bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between depressive symptomatology and the subcortical brain syndrome in dementia
Authors: Lind K. , Edman Å. , Karlsson I. , Sjögren M. , Wallin A.
Published: October 2002

Objectives

The aim of the present study was to elucidate a possible relationship between depressive symptomatology and regional brain symptomatology in demented patients.

Methods

170 consecutive inpatients were studied. They suffered from Alzheimer's disease (103 patients), vascular dementia (48 patients), or frontotemporal dementia (19 patients). The patients underwent a neuropsychiatric investigation, which included assessments of (1) depression, and (2) regional brain symptomatology. Depressive symptomatology was assessed as presence of (a) depressed mood, and (b) anxiety. In the further statistical analysis, the presence of depressed mood and/or anxiety was also evaluated. The principle of the regional symptom analysis was the successive aggregation of observable symptom variables, leading to the final determination of four possible regional brain syndromes (frontal, subcortical, parietal and global), by way of the Stepwise comparative status analysis (STEP). The possible correlations between regional brain symptomatology and depressive symptomatology were analysed by means of (a) χ2 statistics, and (b) a logistic regression analysis in which confounding factors were included (age, degree of dementia, duration).

Results

The subcortical syndrome correlated with depressed mood (χ2, p = 0.002; logistic regression, p = 0.002). A negative correlation was noted between the parietal syndrome and depressed mood (p = 0.010 and p = 0.013, respectively). No other significant correlations between presence of regional brain syndrome and presence of depressive symptomatology could be seen.

Conclusions

Demented patients with a clinically established subcortical dysfunction appear to be more susceptible to depressive symptomatology. The results of this study also suggest that posterior brain dysfunction in dementia is not correlated with depressive symptomatology. Copyright © 2002 John Wiley & Sons, Ltd.
A study of premorbid personality and behavioural and psychological symptoms of dementia in nursing home residents
Authors: Low Lee‐Fay , Brodaty Henry , Draper Brian
Published: October 2002

Objective

To investigate the relationship between pre‐morbid personality and behavioural and psychological symptoms of dementia (BPSD).

Methods

We studied 58 subjects with dementia and depression and/or psychosis residing in 11 Sydney nursing homes cross‐sectionally. Informal caregivers completed ratings of residents' pre‐morbid personality on the NEP Five‐Factor Inventory (NEO‐FFI). Information on BPSD was obtained using the BEHAVE‐AD.

Results

Higher neuroticism was predictive of delusions; higher agreeableness of hallucinations, aggressiveness, affective disturbance and overall behavioural disturbance; and higher openness of affective disorder.

Conclusion

Our findings are inconsistent with previous research and clinical experience. Prospective studies are needed to clarify the association between personality and behavioural disturbance in dementia. Copyright © 2002 John Wiley & Sons, Ltd.
Telluronium ylides in cyclopropanation and catalytic olefination
Authors: Tang Yong , Ye Song , Huang Zheng‐Zheng , Huang Yao‐Zeng
Published: October 2002

Telluronium ylides are versatile reagents for cyclopropanation reaction and Wittig‐type olefination. This review outlines the recent development in stereoselectivity of ylide cyclopropanation and catalytic olefination in our group. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:463–466, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10076
Does prospective payment reduce inpatient length of stay?
Authors: Norton Edward C. , Van Houtven Courtney Harold , Lindrooth Richard C. , Normand Sharon‐Lise T. , Dickey Barbara
Published: October 2002

