Jeffrey Miller - Academia.edu (original) (raw)

Papers by Jeffrey Miller

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Jan 7, 2015

Natural killer (NK) cells are regulated killer immunoglobulin-like receptor (KIR) interactions wi... more Natural killer (NK) cells are regulated killer immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of NK reactivity have been associated with improved outcomes following myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n=612) lacking >1 KIR ligands experienced higher grade III-IV acute graft-vs.-host disease (GvHD) (HR 1.6, 95%CI 1.16-2.28, p=0.005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II-IV (HR 1.4, p=0.002) and III-IV acute GvHD (HR 1.5, p=0.01) compared to HLA-C2+patients. AML patients with KIR2DS1+, HLA-C2 homozygous donors had greater treatment-related mortality compared to others (HR 2.4, 95%CI 1.4-4.2, p=0.002), but did not experience lower ...

Nature Methods, 2015

Articles nAture methods | ADVANCE ONLINE PUBLICATION | transcription activator-like effector (tAl... more Articles nAture methods | ADVANCE ONLINE PUBLICATION | transcription activator-like effector (tAle) proteins have gained broad appeal as a platform for targeted dnA recognition, largely owing to their simple rules for design. these rules relate the base specified by a single tAle repeat to the identity of two key residues (the repeat variable diresidue, or rVd) and enable design for new sequence targets via modular shuffling of these units. A key limitation of these rules is that their simplicity precludes options for improving designs that are insufficiently active or specific. here we address this limitation by developing an expanded set of rVds and applying them to improve the performance of previously described tAles. As an extreme example, total conversion of a tAle nuclease to new rVds substantially reduced off-target cleavage in cellular studies. By providing new rVds and design strategies, these studies establish options for developing improved tAles for broader application across medicine and biotechnology.

Nucleic acids research, 2001

Adenine-DNA glycosylase MutY of Escherichia coli catalyzes the cleavage of adenine when mismatche... more Adenine-DNA glycosylase MutY of Escherichia coli catalyzes the cleavage of adenine when mismatched with 7,8-dihydro-8-oxoguanine (GO), an oxidatively damaged base. The biological outcome is the prevention of C/G-->A/T transversions. The molecular mechanism of base excision repair (BER) of A/GO in mammals is not well understood. In this study we report stimulation of mammalian adenine-DNA glycosylase activity by apurinic/apyrimidinic (AP) endonuclease using murine homolog of MutY (Myh) and human AP endonuclease (Ape1), which shares 94% amino acid identity with its murine homolog Apex. After removal of adenine by the Myh glycosylase activity, intact AP DNA remains due to lack of an efficient Myh AP lyase activity. The study of wild-type Ape1 and its catalytic mutant H309N demonstrates that Ape1 catalytic activity is required for formation of cleaved AP DNA. It also appears that Ape1 stimulates Myh glycosylase activity by increasing formation of the Myh-DNA complex. This stimulation...

The Thoracic and cardiovascular surgeon, 1996

An asymptomatic intrathoracic mass was demonstrated on imaging studies in an adult. Operative rem... more An asymptomatic intrathoracic mass was demonstrated on imaging studies in an adult. Operative removal was accomplished and it proved to be an extrapulmonary hamartoma arising from the soft tissue of the chest wall. This represents a rare location of this benign tumor in an adult.

Journal of applied physiology: respiratory, environmental and exercise physiology, 1982

This study was undertaken to determine if patients who lack muscle phosphorylase (i.e., McArdle&#... more This study was undertaken to determine if patients who lack muscle phosphorylase (i.e., McArdle's disease), and therefore the ability to produce lactic acid during exercise, demonstrate a normal hyperventilatory response during progressive incremental exercise. As expected these patients did not increase their blood lactate above resting levels, whereas the blood lactate levels of normal subjects increased 8- to 10-fold during maximal exercise. The venous pH of the normal subjects decreased markedly during exercise that resulted in hyperventilation. The patients demonstrated a distinct increase in ventilation with respect to O2 consumption similar to that seen in normal individuals during submaximal exercise. However their hyperventilation resulted in an increase in pH because there was no underlying metabolic acidosis. End-tidal partial pressures of O2 and CO2 also reflected a distinct hyperventilation in both groups at approximately 70-85% maximal O2 consumption. These data sh...

Canadian Journal of Zoology-revue Canadienne De Zoologie, 1991

... barbatus. Mary J. Packard, Karl F. Hirsch, Gary C. Packard, Jeffrey D. Miller, and Menna E. J... more ... barbatus. Mary J. Packard, Karl F. Hirsch, Gary C. Packard, Jeffrey D. Miller, and Menna E. Jones. Abstract: Eggshells of the Australian bearded dragon consist of a layer of calcite overlying a multilayered, fibrous shell membrane. ...

