bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression characteristics of CD28null memory phenotype CD8+ T cells and its implication in T‐cell aging
Authors: Fann Monchou , Chiu Wai Kan , Wood William H. , Levine Bruce L. , Becker Kevin G. , Weng Nan‐ping
Published: May 2005

Summary:  Accumulation of CD28nullCD8+ T cells is considered as one of the hallmarks of aging in the human immune system. However, the precise changes of CD28nullCD8+ T cells, compared to those of the precursor CD28+CD8+ memory T cells, have not been determined. In this study, we present an analysis of the global gene expression profiles of CD28+ and CD28null memory phenotype CD8+ T cells. These two CD8+ T subsets exhibited an overall similar gene expression profile with only a few dozen genes that were differentially expressed. A wide range of functions, including co‐stimulation, effector activity, signaling, and transcription, were possessed by these differentially expressed genes, reflecting significant functional changes of CD28null memory phenotype CD8+ T cells from their CD28+ counterparts. In addition, CD28null memory CD8+ T cells expressed several natural killer cell receptors and high levels of granzymes, perforin, and FasL, indicating an increasing capacity for cytotoxicity during memory CD8+ T‐cell aging. Interestingly, in vitro culture of these two subsets with interleukin‐15 showed that similar gene expression changes occurred in both subsets. Our analysis provides the gene expression portraits of CD28null memory phenotype CD8+ T cells and alteration from their CD28+ counterparts and suggests potential mechanisms of T‐cell aging.
Effects of aging on early B‐ and T‐cell development
Authors: Min Hyeyoung , Montecino‐Rodriguez Encarnacion , Dorshkind Kenneth
Published: May 2005

Summary:  Lymphocyte production in the bone marrow and the thymus is reduced during aging, but why this decline occurs has not been fully elucidated. The ability to isolate hematopoietic stem and progenitor cells using sophisticated flow cytometric strategies and to manipulate them in vitro and in vivo has provided insights into the effects of aging on primary lymphopoiesis. These analyses have showed that intrinsic changes in hematopoietic precursors that affect their proliferative potential are one factor that contributes to the age‐related decline in B‐ and T‐cell production. This and other age‐related defects may be exacerbated by changes in the lymphopoietic support potential of the bone marrow and thymic microenvironments as well as by age‐induced fluctuations in the production of various endocrine hormones. Particular attention with regard to the latter point has focused on changes in the production of sex steroids, growth hormone, and insulin‐like growth factor‐I. The present review summarizes recent studies of how age‐related perturbations affect primary lymphopoiesis and highlights how the data necessitate the reevaluation of a number of existing paradigms.
The immune system, amyloid‐β peptide, and Alzheimer's disease
Authors: Weksler Marc E. , Gouras Gunnar , Relkin Norman R. , Szabo Paul
Published: May 2005

Summary:  In this review, the case is made that amyloid‐β peptide in the brain of patients with Alzheimer's disease is a primary cause of the disease and that immunotherapy directed against this peptide has the potential to halt and/or reverse disease progression. This supposition is supported by the capacity of anti‐β‐amyloid peptide antibodies to prevent or reverse the disease in mouse models of Alzheimer's disease. Furthermore, preliminary results obtained in a small number of patients with Alzheimer's disease are consistent with the observations made in the mouse model of this disease. We review the relationship between the immune system, amyloid‐β peptide, and Alzheimer's disease and the progress made in applying immunotherapy to patients with Alzheimer's disease.
Intrinsic versus environmental influences on T‐cell responses in aging
Authors: Linton Phyllis‐Jean , Li Shaokang P. , Zhang Yu , Bautista Beverly , Huynh Quan , Trinh Tan
Published: May 2005

Summary:  A decline in T‐cell responses and a switch to memory T‐cell predominance occur with aging. We have used the T‐cell receptor (TCR) transgenic mouse model to study age‐associated changes in T‐cell responses that are a consequence of shifts in subset representation versus changes intrinsic to T cells versus changes in the ‘aged’ microenvironment. We found that naive transgene‐expressing (Tg+) CD4+ T cells from aged mice respond to antigen with reduced interleukin‐2 (IL‐2) production, decreased cell expansion, and limited differentiation to effectors. Comparable to the characteristic accumulation of memory phenotype T cells in aged humans and conventional rodents, Tg+ CD4+ T cells from old OTII and 6.5 TCR transgenic mice acquire a memory phenotype without immunization and become hyporesponsive. The naive Tg+ CD8+ T cells from aged 2C mice expressed activation markers, produced IL‐2, proliferated, and differentiated into cytotoxic T lymphocytes as efficiently as their young counterparts. Responses by adoptive transferred Tg+ cells from young mice, immunized in young and old conventional hosts, indicated that the host age influences the onset of cell division, level of cell expansion, and number of cytokine‐producing cells. Co‐transfer of dendritic cells (DCs) from young and less so from aged conventional mice partially restored responses. Furthermore, DCs and T‐cell migration to draining lymphoid organs was reduced due to deficiencies intrinsic to aged cells and the aged environment. Thus, alterations in T‐cell responses in aging are attributable to intrinsic and environmental influences.
In vivo regulation of telomerase activity and telomere length
Authors: Hathcock Karen S. , Jeffrey Chiang Y. , Hodes Richard J.
Published: May 2005

