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Biomedical subjects

J S Miller

Publications and source records attributed to J S Miller.

At least 37 records · Page 2Linked to original sources

Photolysis of polycyclic aromatic hydrocarbons in water.

The decomposition of benzo[a]pyrene (BAP), chrysene (CHR) and fluorene (FLU) in an aqueous solution by means of photolysis has been studied. The influence of initial polycyclic aromatic hydrocarbons' (PAHs) concentration, pH of the reaction mixture, temperature, presence of oxygen and tert-butyl alcohol (t-BuOH) on the degradation rate has been observed. BAP and CHR are decomposed by a mechanism different than FLU. Quantum yields of the photolytic decomposition of BAP, CHR and FLU were determined and equal 0.014, 0.0031 and 0.0038, respectively.

Benzo(a)pyrene↗

T-cell factor-1 expression during human natural killer cell development and in circulating CD56(+) bright natural killer cells.

Transcription factors are essential to govern differentiation along the lymphoid lineage from uncommitted hematopoietic stem cells. Although many of these transcription factors have putative roles based on murine knockout experiments, their function in human lymphoid development is less known and was studied further. Transcription factor expression in fresh and cultured adult human bone marrow and umbilical cord blood progenitors was evaluated. We found that fresh CD34(+)Lin(-) cells that are human leukocyte antigen (HLA)-DR(-) or CD38(-) constitutively express GATA-3 but not T-cell factor-1 (TCF-1) or Id-3. Culture with the murine fetal liver cell line AFT024 and defined cytokines was capable of inducing TCF-1 mRNA. However, no T-cell receptor gene rearrangement was identified in cultured progeny. Id-3, a basic helix loop helix factor with dominant negative function for T-cell differentiation transcription factors, also was upregulated and may explain unsuccessful T-cell maturation. To better understand the developmental link between natural killer (NK) cells derived from progenitors, we studied NK cell subsets circulating in blood. CD56(+bright), but not CD56(+dim), NK cells constitutively express TCF-1 by reverse transcriptase polymerase chain reaction and Western blot analysis. The TCF-1 isoform found in CD56(+bright) cells, which express lectin but not immunoglobulin class I recognizing inhibitory receptors, was identical to that induced in NK cell differentiation culture and was distinctly different from isoforms in T cells. These results suggest that TCF-1 does not target human killer immunoglobulin receptor genes, TCF-1 is uniquely expressed in circulating CD56(+bright) NK cells, and specific TCF-1 isoforms may play an important role in regulating NK differentiation from a common NK/T-cell progenitor.

ADP-ribosyl Cyclase↗

Novel therapies for chronic myelogenous leukemia.

The BCR-ABL oncogene is essential to the pathogenesis of chronic myelogenous leukemia, and immune mechanisms play an important role in control of this disease. Understanding of the molecular pathogenesis of chronic myelogenous leukemia has led to the development of several novel therapies, which can be broadly divided into therapies based on 1) inhibition of the BCR-ABL oncogene expression, 2) inhibition of other genes important to the pathogenesis of chronic myelogenous leukemia, 3) inhibition of BCR-ABL protein function, and 4) immunomodulation. We have systematically reviewed each of these novel therapeutic approaches in this article.

Alkyl and Aryl Transferases↗

The biology of natural killer cells in cancer, infection, and pregnancy.

OBJECTIVE: NK cells are important cells of the immune system. They are ultimately derived from pluripotent hematopoietic stem cells. NK cell cytotoxicity and other functions are tightly regulated by numerous activating and inhibitory receptors including newly discovered receptors that selectively recognize major histocompatibility complex class I alleles. Based on their defining function of spontaneous cytotoxicity without prior immunization, NK cells have been thought to play a critical role in immune surveillance and cancer therapy. However, new insights into NK cell biology have suggested major roles for NK cells in infection control and uterine function. The purpose of this review is to provide an update on NK cell function, ontogeny, and biology in order to better understand the role of NK cells in health and disease. DATA SOURCES: In the Medline database, the major subject heading "Natural Killer Cells" was introduced in 1983, identifying 16,848 citations as of December 31, 2000. Since 1986, there have been approximately 1000 citations per year under this subject heading. In this database, 68% of manuscripts are limited to human NK cells; 40% of citations cross with the major sub-heading of cytotoxicity, 40% with cytokines, 36% with neoplasm, 5% with antibody-dependent cellular cytotoxicity, 2.8% with pregnancy, and 1.3% with infection. Of references from the year 2000-2001, 46 were selected to combine with contributions from earlier literature. CONCLUSIONS: NK cells should no longer be thought of as direct cytotoxic killers alone as they clearly serve a critical role in cytokine production which may be important to control cancer, infection, and fetal implantation. Understanding mechanisms of NK cell functions may lead to novel therapeutic strategies for the treatment of human disease.

