Surfactant-induced lysis of lipid-modified microgels.
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Cell Membrane Permeability↗
Biomedical subjects
J S Moore
Publications and source records attributed to J S Moore.
Multiparameter flow cytometric approach for simultaneous evaluation of T lymphocyte-endothelial cell interactions.
Since vascular endothelium is now recognized as an immunologically active tissue, a better understanding of the relationship between endothelial cells and T lymphocytes is critical to the field of solid organ transplantation. Investigations of endothelial cell-T cell interactions have been limited by methodology. We developed a flow cytometric method allowing for concurrent investigation of multiple cell populations within the same culture that can be applied to these complex interactions. Allogeneic CD8+ or CD4+ T cells labeled with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE) were added to a murine endothelial cell monolayer, in which endothelial proliferation was not inhibited by irradiation or addition of a cell cycle-blocking agent. At specific time points, the coculture was analyzed by flow cytometry. T-cell proliferation could be detected by gating on the T-cell subset and evaluating the CFSE fluorescence peaks. By directly analyzing cellular division, we minimized erroneous interpretation of the data encountered by previous studies, which utilized (3)H-thymidine incorporation as sole measure of proliferation. Further subgating on cells that divided facilitated the study of CD8+ lymphocyte activation, differentiation, and acquisition of effector function. By gating on the endothelial cell population, phenotypic changes such as upregulation of surface MHC molecules or immune-mediated apoptosis could be detected. In conclusion, we present a flow cytometric approach that could have important applications for clinical immunological monitoring in allogeneic or xenogeneic transplantation, and might provide the requisite information to better tailor immunotherapy to prevent chronic rejection.
Animals↗
Cooperativity in the folding of helical m-phenylene ethynylene oligomers based upon the 'sergeants-and-soldiers' principle.
The 'Sergeants-and-Soldiers' principle has been examined in a series of m-phenylene ethynylene oligomers containing both chiral and achiral side chains. Circular dichroism (CD) spectroscopy was used to examine the twist sense bias of the helical conformation in the polar solvent acetonitrile. A non-linear dependence of the CD signal on the amount of chiral side chains was observed revealing cooperative interactions among the side chains through the backbone. On the other hand, the experiments indicate that in acetonitrile a full bias of the helicity cannot be accomplished by chiral side chains alone. Nevertheless, the folded oligomers are highly ordered since the placement of a single chiral side chain at the beginning of an oligomer results in the induction of a strong twist sense bias into the ordered helical conformation.
Journal Article↗
Self-assembly of folded m-phenylene ethynylene oligomers into helical columns.
Circular dichroism spectroscopy has been used to study the self-assembly of two series of m-phenylene ethynylene oligomers in highly polar solvents. The helical conformation of shorter oligomer lengths was found to be stabilized in aqueous acetonitrile solutions, while longer oligomers began to interact intermolecularly. The intermolecular aggregation of the oligomers in aqueous solutions revealed a chain length dependent association that required the presence of a stable helical conformation. Evidence for intermolecular interactions is provided by Sergeants and Soldiers experiments in which the twist sense bias of a chiral oligomer is transferred to an achiral oligomer.
Journal Article↗
Synergistic growth inhibition of prostate cancer cells by 1 alpha,25 Dihydroxyvitamin D(3) and its 19-nor-hexafluoride analogs in combination with either sodium butyrate or trichostatin A.
Prostate cancer is a major cause of male cancer death. In vitro and in vivo data support a role for 1 alpha,25 Dihydroxyvitamin D(3) (1 alpha,25(OH)(2)D(3)) in regulating the growth and differentiation of the normal prostate gland yet prostate cancer cells appear significantly less sensitive to this action. Vitamin D(3) receptor (VDR) content or mutational status do not correlate clearly with the antiproliferative effects of 1 alpha,25(OH)(2)D(3) and therefore it is unclear why prostate cancer cell lines are significantly less sensitive to this action. We hypothesized that the antiproliferative responses of prostate cancer cells to 1 alpha,25(OH)(2)D(3) are suppressed by a process involving histone deacetylation. Sodium butyrate (NaB) and trichostatin A (TSA) are inhibitors of histone deacetylase (HDAC) activity. Low doses of NaB or TSA (300 microM and 15 nM respectively), which alone were relatively inactive, synergized with 1 alpha,25(OH)(2)D(3) in liquid and semi-solid agar to inhibit the growth of LNCaP, PC-3 and DU-145 prostate cancer cells. Still greater synergy was observed between vitamin D(3) hexafluoride analogs and either NaB or TSA. The mechanism appeared to involve neither the cyclin-dependent kinase inhibitor, p21((waf1/cip1)) nor cell cycle arrest, but rather induction of apoptosis. These data suggest that cells dysregulate the normal pro-apoptotic signals of 1 alpha,25(OH)(2)D(3) during prostate cancer development by a mechanism involving histone deacetylation. Combination therapy with potent vitamin D(3) analogs and clinically approved HDAC inhibitors may overcome this lesion and improve the treatment of both androgen-dependent and independent prostate cancer.
