bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival of in situ carcinoma of cervix uteri: A 50‐year follow‐up in Finland
Authors: Hakama Matti , Luostarinen Tapio , Hakulinen Timo 
Published: August 2004

AbstractPreinvasive lesions of cervix uteri are regarded a curable disease despite some progression to invasive cancer. The ultimate outcome is not known. We estimated the 45‐year survival of 12,655 patients with carcinoma in situ lesions diagnosed in 1953–2000 and reported to the Finnish Cancer Registry. Up to 30 years of follow‐up there was about 1% decrease in cumulative relative survival per 5 years of follow‐up. After that the excess mortality increased and the survival at 45 years was 84%. The 15‐year survival was 100% in the patients under 30 at diagnosis and became the poorer the older the patient. Survival was 89% in the patients 60–74 at diagnosis. Women with carcinoma in situ are at substantial increased risk of death (>10%) only at high ages and independent of age at diagnosis. © 2004 Wiley‐Liss, Inc.
RLIP76 (RALBP1)‐mediated transport of leukotriene C4 (LTC4) in cancer cells: Implications in drug resistance
Authors: Sharma Rajendra , Singhal Sharad S. , Wickramarachchi Dilki , Awasthi Yogesh C. , Awasthi Sanjay 
Published: August 2004

AbstractIncreased active transport of LTC4 observed frequently in multidrug‐resistant cancer cells have been attributed to ABC‐transporter proteins particularly, MRP1. We have demonstrated recently that a novel non‐ABC transporter, RLIP76 (RALBP1) can also mediate ATP‐dependent transport of GSH‐conjugates (GS‐E) as well as doxorubicin (DOX). We demonstrate RLIP76 reconstituted in artificial liposomes can catalyze ATP‐dependent transport of LTC4, which can be modulated by PKC‐α. The ATPase activity of E. coli expressed homogenous RLIP76 was stimulated in a saturable fashion by LTC4 with half maximal stimulation at 130 nM. Proteoliposomes reconstituted with RLIP76 catalyzed temperature and osmolar sensitive ATP‐dependent transport of LTC4 with Km values of 5.1 mM and 210 nM for ATP and LTC4, respectively. Vmax for transport was found to be 3.2 nmol/min/mg. Colchicine inhibited LTC4 transport to 50% at 5.8 μM. PKC‐α catalyzed phosphorylation of RLIP76 and increased its transport activity by 2–3‐fold. Membrane vesicles prepared from the small (SCLC) and non‐small (NSCLC) lung cancer cell lines as well as HL‐60 (leukemia) and U937 (lymphoma) cell lines exhibited ATP‐dependent transport of LTC4, which was inhibited by anti‐RLIP76 antibodies. The rate of transport of LTC4 in SCLC (H69, H378) was half of that observed in NSCLC cell lines but after transfection with RLIP76, the transport rate of LTC4 in H69 became comparable to that in NSCLC cell lines. Anti‐RLIP76 antibodies inhibited LTC4 transport by 67–81% in all 8 cell lines examined, whereas N‐19 anti‐MRP1 antibodies inhibited transport of LTC4 by only 11–26%. These results suggest that RLIP76 is the major LTC4 transporter in cancer cells and that its transport activity is regulated by PKC‐α‐mediated phosphorylation. © 2004 Wiley‐Liss, Inc.
Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma
Authors: Nakashima Kazue , Shimada Hideaki , Ochiai Takenori , Kuboshima Mari , Kuroiwa Namiko , Okazumi Shinichi , Matsubara Hisahiro , Nomura Fumio , Takiguchi Masaki , Hiwasa Takaki 
Published: August 2004

