bluuebunny/crossref_metadata_2025 huggingface dataset:
Wage policy in the health care sector: a panel data analysis of nurses' labour supply
Authors: Askildsen Jan Erik , Baltagi Badi H. , Holmås Tor Helge
Published: August 2003

Shortage of nurses is a problem in several countries. It is an unsettled question whether increasing wages constitute a viable policy for extracting more labour supply from nurses. In this paper we use a unique matched panel data set of Norwegian nurses covering the period 1993–1998 to estimate wage elasticities. The data set includes detailed information on 19 638 individuals over 6 years totalling 69 122 observations. The estimated wage elasticity after controlling for individual heterogeneity, sample selection and instrumenting for possible endogeneity is 0.21. Individual and institutional features are statistically significant and important for working hours. Contractual arrangements as represented by shift work are also important for hours of work, and omitting information about this common phenomenon will underestimate the wage effect. Copyright © 2003 John Wiley & Sons, Ltd.
Why do the sick not utilise health care? The case of Zambia
Authors: Hjortsberg Catharina
Published: August 2003

When ill the individual faces the options of seeking health care, using self‐medication or doing nothing. In an economic perspective, an individual's propensity to utilise health care is determined by the costs of utilisation and the perceived benefits of health care. The propensity to utilise health care may hence be expected to vary between individuals. In this paper we attempt on the one hand to determine what factors influence sick individuals' propensity to seek health care at a health facility or use self‐medication (or do nothing), and on the other hand attempt to determine the factors that influence the magnitude of their expenditures for health care, in particular what other factors than just health status influence utilisation. For the empirical analysis, data, covering 9700 individuals, from the 1998 Living Conditions Monitoring Survey (LCMS) is used. We use a Multinomial Logit selection model to estimate the equation, which allows us to analyse health‐care utilisation through two separate processes, the decision to seek care and the magnitude of expenditures incurred. In general, we find that the individuals are influenced by income, insurance, type of illness and access variables such as distance and owning a vehicle. Copyright © 2003 John Wiley & Sons, Ltd.
Economics of self‐medication: theory and evidence
Authors: Chang Fwu‐Ranq , K. Trivedi Pravin
Published: August 2003

A pervasive phenomenon in developing countries is that self‐prescribed medications are purchased from drug vendors without professional supervision. In this article we develop a model of self‐medicating behavior of a utility‐maximizing consumer who balances the benefits and risks of self‐medication. The empirical investigation focuses on the role of income and health insurance on the use of self‐medication. Our data are from the World Bank's Living Standards Measurement Survey of Vietnam, 1997–1998. The results show that self‐medication is an inferior good at high income levels and a normal good at low income levels, and it shows a strong and robust negative insurance effect. Copyright © 2003 John Wiley & Sons, Ltd.
An improved description of soil hydraulic and thermal properties of arctic peatland for use in a GCM
Authors: Hall Robin L. , Huntingford Chris , Harding Richard J. , Lloyd Colin R. , Cox Peter M.
Published: August 2003

The UK Meteorological Office Surface Exchange Scheme (MOSES), which is currently implemented within Version 3 of the Hadley Centre GCM, was tested for an arctic peatland site in northern Finland (Kevo). This implementation of MOSES incorporated a new depth‐dependent parameterization of the thermal and hydraulic properties of peat with parameter values derived from measurements reported in the literature. The effect of increasing the number of model soil layers from four to 13 shallower layers was also investigated. Driving data were used that were collected during June, when the peat was still frozen below about 80 mm, to September 1997.

Best model performance was given by the 13‐layer, depth‐dependent parameter description for both surface heat fluxes and soil temperatures. The simulated heat fluxes compared well with measurements, but simulated surface temperatures were too high. In preliminary runs the simulated distribution of unfrozen water in the soil was also unrealistic. In particular the model was unable to predict the rapid transition to above‐freezing conditions that occurred throughout the soil profile about the second week in July. Adjusting a parameter (k) of the soil‐freezing curve, which for peat can be used as a fitting parameter, produced a big improvement in the soil temperature profiles. A more accurate simulation of the freezing and thawing behaviour of organic soils requires that the processes that are hidden in the modified value of k are explicitly represented. Copyright © 2003 John Wiley & Sons, Ltd.
Determination and integration of appropriate spatial scales for river basin modelling
Authors: Booij M. J.
Published: August 2003

Appropriate spatial scales of dominant variables are determined and integrated into an appropriate model scale. This is done in the context of the impact of climate change on flooding in the River Meuse in Western Europe. The objective is achieved by using observed elevation, soil type, land use type and daily precipitation data from several sources and employing different relationships between scales, variable statistics and outputs. The appropriate spatial scale of a key variable is assumed to be equal to a fraction of the spatial correlation length of that variable. This fraction was determined on the basis of relationships between statistics and scale and an accepted error in the estimation of the statistic of 10%. This procedure resulted in an appropriate spatial scale for precipitation of about 20 km in an earlier study. The application to river basin variables revealed appropriate spatial scales for elevation, soil and land use of respectively 0·1, 5·3 and 3·3 km. The appropriate model scale is determined by multiplying the appropriate variable scales with their associated weights. The weights are based on SCS curve number method relationships between the peak discharge and some specific parameters like slope and curve number. The values of these parameters are dependent on the scale of each key variable. The resulting appropriate model scale is about 10 km, implying 225–250 model cells in an appropriate model of the Meuse basin meant to assess the impact of climate change on river flooding. The usefulness of the appropriateness procedure is in its ability to assess the appropriate scales of the individual key variables before model construction and integrate them in a balanced way into an appropriate model scale. Another use of the procedure is that it provides a framework for decisions about the reduction or expansion of data networks and needs. Copyright © 2003 John Wiley & Sons, Ltd.
Sediment sources and transport pathways in a rural catchment, Herefordshire, UK
Authors: Gruszowski K. E. , Foster I. D. L. , Lees J. A. , Charlesworth S. M.
Published: August 2003