Summary:  Telomeres are specialized DNA‐protein structures found at the ends of all linear chromosomes. In mammalian cells, they consist of hexanucleotide (TTAGGG) repeats and multiple associated proteins. Telomeres protect the ends of chromosomes and prevent their recognition as DNA breaks. Loss of functional telomere length below a critical threshold can activate programs leading to cell senescence or death. Telomere length represents a balance between the loss of terminal telomeric repeats, which occurs during cell division with incomplete DNA replication, and the addition of telomeric repeats by the unique RNA‐dependent DNA polymerase telomerase. Although most somatic cells do not express telomerase, telomerase is induced in lymphocytes at critical stages of development and activation. Telomerase expression thus may prolong the replicative capacity of lymphocytes and thereby enhance their function in immune responses. We have used murine model systems to address two broadly defined questions about lymphocyte telomere biology: how is telomerase physiologically regulated in T cells responding to antigen challenge, and what is the effect of transcriptionally altered telomerase expression on telomere length and, consequently, on immune function?
B cells, E2A, and aging
Authors: Riley Richard L. , Blomberg Bonnie B. , Frasca Daniela
Published: May 2005

Summary:  Both mouse and human exhibit deficiencies in humoral immunity during ‘old age’. While alterations in phenotype and function have been well documented, the molecular mechanisms that result in immune senescence remain undefined. B lymphopoiesis is suppressed in senescent mice, which may result from deficits at the pre‐B‐cell stage or earlier (e.g. pro‐B cells). This deficit contrasts with the maintenance of the normal number of total peripheral B lymphocytes in senescent mice. However, mature peripheral B cells in aged mice can exhibit reduced efficiencies of both immunoglobulin isotype switching and somatic hypermutation. The basic helix‐loop‐helix transcription factor E2A is crucial at several stages of B‐lymphocyte differentiation, including the development of pro‐B and pre‐B cells within the bone marrow and in isotype switch and somatic hypermutation among peripheral B cells. Therefore, we have focused on the regulation of E2A expression and function during both B lymphopoiesis and isotype class switching in senescent mice. These studies show that E2A expression is normally under complex control at both post‐transcriptional and post‐translational levels. Alterations in E2A expression at both the B‐cell precursor and mature B‐cell developmental stages are hypothesized to contribute to defects in humoral immunity during senescence.
Impaired apoptosis and immune senescence – cause or effect?
Authors: Hsu Hui‐Chen , Scott Donald K. , Mountz John D.
Published: May 2005

Summary:  Aged animals and humans exhibit a decreased T‐cell activation response although they also exhibit increased susceptibility to responses to self‐antigens and a loss of self‐tolerance. The age‐related alteration in T‐cell reactivity, polyclonal expansion of T cells, and enhanced production of autoantibodies may reflect the numerous age‐associated alterations in the T‐cell arm of the immune system that have been revealed in numerous studies. These studies suggest that subpopulations of T cells are not deleted appropriately in older animals. They further suggest that an age‐related impairment of Fas/Fas ligand (FasL)‐mediated apoptosis – which plays a major role in activation‐induced cell death (AICD) of T cells – may contribute to compromised regulation of the immune system. The likely mechanisms that may lead to impaired induction of FasL in AICD senescent T cells include an age‐related shift from the apoptosis‐sensitive T‐helper 1 cell (Th1) response to the AICD‐resistant Th2 response, aberrant T‐cell receptor/CD3 downstream‐signaling pathways, and altered CD28/B7‐mediated T‐cell costimulatory signals. Pathologically, accumulation of AICD‐senescent T cells is associated with a defective cytotoxic T lymphocyte response and generation of autoreactive T cells. Based on the accumulating evidence, we propose that the emergence of the FasLlo AICD‐senescent T cells is not only an effect of immune aging but also an important cause of T‐cell proliferative senescence in both humans and mice.
Human immunosenescence: is it infectious?
Authors: Pawelec Graham , Akbar Arne , Caruso Calogero , Solana Rafael , Grubeck‐Loebenstein Beatrix , Wikby Anders
Published: May 2005

Summary:  Morbidity and mortality due to infectious disease is greater in the elderly than in the young, at least partly because of age‐associated decreased immune competence, which renders individuals more susceptible to pathogens. This susceptibility is particularly evident for novel infectious agents such as in severe acute respiratory syndrome but is also all too apparent for common pathogens such as influenza. Many years ago, it was noted that the elderly possessed oligoclonal expansions of T cells, especially of CD8+ cells. At the same time, it was established that cytomegalovirus (CMV) seropositivity was associated with many of the same phenotypic and functional alterations to T‐cell immunity that were being reported as biomarkers associated with aging. It was discovered that CMV was the prime driving force behind most of the oligoclonal expansions and altered phenotypes and functions of CD8 cells. Independently, longitudinal studies of a free‐living population of the very old in Sweden over the past decade have led to the emerging concept of an ‘immune risk phenotype’ (IRP), predicting mortality, which was itself found to be associated with CMV seropositivity. These findings support our hypothesis that the manner in which CMV and the host immune system interact is critical in determining the IRP and hence is predictive of mortality. In this sense, then, we suggest that immunosenescence is contagious.
Response of aged mice to primary virus infections
Authors: Murasko Donna M. , Jiang Jiu
Published: May 2005

Summary:  Aging is associated with an increased morbidity to virus infections as well as a delay in clearance of symptoms after infection. Studies of sublethal virus infections of aged mice closely mirror the human situation: there is a delay in clearance of virus. The delay in virus clearance is accompanied by a delay and a decrease in T‐cell response, particularly of CD8+ T cells. Intrinsic alterations of T cells of aged mice contribute to this decrease in virus‐specific T‐cell response; however, evidence suggests that environmental or innate components of the aged host also influence this age‐associated decline in clearance of virus. While the changes in the adaptive immune response have been carefully described, the early events in the generation of the T‐cell response after virus infection have received limited attention. Importantly, age‐associated changes in the innate response to virus infection, particularly production of and response to interferon (IFN)‐α/β, cytotoxicity and IFN‐γ production by natural killer cells, interleukin‐12 induction, and depletion of non‐specific T cells early during virus infection need further evaluation.
Vitamin E and immune response in the aged: molecular mechanisms and clinical implications
Authors: Meydani Simin Nikbin , Han Sung Nim , Wu Dayong
Published: May 2005