A change in payment mechanism for inpatient care from per diem to per episode creates two incentives – a marginal and an average price effect – to change length of stay. The decrease in marginal price per day to zero should reduce the length of stay, while an increase in average price per inpatient stay should increase the length of stay. This study uses data from a natural experiment to estimate both marginal and average price elasticities, and to test whether the length of stay falls after the introduction of prospective payment in a sample of 8509 severely mentally ill patients. We estimate that the marginal price elasticity is zero, but the average price elasticity is between 0.16 and 0.20. The results were generally robust for short‐ and long stayers, and for persons admitted early and late after the change in payment mechanism. The model controlled for hospital fixed effects and individual random effects. Copyright © 2002 John Wiley & Sons, Ltd.
Chemotherapy with or without radiotherapy in patients with locoregionally recurrent nasopharyngeal carcinoma
Authors: Wong Zee‐Wan , Tan Eng‐Huat , Yap Swee‐Peng , Tan Terence , Leong Swan‐Swan , Fong Kam‐Weng , Wee Joseph
Published: October 2002

Background

Treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) is challenging because of prior radiotherapy, morbidities from disease recurrence, and limited therapeutic options available.

Methods

A retrospective study of patients with locoregionally recurrent NPC.

Result

Between March 1994 and December 1999, there were 42 patients; most were Chinese (98%) men (81%) with undifferentiated NPC (86%). A repeat course of radiotherapy was feasible in 20 patients and given concurrently with cisplatin followed by adjuvant cisplatin/5‐fluorouracil (PF) (group 1). The remaining 22 (group 2) received palliative chemotherapy (PF) with a response rate of 50%. Significant morbidities resulted from cranial nerve palsies. The 2‐year progression‐free survival of patients in group 1 was expectedly better (58% vs 38%). Six (14%) developed systemic metastases at 12 months (median) from first recurrence.

Conclusion

Concurrent chemoradiotherapy for locoregional recurrent NPC seems promising. The morbidity experienced resulted from locoregional disease with few progressing to develop systemic involvement. © 2002 Wiley Periodicals, Inc. Head Neck 24: 549–554, 2002
Computer assisted analysis of the microvasculature in metastasized and nonmetastasized squamous cell carcinomas of the tongue
Authors: Hannen Egied J. M. , van der Laak Jeroen A. W. M. , Manni Johannes J. , Freihofer Hans Peter M. , Slootweg Piet J. , Koole Ronald , de Wilde Peter C. M.
Published: October 2002

Background

Quantification of microvessels in solid malignancies is regarded as a potential test to predict their clinicobiologic behavior. However, discordant results have been reported for head and neck cancer that may be explained by varying methods.

Methods

In this retrospective study, we therefore quantified the microvasculature in 20 nonmetastasized and 20 metastasized squamous cell carcinomas of the tongue, using recently developed methods. For immunohistochemical visualization of the vessels, we used anti‐CD34 with a signal amplification step based on the catalyzed deposition of biotinylated tyramine. This protocol results in enhanced staining quality compared with standard protocols. For each tumor, a representative tissue section was systematically sampled with 40 to 60 standardized test fields. True color image analysis system was used to measure microvessel density (MVD) and to obtain additional information with regard to size categories of vessels.

Results

Remarkably, in the group of nonmetastasized tumors, the MVD was greater than in the metastasized tumors (p = .007). However, the microvessels with a diameter in the range of 10 to 15 μm predominated in the group of metastasized tongue carcinomas (p = .03). A logistic regression model based on the percentage of vessels smaller than 5 μm, classified 85% of patients with a metastasized tumor correctly and 75% of patients with a nonmetastasized tumor, independently of the clinical stage of the tumor.

Conclusions

These results suggest that only vessels with a diameter larger than 10 μm, consistent with functional vessels, play a role in the process of metastasis. Further research more specifically into structural and functional characterization of blood and lymphatic vessels might help provide more insight into the relationship between microvasculature and the pathogenesis of metastasis in tongue carcinomas. © 2002 Wiley Periodicals, Inc. Head Neck 24: 643–650, 2002
Performance of a polymer electrolyte fuel cell for automotive applications
Authors: Yoshikawa Hiroo , Hishinuma Yukio , Chikahisa Takemi
Published: October 2002