The relative significance of primary and secondary suspended sediment sources has been identified in a small (15 km2) agricultural catchment through the application of a linear unmixing model using mineral magnetic, geochemical and radionuclide signatures of fine sediments. Roads appear to be important as a secondary source of suspended sediment and in the conveyance of topsoils to the river channel. Roads also alter the source signatures of sediment in transport, especially that derived from agricultural topsoils. Modelling suggests thatc. 30% of the suspended sediment collected from suspended sediment traps in the River Leadon were derived from, or transported via, roads. Relative contributions from primary sources ofc. 43% andc. 27% were estimated from a combined (subsoil and channel bank) subsurface source, and a combined (arable and grassland) topsoil source, respectively. Copyright © 2003 John Wiley & Sons, Ltd.
Simultaneous onset of acute inflammatory response, sepsis‐like symptoms and intestinal mucosal injury after cancer chemotherapy
Authors: Tsuji Eiichi , Hiki Naoki , Nomura Sachiyo , Fukushima Ryoji , Kojima Jun‐ichi , Ogawa Toshihisa , Mafune Ken‐ichi , Mimura Yoshikazu , Kaminishi Michio
Published: August 2003

Chemotherapy is 1 method for the treatment of cancer, but serious side effects can sometimes limit the dosage given. Mild fever and diarrhea are common side effects of cancer chemotherapy. Gastrointestinal injury induced by chemotherapeutic agents may result in bacterial/endotoxin translocation from the gut into the systemic circulation. An experimental study was therefore conducted to clarify the effect of systemic chemotherapeutic agents on gastrointestinal barrier function. Male Wistar rats were divided into a 5‐fluorouracil (5‐FU) group (100 mg/kg/day for 4 days; n = 27) and a control group (n = 5). All rats were fasted and central venous catheterization was performed for total parenteral nutrition and blood sampling. Intestinal tissue was also sampled for pathological examination. Plasma levels of interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα) were determined by ELISA, bacterial translocation was quantified by lymph node culture and plasma endotoxin content of portal blood was measured by the Limulus‐amebocyte‐lysate test. In the 5‐FU group on day 4, a proportion of rats exhibited severe watery diarrhea (73.9%) and occasional vomiting (86.2%). The levels of plasma TNFα and IL‐6 were seen to increase, peaking at day 6 (IL‐6, 350.0 ± 67.8 pg/ml; TNFα, 26.1 ± 3.2 pg/ml). The pathological findings also changed on day 4. On day 6, 90% of the rats in the 5‐FU group showed dramatic sepsis‐like manifestations, whereas the control group did not. Within the 5‐FU group, only at day 6 was bacterial translocation in the rat mesenteric lymph nodes or significantly elevated levels of endotoxin evident. These results suggest that bacterial/endotoxin translocation might cause sepsis‐like manifestations after systemic chemotherapy. © 2003 Wiley‐Liss, Inc.
Resveratrol analog (Z)‐3,5,4′‐trimethoxystilbene is a potent anti‐mitotic drug inhibiting tubulin polymerization
Authors: Schneider Yann , Chabert Philippe , Stutzmann Jeanne , Coelho David , Fougerousse André , Gossé Francine , Launay Jean‐François , Brouillard Raymond , Raul Francis
Published: August 2003

Resveratrol (3,5,4′‐trihydroxystilbene) a natural polyphenol present in medicinal plants, grapes and wines, has potent chemopreventive properties on intestinal carcinogenesis. A methylated derivative (Z‐3,5,4′‐trimethoxystilbene: R3) was synthesized. R3 at 0.3 μM exerted a 80% growth inhibition of human colon cancer Caco‐2 cells and arrested growth completely at 0.4 μM (R3 was 100‐fold more active than resveratrol). The cis conformation of R3 was also 100‐fold more potent than the trans isomer. R3 (0.3 μM) caused cell cycle arrest at the G2/M phase transition. The drug inhibited tubulin polymerization in a dose‐dependent manner (IC50= 4 μM), and it reduced also by 2‐fold ornithine decarboxylase and s‐adenosylmethionine decarboxylase activities. This caused the depletion of the polyamines, putrescine and spermidine, which are growth factors for cancer cells. R3 inhibited partially colchicine binding to its binding site on tubulin, indicating that R3 either partially overlaps with colchicine binding or that R3 binds to a specific site of tubulin that is not identical with the colchicine binding site modifying colchicine binding by allosteric influences. The resveratrol derivative (Z)‐3,5,4′‐trimethoxystilbene (R3) is an interesting anti‐mitotic drug that exerts cytotoxic effects by depleting the intracellular pool of polyamines and by altering microtubule polymerization. Such a drug may be useful for the treatment of neoplastic diseases. © 2003 Wiley‐Liss, Inc.
Stromelysin‐3 expression is an early event in human oral tumorigenesis
Authors: Soni Shilpi , Mathur Meera , Shukla Nootan K. , Deo Suryanarayan V.S. , Ralhan Ranju
Published: August 2003