Summary:  Nutritional status has been indicated as a contributing factor to age‐related dysregulation of the immune response. Vitamin E, a lipid‐soluble antioxidant vitamin, is important for normal function of the immune cells. The elderly are at a greater risk for vitamin E intake that is lower than recommended levels. Vitamin E supplementation above currently recommended levels has been shown to improve immune functions in the aged including delayed‐type hypersensitivity skin response and antibody production in response to vaccination, which was shown to be mediated through increased production of interleukin (IL)‐2, leading to enhanced proliferation of T cells, and through reduced production of prostaglandin E2, a T‐cell suppressive factor, as a result of a decreased peroxynitrite formation. Vitamin E increased both cell‐dividing and IL‐producing capacities of naïve T cells, but not memory T cells. The vitamin E‐induced enhancement of immune functions in the aged was associated with significant improvement in resistance to influenza infection in aged mice and a reduced risk of acquiring upper respiratory infections in nursing home residents. Further studies are needed to determine the signaling mechanisms involved in the upregulation of naïve T‐cell function by vitamin E as well as the specific mechanisms involved in reduction of risk for upper respiratory infections.
Insights into thymic aging and regeneration
Authors: Taub Dennis D. , Longo Dan L.
Published: May 2005

Summary:  The deterioration of the immune system with progressive aging is believed to contribute to morbidity and mortality in elderly humans due to the increased incidence of infection, autoimmunity, and cancer. Dysregulation of T‐cell function is thought to play a critical part in these processes. One of the consequences of an aging immune system is the process termed thymic involution, where the thymus undergoes a progressive reduction in size due to profound changes in its anatomy associated with loss of thymic epithelial cells and a decrease in thymopoiesis. This decline in the output of newly developed T cells results in diminished numbers of circulating naïve T cells and impaired cell‐mediated immunity. A number of theories have been forwarded to explain this ‘thymic menopause’ including the possible loss of thymic progenitors or epithelial cells, a diminished capacity to rearrange T‐cell receptor genes and alterations in the production of growth factors and hormones. Although to date no interventions fully restore thymic function in the aging host, systemic administration of various cytokines and hormones or bone marrow transplantation have resulted in increased thymic activity and T‐cell output with age. In this review, we shall examine the current literature on thymic involution and discuss several interventional strategies currently being explored to restore thymic function in elderly subjects.
Selective down‐regulation of the α6‐integrin subunit in melanocytes by UVB light
Authors: Krengel Sven , Stark Imke , Geuchen Christian , Knoppe Bettina , Scheel Gabriele , Schlenke Peter , Gebert Andreas , Wünsch Lutz , Brinckmann Jürgen , Tronnier Michael
Published: May 2005

Abstract:  In vivo, melanocytes bind to laminin (LM) molecules of the basement membrane (BM) via the integrins α3β1 and α6β1, and they adhere to neighbouring keratinocytes via E‐cadherin. Only few studies have addressed the impact of ultraviolet (UV) light on the interaction of melanocytes with their microenvironment. In this report, we examined the influence of UVB irradiation on the expression of the most important melanocyte‐adhesion molecules (E‐, N‐cadherin, α2‐, α3‐, α5‐, α6‐, αV‐, β1‐, β3‐integrins and ICAM‐1) in vitro by flow cytometry. We were able to demonstrate that the α6‐integrin subunit is selectively and reversibly down‐regulated by UVB in a dwzm 150ose‐dependent manner. In comparison, keratinocytes lacked UVB‐inducible alterations in the expression of α6‐integrin. In the presence of LM‐1, the UVB‐induced down‐regulation of α6‐integrin in melanocytes was significantly reduced. Moreover, LM‐1 increased the resistance of melanocytes to UVB‐induced cell death, as measured by annexinV‐binding analysis. This effect was reversed by preincubation with an α6‐integrin‐blocking antibody. By immunofluorescence, we could demonstrate that UVB leads to a dose‐dependent internalization of α6‐integrin, providing an obvious explanation for the down‐regulation on the outer cell surface observed by flow cytometry. We suggest that adhesion to LM‐1 through α6‐integrin represents a protective mechanism for melanocytes to withstand UVB damage. Through α6‐integrin internalization, sunburns might alter the interaction between melanocytes and the BM, resulting in apoptosis induced by loss of anchorage (anoikis). Repeated sunburns may then lead to the selection of a population of melanocytes which are capable of anchorage‐independent survival, culminating in solar nevogenesis and melanoma development.
E6* oncoprotein expression of human papillomavirus type‐16 determines different ultraviolet sensitivity related to glutathione and glutathione peroxidase antioxidant defence
Authors: Mouret Stéphane , Sauvaigo Sylvie , Peinnequin André , Favier Alain , Beani Jean‐Claude , Leccia Marie‐Thérèse
Published: May 2005

