bluuebunny/crossref_metadata_2025 huggingface dataset:
Olfactory Performances
Authors: Banes Sally
Published: July 2002

For a century at least, in Western cultures, strong odors were mostly regarded as “bad”, stinks to be done away with. Banes finds that performing artists are attempting to restore the sense of smell to the theatrical experience. She anatomizes the rhetoric and practice of “aroma design” in theatrical representation and looks at smell as a paradigm of “liveness.”
A Distributed Virtual Environment for Collaborative Engineering
Authors: Maxfield John , Fernando Terrence , Dew Peter
Published: July 2002

This article details research to develop a distributed collaborative engineering environment (DCEE) system that will allow members of a geographically dispersed multidisciplinary team to collaborate during product development. This article addresses the problems of integrating the information that is generated during product development (product data) with a distributed virtual environment, and the problems of supporting multidisciplinary teams in the development process. The DCEE is an enhanced distributed virtual environment with a rich set of engineering applications and information as it provides an architecture and engineering tools that allow the direct sharing of standard product data among the users with immediate propagation of any changes. Each user has a local environment that can be configured with the tools and data that each specialist requires in the product development lifecycle. An implementation of the architecture has been built to demonstrate this approach, and its performance has also been evaluated.
Battered Women and Their Animal Companions: Symbolic Interaction Between Human and Nonhuman Animals
Authors: Flynn Clifton
Published: July 2002

Only recently have sociologists considered the role of nonhuman animals in human society. The few studies undertaken of battered women and their animal companions have revealed high rates of animal abuse co-existing with domestic violence. This study examines several aspects of the relationship between humans and animals in violent homes. The study explored the role of companion animals in the abusive relationship through in-depth, semi-structured interviews with clients at a battered women's shelter. In particular, the study focused on the use of companion animals by women's violent partners to control, hurt, and intimidate the women; the responses of the animals to the women's victimization; and the role of pets as human surrogates and the resulting symbolic interaction between human and nonhuman family members. The significance of the findings for family violence research and application are discussed, as well as the broader implications for sociological investigation of human-animal interaction.
INTERSEXUALITY IN THE FRESHWATER CRAYFISH SAMASTACUS SPINIFRONS (PHILIPPI, 1882) (DECAPODA, PARASTACIDAE)
Authors: Rudolph Erich
Published: July 2002

Samastacus spinifrons, a South American freshwater crayfish, has always been characterized as gonochoric in the literature. Yet, in 1989, a specimen with anomalous sexual characters was captured in the river Hueyusca. Since then, 13 other specimens showing such anomalous features have been collected in various rivers in the Osorno province, southern Chile. Anatomical dissections disclosed that 4 of them had testes; 4 others had ootestes and 5 had ovaries. Further, all the specimens had gonoducts and gonopores of both sexes, except in one of those with ovaries, wich had oviducts only. Morphometric analyses of abdomens of normal males and females, in comparison with those of intersexual specimens showed that the latter have abdomens with male characteristics. These conditions are all described, the frequency of the phenomenon is reported and a possible explanation for its occurrence is proposed. El camaron de rio de Sudamerica, Samastacus spinifrons, siempre ha sido caracterizado como gonocorico por la literatura. Sin embargo, en 1989 se capturo en el rio Hueyusca un especimen con caracteres sexuales anomalos. Desde entonces, se han colectados otros 13 especimenes con caracteres anomalos en varios rios de la provincia de Osorno, en el sur de Chile. Las disecciones anatomicas demostraron que 4 de ellos tenian testiculos, otros 4 tenian ovotestis, y 5 tenian ovarios. Ademas, todos tenian gonoductos y gonoporos de ambos sexos, excepto uno de aquellos con ovarios que solo tenia oviductos. Analisis morfometricos de los abdomenes de los machos y hembras normales, comparados con aquellos de especimenes intersexo demostraron que estos ultimos tienen un abdomen con caracteristicas masculinas. Se describen todas estas condiciones, se comunica la frecuencia de ocurrencia de este fenomeno y se propone una probable explicacion para el.
Effects of temperature on the duration of the life cycle of a Meloidogyne incognita population
Authors: Ploeg Antoon , Maris Paul
Published: July 2002

The generation time and reproduction of Meloidogyne incognita was studied under five soil temperatures. The life cycle was completed on tomato between average soil temperatures of 16.2°C and 30.0°C but not at 35.4°C. On the marigold(Tagetes hybrid) variety Polynema the life cycle was completed only at 30.0°C. Estimates for the base temperature (Tb) and the required heat sum (S) were 10.1°C and 400°C. day respectively. The thermal time relationship for completion of the life cycle of M. incognita is discussed in relation to those of other Meloidogyne species. Influence de la temperature sur la duree du cycle biologique d'une population de Meloidogyne incognita - La duree du cycle et la reproduction de Meloidogyne incognita ont ete etudiees a cinq temperatures. Sur tomate, le cycle peut s'accomplir a des temperatures moyennes du sol s'etageant de 16,2 a 30,0°C, mais non a 35,4°C. Sur oeillet d'Inde (hybride de Tagetes de la variete Polynema), le cycle ne s'accomplit qu'a 30,0°C. La temperature de base (Tb) et la demande thermique (S) sont estimees a, respectivement, 10,1°C et 400°C/jours. La relation temperature/temps relative a l'accomplissement du cycle biologique est discutee et comparee au cas des autres especes du genre.
La cristallinité de l'illite revisitée: un bilan des connaissances acquises ces trente dernières années
Authors: Kübler B. , Goy-Eggenberger D.
Published: July 2002