AbstractWe applied serological analysis of recombinant cDNA expression libraries (SEREX) to cases of esophageal squamous cell carcinoma (SCC) to identify tumor antigens. One of the clones identified was TROP2, which is known as calcium signal transducer. To evaluate the clinical significance of serum anti‐TROP2 antibodies (s‐TROP2‐Abs) in patients with esophageal SCC, the presence of s‐TROP2‐Abs was analyzed by Western blotting using bacterially expressed TROP2 protein. We found that 23 of 75 (31%) patients were positive for s‐TROP2‐Abs. Positivity in terms of s‐TROP2‐Abs showed a significant association with tumor size but not with other clinicopathological features. The protein expression levels of TROP2 were much higher in esophageal SCC cell lines as compared to those in normal esophageal mucosa and its immortalized cells although the mRNA expression levels were not necessarily elevated in malignant cell lines and tissues. Immunohistochemical studies showed that the expression of TROP2 protein in esophageal SCC specimens was noticeably higher than that found in mild hyperplasia of esophageal mucosae. Thus, s‐TROP2‐Abs seemed useful in the diagnosis of SCC and may be a candidate for serum tumor markers. © 2004 Wiley‐Liss, Inc.
Cigarette smoking and the risk of gastric cancer: A pooled analysis of two prospective studies in Japan
Authors: Koizumi Yayoi , Tsubono Yoshitaka , Nakaya Naoki , Kuriyama Shinichi , Shibuya Daisuke , Matsuoka Hiroo , Tsuji Ichiro 
Published: August 2004

AbstractTo examine the association between cigarette smoking and the risk of gastric cancer, we conducted a pooled analysis of 2 population‐based prospective cohort studies in rural northern Japan. Cohort 1 included 9,980 men (≥40 years old) and Cohort 2 included 19,412 men (40–64 years old). The subjects completed a self‐administered questionnaire on cigarette smoking and other health habits. We identified 228 cases of gastric cancer among Cohort 1 subjects (9 years of follow‐up with 74,073 person‐years) and 223 among Cohort 2 subjects (7 years of follow‐up with 141,675 person‐years). From each cohort, we computed the relative risk (RR) and 95% confidence interval (CI) of gastric cancer associated with smoking using a Cox regression analysis and pooled these estimates to obtain summary measures. The pooled multivariate RRs (95% CIs) for current smokers and past smokers compared to subjects who had never smoked were 1.84 (1.39–2.43) and 1.77 (1.29–2.43), respectively. The higher number of cigarettes smoked per day among current smokers was associated with a linear increase in risk (trend p < 0.05). The significant increase in risk for past smokers remained for up to 14 years after cessation. An increased risk was noted for cancer of the antrum but not for cardia or body lesions. The risk was increased for both differentiated and nondifferentiated histologic subtypes. Our findings support the hypothesis that cigarette smoking is a risk factor for gastric cancer. © 2004 Wiley‐Liss, Inc.
Epigenetic inactivation of SOCS‐1 by CpG island hypermethylation in human gastric carcinoma
Authors: Oshimo Yasuhiro , Kuraoka Kazuya , Nakayama Hirofumi , Kitadai Yasuhiko , Yoshida Kazuhiro , Chayama Kazuaki , Yasui Wataru 
Published: August 2004

AbstractSuppressor of cytokine signaling (SOCS)‐1 inhibits signaling of the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway by several cytokines and has tumor suppressor activity. Methylation of the SOCS‐1 CpG island has been shown to inactivate the SOCS‐1 gene in certain human cancers. In our study, we investigated methylation status of the SOCS‐1 gene by methylation‐specific PCR in 75 gastric carcinoma (GC) tissues, 25 corresponding nonneoplastic mucosae and 10 normal gastric mucosae from healthy young individuals. We also performed bisulfite sequencing of DNAs from 2 GC tissues. In addition, SOCS‐1 mRNA levels were examined in 50 GCs by quantitative RT‐PCR. Hypermethylation of the SOCS‐1 gene was detected in 33 (44%) of 75 GC tissues and in 3 (12%) of 25 corresponding nonneoplastic mucosae; the incidence was significantly different (p = 0.004). None of the 10 normal gastric tissues from healthy individuals showed hypermethylation. Methylation of the SOCS‐1 gene was associated with lymph node metastasis, advanced tumor stage and reduced expression of SOCS‐1 in GC tissues (p = 0.009, 0.034 and 0.002, respectively). Reduced expression of SOCS‐1 in GC tissues was associated with lymph node metastasis and advanced tumor stage (p = 0.013 and 0.002, respectively). Our results suggest that transcriptional inactivation of the SOCS‐1 gene by hypermethylation may be involved in development, progression and metastasis of GC. © 2004 Wiley‐Liss, Inc.
Development and characterization of a canine oral mucosa equivalent in a serum‐free environment
Authors: Song Junhui , Izumi Kenji , Lanigan Thomas , Feinberg Stephen E. 
Published: August 2004

