bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of endogenous lithium in neuropsychiatric disorders—a model for biological transmutation
Authors: Kurup Ravi Kumar , Kurup Parameswara Achutha 
Published: October 2002

AbstractThe human hypothalmus produces an endogenous membrane Na+‐K+ ATPase inhibitor, digoxin. A digoxin induced model of cellular/neuronal quantal state and perception has been described by the authors. Biological transmutation has been described in microbial systems in the quantal state. The study focuses on the plasma levels of digoxin, RBC membrane Na+‐K+ ATPase activity, plasma levels of magnesium and lithium in neuropsychiatric and systemic disorders. Inhibition of RBC membrane Na+‐K+ ATPase activity was observed in most cases along with an increase in the levels of serum digoxin and lithium and a decrease in the level of serum Mg++. The generation of endogenous lithium would obviously occur due to biological transmutation from magnesium. Digoxin and lithium together can produce added membrane Na+‐K+ ATPase inhibition. The role of membrane Na+‐K+ ATPase inhibition in the pathogenesis of neuropsychiatric and systemic disorders is discussed. The inhibition of membrane Na+‐K+ ATPase can contribute to an increase in intracellular calcium and a decrease in magnesium, which can result in a defective neurotransmitter transport mechanism, mitochondrial dysfunction and apoptosis, defective golgi body function and protein processing dysfunction, immune dysfunction and oncogenesis. Copyright © 2002 John Wiley & Sons, Ltd.
Relations of clinical features, subgroups and medication to serum monoamines in schizophrenia
Authors: Oades Robert D. , Klimke Ansgard , Henning Uwe , Rao Marie Luise 
Published: October 2002

AbstractBackgroundPlasma and serum indices of monoaminergic activity reflect partly the illness of schizophrenia (e.g. HVA/deficit syndrome) and sometimes the symptoms (e.g. HVA/anhedonia). But, such studies have rarely taken both metabolites and parent amines or inter‐amine activity ratios into account. We hypothesized that comparing the major symptom dimensions to measures of transmitter activity (with and without control for antipsychotic drug treatment) would show differential patterns of activity useful for the design of pharmacological treatments.MethodsDopamine (DA), noradrenaline (NA), serotonin (5‐HT), their three major metabolites and prolactin were measured in the serum of 108 patients with schizophrenia and 63 matched controls: DA D2‐receptor blocking‐activity was estimated from a regression of butyrophenone displacement in striatum in vitro on to PET reports of drug‐binding in vivo. Symptoms were factored into four dimensions (disorganized/thought disorder, nonparanoid/negative, ideas‐of‐reference and paranoid/positive symptoms).Results(1) Patients' DA activity did not differ from controls: but their 5‐HT and NA turnovers increased/decreased, respectively, and the DA/5HT‐metabolite ratio was lower. Increased DA‐D2‐receptor occupancy was predicted by decreased DA‐metabolism and its ratio to 5‐HT‐metabolism. (2) Patients had higher levels of NA, DA‐metabolites and DA‐/5‐HT‐metabolite ratios on atypical vs typical drugs. (3) Increased D2‐occupancy was associated with lower DA metabolism in paranoid patients but was unrelated to relative increases of DA/5‐HT‐ and NA‐metabolism in nonparanoid patients. (4) Low DA‐/5‐HT‐metabolite ratios, high prolactin and low DA‐metabolism characterized thought‐disordered patients. (5) High DA‐/5‐HT‐metabolite ratios paralleled many ideas‐of‐reference. The metabolites were sensitive, respectively, to control for D2‐occupancy and prolactin.ConclusionsThe role of DA in paranoid, and 5‐HT in thought‐disordered and ideas‐of‐reference dimensions point both to the mechanisms underlying the features typical of these subgroups and the type of medication appropriate. Copyright © 2002 John Wiley & Sons, Ltd.
Antipsychotics in clinical practice: guidelines for safe and effective use
Authors: Curran Stephen , Harris Linda , Macdonald Andrew , Pollock Colin , Roney Gerry , Silkstone David 
Published: October 2002