Acta Crystallographica Section C Crystal Structure Communications, 1992

ABSTRACT 5-(4-Methoxyphenyl)-4-phenyl-2-phenyl-amino-1,3,4-thiadiazolium chloride C21H18N3-OS+.Cl... more ABSTRACT 5-(4-Methoxyphenyl)-4-phenyl-2-phenyl-amino-1,3,4-thiadiazolium chloride C21H18N3-OS+.Cl-, M(r) = 395.91, orthorhombic, Pbca, a = 15.809 (4), b = 12.207 (2), c = 19.772 (5) angstrom, v = 3815.5 (1.4) angstrom3, Z = 8, D(x) = 1.378 g cm-3, lambda(Mo K-alpha) = 0.7107 angstrom, mu = 3.2 cm - 1, F(000) = 1648, T = 297 K, R = 0.041 for 1159 reflections with \F(O)\ > 2-sigma(\F(o)\). The pentatomic ring has two conjugated systems separated by S-C and N-N single bonds.

Acta Crystallographica Section C Crystal Structure Communications, 1993

C2oH~sN3S, Mr = 329.43, monoclinic, P2Jc, a = 11.745 (4), b = 7.600 (4), c = 21.929 (6) A, fi= 11... more C2oH~sN3S, Mr = 329.43, monoclinic, P2Jc, a = 11.745 (4), b = 7.600 (4), c = 21.929 (6) A, fi= 118.36(4) ° , V = 1722.4 (1.0) /~ 3, Z=4, Dx = 1.270 gcm -3, A(Mo Kte) ---0.7107/~, p, = 1.8 cm -1 F(000) = 688, T = 297 K, R = 0.038 for 1372 reflec-

Vaccine, Jan 21, 2005

A potential approach to activate tumor-specific T cells is to use live bacterial vectors to deliv... more A potential approach to activate tumor-specific T cells is to use live bacterial vectors to deliver appropriate antigens in a highly immunostimulatory context. We constructed a recombinant strain of Listeria monocytogenes (rLM) expressing murine tyrosinase-related protein-2 (TRP-2), a nonmutated melanocyte-derived differentiation antigen highly expressed in melanomas. Immunization of C57Bl/6 mice with this rLM strain efficiently primed CD8 T cells to recognize the MHC class I-restricted TRP-2180-188 epitope and express IFN-gamma upon in vitro peptide stimulation. Peptide-loaded target cells were lysed in vitro by TRP-2-specific T cells in cytotoxicity assays, and mice immunized and boosted with rLM expressing TRP-2 were functionally protected from subcutaneous challenge with B16 melanoma cells. These results identify and characterize the anti-"self" T-cell responses induced by recombinant L. monocytogenes expressing an endogenous, nonmutated tumor antigen.

Journal of Experimental Zoology, 1985

Embryos of the agamid lizard Amphibolurus barbatus are at developmental stage 29 of Dufaure and H... more Embryos of the agamid lizard Amphibolurus barbatus are at developmental stage 29 of Dufaure and Hubert at the time of oviposition. Mobilization of calcium and other nutrients from the yolk proceeds slowly for the first half of incubation, during which time embryonic growth also proceeds slowly. During the second half of incubation, however, embryos withdraw calcium and other nutrients from the yolk very rapidly, and growth rates are correspondingly high. Approximately 60% of the calcium used by developing embryos is obtained from the yolk, but fully 40% of their requirement is met by calcium mobilized from the eggshell. Very little calcium remains in residual yolk of hatchlings, so this yolk must be used in maintenance metabolism rather than in growth of neonates. No dichotomy exists among oviparous, amniotic vertebrates with respect to sources of calcium used by developing embryos, but one does exist with respect to patterns of mobilization of this element. Whereas calcium is extracted from yolk of embryonic reptiles throughout incubation, it actually is deposited in yolk of embryonic birds after the midpoint in development.

The Journal of biological chemistry, Jan 8, 2012

SV40 small t-antigen (ST) collaborates with SV40 large T-antigen (LT) and activated rasv12 to pro... more SV40 small t-antigen (ST) collaborates with SV40 large T-antigen (LT) and activated rasv12 to promote transformation in a variety of immortalized human cells. A number of oncogenes or the disruption of the general serine-threonine phosphatase protein phosphatase 2A (PP2A) can replace ST in this paradigm. However, the relationship between these oncogenes and PP2A activity is not clear. To address this, we queried the connectivity of these molecules in silico. We found that p27 was connected to each of those oncogenes that could substitute for ST. We further determined that p27 loss can substitute for the expression of ST during transformation of both rodent and human cells. Conversely, knock-in cells expressing the degradation-resistant S10A and T187A mutants of p27 were resistant to the transforming activities of ST. This suggests that p27 is an important target of the tumor-suppressive effects of PP2A and likely an important target of the multitude of cellular oncoproteins that emu...

Cell cycle (Georgetown, Tex.), 2007

A comprehensive understanding of the mechanisms coupling cell cycle exit and differentiation is i... more A comprehensive understanding of the mechanisms coupling cell cycle exit and differentiation is important for both cancer biology and tissue development. Cancer cells can arise from either stem/progenitor cells that fail to exit the cell cycle and differentiate, or from de-differentiated cells that have re-entered the cell cycle. Much of our current understanding of this coupling is based on observations made in transformed cell lines. These studies have shown that enforcing proliferation prevents differentiation and inducing growth arrest leads to differentiation; thus, one widely-held view is that changes in cell cycle regulators simply induces cell cycle exit, a pre-requisite for differentiation. However, recent evidence indicates that cell cycle regulators can affect differentiation in other ways as well. They can have a role establishing the new transcriptional program that accompanies differentiation--in its most radical form, the molecular mechanism of arrest might even be an...

