bluuebunny/crossref_metadata_2025_split huggingface dataset:
Self- diffusion of H2O in stevensite gel: effects of temperature and clay fraction
Authors: Nakashima Y. 
Published: July 2002

AbstractSelf-diffusion coefficients of water molecules (1H2O) in Na-stevensite gel were measured by pulsed-gradient spin-echo (PGSE) proton nuclear magnetic resonance (NMR). The effects of clay fraction (0.00 37.7 wt.%) and temperature (20.0 60.3°C) were studied. The results show: (1) phenomenologically, the H2O self-diffusivity in the clay gel,D, is expressed byD/D0= exp( 0.0198w) whereD0is the H2O self-diffusivity in bulk water of the temperature andwis the clay weight fraction (wt.%). (2) The activation energy of the diffusivity in the stevensite gel is nearly equal to that in bulk water. Thus, the normalized diffusivity,D/D0, obeys a temperature-independent master curve. (3) The exponential dependence ofD/D0onwforw<25 wt.% (≈ 12 vol.%) can be explained by a random walk model, in which unbound H2O molecules diffuse in the geometrically tortuous pore structure of randomly scattered clay mineral grains. (4) The measured diffusivity can also be explained by a model of unbound H2O diffusing in a polymer network with a specific meshsize or characteristic interval of the crosslinkage.
Tungsten-bearing rutile from the Kori Kollo gold mine, Bolivia
Authors: Rice C. M. , Darke K. E. , Still J. W. , Lachowski E. E. 
Published: July 2002

AbstractW-bearing rutile formed during alteration of jarosite by resurgent hydrothermal fluids in the oxide zone of the Kori Kollo gold deposit. The rutile shows sector zoning in basal sections and well developed multiple growth zones, both defined in backscatter electron images by variations in the W content. The maximum WO3content is 5.3 wt.% and W substitutes for Ti with double substitution of Fe to maintain charge balance. The causes of multiple growth bands are considered to be changes in externally controlled variables occurring in a shallow hydrothermal system. Whereas Ti is probably leached from biotite in dacitic rocks, the W is introduced by hydrothermal fluids.
A soluble form of the murine common γ chain is present at high concentrations in vivo and suppresses cytokine signaling
Authors: Meißner Udo , Blum Horst , Schnare Markus , Röllinghoff Martin , Gessner André 
Published: July 2002

AbstractThe common gamma-chain (γc) is a component of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15 and is essential for their signal transduction. Western blotting and a newly established enzyme-linked immunosorbent assay detected substantial constitutive levels (50-250 ng/mL) of soluble γc (sγc) in sera of murine inbred strains. It was demonstrated that purified immune cells, such as T, B, and natural killer cells, and macrophages released this protein after activation. Transfection experiments with cDNA encoding the full-length γc showed that shedding of the transmembrane receptor led to the release of sγc. The shedding enzymes, however, appeared to be distinct from those cleaving other cytokine receptors because inhibitors of metalloproteases (eg, TAPI) did not influence sγc release. In vivo, superantigen-induced stimulation of T cells enhanced sγc serum concentrations up to 10-fold within 6 hours. Because these findings demonstrated regulated expression of a yet unknown molecule in the immune response, further experiments were performed to assess the possible function(s) of sγc. A physiological role of sγc was indicated by its capacity to specifically inhibit cell growth induced by γc-dependent cytokines. Mutational analysis revealed that the C-terminus and the WSKWS motif are essential for the cytokine inhibitory effect of the sγc and for binding of the molecule to cytokine receptor-expressing cells. Thus, competitive displacement of the transmembrane γc by excess sγc is the most likely mechanism of cell growth inhibition. It was implied that naturally produced sγc is a negative modulator of γc-dependent cytokines.
The soluble murine type I interferon receptor Ifnar-2 is present in serum, is independently regulated, and has both agonistic and antagonistic properties
Authors: Hardy Matthew P. , Owczarek Catherine M. , Trajanovska Suzana , Liu Xiang , Kola Ismail , Hertzog Paul J. 
Published: July 2002

