bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simulation of digital earthquake accelerograms using the inverse discrete Fourier transform
Authors: Thráinsson Hjörtur , Kiremidjian Anne S. 
Published: October 2002

AbstractAcceleration time histories of horizontal earthquake ground motion are obtained by inverting the discrete Fourier transform, which is defined by modelling the probability distribution of the Fourier phase differences conditional on the Fourier amplitude.The Fourier amplitude spectrum is modelled as a scaled, lognormal probability density function. Three parameters are necessary to define the Fourier amplitude spectrum. They are the total energy of the accelerogram, the central frequency, and the spectral bandwidth.The Fourier phase differences are simulated conditional on the Fourier amplitudes. The amplitudes are classified into three categories: small, intermediate and large. For each amplitude category, a beta distribution or a combination of a beta distribution and a uniform distribution are defined for the phase differences. Seven parameters are needed to completely define the phase difference distributions: two for each of the three beta distributions, and the weight of the uniform distribution for phase differences corresponding to small Fourier amplitudes.Approximately 300 uniformly processed horizontal ground motion records from recent California earthquakes are used to develop prediction formulas for the model parameters, as well as to validate the simulation model. The moment magnitude of the earthquakes ranges from 5.8 to 7.3. The source to site distance for all the records is less than 100 km. Copyright © 2002 John Wiley & Sons, Ltd.
Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer
Authors: Boks Dominique E.S. , Trujillo Aliana P. , Voogd Adri C. , Morreau Hans , Kenter Gemma G. , Vasen Hans F.A. 
Published: October 2002

AbstractEndometrial carcinoma (EC) is the most common extracolonic tumor associated with hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC increases the risk of EC compared to the general population. Patients with HNPCC have a better prognosis than patients with common sporadic colorectal cancer. It is unknown, however, whether the survival rate of HNPCC‐associated EC is higher than that of sporadic EC. The aim of our study was to compare the survival rates of HNPCC‐associated EC with sporadic EC. From the registry of the Netherlands Foundation for Hereditary Tumors, 50 patients with HNPCC‐associated EC from 46 families harboring a germline mutation or fulfilling the Amsterdam Criteria II were age‐ and stage‐matched with 100 patients with sporadic EC registered in the Eindhoven Cancer Registry in the Netherlands. Survival rates were analyzed. The overall 5‐year cumulative survival rates for patients with HNPCC‐associated EC was 88% and 82% for patients with sporadic EC (p = 0.59). In Stages IA, IB and IC, the survival rates of patients with HNPCC‐associated EC and sporadic EC were 92% and 91%, respectively (p = 0.90). In Stages IIIA and IIIC, the survival rates for HNPCC‐associated EC and sporadic EC were 72% and 50%, respectively (p = 0.38). Furthermore, there was no significant difference in the distribution of tumor histologic subtypes in the study and control groups (p = 0.55). The outcomes in survival in EC in the general population and in women from families with HNPCC do not differ significantly. These results may have important implications in our understanding of EC and the role of early screening. © 2002 Wiley‐Liss, Inc.
Gender effects in familial cancer
Authors: Hemminki Kari , Li Xinjun 
Published: October 2002

AbstractVery limited data are available on sex ratios in familial cancer. Such data would be valuable in the assessment of sex chromosome effects and of interactions between background and familial rates. We used the nationwide Swedish Family‐Cancer Database on 10.2 million individuals and over 1 million neoplasms to analyze familial risks for male and female offspring by paternal and maternal concordant cancer. Sex ratios for familial cancer were derived for cancer at 15 sites shared by men and women. At 14 sites the sex ratio (male/female) for familial relative risk ranged between 0.78 and 1.41, with no evidence of sex preference, suggesting that sex chromosomes do not contribute to a noticeable extent to familial risks. Furthermore, in cancers where the background incidence varied extensively by sex, such as bladder cancer (sex ratio 2.82) and nonthyroid endocrine tumors (0.65), the familial effect was proportionate to the background incidence and the familial sex ratio was close to unity. In thyroid cancer, the familial sex ratio was 2.48 (1.54–3.98) and the background incidence ratio was 0.31. This was the first evidence of an inverse sex ratio in primary cancer, i.e., higher familial risk in the gender of low background risk. The high familial ratio, 2.85 (95% CI: 1.35–6.03), was due to thyroid adenocarcinoma, encompassing both papillary and follicular types. © 2002 Wiley‐Liss, Inc.
Emerging functions of p21‐activated kinases in human cancer cells
Authors: Kumar Rakesh , Vadlamudi Ratna K. 
Published: October 2002