Abstract:  Clinical observations of non‐melanoma skin cancer in immunocompromised patients, such as organ transplant recipients, suggest co‐operative effects of human papillomavirus (HPV) and ultraviolet (UV) radiation. The aim of the present study is to evaluate UV sensitivity and DNA damage formation according to antioxidant status in HPV16‐infected keratinocytes. We used SKv cell lines, infected with HPV16 and well characterized for their proliferative and tumorigenic capacities. We showed that SKv cell lines presented various E6* (a truncated form of E6) RNA levels. We demonstrated that the higher oncoprotein RNA expression level was associated with a higher resistance to solar‐simulated radiation, more specifically to UVB radiation and to hydrogen peroxide. Moreover, this high resistance was associated with a low oxidative DNA damage formation after UV radiation and was related to high glutathione content and glutathione peroxidase activities. Therefore, the results of our study suggest that E6* levels could modulate the glutathione/glutathione peroxidase pathway providing a mechanism to protect HPV‐infected keratinocytes against an environmental oxidative stress, such as UV radiation.
Production of large numbers of Langerhans' cells with intraepithelial migration ability in vitro
Authors: Hubert Pascale , Bousarghin Latifa , Greimers Roland , Franzen‐Detrooz Elizabeth , Boniver Jacques , Delvenne Philippe
Published: May 2005

Abstract:  Langerhans' cells (LCs) are a subset of immature dendritic cells (DCs) and play a key role in the initiation and regulation of immune responses. Functional studies of these cells have been hampered by difficulties in generating a large number of LCs in vitro. We describe a new method to efficiently generate immature DCs exhibiting morphological, immunohistochemical, and ultrastructural features of LCs (CD1a+, Birbeck Granules+, CD207+, E‐cadherin+, cutaneous lymphocyte‐associated antigen+, and CCR6+) from a limited number of CD34+ cord blood progenitors. This method is based on a two‐step procedure consisting of an amplification phase followed by a terminal differentiation induction. The amplification step is initiated with a combination of hematopoietic growth factors (thrombopoietin/stem cell factor/fetal liver tyrosine kinase‐3 ligand), cytokines (granulocyte–macrophage colony‐stimulating factor, tumor necrosis factor‐α, and interleukin‐4), and 5 ng/ml of transforming growth factor (TGF)‐β1. The differentiation is induced by increasing the concentration of TGF‐β1 to 12.5 ng/ml. These culture conditions were efficient for generating a large number of immature LCs (8.74 × 106 ± 3.2) from 15 × 104 CD34+ progenitor cells. In addition, these LCs were shown to be able to infiltrate an in vitro reconstructed epithelium. Because LCs play an important role in the mucosal immunity, this technique could be useful to study their interactions with epithelial pathogenic agents and to perform pharmacological, toxicological, and clinical research.
The expression of human leukocyte antigen‐DR and CD25 on circulating T cells in cutaneous lupus erythematosus and correlation with disease activity
Authors: Wenzel Joerg , Henze Stephanie , Brähler Sabine , Bieber Thomas , Tüting Thomas
Published: May 2005

Background:  Lupus erythematosus (LE) is a chronic autoimmune disease with a broad clinical spectrum reaching from primarily cutaneous manifestations [cutaneous LE (CLE)] up to systemic disease [systemic LE (SLE)]. In patients with SLE, the expression of activation markers on circulating T cells reflects disease activity. Here, we investigated whether this also holds true for patients with CLE.

Patients and methods:  The expression of the activation markers human leukocyte antigen (HLA)‐DR and CD25 on circulating T lymphocytes was measured by flow cytometry in 24 patients suffering from different types of active CLE. Simultaneously, the disease activity was assessed clinically using a CLE activity index. Eighteen healthy donors were analyzed for control purposes.

Results:  HLA‐DR was expressed on a significantly elevated percentage of both CD4+ and CD8+ circulating T cells in active CLE patients when compared with healthy controls. The percentage of HLA‐DR‐expressing T lymphocytes closely correlated with the disease activity. Interestingly, in disseminated scarring chronic discoid LE, a significantly increased percentage of CD25+ cells was observed only in the subset of skin‐homing cutaneous lymphocyte antigen (CLA)+CD4+ and CD8+ T cells.

Conclusion:  Our results provide evidence that activation markers on peripheral blood T cells might help to objectively assess the disease activity in CLE. Furthermore, a significant population of CD25+CLA+CD8+ T cells can only be detected in a subgroup of patients with disseminated scarring CLE and might reflect the systemic expansion of activated cytotoxic T lymphocytes involved in destruction of epidermal tissue.
5‐aminolaevulinic acid photodynamic therapy in a transgenic mouse model of skin melanoma
Authors: Córdoba F. , Braathen L. R. , Weissenberger J. , Vallan C. , Kato M. , Nakashima I. , Weis J. , Von Felbert V.
Published: May 2005

Abstract:  Photodynamic therapy (PDT) is widely used to treat preneoplastic skin lesions and non‐melanoma skin tumours. Studies analyzing the effects of PDT on malignant melanoma have yielded conflicting results. On the one hand, melanoma cell lines in culture as well as cell lines transplanted into experimental animals were sensitive to PDT. On the other hand, spontaneous melanomas of human patients responded poorly to most PDT regimens tested so far. Here, we analyzed effects of 5‐aminolaevulinic acid (5‐ALA)‐based PDT on melanoma cell lines and on experimental melanomas. To mimic the clinical situation as closely as possible, metallothionein‐I/ret (MT‐ret) mice, a transgenic model of skin melanoma development, were used. Optimal doses of 5‐ALA as well as energy doses and power densities were determined in vitro using a cell line (Mel25) established by us from a melanoma of an MT‐ret transgenic mouse as well as commercially available human and mouse melanoma cell lines. Treatment with light irradiation alone had no effect. In combination with 5‐ALA, however, this illumination readily induced the death of all mouse and human melanoma cell lines examined. Still, 5‐ALA PDT caused only minor focal regressive changes including haemorrhages and fibrosis of MT‐ret melanomas in vivo and did not significantly delay tumour growth. These results show that, even though MT‐ret melanoma cells are vulnerable to 5‐ALA PDT in vitro, malignant MT‐ret melanomas in vivo are quite resistant to this type of therapy at doses which are highly effective in vitro.
Dermal mast cells play a central role in the incidence of scratching behavior in mice induced by multiple application of the hapten, 2,4,6‐trinitrochlorobenzene
Authors: Yamashita Hirotaka , Michibata Yoshiko , Mizukami Hajime , Ogihara Yukio , Morita Akimichi , Nose Mitsuhiko
Published: May 2005

