bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of the MDR1 gene in the development of multidrug resistance in human hepatoblastoma
Authors: Warmann Steven , Hunger Mona , Teichmann Birgit , Flemming Peer , Gratz Klaus Friedrich , Fuchs Jörg 
Published: October 2002

AbstractBACKGROUNDThe P‐glyprotein (P‐gp), which is a membrane channel encoded by the MDR1 gene, represents a possible explanation for multidrug resistance in human hepatoblastoma (HB). P‐gp shows up‐regulation in tumor cells after chemotherapy; however, to date, its exact role in HB has not been described. The authors investigated the role of the MDR1 gene in the clinical course of patients with HB and in an in vivo model of HB. They also studied the effects of the MDR1 antagonizer PSC 833 on chemotherapy in mice xenotransplanted with HB.METHODSResected tumor specimens, including both primary tumors and recurrent tumors, from a child suffering from HB were investigated histologically. Cell suspensions from the originally removed tumor were incorporated subcutaneously into nude mice. Animals were treated with cisplatin (CDDP) plus PSC 833. MDR1 gene expression levels in the different resected tumors from the patient and in the xenotransplants after treatment were determined with polymerase chain reaction analysis.RESULTSMDR1 gene expression was increased in the patient's tumors after every course of chemotherapy from 30% to > 190%. In the xenotransplants, MDR1 gene expression was enhanced significantly after chemotherapy (PCDDP = 0.008; PCDDP+PSC = 0.002). Tumor volumes (P < 0.001) and serum α‐fetoprotein levels (P = 0.0002) were significantly lower in the animals that were treated with CDDP + PSC compared with the animals that were treated with CDDP alone.CONCLUSIONSThe current results suggest that MDR1 gene expression and P‐gp are a potential mechanism of drug resistance in HB. The chemosensitizer PSC 833 significantly improved the effects of chemotherapy in animals xenotransplanted with HB. These data encourage further studies concerning the role of chemosensitizers in overcoming multidrug resistance in patients with HB. Cancer 2002;95:1795–801. © 2002 American Cancer Society.DOI 10.1002/cncr.10858
Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum‐based regimens
Authors: Ricci Sergio , Galli Luca , Chioni Aldo , Iannopollo Mauro , Antonuzzo Andrea , Francesca Francesco , Vocaturo Vittorio , Selli Cesare , Orlandini Cinzia , Conte PierFranco 
Published: October 2002

AbstractBACKGROUNDThe objective of this study was to evaluate the efficacy and toxicity of gemcitabine plus epirubicin in previously untreated patients with advanced urothelial carcinoma who were not eligible for cisplatin‐based regimens.METHODSPatients with advanced urothelial carcinoma and at least one of the following characteristics were eligible: impaired renal function (creatinine clearance < 60 mL per minute), an Eastern Cooperative Oncology Group performance status (PS) ≥ 2, and age ≥ 75 years. The treatment included epirubicin 70 mg/m2 as an intravenous bolus on Day 1 and gemcitabine 1000 mg/m2 over 30 minutes on Days 1 and 8 of a 21‐day cycle.RESULTSThirty‐eight patients entered the study, and a total of 152 cycles were administered, with a median of 4 cycles per patient (range, 1–6 cycles per patient). The following Grade 3–4 hematologic toxicities were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed. Dose intensities of epirubicin and gemcitabine were 19.6 mg/m2 per week (84%) and 532.2 mg/m2 per week (80%), respectively. There were 2 complete responses (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%), and 12 patients with progressive disease (31.6%), for an overall response rate of 39.5% (95% confidence interval, 25.1–55.1). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months, respectively. The 1‐year survival rate was 38%, and the median PFS and OS were 6.4 months and 16.4 months, respectively, in patients with PS 0–1. Thirty patients were symptomatic: Seventeen patients (56.7%) achieved a complete response, and 5 patients (16.7%) achieved a partial symptomatic response.CONCLUSIONSAt the doses given in this study, gemcitabine and epirubicin had a good tolerability profile with interesting activity in patients with advanced urothelial carcinoma who were not fit for cisplatin‐based regimens. Cancer 2002;95:1444–50. © 2002 American Cancer Society.DOI 10.1002/cncr.10860
Promoting early detection tests for colorectal carcinoma and adenomatous polyps
Authors: Levin Bernard , Smith Robert A. , Feldman Gabriel E. , Colditz Graham A. , Fletcher Robert H. , Nadel Marion , Rothenberger David A. , Schroy Paul S. , Vernon Sally W. , Wender Richard ,   National Colorectal Cancer Roundtable
Published: October 2002

