sons, Ltd.
Ontogenetic effects of MAO‐A inhibition on rat pineal n‐acetylserotonin and melatonin during the first month of neonatal life
Authors: Oxenkrug Gregory F , Requintina Pura J , Yuwiler A 
Published: September 2002

AbstractInhibitors of monoamine oxidase A (MAO‐A) but not MAO‐B stimulate the activity of pineal serotonin N‐acetyltransferase (AANAT) in the adult rat pineal leading to increased formation of N‐acetyl serotonin (NAS) and melatonin (MEL). The pineal gland of the neonatal rat has AANAT activity, but the second enzyme in melatonin biosynthesis, HIOMT (hydroxyindole‐O‐methyltransferase) converting NAS to MEL, is absent during the first week of neonatal life. In this study we examined the effects of acute clorgyline treatment in vitro and in vivo, on pineal indoles over the first month of neonatal life. The results show that clorgyline stimulates NAS production by pineal both in vitro and in vivo from day five on with a marked increase between day 14 and day 21. In contrast, MEL is not increased until day 21, with a sharp rise thereafter. Copyright © 2000 John Wiley & Sons, Ltd.
Functional magnetic resonance imaging reflects changes in brain functioning with sedation
Authors: Starbuck Victoria N , Kay Gary G , Platenberg R. Craig , Lin Chin‐shoou , Zielinski Brandon A 
Published: September 2002

AbstractFunctional magnetic resonance imaging (fMRI) studies have demonstrated localized brain activation during cognitive tasks. Brain activation increases with task complexity and decreases with familiarity. This study investigates how sleepiness alters the relationship between brain activation and task familiarity. We hypothesize that sleepiness prevents the reduction in activation associated with practice. Twenty‐nine individuals rated their sleepiness using the Stanford Sleepiness Scale before fMRI. During imaging, subjects performed the Paced Auditory Serial Addition Test, a continuous mental arithmetic task. A positive correlation was observed between self‐rated sleepiness and frontal brain activation. Fourteen subjects participated in phase 2. Sleepiness was induced by evening dosing with chlorpheniramine (CP) (8 mg or 12 mg) and terfenadine (60 mg) in the morning for 3 days before the second fMRI scan. The Multiple Sleep Latency Test (MSLT) was also performed. Results revealed a significant increase in fMRI activation in proportion to the dose of CP. In contrast, for all subjects receiving placebo there was a reduction in brain activation. MSLT revealed significant daytime sleepiness for subjects receiving CP. These findings suggest that sleepiness interferes with efficiency of brain functioning. The sleepy or sedated brain shows increased oxygen utilization during performance of a familiar cognitive task. Thus, the beneficial effect of prior task exposure is lost under conditions of sedation. Copyright © 2000 John Wiley & Sons, Ltd.
A simple rainfall–runoff model based on hydrological units applied to the Teba catchment (south‐east Spain)
Authors: Donker N. H. W. 
Published: September 2002

AbstractA hydrological model (YWB, yearly water balance) has been developed to model the daily rainfall–runoff relationship of the 202 km2 Teba river catchment, located in semi‐arid south‐eastern Spain. The period of available data (1976–1993) includes some very rainy years with intensive storms (responsible for flooding parts of the town of Malaga) and also some very dry years.The YWB model is in essence a simple tank model in which the catchment is subdivided into a limited number of meaningful hydrological units. Instead of generating per unit surface runoff resulting from infiltration excess, runoff has been made the result of storage excess. Actual evapotranspiration is obtained by means of curves, included in the software, representing the relationship between the ratio of actual to potential evapotranspiration as a function of soil moisture content for three soil texture classes.The total runoff generated is split between base flow and surface runoff according to a given baseflow index. The two components are routed separately and subsequently joined. A large number of sequential years can be processed, and the results of each year are summarized by a water balance table and a daily based rainfall runoff time series. An attempt has been made to restrict the amount of input data to the minimum.Interactive manual calibration is advocated in order to allow better incorporation of field evidence and the experience of the model user. Field observations allowed for an approximate calibration at the hydrological unit level. Copyright © 2001 John Wiley & Sons, Ltd.
Measurement of atmospheric water vapour on the ground's surface by radio waves
Authors: Kishii Tokuo , Kuzuha Yasuhisa , Sugita Fumi , Hayano Michiko 
Published: September 2002

