bluuebunny/crossref_metadata_2025 huggingface dataset:
Gibbs sampling–based segregation analysis of asthma‐associated quantitative traits in a population‐based sample of nuclear families
Authors: Palmer Lyle J. , Cookson William O.C.M. , James Alan L. , Musk A. William , Burton Paul R.
Published: August 2002

Asthma is a common, complex human disease. Elevated serum immunoglobulin E (IgE) levels, elevated blood eosinophil counts, and increased airway responsiveness are physiological traits that are characteristic of asthma. Few studies have investigated major gene effects for these traits in a population‐based sample. Further, it is not known if any putative major genes may be common to two or more of these traits. We investigated the existence and nature of major genes modulating asthma‐associated quantitative traits in an Australian population‐based sample of 210 Caucasian nuclear families. The sharing of these major genes was also investigated. Segregation analysis was based upon a Markov Chain Monte Carlo (Gibbs sampling) approach as implemented in the program BUGS v0.6. All models included adjustment for age, height, tobacco smoke exposure, and gender. The segregation of total IgE levels, blood eosinophil counts, and dose‐response slope (DRS) of methacholine challenge were all consistent with major loci at which a recessive allele acted to increase or decrease the phenotype. The respective estimated frequencies of the recessive alleles were 68% (total IgE), 10% (blood eosinophil count), and 27% (DRS). Extensive modelling suggested that the major loci controlling total serum IgE levels, blood eosinophil counts, and airway responsiveness represent different genes. These data provide evidence, for the first time, of the existence of at least 3 distinct genetic pathways involving major gene effects on physiological traits closely associated with asthma. These results have implications for gene discovery programs. Genet. Epidemiol. 20:356–372, 2001. © 2001 Wiley‐Liss, Inc.
Fast and precise independent component analysis for high field fMRI time series tailored using prior information on spatiotemporal structure
Authors: Suzuki Kiyotaka , Kiryu Tohru , Nakada Tsutomu
Published: August 2002

Independent component analysis (ICA) has been shown as a promising tool for the analysis of functional magnetic resonance imaging (fMRI) time series. Each of these studies, however, used a general‐purpose algorithm for performing ICA and the computational efficiency and accuracy of elicited neuronal activations have not been discussed in much detail. We have previously proposed a direct search method for improving computational efficiency. The method, which is based on independent component‐cross correlation‐sequential epoch (ICS) analysis, utilizes a form of the fixed‐point ICA algorithm and considerably reduces the time required for extracting desired components. At the same time, it is shown that the accuracy of detecting physiologically meaningful components is much improved by tailoring the contrast function used in the algorithm. In this study, further improvement was made to this direct search method by integrating an optimal contrast function. Functional resolution of activation maps could be controlled with a suitable selection of the contrast function derived from prior knowledge of the spatial patterns of physiologically desired components. A simple skewness‐weighted contrast function was verified to extract sufficiently precise activation maps from the fMRI time series acquired using a 3.0 Tesla MRI system. Hum. Brain Mapping 15:54–66, 2001. © 2001 Wiley‐Liss, Inc.
Equity in Swedish health care reconsidered: new results based on the finite mixture model
Authors: Gerdtham Ulf‐G. , Trivedi Pravin K.
Published: August 2002

This paper reconsiders the equity issue in Swedish health care utilization previously analysed by Gerdtham (Health Econ 1997; 6: 303–319) within the framework of the standard two‐part model. Departing from the user/non‐user distinction, we use the more flexible framework of the finite mixture model that distinguishes between frequent/infrequent users. Our results indicate that the support for the inequity hypothesis reported by Gerdtham is sensitive to model specification and the way standard errors of coefficients are estimated. The new framework offers an alternative perspective on the magnitude of the income‐related difference in health care utilization. Copyright © 2001 John Wiley & Sons, Ltd.
Effects of lingual gestures on blood flow into the tongue: A pilot study
Authors: Watkin Kenneth L. , Gallagher Tanya M. , Logemann Jeri A. , Rademaker Alfred W.
Published: August 2002

Background

Reduced blood flow has been hypothesized to be a major factor in the formation of postradiation fibrosis. This study examined Doppler ultrasonography as a technique to detect changes in blood flow into the tongue during selected lingual gestures, /t/ and /k/.

Methods

Six normal subjects, three young men (mean age, 26 years) and three older men (mean age, 66 years) were examined in an upright position using Doppler ultrasound imaging of the external carotid artery just below the lingual artery. Measurements were made with a standardized segmentation technique before and after three repetitions of four speech production gestures /t/ and /k/, each with natural and maximal force.

Results

Blood flow peak systole increased significantly after the speech gestures (p < .001). Pooled before and after gesture values for older subjects were significantly lower than those for younger subjects (p ≤ .05).

Conclusions

Ultrasonography is a clinically useful technique for measuring blood flow during a dynamic gesture and may be useful for measuring effects of tumor treatment and in a lingual exercise program. © 2001 John Wiley & Sons, Inc. Head Neck 23: 404–408, 2001.
Malignant triton tumor of the nasal cavity
Authors: Kim Seon Tae , Kim Chan Woo , Han Gyu Cheol , Park Chan , Jang II Hwan , Cha Heung Eog , Choi Geon , Lee Heung‐Man
Published: August 2002

Background

Malignant triton tumor is usually an aggressive sarcoma consisting of a malignant schwannoma with rhabdomyoblastic differentiation. However, malignant triton tumor of the nasal cavity is very rare.