AbstractBACKGROUNDThe purpose of the current study was to provide health professionals, professional organizations, policy makers, and the general public with a practical blueprint for increasing the practice of screening for colorectal carcinoma (CRC) and adenomatous polyps over the next decade. The National Colorectal Cancer Roundtable (NCCRT) was founded in 1997 by the American Cancer Society and the Centers for Disease Control and Prevention to provide strategic leadership, advocacy, long‐range planning, and coordination of interventions targeted at reducing the disease burden of CRC through education, early detection, and prevention. The NCCRT and its three workgroups include CRC survivors; recognized experts in primary care, gastroenterology, radiology, colorectal surgery, nursing, public policy, epidemiology, and behavioral science; patient advocates; and representatives of health plans and insurers, government, and other organizations.METHODSThe NCCRT performed a literature review of published and unpublished data related to CRC screening guidelines, compliance, and barriers to adherence, as well as test effectiveness and cost‐effectiveness. Members of the three NCCRT workgroups developed summary reports regarding professional education, public education and awareness, and health policy. A drafting committee developed the final strategic plan from workgroup reports, which was reviewed by the entire NCCRT membership, amended, and subsequently approved in final form.RESULTS AND CONCLUSIONSAlthough the rationale for population‐wide CRC screening is well established, the majority of adults in the U.S. are not currently being screened for CRC. Thus, the nation foregoes an opportunity to reduce CRC‐related mortality by an estimated ≥ 50%. To increase CRC screening rates, the issues of patient and physician barriers to screening, lack of universal coverage, lack of incentives to motivate adherence, and expanded infrastructure must be addressed. Cancer 2002;95:1618–28. © 2002 American Cancer Society.DOI 10.1002/cncr.10890
Development of cricket mushroom bodies
Authors: Malaterre Jordane , Strambi Colette , Chiang Ann‐Shyn , Aouane Aicha , Strambi Alain , Cayre Myriam 
Published: October 2002

AbstractMushroom bodies are recognized as a multimodal integrator for sensorial stimuli. The present study analyzes cricket mushroom body development from embryogenesis to adulthood. In the house cricket, Kenyon cells were born from a group of neuroblasts located at the apex of mushroom bodies. Our results demonstrate the sequential generation of Kenyon cells: The more external they are, the earlier they were produced. BrdU treatment on day 8 (57% stage) of embryonic life results, at the adult stage, in the labelling of the large Kenyon cells at the periphery of the mushroom body cortex. These cells have specific projections into the posterior calyx, the gamma lobe, and an enlargement at the inner part of the vertical lobe; they represent a part of mushroom bodies of strictly embryonic origin. The small Kenyon cells were formed from day 9 (65% stage) of the embryonic stage onward, and new interneurons are produced throughout the entire life of the insect. They send their projections into the anterior calyx and into the vertical and medial lobes. Mushroom body development of Acheta should be considered as a primitive template, and cross‐taxonomic comparisons of the mushroom body development underscore the precocious origin of the gamma lobe. As a result of continuous neurogenesis, cricket mushroom bodies undergo remodeling throughout life, laying the foundation for future studies of the functional role of this developmental plasticity. J. Comp. Neurol. 452:215–227, 2002. © 2002 Wiley‐Liss, Inc.
Increased brain size and glial cell number in CD81‐null mice
Authors: Geisert Eldon E. , Williams Robert W. , Geisert Grace R. , Fan Liying , Asbury Andrew M. , Maecker Holden T. , Deng Jun , Levy Shoshana 
Published: October 2002