AbstractWater vapour in the atmosphere and various meteorological phenomena are essential to the understanding of the mechanism of the water cycle. However, it is very difficult to observe water vapour in the atmosphere because the quantities are usually observed at a single point not over long intervals or in a specific plane or volume. Accordingly, the use of radio waves is considered to be necessary to observe water vapour. Radio waves can be transmitted over long intervals and across large areas, and generally speaking, the characteristics of radio waves change due to material in the atmosphere, especially water vapour. Usually absorption is used to observe the quantity of water vapour. But the relationship between absorption and the quantity of water vapour is not linear, so we try to utilize the phase difference between two radio waves as an alternative method. First, the relationship between the phase delay and the water vapour was induced by a physical equation and the resulting phase delay was found to be proportional to the quantity of water vapour. Furthermore, the phase difference between two separate points was observed by use of two radio waves in the field, specifically 84 GHz and 245 GHz. For reference and comparison, water vapour density in the atmosphere was simultaneously observed by meteorological observation. As a result, the density of the water vapour was found to be proportional to the phase difference between the two radio waves. The result also shows that this method is able to measure the diurnal changes in water vapour density in each season. Copyright © 2001 John Wiley & Sons, Ltd.
Evaluating the spatial and temporal distribution of snow accumulation, snowmelts and discharge in a multi basin scale: an application to the Tohoku Region, Japan
Authors: Motoya Ken , Yamazaki Takeshi , Yasuda Nobuhisa 
Published: September 2002

AbstractThe main aim of this study is to discuss the temporal and spatial distributions of the snow water equivalent, snowmelt and discharge in a multibasin scale (Tohoku Region, Japan; covering about 77 000 km2), using the heat budget model with the help of remote sensing (satellite images and meteorological radar). The calculated distributions of snow water equivalent were similar to that of the snow map obtained from the satellite images. At the same time, the seasonal variation of discharge in the three basins investigated (Yuda, covering 583 km2, Shichikasyuku, 237 km2 and Okutadami, 426 km2) was in good agreement with the observed one at the dam. Moreover, we conducted sensitivity tests for increasing solar radiation and air temperature by adding 10 W/m2 to the solar radiation and 1 degree to air temperature, respectively. The peaks of the snow cover area did not change so much, although the area in the snowmelt season decreased in these cases. The snow water equivalent in both cases became smaller than the control, particularly in the case of a 1 degree increase in air temperature. The snowmelt and discharge increased in the first half of the snowmelt period but were less than the control in the latter half. The model suggested in this study will be able to estimate changes in the hydrological elements related to snow, if a scenario of the climate change is provided. Copyright © 2001 John Wiley & Sons, Ltd.
Inhibition of glutathione S‐transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance
Authors: Mukanganyama Stanley , Widersten Mikael , Naik Yogeshkumar S. , Mannervik Bengt , Hasler Julia A. 
Published: September 2002

