bluuebunny/crossref_metadata_2025_split huggingface dataset:
Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation
Authors: Roberts Joseph L. , Lengi Andrea , Brown Stephanie M. , Chen Min , Zhou Yong-Jie , O'Shea John J. , Buckley Rebecca H. 
Published: November 2003

AbstractWe found 10 individuals from 7 unrelated families among 170 severe combined immunodeficiency (SCID) patients who exhibited 9 different Janus kinase 3 (JAK3) mutations. These included 3 missense and 2 nonsense mutations, 1 insertion, and 3 deletions. With the exception of 1 individual with persistence of transplacentally transferred maternal lymphocytes, all infants presented with a T–B+NK– phenotype. The patient mutations all resulted in abnormal B-cell Janus kinase 3 (JAK3)–dependent interleukin-2 (IL-2)–induced signal transducer and activator of transcription-5 (STAT5) phosphorylation. Additional analyses of mutations permitting protein expression revealed the N-terminal JH7 (del58A) and JH6 (D169E) domain mutations each inhibited receptor binding and catalytic activity, whereas the G589S JH2 mutation abrogated kinase activity but did not affect γc association. Nine of the 10 patients are currently alive from between 4 years and 18 years following stem cell transplantation, with all exhibiting normal T-cell function. Reconstitution of antibody function was noted in only 3 patients. Natural killer (NK) function was severely depressed at presentation in the 4 patients studied, whereas after transplantation the only individuals with normal NK lytic activity were patients 1 and 5. Hence, bone marrow transplantation is an effective means for reconstitution of T-cell immunity in this defect but is less successful for restoration of B-cell and NK cell functions.
Series introduction: innate host defense of the respiratory epithelium
Authors: Hiemstra Pieter S , Bals Robert 
Published: November 2003

AbstractThis series overviews the current knowledge of the innate-immune system of the lung. Special emphasis is put on mechanisms used by epithelial cells of the respiratory tract to contribute to host defense. This defense function is important, as the lung is especially prone to microbial exposure. The exchange of oxygen and carbon dioxide requires the ventilation of a large volume of environmental air that may contain respiratory pathogens. Furthermore, the digestive pathway shares with the airways the pharynx, opening another possibility for the uptake of microorganisms into the respiratory tract. Host defense is provided by a multilayered and complex system that aims to avoid colonization and infection of the lung. A classic view separates the inborn, innate-immune system from adaptive mechanisms that involve antigen-specific lymphocytes [1].
Glucocorticoid Receptor Counteracts Tumorigenic Activity of Akt in Skin through Interference with the Phosphatidylinositol 3-Kinase Signaling Pathway
Authors: Leis Hugo , Page Angustias , Ramírez Angel , Bravo Ana , Segrelles Carmen , Paramio Jesús , Barettino Domingo , Jorcano José L. , Pérez Paloma 
Published: November 2003

Abstract
The skin-targeted overexpression of the glucocorticoid receptor (GR) in transgenic mice dramatically impairs the inflammatory responses to tumor promoter agents and suppresses skin tumor development. The antiinflammatory, rapid effects of corticosteroids are partially exerted through interference of GR with the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway in several tissues, a highly relevant pathway in the mouse skin tumor progression process. In this work, we aimed to elucidate whether a cross-talk mechanism between GR and PI3K/Akt occurred in intact skin as well as the biological relevance of this interaction during skin tumorigenesis. We report that, in transgenic mice overexpressing the receptor, GR physically associated with p85α/PI3K in skin, resulting in decreased Akt and IκB kinase activity. GR activation by dexamethasone in normal mouse skin also decreased Akt activity within minutes, whereas cotreatment with the GR antagonist RU486 abolished dexamethasone action. Indeed, GR exerted a nongenomic action because keratinocyte transfection with a transcriptionally defective receptor mutant still decreased PI3K and Akt activity. Moreover, GR coexpression greatly reduced the accelerated growth of malignant tumors and increased Akt activity induced by Akt-transfected keratinocytes, as shown by in vivo tumorigenic assays. Overall, our data strongly indicate that GR/PI3K-Akt cross-talk constitutes a major mechanism underlying the antitumor effect of glucocorticoids in skin.
Chronic myelogenous leukemia with e13a3 (b2a3) type of BCR‐ABL transcript having a DNA breakpoint between ABL exons a2 and a3
Authors: Liu Li‐Gen , Tanaka Hideo , Ito Kinro , Kyo Taiichi , Ito Takuo , Kimura Akiro 
Published: November 2003