Antineoplastic Agents↗
HIV infection in women in the United States: status at the Millennium.
CONTEXT: During the past decade, knowledge of human immunodeficiency virus (HIV) infection in women has expanded considerably but may not be easily accessible for use in understanding and prioritizing the clinical needs of HIV-infected women. OBJECTIVES: To perform a comprehensive review of epidemiologic, clinical, psychosocial, and behavioral information about HIV in women, and to recommend an agenda for future activities. DATA SOURCES: A computerized search, using MEDLINE and AIDSline, of published literature was conducted; journal articles from January 1981 through July 2000 and scientific conference presentations from January 1999 through July 2000 were retrieved and reviewed for content; article reference lists were used to identify additional articles and presentations of interest. STUDY SELECTION: Data from surveillance and prospective cohort studies with at least 20 HIV-infected women and appropriate comparison groups were preferentially included. DATA EXTRACTION: Included studies of historical importance and subsequent refined analyses of topics covered therein; these and studies with more current data were given preference. Four studies involving fewer than 20 women were included; 2 studies were of men only. DATA SYNTHESIS: Women account for an increasing percentage of all acquired immunodeficiency syndrome (AIDS) cases, from 6.7% (1819/27 140 cases) in 1986 to 18% (119 810/724 656 cases) in 1999. By the end of 1998, of all newly reported AIDS cases among women, proportionally more were in the South (41%), among black women (61%), and from heterosexual transmission (38%). Of note, increasingly more women have no identified or reported risk, about half or more of whom are estimated to be infected heterosexually. It is estimated that a total of at least 54% of women newly reported with AIDS in 1998 acquired HIV through heterosexual sex, including women in the no identified or reported risk category estimated to have been infected heterosexually, meeting the surveillance heterosexual risk definition. Natural history, progression, survival, and HIV-associated illnesses-except for those of the reproductive tract-thus far appear to be similar in HIV-infected women and men. Although antiretroviral therapy has proven to be highly effective in improving HIV-related morbidity and mortality rates, women may be less likely than men to use these therapies. Drug use, high-risk sex behaviors, depression, and unmet social needs interfere with women's use of available HIV prevention and treatment resources. CONCLUSIONS: Continued research on HIV pathogenesis and treatment is needed; however, emphasis should also be placed on using existing knowledge to improve the clinical care of women by enhancing use of available services and including greater use of antiretroviral therapy options, treating depression and drug use, facilitating educational efforts, and providing social support for HIV-infected women.
AIDS-Related Opportunistic Infections↗
Chain length-dependent affinity of helical foldamers for a rodlike guest.
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Journal Article↗
Autonomic healing of polymer composites.
Structural polymers are susceptible to damage in the form of cracks, which form deep within the structure where detection is difficult and repair is almost impossible. Cracking leads to mechanical degradation of fibre-reinforced polymer composites; in microelectronic polymeric components it can also lead to electrical failure. Microcracking induced by thermal and mechanical fatigue is also a long-standing problem in polymer adhesives. Regardless of the application, once cracks have formed within polymeric materials, the integrity of the structure is significantly compromised. Experiments exploring the concept of self-repair have been previously reported, but the only successful crack-healing methods that have been reported so far require some form of manual intervention. Here we report a structural polymeric material with the ability to autonomically heal cracks. The material incorporates a microencapsulated healing agent that is released upon crack intrusion. Polymerization of the healing agent is then triggered by contact with an embedded catalyst, bonding the crack faces. Our fracture experiments yield as much as 75% recovery in toughness, and we expect that our approach will be applicable to other brittle materials systems (including ceramics and glasses).
Journal Article↗
Surface-directed liquid flow inside microchannels.
Self-assembled monolayer chemistry was used in combination with either multistream laminar flow or photolithography to pattern surface free energies inside microchannel networks. Aqueous liquids introduced into these patterned channels are confined to the hydrophilic pathways, provided the pressure is maintained below a critical value. The maximum pressure is determined by the surface free energy of the liquid, the advancing contact angle of the liquid on the hydrophobic regions, and the channel depth. Surface-directed liquid flow was used to create pressure-sensitive switches inside channel networks. The ability to confine liquid flow inside microchannels with only two physical walls is expected to be useful in applications where a large gas-liquid interface is critical, as demonstrated here by a gas-liquid reaction.
Journal Article↗
A field guide to foldamers.
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Biopolymers↗
Dysregulation of lymphocyte interleukin-12 receptor expression in Sézary syndrome.