Female↗

Designer magnets containing cyanides and nitriles.

Magnets synthesized from molecules have contributed to the renaissance in the study of magnetic materials. Three-dimensional network solids exhibiting magnetic ordering have been made from several first-row metal ions and bridging unsaturated cyanide, tricyanomethanide, and/or dicyanamide ligands. These materials possess several different structural motifs, and the shorter the bridge, the stronger the interaction (i.e., -Ctriple bondN- > -Ntriple bondC-N- >> Ntriple bondC-N-Ctriple bondN- = Ntriple bondC-C-Ctriple bondN-). Cyanide additionally has the ability to discriminate between C- and N-bonding to form ordered heterobimetallic magnets, and the strong coupling can lead to ferro- or ferrimagnetic ordering substantially above room temperature. Tricoordination of tricyanomethanide results in spin-frustrated systems, which possess interpenetrating rutile-like networks. In contrast, single rutile-like frameworks are formed by mu(3)-bonded dicyanamide, which leads to ferromagnetics and weak ferromagnetics.

Journal Article↗

Isolation, synthesis, and structure-activity relationships of bioactive benzoquinones from Miconia lepidota from the Suriname rainforest.

Bioactivity-directed fractionation of an EtOAc extract from the leaves of Miconia lepidota afforded the two benzoquinones 2-methoxy-6-heptyl-1,4-benzoquinone (1) and 2-methoxy-6-pentyl-1,4-benzoquinone (primin) (2). This is the first reported isolation of 1. Both quinones 1 and 2 exhibited activity toward mutant yeast strains based on Saccharomyces cerevisiae, indicative of their cytotoxicity and potential anticancer activity. A number of previously synthesized and new analogues were prepared and tested in the same strains. Compounds 1, 2, 2-methoxy-6-butyl-1,4-benzoquinone (5), and 2-methoxy-6-decyl-1,4-benzoquinone (6) were tested in two cytotoxicity assays. In the M109 tumor cell lines, quinones 1, 2, and 6 had an IC(50) value of 10 microg/mL. In the A2780 cell line, compounds 1, 2 and 5 had IC(50) values of 7.9, 2.9, and 3.2 microg/mL, respectively.

Antineoplastic Agents, Phytogenic↗

Two bioactive saponins from Albizia subdimidiata from the Suriname rainforest.

Bioassay-guided fractionation of a methanol extract of Albizia subdimidiata using the engineered yeast strains 1138, 1140, 1353, and Sc7 of Saccharomyces cerevisiae as the bioassay tool resulted in the isolation of the two active saponins 1 and 2; one of these, albiziatrioside A (1), is described for the first time. The structures of 1 and 2 were established on the basis of HRMS, 1D and 2D NMR spectral data, and GC--MS analysis of the sugar units. Both isolated compounds showed significant cytotoxicity against the A2780 cell line.

Carbohydrate Conformation↗

Phage-displayed peptides that mimic aflatoxin B1 in serological reactivity.

AIMS: To test phage-displayed random peptide libraries as sources of peptides that mimic the binding of aflatoxin B1 to monoclonal antibodies raised against the toxin. METHODS AND RESULTS: For two of the three MAbs tested, clones were obtained by panning, producing phage that bound specifically to MAb 13D1-1D9 (MAb 24; specific for aflatoxins B1 and G1) and MAb 6E12-1E9 (MAb 13; specific for aflatoxins B1, G1 and B2) in ELISA. The amino acid sequences of the binding peptides varied. Those binding to MAb 24 contained the sequence of '...YMD...', and those that bound to MAb 13 contained the dipeptide 'PW'. Mimotope phage was used in a competition ELISA format for assaying aflatoxin concentrations. CONCLUSION: The results show that mimotope preparations are effective substitutes for pure toxin in these ELISA procedures. SIGNIFICANCE AND IMPACT OF THE STUDY: These results should contribute significantly to enhancing the safety and diminishing the costs of aflatoxin assays.