The main reason for the initial determinations of illite crystallinity (IC) was to support the exploration for liquid and gaseous hydrocarbons. The application in 1960 of the Weaver Sharpness Ratio to core materials of a borehole from eastern France indicated that it was not a reliable tool for identifying well-crystallized illite. This ratio was later replaced by the Full Width at Half-Maximum (FWHM), the value of which decreases regularly and consistently towards greenschist facies. The use of FWHM allowed a precise definition of the anchimetamorphic zone between the upper diagenesis and the epimetamorphism. Afterwards, analysis of weak-tointermediate diagenetic sequences showed that illite crystallinity decreases together with the amount of swelling interlayers in mixed-layer clay minerals. Technological improvements, such as computing and modelling of X-ray diffraction patterns, increased the analytical precision relative to measurements of the plain FWHM. Consequently, illite crystallinity went back to its initial use, namely detection of the transitions between diagenesis, anchi- and epi-metamorphism in smectitefree lithologies, where it can be used as a stratigraphic and mineralogic marker of alteration stages.
Chemistry of columbite-tantalite minerals in rare metal granitoids, Eastern Desert, Egypt
Authors: Abdalla H. M. , Helba H. A. , Mohamed F. H.
Published: July 2002

Paragenetic, textural, and chemical characteristics of columbite-tantalite minerals are examined as steps towards identifying the metallogenetic processes of their host granitoids. Columbite-tantalite-bearing granitoids of the Eastern Desert province of Egypt can be categorized into: (i) metaluminous alkali granites; (ii) peraluminous Li-albite granites; and (iii) metasomatized biotite and/or muscovite granite (i.e. apogranites).

Columbite of the alkali granite is of FeNb2O6composition and associated with annite. The low F and Li contents of the associated mica precludes the important role of these volatile elements during the late stage of evolution of the alkali granites, thus delaying fractionation of Mn over Fe and Ta over Nb.

Compositionally, columbite-tantalite of the Li-albite granites is constrained between MnNb2O6and MnTa2O6(the Ta/(Nb+Ta)atom. ratio ranges between 0.10 and 0.80). This low to high ratio and the association of columbite-tantalite with topaz, fluorite and lithian micas (in the series zinnwaldite-white mica) indicate a higher solubility for Ta-fluoride complex compounds and their more stabilized state at lower temperatures in Li- and F-rich sodic melts. The columbite-tantalite commonly exhibits a mottled or patchy zoned texture with the rims consistently higher in Ta than the cores, reflecting the later effect of a corrosive supercritical vapour phase.

The columbites of metasomatized granites range in composition between FeNb2O6and MnNb2O6. They are characterized by high Ti and U, and low Ta contents (the Ta/(Nb+Ta)atom. ranges between 0.01 and 0.15), indicating deposition from alkaline (K+Na+-rich), and relatively high-temperature interacting fluids. However, the Mn-enriched columbites are commonly encountered in the apical parts of the apogranites and formed in response to high μKFand μLiFrequired for stabilizing the associated Li-siderophyllite or zinnwaldite. Columbites of the apogranites commonly exhibit progressive (either normal or reverse) zoning which can be attributed to the disequilibrium conditions (e.g. sudden change in the pH) between the growing crystal and the solutions.
Presentation of ovalbumin internalized via the immunoglobulin-A Fc receptor is enhanced through Fc receptor γ-chain signaling
Authors: Shen Li , van Egmond Marjolein , Siemasko Karyn , Gao Hong , Wade Terri , Lang Mark L. , Clark Marcus , van de Winkel Jan G. J. , Wade William F.
Published: July 2002

The mechanism of enhanced presentation of ovalbumin (OVA) internalized as immunoglobulin A (IgA)–OVA via the IgA Fc receptor (FcαR) was analyzed by focusing on the role of the FcαR-associated γ chain. Comparison of B-cell transfectants expressing FcαR plus wild-type (WT) γ chain or γ chain in which the immunoreceptor tyrosine-based activation motif (ITAM) was altered by tyrosine mutation or substitution with the ITAM of FcγRIIA showed that signaling-competent ITAM was not required for endocytosis of IgA-OVA. However, antigen presentation was impaired by ITAM changes. Signaling-competent γ-chain ITAM appeared necessary for transport of ligated FcαR to a lamp-1+ late endocytic compartment for remodeling and/or activation of that compartment and also for efficient degradation of IgA complexes. Moreover, FcαR ligation also activated efficient processing of nonreceptor-targeted antigen. The results suggest that γ-chain signaling activates the antigen processing compartment.
Erythroblasts are a source of angiogenic factors
Authors: Tordjman Rafaèle , Delaire Stéphanie , Plouët Jean , Ting Stephen , Gaulard Philippe , Fichelson Serge , Roméo Paul-Henri , Lemarchandel Valérie
Published: July 2002

