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Joseph Rogers

Publications and source records attributed to Joseph Rogers.

17 recordsLinked to original sources
PubMed2006

Gene expression profiles in anatomically and functionally distinct regions of the normal aged human brain.

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer's disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders.

Aged↗
PubMed2006

Low-dose dobutamine tissue-tagged magnetic resonance imaging with 3-dimensional strain analysis allows assessment of myocardial viability in patients with ischemic cardiomyopathy.

BACKGROUND: Tissue-tagged magnetic resonance imaging (MRI) with 3-dimensional (3D) myocardial strain analysis allows quantitative assessment of myocardial contractility. We assessed the hypothesis that 3D strain determination at rest and with low-dose dobutamine would discriminate between viable and nonviable myocardium in patients with ischemic cardiomyopathy (ICM). METHODS AND RESULTS: MRI with radiofrequency tissue-tagging at rest and with low-dose dobutamine was performed in 16 normal volunteers and 14 patients with ICM. Three-dimensional global and regional circumferential strains (Ecc) were computed for all subjects at rest and with dobutamine. Results were compared with clinically indicated conventional viability studies. Compared with normal volunteers, global left ventricular Ecc was significantly decreased in patients with ICM at rest (-0.15+/-0.06 versus -0.27+/-0.03; P<0.001) and with dobutamine (-0.17+/-0.08 versus -0.37+/-0.10; P<0.001). Ecc was significantly decreased in nonviable regions compared with viable segments at rest (-0.08+/-0.06 versus -0.17+/-0.10; P<0.001) and with dobutamine (-0.07+/-0.06 versus -0.21+/-0.11; P<0.001). Ecc in viable segments increased significantly in response to dobutamine (P=0.04), whereas Ecc did not change in nonviable segments (P=0.50). Normal controls (96 segments) had increased Ecc at rest (-0.27+/-0.07) and with dobutamine (-0.37+/-0.15) compared with both viable and nonviable regions in ICM patients (P<0.001). CONCLUSIONS: Noninvasive dobutamine tissue-tagged MRI with calculation of 3D strain allows the identification, quantification and display of regionally varying ventricular function. The response of systolic strain to low-dose dobutamine has significant promise in discriminating between viable and nonviable myocardium.

Aged↗
PubMed2006

Inflammation, anti-inflammatory agents and Alzheimer disease: the last 12 years.

Two basic discoveries have spurred research into inflammation as a driving force in the pathology of Alzheimer disease (AD). The first was the identification of activated microglia in association with the lesions. The second was the finding that rheumatoid arthritics were relatively spared from the disease. These findings spurred the first pilot trial of a classical NSAID in the treatment of AD. This trial showed promise for indomethacin as a useful therapeutic agent but appropriate follow up trials have not been done. However, more than 20 epidemiological studies have since been conducted showing a sparing effect for antiinflammatories in AD, including four which specifically addressed the use of classical NSAIDs. Other key findings linking inflammation to AD pathology are the identification of activated complement fragments, including the membrane attack complex, as well as inflammatory cytokines in association with the lesions. In vitro, activated microglia release factors which are toxic to neurons, and these can be partially blocked by NSAIDs. Future directions should include a search for other inflammatory mediators in AD and exploitation of current knowledge to improve available treatments.

Alzheimer Disease↗
PubMed2005

Peripheral clearance of amyloid beta peptide by complement C3-dependent adherence to erythrocytes.

Brain deposits of amyloid beta peptide (Abeta) have been a diagnostic hallmark of Alzheimer's disease (AD) for nearly a century. Recent studies have demonstrated that Abeta is also present in peripheral blood. Here, we present evidence that circulating Abeta42 is subject to complement C3b-dependent adherence to complement receptor 1 (CR1) on erythrocytes, a classical set of mechanisms by which pathogens and proteins recognized as foreign are cleared from the bloodstream. Levels of Abeta42 targeted by this pathway differ significantly in AD compared to mild cognitive impairment and nondemented elderly controls.

Alzheimer Disease↗
PubMed2005

Quantification of cytokines involved in wound healing using surface plasmon resonance.

Sensing of three cytokines related to chronic wound healing, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha), with detection limits at or below 1 ng/mL in buffered saline solution and spiked cell culture medium (CCM) has been achieved. Fiber-optic surface plasmon resonance (SPR) sensors are coated with an antibody binding layer and antibodies specific to the cytokine of interest are covalently attached to this layer. To achieve such detection limits in a complex medium such as CCM, total protein content of 4 mg/mL, the use of a novel N-hydroxysuccinimide ester of 16-mercaptohexadecanoic acid (NHS-MHA) is necessary. A comparison of the detection limits for IL-6 using currently widely used CM-dextran and NHS-MHA shows an improvement by a factor of 3 using NHS-MHA. The detection limits for the monitoring of cytokines in spiked saline solutions and CCM were similar for TNF-alpha and slightly higher for IL-1 and IL-6. The detection of each cytokine in the presence of interfering agents resulted in concentration prediction well within the error of calibration. The SPR sensors are stable in CCM after 20 min of pretreatment in CCM, minimizing the reliance on a reference sensor to quantify the cytokines in complex media. This technique enables a major advancement in the field of real-time monitoring of biologically relevant molecules in complex biological fluids.