Initial phase I and II clinical trials with recombinant human interleukin-12 have demonstrated the therapeutic efficacy of this cytokine in early stage cutaneous T cell lymphoma as compared with more advanced stages such as the leukemic Sézary syndrome. In an effort to optimize the use of recombinant human interleukin-12, using flow cytometry we studied the regulation of the interleukin-12 receptor beta1 (high affinity chain) and beta2 (chain necessary for interleukin-12 signal transduction) on normal volunteer CD4+ and CD8+ T cells and CD4+ and CD8+ cells from eight patients with different degrees of leukemic involvement with Sézary syndrome. The beta1 chain was not readily detectable on resting normal and T cells from Sézary patients, but expression was induced following T cell activation with phytohemagglutinin. Similarly, the beta2 chain was not detectable on resting normal volunteer T cells, but could be induced following phytohemagglutinin stimulation. Moreover, the beta2 chain on normal volunteer T cells was markedly upregulated following short-term culture with interferon-gamma or recombinant human interleukin-12. CD8+ T cells routinely exhibited a greater expression of beta2 than did CD4+ T cells. In marked contrast, both CD4+ and CD8+ T cells from patients with Sézary syndrome and a high tumor cell burden (> 50% circulating atypical Sézary T cells) failed to express the beta2 chain under any culture conditions. Although, culture with anti-interleukin-10 also markedly increased beta2 expression on normal volunteer T cells, this failed to induce expression on either CD4+ or CD8+ T cells from Sézary patients and a high tumor burden. Investigation of patients with Sézary syndrome and a low tumor cell burden (< 15% circulating Sézary T cells) revealed a pattern of beta2 expression that was intermediate between advanced Sézary syndrome and normal volunteers. Both CD4+ and CD8+ peripheral blood T cells from these earlier stage patients were induced to express the beta2 chain, although at a lower frequency of positivity than T cells from normals, following culture with phytohemagglutinin, interferon-gamma, recombinant human interleukin-12, or anti-interleukin-10. These results indicate that short-term culture with interferon-gamma and recombinant human interleukin-12 potently upregulates beta2 chain expression on T cells from normal volunteers, whereas a similar, but less marked effect occurs on T cells from Sézary syndrome patients and a low circulating tumor cell burden. In contrast, the beta2 chain appears to be suppressed on both CD4+ and CD8+ T cells from Sézary patients with a heavy circulating tumor cell burden and it is not induced by interferon-gamma or recombinant human interleukin-12. Therefore, recombinant human interleukin-12 is likely to be most effective for early stage cutaneous T cell lymphoma due to a greater display of beta2 receptors on responding CD8+ anti-tumor cytotoxic T cells.
Antibodies↗
Predictive validity of the Strain Index in turkey processing.
The Strain Index is a job analysis method for determining if workers are exposed to increased risk of developing distal upper extremity disorders. Its predictive and external validity was initially demonstrated in a pork processing plant. The purpose of this study was to evaluate the predictive validity of the Strain Index in one turkey processing plant. While blinded to health outcomes, investigators analyzed the right and left sides of workers in 28 jobs using the Strain Index and classified them as "hazardous" or "safe" based on the Strain Index score. Subsequently, OSHA 200 logs were used to ascertain the occurrence of distal upper extremity disorders retrospectively. If at least one such disorder had occurred on the right or left side during the previous 3 years, that side was classified as "positive." If no such disorder was reported during the previous 3 years, that side was classified as "negative." When comparing sides, symmetry between morbidity and hazard classification was required. When comparing jobs, such symmetry was not required. Evidence of association between the hazard classifications and the morbidity classifications for the 56 sides and the 28 jobs was evaluated using 2 x 2 contingency tables. For the sides, the association between hazard classification and morbidity classification was statistically significant, with an odds ratio of 22.0. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.86, 0.79, 0.92, and 0.65, respectively. Similar results were noted for the jobs--the odds ratio was 50.0, and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.91, 0.83, 0.95, and 0.71. These results provide additional evidence of the external validity and predictive validity of the Strain Index.
Animals↗
Clinical cytokine network cytometry.
Cytokines play an important role in human health and disease. Monitoring their effects and detecting alterations in the complex balance of cytokines within a patient will undoubtedly become increasingly common in the clinical laboratory. Because of the complexity of the network interactions, multiple assays measuring soluble cytokines ("what"), cytokine-producing cells ("who"), surface receptors ("where"), and function (how) simultaneously are necessary to provide clinically useful information. The explosion of reagents and applications for use in the clinical flow cytometry laboratory makes this the perfect setting to perform the multidimensional studies required. Clinical cytokine network cytometry exemplifies the power of multiparameter, high throughput technologies that will change the face of clinical laboratories in the twenty-first century.
Cell Communication↗
Microfluidic tectonics: a comprehensive construction platform for microfluidic systems.