In adult bone marrow, mature erythroblasts are produced within structures called erythroblastic islands and then cross the endothelial barrier to reach circulation. Erythroblastic islands are composed of a central macrophage surrounded by maturing erythroblasts. In this study, it is shown that erythroid cells, but not the other mature hematopoietic cells, coexpress 2 angiogenic factors, vascular endothelial growth factor A (VEGF-A) and placenta growth factor (PlGF). Secretion of both VEGF-A and PlGF increases during in vitro erythroid differentiation. Erythroblast-conditioned medium can induce both migration of monocytes and endothelial cells and the permeability of endothelial cells. These effects are inhibited by anti-PlGF and/or anti-VEGF antibodies. Finally, it is shown that VEGF-A and PlGF proteins are expressed by bone marrow erythroblasts in vivo. Angiogenic factors secreted by erythroblasts may promote interactions either with macrophages in erythroblastic islands or with endothelial cells that would facilitate the passage of erythroid cells through the endothelial barrier.
Primary human herpesvirus 8 infection generates a broadly specific CD8+ T-cell response to viral lytic cycle proteins
Authors: Wang Qiong J. , Jenkins Frank J. , Jacobson Lisa P. , Kingsley Lawrence A. , Day Richard D. , Zhang Zhi-Wei , Meng Yuan-Xiang , Pellet Philip E. , Kousoulas Konstantin G. , Baghian Abolghasem , Rinaldo Charles R.
Published: July 2002

Human herpesvirus 8 (HHV-8) is a recently discovered gammaherpesvirus that is the etiologic agent of Kaposi sarcoma (KS). The natural history of primary HHV-8 infection, including clinical outcome and host immune responses that may be important in preventing disease related to HHV-8, has not been elucidated. The present study characterized the clinical, immunologic, and virologic parameters of primary HHV-8 infection in 5 cases detected during a 15-year longitudinal study of 108 human immunodeficiency virus type 1 seronegative men in the Multicenter AIDS Cohort Study. Primary HHV-8 infection was associated with mild, nonspecific signs and symptoms of diarrhea, fatigue, localized rash, and lymphadenopathy. There were no alterations in numbers of CD4+ or CD8+ T cells or CD8+ T-cell interferon γ (IFN-γ) production to mitogen or nominal antigen. CD8+ cytotoxic T-lymphocyte precursor (CTLp) and IFN-γ reactivity were detected during primary HHV-8 infection, with broad specificity to 5 lytic cycle proteins of HHV-8 encoded by open reading frame 8 (ORF 8; glycoprotein B homolog of Epstein-Barr virus), ORF 22 (gH homolog), ORF 25 (major capsid protein homolog), ORF 26 (a minor capsid protein homolog), or ORF 57 (an early protein homolog), in association with increases in serum antibody titers and appearance of HHV-8 DNA in blood mononuclear cells. CD8+ T-cell responses to HHV-8 decreased by 2 to 3 years after primary infection. This antiviral T-cell response may control initial HHV-8 infection and prevent development of disease.
Morbidity and mortality in adults with idiopathic thrombocytopenic purpura
Authors: Portielje Johanna E. A. , Westendorp Rudi G. J. , Kluin-Nelemans Hanneke C. , Brand Anneke
Published: July 2002

To study outcomes of adults with idiopathic thrombocytopenic purpura (ITP), we performed a follow-up study in a cohort of 152 consecutive patients who were treated according to a well-defined algorithm. Long-term outcomes were determined relative to the response 2 years after diagnosis, because most (93%) patients who ultimately attained platelet counts above 30.0 × 109/L (30 000/μL) did so within this time frame. Complete follow-up for mortality could be studied in 99% of patients and for morbidity in 95% of patients, with a mean of 10.5 years. Within 2 years after diagnosis, 4 patients died, 2 were lost to follow-up, and 12 were reclassified as having secondary immune thrombocytopenia. Of the remaining 134 patients, 114 (85%) had obtained platelet counts above 30.0 × 109/L while all therapies had been discontinued. These patients had a long-term mortality risk equal to the general population. Twelve of 134 patients (9%), all with severe thrombocytopenia, had refractory disease and suffered a mortality risk of 4.2 (95% confidence interval, 1.7-10.0). Bleeding and infection equally contributed to the death of these patients. Another 8 patients (6%) had platelet counts above 30.0 × 109/L while on maintenance therapy. Similar to patients with refractory disease, these latter patients had considerably increased ITP-related hospital admissions, but mortality was only slightly higher than in the general population. In conclusion, most adults with ITP have a good outcome with infrequent hospital admissions and no excess mortality. The absence of gross morbidity and mortality in patients with moderate thrombocytopenia supports clinical practice refraining from further treatment.
Localization of recombination activating gene 1/green fluorescent protein (RAG1/GFP) expression in secondary lymphoid organs after immunization with T-dependent antigens in rag1/gfpknockin mice
Authors: Igarashi Hideya , Kuwata Naomi , Kiyota Kumiko , Sumita Kiminobu , Suda Toshio , Ono Shiro , Bauer Steven R. , Sakaguchi Nobuo
Published: July 2002

Secondary rearrangements of immunoglobulin gene segments that generate a new antibody repertoire in peripheral B cells have been described as receptor revision and occur by as yet unknown mechanisms. To determine the importance of recombination activating gene (RAG) expression in receptor revision, heterozygous rag1/green fluorescent protein (gfp) knockin mice were used to examine the location of RAG1 expression in the germinal centers (GCs) of lymphoid follicles after immunization with a variety of T-cell–dependent antigens. Immunization of rag1/gfp heterozygous mice orrag1 homozygous knockout mice reconstituted withrag1/gfp heterozygous spleen cells caused the down-regulation of RAG1/GFP signal in GCs. Although some RAG1/GFP+ cells appeared in regions surrounding the peanut agglutinin (PNA)+GL-7+ GC area, RAG1/GFP+ cells did not accumulate in the central region. In addition, the stimulation of spleen B cells with anti-μ antibody plus interleukin-4 (IL-4) or with anti-CD40 monoclonal antibody plus IL-7 did not induce GFP signals at detectable levels in vitro. These results clearly demonstrate that RAG1 re-expression either does not occur or is at extremely low levels in antigen-driven B cells in GCs of secondary lymphoid follicles, suggesting that other mechanisms may mediate the gene rearrangements observed in receptor revision.
PU.1 exhibits partial functional redundancy with Spi-B, but not with Ets-1 or Elf-1
Authors: Garrett-Sinha Lee Ann , Dahl Richard , Rao Sridhar , Barton Kevin P. , Simon M. Celeste
Published: July 2002