Abstract:  Repeated application of 1% 2,4,6‐trinitrochlorobenzene (TNCB) in acetone solution causes chronic skin inflammation in BALB/c mice. Associated scratching behavior gradually appeared, and chronic scratching behavior was established over 40 days after the initial application of TNCB. In order to explore the possible involvement of T cells and mast cells in the appearance of pruritus, we examined the response of athymic nude mice and genetically mast‐cell‐deficient mice. We could not detect either severe skin inflammation or immunoglobulin (Ig)E production in T‐cell‐deficient BALB/c nu/nu mice even after 80 days of TNCB treatment, whereas typical severe skin inflammation and IgE production were observed in mast‐cell‐deficient WBB6F1‐W/Wv and WBB6F1‐Sl/Sld mice. Furthermore, we observed persistent scratching behavior in WBB6F1‐W/Wv mice, but not in BALB/c nu/nu and WBB6F1‐Sl/Sld mice. Histological examination of TNCB‐treated animals revealed the development of dermal mast cells in W/Wv mice but not in Sl/Sld mice. Degranulation of dermal mast cells was observed in the WBB6F1‐W/Wv genotype, but most mast cells remained intact in TNCB‐treated BALB/c nu/nu mice. These results suggest that mast cells play a pivotal role in the incidence of scratching behavior in this chronic pruritus model.
Atopic dermatitis‐like pruritic skin inflammation caused by feeding a special diet to HR‐1 hairless mice
Authors: Fujii Masanori , Tomozawa Junko , Mizutani Nobuaki , Nabe Takeshi , Danno Kiichiro , Kohno Shigekatsu
Published: May 2005

Abstract:  Dry skin/barrier dysfunction is considered to be one of the characteristic features of atopic dermatitis (AD). When HR‐1 hairless mice are fed a special diet, HR‐AD, dry red skin is induced. We examined whether HR‐AD–fed mouse could be used as a model for AD by showing itch‐associated scratching behaviour and by analysing the immunological change. HR‐1 mice were fed HR‐AD from 4 weeks old. HR‐AD–fed mice showed severe dry skin symptoms accompanied by a decrease in dermal water content and an increase in transepidermal water loss and prolonged scratching bout duration on day 14 or 28. These symptoms became gradually worse until day 56. Marked epidermal hyperplasia and slight increase in CD4+ cells in the skin were observed from day 28. In contrast, increases in circulating T cells and serum immunoglobulin E were seen from day 41. Other skin‐infiltrating inflammatory cells, such as eosinophils and mast cells, were increased on day 56 but not on day 28. Though daily oral treatment with dexamethasone reduced the increased numbers of these cells, it did not affect the dry skin symptoms or the prolonged scratching episodes. In contrast, the development of dry skin was inhibited by feeding with 10% normal diet‐containing HR‐AD. The skin barrier dysfunction in HR‐AD–fed mice is closely associated with the development of AD‐like pruritus. Changes in the immunological parameters observed may be the consequence of skin barrier dysfunction. Our findings suggest that HR‐AD–fed mouse could be used as a dry skin‐based experimental model for AD.
Method for Measuring Short‐Crack R‐Curves without Calibration Parameters: Case Studies on Alumina and Alumina/Aluminum Composites
Authors: Stech Martin , Rödel Jürgen
Published: May 2005

A method to measure short‐crack R‐curves is introduced which does not require an independent determination of calibration factors and which utilizes an equilibrium crack shape condition to compute the shape factor of a surface crack, R‐curves of an alumina with two different grain sizes and of an aluminum/alumina composite were measured in the crack length regime of below 100 μm up to almost 1000 μm. Calculated and experimentally obtained crack depth profiles were in good agreement with deviations being between −22% and +26% for the crack ellipticity and confirmed the reliability of the method.
Influence of Reinforcement Content and Diameter on the R‐Curve Response in SiC‐Whisker‐Reinforced Alumina
Authors: Becher Paul F. , Hsueh Chun‐Hway , Alexander Kathleen B. , Sun Ellen Y
Published: May 2005

Experimental studies were conducted to examine the fracture resistance or R‐curve response of fine‐grained (1 to 2 μm grain size) alumina‐based composites reinforced with SiC whiskers. A precracked applied moment double cantilever beam (DCB) specimen was employed where initial crack lengths of ≥50 μm were attained by back‐cutting the crack tip wake region. For a given crack length, the results show that the fracture resistance is shifted upward with whisker content in composites reinforced with 0.8 μm diameter SiC whiskers for all crack lengths ≥50 μm. When the whisker content is fixed at 20 vol% but the whisker size is varied, measurements show that the R‐curve response increases with the average diameter of the whiskers for all crack lengths ≥100 μm. These experimental results are consistent with analytical descriptions of the R‐curve contribution for frictional bridging and pullout processes. The frictional bridging component, involving the displacement within an intact but partially debonded bridging whisker, reflects the significant radial compressive stresses acting on the interface due to the larger thermal contraction of the matrix. Because of the large tensile or bending stresses imposed on the whisker during crack opening, frictional bridging is limited to the region immediately behind the crack tip. Pullout of such bridging whiskers can occur when they fracture or separate from the matrix away from the crack; this can occur close to the crack tip but should become more dominant with increasing distance behind the crack tip. Observations of crack wake zones support these conclusions. Both the experimental results and the constitutive models suggest approaches to tailor the R‐curve response of ceramics reinforced by discontinuous fibers (e.g., whiskers or elongated grains).
Effect of Loading Rate on the Monotonic Tensile Behavior of a Continuous‐Fiber‐Reinforced Glass‐Ceramic Matrix Composite
Authors: Sørensen Bent F. , Holmes John W.
Published: May 2005

