bluuebunny/crossref_metadata_2025_split huggingface dataset:
The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig VL germ line gene use and clonal plasma cell burden
Authors: Comenzo Raymond L. , Zhang Yana , Martinez Carmen , Osman Keren , Herrera Guillermo A. 
Published: July 2002

AbstractPrimary systemic amyloidosis (AL) is a protein conformation disorder in which monoclonal immunoglobulin light chains produced by clonal plasma cells are deposited as amyloid in the kidneys, heart, liver, or other organs. Why patients with AL present with amyloid disease that displays such organ tropism is unknown. This study tested the hypothesis that both the light-chain variable region (IgVL) germ line genes used by AL clones and the plasma cell burden influenced AL organ tropism. To assess the renal tropism of some light chains, an in vitro renal mesangial cell model of amyloid formation was used. With reverse transcription-polymerase chain reaction, Ig VL genes were sequenced from 60 AL patients whose dominant involved organs were renal (52%), cardiac (25%), hepatic (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients with clones derived from the 6a VλVI germ line gene were more likely to present with dominant renal involvement, whereas those with clones derived from the 1c, 2a2, and 3r Vλ genes were more likely to present with dominant cardiac and multisystem disease. Patients withVκ clones were more likely to have dominant hepatic involvement and patients who met the Durie criteria for myeloma (38%, 23 of 60) were more likely to present with dominant cardiac involvement independent of germ line gene use. In the in vitro model, unlike all other AL light chains tested, λVI light chains formed amyloid rapidly both with and without amyloid-enhancing factor. These data support the hypothesis that germ line gene use and plasma cell burden influence the organ tropism of AL.
Basic helix-loop-helix proteins E2A and HEB induce immature T-cell receptor rearrangements in nonlymphoid cells
Authors: Langerak Anton W. , Wolvers-Tettero Ingrid L. M. , van Gastel-Mol Ellen J. , Oud Monique E. C. M. , van Dongen Jacques J. M. 
Published: July 2002

AbstractT-cell receptor (TCR) gene rearrangements are mediated via V(D)J recombination, which is strictly regulated during lymphoid differentiation, most probably through the action of specific transcription factors. Investigated was whether cotransfection ofRAG1 and RAG2 genes in combination with lymphoid transcription factors can induce TCR gene rearrangements in nonlymphoid human cells. Transfection experiments showed that basic helix-loop-helix transcription factors E2A and HEB induce rearrangements in the TCRD locus (Dδ2-Dδ3 and Vδ2-Dδ3) and TCRG locus (ψ Vγ7-Jγ2.3 and Vγ8-Jγ2.3). Analysis of these rearrangements and their circular excision products revealed some peculiar characteristics. The Vδ2-Dδ3 rearrangements were formed by direct coupling without intermediate Dδ2 gene segment usage, and most Dδ2-Dδ3 recombinations occurred via direct coupling of the respective upstream and downstream recombination signal sequences (RSSs) with deletion of the Dδ2 and Dδ3 coding sequences. Subsequently, the E2A/HEB–induced TCR gene recombination patterns were compared with those in early thymocytes and acute lymphoblastic leukemias of T- and B-lineage origin, and it was found that the TCR rearrangements in the transfectants were early (immature) and not necessarily T-lineage specific. Apparently, some parts of theTCRD (Vδ2-Dδ region) and TCRG genes are accessible for recombination not only in T cells, but also in early B-cells and even in nonlymphoid cells if the appropriate transcription factors are present. The transfection system described here appeared to be useful for studying the accessibility of immunoglobulin and TCR genes for V(D)J recombination, but might also be applied to study the induction of RSS-mediated chromosome aberrations.
Human CD4+CD25+ cells: a naturally occurring population of regulatory T cells
Authors: Ng Wan Fai , Duggan Phillip J. , Ponchel Frederique , Matarese Giuseppe , Lombardi Giovanna , Edwards A. David , Isaacs John D. , Lechler Robert I. 
Published: July 2002