Previously it was shown that the Ets proteins, PU.1 and Spi-B, exhibit functional redundancy in B lymphocytes. To investigate the possibility that PU.1 or Spi-B or both share overlapping roles with Ets-1 or Elf-1, PU.1+/−Ets-1−/−, PU.1+/−Elf-1−/−, and Spi-B−/−Ets-1−/− animals were generated. No blood cell defects were observed in these animals except those previously reported for Ets-1−/− mice. Therefore, no genetic overlap was detected between PU.1 or Spi-B with Ets-1 or Elf-1. In contrast, the results confirmed functional redundancy for PU.1 and Spi-B in that PU.1+/−Spi-B−/− bone marrow progenitors yielded smaller colonies in methylcellulose cultures than did wild-type, PU.1+/− or Spi-B−/−progenitors. In addition, PU.1+/−Spi-B+/+, PU.1+/−Spi-B+/−, and PU.1+/− Spi-B−/− mice displayed extramedullary splenic hematopoiesis. In summary, PU.1 and Spi-B regulate common target genes required for proliferation of hematopoietic progenitors or their committed descendants, whereas Ets-1 or Elf-1 do not appear to regulate shared target genes with PU.1 or Spi-B.
Pro-B-cell to pre-B-cell development in B-lineage acute lymphoblastic leukemia expressing the MLL/AF4 fusion protein
Authors: Bertrand Fred E. , Vogtenhuber Christine , Shah Nisha , LeBien Tucker W.
Published: July 2002

The most common chromosomal abnormality of infant acute lymphoblastic leukemia (ALL) is the t(4;11)(q21;q23) that gives rise to the MLL/AF4 fusion gene. Leukemic blasts expressing MLL/AF4 are arrested at an early progenitor stage with lymphoid or monocytoid characteristics. A novel B-lineage ALL cell line termedB-lineage–3 (BLIN-3) requiring human bone marrow (BM) stromal cell contact and interleukin-7 (IL-7) for optimal proliferation has been established. BLIN-3 cells have a CD19+/CD10− phenotype typical of infant ALL, and they harbor the t(4;11)(q21;q23) chromosomal translocation. Reverse transcription–polymerase chain reaction and Western blot analysis confirmed the presence of the MLL/AF4 fusion mRNA and protein in BLIN-3. Initial BLIN-3 cultures had a pro-B cell phenotype and did not express cytoplasmic or surface μ heavy chain. After approximately 5 months in culture on BM stromal cells plus IL-7, BLIN-3 sublines emerged expressing μ heavy chain and VpreB on the cell surfaces (ie, pre-B-cell receptor [BCR]+). BLIN-3 cells expressing pre-BCR had the t(4;11)(q21;q23) translocation and expressed the MLL/AF4 fusion protein. Cross-linking the BLIN-3 pre-BCR led to enhanced cell proliferation, demonstrating that BLIN-3 expressed a functional pre-BCR. Increased acquisition of surface pre-BCR in BLIN-3 sublines was associated with loss of DJ rearrangements and the appearance of VDJ rearrangements. These results indicate that expression of the MLL/AF4 fusion protein is compatible with BM stromal cell and cytokine dependency, functional immunoglobulin gene segment rearrangement, and subsequent expression of a potentially diverse antigen receptor repertoire. Thus, the expression of MLL/AF4 is compatible with the normal developmental program of human B-lineage cells.
Acquired pure red cell aplasia associated with lymphoproliferative disease of granular T lymphocytes
Authors: Go Ronald S. , Li Chin-Yang , Tefferi Ayalew , Phyliky Robert L.
Published: July 2002

Acquired pure red cell aplasia (PRCA) can be associated with lymphoproliferative disease of granular T lymphocytes (T-LDGL), also known as T-cell large granular lymphocyte leukemia. Fifteen adult patients with PRCA associated with T-LDGL comprise this study. Neutropenia and rheumatoid arthritis were uncommon. All patients responded to immunosuppressive therapy. The 2 most commonly used treatments were prednisone and cyclophosphamide ± corticosteroids, producing overall response rates of 50% and 60%, respectively. Treatment with cyclophosphamide was associated with a more durable remission (median, 60 versus 7.5 months). After a median follow-up of 67 months, 2 patients died of treatment-related complications, one from myelodysplasia and another from cyclosporine-induced renal failure. The clinical course and treatment responses of PRCA associated with T-LDGL in this series were similar to the general group of PRCA. Because T-LDGL is frequently underdiagnosed, it is likely that a significant proportion of idiopathic or primary PRCA is in fact secondary to T-LDGL.
Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma
Authors: Lossos Izidore S. , Jones Carol D. , Warnke Roger , Natkunam Yasodha , Kaizer Herbert , Zehnder James L. , Tibshirani Rob , Levy Ronald
Published: July 2002

Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree of morphologic and clinical heterogeneity. Establishment of parameters that can predict outcome could help to identify patients who may benefit from risk-adjusted therapies. BCL-6 is a proto-oncogene commonly implicated in DLBCL pathogenesis. A real-time reverse transcription–polymerase chain reaction assay was established for accurate and reproducible determination of BCL-6 mRNA expression. The method was applied to evaluate the prognostic significance ofBCL-6 expression in DLBCL. BCL-6 mRNA expression was assessed in tumor specimens obtained at the time of diagnosis from 22 patients with primary DLBCL. All patients were subsequently treated with anthracycline-based chemotherapy regimens. These patients could be divided into 2 DLBCL subgroups, one with high BCL-6 gene expression whose median overall survival (OS) time was 171 months and the other with low BCL-6 gene expression whose median OS was 24 months (P = .007). BCL-6 gene expression also predicted OS in an independent validation set of 39 patients with primary DLBCL (P = .01). BCL-6 protein expression, assessed by immunohistochemistry, also predicted longer OS in patients with DLBCL. BCL-6 gene expression was an independent survival predicting factor in multivariate analysis together with the elements of the International Prognostic Index (IPI) (P = .038). By contrast, the aggregate IPI score did not add further prognostic information to the patients' stratification byBCL-6 gene expression. High BCL-6 mRNA expression should be considered a new favorable prognostic factor in DLBCL and should be used in the stratification and the design of risk-adjusted therapies for patients with DLBCL.
Rituximab chimeric anti-CD20 monoclonal antibody treatment for adults with chronic idiopathic thrombocytopenic purpura
Authors: Stasi Roberto , Pagano Adalberto , Stipa Elisa , Amadori Sergio
Published: July 2002

The role of rituximab, a chimeric monoclonal antibody directed against the CD20 antigen, in the treatment of patients with chronic idiopathic thrombocytopenic purpura (ITP) has not been determined. The effectiveness and side effects of this therapeutic modality were investigated in a cohort of 25 individuals with chronic ITP. All patients had ITP that had been resistant to between 2 and 5 different therapeutic regimens, including 8 patients who had already failed splenectomy. Patients were scheduled to receive intravenous rituximab at the dose of 375 mg/m2 once weekly for 4 weeks. Rituximab infusion-related side effects were observed in 18 patients, but were of modest intensity and did not require discontinuation of treatment. A complete response (platelet count greater than 100 × 109/L) was observed in 5 cases, a partial response (platelet count between 50 and 100 × 109/L) in 5 cases, and a minor response (platelet count below 50 × 109/L, with no need for continued treatment) in 3 cases, with an overall response rate of 52%. In 7 cases, responses were sustained (6 months or longer). In 2 patients with relapsed disease, repeat challenge with rituximab induced a new response. In patients with a complete or partial response, a significant rise in platelet concentrations was observed early during the course of treatment, usually 1 week after the first rituximab infusion. No clinical or laboratory parameter was found to predict treatment outcome, although there was a suggestion that women and younger patients have a better chance of response. In conclusion, rituximab therapy has a limited but valuable effect in patients with chronic ITP. In view of its mild toxicity and the lack of effective alternative treatments, its use in the setting of chronic refractory ITP is warranted.
Detection of N-Ras codon 61 mutations in subpopulations of tumor cells in multiple myeloma at presentation
Authors: Kalakonda Nagesh , Rothwell Dominic G. , Scarffe J. Howard , Norton John D.
Published: July 2002

Activating point mutations in codons 12, 13, or 61 of the K-ras and N-ras genes have been reported to occur in up to 40% of patients with multiple myeloma at presentation. In a study of 34 presentation myeloma cases using a sensitive polymerase chain reaction-restriction fragment length polymorphism strategy on enriched tumor cell populations, the present study detected N-ras codon 61 mutation-positive cells in all patients. Quantitative plaque hybridization using allele-specific oligonucleotide probes showed that in the majority of patients, ras mutation-positive cells comprise only a subpopulation of the total malignant plasma cell compartment (range, 12%-100%). Using clonospecific point mutations in the 5′ untranslated region of the BCL6 gene to quantitate clonal B cells in FACS-sorted bone marrow populations from 2 patients, the representation of ras mutation-positive cells was independent of immunophenotype. These observations imply that mutational activation of N-ras codon 61 is a mandatory event in the pathogenesis of multiple myeloma; such mutations provide a marker of intraclonal heterogeneity that may originate at an earlier ontologic stage than immunophenotypic diversification of the malignant B cell clone.
Interleukin-18 stimulates hematopoietic cytokine and growth factor formation and augments circulating granulocytes in mice
Authors: Ogura Takeharu , Ueda Haruyasu , Hosohara Katsushi , Tsuji Risa , Nagata Yuki , Kashiwamura Shin-ichiro , Okamura Haruki
Published: July 2002

Because interleukin-18 (IL-18) is similar to IL-1 and is known to be involved in the hematopoietic progenitor cell growth, the effect of IL-18 on circulating cell populations was examined. Repeated administration of IL-18 induced significant amounts of neutrophilia in mice. In parallel, high levels of interferon-γ (IFN-γ), IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were detected in the serum of these mice. Interestingly, the cytokine profiles as well as the cell populations in circulation altered around 2 weeks after the beginning of IL-18 administration. A weak but definite eosinophilia was observed concurrently with the appearance of serum IL-5. Consistent with these observations, IL-18 induced secretion of IFN-γ, GM-CSF, and IL-6 from splenocytes in culture. IL-18 also induced low levels of IL-5 in the splenocyte culture, which was inhibited by IL-12. However, markedly high levels of IL-5 were secreted into the culture medium when splenocytes from IFN-γ–deficient mice were stimulated by IL-18. CD4+ T cells strongly responded to IL-18 to secrete IL-5 and GM-CSF. IL-18 stimulated secretion of IL-6 and expression of G-CSF mRNA in splenic adherent cells. Expression of IL-18 receptors was detected in CD4+ T cells and splenic adherent cells (macrophages). These results show that IL-18 stimulates CD4+ T cells and macrophages to secrete IL-5, GM-CSF, IL-6, and granulocyte–colony stimulating factor in the absence of IL-12, which in turn induces hematopoietic cell proliferation causing neutrophilia and eosinophilia in mice.
CD8+ T lymphocytes induce polarized exocytosis of secretory lysosomes by dendritic cells with release of interleukin-1β and cathepsin D
Authors: Gardella Stefania , Andrei Cristina , Lotti Lavinia Vittoria , Poggi Alessandro , Torrisi M. Rosaria , Zocchi M. Raffaella , Rubartelli Anna
Published: July 2002