AbstractAntipsychotic drugs have made a significant contribution to the treatment of schizophrenia but the older drugs in particular have significant side‐effects. The newer atypical drugs are effective for the treatment of both positive and negative symptoms and they also have significantly fewer serious side‐effects. However, these drugs are considerably more expensive that the older drugs and this has generated intense debate about their cost effectiveness. There is now good evidence that when all factors are taken into consideration the atypical drugs are both cost effective and improve the quality of life of patients with schizophrenia. Despite the importance of these drugs there is widespread variation in their use and a national consensus on this important issue is long overdue. Copyright © 2002 John Wiley & Sons, Ltd.
The effects of transdermal nicotine on inspection time
Authors: Thompson J. C. , Wilby G. , Stough C. 
Published: October 2002

AbstractRationaleThe acute administration of nicotine via a cigarette has been demonstrated to enhance inspection time (IT), a measure of rapid visual information processing, while the nicotinic antagonist mecamylamine impairs IT. However, as transdermal nicotine patches provide a slow delivery of nicotine, it is unclear if they produce similar effects to nicotine administered by more rapid methods.ObjectivesTo examine the effects of transdermal nicotine on inspection time.MethodsTen moderate smokers were administered nicotine (21 mg/day) or placebo via a transdermal patch in a randomized, double‐blind, repeated measures design. Subjects were administered the IT task at baseline, then 1, 3, and 6 h subsequent to patch application.ResultsThe change in IT from baseline was significantly different in the nicotine condition, relative to placebo, at 3 h but not 1 or 6 h.ConclusionsThe findings suggest that nicotine administered via transdermal patches improves IT, but this improvement may be subject to tolerance. Data from previous studies on tolerance to the cognitive effects of nicotine have been inconclusive. However, the slow delivery of nicotine from patches may be more likely to produce such effects. Copyright © 2002 John Wiley & Sons, Ltd.
Evidence‐based analysis of the worldwide abuse of licit and illicit drugs
Authors: Costa e Silva J. A. 
Published: October 2002

AbstractIn order to place the issues of drug abuse in a proper perspective and to allow rational, evidence‐based decision‐making, an analysis of the international data on the use of illicit drugs and the misuse of legally prescribed psychotropic drugs was undertaken. The data show that by far the most widely abused drug is cannabis, followed, according to region, by amphetamine‐type stimulants or cocaine. While opiate abuse is far less widespread, it accounts for a disproportionately large proportion of medical and social problems. The illicit use of licit medicines is a very small, and declining, problem. The implications of these data for physicians, politicians, regulators and administrators are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
The cation and silica chemistry of a Subandean river basin in western Amazonia
Authors: Sobieraj J. A. , Elsenbeer H. , McClain M. 
Published: October 2002

AbstractWe sampled river water at 13 locations in the Pichis basin, a 10 500 km2 large rainforest‐covered drainage basin in Peru, to assess the influence of lithological variability and seasonality on water chemistry. The concentrations of major cations and silica show a strong seasonal dependence and a remarkable variability over short distances that is only weakly reduced in the wet season; cation concentrations in streams differ by up to 100% within a few kilometres. The lowest cation concentrations were associated with relatively cation‐depleted upper Tertiary and lower Quaternary formations, whereas relatively cation‐rich lower Tertiary and Jurassic formations left a clear calcium and sodium signal in the respective rivers. Cluster analysis, in conjunction with boxplots, suggests that the sampling locations can be segregated into three groups based on similarities of their geochemical signals. According to the previously defined criteria, one river is classified as a Group 2 river with 200 < TZ+ < 450 µeq/L, whereas all other rivers fall into Group 3 with 450 < TZ+ < 3000 µeq/L (where TZ+ refers to the total cation charge). Based on a comparison with other studies at different sections of the Amazon mainstem, the river chemistry of our study area is relatively enriched in K+, Mg2+ and Ca2+, and, consequently, has a higher TZ+ value, while being relatively depleted in silica. The influence of lithological variability on water chemistry must be considered in land‐use change studies even at watershed areas of 26–3382 km2. Copyright © 2002 John Wiley & Sons, Ltd.
Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines
Authors: Dirks Willy G. , Fähnrich Silke , Lis Yvonne , Becker Elisabeth , MacLeod Roderick A.F. , Drexler Hans G. 
Published: October 2002