AbstractDespite thymic deletion of cells with specificity for self-antigens, autoreactive T cells are readily detectable in the normal T-cell repertoire. In recent years, a population of CD4+ T cells that constitutively express the interleukin-2 receptor-α chain, CD25, has been shown to play a pivotal role in the maintenance of self-tolerance in rodent models. This study investigated whether such a regulatory population exists in humans. A population of CD4+CD25+ T cells, taken from the peripheral blood of healthy individuals and phenotypically distinct from recently activated CD4+ T cells, was characterized. These cells were hyporesponsive to conventional T-cell stimuli and capable of suppressing the responses of CD4+CD25− T cells in vitro. Addition of exogenous interleukin-2 abrogated the hyporesponsiveness and suppressive effects of CD4+CD25+ cells. Suppression required cell-to-cell contact but did not appear to be via the inhibition of antigen-presenting cells. In addition, there were marked changes in the expression of Notch pathway molecules and their downstream signaling products at the transcriptional level, specifically in CD4+CD25+ cells, suggesting that this family of molecules plays a role in the regulatory function of CD4+CD25+ cells. Cells with similar phenotype and function were detected in umbilical venous blood from healthy newborn infants. These results suggest that CD4+CD25+ cells represent a population of regulatory T cells that arise during fetal life. Comparison with rodent CD4+CD25+ cells suggests that this population may play a key role in the prevention of autoimmune diseases in humans.
Establishment of a murine model for therapy-treated chronic myelogenous leukemia using the tyrosine kinase inhibitor STI571
Authors: Wolff Nicholas C. , Ilaria Robert L. 
Published: July 2002

AbstractThe murine bone marrow retroviral transduction and transplantation model of chronic myelogenous leukemia (CML) imperfectly mimics human CML because the murine CML-like disease causes death of all animals from an overwhelming granulocytosis within 3 to 4 weeks. In this report, mice reconstituted with P210BCR/ABL-transduced bone marrow cells received posttransplantation therapy with either the tyrosine kinase inhibitor STI571 or placebo. Compared with the rapidly fatal leukemia of placebo-treated animals, 80% of the STI571-treated mice were alive on day 74, with marked improvement in peripheral white blood counts and splenomegaly. There was decreased tyrosine phosphorylation of STAT5, Shc, and Crk-L in leukemic cells from STI571-treated animals, consistent with STI571-mediated inhibition of the Bcr/Abl tyrosine kinase in vivo. In some STI571-treated animals Bcr/Abl messenger RNA and protein expression were markedly increased. In contrast to the polyclonal leukemia of placebo-treated mice, STI571-treated murine CML was generally oligoclonal, suggesting that STI571 eliminated or severely suppressed certain leukemic clones. None of the STI571-treated mice were cured of the CML-like myeloproliferative disorder, however, and STI571-treated murine CML was transplanted to secondary recipients with high efficiency. These results demonstrate the utility of this murine model of CML in the evaluation of novel therapeutic agents against Bcr/Abl-induced leukemias. This improved murine chronic-phase CML model may be a useful tool for the study of STI571 resistance, CML progression, and the anti-CML immune response.
Development of drug-resistant herpes simplex virus infection after haploidentical hematopoietic progenitor cell transplantation
Authors: Langston Amelia A. , Redei Istvan , Caliendo Angela M. , Somani Jyoti , Hutcherson Don , Lonial Sagar , Bucur Silvana , Cherry Judy , Allen Andrew , Waller Edmund K. 
Published: July 2002

Abstract
An unusually high incidence of acyclovir- and foscarnet-resistant herpes simplex virus (HSV) infection was noted after lymphocyte-depleted blood hematopoietic progenitor cell (HPC) transplantation from HLA-haploidentical family donors. Fourteen adults with hematologic malignancies underwent blood HPC transplantation from haploidentical family donors. Pheresis products were stringently depleted of T and B cells by immunomagnetic adsorption, and patients received no immunosuppression after transplantation. HSV reactivation occurred in all 7 evaluable HSV-1– or HSV-2–seropositive patients, at a median of 40 days after transplantation. Susceptibility testing of clinically resistant viral isolates demonstrated acyclovir resistance in all 5 cases tested. Second-line therapy produced only partial responses, and in vitro evidence of foscarnet resistance developed rapidly in all 3 patients treated with foscarnet. Healing of lesions coincided with T-cell recovery. The prolonged immunodeficiency associated with stringent lymphocyte depletion of the graft appears to strongly predispose to emergence of drug-resistant HSV. Furthermore, immune reconstitution is necessary for eradication of infection.
Self-Rated Health as a Predictor of Survival Among Patients With Advanced Cancer
Authors: Shadbolt Bruce , Barresi Jane , Craft Paul 
Published: July 2002