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2014

Acute graft-versus-host disease (GVHD) occurs in 40% to 60% of recipients of partially matched um... more Acute graft-versus-host disease (GVHD) occurs in 40% to 60% of recipients of partially matched umbilical cord blood transplantation (UCBT). In a phase I study, adoptive transfer of expanded CD4(+)CD25(+)Foxp3(+) natural regulatory T cells (nTregs) resulted in a reduced incidence of grade II-IV acute GVHD. To investigate potential mechanisms responsible for the reduced GVHD risk, we analyzed peripheral blood mononuclear cell mRNA expression of a tolerance gene set previously identified in operation- tolerant kidney transplant recipients, comparing healthy controls and patients who received nTregs and those who did not receive nTregs with and without experiencing GVHD. Samples from patients receiving nTregs regardless of GVHD status showed increased expression of Foxp3 expression, as well as B cell-related tolerance marker. This was correlated with early B cell recovery, predominately of naïve B cells, and nearly normal T cell reconstitution. CD8(+) T cells showed reduced signs of act...

Journal of neurosurgery. Pediatrics, 2008

The spontaneous resolution of isolated tonsillar ectopia in Chiari malformation Type I (CM-I) is ... more The spontaneous resolution of isolated tonsillar ectopia in Chiari malformation Type I (CM-I) is a known and reported entity in 2 previous single study case reports. However, it has not been previously described in monozygotic twins. Two children, approximately 1 year of age with CM-I and presumed episodes of pallid syncope or breath-holding spells presented for neurosurgical evaluation. Although Chiari decompression was considered, the authors decided to proceed with conservative management with close follow-up due to the uncertain nature of these episodes. Approximately 4 years later, both children's symptoms had resolved. Repeated MR imaging examinations also showed spontaneous resolution of the malformation in both girls. These cases emphasize that when patients with CM-I present with atypical symptoms, spontaneous resolution or improvement is possible, which may influence the decision to pursue a trial of nonsurgical management. The possible pathophysiological mechanisms an...

Journal of the American Academy of Dermatology, 2014

AJR. American journal of roentgenology, 2003

... Pratik Mukherjee, Jeffrey H. Miller, Joshua S. Shimony, Thomas E. Conturo, Benjamin CP Lee, R... more ... Pratik Mukherjee, Jeffrey H. Miller, Joshua S. Shimony, Thomas E. Conturo, Benjamin CP Lee, Robert C. McKinstry Mallinckrodt Institute of ... 3). Materials and Methods: Retrospective analysis was performed on normal MR examinations in 153 subjects (ages 1 day to 11 years ...

American journal of respiratory cell and molecular biology, 2010

Mesenchymal stem cells (MSCs) reside within tissues such as bone marrow, cord blood, and dental p... more Mesenchymal stem cells (MSCs) reside within tissues such as bone marrow, cord blood, and dental pulp and can differentiate into other mesenchymal cell types. Differentiated MSCs, called circulating fibrocytes, have been demonstrated in human lungs and migrate to injured lung tissue in experimental models. It is likely that MSCs migrate from the bone marrow to sites of injury by following increasing chemokine concentrations. In the present study, we show that primary mouse bone marrow mesenchymal stem cells (BM-MSCs) exhibit directed chemotaxis through transwell inserts toward increasing concentrations of the chemokines complement component 5a, stromal cell-derived factor-1alpha, and monocyte chemotactic protein-1. Prior research has indicated that myristoylated alanine-rich C kinase substrate (MARCKS) protein is critically important for motility in macrophages, neutrophils, and fibroblasts, and here we investigated a possible role for MARCKS in BM-MSC directed chemotaxis. The presen...

AJNR. American journal of neuroradiology

Wallerian degeneration, the secondary degeneration of axons from cortical and subcortical injury,... more Wallerian degeneration, the secondary degeneration of axons from cortical and subcortical injury, is associated with poor neurologic outcome. Since diffusion-weighted (DW) imaging is sensitive to early changes of cytotoxic edema, DW imaging may depict the acute injury to descending white matter tracts that precedes Wallerian degeneration; this injury is not visible on conventional CT or MR images in the maturing human brain. Two neuroradiologists retrospectively analyzed clinical MR images in six children (aged 3 days to 5 months) with DW findings consistent with acute injury of the descending white matter tract due to territorial anterior or middle cerebral artery infarction. In five patients, images were obtained as a part of routine clinical evaluation. The remaining patient was a part of a prospective study of brain injury. Imaging findings were correlated with clinical outcomes. In all six patients, DW imaging performed 2-8 days after the onset of ischemia depicted injury to th...

Journal of the American Academy of Dermatology, 2015