Methods

A case report of a 38‐year‐old woman with polypoid mass, which bled easily in the right nasal cavity, and nasal obstruction is presented with a review of the literature pertaining to this unusual case.

Results

The malignant triton tumor was treated with wide surgical excision followed by radiation therapy. Histopathological diagnosis of the malignant triton tumor was made on the surgical specimen. The patient's postoperative course was unremarkable, and follow‐up at 5 years reveals no evidence of disease.

Conclusions

A malignant triton tumor in the nasal cavity is a rare disease. Head and neck surgeons should recognize the possibility of malignant triton tumor occurring in the nasal cavity. © 2001 John Wiley & Sons, Inc. Head Neck 23: 1075–1078, 2001.
Aberrant synaptic transmission in the hippocampal CA3 region and cognitive deterioration in protein‐repair enzyme‐deficient mice
Authors: Ikegaya Yuji , Yamada Mitsunori , Fukuda Tetsuya , Kuroyanagi Hidehito , Shirasawa Takuji , Nishiyama Nobuyoshi
Published: August 2002

L‐aspartate is the amino‐acid residue most susceptible to spontaneous isomerization. This denaturation causes an alteration in the biological activity of the protein and is regarded as an aging process of the protein. Protein L‐isoaspartyl methyltransferase (PIMT) repairs this posttranslational modification and thus is implicated in retarding the aging process of proteins. PIMT is highly expressed in the brain, and its deficiency results in progressive epilepsy after 4 weeks of age, with a fatal seizure in mice. Here we report the pathophysiological role of this repair system in the hippocampal slice of PIMT‐deficient mice. The hippocampal mossy fiber‐CA3 synapses of PIMT‐deficient mice showed hyperexcitation that was repressed by a γ‐aminobutyric acid (GABA)A receptor agonist muscimol. In addition, the mossy fiber‐CA3 synapses failed to show long‐term potentiation or paired‐pulse facilitation. No abnormality, however, was observed in Schaffer collateral‐CA1 synapses or in perforant path‐dentate gyrus synapses. Electron microscopic study revealed aberrant distribution of synaptic vesicles in the mossy fiber terminals and vacuolar degeneration at the axon hillock of dentate granule cells in PIMT‐deficient mice. Furthermore, the PIMT‐deficient mice showed impaired spatial memory in Morris water maze test and exhibited fewer anxiety‐related behaviors in the elevated‐plus test. These results suggest that the mossy fiber‐CA3 system is vulnerable to aspartate isomerization and that the PIMT‐mediated repair system is essential for maintenance of normal functions of the hippocampus. Hippocampus 2001;11:287–298. © 2001 Wiley‐Liss, Inc.
Chronic food restriction is associated with subtle dendritic alterations in granule cells of the rat hippocampal formation
Authors: Andrade José P. , Lukoyanov Nikolai V. , Paula‐Barbosa Manuel M.
Published: August 2002

The hippocampal formation undergoes significant morphological and functional changes after prolonged feeding with low‐protein diets. In this study we tested whether prolonged food restriction causes deleterious alterations in this brain region as well. It was found that the total number of dentate granule cells and hippocampal CA3 and CA1 pyramidal neurons did not differ between controls and rats submitted to food restriction (40%) for 36 weeks. Likewise, no effects of this dietary regimen have been detected on the morphology of the dendritic trees of hippocampal pyramids, and on the total number of the mossy fiber‐CA3 synapses. By contrast, the dendritic arborizations of granule cells were found to have a reduced number of segments in food‐restricted rats. However, the spine density on the distal segments of their dendritic trees and the total number of axospinous synapses in the outer molecular layer of the dentate gyrus were increased in these animals. In addition, the total dendritic length of the granule cells and the overall surface area of the active zones of the synapses in the outer molecular layer were preserved, indicating that the capacity of dentate granule cells to process afferent stimuli is likely to be unaffected by this dietary treatment. Supporting this view are the results obtained in the water maze experiment which show that food‐restricted rats exhibit unimpaired spatial abilities, which are known to be dependent on the entorhinal drive towards the hippocampal formation. These results show that, among hippocampal neurons, dentate granule cells are selectively vulnerable to food restriction. Nonetheless, the reorganization which takes place in their dendrites and synapses is capable of minimizing the functional impairments that were expected to occur following changes in the hippocampal neuronal circuitry induced by this type of dietary restriction. Hippocampus 2002;12:149–164. © 2002 Wiley‐Liss, Inc.
Vertical or holistic decentralization of the health sector? Experiences from Zambia and Uganda
Authors: Jeppsson Anders , Okuonzi Sam Agatre
Published: August 2002

Many countries in Africa have embarked on health sector reforms. The design of the reforms differs considerably. A key feature of the reforms is decentralization, of which Uganda and Zambia are implementing two different models. This paper analyses the two models of health sector reform, and their implications for ultimate development goals. In Uganda, the whole government has been decentralized, with a wide range of powers and resources transferred to the districts. The health care system is part of the political set up of the country. In Zambia, only the health sector has been decentralized. Power and resources for health care have been divested to new parallel organizations. While useful lessons can be drawn from the managerial and administrative experience in the two countries, not least concerning donor coordination, it seems that neither form of decentralization has so far led to a clear and appreciable improvement of health services and, ultimately, to a clear focus on development goals, such as poverty alleviation. The conditions for this to happen are discussed in this paper. Copyright © 2000 John Wiley & Sons, Ltd.
Mapping capacity in the health sector: a conceptual framework
Authors: LaFond Anne K. , Brown Lisanne , Macintyre Kate
Published: August 2002