The stress‐strain behavior of a continuous‐fiber‐reinforced ceramic matrix composite has been measured over a wide range of loading rates (0.01 to 500 MPa/s). It was found that the loading rate has a strong effect on almost every feature of the stress‐strain curve: The proportionality stress, the composite strength and failure strain increase with increasing loading rate. The microstructural damage varies also with the loading rate; with increasing loading rate, the average matrix crack spacing increases and the average fiber pullout length decreases. Using simple models, it is suggested that these phenomena are caused partly by time‐dependent matrix cracking (due to stress corrosion) and partly by an increasing interfacial shear stress with loading rate.
27Al Nuclear Magnetic Resonance of Glassy and Crystalline Zr(1−x)AlxO(2−x/2) Materials Prepared from Solution Precursors
Authors: Balmer Mari Lou , Eckert Hellmut , Das Nandini , Lange Fred F.
Published: May 2005

The local environment of the aluminum atoms in a series of metastable Zr(1−x)AlxO(2−x/2) crystalline materials (0.08 ≤x≤ 0.57), prepared by diffusion‐limited crystallization of amorphous precursors, has been determined by 27Al magic angle spinning nuclear magnetic resonance (MAS NMR). Results show the existence of aluminum in 4‐, 5‐, and 6‐fold coordination in both the amorphous and crystalline states. Although the relative amounts of each type of coordination show no compositional dependence in the amorphous state, the results for the crystalline materials show a systematic decrease in the average aluminum coordination number with increasing aluminum content. Comparisons of MAS NMR results between pure Al2O3 precursors and Zr (1‐x)AlxO(2‐x/2) crystalline materials processed under similar conditions show a profound effect of ZrO2 on the coordination environment of the aluminum atom. Both a random distribution model and a model that assumes small‐scale clustering of aluminum ions are considered to explain the trends in the type of aluminum coordination as a function of composition.
Photochemical Hole Burning and Local Structural Change in Sm2+‐Doped Borate Glasses
Authors: Cho Doo‐Hee , Hirao Kazuyuki , Fujita Koji , Soga Naohiro
Published: May 2005

Photochemical hole burning (PHB) not only can be applied for data storage systems but also serves as a powerful method for studying the local structure around optical centers. The present work investigated the effects of aluminum, magnesium, and silicon ions on hole burning and the phonon sideband for borate glasses that exhibit PHB at room temperature. Hole burning was measured for the 5D0−7F0 transition of Sm2+ and the phonon sideband spectrum for the 5D0‐7F0 transition of Eu3+. The hole width was closely related to local structural change, especially as it seemed to decrease with decreases in the number of nonbridging oxygens produced around the rare‐earth ions. In the case of sodium aluminoborate glasses, the hole width decreased considerably with increasing alumina content. The ratio Γih/Γh for 85B2O3·10Al2O3·5Na2O·1Sm2O3 glass, then, was 80 at room temperature, the largest value ever reported.
Capillary Infiltration Rates into Porous Media with Applications to Silcomp Processing
Authors: Einset Erik O.
Published: May 2005

The rate of capillary rise of a liquid into a porous medium made up of consolidated particulates is analyzed. The infiltration distance is parabolic in time and can be modeled using the Washburn analysis. The effective pore radius is measured to be one to two orders of magnitude smaller than the particle size, particle spacing, and the median pore size as measured by mercury porosimetry. This result is interpreted using a modification of the Washburn model which models the porous medium as a single pore with varying diameter. Using a two‐sized single pore model, the predicted infiltration rate is consistent with the measured values. In applying the two‐sized single pore model to the reactive capillary infiltration of silicon into a carbonaceous preform in the Silcomp process, the effect of pore closure by the conversion of carbon to SiC is predicted. Using pore closure dimensions measured in a partial infiltration experiment, a decrease in the infiltration rate constant is predicted and is consistent with the measured infiltration rate.
29Si and 31P MAS‐NMR Spectra of Li2S‐SiS2‐Li3PO4 Rapidly Quenched Glasses
Authors: Hirai Koichi , Tatsumisago Masahiro , Takahashi Masanari , Minami Tsutomu
Published: May 2005

29Si and 31P MAS‐NMR spectra were measured for the Li2S‐SiS2‐Li3PO4 glasses. 29Si MAS‐NMR spectra revealed that a large number of silicon atoms in the glasses were coordinated with both sulfur and oxygen atoms. 31P MAS‐NMR spectra showed that some phosphorus atoms were also coordinated with both sulfur and oxygen atoms. Such structural units resulted in the improvement of the conductivity and the glass stability against crystallization by the doping of Li3PO4 to the Li2S‐SiS2 glasses.
Thermodynamic Evaluation of the Bi‐Cu‐O System
Authors: Hallstedt Bengt , Risold Daniel , Gauckler Ludwig J.
Published: May 2005