The objectives of this study were to fabricate a self‐humidifying fuel cell stack of 10 cells with 104 cm2 cell areas humidified with water recovered at cathodes, and to measure and simulate the performance of the stack. This involves the simulation of a three‐dimensional model of the heat and mass transfer of the water and the gaseous reactants in the fuel cell components with a water‐cooling system. The results of the stack experiments indicated a maximum power of 250 kW at a current density of 0.5 A/cm2. The simulation showed good agreement with the actual performance of the stack. The performance of the self‐humidifying stack with a vapor‐permeating membrane is comparable to a conventional stack with external humidifiers, and it appears very effective in simplifying stack systems. The modeling analysis indicated that for the gas flow directions, at anode and cathode, a parallel flow is superior to a cross flow, and that one cooling cell is necessary for two to three generating cells in order to maintain the fuel cell temperature below 100 °C. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(6): 421–429, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10041
Optical measurement of thermal contact conductance between thin, waferlike solid samples by using laser AC heating and reflectance thermometry: Reconsideration of the loading method for the samples
Authors: Ohsone Yasuo
Published: October 2002

A noncontact optical technique for measuring the thermal contact conductance between two thin, waferlike solid samples was developed. In this technique, one solid surface is heated with a modulated laser beam; the corresponding temperature modulation of the other solid surface across their interface is monitored by using the reflectance of a probe laser beam. Each sample can become slightly bent if its edge is compressed by the sample holder, so the contact pressure between the samples (in the range of 0.8 to 10 MPa) was calculated by elastic and plastic numerical analyses. By using the calculated contact pressure, the correlation between contact pressure and thermal contact conductance could be determined more accurately. Also, the appropriate thickness of the glass plates used to fix the samples was derived by calculating the thickness where the local contact pressure is almost the same as the averaged pressure. © 2002 Wiley Periodicals, Inc. Heat Trans Asian Res, 31(6): 498–512, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/htj.10049
Verbal fluency facilitated by the cholinergic blocker, scopolamine
Authors: Pompéia S. , Rusted J. M. , Curran H. V.
Published: October 2002

This study was designed to explore putative facilitatory effects of low doses of scopolamine (SP) on phonemic (letter) and semantic (category) verbal fluency. A double‐blind, parallel‐group design was used with 36 subjects who completed a test battery before and 2 h after 0.6 mg or 1.2 mg of SP or placebo. Fluency measures included total number of words generated, clustering (the production of words within semantic or phonemic subcategories) and switching (the ability to shift efficiently to new subcategories). Low doses of scopolamine increased phonemic fluency, as has been shown previously. Semantic fluency was not increased by SP, although subjects treated with 1.2 mg of SP generated higher‐frequency words. SP did not affect clustering or switching. It is suggested that phonemic and semantic fluency reflect distinct cognitive processes. Copyright © 2002 John Wiley & Sons, Ltd.
Detection of endogenous lithium in neuropsychiatric disorders—a model for biological transmutation
Authors: Kurup Ravi Kumar , Kurup Parameswara Achutha
Published: October 2002

The 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

Background

Plasma 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.

Methods

Dopamine (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.

Conclusions

The 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

Antipsychotic 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

Rationale

The 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.

Objectives

To examine the effects of transdermal nicotine on inspection time.

Methods

Ten 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.

Results

The change in IT from baseline was significantly different in the nicotine condition, relative to placebo, at 3 h but not 1 or 6 h.

Conclusions

The 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

In 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

We 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

The 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

The 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

Chondrosarcoma 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

TRA‐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

Iron 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

Heregulin (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

In 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.
Subchronic toxicity of chloral hydrate on rats: a drinking water study
Authors: Poon R. , Nakai J. , Yagminas A. , Benoit F. , Moir D. , Chu I. , Valli V. E.
Published: October 2002