AbstractThe p21 activated kinases (Paks), an evolutionarily conserved family of serine/threonine kinases, are important for a variety of cellular functions including cell morphogenesis, motility, survival, mitosis, and angiogenesis. Paks are widely expressed in numerous tissues and are activated by growth factors and extracellular signals through GTPase‐dependent and ‐independent mechanisms. Overexpression of Paks in epithelial cancer cells has been shown to increase migration potential, increase anchorage independent growth, and cause abnormalities in mitosis. Dysregulation of Paks has been reported in several human tumors and neurodegenerative diseases. A growing list of novel Pak interacting proteins has opened up exciting avenues of investigation by which to understand the functions of Paks in tumorigenesis. In this review, we will summarize the current knowledge of the Paks family with respect to emerging cellular functions and possible contributions to cancer. © 2002 Wiley‐Liss, Inc.
Lipopolysaccharide‐induced reductions in cellular coupling correlate with tyrosine phosphorylation of connexin 43
Authors: Lidington Darcy , Tyml Karel , Ouellette Yves 
Published: October 2002

AbstractWe have previously shown in cultured rat microvascular endothelial cells (RMEC) that lipopolysaccharide (LPS) stimulates a protein tyrosine kinase (PTK)‐dependent reduction in cellular coupling. We hypothesized that connexin 43 (Cx43) becomes phosphorylated following exposure to LPS. Cx43 was immunoprecipitated from control and LPS‐treated RMEC monolayers. Tyrosine phosphorylation of Cx43, detected by immunoblot, was found only in the LPS treatment. To verify these results, Cx43 was radiolabeled with [32P]‐orthophosphate. Radiolabeled Cx43 exhibited a slight increase in phosphorylation in response to LPS; phosphoamino acid analysis displayed equivalent amounts of phosphoserine in control and LPS treatments, but detected phosphotyrosine only in the LPS treatment. The PTK inhibitors PP‐2 (10 nM) and geldanamycin (200 nM) were found to block the response to LPS in terms of Cx43 tyrosine phosphorylation and cellular coupling. The phosphatase inhibitor BpV (1 μM) accentuated the effect of LPS, while the putative phosphatase activator C6‐ceramide prevented it. When measuring cell communication, phosphatase inhibition also blocked the reversal of the LPS response following LPS washout. We conclude that Cx43 is tyrosine phosphorylated following exposure to LPS and suggest that the LPS‐induced increase in intercellular resistance may be mediated by tyrosine phosphorylation of this connexin. Altering tyrosine kinase and phosphatase activities can modulate the LPS‐induced tyrosine phosphorylation of Cx43 and reductions in cellular coupling. J. Cell. Physiol. 193: 373–379, 2002. © 2002 Wiley‐Liss, Inc.
Cellular distribution of oxygen sensor candidates—Oxidases, cytochromes, K+‐channels—in the carotid body
Authors: Kummer Wolfgang , Yamamoto Yoshio 
Published: October 2002

AbstractThe specific tissue of the carotid body is built up of groups of glomus cells, enveloped by glial‐type sustentacular cells, and innervated by sensory nerve fibers. These units sense arterial pO2 and respond to hypoxia by a variety of reactions that include initiation of the arterial chemoreflex, i.e., increasing firing activity in the carotid sinus nerve. Until now, neither the cellular localization of the initial events that lead to stimulation of chemoreceptor afferents nor the molecular mechanism of oxygen sensing in the carotid body have been unequivocally identified. Proposed molecular candidates for the mechanism of oxygen sensing include: 1) components of the mitochondrial respiratory chain, 2) NADPH oxidases generating reactive oxygen species in an oxygen‐dependent manner, 3) oxygen‐regulated plasmalemmal K+‐channels, and 4) nonoxidase iron‐proteins. Our still limited knowledge on their cellular distribution within the carotid body is reviewed here. It is evident that: 1) the distribution of at least some oxygen sensor candidates is not ubiquitous but cell‐type‐specific, and 2) each specific parenchymal cell type of the carotid body contains at least one of the proposed oxygen sensor candidates. This applies also for the glial‐type sustentacular cells that exhibit immunoreactivity to the two‐pore domain K+‐channel, TASK‐1. These observations fit best with the assumption that each cell type within the carotid body is principally responsive to hypoxia. The differential equipping of glomus cells, nerve endings, and sustentacular cells with sensor proteins might serve to determine different thresholds of sensitivity and/or to connect the process of oxygen sensing to different signaling pathways. It also favors the assumption that several mechanisms of oxygen sensing may act simultaneously. The cellular identification of the cell type initiating the chemoreceptor reflex, however, has to await the molecular identification of the particular oxygen sensor molecule that initiates increased carotid sinus nerve activity. Microsc. Res. Tech. 59:234–242, 2002. © 2002 Wiley‐Liss, Inc.
Carotid body chemoreceptors in dissociated cell culture
Authors: Nurse C.A. , Fearon I.M. 
Published: October 2002