AbstractThe ability to modify responses to type I interferons (IFNs) could alter processes such as hematopoiesis and immunity, which involve endogenous IFNs and responses to exogenous IFNs. The data presented here support a significant role for a recently identified soluble isoform of the murine type I IFN receptor, muIfnar-2a, as an efficient regulator of IFN responses. The messenger RNA (mRNA) transcript encoding muIfnar-2a is generally more abundant than that encoding the transmembrane isoform, muIfnar-2c. Furthermore, the ratio ofmuIfnar-2a:2c transcripts varied from more than 10:1 in the liver and other organs to less than 1:1 in bone-marrow macrophages, indicating independent regulation of the 2 transcripts encoding receptor isoforms and suggesting that the soluble muIfnar-2a levels are biologically relevant in some organs. Western blot analysis showed that soluble muIfnar-2 was present at high levels in murine serum and other biologic fluids and bound type I IFN. Recombinant muIfnar-2a competitively inhibited the activity of both IFNα and β in reporter assays using the L929 cell line and in antiproliferative and antiviral assays using primary cells. Surprisingly, using primary thymocytes fromIfnar-2−/− mice, recombinant muIfnar-2a formed a complex with IFN α or β and muIfnar-1 at the cell surface and transmitted an antiproliferative signal. These data indicate potential dual actions of soluble muIfnar-2 and imply that a signal can be transduced through the Ifnar-1 chain of the receptor complex in the absence of the cytoplasmic domain of Ifnar-2. Therefore, our results suggest that soluble Ifnar-2 is an important regulator of endogenous and systemically administered type I IFN.
Characterization of novel natural killer (NK)–cell and γδ T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus
Authors: Nagata Hiroshi , Konno Akiyoshi , Kimura Nobuhiro , Zhang Yu , Kimura Michiko , Demachi Ayako , Sekine Teruaki , Yamamoto Kohtaro , Shimizu Norio 
Published: July 2002

AbstractStudies on nasal T/natural killer (NK)–cell lymphoma have been hampered by its tendency to cause necrosis. Thus, the establishment of cell lines of this neoplasm would seem to be valuable. This study attempted to establish cell lines from primary lesions of this tumor, and successfully obtained 2 novel Epstein-Barr virus (EBV)–positive cell lines, SNK-6 and SNT-8, by means of high-dose recombinant interleukin 2. Flow cytometry showed that SNK-6 had an NK-cell phenotype, CD3−CD4−CD8−CD19−CD56+T-cell receptor (TCR) α/β− TCR γ/δ−, whereas SNT-8 was CD3+CD4−CD8−CD19−CD56+TCR α/β− TCR γ/δ+. These were consistent with immunophenotypes of their original tumors, and the cell lines had monoclonal EBV clones identical to ones in their original tumors. Thus, the cell lines developed from cells forming the primary lesions. Genotypic analysis showed that SNK-6 had unrearranged TCR and immunoglobulin heavy-chain genes, supporting the conclusion that SNK-6 was of NK-cell lineage. On the other hand, SNT-8 had rearranged TCR β-, γ-, and δ-chain genes, and together with its phenotype, SNT-8 proved to be a γδ T-cell line. This is the first report of the establishment of cell lines from primary lesions of nasal T/NK cell lymphomas, and the results demonstrated that there are at least 2 lineages, NK- and γδ T-cell, in this neoplasm. Moreover, it has been suggested that nasal T/NK cell lymphomas of these lineages may belong to the same clinicopathologic entity because both types of cases shared common clinical and histopathologic features.
Selective down-regulation of high-affinity IgE receptor (FcεRI) α-chain messenger RNA among transcriptome in cord blood–derived versus adult peripheral blood–derived cultured human mast cells
Authors: Iida Makoto , Matsumoto Kenji , Tomita Hisashi , Nakajima Toshiharu , Akasawa Akira , Ohtani Noriko Yuyama , Yoshida Ning Lu , Matsui Keiko , Nakada Akiko , Sugita Yuji , Shimizu Yuji , Wakahara Shunichi , Nakao Toru , Fujii Yasuyuki , Ra Chisei , Saito Hirohisa 
Published: July 2002