AbstractA strategy to overcome multidrug resistance in cancer cells involves treatment with a combination of the antineoplastic agent and a chemomodulator that inhibits the activity of the resistance‐causing protein. The aim of our study was to investigate the effects of antimalarial drugs on human recombinant glutathione S‐transferase (GSTs) activity in the context of searching for effective and clinically acceptable inhibitors of these enzymes. Human recombinant GSTs heterologously expressed in Escherichia coli were used for inhibition studies. GST A1‐1 activity was inhibited by artemisinin with an IC50 of 6 μM, whilst GST M1‐1 was inhibited by quinidine and its diastereoisomer quinine with IC50s of 12 μM and 17 μM, respectively. GST M3‐3 was inhibited by tetracycline only with an IC50 of 47 μM. GST P1‐1 was the most susceptible enzyme to inhibition by antimalarials with IC50 values of 1, 2, 1, 4, and 13 μM for pyrimethamine, artemisinin, quinidine, quinine and tetracycline, respectively. The IC50 values obtained for artemisinin, quinine, quinidine and tetracycline are below peak plasma concentrations obtained during therapy of malaria with these drugs. It seems likely, therefore, that GSTs may be inhibited in vivo at doses normally used in clinical practice. Using the substrate ethacrynic acid, a diuretic drug also used as a modulator to overcome drug resistance in tumour cells, GST P1‐1 activity was inhibited by tetracycline, quinine, pyrimethamine and quinidine with IC50 values of 18, 27, 45 and 70 μM, respectively. The ubiquitous expression of GSTs in different malignancies suggests that the addition of nontoxic reversing agents such as antimalarials could enhance the efficacy of a variety of alkylating agents. © 2001 Wiley‐Liss, Inc.
Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii
Authors: Lawson James S. , Field Andrew S. , Tran Dinh D. , Killeen Jeffrey , Maskarenic Gertraud , Ishikura Hiroshi , Trichopoulos Dimitrios 
Published: September 2002

AbstractWe have undertaken a study to examine whether the difference in breast cancer incidence between 2 populations of similar genetic background is reflected in a similar pattern of estrogen receptor α expression in normal mammary gland. Study participants were 92 Japanese women from Sapporo, Japan (mean age 48.2 years) and 49 Japanese women from Honolulu, Hawaii (mean age 45.4 years), who underwent biopsy indicating normal breast tissue or benign, nonproliferative breast disease in hospitals in Sapporo, Japan and Honolulu, Hawaii. The breast tissue samples were formalin‐fixed and paraffin‐embedded. The estrogen receptor immunohistochemistry assays were conducted using Dako kits. Japanese women in Hawaii, who have a higher incidence of breast cancer compared with Japanese women in Sapporo, also had, as predicted, higher mean percentage of estrogen receptor α‐positive normal mammary cells (2‐tailed test, p ∼ 0.09). The results of our study are compatible with the hypothesis that estrogen receptor α expression in normal mammary tissue increases breast cancer risk and they also indicate that the expression of these receptors is dependent, at least in part, on nongenetic factors. © 2001 Wiley‐Liss, Inc.
Lung cancer incidence in Australia: Impact of filter‐tip cigarettes with unchanged tar yields
Authors: Blizzard Leigh , Dwyer Terence 
Published: September 2002

AbstractFilter‐tip cigarettes became popular in Australia in the late 1950s, but “tar” yields remained high for another decade. Because of this, the effect of filters independently of tar reductions can be estimated by comparing the age‐adjusted incidence of lung cancer for relevant birth cohorts of Australians. Separate analyses by histologic type may throw some light on the specific effects of filters. Age‐adjusted incidence of squamous cell carcinoma (SCC), small cell lung carcinoma (SCLC) and adenocarcinoma (AC) was estimated by Poisson regression for 5‐year birth cohorts of Australians using lung cancer registration data for 1982–95. To take account of changes in smoking prevalence, ever‐smoker less never‐smoker differences in age‐adjusted incidence were estimated. Comparisons were made for smokers born during 1930–34 and 1940–44. Smokers born in 1940–44 commenced smoking at the time of introduction of filter‐tips. Age‐adjusted incidence of SCC (−23%) and SCLC (−21%) but not AC (+7%) was lower for female smokers born during 1940–44. For male smokers, rates of SCC (−42%), SCLC (−43%) and AC (−24%) were each lower. The high rates overall of 1940s‐born women were due to disproportionately higher incidence of AC, the type that comprised 42% of diagnoses with histologic confirmation. In Australia, the switch to filter‐tip cigarettes prior to any reduction in tar yields was associated with reduced incidence of SCC and SCLC, and of AC for men only. Rates of AC were not reduced for women, indicating that other factors were important for this type of lung cancer. © 2001 Wiley‐Liss, Inc.
Family history and the risk of stomach cancer death in Japan: Differences by age and gender
Authors: Yatsuya Hiroshi , Toyoshima Hideaki , Mizoue Tetsuya , Kondo Takaaki , Tamakoshi Koji , Hori Yoko , Tokui Noritaka , Hoshiyama Yoshiharu , Kikuchi Shogo , Sakata Kiyomi , Hayakawa Norihiko , Tamakoshi Akiko , Ohno Yoshiyuki , Yoshimura Takesumi 
Published: September 2002