AbstractCarotid body (CB) glomus or type 1 cells act as peripheral chemoreceptors which detect changes in arterial PO2, PCO2, and pH and help maintain homeostasis via the reflex control of ventilation. Over the last ∼12 years significant progress has been made towards understanding chemotransduction mechanisms using freshly isolated or cultured type 1 cells. The latter preparation allows several powerful experimental manipulations (e.g., co‐culture with sensory neurons) resulting in significant advances in our understanding of CB chemoreception. Here, we review several properties of type 1 cells after several days to weeks in culture. Typically, cultured type 1 cells grow in monolayer clusters enveloped by glial‐like, type II, or sustentacular cells, which are immunopositive for the glial marker, glial fibrillary acid protein (GFAP). These cells can undergo DNA synthesis, evidenced by uptake of bromodeoxyuridine (BrdU), and show a limited capacity for cell division. Mitosis and survival of type 1 cells can be regulated by oxygen tension and/or growth factors (e.g., bFGF, insulin). In the rat, type 1 cells are immunopositive for several monoaminergic markers, including tyrosine hydroxylase (TH), dopamine transporter (DAT), and 5‐HT. They also express cholinergic markers (e.g., vesicular acetylcholine transporter; VAChT), the highly conserved synaptic vesicle protein (SV2), and gap junctional proteins including Connexin 32 (Cx32). Moreover, in long‐term culture (∼2 weeks) they retain expression of O2‐sensitive, TASK‐1‐like, and Ca2+‐dependent (BK), K+ channels as revealed by immunocytochemistry or RT‐PCR analysis of mRNA extracted from type 1 clusters after removal from the culture surface. Microsc. Res. Tech. 59:249–255, 2002. © 2002 Wiley‐Liss, Inc.
Inhibition of interleukin‐1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis
Authors: Coxon Angela , Bolon Brad , Estrada Juan , Kaufman Stephen , Scully Sheila , Rattan Alana , Duryea Diane , Hu Yi‐Ling , Rex Karen , Pacheco Efrain , Van Gwyneth , Zack Debra , Feige Ulrich 
Published: October 2002

AbstractObjectiveTo assess the capacities of the cytokine inhibitors interleukin‐1 receptor antagonist (IL‐1Ra; anakinra) and PEGylated soluble tumor necrosis factor receptor I (PEG sTNFRI; pegsunercept) to suppress neovascularization.MethodsA corneal angiogenesis assay was performed by implanting nylon discs impregnated with an angiogenic stimulator (basic fibroblast growth factor or vascular endothelial growth factor) into one cornea of female Sprague‐Dawley rats. Animals were treated with IL‐1Ra or PEG sTNFRI for 7 days, after which new vessels were quantified. In a parallel study, male Lewis rats with mycobacteria‐induced adjuvant‐induced arthritis were treated with IL‐1Ra or PEG sTNFRI for 7 days beginning at disease onset, after which scores for inflammation and bone erosion as well as capillary counts were acquired from sections of arthritic hind paws.ResultsTreatment with IL‐1Ra yielded a dose‐dependent reduction in growth factor–induced corneal angiogenesis, while PEG sTNFRI did not. IL‐1Ra, but not PEG sTNFRI, significantly reduced the number of capillaries in arthritic paws, even though both anticytokines reduced inflammation and bone erosion to a similar degree.ConclusionThese data support a major role for IL‐1, but not TNFα, in angiogenesis and suggest that an additional antiarthritic mechanism afforded by IL‐1 inhibitors, but not anti‐TNF agents, is the suppression of the angiogenic component of pannus.
On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles
Authors: Morris Richard W. , Kaplan Norman L. 
Published: October 2002