A thermodynamic evaluation of the ternary Bi‐Cu‐O system has been made and a set of parameters consistently describing the system at 1 bar total pressure has been determined. The ternary system contains a liquid phase which is continuous at high temperature and separates into a metal liquid and an oxide liquid at low temperature and the ternary compound Bi2CuO4 in addition to the binary compounds. Concentration/temperature diagrams are given for the Bi2O3‐CuOx system at oxygen partial pressures of 1, 0.21 and 10−5 bar, as well as a potential diagram. Selected isothermal sections at 1100 and 1473 K are also presented. Available experimental data are rather limited and often show a relatively large scatter, but nevertheless make it possible to determine a sufficient set of thermodynamic parameters.
Synthesis of Transparent Nd‐doped HfO2‐Y2O3 Ceramics Using HIP
Authors: Ikesue Akio , Kamata Kiichiro , Yoshida Kunio
Published: May 2005

A Nd‐doped HfO2‐Y2O3 ceramic having excellent transmittance was synthesized by HIPing, using high‐purity powders (>99.99 wt%) of Y2O3, Nd2O3, and HfO2. The mixed powder compacts of these powders were sintered at 1650°C for 1 h under vacuum and HIPed at 1700°C for 3 h under 196 MPa of Ar. The specimen after HIPing consisted of uniform grains measuring about 30 μm and having pore‐free structure. The optical transmittance of 1 at.% Nd‐doped 2.6 mol% HfO2‐Y2O3 ceramics ranging between visible and infrared wavelength was almost equivalent or superior to that of a Nd:Y2O3 single crystal grown by the Verneuil method.
Mechanism of Nitridation of Silicon Powder in a Fluidized‐Bed Reactor
Authors: Koike Junichi , Kimura Shoichi
Published: May 2005

Direct nitridation of 400 μm average‐sized silicon granules, composed of 2 μm average‐sized particles, was carried out in a fluidized‐bed reactor. Nitridation progress was studied by transmission electron microscopy (TEM). TEM photomicrographs suggested that the formation of surface nitride layers on individual silicon particles and the subsequent spallation of these layers were the dominant process of the direct nitridation of silicon. The spallation was modeled based on a simple crack theory, and the critical thickness of nitride layers leading to spallation was estimated to be 57 nm. This agreed reasonably well with the experimentally observed values of 20–100 nm.
Massive Transformation in Gd2O3‐Bi2O3 Ceramics
Authors: Su Pomin , Virkar Anil Y
Published: May 2005

Gd2O3‐doped Bi2O3 polycrystalline ceramic samples containing between 10 and 26 mol% Gd2O3 were fabricated by pressureless sintering of powder compacts. As‐sintered samples were cubic (CaF2 structure). The cubic solid solutions underwent transformation to a rhombohedral phase when annealed at lower temperatures. Under certain conditions, the cubic phase fully transformed to the rhombohedral phase of the same composition, and the kinetics were thermally activated. This suggested that the cubic → rhombohedral transformation was a massive transformation. The transition temperatures for the occurrence of a massive transformation were experimentally determined by measuring the conductivity as a function of temperature, as well as by measuring growth rate of the rhombohedral precipitates as a function of temperature. The activation enthalpy for interface motion was measured to be ∼200 kJ/mol for the samples studied. The kinetics of cubic → rhombohedral transformation could be described by the Johnson‐Mehl‐Avrami equation.
Order‐Disorder Transition in (A′A″)BO3 and A(B′B″)O3 Complex Perovskite Crystals
Authors: Gui Hong , Gu Bing‐lin , Zhang Xiao‐wen
Published: May 2005

A criterion of ordering was given in an earlier paper for A(B′B′″)O3 crystals with B′ and B″ ions having a charge difference. It has been extended in this paper to (A′A″)BO3 crystals and to the cases where the cations have the same valence. The formulae of the effective interaction energy parameter J in (A′A″)BO3 and A(B′B″)O3 are deduced separately, considering the interaction between ions to be a sum of the Coulomb interaction and Lennard‐Jones overlap interaction. When the charge difference Δq¦ 0, the Coulomb energy difference between the ordered and disordered states caused by the charge difference is the main driving force of ordering. When Δq= 0, the overlap interaction term becomes important.
Synthesis of Yttrium Aluminum Garnet from Yttrium and Aluminum Isobutyrate Precursors
Authors: Liu Yin , Zhang Zhi‐Fan , King Bruce , Halloran John , Laine Richard M.
Published: May 2005

Mixtures of yttrium and aluminum isobutyrates, M(O2CCHMe2)3= M(O2CiPr)3 (M = Y or Al), were examined as precursors for processing yttrium aluminum garnet (YAG, A15Y3O12). Both precursors were synthesized by reacting the respective metal with isobutyric acid. The individual compounds and the 5Al(O2CiPr)3:3Y(O2CiPr)3 YAG composition mixture were characterized by TGA, DTA, XRD, NMR, and FTIR. Pyrolytic decomposition of Al(O2CiPr)3 at temperatures ≤700°C produces amorphous A12O3, which partially crystallizes to α‐alumina at 840°C (by DTA), and finally to a‐alumina at 1120°C. The pyrolysis behavior of Y(O2CiPr)3 is quite different. Samples start to decompose at 260°C, producing mixtures of Y2O3 with minor quantities of a yttrium carbonate species. On further heating to 300°C, the amorphous Y2O3 crystallizes (bcc). The carbonate remains stable until ∼900°C, and phase‐pure, bcc Y2O3 is obtained only on heating to 1400°C. Mixtures of Al(O2CiPr)3 and Y(O2CiPr)3 provide a precursor to polycrystalline YAG. Rheologically useful solutions are obtained by dissolving a 5:3 mixture of Al(O2CiPr)3 and Y(O2CiPr)3 in THE Solvent removal provides bulk samples of the YAG precursor. The pyrolytic decomposition patterns of bulk samples of this YAG precursor were studied by heating to selected temperatures and characterizing by TGA, DTA, XRD, and FTIR. The crystallization behavior of the mixture is quite different from the constituent compounds. The precursor decomposes to an amorphous material on heating above 300°C. On continued heating (5°C/ min/air) this amorphous intermediate crystallizes (∼910°C) to phase‐pure YAG with a final ceramic yield of 26% at 1000°C. No other phases are observed to form over this temperature range.
Crack‐Interface Interactions in a Tungsten‐Yttria‐Stabilized‐Zirconia Directionally Solidified Eutectic
Authors: Isabell Thomas C. , Dravid Vinayak P. , Hill D. Norman
Published: May 2005