Stromelysin‐3 (ST3/MMP11) is associated with human tumour progression. To determine the clinical significance of ST3 in oral tumorigenesis, its expression was analysed in different stages of tobacco‐associated oral cancer. Immunohistochemical analysis of ST3 expression in 79 oral precancerous lesions, 177 SCCs and 35 histologically normal oral tissues was carried out and corroborated by immunoblotting and RT‐PCR. ST3/MMP11 protein expression was observed in 45/79 (57%) precancerous lesions [28/48 (58%) with hyperplasia and 17/31 (55%) with dysplasia] and in 123/177 (70%) oral SCCs. In precancerous lesions, ST3 expression was higher compared to normal oral tissues (p = 0.000) and associated with MVD (p = 0.05), a marker for angiogenesis. ST3 was also expressed in cells cultured from precancerous and cancerous lesions that had undergone epithelial‐to‐mesenchymal transition. In oral cancer patients, ST3 positivity was associated with lymph node involvement (p = 0.025) and increased intratumoral MVD (p = 0.009). Ninety‐eight oral SCC patients were followed up for a period of 94 months (median 22.5 months). Kaplan‐Meier survival analysis showed that ST3 expression was not a significant prognostic indicator. ST3 expression in oral hyperplastic and dysplastic lesions suggests its association with progression of phenotypic alterations acquired early during the malignant transformation pathway of oral epithelium and implicates it not only in angiogenesis and invasion but also in tumorigenesis. Thus, ST3 may serve as a potential target for developing molecular therapeutics for early intervention in oral tumorigenesis. © 2003 Wiley‐Liss, Inc.
Increased TIA‐1 gene expression in the tumor microenvironment after locoregional administration of tumor necrosis factor‐α to patients with soft tissue limb sarcoma
Authors: Mocellin Simone , Provenzano Maurizio , Lise Mario , Nitti Donato , Rossi Carlo Riccardo
Published: August 2003

Although it is known that TNF‐α is effective in the treatment of advanced solid tumors such as melanoma and soft tissue sarcoma, the molecular mechanism underlying its anticancer activity remains unclear. Nineteen patients with locally advanced soft tissue sarcoma underwent isolated limb perfusion with doxorubicin alone (n = 9) or combined with TNF‐α (n = 10). mRNA from posttreatment tumor biopsies was linearly amplified to create an RNA bank. The transcriptional levels of 22 genes were analyzed by qrt‐PCR. On the basis of in vivo findings, we investigated the in vitro gene expression of different cell types representing the tumor microenvironment cell population. TIA‐1, which encodes an RNA‐binding protein with translation‐regulatory functions, was the only gene differentially expressed between the 2 study groups, its transcriptional levels in tumor biopsies from patients receiving TNF‐α being higher than in those from patients not given the cytokine. In vitro, TIA‐1 was expressed by endothelial cells, fibroblasts, CTLs and NK cells. TNF‐α significantly upregulated TIA‐1 gene expression only in endothelial and NK cells. Furthermore, TIA‐1 transcriptional levels significantly increased during NK activity, which was enhanced by TNF‐α. These findings support the hypothesis that TNF‐α‐induced TIA‐1 overexpression might sensitize endothelial cells to proapoptotic stimuli present in the tumor microenvironment and enhance NK cell cytotoxic activity against cancer cells. © 2003 Wiley‐Liss, Inc.
Expression of CCL5/RANTES by Hodgkin and Reed‐Sternberg cells and its possible role in the recruitment of mast cells into lymphomatous tissue
Authors: Fischer Marie , Juremalm Mikael , Olsson Niclas , Backlin Carin , Sundström Christer , Nilsson Kenneth , Enblad Gunilla , Nilsson Gunnar
Published: August 2003

HL is a malignant lymphoma characterized by a small number of malignant HRS cells among a major population of infiltrating reactive cells, e.g., lymphocytes and eosinophils. We previously reported that mast cells are present in HL‐affected lymph nodes and therein are the predominant CD30L‐expressing cells. The CD30L expressed on mast cells is functionally active and can provide stimulatory signals to HRS cells. Thus, mast cells constitute an important portion of the infiltrating reactive cells that contribute to tumor progression in HL. Control of the recruitment of this previously unrecognized cell and its interactions with tumor cells are essentially unknown. To elucidate if mast cells might be specifically attracted to the tumor area by chemokines produced by HRS cells, we investigated chemokine expression in HL cell lines and in vivo. By RNase protection assay, mRNA expression of several chemokines could be detected in the cell lines. Despite the heterogeneous expression profile exhibited by the cell lines, 4 of 5 expressed CCL5 (RANTES) mRNA. RT‐PCR and immunohistochemistry confirmed expression of CCL5 in vivo. Furthermore, secreted CCL5 was detected in conditioned media from 3 of the cell lines. In a migration assay, we found that CCL5 present in conditioned medium could induce mast cell migration. Taken together, our results suggest that CCL5 produced by HRS cells is one mechanism by which mast cells can be attracted into the tumor tissue in HL. © 2003 Wiley‐Liss, Inc.
Comparative genomic hybridization analysis of tonsillar cancer reveals a different pattern of genomic imbalances in human papillomavirus‐positive and ‐negative tumors
Authors: Dahlgren Liselotte , Mellin Hanna , Wangsa Danny , Heselmeyer‐Haddad Kerstin , Björnestål Linda , Lindholm Johan , Munck‐Wikland Eva , Auer Gert , Ried Thomas , Dalianis Tina
Published: August 2003