AbstractThe initial identification of the ALK gene, expressed as C‐terminal part of the transforming fusion protein NPM‐ALK in the t(2;5)(p23;q35) lymphoma‐associated chromosomal translocation, revealed a novel receptor tyrosine kinase (RTK). In order to expand the knowledge on ALK expression in the human system, we examined a panel of human cell lines for ALK expression and found that transcription is completely repressed in cell lines of entodermal origin (0/21). Furthermore, full length receptor expression is absent in cell lines of the hematopoietic system with the exception of t(2;5)‐associated anaplastic large cell lymphomas lines (ALCL), which are known to express chimeric NPM‐ALK mRNA. Cell lines established from solid tumors of ectodermal origin, including melanoma and breast carcinoma, exhibited widespread mRNA expression of the ALK receptor at a broad range (53/64), an association which was found to be strongest in cell lines derived from neuroblastoma (6/6), glioblastoma (8/8) as well as in cell lines established from Ewing sarcoma (4/4) and retinoblastomas (2/2). Because of the reported involvement of neutrophin tyrosine kinase receptors in autocrine differentiation in neuroblastomas, we analyzed cell lines positive for full length or chimeric ALK protein for the presence of phoshotyrosine residues within the intracellular region of ALK. While the constitutive activation of chimeric NPM‐ALK molecules could be shown, no evidence was found for induced or constitutively activated ALK receptors in neuroblastoma, melanoma or breast carcinoma cell lines. Although the receptor could be shown to be consistently expressed with exclusive specificity in tissues developed from the ectoderm, our results do not support any involvement of ALK in the stimulation of tumorigenic cell growth or differentiation so far, indicating that ALK expression is a physiologic rather than a pathologic phenomenon. © 2002 Wiley‐Liss, Inc.
Physical activity and risk for breast cancer a prospective cohort study among Swedish twins
Authors: Moradi Tahereh , Adami Hans‐Olov , Ekbom Anders , Wedrén Sara , Terry Paul , Floderus Birgitta , Lichtenstein Paul 
Published: October 2002

AbstractThe epidemiologic association between physical activity and breast cancer has been corroborated in many studies. Some inconsistencies remain, possibly due to variation in life periods for exposure assessment, confounding and undetected effect modification. In our cohort study, we address some of these questions by taking into account physical activity in different periods of life and by investigating effect modification by birth cohort and body mass index (BMI). Altogether 9,539 same‐sex twin women aged 42–70 years who answered a questionnaire about their work and leisure‐time physical exercise from ages 25 to 50 during 1967 and 1970 were included in our cohort. During follow‐up, 506 breast cancer cases occurred through 1997. We used multivariate Cox models to estimate relative risk (RR) with 95% confidence interval (CI). We found no associations between physical activity and breast cancer overall. Women born between 1901 and 1917 (aged 51–70 at baseline) who reported regular leisure‐time activity had a borderline significant 40% lower risk compared with those who reported no activity (RR 0.6; 95% CI 0.4–1.0; test for trend, p = 0.07). This association appeared to be confined to women with a low BMI after the age of 50 and to women with a high BMI during the premenopausal period. We found no evidence that work activity reduces risk for breast cancer. The importance of physical activity for breast cancer risk seems to depend on birth cohort. The association may be limited to normal‐weight postmenopausal women and overweight premenopausal women. © 2002 Wiley‐Liss, Inc.
Molecular profiling of human chondrosarcomas for matrix production and cancer markers
Authors: Söderström Mirva , Böhling Tom , Ekfors Tauno , Nelimarkka Lassi , Aro Hannu T. , Vuorio Eero 
Published: October 2002

AbstractChondrosarcoma is the second most common malignant bone tumor, characterized by production of abundant extracellular matrix resembling hyaline cartilage. To better understand the molecular pathogenesis of chondrosarcoma, we analyzed 12 chondrosarcomas for their production of connective tissue components and SOX9, a key regulator of normal chondrocyte differentiation. Furthermore, 10 chondrosarcoma samples were screened for additional changes in gene expression using cDNA array analysis. In Northern analysis, several tumors were found to express type II collagen mRNA at levels comparable to fetal cartilage used as a control. Interestingly, the highest levels of type II collagen mRNA were seen in 2 of the 3 grade 3 chondrosarcomas, which also exhibited the highest mRNA levels of SOX9 and “prechondrogenic” proα1(IIA) collagen. Expression of SOX9 in human chondrosarcomas is novel and suggests that chondrosarcomas originate from a multipotent stem cell committed to differentiation along the chondrogenic pathway. Results of the cDNA array analyses emphasize the heterogenous nature of chondrosarcoma as no single transcript was systematically up‐ or downregulated in all tumors analyzed. Among the interesting changes observed was upregulation of decorin mRNA in 7 of the 10 tumors analyzed. Further studies are needed to determine whether decorin plays a role in the pathogenesis of chondrosarcoma. The cDNA arrays also revealed discrepancies from Northern and RNase protection analyses in transcript levels of matrix components, emphasizing the need to validate cDNA array data with other techniques. © 2002 Wiley‐Liss, Inc.
Clinical use of serum TRA‐1‐60 as tumor marker in patients with germ cell cancer
Authors: Lajer Henrik , Daugaard Gedske , Andersson Anna‐Maria , Skakkebæk Niels Erik 
Published: October 2002