PURPOSE: Evidence is emerging about the strong predictive relationship between self-rated health (SRH) and survival, although there is little evidence on palliative populations where an accurate prediction of survival is valuable. Thus, the relative importance of SRH in predicting the survival of ambulatory patients with advanced cancer was examined. SRH was compared to clinical assessments of performance status, as well as to quality-of-life measures. PATIENTS AND METHODS: By use of a prospective cohort design, 181 patients (76% response rate) with advanced cancer were recruited into the study, resurveyed at 18 weeks, and observed to record deaths. RESULTS: The average age of patients was 62 years (SD = 12). The median survival time was 10 months. SRH was the strongest predictor of survival from baseline. Also, a Cox regression comparing changes in SRH over time yielded hazard ratios suggesting the relative risk (RR) of dying was greater for fair ratings at 18 weeks (approximately 3 times) compared with consistent good or better ratings; the RR was even greater (4.2 and 6.2 times) for poor ratings, especially when ratings were poor at baseline and 18 weeks (31 times). Improvement in SRH over time yielded the lowest RR. CONCLUSION: SRH is valid, reliable, and responsive to change as a predictor of survival of advanced cancer. These qualities suggest that SRH should be considered as an additional tool by oncologists to assess patients. Similarly, health managers could use SRH as an indicator of disease severity in palliative care case mix. Finally, SRH could provide a key to help us understand the human side of disease and its relationship with medicine.
Randomized, Double-Blind, Placebo-Controlled Trial of Recombinant Human Erythropoietin, Epoetin Beta, in Hematologic Malignancies
Authors: Österborg A. , Brandberg Y. , Molostova V. , Iosava G. , Abdulkadyrov K. , Hedenus M. , Messinger D. 
Published: July 2002

PURPOSE: To investigate the effect of recombinant human erythropoietin (epoetin beta) on anemia, transfusion need, and quality of life (QOL) in severely anemic patients with low-grade non-Hodgkin’s lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma (MM). PATIENTS AND METHODS: Transfusion-dependent patients with NHL (n = 106), CLL (n = 126), or MM (n = 117) and a low serum erythropoietin concentration were randomized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks. Primary efficacy criteria were transfusion-free and transfusion- and severe anemia–free survival (hemoglobin [Hb] > 8.5 g/dL) between weeks 5 to 16. Response was defined as an increase in Hb ≥ 2 g/dL with elimination of transfusion need. QOL was assessed by the Functional Assessment of Cancer Therapy scale. RESULTS: Transfusion-free (P = .0012) survival and transfusion- and severe anemia–free survival (P = .0001) were significantly greater in the epoetin beta group versus placebo (Wald χ2 test), giving a relative risk reduction of 43% and 51%, respectively. The response rate was 67% and 27% in the epoetin beta versus the placebo group, respectively (P < .0001). After 12 and 16 weeks of treatment, QOL significantly improved in the epoetin beta group compared with placebo (P < .05); this improvement correlated with an increase in Hb concentration (≥ 2 g/dL). A target Hb that could be generally recommended could not be identified. CONCLUSION: Many severely anemic and transfusion-dependent patients with advanced MM, NHL, and CLL and a low performance status benefited from epoetin therapy, with elimination of severe anemia and transfusion need, and improvement in QOL.
Concurrent Chemotherapy-Radiotherapy Compared With Radiotherapy Alone in Locoregionally Advanced Nasopharyngeal Carcinoma: Progression-Free Survival Analysis of a Phase III Randomized Trial
Authors: Chan A.T.C. , Teo P.M.L. , Ngan R.K. , Leung T.W. , Lau W.H. , Zee B. , Leung S.F. , Cheung F.Y. , Yeo W. , Yiu H.H. , Yu K.H. , Chiu K.W. , Chan D.T. , Mok T. , Yuen K.T. , Mo F. , Lai M. , Kwan W.H. , Choi P. , Johnson P.J. 
Published: July 2002

PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho’s N2 or N3 stage or N1 stage with nodal size ≥ 4 cm were randomized to receive cisplatin 40 mg/m2 weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P = .10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho’s stage T3 (P = .0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P = .016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.
Laboratory Detection of Bacteremia and Fungemia
Authors: T. Harrington Amanda , Jean Sophonie , Hilt Evann E. 
Published: December 2024

Abstract
Clinical microbiology laboratories play an essential role in establishing an etiologic diagnosis for sepsis and bloodstream infection. Diagnosis requires multiple steps, including one or more blood cultures drawn from different sites, recovery and identification of microorganisms detected in blood culture, antimicrobial susceptibility testing of clinically significant organisms, and interpretation of results in conjunction with other clinical, radiographic, and laboratory findings. This chapter provides a summary of the clinical importance of bacteremia and fungemia, the scientific and medical principles underlying current diagnostic methods, and diagnostic approaches. Determining the clinical significance can be difficult for coagulase‐negative staphylococci, as the identity of this organism group is of little or no help. Preparation for blood culture collection and transport to the laboratory includes a number of stepwise processes. Matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry is an extensively studied approach to rapid microbial identification of blood culture isolates.
Laboratory Automation in Clinical Microbiology
Authors: McElvania Erin , Doern Christopher D. , Culbreath Karissa 
Published: December 2024

Abstract
The practice of clinical microbiology has been revolutionized by technological innovations such as the advent of molecular diagnostics and polymerase chain reaction, matrix‐assisted laser desorption ionization–time of flight mass spectrometry, and most recently laboratory automation. This chapter focuses on the automation of culture‐based bacteriology. It discusses the various components of culture‐based automation along with some important considerations for those looking to adopt automation in their microbiology laboratory, such as how to select the right system, change management, and system validation. The chapter also includes some details of each system for the purposes of facilitating a capability comparison. The automation of microbiological specimen processing improves the quality of plate streaking, avoids cross‐contamination, alleviates ergonomic issues, and reduces processing time and costs. Total laboratory automation will likely become commonplace in high‐volume laboratories and may eventually be found in smaller laboratories.
Aerococcus
, Abiotrophia, and Other Aerobic Catalase‐Negative, Gram‐Positive Cocci
Authors: Nielsen Xiaohui Chen , Christensen Jens Jørgen 
Published: December 2024

Abstract

The catalase‐negative, Gram‐positive cocci form a taxonomically diverse group of bacteria that are isolated infrequently as opportunistic agents of infection. Most of these organisms resemble other, better‐known clinical isolates and consequently may be mistaken for members of those genera. Some strains of
Aerococcus
may exhibit weakly positive catalase reactions due to nonheme catalase activity. Organisms in the genera
Abiotrophia
and
Granulicatella
are normal residents of the oral cavity and are recognized as agents of endocarditis involving both native and prosthetic valves.
Pediococcus
strains have been isolated from bacteremia and cases of sepsis and hepatic abscess in compromised patients.
Vagococci
are motile organisms that, like lactococci, express Lancefield group N antigen.
Weissella
strains are usually isolated in polymicrobial infections. Antimicrobial susceptibility studies on the organisms have generally employed dilution testing methods.
Nocardia, Rhodococcus, Gordonia, Actinomadura, Streptomyces, and Other Aerobic Actinomycetes
Authors: Brown‐Elliott Barbara A. , Zelazny Adrian M. , Conville Patricia S. 
Published: December 2024

Abstract

The anaerobic organisms now in the genus
Actinomyces
and the aerobic organisms grouped together as the “aerobic actinomycetes” were previously presumed to be related to one another on the basis of shared features of microscopic and colonial morphology. The microscopic and colonial morphologies of organisms in the genus
Actinomadura
, which contains more than 100 validly named species or subspecies, are very similar to those in the genus
Streptomyces
. Species in the genus
Saccharopolyspora
were initially thought to be related to
Nocardia
and
Streptomyces
by biochemical characteristics but are phylogenetically distinct from those genera. However, an unknown number of
Gordonia
infections may be missed, either because the isolate is considered an insignificant coryneform Gram‐positive rod or because the isolate is misidentified by biochemical methods as belonging to another genus, such as
Nocardia
or
Rhodococcus
.
Peptide‐Induced Hydrogelation with Ordered Metal‐Organic Framework Nanoparticles Generating Reactive Oxygen Species for Integrated Wound Repair
Authors: Li Ping , Li Yiying , Yao Jiahui , Li Li‐Li 
Published: December 2024