The subchronic toxicity of chloral hydrate, a disinfection byproduct, was studied in rats following 13 weeks of drinking water exposure. Male (262 ± 10 g) and female (190 ± 8 g) Sprague‐Dawley rats, ten animals per group, were administered chloral hydrate via drinking water at 0.2, 2, 20 and 200 ppm. Control animals received distilled water only. Gross and microscopic examinations, serum chemistry, hematology, biochemical analysis, neurogenic amine analysis and serum trichloroacetic acid (TCA) analysis were performed at the end of the treatment period. Bronchoalveolar fluids were collected at necropsy and urine specimens were collected at weeks 2, 6 and 12 for biochemical analysis. No treatment‐related changes in food and water intakes or body weight gains were observed. There were no significant changes in the weights of major organs. Except for a mild degree of vacuolation within the myelin sheath of the optic nerves in the highest dose males, there were no notable histological changes in the tissues examined. Statistically significant treatment‐related effects were biochemical in nature, with the most pronounced being increased liver catalase activity in male rats starting at 2 ppm. Liver aldehyde dehydrogenase (ALDH) was significantly depressed, whereas liver aniline hydroxylase activity was significantly elevated in both males and females receiving the highest dose. A dose‐related increase in serum TCA was detected in both males and females starting at 2 ppm. An in vitro study of liver ALDH confirmed that chloral hydrate was a potent inhibitor, with an IC50 of 8 µM, whereas TCA was weakly inhibitory and trichloroethanol was without effect. Analysis of brain biogenic amines was conducted on a limited number (n = 5) of male rats in the control and high dose groups, and no significant treatment‐related changes were detected. Taking into account the effect on the myelin sheath of male rats and the effects on liver ALDH and aniline hydroxylase of both males and females at the highest dose level, the no‐observed‐effect level (NOEL) was determined to be 20 ppm or 1.89 mg kg−1 day−1 in males and 2.53 mg kg−1 day−1 in females. This NOEL is ca. 1000‐fold higher than the highest concentration of chloral hydrate reported in the municipal water supply. Copyright © 2002 Crown in the right of Canada. Published by John Wiley & Sons, Ltd.
A Quick Guide to Accounting for Software and Web Sites
Authors: Munter Paul
Published: October 2002

In today's competitive environment, investing in technology is one of your firm's key strategies. But

what do the latest accounting rules require? © 2002 Wiley Periodicals, Inc.
Targeted disruption of hsf1 leads to lack of thermotolerance and defines tissue‐specific regulation for stress‐inducible Hsp molecular chaperones
Authors: Zhang Yan , Huang Lei , Zhang Jing , Moskophidis Demetrius , Mivechi Nahid F.
Published: October 2002

The rapid synthesis of heat shock proteins (Hsps) in cells subjected to environmental challenge is controlled by heat shock transcription factor‐1 (Hsf1). Regulation of Hsps by Hsf1 is highly complex and, in the whole organism, remains largely unexplored. In this study, we have used mouse embryo fibroblasts and bone marrow progenitor cells from hsf1−/− mice as well as hsp70.3‐lacZ knock‐in mice bred on the hsf1deficient genetic background (hsf1−/−‐hsp70.3+/−‐lacZ), to further elucidate the function of Hsf1 and its participation as a transcriptional activator of Hsp70 synthesis under normal or heat‐induced stress conditions in vitro and in vivo. The results revealed that heat‐induced Hsp70 expression in mouse tissue is entirely controlled by Hsf1, whereas its activity is not required for tissue‐specific constitutive Hsp70 expression. We further demonstrate that Hsf1 is critical for maintaining cellular integrity after heat stress and that cells from hsf1−/− mice lack the ability to develop thermotolerance. This deficiency is explained by the elimination of stress‐inducible Hsp70 and Hsp25 response in the absence of Hsf1 activity, leading to a lack of Hsp‐mediated inhibition of apoptotic cell death via both caspase‐dependent and caspase‐independent pathways. The pivotal role of the Hsf1 transactivator in regulating rapid synthesis of Hsps as a critical cellular defense mechanism against environmental stress‐induced damage is underlined. J. Cell. Biochem. 86: 376–393, 2002. © 2002 Wiley‐Liss, Inc.
Constitutive activation of met kinase in non‐small‐cell lung carcinomas correlates with anchorage‐independent cell survival
Authors: Qiao Hui , Hung Wesley , Tremblay Eric , Wojcik Joanna , Gui Jin , Ho Janet , Klassen Jennifer , Campling Barbara , Elliott Bruce
Published: October 2002