We recently reported that human dendritic cells release the leaderless secretory protein interleukin-1β (IL-1β) following specific interaction with alloreactive T lymphocytes. To clarify the molecular mechanism underlying this secretion, this study investigated the intracellular trafficking of IL-1β in dendritic cells and the signal(s) regulating its release. Results show that a fraction of the intracellular IL-1β precursor colocalizes with the hydrolase cathepsin D in endolysosomes of dendritic cells; secretion of both proteins is elicited by stimuli that induce intracellular calcium increases. Alloreactive CD8+ T lymphocytes generate a Ca++ influx in dendritic cells followed by enrichment in endolysosomes containing IL-1β and cathepsin D beneath the membrane in contact with T cells. These events result in polarized exocytosis of secretory lysosomes, mediated by microtubules, with release of IL-1β and cathepsin D toward the interacting CD8+ T cell.
Shear-dependent tether formation during platelet translocation on von Willebrand factor
Authors: Dopheide Sacha M. , Maxwell Mhairi J. , Jackson Shaun P.
Published: July 2002

The adhesion and aggregation of platelets at sites of vascular injury is dependent on the initial binding of the GP Ib/V/IX receptor complex to immobilized von Willebrand factor (VWF). Under flow conditions, this interaction supports platelet translocation that is characteristically stop-start in nature. High resolution imaging of platelets during surface translocation on immobilized VWF revealed that thin membrane tethers (length: 0.91 μm-47.90 μm) were pulled from the surface of these cells. Membrane tethers were dynamic structures that extended from small, localized adhesion contacts under the influence of flow. Perfusion of platelets in the presence of blocking antibodies against integrin αIIbβ3, or over isolated A1 domains, demonstrated that the VWF–GP Ib interaction was sufficient to induce membrane tether formation. The rate and extent of tether elongation was shear-dependent (shear range: 150 s−1-10 000 s−1), with mean tether length ranging from 3.23 μm to 16.55 μm, tether frequency from 2.67% to 97.33%, and tether growth rate from 0.04 μm/sec to 8.39 μm/sec. Tether formation and retraction did not require platelet activation; however, the growth rate, lifetime, and dimensions were significantly affected by the actin polymerization inhibitor, cytochalasin D, and by chelating intracellular calcium. Single-cell analysis revealed that formation of membrane tethers regulates the stop-start phases of platelet translocation on VWF, suggesting a potentially important role for this phenomenon in regulating the dynamics of the platelet-VWF interaction under flow.
Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene
Authors: Cartron Guillaume , Dacheux Laurent , Salles Gilles , Solal-Celigny Philippe , Bardos Pierre , Colombat Philippe , Watier Hervé
Published: July 2002

Given that the FcγRIIIa receptor 158V allotype displays a higher affinity for human immunoglobulin G1 and increased antibody-dependent cellular cytotoxicity, the aim of this study was to determine the influence of that FCGR3A polymorphism on the therapeutic response to rituximab, an anti-CD20 humanized immunoglobulin G1 increasingly used in the treatment of non-Hodgkin lymphomas. TheFCGR3A-158V/F genotype was determined in 49 patients having received rituximab for a previously untreated follicular non-Hodgkin lymphoma. The clinical response and the disappearance of theBCL2-JH gene rearrangement in both peripheral blood and bone marrow were evaluated at 2 months (M2) and at 1 year (M12). The study population consisted of 20% FCGR3A-158V homozygous patients, 35% FCGR3A-158F homozygous patients, and 45% heterozygous patients (FCGR3A-158F carriers). The objective response rates at M2 and M12 were 100% and 90%, respectively, inFCGR3A-158V homozygous patients compared with 67% (P = .03) and 51% (P = .03), respectively, in FCGR3A-158F carriers. A disappearance of theBCL2-JH gene rearrangement in both peripheral blood and marrow was observed at M12 in 5 of 6 of homozygousFCGR3A-158V patients compared with 5 of 17 ofFCGR3A-158F carriers (P = .03). The homozygous FCGR3A-158V genotype was confirmed to be the single parameter associated with clinical and molecular responses by multivariate analysis. This study showed an association between theFCGR3A genotype and clinical and molecular responses to rituximab. This finding will certainly give rise to new pharmacogenetic approaches to the management of patients with non-Hodgkin lymphomas.
Oncologists’ Attitudes and Practices Regarding Banking Sperm Before Cancer Treatment
Authors: Schover Leslie R. , Brey Kimberly , Lichtin Alan , Lipshultz Larry I. , Jeha Sima
Published: July 2002

PURPOSE: The goal of this study was to survey oncologists in three different practice settings to determine their knowledge, attitudes, and practices regarding referring patients to bank sperm before cancer treatment.