AbstractTRA‐1‐60 antigen has been related to the presence of embryonal germ cell carcinoma (EC) and carcinoma in situ. Our study further investigated the clinical efficacy of TRA‐1‐60 as a serum tumor marker for germ cell cancer in the testis. Three groups of patients with germ cell tumors were included: Group 1, 34 patients with disseminated disease (24 nonseminomatous germ cell tumors [NSGCT] and 10 seminomatous germ cell tumors [SGCT]); this group of patients were followed during the course of chemotherapy with measurements of TRA‐1‐60, HCG and AFP; Group 2, 28 patients with Stage I NSGCT (22 with embryonal carcinoma [EC]‐component and 6 without EC‐component, median follow‐up 15 months); and Group 3, 40 patients with Stage I pure SGCT (median follow‐up 15 months). Seventy‐eight percent of patients with disseminated EC‐positive NSGCT had increased levels of TRA‐1‐60 before chemotherapy. After chemotherapy, levels of TRA‐1‐60 had dropped significantly (p < 0.01). Levels of TRA‐1‐60 did not normalize in 15% of NSGCT and 30% of SGCT patients after chemotherapy. This was not associated with recurrent disease. Approximately one‐third of patients with Stage I NSGCT had increased values of TRA‐1‐60 during follow‐up without having a relapse. Contrary to earlier reports TRA‐1‐60 is not at present useful as a tumor marker in patients with germ cell tumors. Although detecting a few early relapses the rate of false positive elevations in the tumor marker makes it unreliable in the clinical setting. Our study did confirm that elevated levels of TRA‐1‐60 were present in ∼80% of patients with disseminated EC‐positive NSGCT before start of chemotherapy and chemotherapy induced a significant decrease in levels of TRA‐1‐60. Thus, the TRA‐1‐60 antigen might still prove clinically useful provided that the reliability of the assay can be increased. © 2002 Wiley‐Liss, Inc.
Desferrioxamine enhances aids‐associated Kaposi's sarcoma tumor development in a xenograft model
Authors: Simonart Thierry , Boelaert Johan R. , Andrei Graciela , van den Oord Joost J. , Degraef Chantale , Hermans Philippe , Noel Jean‐Christophe , Van Vooren Jean‐Paul , Heenen Michel , De Clercq Erik , Snoeck Robert 
Published: October 2002

AbstractIron is suspected to be involved in the induction and/or progression of various human tumors. More particularly, we have previously shown that iron may be involved in the pathogenesis of Kaposi's sarcoma (KS). We have also shown that the iron chelator desferrioxamine (DFO) has a potent anti‐KS activity in vitro, suggesting that it may represent a potential therapeutic approach for the treatment of KS. The present study was designed to investigate the effect of DFO on the growth of human KS xenografts in immunodeficient mice. Unexpectedly, we found that mice treated with DFO (400 mg/kg, 3 times weekly) (n = 30) exhibited a marked enhancement of tumor growth compared with control mice (n = 33) (230 ± 134 mm2 versus 143 ± 70 mm p < 0.01). No enhancement of tumor growth was seen in mice treated with iron‐saturated DFO. At least 2 findings suggest that this paradoxic pro‐KS activity occurred independently of mice iron stores. First, treatment with DFO had only a marginal effect on ferritin and hematocrit levels. Second, induction of effective iron depletion by an iron‐poor diet (6.7 mg iron/kg diet) (n = 23) did not have a deleterious effect on the growth of the KS xenografts. The lesions obtained from the DFO‐treated animals exhibited a significantly decreased apoptotic index (p < 0.05), indicating that some antiapoptotic mechanism induced by DFO may be operating in vivo to favour tumor growth. In conclusion, our data show that DFO has a stimulatory effect on KS growth in imunodeficient mice, suggesting that this drug is not indicated in patients with KS. © 2002 Wiley‐Liss, Inc.
Heregulin inhibits proliferation via ERKs and phosphatidyl‐inositol 3‐kinase activation but regulates urokinase plasminogen activator independently of these pathways in metastatic mammary tumor cells
Authors: Puricelli Lydia , Proiettii Cecilia J. , Labriola Leticia , Salatino Mariana , Balañá María E. , Ghiso Julio Aguirre , Lupu Ruth , Pignataro Omar P. , Charreau Eduardo H. , Bal de Kier Joffé Elisa , Elizalde Patricia V. 
Published: October 2002