Aflatoxin B1↗

Abdominal compartment syndrome after mesenteric revascularization.

Abdominal compartment syndrome (ACS) results from increased pressure within the abdominal cavity leading to multisystem organ dysfunction. The most common cause of ACS is increased intraperitoneal volume from any source, but extrinsic compression can also cause increased intra-abdominal pressure. Although ACS has been well described in patients with trauma, little has been reported on ACS in postoperative patients without traumatic injuries. We report on a patient who had acute ACS 2 days after surgical revascularization for chronic mesenteric ischemia. With appropriate treatment, the patient made a rapid and complete recovery. We present this case of acute ACS in the postoperative patient without trauma to increase awareness and help minimize death caused by this devastating syndrome.

Abdomen↗

A comparison of suicidal thinking and reasons for living among younger and older adults.

A cross-sectional design was used to examine age-related differences in suicidal thinking and reasons for living among younger (n = 82; M age = 21) and older (n = 82; M age = 68) adults. Volunteers anonymously completed the Beck Scale for Suicide Ideation and the Reasons for Living Inventory. Findings indicated that older adults do not manifest suicidal ideation differently than younger adults. However, there does appear to be some age-related differences in reasons for not committing suicide. Compared to the younger group, the older group reported moral objections and child-related concerns as stronger reasons for not committing suicide. An implication is that the identification of specific reasons that deter individuals from committing suicide may be clinically useful and provide some assistance in suicide prevention efforts.

Adaptation, Psychological↗

The biology of natural killer cells and implications for therapy of human disease.

Natural killer (NK) cells are unique lymphocytes capable of lysing target cells without prior immunization. NK cells activated with cytokines, like interleukin-2 (IL-2), have been used since the 1980s as adoptive immunotherapy against metastatic solid tumors, but their effectiveness has been limited. The mechanisms by which NK cells recognize their targets are complex, including newly identified receptors that recognize class I MHC molecules. Understanding these mechanisms may support the use of NK cells as clinical therapy against infectious diseases and cancer. We have been interested in the use of NK cells clinically for their potential to eradicate minimal residual disease and prevent relapses after autologous stem cell transplantation. Several strategies are discussed to increase the specificity and efficacy of NK cell therapy. One method is to increase the targeting of NK cells by the use of monoclonal antibodies. Another approach uses allogeneic NK cells to overcome the inhibitory receptor mechanisms that may block target cell lysis by recognition of class I molecules. These and other novel strategies may prove to be attractive and effective immunotherapeutic tools to manipulate NK cells to fight human disease.

Communicable Diseases↗

Private LTC insurance. The home care claimant experience.

An understanding of claimants and their behavior should help consumers make more informed choices about financing their potential LTC needs, help the private insurance industry better meet those needs, and inform public policies designed to support and regulate the market. To this end, LifePlans, Inc. and the Center for Health and Long-Term Care Research conducted in-person interviews with more than 1,000 private long-term care insurance claimants residing both in the community and in institutions.

Aged↗

Copper(II) benzoate nitroxide dimers and chains: structure and magnetic studies.

Copper(II) benzoate dimers and linear chains have been synthesized and exhibit very different magnetic behaviors. The benzoate dimers, 1a, show typical dimeric singlet-triplet transitions and strong antiferromagnetic coupling (JST = -206 K (-143 cm-1); H = -2JSTSa.Sb). The bromobenzoate dimer can be converted into linear chains of hydrogen-bonded monomers, showing 1-D ferromagnetic coupling (6a, theta = +9 K). Copper(II) sites can also be bridged by nitroxide-substituted benzoates, 1b and 1c, that is, 2-(4'-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (NNBA, 3a), with JST = -216 K (-150 cm-1), with comparable interactions between the nitroxide and triplet Cu(II) spins, theta T = -157 K. A 1-D chain similar to the bromobenzoate monomers can also be produced with NNBA, also exhibiting ferromagnetic coupling (6b, theta = +0.67 K), albeit much weaker. Other nitroxides have been introduced into the Cu(II) dimer system by capping copper(II) acetate with the polydentate 2-(4'-pyridyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PYNN, 3b), which exhibits almost no coupling to the copper centers when both ends of the dimer are capped (1d, theta = -5.8 K). In contrast, strong coupling is observed when only one PYNN is used (2, theta = -300 K), which is the result of direct coordination of the nitroxide to the copper centers, producing a chain of the dimer units.