Capacity improvement has become central to strategies used to develop health systems in low‐income countries. Experience suggests that achieving better health outcomes requires both increased investment (i.e. financial resources) and adequate local capacity to use resources effectively. International donors and non‐governmental agencies, as well as ministries of health, are therefore increasingly relying on capacity building to enhance overall performance in the health sector. Despite the growing interest in capacity improvement, there has been little consensus among practitioners and academics on definitions of ‘capacity building’ and how to evaluate it. This paper aims to review current knowledge and experiences from ongoing efforts to monitor and evaluate capacity building interventions in the health sector in developing countries. It draws on a wide range of sources to develop (1) a definition of capacity building and (2) a conceptual framework for mapping capacity and measuring the effects of capacity building interventions. Mapping is the initial step in the design of capacity building interventions and provides a framework for monitoring and evaluating their effectiveness. Capacity mapping is useful to planners because it makes explicit the assumptions underlying the relationship between capacity and health system performance and provides a framework for testing those assumptions. Copyright © 2002 John Wiley & Sons, Ltd.
Expression of membrane type 1 matrix metalloproteinase (MT1‐MMP) in A2058 melanoma cells is associated with MMP‐2 activation and increased tumor growth and vascularization
Authors: Sounni Nor Eddine , Baramova Eugenia N. , Munaut Carine , Maquoi Erik , Frankenne Francis , Foidart Jean‐Michel , Noël Agnès
Published: August 2002

Membrane‐type metalloproteinase‐1 (MT1‐MMP) is a transmembrane metalloproteinase overexpressed in tumors, which plays a major role in the first step of pro‐MMP‐2 activation, leading to the generation of an intermediate 62 kDa species. The second step of MMP‐2 activation that yields to the mature form is less understood and could involve an autocatalytic process and/or the activity of the plasminogen/plasmin system. Human melanoma A2058 cells, which express MMP‐2 only in its pro‐form, were used to determine the role of MT1‐MMP during pericellular proteolysis and tumor progression. The induction of MT1‐MMP overexpression by MT1‐MMP cDNA transfection initiated the first step of MMP‐2 activation. We provide evidence that a cooperation between the plasminogen/plasmin system and MT1‐MMP endowed the cells with the ability to fully activate MMP‐2 and with enhanced invasive properties in vitro. When injected subcutaneously in nude mice, MT1‐MMP expressing clones induced rapid tumor growth and high tumor vascularization, while the control clones were poorly or not tumorigenic. Our data provide the first demonstration, in an experimental model, that MT1‐MMP expression by tumor cells promotes tumor vascularization. © 2001 Wiley‐Liss, Inc.
Cancer chemoresistance: The relationship between p53 and multidrug transporters
Authors: Bush Jason A. , Li Gang
Published: August 2002

Extensive studies indicate that both p53 and multidrug transporters play important roles in chemoresistance. Since the initial reports a decade ago demonstrating a transcriptional dependence of the ABCB1 gene (MDR) promoter by p53, much data have been accumulated. However, despite being the subject of intense study, this p53‐MDR relationship remains unclear in human cancers. The data are confounded by variable and contrasting results when considering the in vitro regulation and attempting to draw parallels in tissue specimens. The original model suggested that wild‐type p53 downregulates the ABCB1 promoter, whereas mutant p53 increases expression of ABCB1. This review summarizes the data for and against this hypothesis. What emerges from these studies is a complex picture, where data have been obtained in support of this hypothesis, but there are also many circumstances where it is not supported. Taken together, these data suggest that the relationship between p53 and multidrug transporters is conditional. It is dependent on cellular environment, the drug used, and the nature of the p53 mutation. © 2002 Wiley‐Liss, Inc.
Basigin (cd147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts
Authors: Kanekura Takuro , Chen Xiang , Kanzaki Tamotsu
Published: August 2002

EMMPRIN, which is identical to human basigin (CD147), interacts with fibroblasts and stimulates expression of MMPs, which play an important role in tumor invasiveness and metastasis. In the present study, we demonstrated that coculture of basigin‐expressing human MM cells with dermal fibroblasts resulted in the induction of MMP‐1, MMP‐2, MMP‐3 and MT1‐MMP production by fibroblasts and of melanoma cell invasion through a reconstituted basement membrane. Antibody to basigin inhibited both the production of MMPs by fibroblasts and the invasiveness of melanoma cells. Expression of basigin and MMPs in MM and surrounding fibroblasts was examined immunohistochemically in 28 specimens from 18 MM patients without metastasis and 10 with metastasis, to investigate whether basigin plays a role in metastasis of MM in vivo. Basigin was expressed in melanoma cells but not in fibroblasts. MM with metastasis had significantly higher basigin expression compared to MM without metastasis. There were significant differences between MMs with and without metastasis in the expression of MMPs in both melanoma cells and fibroblasts. Expression of MMPs in fibroblasts was positively correlated with expression levels of basigin. These immunohistochemic findings indicate that MMPs might be expressed in fibroblasts as well as melanoma cells concomitantly with basigin, which was expressed in melanoma cells more frequently in MM with metastasis. Basigin is highly expressed in melanoma cells and may play an important role in their invasiveness and metastasis by stimulating surrounding fibroblasts to express MMPs. © 2002 Wiley‐Liss, Inc.
Prognostic significance of p53 mutations in colon cancer at the population level
Authors: Samowitz Wade S. , Curtin Karen , Ma Khe‐ni , Edwards Sandra , Schaffer Donna , Leppert Mark F. , Slattery Martha L.
Published: August 2002