Lung cancer is currently the most frequent cause of cancer death in North America. Hepatocyte growth factor (HGF) and its receptor Met are frequently over‐expressed in non‐small‐cell lung carcinomas (NSCLC), but their potential role in tumor progression is not clearly known. To assess the role of HGF/Met signaling in lung carcinomas, we have examined the expression, activation status, and function of Met in NSCLC cell lines (n = 7), established from primary tumors or pleural fluids of cancer patients. We observed Met expression in three NSCLC cell lines, two of which exhibited constitutive tyrosine‐phosphorylation of Met, and Met kinase activity. In addition, the observed constitutive activation of Met was sustained under anchorage‐independent conditions, and correlated with phosphatidyl inositol 3‐kinase‐dependent cell survival. Immunoreactive HGF‐like protein was secreted by two Met‐positive and two Met‐negative NSCLC cell lines. However HGF activity, as determined by the ability to induce cell scattering and tyrosine‐phosphorylation of Met in reporter cell lines, was detected in conditioned medium from only one Met‐negative NSCLC cell line: none of the conditioned media from Met‐expressing NSCLC cell lines showed detectable HGF activity. Thus, constitutive activation of Met in NSCLC cell lines may occur at least in part through intracrine, or HGF‐independent mechanisms. Interestingly, additional paracrine stimulation with exogenous recombinant HGF was required for DNA synthesis and correlated with increased activation of ERK1/2 in all Met‐positive NSCLC cell lines, regardless of the basal activation status of Met. These findings indicate that a medium level of constitutive activation of Met occurs in some NSCLC cell lines, and correlates with survival of detached carcinoma cells; whereas additional paracrine stimulation by recombinant HGF is required for DNA synthesis. Thus constitutive and paracrine activation of Met may provide complementary signals that promote survival and proliferation, respectively, during tumor progression of NSCLC. J. Cell. Biochem. 86: 665–677, 2002. © 2002 Wiley‐Liss, Inc.
Expression of a releasable form of annexin II by human keratinocytes
Authors: Karimi‐Busheri Feridoun , Marcoux Yvonne , Tredget Edward E. , Li Liang , Zheng Jing , Ghoreishi Mina , Weinfeld Michael , Ghahary Aziz
Published: October 2002

Annexin II is a multifunctional calcium‐dependent phospholipid binding protein whose presence in epidermis has previously been reported. However, like other members of annexin family, annexin II has been regarded as either an intracellular protein or associated with the cellular membrane. Here, we report the presence of a releasable annexin II and p11, two monomers of annexin II tetramer, in keratinocyte‐conditioned medium (KCM). Proteins present in KCM were fractionated on a gel filtration column and following further evaluation, a releasable protein with apparent MW of 36 kDa was identified. Further characterization identified this protein as the p36 monomer of annexin II tetramer. The phospho‐tyrosine antibody did not visualize this protein as the phosphorylated form of p36. Several experiments were conducted to examine whether this protein is soluble or associated with keratinocyte cell membranes in the conditioned medium. A centrifugation of conditioned medium was not able to bring this protein down into the pellet. Surprisingly, the results of Western analysis identified p36 and p11, two monomers of the annexin II tetramer, in conditioned medium derived from either keratinocytes cultured alone or keratinocytes co‐cultured with fibroblasts. In contrast to the keratinocyte‐conditioned medium in which annexin II was easily detectable, both monomers were barely detectable in conditioned medium collected from dermal fibroblasts. This finding was in contrast to the cell lysates in which p36 was detectable in both keratinocytes and fibroblasts. However, the amount of this protein was markedly higher in keratinocyte lysate relative to that of dermal fibroblasts. Conditioned medium derived from keratinocyte established from adult showed a higher level of annexin II compared to that of keratinocytes established from newborn babies. The expression of p11 seems to increase with differentiation of keratinocytes derived from either adult or newborn skin samples. When the site of annexin synthesis in human skin was examined by immunohistochemical staining, the antibody for p36 localized the annexin to the keratinocyte cell members in the basal and suprabasal keratinocytes. In conclusion, Western blot detection of both p36 and p11 in conditioned medium from skin cells revealed that human keratinocytes, but not fibroblasts, express a releasable monomer form of annexin II which is regulated by differentiation status of keratinocytes. This finding is consistent with the localization of annexin II detected by immunohistochemical staining. J. Cell. Biochem. 86: 737–747, 2002. © 2002 Wiley‐Liss, Inc.
Involvement of PI3‐kinase and its association with c‐Src in PTH‐stimulated rat enterocytes
Authors: Gentili Claudia , Morelli Susana , Russo de Boland Ana
Published: October 2002