Biomarkers↗
PubMed2005

Gene expression correlates of neurofibrillary tangles in Alzheimer's disease.

Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer's disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD.

Aged, 80 and over↗
PubMed2005

Microglial responses to amyloid beta peptide opsonization and indomethacin treatment.

BACKGROUND: Recent studies have suggested that passive or active immunization with anti-amyloid beta peptide (Abeta) antibodies may enhance microglial clearance of Abeta deposits from the brain. However, in a human clinical trial, several patients developed secondary inflammatory responses in brain that were sufficient to halt the study. METHODS: We have used an in vitro culture system to model the responses of microglia, derived from rapid autopsies of Alzheimer's disease patients, to Abeta deposits. RESULTS: Opsonization of the deposits with anti-Abeta IgG 6E10 enhanced microglial chemotaxis to and phagocytosis of Abeta, as well as exacerbated microglial secretion of the pro-inflammatory cytokines TNF-alpha and IL-6. Indomethacin, a common nonsteroidal anti-inflammatory drug (NSAID), had no effect on microglial chemotaxis or phagocytosis, but did significantly inhibit the enhanced production of IL-6 after Abeta opsonization. CONCLUSION: These results are consistent with well known, differential NSAID actions on immune cell functions, and suggest that concurrent NSAID administration might serve as a useful adjunct to Abeta immunization, permitting unfettered clearance of Abeta while dampening secondary, inflammation-related adverse events.

Journal Article↗
PubMed2005

Principal strain orientation in the normal human left ventricle.

BACKGROUND: Methods that can improve the accuracy of application of directed intervention in the treatment of coronary artery disease deserve investigation. Magnetic resonance imaging with tissue tagging allows for noninvasive, quantitative determination of regionally varying minimum principal strain. Because the directional vector of minimum principal strain has been shown to be sensitive to ischemic involvement, my colleagues and I sought to fully characterize the normal range of vector direction in the in vivo human left ventricle at rest and during inotropic stimulation. METHODS: Tagged magnetic resonance imaging image sets were acquired in 20 healthy volunteers at rest and during dobutamine infusion. Strain was computed from the measured displacement data by using finite element software. Orientation of minimum principal strain was characterized by measuring the angle (principal strain angle) between the minimum principal strain vector and the local circumferential-longitudinal plane. Values of this angle were computed in 6 ventricular regions and globally. RESULTS: Resting values of the principal strain angle were small in every region, confirming that maximal normal myocardial contraction occurs primarily in the circumferential-longitudinal plane. Angles were similar during dobutamine infusion. Comparisons between ventricular walls, both at rest and with dobutamine, revealed no marked regional differences in the principal strain angle. CONCLUSIONS: The direction of maximal myocardial contraction is known to change with ischemic injury to the myocardium and can be a sensitive, regionally varying index of myocardial ischemia. The critical first step in the clinical application of this technology is to accurately characterize normal ranges of principal strain angles.

Adult↗
PubMed2005

Blood transfusions decrease the incidence of acute rejection in cardiac allograft recipients.

BACKGROUND: Cardiac transplant recipients frequently receive a large number of transfusions. The objective of this study was to determine whether there is an association between total number of blood transfusions and cardiac allograft rejection. METHODS: A retrospective analysis of all cardiac transplants between October 1, 1997, and December 31, 2001, was performed. Total number of transfusions, total number of rejection episodes Grade 3A or more, rejection-free survival, and overall survival were analyzed. Comparisons between patients bridged to transplantation with a Novacor left ventricular assist device (LVAD) and the primary transplant group were also made. RESULTS: Eighty-two patients were transplanted. Fifteen were bridged to transplantation, and 67 underwent primary heart transplantation. Age and sex were similar for the LVAD group and the primary transplant group (45 +/- 11 vs 47 +/- 15 years and 67% vs 58% male sex, respectively). Mean follow-up was 658 +/- 486 days for the LVAD group and 708 +/- 548 days for the primary transplant group. Transfusions received were 50 +/- 34 U of packed red blood cells for the LVAD group and 7 +/- 12 for the primary transplant group (p < 0.001). There were no differences in donor characteristics between the 2 groups. The incidence of acute rejection within 1 year was 27% for the LVAD group and 39% for the primary transplant group (p = .28). Freedom from rejection was 71% at 1 year in the LVAD group compared with 59% for the primary transplant group (p = 0.39). In all 82 patients, the total number of transfusions was inversely correlated with the development of acute rejection (p = 0.011). Survival was 80% and 62% for the LVAD group at 1 and 3 years after transplantation and 88% and 85%, respectively, for the primary transplant group (p = 0.045). CONCLUSIONS: The number of blood transfusions received by heart transplant recipients is inversely related with the number of acute rejection episodes.

Adult↗
PubMed2004

CCAAT/enhancer binding protein delta (C/EBPdelta) expression and elevation in Alzheimer's disease.