AbstractA key issue in the development of the central nervous system (CNS) is understanding the molecular mechanisms regulating cell number. The present study examines the role of CD81 (previously known as TAPA, the target of the antiproliferative antibody) in the control of brain size and glial cell number. CD81 is a member of the tetraspanin family of proteins. This group of small membrane proteins is associated with the regulation of cell migration and mitotic activity. Glial cells express CD81, and antibodies directed against this protein suppress the mitotic activity of cultured cells. In this study, we examine the effects of the CD81 −/− mutation on the CNS of mature mice. These mice have extremely large brains, as much as 30% larger than the brains of wild‐type (+/+) littermates. The increase in brain weight is accompanied by an increase in the number astrocytes and microglia, whereas the number of neurons and oligodendrocytes in the CD81 −/− animals appears to be normal. When the CD81 −/− mutation is placed on different genetic backgrounds, there is a remarkable range in the penetrance of the null allele phenotype, demonstrating that the mutation can be affected by modifier loci. This work provides support for the role of CD81 in the regulation of astrocyte and microglial number, perhaps by regulating cell proliferation by a contact inhibition‐dependent mechanism. J. Comp. Neurol. 453:22–32, 2002. © 2002 Wiley‐Liss, Inc.
Quantitative organization of neurotransmitters in the deep cerebellar nuclei of the Lurcher mutant
Authors: Sultan Fahad , König Thomas , Möck Martin , Thier Peter 
Published: October 2002

AbstractThe Lurcher mutant mouse is characterized by a primary selective loss of Purkinje cells, leading to the near total apoptotic death of these neurons. In contrast to the subsequent massive secondary degeneration of the granule cells and the inferior olivary neurons, only mild degeneration occurs in the deep cerebellar nuclei (DCN). However, it is not known to what extent the different populations of DCN neurons—glutamatergic principal projection neurons, γ‐aminobutyric acid (GABA)‐ergic inferior olivary projection neurons, and glycinergic neurons—are affected in their neurotransmitter composition. To answer this question we studied the neurotransmitter contents (glutamate, GABA, and glycine) of DCN neurons and the size of synaptic boutons immunohistochemically on serial semithin sections in both Lurcher and wild‐type mice. Applying the physical dissector counting method, our results confirmed the mild degeneration (a reduction by 20%) of large glutamatergic neurons and a more pronounced degeneration of GABAergic (by 42%) and glycinergic neurons (by 45%). On the other hand, an analysis of neurons colabeled for both GABA and glycine, revealed that this specific colabeling increased in the Lurcher mutant (by 40%). In addition, both the GABA‐immunolabeled (IL) (by 56%) and the glycine‐IL (by 45%) synaptic boutons showed an increase in diameter in the mutant. The density of these boutons showed a decrease of 30% each. In summary, the increase in the number of neurons colabeled for GABA and glycine, together with the increase in the size of the inhibitory synaptic boutons, could help in providing the minimum inhibition needed to maintain a residual “cerebellar” functionality in the Lurcher DCN. J. Comp. Neurol. 452:311–323, 2002. © 2002 Wiley‐Liss, Inc.
Androgen receptors in the embryonic zebra finch hindbrain suggest a function for maternal androgens in perihatching survival
Authors: Godsave Susan F. , Lohmann Ragna , Vloet Rianka P.M. , Gahr Manfred 
Published: October 2002

AbstractBird embryos are exposed to maternal androgens deposited in the egg, but the role of these hormones in embryonic development and hatchling survival is unclear. To identify possible target organs, we used in situ hybridization to study the distribution of androgen receptor (AR) RNA in the developing zebra finch brain. The first brain expression domain of AR mRNA is in the hindbrain. From embryonic day 7 (E7) onward, when the hypoglossal motor nucleus (nXII) has just formed, there was AR mRNA expression in both its lingual (nXIIl) and its tracheosyringeal (nXIIts) parts, and this was the major site of hindbrain expression at all embryonic stages and in both sexes. From E8 onward, we also found AR mRNA in the supraspinal motor nucleus (nSSp), which innervates neck muscles. Furthermore, the syrinx, the target of the nXIIts, contained AR mRNA by E10, localized principally in the perichondria. Muscle was first evident in the syringeal region at E9, but no AR was detected in syringeal muscles until after hatching. The expression pattern of AR in the zebra finch embryo suggests that maternal androgens act via AR in the brainstem and syrinx to influence hatching as well as acoustic and visual components of food‐begging behavior. Maternal androgens seem unlikely to function in the development of sexual dimorphisms in the zebra finch nXIIts and syrinx, insofar as these are not evident until between 10 and 20 days posthatching. J. Comp. Neurol. 453:57–70, 2002. © 2002 Wiley‐Liss, Inc.
Boundary concentration phenomena for a singularly perturbed elliptic problem
Authors: Malchiodi Andrea , Montenegro Marcelo 
Published: October 2002