METHODS: A postal survey about knowledge, attitudes, and practices regarding banking sperm before cancer treatment was sent to 718 oncology staff physicians and fellows at two cancer centers and at sites in a Community Clinical Oncology Program.

RESULTS: The return rate was 24% and did not differ by institution, oncologic specialty, or sex. Fellows were significantly more likely to participate (37%) than staff physicians (20%). Ninety-one percent of respondents agreed that sperm banking should be offered to all men at risk of infertility as a result of cancer treatment, but 48% either never bring up the topic or mention it to less than a quarter of eligible men. Neither greater knowledge about sperm banking nor seeing large numbers of eligible men yearly increased the likelihood of discussing the option. Barriers cited included lack of time for the discussion, perceived high cost, and lack of convenient facilities. Oncologists reported they would be less likely to offer sperm banking to men who were homosexual, HIV-positive, had a poor prognosis, or had aggressive tumors. Oncologists overestimated the costs of sperm banking and the number of samples needed to make cryopreservation worthwhile.

CONCLUSION: Sperm banking should be offered as an option to all men at risk of infertility because of their cancer treatment. Clearer practice standards could help oncologists increase their knowledge about sperm banking and avoid dependence on biased patient selection criteria.
Knowledge and Experience Regarding Cancer, Infertility, and Sperm Banking in Younger Male Survivors
Authors: Schover Leslie R. , Brey Kimberly , Lichtin Alan , Lipshultz Larry I. , Jeha Sima
Published: July 2002

PURPOSE: The goal of this study was to survey male patients aged 14 to 40 years at diagnosis and recently treated in two cancer centers to determine their knowledge, attitudes, and experiences regarding cancer-related infertility and sperm banking.

PATIENTS AND METHODS: A postal survey about cancer-related infertility and sperm banking was offered to 904 men diagnosed with cancer within the previous 2 years. Eight percent opted out of the study. The others were sent the survey, with a cover letter stating elements of informed consent.

RESULTS: Although the return rate was only 27%, yielding a sample of 201 men, responders did not differ significantly from nonresponders by institution, age, ethnicity, or cancer site. Overall, 51% of men wanted children in the future, including 77% of men who were childless at cancer diagnosis. Despite some anxieties about their own survival and risks to their children’s health, men felt that the experience of cancer increased the value they placed on family closeness and would make them better parents. Only 60% of men recalled being informed about infertility as a side effect of cancer treatment, and just 51% had been offered sperm banking. Those who discussed infertility with their physicians had higher knowledge about cancer-related infertility and were significantly more likely to bank sperm. Only 24% of men banked sperm, including 37% of childless men. Lack of information was the most common reason for failing to bank sperm (25%).

CONCLUSION: All men who are about to receive cancer treatment that could impair fertility should be counseled about such side effects and given adequate information to make an informed decision about banking sperm.
How Sociodemographics, Presence of Oncology Specialists, and Hospital Cancer Programs Affect Accrual to Cancer Treatment Trials
Authors: Sateren Warren B. , Trimble Edward L. , Abrams Jeffrey , Brawley Otis , Breen Nancy , Ford Leslie , McCabe Mary , Kaplan Richard , Smith Malcolm , Ungerleider Richard , Christian Michaele C.
Published: July 2002

PURPOSE: We chose to examine the impact of socioeconomic factors on accrual to National Cancer Institute (NCI)–sponsored cancer treatment trials.

PATIENTS AND METHODS: We estimated the geographic and demographic cancer burden in the United States and then identified 24,332 patients accrued to NCI-sponsored cancer treatment trials during a 12-month period. Next, we examined accrual by age, sex, geographic residence, health insurance status, health maintenance organization market penetration, several proxy measures of socioeconomic status, the availability of an oncologist, and the presence of a hospital with an approved multidisciplinary cancer program.

RESULTS: Pediatric patients were accrued to clinical trials at high levels, whereas after adolescence, only a small percentage of cancer patients were enrolled onto clinical trials. There were few differences by sex. Black males as well as Asian-American and Hispanic adults were accrued to clinical trials at lower rates than white cancer patients of the same age. Overall, the highest observed accrual was in suburban counties. Compared with the United States population, patients enrolled onto clinical trials were significantly less likely to be uninsured and more like to have Medicare health insurance. Geographic areas with higher socioeconomic levels had higher levels of clinical trial accruals. The number of oncologists and the presence of approved cancer programs both were significantly associated with increased accrual to clinical trials.

CONCLUSION: We must work to increase the number of adults who enroll onto trials, especially among the elderly. Ongoing partnership with professional societies may be an effective approach to strengthen accrual to clinical trials.
Allogeneic Stem-Cell Transplantation of Renal Cell Cancer After Nonmyeloablative Chemotherapy: Feasibility, Engraftment, and Clinical Results
Authors: Rini Brian I. , Zimmerman Todd , Stadler Walter M. , Gajewski Thomas F. , Vogelzang Nicholas J.
Published: July 2002

PURPOSE: To evaluate the feasibility and safety of nonmyeloablative allogeneic stem-cell transplantation in patients with metastatic renal cell cancer (RCC) and to evaluate efficacy with respect to engraftment and tumor regression.

PATIENTS AND METHODS: Between February 1999 and June 2001, patients with refractory, metastatic RCC were screened for enrollment. A fludarabine and cyclophosphamide–based conditioning regimen was used. Patients received granulocyte-macrophage colony-stimulating factor–mobilized, unmanipulated stem cells from a 6/6 HLA-matched sibling donor. Prophylaxis against graft rejection and graft-versus-host disease (GVHD) included tacrolimus and mycophenolate mofetil.