The CCAAT-enhancer binding protein (C/EBP) family of transcription factors, particularly C/EBPdelta, is well known to regulate or co-regulate a wide range of inflammatory mediators and mechanisms in the periphery, including interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). These cytokines, in turn, can induce C/EBPdelta expression and translocation to the nucleus as an active transcription factor. Because IL-1, IL-6, and TNF-alpha are increased in pathologically vulnerable regions of the Alzheimer's disease (AD) brain, we sought to determine if C/EBPdelta might be expressed in AD cortex. Immunohistochemistry of AD tissue sections revealed profuse C/EBPdelta staining of astrocytes, particularly reactive astrocytes surrounding amyloid beta peptide deposits. Substantially less immunoreactivity was observed in comparable sections from nondemented elderly control (ND) patients. These qualitative findings were consistent with quantitative Western blot densitometry results showing significant increases in C/EBPdelta in AD compared to ND cortex samples. Additional in vitro studies were pursued in order to characterize functional activity of C/EBPdelta in human elderly astrocytes. Consistent with a functionally active transcription factor, C/EBPdelta immunoreactivity predominated in the nucleus of cultured AD and ND astrocytes, and exhibited increases and nuclear localization, as determined by Western blots and electrophoretic mobility shifts after exposure to C/EBPdelta-inducing cytokines.

Active Transport, Cell Nucleus↗
PubMed2002

Microglia and inflammatory mechanisms in the clearance of amyloid beta peptide.

There is now abundant evidence that brain microglia, when activated, have the lineage, receptors, and synthetic capacity to participate in both potentially neurotoxic inflammatory responses and potentially beneficial phagocytic responses. Amyloid beta peptide (Abeta) forms highly insoluble, beta-pleated aggregates that are widely deposited in the Alzheimer's disease (AD) cortex and limbic system. Aggregated Abeta also activates the classical and alternative complement cascades. These properties make Abeta an excellent target for microglial phagocytosis, a view supported by multiple reports, through well established mechanisms of phagocyte clearance.

Alzheimer Disease↗
PubMed2002

Association of factor H of the alternative pathway of complement with agrin and complement receptor 3 in the Alzheimer's disease brain.

Factor H, a regulatory protein of the alternative pathway of complement (APC), is present in amyloid-beta (Abeta) plaques in Alzheimer's disease (AD). Abeta plaques also contain significant amounts of heparan sulfate proteoglycans (HSPGs), such as agrin, as well as numerous activated microglia expressing increased levels complement receptor 3 (CR3). Here, we show the colocalization of each of these molecules in the AD brain and the functional capacity for these molecules to bind to one another in vitro. We propose that CR3 receptors expressed by microglia are used for ligand binding to factor H bound to HSPGs and Abeta in plaques in the AD brain.

Aged↗
PubMed2002

Effects of estrogen treatment on glutamate uptake in cultured human astrocytes derived from cortex of Alzheimer's disease patients.

Estrogen is thought to play a protective role against neurodegeneration through a variety of mechanisms including the activation of growth factors, the control of synaptic plasticity, and the reduction of response to various insults, such as iron and glutamate. Increasing evidence indicates an increased level of extracellular glutamate and a down-regulation of glutamate transporters in Alzheimer's disease (AD). In this study, we show that glutamate uptake in astrocytes derived from Alzheimer's patients is significantly lower than that from non-demented controls. Estrogen treatment increases glutamate uptake in a dose-dependent pattern. Two glutamate transporters, GLT-1 and GLAST, are expressed in the astrocytes. Up-regulation of the glutamate transporters is induced by estrogen treatment in AD astrocytes only. Our data suggest that the action of estrogen on glutamate uptake by astrocytes might contribute to its potential neuroprotective role in AD.

Alzheimer Disease↗
PubMedDate not supplied

Long-term destination therapy with the HeartMate XVE left ventricular assist device: improved outcomes since the REMATCH study.

The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial demonstrated increased 1- and 2-year survival and improved quality of life for end-stage heart failure patients implanted with the HeartMate VE Left Ventricular Assist Device (LVAD) (Thoratec Corporation, Pleasanton, CA) compared with optimal medical management. This is the first report of Destination Therapy (DT) experience since REMATCH and incorporates improvements with the HeartMate XVE LVAD and patient management. Forty-two patients with end-stage heart failure at higher volume institutions were supported with the LVAD over a duration of 26.7 patient years (mean 232 days). Compared with REMATCH, DT patients had a 40% lower rate of death (0.49 vs. 0.84 deaths per patient year). Kaplan-Meier estimates of survival in the DT and REMATCH LVAD groups at 30 days were 90% and 81%, and at 1 year were 61% and 52%. The death rate due to sepsis was 8.3 times lower in DT patients (risk ratio, 0.12; 95% confidence interval, 0.02-0.90). DT patients were 2.1 times less likely to experience an adverse event (risk ratio, 0.47; 95% confidence interval, 0.35-0.63). These results demonstrate continued improvement with outcomes in long-term DT with LVADs. Given that these DT patients were similar to those in the REMATCH trial, the improved outcomes likely reflect improvements in the HeartMate XVE LVAD and experience with patient management.

Adult↗