AbstractThe objectives of this study were to develop a serum‐free system for culturing canine oral keratinocytes, the construction and characterization of a canine ex vivo produced oral mucosa equivalent (EVPOME), and transduction green fluorescent protein (GFP) into keratinocytes as a post‐grafting tracking marker. Dissociated canine buccal mucosa keratinocytes were cultured in a chemically defined serum‐free medium, Epilife™. First‐passage keratinocytes were transfected with the GFP gene using a lentiviral vector, sorted by flow cytometer and seeded onto a dermal equivalent, AlloDerm® to form EVPOMEs. The EVPOME was characterized by histology and immunohistochemistry, for p63, Ki‐67, and involucrin. Laser confocal microscopy was used to locate GFP‐transfected keratinocytes within the EVPOME. Cultured canine oral keratinocytes grew rapidly over the first three passages and then the proliferative rate decreased. The canine EVPOME formed a well‐stratified epithelial layer. The majority of p63 and Ki‐67 immunopositive cells were located in the basal layer whereas cytoplasmic involucrin expression was seen in the suprabasal layers, similar to native canine buccal mucosa. Under laser confocal microscopy, significant green fluorescence was observed throughout the EVPOME. In conclusion, canine EVPOMEs were successfully fabricated in a defined serum‐free system with similar characteristics to native buccal mucosa. GFP‐transfected canine oral keratinocytes could be identified within the EVPOME. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 143–153, 2004
Designing scaffolds for valvular interstitial cells: Cell adhesion and function on naturally derived materials
Authors: Masters Kristyn S. , Shah Darshita N. , Walker Gennyne , Leinwand Leslie A. , Anseth Kristi S. 
Published: August 2004

AbstractValvular interstitial cells (VICs) possess many properties that make them attractive for use in the construction of a tissue‐engineered valve; however, we have found that the surfaces to which VICs will adhere and spread are limited. For example, VICs adhere and spread on collagen and laminin‐coated surfaces, but display altered morphology and do not proliferate. Interestingly, fibronectin (FN) was one adhesion protein that facilitated VIC adhesion and proliferation. Yet VICs did not spread on surfaces modified with RGD, a ubiquitous cell‐adhesive peptide, nor with other FN‐specific peptide sequences such as EILDV and PHSRN. Hyaluronic acid (HA) is a highly elastic polysaccharide that is involved in natural valve morphogenesis and possesses binding interactions with FN. Hyaluronic acid was modified to form photopolymerizable hydrogels, and VICs were found to spread and proliferate on HA‐based gels, forming a confluent monolayer on the gels within 4 days. Modified HA retained its ability to specifically bind FN, allowing for the formation of gels containing both HA and FN. Valvular interstital cells cultured on HA surfaces displayed significantly increased production of extracellular matrix proteins, indicating that HA‐based scaffolds may provide useful biological cues to stimulate heart valve tissue formation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 172–180, 2004
Carrier dependent cell differentiation of bone morphogenetic protein‐2 induced osteogenesis and chondrogenesis during the early implantation stage in rats
Authors: Takita H. , Vehof J. W. M. , Jansen J. A. , Yamamoto M. , Tabata Y. , Tamura M. , Kuboki Y. 
Published: August 2004