Our aim was to map and compare genomic imbalances in human papillomavirus (HPV)‐positive and ‐negative squamous cell carcinomas of the tonsil. Twenty‐five primary carcinomas were analyzed by comparative genomic hybridization. Fifteen (60%) were found to be HPV‐positive by PCR, and the majority were HPV‐16. There were statistically significant differences in the distribution of DNA gains and losses between the HPV‐positive and ‐negative samples. Eleven of 15 HPV‐positive samples (73%) showed gain on chromosome 3q24‐qter, while only 4/10 (40%) HPV‐negative samples had the same gain (p = 0.049). Furthermore, 4/10 (40%) HPV‐negative samples but no HPV‐positive samples had gain on chromosome 7q11.2‐q22 (p = 0.017). As expected, and similar to previous studies, patients with an HPV‐positive tumor had a statistically significantly better disease‐specific survival than patients with an HPV‐negative tumor (p = 0.002). The most common changes, e.g., gain on 3q or 8q, loss on 11q or 13 and loss on chromosome 7q in HPV‐negative tumors, did not have any influence on prognosis. However the number of cases in each subgroup was limited. © 2003 Wiley‐Liss, Inc.
Gastrointestinal stromal tumors: From a surgical to a molecular approach
Authors: Rossi Carlo Riccardo , Mocellin Simone , Mencarelli Roberto , Foletto Mirto , Pilati Pierluigi , Nitti Donato , Lise Mario
Published: August 2003

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. These tumors span a wide clinical spectrum from benign to malignant and have long been recognized for their nearly absolute resistance to chemotherapy and radiation treatment. We reviewed the worldwide experience on GIST diagnosis, prognosis and treatment and describe our own series. PubMed was searched for references using the terms gastrointestinal stromal tumor, GIST and gastrointestinal sarcoma. Recent reports were given emphasis because GIST is a novel clinical entity and older published work on gastrointestinal sarcomas might be contaminated with other histologic tumor types. At present, surgery is the standard treatment for primary resectable GIST. To increase the activity of conventional chemotherapeutic agents, locoregional therapies are being implemented in the clinical setting. A major breakthrough is the development of a new class of anticancer agents targeting tumor‐specific molecular abnormalities. Preliminary results on administration of imatinib mesylate, a signal transduction inhibitor, are particularly encouraging, showing potent activity of this drug against metastatic GIST. Molecular targeting of the critical pathogenetic mechanism underlying GIST might not only revolutionize the strategy to treat locally advanced and metastatic GIST but also improve disease control after macroscopically radical surgery. © 2003 Wiley‐Liss, Inc.
Mistletoe for cancer?
Authors: Ernst Eduard , Schmidt Katja , Steuer‐Vogt Miriam Katharina
Published: August 2003

Mistletoe extracts are widely used in the treatment of cancer. The results of clinical trials are however highly inconsistent. We therefore conducted a systematic review of all randomised clinical trials of this unconventional therapy. Eight databases were searched to identify all studies that met our inclusion/exclusion criteria. Data were independently validated and extracted by 2 authors and checked by the 3rd according to predefined criteria. Statistical pooling was not possible because of the heterogeneity of the primary studies. Therefore a narrative systematic review was conducted. Ten trials could be included. Most of the studies had considerable weaknesses in terms of study design, reporting or both. Some of the weaker studies implied benefits of mistletoe extracts, particularly in terms of quality of life. None of the methodologically stronger trials exhibited efficacy in terms of quality of life, survival or other outcome measures. Rigorous trials of mistletoe extracts fail to demonstrate efficacy of this therapy. © 2003 Wiley‐Liss, Inc.
Glycolysis and glucose transporter 1 as markers of response to hormonal therapy in breast cancer
Authors: Rivenzon‐Segal Dalia , Boldin‐Adamsky Swetlana , Seger Dalia , Seger Rony , Degani Hadassa
Published: August 2003

Estrogen plays a key role in the development and progression of breast cancer; hence, antiestrogens, such as tamoxifen, have a marked impact on the treatment and outcome of breast cancer patients. Estrogen‐induced growth requires continuous replenishment of energy, predominantly generated by glycolysis. Previous work from this laboratory demonstrated estrogen induction and tamoxifen inhibition of glycolysis in MCF7 human breast cancer cells in vitro (Furman et al., J Steroid Biochem Mol Biol 1992;43:189–95). We present here studies of estrogen vs. tamoxifen regulation of glycolysis in orthotopic MCF7 human breast cancer xenografts in vivo. In addition we investigated mediation of this metabolic regulation through glucose transporter 1, in the same cells, in vitro, as well as in 2 other hormone‐responsive human breast cancer cells. Tumor response and glycolysis were monitored noninvasively by means of magnetic resonance imaging and 13C spectroscopy, respectively. During estrogen‐stimulated tumor growth (from ≈0.5 to ≈1.3 cm3 in 10 days), the rate of glucose metabolism through glycolysis in vivo was high at 40 ± 4 μmole/g/min. However, treatment for 10 days with tamoxifen induced growth arrest and a concomitant decrease of 2‐fold in the rate of glycolysis. In congruence, glucose transporter 1 expression was stimulated by estrogen, reaching after 72 hr a 2‐ to 3‐fold higher level of expression relative to that in tamoxifen‐treated cells. Thus, estrogen‐induced changes in glycolysis appeared to be mediated via its regulation of glucose transporter 1 expression. The in vivo monitoring of glycolysis may serve as a tool to expose hormonal regulation of glucose transporter 1 expression in breast cancer tumors, as well as to assess response to hormonal therapy. © 2003 Wiley‐Liss, Inc.
Physical activity and breast cancer risk among female physical education and language teachers: A 34‐year follow‐up
Authors: Rintala Pirjo , Pukkala Eero , Läärä Esa , Vihko Veikko
Published: August 2003