AbstractHeregulin (HRG) and type I receptor tyrosine kinase (RTK) expression was investigated in the highly invasive and metastatic LM3 cell line, our previously described model of metastasis for mammary cancer (Bal de Kier Joffe et al. [1986] Invasion Metastasis 6:302–12; Urtreger et al. [1997] Int J Oncol 11:489–96). Although LM3 cells do not express HRG, they exhibit high levels of ErbB‐2 and ErbB‐3 as well as moderate expression of ErbB‐4. Addition of exogenous HRGβ1 resulted in inhibition of both proliferation and migration of LM3 cells. HRGβ1 was also able to decrease the activity of urokinase‐type plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP‐9), 2 key enzymes in the invasion and metastatic cascade. HRGβ1 treatment of LM3 cells induced tyrosine phosphorylation of ErbB‐2, ErbB‐3 and ErbB‐4 as well as the formation of ErbB‐2/ErbB‐3 and ErbB‐2/ErbB‐4 heterodimers. Assessment of the signaling pathways involved in HRGβ1 action indicated that the addition of HRGβ1 to LM3 cells resulted in activation of phosphatidylinositol 3‐ kinase (PI‐3K) and in strong induction of the association of the p85 subunit of PI‐3K with ErbB‐3. HRGβ1 also caused the rapid activation of ERK1/ERK2 and Stat3 and Stat5 (signal transducers and activators of transcription [STAT]). This is the first demonstration of the ability of HRGβ1 to activate STATs in mammary tumor cells. Blockage of PI‐3K activity with its chemical inhibitor wortmannin, or of MEK1/ERKs activity with PD98059, resulted in suppression of the ability of HRGβ1 to inhibit LM3 cell growth. Notwithstanding the suppression of these 2 signaling pathways, HRGβ1 still proved capable of inhibiting uPA activity. Therefore, our results provide evidence that signaling pathways involved in HRGβ1‐induced proliferation appear to be distinct from those involved in HRGβ1 regulation of uPA, a protease that plays a pivotal role in invasion and metastasis. © 2002 Wiley‐Liss, Inc.
Incidence and survival of squamous cell carcinoma of the tongue in Scandinavia, with special reference to young adults
Authors: Annertz Karin , Anderson Harald , Biörklund Anders , Möller Torgil , Kantola Saara , Mork Jon , Olsen Jörgen H. , Wennerberg Johan 
Published: October 2002

AbstractIn several countries, increased incidence of squamous cell carcinoma (SCC) of the tongue in young adults has been suspected during the last decades. Some reports indicate a lower survival rate for young patients compared to older patients. In other reports, there has not been any considerable difference in survival when comparing young adults to older patients, whereas some authors have shown better survival for young adults. This disease is rare in young adults, and early reports were based on comparable small numbers and selected patients. Our aim was first to perform a population‐based study to determine if an increased incidence in SCC of the tongue could be verified in a larger population comprising the Scandinavian countries Denmark, Finland, Sweden and Norway. A second aim was to determine survival rates for young adults compared to older patients. The material was based on the annual cancer incidence and survival reports from the Scandinavian cancer registries. The study period was 1960–1994. During that period, 5,024 SCCs of the tongue were reported. Of these, 276 (5.5%) were young adults (20–39 years). The incidence increased at all ages except for women 65–79 years old. The increase was most pronounced in young adults: 0.06–0.32 for men and 0.03–0.19 for women, counted by 100,000 person‐years. Relative survival was significantly better for young adults compared to older patients. © 2002 Wiley‐Liss, Inc.