Some studies have reported that p53 mutations or certain types of p53 mutation are associated with poor prognosis in colon cancer, while other studies have failed to show such a relationship. None of these previous studies was population‐based. We therefore evaluated the prognostic significance of p53 mutations in a large, population‐based study of 1,464 individuals with colon cancer from Utah and California. Mutations in exons 5–8 were detected by SSCP analysis, followed by sequencing of aberrant bands. p53 mutations were identified in colon cancers from 665 of 1,464 (45.4%) individuals. p53 mutations were significantly more common in distal tumors (p < 0.01), tumors of relatively high stage (p = 0.04), tumors without MSI (p < 0.01) and tumors without Ki‐ras mutations (p < 0.01). In a univariate analysis, tumors with p53 mutations were associated with a significantly worse 5‐year survival than those with wild‐type p53 (53.4% vs. 58.8%, p = 0.04); significantly worse prognosis also was seen with missense mutations, transitions, transversions, mutations affecting the structure of the p53 molecule, mutations within the β‐sandwich motif and mutations in proximal tumors. In multivariate analyses, however, the only significant predictors of poor prognosis were G245 hot spot mutations (HRR = 2.16, 95% CI 1.06–4.40) and p53 mutations in proximal tumors (HRR = 1.34, 95% CI 1.07–1.63). We conclude that overall p53 mutational status is not an independent predictor of poor prognosis in colon cancer. However, specific classes of mutations, namely, the G245 hot spot mutation and mutations in proximal tumors, are related to significantly worse survival even after adjusting for age and stage. © 2002 Wiley‐Liss, Inc.
Intensity‐modulated radiotherapy with an integrated boost to the macroscopic tumor volume in the treatment of high‐grade gliomas
Authors: Thilmann Christoph , Zabel Angelika , Grosser Karl Heinz , Hoess Angelika , Wannenmacher Michael , Debus Juergen
Published: August 2002

Integrated boost radiotherapy (IBRT) delivers a higher fraction size to the gross tumor volume and a conventional fraction size to the surrounding tissue of microscopic spread. We compared stereotactic conformal radiotherapy (SCRT) and intensity‐modulated radiotherapy (IMRT) with regard to their suitability for IBRT in the treatment of high‐grade gliomas. In 20 patients treated with conventional radiotherapy, an additional treatment plan for IBRT [planning target volume (PTV1) defined as contrast‐enhancing lesion plus margin due to setup errors 75 Gy, PTV2 defined as edema plus margin due to microscopic spread and setup error 60 Gy] with 7 non‐coplanar beams for IMRT and for SCRT was carried out and compared. The part of the PTV2 irradiated with more than 107% of the prescribed dose was 13.9% for IMRT and 30.9% for SCRT (P < 0.001). Dose coverage of PTV2 (volume above 95% of the prescribed dose) was improved with IMRT (88.4% vs. 75.3% with SCRT, P < 0.001). Dose coverage of PTV1 was slightly higher with SCRT (93.7% vs. 87.5% with IMRT), but the conformity to the boost shape was improved by IMRT [conformity index (COIN95) = 0.85 vs. 0.69 with SCRT]. Simultaneously the brain volume irradiated with > 50 Gy was reduced from 60 to 33 cc (P < 0.001). We conclude that IMRT is suitable for local dose escalation in the enhancing lesion and for delivering a homogeneous dose to the PTV2 outside the PTV1 at the same time. Our encouraging results justify application of IMRT for IBRT in the treatment of high‐grade gliomas. For clinical evaluation a phase III study has been initiated. © 2001 Wiley‐Liss, Inc.
Cancer risks in twins: Results from the Swedish family‐cancer database
Authors: Hemminki Kari , Li Xinjun
Published: August 2002

Twin studies on cancer have addressed two general questions, one about the possible carcinogenic effects of twinning and the second about heritable effects of cancer. The first question is answered by comparing the occurrence of cancer in twins to that in singletons; the second is answered in probandwise analysis of monozygotic twins compared to dizygotic twins or siblings. We used the nationwide Swedish Family‐Cancer Database on 10.2 million individuals and 62,574 0–66‐year‐old twins to calculate standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all main cancer compared to cancer in singletons. In probandwise analysis, the SIR was calculated for the co‐twin of an affected twin. The overall risk of cancer in same or opposite sex twins was at the level of the risk for singletons. Testicular cancer was increased among same sex twins and all twins to an SIR of 1.43. Melanoma was decreased in these groups of twins to an SIR of 0.84. Some other cancer sites were increased or decreased in some groups of twins, but none in all twins. The SIR of breast cancer was 1.01 and 1.04 in same and opposite sex twins, respectively. Probandwise analysis showed increased risks for Hodgkin's disease in males and breast cancer and childhood acute lymphoid leukemia among females. The data on this unselected population of twins suggest that twinning per se is not a risk factor of cancer. However, because twins are smaller than singletons at birth, some possible effects could be masked by such differences. In utero hormonal exposures may be related to the risk of testicular cancer. The protective effects in melanoma may be due to socioeconomic factors. © 2002 Wiley‐Liss, Inc.
Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: Implications for genetic testing
Authors: de la Hoya Miguel , Osorio Ana , Godino Javier , Sulleiro Sara , Tosar Alicia , Perez‐Segura Pedro , Fernandez Cristina , Rodríguez Raquel , Díaz‐Rubio Eduardo , Benítez Javier , Devilee Peter , Caldés Trinidad
Published: August 2002

Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breast cancer susceptibility genes BRCA1 and BRCA2. Overall, the prevalence of mutations was 43% in female breast/ovarian cancer families, 15% in female breast cancer families and 100% in male breast cancer families. Three recurrent mutations (185delAG, 589delCT and A1708E) explained 63% of BRCA1‐related families. Early age at diagnosis of breast cancer, ovarian cancer, bilateral breast cancer, concomitant breast/ovarian cancer in a single patient and prostate cancer but not unilateral breast cancer were associated with BRCA1 and BRCA2 mutations. Male breast cancer was associated with BRCA2 mutations. The presence of male breast cancer was the only cancer phenotype that distinguished BRCA2‐ from BRCA1‐related families. We have developed a logistic regression model for predicting the probability of harbouring a mutation in either BRCA1 or BRCA2 as a function of the cancer phenotype present in the family. The predictive positive and negative values of this model were 77.4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost‐effectiveness of genetic testing in familial cancer clinics. © 2001 Wiley‐Liss, Inc.
International migration and the change of women's position among the left‐behind in rural Bangladesh
Authors: Hadi Abdullahel
Published: August 2002

While the impact of remittances upon the economic conditions of the sending communities has received much attention, the effects of international migration on women's position in society among the left‐behind have not been adequately explored. This paper examines the changes in the left‐behind women's position at the family level as a result of the migration of adult men overseas. Data came from a demographic surveillance system covering 70 villages in Bangladesh. All migrant families having at least one male member working abroad for more than six months were identified in the study villages in 1996. A comparable number of non‐migrant families were selected at random from the same villages to yield a total sample of 1030 families. In‐depth interviews were conducted with adult women of the sample families. Findings reveal that the overseas migration of adult males has a significant positive association with women's decision‐making capacity and education of girls in the migrant families. The remittances as well as the influence of secular values have reduced the practice of dowry in marriages. Multivariate analysis suggests not only that remittances have increased the financial capacity of the migrant families, but also that secular influences from overseas might have modified the position of women when the role of other socio‐economic factors is controlled. The study concludes that the overseas migration of adult men can create a context for change of the women's position in traditional communities. Copyright © 2001 John Wiley & Sons, Ltd.
Maternal substance use and mother–infant feeding interactions
Authors: Eiden Rina Das
Published: August 2002

The purpose of this study was to examine the impact of maternal polydrug cocaine use during pregnancy and associated risk factors such as maternal psychopathology and negative infant temperament on the quality of mother–infant feeding interactions at 2 months of infant age. Participants were 45 mother–infant dyads (19 cocaine‐exposed and 26 nonexposed) who were recruited at birth and assessed again 2 months of infant age. Mother–infant interactions during feeding were videotaped and coded with regard to dyadic reciprocity, maternal noncontingency, and dyadic conflict. Results indicated that maternal cocaine use was associated with higher dyadic conflict. Moreover, cocaine‐using mothers were also more likely to use marijuana and alcohol, and use of such substances was associated with lower dyadic reciprocity and higher maternal noncontingency during interactions. Results also suggested that one pathway to higher dyadic conflict during interactions among cocaine‐using mothers was through the impact of cocaine on infant risk conditions like lower gestational age and negative temperament (e.g., higher distress to novelty). Interventions focusing on promoting the quality of mother–infant interactions in combination with substance abuse treatment may be especially promising for this population. ©2001 Michigan Association for Infant Mental Health.
Prenatal maternal representations: Mothers at psychosocial risk
Authors: Pajulo Marjaterttu , Savonlahti Elina , Sourander Andre , Piha Jorma , Helenius Hans
Published: August 2002

The aim of the study was to explore differences in the content of prenatal mental representations between a risk group (n = 84) and a low‐risk group (n = 296) of pregnant women, enrolled from maternity care centers in southwestern Finland. The method used was semantic differentials of IRMAG (Interview of Maternal Representations During Pregnancy). The risk group was defined by means of questionnaire screens that concerned chemical dependency, depression, difficulties in social environment, and low social support. The ratings on all target subjects, i.e., child, self, partner, self‐as‐mother and own mother‐as‐mother, were significantly more negative in the risk group. The representation profiles of the groups differed: especially the ratings of partner and own mother‐as‐mother were more consistently and strongly negative among the risk mothers. © 2001 Michigan Association for Infant Mental Health.
Technologies, Products, and Models Supporting Knowledge Management
Authors: Luan Jing , Serban Andreea M.
Published: August 2002