The cohort consisted of 1,489 Finnish female physical education and 8,560 language teachers born after 1920 and alive in 1967. The 2 study populations were similar in social class and way of living and clearly discordant in physical activity both during their university studies and later in life. The incidence of breast cancer among these teachers up to the year 2000 was assessed through a record linkage with the Finnish Cancer Registry. The number of breast cancer cases among physical education teachers was 61 in 32,862 person‐years and among language teachers was 404 in 177,188 person‐years. In Poisson‐regression analysis, the incidence rate ratio—adjusted for age, calendar time, number of children and age at first birth—for physical education vs. language teachers was overall 0.83 (95% confidence interval 0.63–1.09). This relative rate was 0.79 (0.46–1.36) in ages <50 years and 0.86 (0.62–1.18) in ages ≥50 years. Our study is concordant with the hypothesis that life‐long physical activity may reduce the risk of breast cancer. © 2003 Wiley‐Liss, Inc.
Identification of TDE2 gene and its expression in non‐small cell lung cancer
Authors: Player Audrey , Gillespie John , Fujii Takeshi , Fukuoka Junya , Dracheva Tatiana , Meerzaman Dauod , Hong Kyeong Man , Curran John , Attoh Goziam , Travis William , Jen Jin
Published: August 2003

TDE2, a gene with sequence similarity to the mouse testicular tumor‐differentially‐expressed (Tde1/MUSTETU) gene, was identified by serial analysis of gene expression (SAGE) in nonsmall cell lung cancers (NSCLC). Here we characterized the TDE2 gene and determined its transcript levels in a panel of lung tumors, adjacent nonmalignant lung tissues and a variety of normal human tissues. In addition, we show that TDE2 is a potential transmembrane protein with 11 putative transmembrane helices. Using real‐time quantitative PCR, we showed that TDE2 transcript levels were higher in NSCLC compared to nonmalignant samples. In nonpulmonary normal tissues, the level of TDE2 was the highest in bladder, kidney and muscle; moderate to low in stomach, liver, skin, placenta and ovary tissues; and undetectable in brain, spleen and heart. By in situ hybridization, we showed that 10 of 18 lung tumors and only 1 of 14 adjacent nonmalignant regions had high levels of TDE2 transcripts. Alternatively, only 2 of 18 tumors and 8 of 14 adjacent nonmalignant bronchiole epithelium regions demonstrated negative to low levels of TDE2 signals. © 2003 Wiley‐Liss, Inc.
Overexpression of BAD preferentially augments anoikis
Authors: Idogawa Masashi , Adachi Masaaki , Minami Takae , Yasui Hiroshi , Imai Kohzoh
Published: August 2003

BAD is a BH3‐only protein, and its proapoptotic activity is negatively regulated by serine phosphorylation. Here, we show that overexpression of BAD preferentially augments anchorage loss–induced apoptosis (anoikis). Gene transfer–mediated BAD overexpression alone did not induce apoptosis in attached MDCK cells but strongly augmented apoptosis when cells were cultured in suspension. In contrast, overexpression of another BH3‐only protein, BID, displayed much lower augmentation of anoikis, suggesting a preferential contribution of BAD to anoikis. During suspension culture, unphosphorylated BAD was gradually increased and targeted to the mitochondria. Cotransfection of BAD with constitutively active Akt cDNA strongly inhibited this change. In contrast, the increase of unphosphorylated BAD was not significantly inhibited by several phosphatase inhibitors or cotransfection with a dominant negative calcineurin cDNA, implying that the increase may be mainly due to a decrease of serine kinase activity, such as that of Akt. Similar results were observed in COS‐7 cells, suggesting that BAD overexpression can increase sensitivity of anchorage‐dependent cancer cells to anoikis. Thus, we propose that BAD can serve as a valuable gene therapeutic molecule to inhibit carcinoma progression. © 2003 Wiley‐Liss, Inc.
Radiation‐related mortality among offspring of atomic bomb survivors: A half‐century of follow‐up
Authors: Izumi Shizue , Suyama Akihiko , Koyama Kojiro
Published: August 2003

Our objective was to examine whether parental exposure to atomic bomb radiation has led to increased cancer and/or noncancer mortality rates among the offspring. We studied 41,010 subjects born from May 1946 through December 1984 (i.e., conceived between 1 month and 38 years after the bombings) and surviving for at least 1 year. One or both parents were in Hiroshima or Nagasaki at the time of the bombings and childbirth. We analyzed mortality data from 1946 to 1999 using the Japanese family registry system by Cox regression model and examined the effects of paternal and maternal irradiation with adjustment for city, sex, year of birth and parental age at childbirth. During follow‐up, 314 cancer deaths and 1,125 noncancer disease deaths occurred. The mean age of living subjects was 45.7 years. Median doses were 143 mSv for 12,722 exposed fathers and 132 mSv for 7,726 exposed mothers. Cancer and noncancer mortality rates were no higher for subjects with exposed parents (5+ mSv or unknown dose) than for reference subjects (0–4 mSv), and mortality did not increase with increasing dose. For subjects with both parents exposed, the adjusted hazard ratios were 1.16 [95% confidence interval (CI) 0.92‐1.46] for noncancer and 0.96 (95% CI 0.59–1.55) for cancer. This was true of deaths occurring both before and after 20 years of age. However, because of uncertainty due to the small number of deaths and relatively young ages of subjects, we cannot rule out an increase in disease mortality at this time. © 2003 Wiley‐Liss, Inc.
Expression of prostate specific membrane antigen and three alternatively spliced variants of PSMA in prostate cancer patients
Authors: Schmittgen Thomas D. , Teske Sabine , Vessella Robert L. , True Lawrence D. , Zakrajsek Brian A.
Published: August 2003