Journal Article↗

Polyploidy and the evolution of gender dimorphism in plants.

Gender dimorphism and polyploidy are important evolutionary transitions that have evolved repeatedly in many plant families. We show that gender dimorphism in North American Lycium (Solanaceae) has evolved in polyploid, self-compatible taxa whose closest relatives are cosexual, self-incompatible diploids. This has occurred independently in South African Lycium. We present additional evidence for this pathway to gender dimorphism from 12 genera involving at least 20 independent evolutionary events. We propose that polyploidy is a trigger of unrecognized importance for the evolution of gender dimorphism, which operates by disrupting self-incompatibility and leading to inbreeding depression. Subsequently, male sterile mutants invade and increase because they are unable to inbreed.

Alleles↗

Magnetic ordering and spin-glass behavior in first-row transition metal hexacyanomanganate(IV) Prussian blue analogues.

Magnetically ordered Prussian blue analogues with the general formulation of M[Mn(CN)6] (M = V, Cr, Mn, Co, Ni) were made in aprotic media utilizing [MnIV(CN)6]2-. These analogs are valence-ambiguous, as they can be formulated as MII[MnIV(CN)6] or MIII[MnIII(CN)6]. The X-ray powder diffraction of each member of this family can be indexed to the face-centered cubic (fcc) Prussian blue structure type, with atypically reduced unit cell parameters (a approximately 9.25 +/- 0.25 A) with respect to hydrated Prussian blue structured materials (a > or = 10.1 A). The reduced a-values are attributed to a contraction of the lattice in the absence of water or coordinating solvent molecule (i.e., MeCN) that is necessary to help stabilize the structure during lattice formation. Based on vCN IR absorptions, X-ray photoelectron spectra, and magnetic data, the following oxidation state assignments are made: MII[MnIV(CN)6] (M = Co, Ni) and MIII[MnIII(CN)6] (M = V, Cr, Mn). Formation of MnIII[MnIII(CN)6] is in contrast to MnII[MnIV(CN)6] prepared from aqueous media. Above 250 K, the magnetic susceptibilities of M[Mn(CN)6] (M = V, Cr, Mn, Co, Ni) can be fit to the Curie-Weiss equation with theta = -370, -140, -105, -55, and -120 K, respectively, suggesting strong antiferromagnetic coupling. The room temperature effective moments, respectively, are 3.71, 4.62, 5.66, 4.54, and 4.91 microB, consistent with the above oxidation state assignments. All compounds do not exhibit magnetic saturation at 50 kOe, and exhibit frequency-dependent chi'(T) and chi"(T) responses characteristic of spin-glass-like behavior. M[Mn(CN)6] order as ferrimagnets, with Tc's taken from the peak in the 10 Hz chi'(T) data, of 19, 16, 27.1, < 1.75, and 4.8 K for M = V, Cr, Mn, Co, and Ni, respectively. The structural and magnetic disorder prevents NiII[MnIV(CN)6] from ordering as a ferromagnet as anticipated, and structural inhomogeneities allow CoII[MnIV(CN)6] and VIII[MnIII(CN)6] to unexpectedly order as ferrimagnets. Also, MnIII[MnIII(CN)6] behaves as a reentrant spin glass showing two transitions at 20 and 27.1 K, and similar behavior is evident for CrIII[MnIII(CN)6]. Hysteresis with coercive fields of 340, 130, 8, 9, and 220 Oe and remanent magnetizations of 40, 80, 1500, 4, and 250 emuOe/mol are observed for M = V, Cr, Mn, Co, and Ni, respectively.

Journal Article↗