AbstractWe describe a patient with chronic myelogenous leukemia (CML), in whom the DNA breakpoint in the BCR‐ABL fusion gene was determined to result in a rare e13a3 (b2a3) transcript. The breakpoint in BCR was intron 13, which was 30 bp downstream from exon 13, and the breakpoint in ABL was intron 2, and was 46 bp downstream from exon a2. This case conforms to the mechanism of DNA breakage occurring within ABL intron 2, but not at 5′ to ABL exon a2. With our review of this case and the literature, it seems that CML with the BCR‐a3 fusion product is associated with a low proportion of circulating immature cells, mild or lack of splenomegaly, slow progressiveness, rather resistance to IFN‐α, and good response to imatinib mesylate. This is the first report of BCR‐a3‐type CML in which the exact DNA breakpoint was identified and located between exons a2 and a3 of the ABL gene. Am. J. Hematol. 74:268–272, 2003. © 2003 Wiley‐Liss, Inc.
Extranodal diffuse follicular center lymphoma mimicking mantle cell lymphoma of the intestine
Authors: Tomita Shigeki , Kojima Masaru , Imura Johji , Hori Hiroshige , Ueda Yoshihiko , Koitabashi Ayako , Suzuki Yasunaga , Nakamura Tetsuya , Nakamura Yuichi , Mitani Kinuko , Terano Akira , Ohkura Yasuo , Kawamata Hitoshi , Fujimori Takahiro 
Published: November 2003

AbstractWe report a case of diffuse follicular center lymphoma (FCL), which is a morphological variant of follicular lymphoma, resembling multiple lymphomatous polyposis (mantle cell lymphoma of the intestine). The patient was a 48‐year‐old Japanese man who was found, by colonoscopy, to have numerous small polypoid lesions along the entire large intestine. Abdominal computed tomography revealed hepatosplenomegaly and enlargement of multiple mesenteric lymph nodes. Histologically, the lesion was characterized by diffuse proliferation of small‐ to medium‐sized lymphocytes with cleaved nuclei in the mucosa and submucosa. Immunohistochemical studies showed that the tumor cells were CD20+, CD10+, BCL‐2+, CD5–, surface IgM–, and cyclin D1–. Moreover, a cytogenetic study showed a translocation at (14;18)(q32;q21). Finally, this case was diagnosed as diffuse FCL, although the tumor was mimicking mantle cell lymphoma. Am. J. Hematol. 74:287–289, 2003. © 2003 Wiley‐Liss, Inc.
Proportionate cancer mortality among workers in the Belarussian tanning industry
Authors: Veyalkin Ilya V. , Milyutin Alexander A. 
Published: November 2003

AbstractBackgroundThe tanning industry involves many occupational exposures. This study evaluates proportionate cancer mortality among workers employed in the Belarussian tanning plant in Minsk.MethodsA total of 768 workers with seniority of not less than 6 months who were hired after January 1, 1953 and died before December 31, 2000 was investigated. Proportionate mortality ratios (PMRs) were calculated using the population of Minsk to generate expected numbers.ResultsAmong women employed in the tannery, there was a significant excess of pancreatic cancer, based on eight deaths (expected = 2.56, PMR = 3.13, 95% CI = 1.35–6.17). Six of the eight pancreatic cancer deaths occurred among women occupied in dyeing–stuffing workshops (expected = 1.64, PMR = 3.67, 95% CI = 1.34–7.97), all among workers hired between 1962 and 1984 (expected = 1.06, PMR = 6.54, 95% CI = 2.6–13.4).ConclusionsWomen in this tanning industry cohort experienced excess mortality of cancer of the pancreas, with suggested increases of corpus and cervix uteri, melanoma, and kidney cancers. For men, an insignificant increase in PMR of oral cavity–pharynx and pancreatic cancers was seen. Further prospective follow‐up of living members of this cohort, will allow more in‐depth analysis of rare cancer sites, latency, and duration of employment, and is warranted. Am. J. Ind. Med. 44:637–642, 2003. © 2003 Wiley‐Liss, Inc.
Psychosocial risk factors for musculoskeletal symptoms among women working in geriatric care
Authors: Gunnarsdottir Holmfridur K. , Rafnsdottir Gudbjoerg L. , Helgadottir Berglind , Tomasson Kristinn 
Published: November 2003