Prostate specific membrane antigen (PSMA) is a folate γ glutamyl carboxypeptidase that is oriented on the plasma membrane of normal and prostate cancer cells. A cytosolic version of PSMA, PSM′, results from alternative splicing of the PSMA gene. Two additional alternatively spliced variants of PSMA, PSM‐C and PSM‐D, have been described recently. The ratio of PSMA to PSM′ mRNA was higher in a small number of prostate cancer specimens compared to normal prostate cancer and benign prostatic hypertrophy (Su et al. Cancer Res 1995;55:1441). The intent of our study was to measure the gene expression of PSMA and the 3 PSMA splice variants in a large number of patient's tissues. A real‐time, quantitative PCR assay was developed to quantify PSMA, PSM′, PSM‐C and PSM‐D. Discrimination among the variants was achieved by designing unique primers and TaqMan probes for each gene. Amplification and detection was specific for the desired splice variant and was sensitive to one gene copy per reaction. The assay was used to quantify the gene expression in specimens of normal, benign, primary and metastatic prostate cancer from 72 patients. The mean PSMA expression (relative to 18S rRNA) was 2‐ to 3‐fold lower in normal prostate (n = 4) compared to primary (n = 55, p = 0.31) and metastatic (n = 20, p = 0.33) prostate cancer. There was no difference in the PSMA expression between benign and cancerous prostate tissue from the same patients (n = 35). The ratio of PSMA to PSM′ was lowest in the normal prostate and increased with increasing Gleason score (p < 0.001). The increased ratio in these tissues was a reflection of both increasing PSMA levels and decreasing PSM′ mRNA. The expression of PSM‐C did not differ in any of the tissue categories studied. The expression of PSM‐D was similar in normal and primary prostate cancer but was 2‐fold higher in lymph node (p < 0.005) and bone metastases (p < 0.05) compared to the primary tumors. Our results of the first detailed quantitative analysis of PSMA mRNA expression in patient's tissues demonstrate that PSMA and the 3 PSMA splice variants are expressed in normal, benign, cancerous and metastatic prostate cancer. We note increased PSMA expression in some malignant tissues, however, these increases are modest in magnitude. We also report that the expression of a novel splice variant, PSM‐D, is elevated in prostate cancer metastases. © 2003 Wiley‐Liss, Inc.
Dimensional versus categorical classification of prototypic and nonprototypic cases of personality disorder
Authors: Sprock June
Published: August 2003

This study examined interrater reliability and ratings of confidence and clinical utility (professional communication, case conceptualization, treatment planning) of categorical and dimensional approaches to diagnosing prototypic and nonprototypic personality disorder cases. Two national samples of psychologists (n= 93,n= 92) participated. Interrater reliability was higher for prototypic cases than nonprototypic cases for the categorical system, but similar for prototypic and nonprototypic cases using dimensional ratings. Across cases, interrater reliability and confidence were highest for the categorical model, hybrid models, and the five‐factor model. However, ratings of clinical utility were highest for the categorical and the hybrid models, even when interrater reliability was inadequate, suggesting clinician preference for a classification based on the existing categories. Mean ratings for the prototypic cases supported the theorized relationships between the dimensional models and the personality disorders. Reasons for these findings and implications for moving towards a dimensional model of personality disorder are discussed. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
The Schizophrenia Proneness (SzP) scale: An MMPI‐2 measure of schizophrenia liability
Authors: Bolinskey P. Kevin , Gottesman Irving I. , Nichols David S.
Published: August 2003

We examined the psychometric properties and construct validity for a Minnesota Multiphasic Personality Inventory–2 Schizophrenia Proneness (SzP) scale (Bolinskey et al., 2001) and provided normative statistics. Premorbid participants were offspring of parents with schizophrenia‐related illness (SRI), with comparison groups of offspring of parents with major affective disorders and offspring of normals. Postmorbid participants were twins affected with SRI; their unaffected relatives served as a comparison group. Results suggest that an SzP T score of 65 or above is an effective indicator of personality processes associated with increased liability to developing SRI. © 2003 Wiley Periodicals, Inc. J Clin Psychol
Personality traits predicting long‐term adjustment after surgery for ulcerative colitis
Authors: Weinryb Robert M. , Gustavsson J. Petter , Barber Jacques P.
Published: August 2003