AbstractSubstantial numbers of human mast cells (MCs) were generated from umbilical cord blood (CB) and from adult peripheral blood (PB). A single CB progenitor produced 15 436 MCs, whereas a single PB progenitor produced 807 MCs on average. However, PB-derived MCs were far more active than CB-derived MCs in terms of high-affinity IgE receptor (FcεRI)-mediated reactions. One million sensitized PB-derived MCs released 3.6 μg histamine, 215 pg IL-5, and 14 ng granulocyte macrophage–colony-stimulating factor (GM-CSF), whereas 106 sensitized CB-derived MCs released only 0.8 μg histamine, 31 pg IL-5, and 0.58 ng GM-CSF on anti-IgE challenge. However, ionophore A23 187 released similar levels of histamine from the 2 MC types. PB-derived MCs highly expressed surface FcεRI α chain, and CB-derived MCs almost lacked it in the absence of IgE. PB-derived MCs expressed approximately 5 times higher levels of messenger RNA (mRNA) for FcεRI α chain than CB-derived MCs, but mRNAs for β and γ chains of the receptors were equally expressed. Among the approximately 5600 kinds of full-length human genes examined by using the high-density oligonucleotide probe-array system, FcεRIα was ranked the fifth most increased transcript in PB-derived MCs. The 4 other increased transcripts were unrelated to MC function. These results suggest that IgE-mediated reactions may be restricted during early infancy through the selective inhibition of FcεRIα transcription, which is probably committed at progenitor stages and is, at least in part, cytokine-insensitive.
Phorbol ester up-regulates capacities for nuclear translocation and phosphorylation of 5-lipoxygenase in Mono Mac 6 cells and human polymorphonuclear leukocytes
Authors: Werz Oliver , Klemm Jenny , Samuelsson Bengt , Rådmark Olof 
Published: July 2002

AbstractThe leukotrienes are inflammatory mediators derived from arachidonic acid. It was demonstrated that the priming of leukocytes with phorbol-12-myristate-13-acetate (PMA) leads to the increased formation of 5-lipoxygenase (5-LO) products in parallel with the increased association of 5-LO with the nucleus and the activation of kinases that can phosphorylate 5-LO in vitro. Stimulation of the monocytic cell line Mono Mac 6 with calcium ionophore gave low 5-LO product formation and no detectable redistribution of 5-LO. However, after priming of Mono Mac 6 cells with phorbol esters, ionophore led to the association of 45% to 75% of cellular 5-LO with the nuclear membrane, to 5-LO kinase activation, to enhanced release of arachidonate, and to substantial leukotriene synthesis. Similar results were obtained for human polymorphonuclear leukocytes stimulated with low-dose ionophore. In addition, for each cell type, PMA priming up-regulated leukotriene biosynthesis in the presence of exogenous arachidonic acid. A protein kinase inhibitor, calphostin C, reduced the association of 5-LO with the nucleus and 5-LO kinase activity, and the formation of 5-LO products was inhibited. These results suggest that PMA up-regulates leukotriene biosynthesis not only by increasing the release of endogenous arachidonate, but also by increasing the capacity for 5-LO phosphorylation and for the translocation of 5-LO to the nucleus in leukocytes.
Cyclin D3 at 6p21 is dysregulated by recurrent chromosomal translocations to immunoglobulin loci in multiple myeloma
Authors: Shaughnessy John , Gabrea Ana , Qi Ying , Brents Leslie , Zhan Fenghaung , Tian Erming , Sawyer Jeffrey , Barlogie Bart , Bergsagel P. Leif , Kuehl Michael 
Published: July 2002

AbstractReciprocal chromosomal translocations, which are mediated by errors in immunoglobulin heavy chain (IgH) switch recombination or somatic hypermutation as plasma cells are generated in germinal centers, are present in most multiple myeloma (MM) tumors. These translocations dysregulate an oncogene that is repositioned in proximity to a strong IgH enhancer. There is a promiscuous array of nonrandom chromosomal partners (and oncogenes), with the 3 most frequent partners (11q13 [cyclin D1]; 4p16 [FGFR3 and MMSET]; 16q23 [c-maf]) involved in nearly half of MM tumors. It is now shown that a novel t(6;14)(p21;q32) translocation is present in 1 of 30 MM cell lines and that this cell line uniquely overexpresses cyclin D3. The cloned breakpoint juxtaposes gamma 4 switch sequences with 6p21 sequences that are located about 65 kb centromeric to the cyclin D3 gene. By metaphase chromosome analysis, the t(6;14) (p21;q32) translocation was identified in 6 of 150 (4%) primary MM tumors. Overexpression of cyclin D3 messenger RNA (mRNA) was identified by microarray RNA expression analysis in 3 of 53 additional primary MM tumors, each of which was found to have a t(6;14) translocation breakpoint by interphase fluorescence in situ hybridization analysis. One tumor has a t(6;22)(p21;q11) translocation, so that cyclin D3 is bracketed by the IgL and IgH breakpoints. These results provide the first clear evidence for primary dysregulation of cyclin D3 during tumorigenesis. It is suggested that the initial oncogenic event for most MM tumors is a primary immunoglobulin translocation that dysregulates cyclin D1, cyclin D3, and other oncogenes to provide a proliferative stimulus to postgerminal center plasma cells.
Lipoprotein (a) binds and inactivates tissue factor pathway inhibitor: a novel link between lipoproteins and thrombosis
Authors: Caplice Noel M. , Panetta Carmelo , Peterson Timothy E. , Kleppe Laurel S. , Mueske Cheryl S. , Kostner Gert M. , Broze George J. , Simari Robert D. 
Published: July 2002