AbstractWe exhibit new concentration phenomena for the equation − ε2 Δu + u = up in a smooth bounded domain Ω ⊆ ℝ2 and with Neumann boundary conditions. The exponent p is greater than or equal to 2 and the parameter ε is converging to 0. For a suitable sequence εn → 0 we prove the existence of positive solutions un concentrating at the whole boundary of Ω or at some component. © 2002 Wiley Periodicals, Inc.
Simulating multiple inheritance in Java
Authors: Lyon Douglas 
Published: October 2002

AbstractTheCentiJsystem automatically generates code that simulates multiple inheritance in Java. The generated code inputs a series of instances and outputs specifications that can be combined using multiple inheritance. The multiple inheritance of implementation is obtained by simple message forwarding. ThereflectionAPI of Java is used to reverse engineer the instances, and so the program can generate source code, but does not require source code on its input. Advantages ofCentiJinclude compile‐time type checking, speed of execution, automatic disambiguation (name space collision resolution) and ease of maintenance.Simulation of multiple inheritance was previously available only to Java programmers who performed manual delegation or who made use of dynamic proxies. The technique has been applied at a major aerospace corporation. Copyright © 2002 John Wiley & Sons, Ltd.
Detection of in situ activation of transglutaminase during apoptosis: Correlation with the cell cycle phase by multiparameter flow and laser scanning cytometry
Authors: Grabarek Jerzy , Ardelt Barbara , Kunicki Jan , Darzynkiewicz Zbigniew 
Published: October 2002

AbstractBackgroundOne of the hallmarks of apoptosis is activation of tissue transglutaminase (Tgase; also called transglutaminase type 2 [TGase 2]). Its activation causes cross‐linking of cytoplasmic proteins, making them insoluble and presumably less immunogenic. Several biochemical and cytochemical methods to detect activity of TGase 2 exist, but none has been adapted for multiparameter flow or image cytometry.MethodsApoptosis of HL‐60 or U‐937 leukemic cells was induced by camptothecin, tumor necrosis factor α, hyperthermia, or the cytotoxic RNase onconase. Two different approaches to detect TGase 2 activation were developed: (a) the unfixed cells were treated with 4′,6′‐diamidino‐2‐phenylindole, and sulforhodamine 101 in solutions of nonionic detergents; (b) the TGase 2 substrate fluoresceinated polyamine cadaverine (F‐CDV) was administered into the cultures for several hours before cell harvesting. The cells were then fixed and their DNA counterstained with propidium. Cellular fluorescence was measured by flow or laser scanning cytometry.Results(a) Exposure of nonapoptotic cells to detergents caused their full lysis, resulting in preparation of isolated nuclei devoid of cytoplasm. Conversely, the cross‐linking of cytoplasmic protein by activated TGase 2 in apoptotic cells provided resistance to detergents: the nuclei or nuclear (chromatin) fragments of apoptotic cells remained attached to the cytoplasmic protein, embedded within the proteinaceous “shell.” Such cells were identified by their high protein content: intensity of fluorescence after staining with the protein fluorochrome sulforhodamine 101 was markedly higher than that of isolated nuclei. (b) Activation of TGase 2 was also detected by virtue of intense cell labeling with fluoresceinated polyamine cadaverine. Interestingly, in many cells apoptosis progressed without evidence of activation of TGase 2, suggesting that this event may not be a prerequisite for completion of apoptosis.ConclusionsActivation of TGase 2 can be detected simply by cell resistance to detergents or in situ reactivity with F‐CDV. Both methods allow one to correlate activation of TGase 2 with the cell cycle position. However, because activation of TGase 2 is not always detected during apoptosis, the lack of the activation cannot be considered a marker of nonapoptotic cells. Hence, an apoptotic index based solely on TGase 2 activation may underestimate incidence of apoptosis. Cytometry 49:83–89, 2002. © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of a case of HIV‐associated anaplastic myeloma
Authors: Stewart John M.M. , Krishnamurthy Savitri 
Published: October 2002