Based on a taxonomy of knowledge management processes, this chapter provides a synopsis of technologies that support knowledge management. It proposes a model for classifying the various types of technologies related to knowledge management that are most often used in institutional research.
Preparation of blood‐compatible hollow fibers from a polymer alloy composed of polysulfone and 2‐methacryloyloxyethyl phosphorylcholine polymer
Authors: Hasegawa Takashi , Iwasaki Yasuhiko , Ishihara Kazuhiko
Published: August 2002

Blood‐compatible hollow fibers were successfully prepared from a polymer alloy composed of polysulfone (PSf) and the 2‐methacryloyloxyethyl phosphorylcholine (MPC) polymer. To improve the hydrophilicity, fouling‐resistance characteristics, and blood compatibility of the PSf hollow fiber in a hemodialyzer, an MPC polymer that can be blended with PSf was synthesized in order to prepare the polymer alloy (PSf/MPC polymer). The contents of the MPC polymer blended in the PSf were 7 and 15 wt%. The PSf/MPC polymer hollow fiber could be prepared by both wet and dry–wet processing methods. The hollow fiber took an asymmetric structure, that is, the hollow‐fiber membrane had a dense skin layer on the porous sponge‐like structure. The mechanical strength was higher than that of conventional PSf hollow fibers for hemodialysis. The surface characterization of the PSf/MPC polymer hollow fiber by x‐ray photoelectron spectroscopy revealed that the MPC units were concentrated at the surface. The permeability for solutes through the PSf/MPC polymer hollow fibers was measured for 4 h. The permeabilities of both a low‐molecular‐weight compound and protein were greater than those of the PSf hollow fibers. The amount of adsorbed protein was lower on the PSf/MPC polymer hollow fiber when compared to that of the PSf hollow fiber. Moreover, platelet adhesion was also effectively inhibited on the PSf/MPC polymer hollow fiber. Based on these results, the addition of the MPC polymer to the PSf is a very useful method to improve the functions and blood compatibility of the hollow fiber. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 333–341, 2002
In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA
Authors: Park Jeong‐Sook , Oh Yu‐Kyoung , Yoon Ho , Kim Jung Mogg , Kim Chong‐Kook
Published: August 2002

Nasal administration of plasmid DNA is emerging as a new route of delivery for therapeutic genes and DNA vaccines. To improve the intranasal absorption of plasmid DNA, we designed delivery systems composed of in situ gelling and mucoadhesive polymers. Poloxamers (Pol) were used to provide in situ gelling property. Polycarbophil (PC) or polyethylene oxide (PEO) was used as mucoadhesive polymers. The gelation temperatures of the formulations slightly decreased by the mucoadhesive polymers, but not by plasmid DNA. The in vitro release of plasmid DNA from the gels followed Fickian diffusion. The absorption of plasmid DNA varied with the contents and type of mucoadhesive polymers. Of vehicles, Pol/PC 0.2% showed the highest absorption with an area under the curve value 11‐fold higher than saline, the conventional vehicle. The nasal retention of plasmid DNA was highly prolonged by mucoadhesive polymers. At 3 h postdose, the nasal tissue levels of plasmid DNA given in Pol/PC and Pol/PEO 0.8% were 10‐ and 40‐fold higher relative to saline. The histopathology of nasal tissues was not altered after repeated dosing over 2 weeks. The mRNA expression of plasmid DNA delivered by Pol or Pol/PEO 0.4% was observed in the nasal tissues. These results indicate that the nasal absorption of plasmid DNA can be effectively and safely enhanced by using in situ gelling and mucoadhesive polymer‐based vehicles. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 144–151, 2002
Paired comparison of apheresis platelet function after storage in two containers
Authors: Zingsem Jürgen , Glaser Anke , Zimmermann Robert , Weisbach Volker , Kalb Rainer , Ruf Andreas , Eckstein Reinhold
Published: August 2002

Platelet quality after storage strongly depends on the pre‐storage quality as well as on the storage conditions determined by the storage container. In this paired study, we evaluated two different containers (MedSep CLX™ and Delmed DPL‐110). The Fresenius AS104 cell separator was used to prepare 17 platelet concentrates that were split and distributed into the containers to be compared. Cell counts, blood gas analysis, morphological scores, glucose and lactate levels, platelet activation, and platelet aggregation were measured before splitting at the day of preparation and after storage at day 3 and day 5. At day 3, there was no significant difference between the two bags apart from increased lactate and decreased pCO2 concentrations in the CLX™ bags. At day 5 there were significantly higher lactate concentrations, pO2 levels, and aggregation after stimulation in the CLX™ group, while the glucose and pCO2 concentrations were significantly lower in these platelet concentrates as compared to the DPL‐110 group. However, these parameters did not influence the functional parameters tested. While the platelet quality decreased during storage in all bags, the functional changes were nearly identical in both bags tested. We conclude that both bags are equivalent for 5‐day storage of platelet concentrates. J. Clin. Apheresis. 16:10–14, 2001. © 2001 Wiley‐Liss, Inc.
Cortisol regulates the expression of Notch in osteoblasts
Authors: Pereira Rosa M.R. , Delany Anne M. , Durant Deena , Canalis Ernesto
Published: August 2002