AbstractLipoprotein (a) [Lp(a)] has been associated with both anti-fibrinolytic and atherogenic effects. However, no direct link currently exists between this atherogenic lipoprotein and intravascular coagulation. The current study examined the binding and functional effects of Lp(a), its lipoprotein constituents, apoliprotein (a) [apo(a)] and low-density lipoprotein (LDL), and lysine-plasminogen (L-PLG), which shares significant homology with apo(a), on tissue factor pathway inhibitor (TFPI), a major regulator of tissue factor-mediated coagulation. Results indicate that Lp(a), apo(a), and PLG but not LDL bound recombinant TFPI (rTFPI) in vitro and that apo(a) bound to a region spanning the last 37 amino acid residues of the c-terminus of TFPI. The apparent binding affinity for TFPI was much higher for Lp(a) (KD ∼150 nM) compared to PLG (KD ∼800 nM) and nanomolar concentrations of apo(a) (500 nM) inhibited PLG binding to TFPI. Lp(a) also inhibited in a concentration-dependent manner rTFPI activity and endothelial cell surface TFPI activity in vitro, whereas PLG had no such effect. Moreover physiologic concentrations of PLG (2 μM) had no effect on the concentration-dependent inhibition of TFPI activity induced by Lp(a). In human atherosclerotic plaque, apo(a) and TFPI immunostaining were shown to coexist in smooth muscle cell–rich areas of the intima. These data suggest a novel mechanism whereby Lp(a) through its apo(a) moiety may promote thrombosis by binding and inactivating TFPI.
Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD): evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD
Authors: Miura Yuji , Thoburn Christopher J. , Bright Emilie C. , Sommer Matthias , Lefell Susan , Ueda Mikio , Nakao Shinji , Hess Allan D. 
Published: July 2002

AbstractAdministration of cyclosporine A (CsA) after autologous stem cell transplantation elicits an autoimmune syndrome with pathology similar to graft-versus-host disease (GVHD). This syndrome, termed autologous GVHD, is associated with the appearance of autoreactive T cells directed at major histocompatibility class (MHC) class II antigens. In the rat model of autologous GVHD, clonal analysis reveals that the effector T cells are highly conserved and recognize a peptide from the invariant chain peptide presented by MHC class II. Although human autologous GVHD effector T cells share a similar phenotypic specificity, clonality of the response in humans has not been determined. To examine the human effector T-cell response, the T-cell repertoire of peripheral blood lymphocytes was assessed by complementarity-determining region 3 (CDR3) size distribution analysis and T-cell clonotype analysis in 26 patients treated with CsA after transplantation. Autologous GVHD developed in 3 of 4 patients with human leukocyte antigen (HLA)-DRB1*0701, and clonal expansions of β-chain variable region (BV)16+ T cells were shared. Clonal expansions within BV15+ and BV22+ T cells were also detected in 4 of 6 patients with HLA-DRB1*1501 and in 3 of 4 patients with HLA-DRB1*0401, respectively. Sequencing of BV16 cDNA for which the CDR3 size pattern exhibited apparent clone predominance revealed an identical CDR3 peptide sequence in 2 different patients, one with HLA-DRB1*0701 and the other with HLA-DRB1*1502. These findings indicate that the discrete antigen-driven expansion of T cells is involved in autologous GVHD.
Successful treatment of pure red cell aplasia with rituximab in patients with chronic lymphocytic leukemia
Authors: Ghazal Hassan 
Published: July 2002

Abstract
Pure red cell aplasia (PRCA) is a rare complication in patients with chronic lymphocytic leukemia (CLL). It is characterized by reticulocytopenia and by an absence of red cell precursors in the bone marrow. Unlike autoimmune hemolytic anemia, which is characterized by an increased number of reticulocytes, positive Coombs test findings, and a high serum level of lactate dehydrogenase. Two patients with B-cell CLL are reported to have developed PRCA, one while on chemotherapy with fludarabine and one seeking treatment for de novo PRCA. Both responded dramatically to therapy with monoclonal antibody rituximab (Rituxan) in a short period of time and continued to be transfusion-independent. These are the first 2 reported patients for whom rituximab treatment for PRCA in CLL was successful, and this treatment deserves further investigation.
Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release
Authors: Mattia Gianfranco , Vulcano Francesca , Milazzo Luisa , Barca Alessandra , Macioce Giampiero , Giampaolo Adele , Hassan H. Jane 
Published: July 2002