Very few studies have examined the relationship between personality traits and long‐term postoperative psychosocial adjustment. In a sample of 46 patients, we examined the relation between personality traits before pelvic pouch surgery for ulcerative colitis and psychosocial adjustment seven years postoperatively, controlling for the effects of surgical functional outcome. The Karolinska Psychodynamic Profile (KAPP) was used for personality assessment. Surgical functional outcome scales and the Psychosocial Adjustment to Illness Scale were also used. As assessed by the KAPP, poor frustration tolerance, long‐standing preoperative problems in sexual functioning, perfectionistic body ideals, and lack of alexithymia predicted poorer postoperative long‐term psychosocial adjustment in the areas of health concerns, sexuality, family relations, and psychological distress. Surgical functional outcome itself was a poor predictor of long‐term adjustment. The results indicate that it may be beneficial to take personality factors into account in preoperative assessment. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
MMPI‐2 based classification of forensic psychiatric outpatients: An exploratory cluster analytic study
Authors: Nieberding Ron J. , Gacono Carl B. , Pirie Mark , Bannatyne Lynne A. , Viglione Donald J. , Cooper Bruce , Bodholdt Robert H. , Frackowiak Marita
Published: August 2003

The Minnesota Multiphasic Personality Inventory (MMPI), and now the MMPI‐2, are the most widely researched personality assessment tools in correctional and related forensic settings (MMPI; Hathaway & McKinley, 1940; MMPI‐2; Butcher, Dahlstrom, Graham, Tellegen, & Kaemmer, 1989). Using the original MMPI, Megargee (1977a) and colleagues (Megargee & Bohn, 1977; Megargee & Dorhout, 1977) developed an extensive and meaningful classification system for correctional inmates. However, few studies, with the exception of Toch and Adams (1994) cluster analytic study of emotionally disturbed violent offenders, have explored possibilities of a statistically derived categorical classification paradigm within the growing population of forensic psychiatric patients awaiting discharge into the community (Bannatyne, 1996). The present exploratory study investigates the utility of a commonly employed and replicable cluster analytic method in establishing an MMPI‐2‐based categorical classification system within a substantial forensic psychiatric outpatient sample (N = 300). Here, we present results of a seven‐cluster solution, augmented by contemporaneous Rorschach inkblot data utilizing Exner's Comprehensive System (Exner, 1991; Exner et al., 1995). Descriptive cluster characteristics are provided along with potential clinical correlates in an attempt to move closer to the goal of pairing informed assessment with effective treatment in this growing, but unique, population. © 2003 Wiley Periodicals, Inc. J Clin Psychol.
Adaptation to the sky: Defining the feather with integument fossils from mesozoic China and experimental evidence from molecular laboratories
Authors: Chuong Cheng‐Ming , Wu Ping , Zhang Fu‐Cheng , Xu Xing , Yu Minke , Widelitz Randall B. , Jiang Ting‐Xin , Hou Lianhai
Published: August 2003

In this special issue on the Evo‐Devo of amniote integuments, Alibardi has discussed the adaptation of the integument to the land. Here we will discuss the adaptation to the sky. We first review a series of fossil discoveries representing intermediate forms of feathers or feather‐like appendages from dinosaurs and Mesozoic birds from the Jehol Biota of China. We then discuss the molecular and developmental biological experiments using chicken integuments as the model. Feather forms can be modulated using retrovirus mediated gene mis‐expression that mimics those found in nature today and in the evolutionary past. The molecular conversions among different types of integument appendages (feather, scale, tooth) are discussed. From this evidence, we recognize that not all organisms with feathers are birds, and that not all skin appendages with hierarchical branches are feathers. We develop a set of criteria for true avian feathers: 1) possessing actively proliferating cells in the proximal follicle for proximo‐distal growth mode; 2) forming hierarchical branches of rachis, barbs, and barbules, with barbs formed by differential cell death and bilaterally or radially symmetric; 3) having a follicle structure, with mesenchyme core during development; 4) when mature, consisting of epithelia without mesenchyme core and with two sides of the vane facing the previous basal and supra‐basal layers, respectively; and 5) having stem cells and dermal papilla in the follicle and hence the ability to molt and regenerate. A model of feather evolution from feather bud → barbs → barbules → rachis is presented, which is opposite to the old view of scale plate → rachis → barbs → barbules (Regal, '75; Q Rev Biol 50:35). J. Exp. Zool. (Mol. Dev. Evol.) 298B:42–56, 2003. © 2003 Wiley‐Liss, Inc.
A hierarchical model of plumage: Morphology, development, and evolution
Authors: Prum Richard O. , Dyck Jan
Published: August 2003

Plumage is a complex component of the avian phenotype. The plumage of an individual is composed of numerous hierarchically arranged developmental and morphological modules. We present a hierarchical model of plumage that provides an intellectual framework for understanding the development and evolution of feathers. Independence, covariation, and interaction among plumage modules create numerous opportunities for developmental and evolutionary diversification of feather complexity and function. The hierarchical relationships among plumage modules are characterized by both top‐down and bottom‐up effects in which properties of modules at one level of the hierarchy determine or influence the properties of modules at lower or higher levels of the hierarchy. Plumage metamodules are created by covariation or interaction among modules at different levels of the hierarchy. J. Exp. Zool. (Mol. Dev. Evol.) 298B: 73–90, 2003. © 2003 Wiley‐Liss, Inc.
Variations in the morphology, distribution, and arrangement of feathers in domesticated birds
Authors: Bartels Thomas
Published: August 2003