AbstractHydrogels, with their high water content and flexible nature, are a promising class of medical dressings for combating bacterial wound infections. However, their development has been hindered by low sterilization efficiency. Here, this issue is addressed by designing a peptide hydrogel that assembles ordered metal‐organic framework (MOF) nanoparticles with photocatalytic bactericidal activity. Specifically, a short peptide, Nap‐Gly‐Phe‐Phe‐His (Nap‐GFFH), is used to induce the assembly of zinc‐imidazolate MOF (ZIF‐8) into a hydrogel (NHZ gel). This innovative structure integrates three key features: 1) ZIF‐8 nanoparticles are encapsulated within the hydrogel, overcoming their inherent brittleness, insolubility, and limited moldability; 2) the ordered ZIF‐8 structure enhances charge transfer, enabling efficient generation of reactive oxygen species (ROS); and 3) ZIF‐8 simultaneously improves the photocatalytic bactericidal efficiency and mechanical properties of the hydrogel. The NHZ gel demonstrates remarkable antibacterial performance, achieving >99.9% and 99.99% inactivation of Escherichia coli and Staphylococcus aureus, respectively, within 15 min of simulated solar radiation. Additionally, the NHZ gel exhibits excellent biocompatibility, water retention, and exudate absorption, highlighting its broad potential for wound healing.
Regioselective Cobalt‐Catalyzed Protoboration of Alkynes
Authors: Hwang Ho Seong , Cho Eun Jin 
Published: December 2024

AbstractA regioselective cobalt‐catalyzed protoboration of alkynes has been developed, utilizing diboron as the borylation source for the efficient synthesis of alkenylborates. The reaction proceeds via cobalt‐boryl intermediates, diverging from conventional Co−H chemistry. By fine‐tuning the phosphine ligand side chains, we achieved excellent reactivity and regioselectivity across a wide range of internal and terminal alkynes. This Co‐catalyzed method offers significant advantages in terms of both efficiency and environmental impact, making it an attractive approach for the synthesis of complex organic molecules.
Regiospecific Alkene Oxyamination via N‐Alkylation‐ Hydroxylation‐Transesterification Cascades
Authors: Zhang Hong‐Xia , Kou Li‐Gang , Gao Ya‐Ru , Jia Qiong , Wang Yong‐Qiang 
Published: December 2024

AbstractAn unprecedented cascade reaction of simple inactive alkenes, azo compounds and H2O to produce valuable poly‐substituted oxazolidinones is reported herein. The transformation possesses exclusive regioselectivity and features mild reaction conditions and a broad substrate scope. Mechanistic studies indicated this transformation underwent a N‐alkylation‐hydroxylation‐transesterification cascade process. This research not only pushes the boundaries of the essential difunctionalization of alkenes but also exploits a new chemistry for azo compounds.
Targeted SPP1 Inhibition of Tumor‐Associated Myeloid Cells Effectively Decreases Tumor Sizes
Authors: Kartal Benan , Garris Christopher S. , Kim Hyung Shik , Kohler Rainer H. , Carrothers Jasmine , Halabi Elias A. , Iwamoto Yoshiko , Goubet Anne‐Gaëlle , Xie Yuxuan , Wirapati Pratyaksha , Pittet Mikaël J. , Weissleder Ralph 
Published: December 2024

AbstractSecreted phosphosprotein 1 (SPP1)High tumor‐associated macrophages (TAM) are abundant tumor myeloid cells that are immunosuppressive, pro‐tumorigenic, and have a highly negative prognostic factor. Despite this, there is a lack of efficient TAM‐specific therapeutics capable of reducing SPP1 expression. Here, on a phenotypic screen is reported to identify small molecule SPP1 modulators in macrophages. Several hits and incorporated them into a TAM‐avid systemic nanoformulation are identified. It is shown that the lead compound (CANDI460) can down‐regulate SPP1 in vitro and in vivo and lead to tumor remissions in different murine models. These findings are important as they offer a promising avenue for developing novel therapeutic strategies targeting TAM.