A directionally solidified eutectic (DSE) of W‐ZrO2(Y2O3) consists of faceted fibers of tungsten embedded in yttriastabilized cubic zirconia. The W‐ZrO2 interfaces in this system are devoid of any impurity phases or a reaction product. Microindentation‐induced cracks and their interactions with interphase interfaces are investigated using scanning and transmission electron microscopy. Crack‐interface interactions are found to fall into one of four categories: propagation along the metal‐ceramic interface, deflection away from the interface, crack‐interface bridging, and shearing of tungsten fibers. Further crack propagation is investigated in situ in a TEM with a propagation induced by local electron beam heating. These crack path selections are analyzed within the framework of phenoin‐enological understanding of crack‐interface interactions in composites.
Concept for a Damage‐Tolerant Ceramic Composite with “Strong” Interfaces
Authors: Tu Wen‐Chiang , Lange Fred F. , Evans Anthony G.
Published: May 2005

A ceramic‐matrix composite (CMC) that exhibits damage‐tolerant behavior without “weak” interfaces has been demonstrated. The concept relies on the heterogeneous distribution of fiber bundles within a porous matrix having homogeneous, fine porosity. It also depends on the development of residual stress from thermal expansion mismatch. The present demonstration uses Al2O3 fibers with either a silicon nitride or a mullite matrix. The latter is inherently oxidation resistant.
Room‐Temperature Cyclic Fatigue of Reaction‐Bonded Silicon Nitride Using the Double Cleavage Drilled Compression Specimen
Authors: Christensen Renee J. , Faber K. T.
Published: May 2005

The double cleavage drilled compression specimen was used to study the room‐temperature cyclic fatigue behavior of reaction‐bonded silicon nitride (RBSN). Fatigue results were compared with slow crack growth under static loading. The fatigue exponent for RBSN was found to be 40, although no slow crack growth occurred under static loading. The fatigue threshold for RBSN was as low as 0.5/Klc and dependent upon loading conditions. Crack growth behavior and electron microscopy provided evidence that the fatigue mechanism was due to asperity and debris wedging at the crack face.
Effect of Poly(vinyl alcohol) Adsorption on Binder Segregation during Drying
Authors: Zhang Yao , Suga Takehumi , Kawasaki Mutsurou , Tang Xiao‐Xia , Uchida Nozomu , Uematsu Keizo
Published: May 2005

The effect of poly(vinyl alcohol) adsorption on segregation was quantitatively studied by a model experiment of one–dimension drying and simulated by a mathematical model. It was clear that the adsorption of PVA on alumina particle was a slow process, and the adsorbed binder was not desorbed at higher temperature. PVA segregation can significantly be limited by fully adsorbing the binder before drying. The simulation and experiments agreed very well. The effects of drying temperature, initial concentration of the binder, and thickness of specimen on the surface segregation are discussed quantitatively. Mathematical simulation has a great potential for predicting the segregation of soluble components during drying, especially for such cases as thin films and small granules where it is difficult to determine the distribution of the component directly.
Synthesis and Electrical Characterization of Thin Films of PT and PZT Made from a Diol‐Based Sol‐Gel Route
Authors: Tu Yeur‐Luen , Calzada Maria L. , Phillips Nicolas J. , Milne Steven J.
Published: May 2005

Lead titanate (PT) sols were prepared using propanediol, butanediol, or pentanediol solutions of lead acetate trihydrate and titanium diisopropoxide bis(acetylacetonate). Precursor sols for PbZr0.53Ti0.47O3 (PZT) films were prepared from propanediol solutions, with zirconium tetrapropoxide being used as the zirconium source. Films were formed by spin‐coating the sols onto silicon and platinized silicon substrates; the resulting gel layers were converted to ceramic films by adopting a two‐stage heating schedule with final firing temperatures of 600–700°C. Information on film crystallization, microstructure development, and electrical properties is presented for both compositions. The limiting thickness of surface‐smooth crack‐free single‐layer films was ∼1 μm. The PT films exhibited a “linear” polarization‐electric field (P‐E) response, while the PZT films gave rise to characteristic ferroelectric P‐E hysteresis loops. A 0.5 μm thick single‐layer PZT film exhibited remanent polarization (Pr) values of ∼34 μC·Cm−2, with a coercive field (Ec) of ∼45 kV·Cm−2; the relative permittivity (ɛr) and the dissipation factor (D) were ∼1250 and 0.07. For a 1 μm single‐layer PZT film, the respective values were Pr∼19 μC∼Cm−2, Ec∼40 kV∼Cm−2, ɛr∼750, and D= 0.03.