A microfluidic platform for the construction of microscale components and autonomous systems is presented. The platform combines liquid-phase photopolymerization, lithography, and laminar flow to allow the creation of complex and autonomous microfluidic systems. The fabrication of channels, actuators, valves, sensors, and systems is demonstrated. Construction times can be as short as 10 min, providing ultrarapid prototyping of microfluidic systems.
Journal Article↗
Immune monitoring in xenotransplantation: the multiparameter flow cytometric mixed lymphocyte culture assay.
Xenotransplantation requires monitoring of complex cellular interactions in vitro. A tool to monitor cell proliferation in detail would be instrumental in understanding these cellular interactions in heterogeneous xenogeneic lymphocyte cultures and in patients after xenotransplantation. To accomplish this, we used a fluorescent cell proliferation marker, 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), in combination with flow cytometry. CFSE, a green fluorescent molecule, binds covalently to intracellular macromolecules. Each cell division reduces the fluorescent intensity per cell by half and shows a characteristic multipeak pattern in flow cytometric analysis. For this study, human lymphocytes were labeled with CFSE and cultured in the presence of irradiated porcine lymphocytes. Cell proliferation was detected in CFSE-labeled lymphocytes in both a single and a multiparameter flow cytometry setting. Concurrently, tritiated ((3)H) thymidine incorporation, a common method to measure gross cell proliferation, was assessed. The kinetics of CFSE-labeled cell proliferation correlated with (3)H-thymidine incorporation in that both methods showed a lag phase for days 1-3 and a log phase for days 4-7. Multiparameter flow cytometric monitoring of mixed lymphocyte cultures allowed phenotyping and assessment of viability of proliferating populations in heterogeneous xenogeneic stimulated human lymphocyte cultures and complemented the classical (3)H-thymidine incorporation assay. The use of this technique will allow a wide array of immunologic parameters to be measured in a heterogeneous xenogeneic mixed lymphocyte culture. The information gained from these assays is essential to understanding the biological significance of xenogeneic cellular interaction and for monitoring the immune status of the xenotransplanted patient.
Cell Division↗
Novel polymers: molecular to nanoscale order in three dimensions.
The assembly of polymer chains in solution is a powerful method that is leading to the preparation of interesting and unique macromolecular-based synthetic nanostructures. Specific control over the intramolecular and intermolecular physical interactions dictates either the folding of single chains or the aggregation and ordering of multiple chains. This control is provided through the selective placement of functional groups along the polymer backbone and the relative strengths of their attractive and repulsive interactions.
Journal Article↗
Replacement of graft-resident donor-type antigen presenting cells alters the tempo and pathogenesis of murine cardiac allograft rejection.
BACKGROUND: Graft-resident antigen presenting cells (APCs) are potent stimulators of the alloresponse. To test whether replacement of graft-resident donor-type APCs with those of recipient-type alters allorecognition and the pathogenesis of both acute and chronic rejection, we created chimeric hearts for transplantation into naive recipients. METHODS: To replace donor-type APCs with those of recipient-type, chimeric animals were created by bone marrow transplantation (BMT) in fully allogeneic mouse and rat strain combinations. The degree of APC replacement in chimeric organs was assessed phenotypically and functionally. Chimeric hearts were transplanted heterotopically into untreated recipients. RESULTS: Flow cytometric and immunohistochemical analysis did not detect residual bone marrow recipient-type APCs in mouse BMT chimeras. Although semi-quantitative reverse transcription polymerase chain reaction detected 0.001-0.01% residual cells, APCs isolated from chimeric organs were functionally unable to stimulate donor-type cells. When transplanted into naive recipients, chimeric mouse hearts had significantly prolonged survival but were nevertheless rejected acutely. Similar results were obtained in the ACI --> LEW rat strain combination. However, in the PVG --> DA rat model, the majority of chimeric hearts survived >100 days and all long-surviving hearts developed cardiac allograft vasculopathy. CONCLUSIONS: BMT leads to near complete replacement of organ-resident APCs. The virtual absence of donor-type APCs in chimeric hearts delays or prevents acute rejection in a strain-dependent manner. In contrast, this type of graft modification does not prevent cardiac allograft vasculopathy. This suggests that, although the CD4+ direct pathway may play a role in acute rejection, it is not essential for the development of chronic rejection in rodent cardiac allografts.
Acute Disease↗
Classification criteria and severity assessment in work-associated upper extremity disorders: methods matter.
Work-associated musculoskeletal disorders of the upper extremity are common and disabling. Research on these disorders is needed and requires valid methods of classification of the disorders for epidemiologic studies and measurement of their impact on functional status. This commentary discusses the methodologic aspects of classification and functional status assessment in upper extremity musculoskeletal disorders.
Classification↗