AbstractBackgroundNursing is a stressful, physically demanding occupation and a rush setting for musculoskeletal problems. The aim of this study is to explore the extent of the association between psychosocial work characteristics and musculoskeletal symptoms among women working in geriatric care.MethodsThe participants were female employees of all geriatric nursing homes and geriatric hospital wards in Iceland having a staff of 10 or more. A total of 1,886 questionnaires were distributed. The response rate was 80%.ResultsFinding the job mentally difficult, mental exhaustion after one's shift, dissatisfaction with supervisors or the flow of information, insufficient influence at work, dissatisfaction with the hierarchy, intense time pressure, lack of solidarity, dissatisfaction with the job, harassment, violence or threats at work; all of the aforementioned gave crude odds ratios (OR) two or above for one or more musculoskeletal symptoms. Mental exhaustion and harassment, violence, and threats were the factors connected with symptoms from all the body regions studied.ConclusionsThe extent of the association of work‐related psychosocial factors and musculoskeletal symptoms among the geriatric female nursing staff is substantial and needs to be taken into account by occupational health services and others involved in preventive work. Am. J. Ind. Med. 44:679–684, 2003. © 2003 Wiley‐Liss, Inc.
Starting the protein synthesis machine: eukaryotic translation initiation
Authors: Preiss Thomas , W. Hentze Matthias 
Published: November 2003

AbstractThe final assembly of the protein synthesis machinery occurs during translation initiation. This delicate process involves both ends of eukaryotic messenger RNAs as well as multiple sequential protein–RNA and protein–protein interactions. As is expected from its critical position in the gene expression pathway between the transcriptome and the proteome, translation initiation is a selective and highly regulated process. This synopsis summarises the current status of the field and identifies intriguing open questions. BioEssays 25:1201–1211, 2003 © 2003 Wiley Periodicals, Inc.
Perpetuating the double helix: molecular machines at eukaryotic DNA replication origins
Authors: Méndez Juan , Stillman Bruce 
Published: November 2003

AbstractThe hardest part of replicating a genome is the beginning. The first step of DNA replication (called “initiation”) mobilizes a large number of specialized proteins (“initiators”) that recognize specific sequences or structural motifs in the DNA, unwind the double helix, protect the exposed ssDNA, and recruit the enzymatic activities required for DNA synthesis, such as helicases, primases and polymerases. All of these components are orderly assembled before the first nucleotide can be incorporated. On the occasion of the 50th anniversary of the discovery of the DNA structure, we review our current knowledge of the molecular mechanisms that control initiation of DNA replication in eukaryotic cells, with particular emphasis on the recent identification of novel initiator proteins. We speculate how these initiators assemble molecular machines capable of performing specific biochemical tasks, such as loading a ring‐shaped helicase onto the DNA double helix. BioEssays 25:1158–1167, 2003. © 2003 Wiley Periodicals, Inc.
Move it on over: getting proteins across biological membranes
Authors: Eichler Jerry , Irihimovitch Vered 
Published: November 2003

AbstractThe translocation of proteins across membranes is a central problem in biology. Regardless of the system in question, delivering proteins across a given membrane relies on many of the same basic themes. At the same time, however, each membrane translocation system, beit signal‐gated or signal‐assembled, makes use of components unique to that system. The latest findings on protein translocation across a variety of biological membranes have been presented in a recent review article.1 BioEssays 25:1154–1157, 2003. © 2003 Wiley Periodicals, Inc.
Absolute configuration of the thyroid hormone analog KAT‐2003 as determined by the 1H NMR anisotropy method with a novel chiral auxiliary, MαNP acid
Authors: Nishimura Toshihiro , Taji Hiromi , Harada Nobuyuki 
Published: November 2003

AbstractThe absolute configuration of the chiral thyroid hormone analog KAT‐2003 (+)‐2, showing hypocholesterolemic activities, decreases of hepatic triglyceride contents with lowering cardiac side effects, and significant inhibitory effect for the second primary hepatocellular carcinoma, was determined as S by the 1H NMR anisotropy method using a novel chiral auxiliary, 2‐methoxy‐2‐(1‐naphtyl)propionic acid (MαNP acid). Chirality 16:13–21, 2004. © 2003 Wiley‐Liss, Inc.
Chiral aldehydes in hydrocarbons: diastereoselective nucleophilic addition, NMR, and CD spectroscopy reveal dynamic solvation effects
Authors: Cainelli Gianfranco , Galletti Paola , Pieraccini Silvia , Quintavalla Arianna , Giacomini Daria , Piero Spada Gian 
Published: November 2003