Phosphoinositide‐3‐kinase (PI3K) is a lipid kinase, which phosphorylates the D3 position of phosphoinositides, and is known to be activated by a host of protein tyrosine kinases. PI3K plays an important role in mitogenesis in several cell systems. However, whether parathyroid hormone (PTH) affects the activity and functional roles of PI3K in intestinal cells remain to be determined. The objective of this study was to identify and characterize the PI3K pathway, and its relation to other non‐receptor tyrosine kinases in mediating PTH signal transduction in rat enterocytes. PTH dose‐ and time‐dependently increased PI3K activity with a peak occurring at 2 min. The tyrosine kinase inhibitor genistein, c‐Src inhibitor PP1 and two structurally different inhibitors of PI3K, LY294002 and wortmannin, suppressed PI3K activity dependent on PTH. Co‐immunoprecipitation analysis showed a constitutive association between c‐Src and PI3K, which was enhanced by PTH treatment, suggesting that the cytosolic tyrosine kinase forms an immunocomplex with PI3K probably via the N‐SH2 domain of the p85α regulatory subunit. In response to PTH, tyrosine phosphorylation of p85α was enhanced, effect that was abolished by PP1, the inhibitor of c‐Src kinase. PTH causes a rapid (0.5–5 min) phosphorylation of Akt/PKB, effect that was abrogated by PI3K inhibitors, indicating that in rat enterocytes, PI3K is an upstream mediator of Akt/PKB activation by PTH. We report here that PI3K is also required for PTH activation of the mitogen‐activated protein kinases ERK1 and ERK2. Taken together, the present study demonstrate, for the first time, that PTH rapidly and transiently stimulates PI3K activity and its down effector Akt/PKB in rat enterocytes playing c‐Src kinase a central role in PTH‐dependent PI3K activation and that PI3K signaling pathway contributes to PTH‐mediated MAPK activation. J. Cell. Biochem. 86: 773–783, 2002. © 2002 Wiley‐Liss, Inc.
Runx1, c‐Myb, and C/EBPα couple differentiation to proliferation or growth arrest during hematopoiesis
Authors: Friedman Alan D.
Published: October 2002

Immature hematopoietic precursors proliferate as they differentiate, whereas terminal differentiation is associated with cell cycle arrest. Stem cell lineage commitment and subseqent maturation is regulated predominantly by transcription factors. Runx1 and c‐Myb act in early stage hematopoietic cells to both stimulate proliferation and differentiation, whereas C/EBPα, and perhaps other C/EBP family members, block progression from G1 to S and induce terminal maturation. Coupling of differentiation to either proliferation or growth arrest by transcription factors is likely an important regulatory mechanism in multiple developmental systems. J. Cell. Biochem. 86: 624–629, 2002. © 2002 Wiley‐Liss, Inc.