Abstract
Ploidy could be the key to understanding megakaryocyte (MK) biology and platelet production. Human CD34+ cells purified from umbilical cord blood (CB) and peripheral blood (PB) were investigated on their capability to give rise, in a serum-free medium containing thrombopoietin, to MKs and platelets. CB-MKs showed reduced polyploidization and platelet number compared with PB-MKs, but a similar membrane phenotype. Most CB-MKs showed a 2N content of DNA (∼80%) and only 2.6% had 8N, whereas 40% of the PB cells had 8N or more. Platelets were substantially released in PB culture from day 12; at day 14 the CB-derived MKs were able to release platelets although at a reduced level (∼35%), correlating with their reduced size. A direct correlation was demonstrated by sorting polyploid cells from PB-MKs and evaluating the platelets released in the supernatant. Furthermore, the study analyzed the expression and distribution of cyclin D3 and cyclin B1. Cyclin D3 protein was increased in PB in comparison to CB-MKs; in PB culture most cells rapidly became positive, whereas in CB-derived cells cyclin D3 expression was evident only from day 9 and in a reduced percentage. Cyclin B1 was essentially localized at the nuclear level in the CB and was expressed during the whole culture. In PB-MKs, at day 9, a reduction was observed, correlating with an advanced ploidy state. The data indicate the inability of the CB-MKs to progress in the endomitotic process and a direct correlation between DNA content and platelet production.
Glycated Hemoglobin A1c Time in Range and Dementia in Older Adults With Diabetes
Authors: Underwood Patricia C. , Zhang Libin , Mohr David C. , Prentice Julia C. , Nelson Richard E. , Budson Andrew E. , Conlin Paul R. 
Published: August 2024

ImportanceIndividuals with diabetes commonly experience Alzheimer disease and related dementias (ADRD). Factors such as hypoglycemia, hyperglycemia, and glycemic variability have been associated with increased risk of ADRD. Traditional glycemic measures, such as mean glycated hemoglobin A1c (HbA1c), may not identify the dynamic and complex pathophysiologic factors in the association between diabetes and ADRD. The HbA1c time in range (TIR) is a previously developed measure of glycemic control that expresses HbA1c stability over time within specific ranges. This measure may inform the current understanding of the association between glucose levels over time and ADRD incidence.ObjectiveTo examine the association between HbA1c TIR and incidence of ADRD in older veterans with diabetes.Design, Setting, and ParticipantsThe study sample for this cohort study was obtained from administrative and health care utilization data from the Veterans Health Administration and Medicare from January 1, 2004, to December 31, 2018. Veterans 65 years or older with diabetes were assessed. Participants were required to have at least 4 HbA1c tests during the 3-year baseline period, which could start between January 1, 2005, and December 31, 2014. Data analysis was conducted between July and December 2023.Main Outcomes and MeasuresHemoglobin A1c TIR was calculated as the percentage of days during baseline in which HbA1c was in individualized target ranges based on clinical characteristics and life expectancy, with higher HbA1c TIR viewed as more favorable. The association between HbA1c TIR and ADRD incidence was estimated. Additional models considered ADRD incidence in participants who were above or below HbA1c target ranges most of the time.ResultsThe study included 374 021 veterans with diabetes (mean [SD] age, 73.2 [5.8] years; 369 059 [99%] male). During follow-up of up to 10 years, 41 424 (11%) developed ADRD. Adjusted Cox proportional hazards regression models showed that lower HbA1c TIR was associated with increased risk of incident ADRD (HbA1c TIR of 0 to &amp;lt;20% compared with ≥80%: hazard ratio, 1.19; 95% CI, 1.16-1.23). Furthermore, the direction of out-of-range HbA1c levels was associated with incident ADRD. Having greater time below range (≥60%, compared with ≥60% TIR) was associated with significantly increased risk (hazard ratio, 1.23; 95% CI, 1.19-1.27). Findings remained significant after excluding individuals with baseline use of medications associated with hypoglycemia risk (ie, insulin and sulfonylureas) or with hypoglycemia events.Conclusions and RelevanceIn this study of older adults with diabetes, increased HbA1c stability within patient-specific target ranges was associated with a lower risk of ADRD. Lower HbA1c TIR may identify patients at increased risk of ADRD.