AbstractTemperature‐dependent studies on the diastereoselective nucleophilic addition of n‐ BuLi to α‐chiral aldehydes as (S)‐O‐(t‐butyl‐dimethylsilyl)lactal, (S)‐O‐(t‐butyl‐dimethylsilyl) mandelic aldehyde, and (R)‐2‐phenylpropanal in n‐decane and n‐dodecane reveal dynamic solvation phenomena with the presence of inversion temperatures (Tinv) in the Eyring plots of ln (anti/syn) vs. 1/ T. These dynamic solvent effects were disclosed by temperature‐dependent studies of the 13C NMR, CD, and UV spectra of the starting aldehydes in solution of n‐decane and n‐dodecane. The concomitant presence of three peculiar temperatures TCD, TUV, and TNMR, whose values are identical and match Tinv, clearly confirms our earlier interpretation of the solvent‐dependent nature of Tinv. The inversion temperature, as well as TCD, TUV, and TNMR represents the interconversion temperature of two different solvation clusters which act as two different supramolecules with different stereoselectivities. Chirality 16:50–56, 2004. © 2003 Wiley‐Liss, Inc.
Multidimensional viscous shocks II: The small viscosity limit
Authors: Guès Olivier , Métivier Guy , Williams Mark , Zumbrun Kevin 
Published: November 2003

AbstractIn this paper we prove the existence of curved, multidimensional viscous shocks and also justify the small‐viscosity limit.Starting with a curved, multidimensional (inviscid) shock solution to a system of hyperbolic conservation laws, we show that the shock can be obtained as a small‐viscosity limit of solutions to an associated parabolic problem (viscous shocks). The two main hypotheses are a natural Evans function assumption on the viscous profile, together with a restriction on how much the shock can deviate from flatness. The main tools are a conjugation lemma that removes xN/ϵ dependence from the linearization of the parabolic problem about the viscous profile, new degenerate Kreiss‐type symmetrizers used to prove an L2 estimate for the linearized problem, and a finite‐regularity calculus of semiclassical and mixed type (classical‐semiclassical) pseudodifferential operators. © 2003 Wiley Periodicals, Inc.
GADD34 induces p53 phosphorylation and p21/WAF1 transcription
Authors: Yagi Ayako , Hasegawa Yoshinori , Xiao Hengyi , Haneda Masataka , Kojima Eiji , Nishikimi Akihiko , Hasegawa Tadao , Shimokata Kaoru , Isobe Ken‐Ichi 
Published: November 2003

AbstractRecently, others and we have shown that one of the functions of GADD34 is a recovery from a shutoff of protein synthesis induced by endoplasmic reticulum stress. GADD34 has been shown to induce growth arrest and apoptosis. Main protein of apoptosis is p53, especially phosphorylation of p53. And one of the main proteins of growth arrest is p21/WAF1. Here we analyzed the effects of GADD34 on p53 phosphorylation and p21/WAF1 transcription. Transfected Myc‐tagged p53 was dose‐dependently phosphorylated at Ser15 by increasing the amount of GADD34. Transfection of GADD34 also induced the endogenous phosphorylation of p53 and enhanced p21 protein expression. Transfection of GADD34 induced p21/WAF1 promoter activity. This activity was dependent on p53, because GADD34 transfection to p53‐deficient cells produced only a slight increase of p21/WAF1 promoter activity. The p21/WAF1 promoter activity was greatly enhanced by the transfection of p53. Both GADD34 and p53 transfection induced much higher p21/WAF1 promoter activity. The promoter activity of p21/WAF1 was very low in GADD34 deficient MEF. The transfection of GADD34 increased the p21/WAF1 promoter activity in GADD34 deficient MEF. © 2003 Wiley‐Liss, Inc.
Inositol 1,4,5‐trisphosphate receptor (type 1) phosphorylation and modulation by Cdc2
Authors: Malathi Krishnamurthy , Kohyama Shinya , Ho Michael , Soghoian Damien , Li Xiaogui , Silane Michael , Berenstein Alejandro , Jayaraman Thottala 
Published: November 2003