AbstractTo evaluate the osteoinductive effects of recombinant human bone morphogenetic protein (rhBMP)‐2 during the early stages of rat ectopic bone formation, we prepared two distinct carriers. Two carriers, insoluble bone matrix (IBM) and fibrous glass membrane (FGM) were combined with rhBMP‐2 and implanted into the backs of rats to evaluate the osteoinductive effects of the two rhBMP‐2 carrier systems. Insoluble bone matrix particle size was 320 to 620 μm. Fibrous glass membrane was constructed from unwoven glass fibers 1 μm in diameter. Alkaline phosphatase (ALP) activity and type II collagen were detected in IBM/rhBMP‐2 at 5 days postimplantation. Calcium (Ca) was also detected in IBM/rhBMP‐2 at 7 and 9 days postimplantation. In contrast, ALP and type II collagen were detected in FGM/rhBMP‐2 at 7 days. Calcium was undetected, indicating that the bone formation in IBM/rhBMP‐2 proceeded faster than in FGM/rhBMP‐2 during the early stage of BMP‐induced osteogenesis. In addition, mRNA expression level of KDR, a receptor for vascular endothelial growth factor, was also increased in IBM/rhBMP‐2. To investigate the in vivo release profile of rhBMP‐2, iodine 125 (125I)‐labeled BMP‐2–incorporating IBM and FGM implants were inserted into the back subcutis of mice. More than 60% of the rhBMP‐2 was released from the IBM/rhBMP‐2 carrier within 1 day after implantation, whereas 50% of the rhBMP‐2 was released from the FGM/rhBMP‐2 10 days postimplantation. These results indicated that osteo‐ and chondrogenesis depends highly upon the geometry of the carrier and the in situ retention of rhBMP‐2 during the early stage of rhBMP‐2 induced bone formation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 71A: 181–189, 2004
On the complexity of the circular chromatic number
Authors: Hatami H. , Tusserkani R. 
Published: August 2004

AbstractCircular chromatic number, χcis a natural generalization of chromatic number. It is known that it isNP‐hard to determine whether or not an arbitrary graphGsatisfies χ(G)=χc(G). In this paper we prove that this problem isNP‐hard even if the chromatic number of the graph is known. This answers a question of Xuding Zhu. Also we prove that for all positive integersk ≥ 2 andn ≥ 3, for a given graphGwith χ(G) = n, it isNP‐complete to verify if$\chi _c(G) \le n- {1\over k}$. © 2004 Wiley Periodicals, Inc. J Graph Theory 47: 226–230, 2004
Pancyclicity of 3‐connected graphs: Pairs of forbidden subgraphs
Authors: Gould Ronald J. , Łuczak Tomasz , Pfender Florian 
Published: August 2004

AbstractWe characterize all pairs of connected graphs {X, Y} such that each 3‐connected {X, Y}‐free graph is pancyclic. In particular, we show that if each of the graphs in such a pair {X, Y} has at least four vertices, then one of them is the claw K1,3, while the other is a subgraph of one of six specified graphs. © 2004 Wiley Periodicals, Inc. J Graph Theory 47: 183–202, 2004
Uncatalyzed microwave deuterium exchange labeling of bleomycin A2
Authors: de Keczer Steve A. , Lane Tim S. , Masjedizadeh Mohammad R. 
Published: August 2004

AbstractBleomycin sulfate in D2O was deuterated using microwave irradiation under catalyst free conditions. Following the removal of labile deuterium and purification, bleomycin A2 with mass M + 1 to M + 7 was obtained. Successful selective uncatalyzed microwave deuterium exchange reactions on examples from the following classes of heterocycles are also described: imidazole, thiazole, indole, purine, and quinazoline. The described method was used as a test for non‐labile active protons. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis of 14C‐labelled EM‐800 (SCH 57050) and EM‐652·HCl (SCH 57068·HCl, acolbifene), pure selective estrogen receptor modulators
Authors: Sancéau Jean‐Yves , Labrie Fernand , Gauthier Sylvain 
Published: August 2004