Glucocorticoids have important effects on osteoblastic replication, differentiation, and function, and the Notch family of receptors is considered to play a role in osteoblastic cell differentiation. We postulated that cortisol could regulate Notch and Notch ligand expression in osteoblastic cells, providing an additional mechanism by which glucocorticoids could regulate osteoblastic differentiation. We examined the expression and regulation of Notch1, 2, 3, and 4 and their ligands Jagged 1 and 2 and Delta 1 and 3 by cortisol in cultures of osteoblastic MC3T3‐E1 cells. Cortisol caused a time‐dependent increase in Notch1 and 2 mRNA levels in MC3T3 cells. Notch3 and 4 were not detected in the presence or absence of cortisol. MC3T3 cells expressed Delta 1 and Jagged 1 but not Jagged 2 or Delta 3 mRNAs, and cortisol did not have a substantial effect on the expression of any of these ligands. Cortisol increased the rate of Notch1 and 2 transcription and, in transcriptionally arrested cells, did not modify the decay of the transcripts, indicating a transcriptional level of control. In conclusion, cortisol stimulates Notch1 and 2 transcription in osteoblasts. Since Notch signaling appears to play a negative role in osteoblastic differentiation, its increased expression could be relevant to the actions of cortisol in bone. J. Cell. Biochem. 85: 252–258, 2002. © 2002 Wiley‐Liss, Inc.
Human papillomavirus‐16 E7 protein inhibits the DNA interaction of the TATA binding transcription factor
Authors: Maldonado Edio , Cabrejos María Eugenia , Banks Lawrence , Allende Jorge E.
Published: August 2002

Previous studies have shown that the HPV‐16 E7 protein interacts with TBP. This interaction was found to take place through residues in the carboxy terminal half of E7, mutation of which resulted in weaker transforming activity. In addition, binding of E7 to TBP was found to be increased following protein kinase CK2 (casein kinase II) phosphorylation of E7, and mutation of this CK2 site also reduces E7's transforming activity. To date, however, there is no information on the effects of E7 upon TBP function. In order to address this we have performed a series of assays to investigate the effects of E7 upon the ability of human and S. pombe TBP to bind DNA. We show that HPV‐16 E7 is indeed a potent inhibitor of TBP DNA binding activity. Further, this activity of E7 is increased following CK2 phosphorylation of E7, consistent with it having an increased affinity for TBP. Finally, a mutant E7 protein defective in its ability to bind TBP, has no effect upon TBP binding to DNA. These results demonstrate that one consequence of the E7–TBP interaction is abolition of TBP DNA binding activity, and may provide an explanation for the transcriptional inhibitory effects of E7. J. Cell. Biochem. 85: 663–669, 2002. © 2002 Wiley‐Liss, Inc.
Characterization of the upstream mouse Cbfa1/Runx2 promoter*
Authors: Xiao Z. S. , Liu Shi‐Guang , Hinson T. K. , Quarles L. D.
Published: August 2002

Cbfa1 (or Runx2/AML‐3/PEPB2α) is a transcriptional activator of osteoblastic differentiation. To investigate the regulation of Cbfa1 expression, we isolated and characterized a portion of the 5′‐flanking region of the Cbfa1 gene containing its “bone‐related” or P1 promoter and exon 1. We identified additional coding sequence in exon 1 and splice donor sites that potentially give rise to a novel Cbfa1 isoform containing an 18 amino acid insert. In addition, primer extension mapping identified in the Cbfa1 promoter a minor mRNA start site located ∼0.8 kb 5′ upstream of the ATG encoding the MASN/p57 isoform and ∼0.4 kb upstream of the previously reported start site. A luciferase reporter construct containing 1.4 kb of the mouse Cbfa1 promoter was analyzed in Ros 17/2.8 and MC3T3‐E1 osteoblast cell lines that express high levels of Cbfa1 transcripts. The activity of this construct was also examined in non‐osteoblastic Cos‐7 and NIH3T3 cells that do not express Cbfa1 and mesenchymal‐derived cell lines, including CH3T101/2, C2C12, and L929 cells, that express low levels of mature Cbfa1 transcripts. The 1.4 kb 5′ flanking sequence of the Cbfa1 gene directed high levels of transcriptional activity in Ros 17/2.8 and MC3T3‐E1 osteoblasts compared to non‐osteoblasts Cos‐7 cells, but this construct also exhibited high levels of expression in C310T1/2, L929, and C2C12 cells as well as NIH3T3 cells. In addition, Cbfa1 mRNA expression, but not the activity of the Cbfa1 promoter, was upregulated in a dose‐dependent manner in pluripotent mesenchymal C2C12 by bone morphogenetic protein‐2 (BMP‐2). These data indicate that Cbfa1 is expressed in osteogenic as well as non‐osteogenic cells and that the regulation of Cbfa1 expression is complex, possibly involving both transcriptional and post‐transcriptional mechanisms. Additional studies are needed to further characterize important regulatory elements and to identify additional regions of the promoter and/or post‐transcriptional events responsible for the cell‐type restricted regulation of Cbfa1 expression. J. Cell. Biochem. 82: 647–659, 2001. © 2001 Wiley‐Liss, Inc.
Characterisation of the temporal sequence of osteoblast gene expression during estrogen‐induced osteogenesis in female mice
Authors: Plant Andrea , Tobias Jonathan H.
Published: August 2002