Domesticated birds exhibit a greater diversity in the morphology of their integument and its appendages than their wild ancestors. Many of these variations affect the appearance of a bird significantly and have been bred selectively by poultry and pigeon fanciers and aviculturists for the sake of visual appeal. Variations in feather distribution (e.g., feathering of legs and feet, featherless areas in normally feather‐bearing skin) are widespread in chickens and pigeons. Variations in the number of feathers (e.g., increased number of tail feathers, lack of tail feathers) occur in certain pigeon and poultry breeds. Variations in feather length can affect certain body regions or the entire plumage. Variations in feather structure (e.g., silkiness, frilled feathering) can be found in exhibition poultry as well as in pet birds. Variations in feather arrangement (e.g., feather crests and vortices) occur in many domesticated bird species as a results of mutation and intense selective breeding. The causes of variations in the structure, distribution, length and arrangement of feathers is often unknown and opens a wide field for scientific research under various points of view (e.g., morphogenesis, pathogenesis, ethology, etc.). To that extent, variations in the morphology, distribution and arrangement of feathers in domesticated birds require also a concern for animal welfare because certain alleles responsible for integumentary variations in domesticated birds have pleiotropic effects, which often affect normal behaviour and viability. J. Exp. Zool. (Mol. Dev. Evol.) 298B:91–108, 2003. © 2003 Wiley‐Liss, Inc.
Evolution and development of mammalian limb integumentary structures
Authors: Hamrick Mark W.
Published: August 2003

The adaptive radiation of mammalian clades has involved marked changes in limb morphology that have affected not only the skeleton but also the integumentary structures. For example, didelphid marsupials show distinct differences in nail and claw morphology that are functionally related to the evolution of arboreal, terrestrial, and aquatic foraging behaviors. Vespertilionoid bats have evolved different volar pad structures such as adhesive discs, scales, and skin folds, whereas didelphid marsupials have apical pads covered either with scales, ridges, or small cones. Comparative analysis of pad and claw development reveals subtle differences in mesenchymal and ectodermal patterning underlying interspecific variation in morphology. Analysis of gene expression during pad and claw development reveals that signaling molecules such as Msx1 and Hoxc13 play important roles in the morphogenesis of these integumentary structures. These findings suggest that evolutionary change in the expression of these molecules, and in the response of mesenchymal and ectodermal cells to these signaling factors, may underlie interspecific differences in nail, claw, and volar pad morphology. Evidence from comparative morphology, development, and functional genomics therefore sheds new light on both the patterns and mechanisms of evolutionary change in mammalian limb integumentary structures. J. Exp. Zool. (Mol. Dev. Evol.) 298B:152–163, 2003. © 2003 Wiley‐Liss, Inc.
Molecular biology of hair morphogenesis: Development and cycling
Authors: Botchkarev Vladimir A. , Paus Ralf
Published: August 2003

In mammals, hair follicles produce hairs that fulfill a number of functions including thermoregulation, collecting sensory information, protection against environmental trauma, social communication, and mimicry. Hair follicles develop as a result of epithelial‐mesenchymal interactions between epidermal keratinocytes committed to hair‐specific differentiation and cluster of dermal fibroblasts that form follicular papilla. During postnatal life, hair follicles show patterns of cyclic activity with periods of active growth and hair production (anagen), apoptosis‐driven involution (catagen), and relative resting (telogen). During last decade, substantial progress has been achieved in delineating molecular mechanisms that control hair follicle development and cyclic activity. In this review, we summarize the data demonstrating that regulation of hair follicle development in the embryo and control of hair follicle growth during postnatal life are highly conserved and both require involvement of similar molecular mechanisms. Since many of the molecules that control hair follicle development and cycling are also involved in regulating morphogenesis and postnatal biology of other ectodermal derivatives, such as teeth, feathers, and mammary glands, basic principles and molecular mechanisms that govern hair follicle development and growth may also be applicable for other developmental systems. J. Exp. Zool. (Mol. Dev. Evol.) 298B: 164–180, 2003. © 2003 Wiley‐Liss, Inc.
Inhibition of type I procollagen production by tRNAVal CTE‐HSP47 ribozyme
Authors: Hagiwara Seiya , Nakamura Kiminori , Hamada Hirofumi , Sasaki Katsunori , Ito Yoshinori , Kuribayashi Kageaki , Sato Tsutomu , Sato Yasushi , Takahashi Minoru , Kogawa Katsuhisa , Kato Junji , Terui Takeshi , Takayama Tetsuji , Matsunaga Takuya , Taira Kazunari , Niitsu Yoshiro
Published: August 2003

Background

Fibrosis characteristically occurs in the advanced stages of chronic inflammatory diseases, occasionally as the primary lesion, and frequently determines the disease prognosis. Fibrotic lesions consist mostly of collagen, and therefore it may be possible to prevent or treat fibrosis by inhibiting collagen production. Of the currently available therapeutic approaches, however, none is sufficiently effective and specific for inhibition of collagen. Heat shock protein 47 (HSP47) is a collagen‐specific molecular chaperone that has been reported to play a pivotal role in secretion of procollagen molecules. Therefore, we have tried to suppress its function to inhibit these various types of collagen.

Methods

We have developed a novel type of ribozyme by ligating a hammerhead sequence to a tRNAVal promoter to facilitate displacing the ribozyme from nucleus to cytoplasm and to constitutive transport element, a binding motif of helicase which unwinds mRNA to render the target sequence on the mRNA accessible to the ribozyme.

Results

The ribozyme thus constructed showed strong activity to cleave HSP47 mRNA and suppress the secretion of type I procollagen in the human primary fibroblast.

Conclusion

We suggest applicability of this ribozyme as a new modality for antifibrosis therapy. Copyright © 2003 John Wiley & Sons, Ltd.