AbstractEM‐800 (SCH 57050) and EM‐652·HCl (SCH 57068·HCl, acolbifene) are orally active pure selective estrogen receptor modulators. The corresponding 14C2‐radiolabelled compounds 1 and 2 were synthesized for metabolic studies with uniform labelling of two carbons within the benzene ring of the 2H‐1‐benzopyran moiety by optical resolution of racemic (±)‐[14C2]EM‐343 4. This pivotal intermediate amine was prepared in 6 steps with 38% yield from commercially available [U‐14C2]resorcinol (3). Resolution by selective crystallization of the diastereomeric mixture of (S)‐(+)‐camphorsulfonates salts gave the desired (+)‐[14C2]EM‐652·(+)‐CSA 13. Moreover, the racemic amine 4 was recovered from mother liquors by basic treatment, and resolved again. We obtained salt 13, at a 52% yield with 97% diastereomeric excess by repeating the resolution–racemization process. Finally, the corresponding dipivaloate (+)‐[14C2]EM‐800 1 and hydrochloride salt (+)‐[14C2]EM‐652·HCl 2 were prepared at respective specific activities of 19.7 and 24.5 µCi/mg with 96.3% radiochemical purity. Copyright © 2004 John Wiley & Sons, Ltd.
Design of a radiopharmaceutical for the palliation of painful bone metastases: rhenium‐186‐labeled bisphosphonate derivative
Authors: Ogawa Kazuma , Mukai Takahiro , Arano Yasushi , Hanaoka Hirofumi , Hashimoto Kazuyuki , Nishimura Hiroshi , Saji Hideo 
Published: August 2004

AbstractTo develop a radiopharmaceutical for the palliation of painful bone metastases based on the concept of bifunctional radiopharmaceuticals, we designed a bisphosphonate derivative attached to a stable 186Re‐monoaminemonoamidedithiol (MAMA) chelate (186Re‐MAMA‐BP) to improve the instability of 186Re‐HEDP. The precursor (Tr‐MAMA‐BP) of 186Re‐MAMA‐BP was synthesized by coupling the carboxyl group of the Tr‐MAMA derivative with the amino group of the bisphosphonate derivative. This 186Re‐labeled compound was prepared by a ligand exchange reaction using 186Re‐glucoheptonate with a radiochemical yield of 32.0 ± 4.1%. In the incubation study in buffered solution (pH 7.0), 186Re‐MAMA‐BP was more stable than 186Re‐HEDP. This suggests that 186Re‐MAMA‐BP is a potential radiopharmaceutical for the palliation of painful bone metastases. Copyright © 2004 John Wiley & Sons, Ltd.
Spectrum of movement disorders in neuroferritinopathy
Authors: Crompton Douglas E. , Chinnery Patrick F. , Bates David , Walls Timothy J. , Jackson Margaret J. , Curtis Andrew J. , Burn John 
Published: August 2004

AbstractNeuroferritinopathy is a recently recognized, dominantly inherited movement disorder caused by a mutation of the ferritin light chain gene. We present video case reports of 4 individuals with neuroferritinopathy chosen to illustrate how this disorder can present and subsequently progress clinically. The clinical phenotype of this disorder is highly variable with symptoms beginning in the third to sixth decades. Chorea, dystonia, or an akinetic‐rigid syndrome can predominate in different individuals. Neuroferritinopathy is not restricted to the UK and it has been described in apparently sporadic cases. The diagnosis should therefore be considered in patients with a wide variety of different movement disorders. Characteristic neuroimaging assists in identifying affected individuals. © 2004 Movement Disorder Society
Clinical utility of electrodiagnostic consultation in suspected polyneuropathy
Authors: Cho S. Charles , Siao‐Tick‐Chong Peter , So Yuen T. 
Published: August 2004