AbstractPlasma cell neoplasia occurs much less frequently than high‐grade B‐cell non‐Hodgkins lymphoma in HIV‐infected patients, but is nevertheless an AIDS‐associated malignancy. In this report, we describe the fine‐needle aspiration (FNA) findings of a mass in the left parotid region with plasmablastic features that occurred in a 41‐yr‐old HIV‐infected homosexual man whom we diagnosed as having anaplastic myeloma. The patient had normochromic, normocytic anemia with a hematocrit of 21%, a white blood count of 2.2 × 109/l with 76% neutrophils, and a CD4 count of 31%. He also had elevated levels of calcium (13.2 mg/dl), alkaline phosphatase (25,400 IU/l), blood urea nitrogen (2,600 mg/dl), and creatinine (2.5 mg/dl). Serum protein electrophoresis showed polyclonal hypergammaglobulinemia without any monoclonal component. A bone survey revealed multiple punched‐out lytic lesions. FNA smears showed large plasmacytoid cells with eccentrically placed nuclei, prominent nucleoli, and moderate amounts of basophilic cytoplasm. By immunocytochemical staining, tumor cells were negative for CD19, CD20, and leukocyte‐common antigen (LCA), but strongly positive for CD38 and kappa light chain.Anaplastic myeloma and plasmablastic lymphoma were considered in the differential diagnosis. Although the cytomorphologic and immunophenotypic findings of our case overlapped with those of plasmablastic lymphoma, the pattern of bone involvement with punched‐out lytic lesions and absence of localization of the tumor to the mucosa of the oral cavity led us to a diagnosis of anaplastic myeloma. The patient initially received antiretroviral therapy followed by thalidomide and pulse dexamethasome therapy, but his response was poor. His HIV load increased, and his malignancy rapidly progressed with the development of multiple vertebral lesions, extraosseous extension, and eventually cord compression. He died of the disease less than 2 mo after presentation. Diagn. Cytopathol. 2002;27:218–222. © 2002 Wiley‐Liss, Inc.
Metals and oxidative homeostasis in Alzheimer's disease
Authors: Perry George , Cash Adam D. , Srinivas Ravi , Smith Mark A. 
Published: October 2002

AbstractOxidative damage to every class of biological macromolecule has been characterized in Alzheimer's disease. Abnormalities in iron and copper metabolism are also being implicated as playing a crucial role in neurodegenerative disease pathogenesis. Metal homeostasis as it pertains to alterations in brain function in neurodegenerative diseases is reviewed here with its relationship to oxidative stress. While there is documented evidence for alterations in transition metal homeostasis, redox‐activity, and localization, it is also important to realize that alterations in specific copper‐ and iron‐containing metalloenzymes also contribute to the neurodegenerative process. These changes offer the opportunity to identify pathways where modification of the disease process can offer new routes for clinical efficacy, from gene therapy to use of antioxidant and chelating drugs. Drug Dev. Res. 56:293–299, 2002. © 2002 Wiley‐Liss, Inc.
Regulated expression of α2B adrenoceptor during development
Authors: Wang Guey‐Shin , Chang Nan‐Chi , Wu Shinn‐Chih , Chang Alice Chien 
Published: October 2002

AbstractThere are three subtypes of α2 adrenoceptor, i.e., α2A, α2B, and α2C, mediating the specific effect of epinephrine and norepinephrine in various tissues by means of G protein–coupled signal transduction pathways. In an attempt to delineate the regulatory mechanism of the α2B receptor subtype (encoded by subtype gene Adra2b) expression in the central nervous system (CNS), we have established transgenic (Tg) mice lines in which the transgene (NN‐lacZ) was composed of the promoter region of Adra2b (NcoI fragment, 4.7 kb immediately upstream from receptor coding region) and a reporter gene lacZ (encoding β‐galactosidase). The selective expression of α2B in brain as indexed by β‐galactosidase, under the direction of this promoter region, may be traced in situ by using X‐gal staining. The expression pattern of Adra2b‐NN‐lacZ in CNS of Tg mice during development was examined. The temporal course of examination was from gestation day 9.5 (E9.5) to postnatal day 28 (P28). Significant X‐gal staining was detected in the dorsal root ganglion and cranial nerves V and VII at E12.5. By E18.5, expression was noted in the cerebral cortex, anterior olfactory nucleus, hypothalamus, brainstem, and cerebellar Purkinje cells, among others, and persisted through postnatal development. Adra2b‐NN–directed reporter expression was detected in the hippocampal dentate gyrus first at P4. The temporal course of expression up to P28 in this area is in accordance with the developmental profiles of granule neurons of dentate gyrus. From P7 on, transgene expression was detected in additional brain areas, including the septum and thalamus. The expression correlates well with the noradrenergic innervations as evidenced by colocalization by using tyrosine hydroxylase or dopamine‐β‐hydroxylase immunocytochemistry. © 2002 Wiley‐Liss, Inc.