AbstractFamilial aggregation of stomach cancer has long been observed. The effect on disease risk of family history and its magnitude according to the type of affected relatives, however, is not well known. We conducted a prospective analysis using the JACC study (Japan Collaborative Cohort Study For Evaluation of Cancer Risk, sponsored by Monbusho) data. During the follow‐up period, 662 stomach cancer deaths were documented. A positive history of stomach cancer in one or more first‐degree relatives was associated with a significantly increased risk of death from the disease in both men (RR 1.60; 95% CI 1.11–2.31) and women (RR 2.47; 95% CI 1.50–4.06). In the subanalysis stratified by age, the association between positive family history and stomach cancer was stronger in the age group from 40–59 (RR 2.62; 95% CI 1.34–5.11 for men and RR 5.88; 95% CI 2.70–12.82 for women) than in the age group from 60–79 (RR 1.31; 95% CI 0.84–2.05 for men and RR 1.44; 95% CI 0.72–2.88 for women). In the age group from 40–59, men with father's history and women with mother's and sister's history of the disease had a significantly increased risk (RR 3.14; 95% CI 1.51–6.55, RR 10.46; 95% CI 4.54–24.12, RR 13.39; 95% CI 3.89–46.12, respectively). When 2 or more family members were affected, the increment in the risk was prominent especially in women (RR 9.45; 95% CI 4.46–20.05). These results suggest the existence of a certain subtype of stomach cancer that is inherited more often by women from one generation to the next in gender‐influenced fashion. Any preventive strategy should take into account the degree of individual susceptibility. © 2001 Wiley‐Liss, Inc.
Inhibition of tumor growth and metastatic spreading by overexpression of inter‐alpha‐trypsin inhibitor family chains
Authors: Paris Sébastien , Sesboüé Richard , Delpech Bertrand , Chauzy Claude , Thiberville Luc , Martin Jean‐Pierre , Frébourg Thierry , Diarra‐Mehrpour Maryam 
Published: September 2002

AbstractThe inter‐α trypsin inhibitor (ITI) family is a group of proteins built up from different combinations of 1 light chain (ITI‐L) and 3 highly homologous heavy chains (ITI‐H1, ‐H2 and ‐H3). To investigate a potential role of the ITI family chains in cancer and metastasis spreading, we engineered human H460M cell lines expressing both the green fluorescent protein (GFP) and one of these chains. These clones were subcutaneously injected in athymic nude mice, and lung metastasis number and primary tumor weight were determined after 28 days. Expression of the ITI‐L chain considerably decreased tumor weight and fluorescent lung metastasis number. ITI‐H1 and ITI‐H3 chain expression induced a significant decrease of metastasis number, whereas no decrease of tumor weight could be detected. In vitro, ITI‐L expression significantly decreased chemotaxis and ITI‐H1 and ITI‐H3 expression increased cell attachment. These results argue for the antitumoral or antimetastatic properties of ITI‐L, ‐H1 and ‐H3 chains. © 2001 Wiley‐Liss, Inc.
Transcriptional profiling of a human papillomavirus 33–positive squamous epithelial cell line which acquired a selective growth advantage after viral integration
Authors: Ruutu Merja , Peitsaro Panu , Johansson Bo , Syrjänen Stina 
Published: September 2002