AbstractAlthough paresthesias of the distal lower limbs are characteristic features of polyneuropathy, they may also herald the presence of a focal neuropathy, polyradiculopathy, or myelopathy. Electromyography and nerve conduction studies (EMG/NCS) are widely used in the evaluation of such symptoms, but their utility has not been subjected to vigorous scrutiny. We investigated the clinical impact of the electrodiagnostic consultation in assessing suspected polyneuropathy. When compared with the clinical impression, the result of the electrodiagnostic consultation was confirmatory in only 39% of all patients, and changed the diagnosis or uncovered an additional diagnosis in 43%. An alternative diagnosis was likely when either weakness was present (75%) or the Achilles stretch reflex was preserved (48%). These data support the use of EMG/NCS in the diagnostic evaluation of patients presenting with distal paresthesias, especially in those with preserved Achilles reflexes or motor deficits. Muscle Nerve 2004
Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations
Authors: Muchir A. , Medioni J. , Laluc M. , Massart C. , Arimura T. , Kooi A. J. Van Der , Desguerre I. , Mayer M. , Ferrer X. , Briault S. , Hirano M. , Worman H. J. , Mallet A. , Wehnert M. , Schwartz K. , Bonne G. 
Published: August 2004

AbstractMutations in LMNA, the gene that encodes nuclear lamins A and C, cause up to eight different diseases collectively referred to as “laminopathies.” These diseases affect striated muscle, adipose tissue, peripheral nerve, and bone, or cause features of premature aging. We investigated the consequences of LMNA mutations on nuclear architecture in skin fibroblasts from 13 patients with different laminopathies. Western‐blotting showed that none of the mutations examined led to a decrease in cellular levels of lamin A or C. Regardless of the disease, we observed honeycomb nuclear structures and nuclear envelope blebs in cells examined by immunofluorescence microscopy. Concentrated foci of lamin A/C in the nucleoplasm were also observed. Only mutations in the head and tail domains of lamins A and C significantly altered the nuclear architecture of patient fibroblasts. These results confirm that mutations in lamins A and C may lead to a weakening of a structural support network in the nuclear envelope in fibroblasts and that nuclear architecture changes depend upon the location of the mutation in different domains of lamin A/C. Muscle Nerve 30: 444–450, 2004
Influence of body mass index on median nerve function, carpal canal pressure, and cross‐sectional area of the median nerve
Authors: Werner Robert A. , Jacobson Jon A. , Jamadar David A. 
Published: August 2004

AbstractObese individuals have slowed conduction in the median nerve across the wrist, but the mechanism for this is not established. This case‐control study of 27 obese subjects and 16 thin subjects was designed to test the hypothesis that obese individuals have higher carpal canal pressures and more median nerve swelling than thin individuals. All subjects were asymptomatic for hand symptoms, and had measurements of median and ulnar sensory nerve conduction in the nondominant hand, ultrasound measurement of the median nerve cross‐sectional area proximal to the carpal canal, and carpal canal pressure measurement. There was no difference in age or gender ratio between the obese and thin groups. The median nerve cross‐sectional area was equal in the obese and thin groups (9.3 mm2 vs. 9.4 mm2), as was the carpal canal pressure (16.2 mmHg vs. 15.5 mmHg, respectively). There was a strong correlation between median nerve conduction slowing across the wrist and median nerve cross‐sectional area at the wrist (r = 0.55, P = 0.002). Obesity does not influence carpal canal pressure or the size of the median nerve at the wrist. However, there is a strong association between slowed median nerve conduction and increased nerve size which suggests endoneurial edema as a metabolic mechanism; the conduction slowing does not appear to be related to mechanical stress. Muscle Nerve 30: 481–485 2004
Distribution and morphometry of skeletal muscle fibers in patients with chronic obstructive pulmonary disease and chronic hypoxemia
Authors: Pereira Mônica C. , Isayama Ricardo N. , Seabra José C. , Campos Gerson E. R. , Paschoal Ilma A. 
Published: August 2004

AbstractThis study was designed to assess the size and distribution of muscle fiber types in patients with severe chronic obstructive pulmonary disease and stable chronic hypoxemia. Brachial biceps biopsies were performed in 8 patients and 12 controls. Histochemistry was used to count and determine the cross‐sectional area of the various fiber‐types (1, 2a, and 2b). A significant reduction (P < 0.05) in the proportion of type 2a fibers and an increase in the proportion and cross‐sectional area of type 2b fibers were seen in hypoxemic patients. These findings suggest an adaptation of the muscle fibers to a low partial pressure of oxygen in arterial blood. Muscle Nerve 2004