AbstractWe investigated the effect of multiple susceptibility alleles at a single disease locus on the statistical power of a likelihood ratio test to detect association between alleles at a marker locus and a disease phenotype in a case‐control design. Using simplifying assumptions to obtain the joint frequency distribution of marker and disease locus alleles, we present numerical results that illustrate the impact of historical variation of initial associations between marker alleles and susceptibility alleles on the power of a likelihood ratio test for association. Our results show that an increase in the number of susceptibility alleles produces a decrease in power of the likelihood ratio test. The decrease in power in the presence of multiple susceptibility alleles, however, is less for markers with multiple alleles than for markers with two alleles. We investigate the implications of this observation for tests of association based on haplotypes made up of tightly linked single‐nucleotide polymorphisms (SNPs). Our results suggest that an analysis based on haplotypes can be advantageous over an analysis based on individual SNPs in the presence of multiple susceptibility alleles, particularly when linkage disequilibria between SNPs is weak. The results provide motivation for further development of statistical methods based on haplotypes for assessing the potential for association methods to identify and locate complex disease genes. Genet. Epidemiol. 23:221–233, 2002. © 2002 Wiley‐Liss, Inc.
Chronic hypoxia‐induced morphological and neurochemical changes in the carotid body
Authors: Wang Zun‐Yi , Bisgard Gerald E. 
Published: October 2002

AbstractThe carotid body (CB) plays an important role in the control of ventilation. Type I cells in CB are considered to be the chemoreceptive element which detects the levels of PO2, PCO2, and [H+] in the arterial blood. These cells originate from the neural crest and appear to retain some neuronal properties. They are excitable and produce a number of neurochemicals. Some of these neurochemicals, such as dopamine and norepinephrine, are considered to be primarily inhibitory to CB function and others, such as adenosine triphosphate, acetylcholine, and endothelin, are thought to be primarily excitatory. Chronic hypoxia (CH) induces profound morphological as well as neurochemical changes in the CB. CH enlarges the size of CB and causes hypertrophy and mitosis of type I cells. Also, CH changes the vascular structure of CB, including inducing marked vasodilation and the growth of new blood vessels. Moreover, CH upregulates certain neurochemical systems within the CB, e.g., tyrosine hydroxylase and dopaminergic activity in type I cells. There is also evidence that CH induces neurochemical changes within the innervation of the CB, e.g., nitric oxide synthase. During CH the sensitivity of the CB chemoreceptors to hypoxia is increased but the mechanisms by which the many CH‐induced structural and neurochemical changes affect the sensitivity of CB to hypoxia remains to be established. Microsc. Res. Tech. 59:168–177, 2002. © 2002 Wiley‐Liss, Inc.
Carotid labyrinth of amphibians
Authors: Kusakabe Tatsumi 
Published: October 2002

AbstractThe amphibian carotid labyrinth is a characteristic maze‐like vascular expansion at the bifurcation of the common carotid artery into the internal and external carotid arteries. The carotid labyrinths of anurans are spherical and those of urodeles are oblong. In the intervascular stroma of both anuran and urodelan carotid labyrinths, the glomus cells (type I cells, chief cells) are distributed singly or in clusters between connective tissue cells and smooth muscle cells. In fluorescence histochemistry, the glomus cells emit intense fluorescence for biogenic monoamines. In fine structure, the glomus cells are characterized by a number of dense‐cored vesicles in their cytoplasm. The glomus cells have long, thin cytoplasmic processes, some of which are closely associated with smooth muscle cells, endothelial cells, and pericytes. Afferent, efferent, and reciprocal synapses are found on the glomus cells. The morphogenesis of the carotid labyrinth starts in the larvae at the point where the carotid arch descends to the internal gills. Through the early stages of larval development, the slightly expanded region of the external carotid artery becomes closely connected with the carotid arch. By the end of the foot stage, the expanded region becomes globular, and at the final stage of metamorphosis the carotid labyrinth is close to its adult form. In fine structure, the glomus cells appear as early as the initial stage of larval development. At the middle stages of development, the number of dense‐cored vesicles increases remarkably. Distinct afferent synapses are found in juveniles, although efferent synapses can be seen during metamorphosis. The carotid labyrinth is innervated by nerve fibers containing several kinds of regulatory neuropeptides. Double‐immunolabeling in combination with a multiple dye filter system demonstrates the coexistence of two different neuropeptides. The amphibian carotid labyrinth has been electrophysiologically confirmed to have arterial chemo‐ and baroreceptor functions analogous to those of the mammalian carotid body and carotid sinus. The ultrastructural characteristics of the glomus cells during and after metamorphosis suggest that the glomus cells contribute to the chemoreception after metamorphosis. The three‐dimensional fine structure of vascular corrosion casts suggests that the amphibian carotid labyrinth has the appropriate architecture for controlling vascular tone and the findings throughout metamorphosis reveal that the vascular regulatory function begins at an early stage of metamorphosis. In addition, immunohistochemical studies suggest that the vascular regulation in the carotid labyrinth is under peptidergic innervation. Thus, the multiple functions of the carotid labyrinth underline the importance of this relatively small organ for maintenance of homeostasis and appropriate blood supply to the cephalic region. Microsc. Res. Tech. 59:207–226, 2002. © 2002 Wiley‐Liss, Inc.
Synthetic peptides as cancer vaccines
Authors: Sundaram Roshni , Dakappagari Naveen K. , Kaumaya Pravin T. P. 
Published: October 2002