AbstractAlterations in gene expression represent key events in carcinogenesis. We have studied HPV‐induced cervical carcinogenesis, using an HPV‐33‐positive cell line (UT‐DEC‐1) established from a low‐grade vaginal dysplasia (VAIN‐I). Early‐passage cells contained HPV‐33 in episomal form, but these were superseded at later passages by cells carrying only integrated virus. To gain insight into the biologic significance of HPV integration, we compared the level of gene expression in normal vaginal keratinocytes, early‐passage and late‐passage UT‐DEC‐1 cells, using cDNA microarrays. Total RNA was isolated from cells by CsCl‐gradient centrifugation, reverse‐transcribed with MMLV reverse transcriptase and labeled with α‐32P ATP. A cDNA microarray expression profile analysis was performed with Clontech's Human Cancer 1.2 cDNA expression array kit. The 16 upregulated genes (cut‐off 2‐fold), identified by comparing both cell types to control keratinocytes, appeared to support cell‐cycle progression or to be functional in mitosis. These included, e.g., MCM4 DNA replication licensing factor, cdc2p34 and chromatin assembly factor 1 p48 subunit. Downregulated genes (44 altogether) interfered with apoptosis and cell adhesion, including the apoptosis‐inducing genes FRAP, Bik and caspase‐9 precursor. The most significant differences between the late and early passages (29 and 46 constantly up‐ and downregulated genes without any fluctuation) were overexpression of the transcription factors E2F5 with its dimerization partner DP1, NF‐κB and serine/threonine kinases and underexpression of enzymes of the MAPK pathway. Acquisition of a selective growth advantage after viral integration might be explained by a major shift from a MAPK pathway to cell‐cycle dysregulation (G2/M). © 2002 Wiley‐Liss, Inc.
Pharmacokinetic and tumor‐seeking properties of recombinant and nonrecombinant anti‐carcinoembryonic antigen antibody fragments
Authors: Groulet Agnès , Dorvillius Mylène , Pèlegrin André , Barbet Jacques , Baty Daniel 
Published: September 2002

AbstractProduction of recombinant antibody fragments in bacterial expression systems results in intentional or fortuitous differences compared to the original products prepared by hybridoma technology. These differences may have significant effects not only on antigen‐binding properties but also on pharmacokinetic and tumor‐seeking properties. Our major goal was to investigate some of these possible differences. We produced in Escherichia coli an rFab′ fragment containing only 1 cysteine residue in the hinge region; the fragment was derived from a mouse MAb (F6) specific for CEA. The rFab′ had a slightly lower m.w. and a higher isoelectric point relative to the corresponding nonrecombinant fragment (pFab′). This was explained by the absence of N‐glycosylation on the Vκ domain of rFab′. Vκ glycosylation had no significant effect on antibody‐binding affinity and kinetics. However, rFab′ was eliminated from the circulation much faster than pFab′, and the maximal dose accumulated in the tumor was reduced relative to pFab′. Thus, glycosylation appears to modify the targeting efficiency of antibody fragments. rF(ab′)2 fragments were obtained either spontaneously from the culture supernatant of E. coli or by chemical cross‐linking [rcF(ab′)2]. We observed improved tumor targeting with rcF(ab′)2 compared to rF(ab′)2, which could be explained by the greater stability of the thioether compared to the disulfide linkage. These results demonstrate that a single cysteine residue in the hinge region of rFab′ is particularly well suited to prepare stable, chemically coupled, bivalent or bispecific antibodies, avoiding intrahinge disulfide bonding and thus achieving higher production yields. © 2002 Wiley‐Liss, Inc.