Osteoblast differentiation under in vitro conditions is associated with increased expression of non‐collagenous bone proteins including osteocalcin, osteopontin, and osteonectin, the exact function of which remain poorly understood. To determine whether these proteins play an important role in the formation of mineralised bone matrix by osteoblasts in vivo, we analysed the time‐course of their expression during estrogen‐induced osteogenesis in female mice, and compared this with the formation of new cancellous bone. Female mice were sacrificed prior to or following treatment with 17β‐estradiol for up to 32 days (500 μg/animal/week). Total RNA was extracted from femurs, and changes in expression of genes for a range of osteoblast‐derived proteins assessed by Northern blot analysis. In parallel experiments, the time course of cancellous bone formation was determined by measuring bone mineral density (BMD) of the distal femur. Estrogen led to a rapid increase in BMD, which reached significance by Day 16. This was preceded by three‐fold increases in expression of alkaline phosphatase (ALP) and type I collagen (COL I) at Days 8 and 12 respectively. In contrast, osteocalcin, osteopontin, and osteonectin expression showed no change during this initial period, although modest increases were observed at later times (i.e., Days 20 and 24). Our results suggest that osteocalcin, osteopontin, and osteonectin are not involved in the initial phase of the osteogenic response to estrogen, suggesting that these non‐collagenous bone proteins do not play a direct role in the formation of mineralised bone matrix by osteoblasts in vivo. J. Cell. Biochem. 82: 683–691, 2001. © 2001 Wiley‐Liss, Inc.
Calculation of electronic g‐tensors for transition metal complexes using hybrid density functionals and atomic meanfield spin‐orbit operators
Authors: Kaupp Martin , Reviakine Roman , Malkina Olga L. , Arbuznikov Alexei , Schimmelpfennig Bernd , Malkin Vladimir G.
Published: August 2002

We report the first implementation of the calculation of electronic g‐tensors by density functional methods with hybrid functionals. Spin‐orbit coupling is treated by the atomic meanfield approximation. g‐Tensors for a set of small main group radicals and for a series of ten 3d and two 4d transition metal complexes have been compared using the local density approximation (VWN functional), the generalized gradient approximation (BP86 functional), as well as B3‐type (B3PW91) and BH‐type (BHPW91) hybrid functionals. For main group radicals, the effect of exact‐exchange mixing is small. In contrast, significant differences between the various functionals arise for transition metal complexes. As has been shown previously, local and in particular gradient‐corrected functionals tend to underestimate the “paramagnetic” contributions to the g‐tensors in these cases and thereby recover only about 40–50% of the range of experimental g‐tensor components. This is improved to ca. 60% by the B3PW91 functional, which also gives slightly reduced standard deviations. The range increases to almost 100% using the half‐and‐half functional BHPW91. However, the quality of the correlation with experimental data worsens due to a significant overestimate of some intermediate g‐tensor values. The worse performance of the BHPW91 functional in these cases is accompanied by spin contamination. Although none of the functionals tested thus appears to be ideal for the treatment of electronic g‐tensors in transition metal complexes, the B3PW91 hybrid functional exhibited the overall most satisfactory performance. Apart from the validation of hybrid functionals, some aspects in the treatment of spin‐orbit contributions to the g‐tensor are discussed. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 794–803, 2002
Parameterization of OPLS–AA force field for the conformational analysis of macrocyclic polyketides
Authors: Kahn Kalju , Bruice Thomas C.
Published: August 2002

The parameters for the OPLS–AA potential energy function have been extended to include some functional groups that are present in macrocyclic polyketides. Existing OPLS–AA torsional parameters for alkanes, alcohols, ethers, hemiacetals, esters, and ketoamides were improved based on MP2/aug‐cc‐pVTZ and MP2/aug‐cc‐pVDZ calculations. Nonbonded parameters for the sp3 carbon and oxygen atoms were refined using Monte Carlo simulations of bulk liquids. The resulting force field predicts conformer energies and torsional barriers of alkanes, alcohols, ethers, and hemiacetals with an overall RMS deviation of 0.40 kcal/mol as compared to reference data. Densities of 19 bulk liquids are predicted with an average error of 1.1%, and heats of vaporization are reproduced within 2.4% of experimental values. The force field was used to perform conformational analysis of smaller analogs of the macrocyclic polyketide drug FK506. Structures that adopted low‐energy conformations similar to that of bound FK506 were identified. The results show that a linker of four ketide units constitutes the shortest effector domain that allows binding of the ketide drugs to FKBP proteins. It is proposed that the exact chemical makeup of the effector domain has little influence on the conformational preference of tetraketides. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 977–996, 2002
Necessary existence criteria for mandatory representation designs MRD (4, k; ν)
Authors: Grüttmüller Martin , Rees R. S.
Published: August 2002

A mandatory representation design MRD (K; ν) is a pairwise balanced design on ν points with block sizes from the set K in which for each k ∈ K there is at least one block in the design of size k. A survey of known results on MRDs has been given in [J Comb Math Comb Comput, to appear] by Rees. MRDs with K = {3, k} have been extensively studied by Mendelsohn and Rees [J Comb Theory Ser A 49 ( 1988), 349–362], Rees [J Stat Plann Inference 86 (2000), 567–594], Rees and Grüttmüller [Congr Numerantium, 147 (2000), 41–51] and Grüttmüller [J Comb Des 8 (2000) 122–131; On the existence of pairwise balanced designs, Ph.D. Thesis, University of Rostock, 1999]. In this paper, we investigate necessary conditions for the existence of MRDs with K = {4, k}. © 2001 John Wiley & Sons, Inc. J Combin Designs 9: 309–333, 2001