RESULTS: A total of 284 patients with metastatic RCC were seen during this time period. Eighty-four patients who had siblings available for HLA typing were actively screened for enrollment, and 15 patients have undergone treatment. Durable donor engraftment was achieved in one of the first four patients treated. Patients no. 5 through 15 received a more immunosuppressive conditioning regimen, and all have achieved sustained donor engraftment. In the 12 patients with at least 180 days of follow-up, acute GVHD has occurred in two patients and chronic GVHD in six patients, with four transplant-related mortalities. Four partial responses have been observed (response rate, 33% in all patients; 44% in the nine patients with sustained donor engraftment).

CONCLUSION: Nonmyeloablative allogeneic stem-cell transplantation is feasible for a minority of patients with metastatic RCC. Adequately immunosuppressive conditioning is required for sustained donor engraftment, which is required for an antitumor response. Acute and chronic GVHD are the major causes of substantial morbidity and mortality. Metastatic RCC is susceptible to a graft-versus-tumor effect promoted by allogeneic stem-cell transplantation.
Consumer Wearables—Advancing Atrial Fibrillation Care or Too Much Information?
Authors: Chew Derek S. , Zeitler Emily P. , Mark Daniel B.
Published: November 2024

This Viewpoint describes the diffusion of direct-to-consumer wearable devices capable of early atrial fibrillation detection and the unclear implications for initiation of anticoagulation therapy based on such findings.
Hypotension and Adverse Outcomes in Moderate to Severe Traumatic Brain Injury
Authors: Lee Jun Won , Wang Wendy , Rezk Amal , Mohammed Ayman , Macabudbud Kyle , Englesakis Marina , Lele Abhijit , Zeiler Frederick A. , Chowdhury Tumul
Published: November 2024

Importance

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Hypotension in patients with TBI is associated with poorer outcomes. A comprehensive review examining adverse outcomes of hypotension in patients with TBI is needed.

Objective

To investigate the mortality and incidence of hypotension in patients with TBI.

Data Sources

A search of studies published before April 2024 was conducted using MEDLINE, MEDLINE In Process, ePubs, Embase, Classic+Embase, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews for primary research articles in English, including randomized control trials, quasirandomized studies, prospective cohorts, retrospective studies, longitudinal studies, and cross-sectional surveys.

Study Selection

Inclusion criteria were patients aged at least 10 years with moderate to severe TBI with hypotension. The exclusion criteria were mild TBI (due to the differences in management principles from moderate to severe TBI). Data were screened using Covidence software with multiple reviewers.

Data Extraction and Synthesis

This meta-analysis conforms to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines for assessing data quality and validity. Primary outcomes (unadjusted and adjusted odds ratios [ORs]) were calculated using a random-effect model with 95% CIs. Incidence of hypotension was derived using logit transformation.

Main Outcomes and Measures

Main outcomes were association of hypotension with death and/or vegetative state within 6 months and incidence of hypotension. Vegetative state was not reported due to lack of data from included studies. Hypothesis testing occurred before data collection.

Results

The search strategy identified 17 676 unique articles. The final review included 51 studies (384 329 patients). Pooled analysis of found a significant increase in mortality in patients with hypotension and moderate to severe TBI (crude OR, 3.82; 95% CI, 3.04-4.81; P < .001; I2 = 96.98%; adjusted OR, 2.22; 95% CI, 1.96-2.51; P < .001; I2 = 92.21%). The overall hypotension incidence was 18% (95% CI, 12%-26%) (P < .001; I2 = 99.84%).

Conclusions and Relevance

This meta-analysis of nearly 400 000 patients with TBI found a significant association of greater than 2-fold odds of mortality in patients with hypotension and TBI. This comprehensive analysis can guide future management recommendations, specifically with respect to blood pressure threshold management to reduce deaths when treating patients with TBI.
A‐Site Cation Incorporation Into the Hole Transport Layer for Efficient Quasi‐2D Perovskite Solar Cells
Authors: Chai Yuru , Li Hongxiang , Guo Xihong , Shen Zhibang , Wang Zhen , Yu Yang , Zhou Jingling , Chen Yu , Sun Baoyun
Published: November 2024

The buried interface of perovskite plays a crucial role in attaining superior performance, partly due to its influence on the structure of the overlying perovskite. Here, a novel buried‐interface strategy is proposed that incorporates A‐site cations (FA+ or Rb+) into the hole transport layer (HTL) to optimize perovskite crystallization. The introduction of A‐site cations results in the formation of perovskite as seed at the interface, which effectively promotes the growth of the overlying perovskite with improved orientation, crystallinity, and rearranged phase distribution. Furthermore, an in‐depth understanding of the influence of the crystallization process is tracked by in situ grazing‐incidence wide‐angle X‐ray scattering (GIWAXS) techniques. Meanwhile, it is found that that FA+, due to the black phase α‐FAPbI3, is more suitable for optimizing the upper perovskite compared with Rb+ (δ‐RbPbI3), and their incorporation can alter the structure of the PEDOT chains, thereby enhancing the carrier transport efficiency. With this approach, the 2D perovskite devices (n = 4) based on FACl‐PEDOT:PSS achieve a remarkable power conversion efficiency (PCE) of 18.37%. The optimized device without encapsulation retains 87% of its initial efficiency after 1440 h of exposure in ambient.