AbstractEffective cancer therapy or prevention has been the dream of physicians and scientists for many years. Although we are still very far from our ultimate goal of cancer prevention, significant milestones have been realized in terms of our knowledge base and understanding of the pathogenesis of cancerous cells and the involvement of the immune system against both self‐ and virus‐associated tumor antigens. Immunotherapeutic strategies are now accepted to being superior in terms of the exquisite specificity that they offer in targeting only tumor cells as opposed to the existent chemotherapy or radiation therapy that is more general and invasive with many associated side effects. There are several immunotherapeutic strategies that are currently under investigation. This review primarily focuses on the significant advances made in the use of synthetic peptides in the development of subunit cancer vaccines. We have attempted to highlight some of the fundamental issues regarding antigen processing and presentation, Major Histocompatibility Complex (MHC) restriction, T‐cell help, structural determinants in antibody recognition, and the use of these concepts in the rational design and delivery of peptide vaccines to elicit protective humoral and cell mediated immune responses. The recent use of costimulatory molecules and cytokines to augment immune responses also has been discussed along with the contributions of our laboratory to the field of synthetic peptide vaccine development. © 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 200–216, 2002
P2P‐R protein overexpression restricts mitotic progression at prometaphase and promotes mitotic apoptosis
Authors: Gao Sizhi , Scott Robert E. 
Published: October 2002

AbstractMitotic cells show a tenfold increase in immunoreactive P2P‐R protein. During mitosis, the distribution of P2P‐R protein also changes from a primary nucleolar localization in interphase cells to the periphery of chromosome in mitotic cells. These findings suggest that P2P‐R might serve a functional role in mitosis. To test this possibility, human Saos2 cells were stably transfected with P2P‐R DNA constructs and the biological effects of P2P‐R overexpression were evaluated. Overexpression of near full‐length P2P‐R was found to have paradoxical effects on the relationship between proliferation and mitosis in the nine Saos2 cell clones that were studied. A significant repression in the population doubling rates was observed in all nine clones even though a significant increase in the frequency of easily detached cells with a mitotic morphology was apparent. Flow cytometric analysis confirmed that greater than two thirds of the cells with a mitotic morphology had a 4n DNA content. Confocal microscopy further established that 85% of the mitotic cell population had prometaphase characteristics suggesting that P2P‐R overexpression restricts mitotic progression at prometaphase. Many cells with a mitotic morphology also showed signs of apoptosis with prominent cell surface blebs. Confocal microscopy confirmed that 25–40% of such mitotic cells were apoptotic with chromosomal abnormalities and cell surface blebbing. In association with mitotic apoptosis, P2P‐R protein appears to dissociate from the periphery of chromosomes and localize in the cytoplasm and in cell surface blebs. The presence of P2P‐R in cell surface blebs was confirmed by analysis of highly enriched populations of apoptotic cell surface blebs wherein Western blotting documented the presence of 250 kDa P2P‐R. These results therefore suggest that P2P‐R overexpression promotes both prometaphase arrest in mitosis and mitotic apoptosis. © 2002 Wiley‐Liss, Inc.