AbstractCalcium (Ca2+) release from the endoplasmic reticulum (ER) controls numerous cellular functions including proliferation, and is regulated in part by inositol 1,4,5‐trisphosphate receptors (IP3Rs). IP3Rs are ubiquitously expressed intracellular Ca2+‐release channels found in many cell types. Although IP3R‐mediated Ca2+ release has been implicated in cellular proliferation, the biochemical pathways that modulate intracellular Ca2+ release during cell cycle progression are not known. Sequence analysis of IP3R1 reveals the presence of two putative phosphorylation sites for cyclin‐dependent kinases (cdks). In the present study, we show that cdc2/CyB, a critical regulator of eukaryotic cell cycle progression, phosphorylates IP3R1 in vitro and in vivo at both Ser421 and Thr799 and that this phosphorylation increases IP3 binding. Taken together, these results indicate that IP3R1 may be a specific target for cdc2/CyB during cell cycle progression. © 2003 Wiley‐Liss, Inc.
Biochemical and functional changes of rat liver spheroids during spheroid formation and maintenance in culture: II. nitric oxide synthesis and related changes
Authors: Xu Jinsheng , Ma Mingwen , Purcell Wendy M. 
Published: November 2003

AbstractLiver cells isolated from intact tissue can reaggregate to form three‐dimensional, multicellular spheroids in vitro. During this process, cells undergo a histological and environmental change. How cells respond biochemically to this change has not been studied in detail previously. We have investigated some biochemical changes in rat liver cells during the formation and maintenance of spheroids. Liver cells were isolated from male Sprague rats and spheroids cultured by a gyrotatory‐mediated method. Liver cells were shown to respond to the isolation procedure and the formation of spheroids triggered histological environmental changes that increased arginine uptake, nitric oxide (NO) and urea syntheses, as well as raised levels of GSH, GSSG, glutamic acid and aspartic acid secretion within the first couple of days after cell isolation. Levels were maintained at a relatively stable level in the mature spheroids (>5 days) over the 3 week period of observation. P450 1A1 activity was lost in the first 2 days and gradually recovered thereafter. This study, for the first time, shows that liver cells after isolation and during spheroid formation actively uptake arginine and increase NO and urea syntheses. A high level of NO is likely to play an important role in modulating a series of biochemical changes in liver cells. It is considered that liver cells actively respond to the ‘challenge’ induced by the isolation procedure and subsequent histological environmental changes, and biochemical modulation and instability result. The stable cell–cell contacts and histological environment in mature spheroids permit and support functional recovery and maintenance in vitro. This period of stability permits the use of spheroids in toxicity studies to establish acute and chronic paradigms. © 2003 Wiley‐Liss, Inc.
Induction of GADD gene expression by phenethylisothiocyanate in human colon adenocarcinoma cells
Authors: Powolny Anna , Takahashi Keiko , Hopkins Robin G. , Loo George 
Published: November 2003

AbstractPhenethylisothiocyanate (PEITC), a potential cancer chemopreventive agent, induces colon cancer cell death, but the mechanism is not entirely clear. Therefore, the aim of this study was to further clarify the molecular effects of PEITC in causing death of human colon adenocarcinoma cells. When incubated with PEITC, HCT‐116 colonocytes showed morphological features characteristic of apoptosis, such as irregular cell shape, translocation of plasma membrane phosphatidylserine, and also chromatin condensation and fragmentation. These changes occurred after single‐strand breaks in DNA were detected, suggesting that PEITC induced irreparable DNA damage, which in turn triggered the process of apoptosis. DNA macroarray analysis of a selected small cluster of apoptosis‐related genes revealed noticeably higher expression of only GADD45, which was confirmed by gene‐specific relative RT‐PCR analysis. This led to investigation of other GADD gene members possibly affected by PEITC. Whereas GADD34 mRNA expression increased just slightly, there was an appreciable elevation of the mRNA for GADD153, which is recognized as a pro‐apoptotic gene. The effect of PEITC on GADD153 was attenuated by either actinomycin D or N‐acetylcysteine, suggesting that PEITC‐induced upregulation of GADD153 mRNA expression was partly at the level of transcriptional activation involving reactive oxygen species. Additionally, PEITC‐induced upregulation of GADD153 mRNA expression did not appear to require p53, based on the observation that PEITC also increased GADD153 mRNA expression in HCT‐15 colonocytes, which are known to express mutant p53. These findings suggest that PEITC creates an oxidative cellular environment that induces DNA damage and GADD153 gene activation, which in turn helps trigger apoptosis. © 2003 Wiley‐Liss, Inc.