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J L Anderson

Publications and source records attributed to J L Anderson.

At least 19 recordsLinked to original sources
PubMed2007

Gene mutations, atrial fibrillation, and the elusive cigar.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The term lone AF describes nonsyndromic atrial fibrillation that occurs in the absence of underlying structural heart disease or predisposing clinical conditions. A hereditable component leading to conduction abnormalities in AF has long been suspected, and epidemiological evidence of elevated risk for AF among first-degree relatives of probands was recently documented. The first AF-associated molecular defect was found in an affected Chinese family; initial studies narrowed the chromosomal location by linkage analysis, and Yihan Chen et al. found a specific gain-of-function mutation in KCNQ1, the gene for the alpha subunit of potassium channels.

Atrial Fibrillation↗
PubMed2006

Evaluation of dried and wet distillers grains included at two concentrations in the diets of lactating dairy cows.

The purpose of this study was to determine the lactation performance of dairy cows fed dried or wet distillers grains (DG) with solubles (DDGS or WDGS) at 2 dietary concentrations. A trial using 15 cows was designed as a replicated 5 x 5 Latin square with periods of 4 wk each and data collected during wk 3 and 4 of each period. Diets, on a dry matter basis, were: control, 10% DDGS, 20% DDGS, 10% WDGS, and 20% WDGS. All diets contained 25% corn silage, 25% alfalfa hay, and 50% of the respective concentrate mixes. Dry matter intake (DMI) tended to be greater for cows fed control than DG (23.4, 22.8, 22.5, 23.0, and 21.9 kg/d for control, 10% DDGS, 20% DDGS, 10% WDGS, and 20% WDGS). Milk yield (39.8, 40.9, 42.5, 42.5, and 43.5 kg/d) was greater for cows fed DG than control. Milk fat percentage (3.23, 3.16, 3.28, 3.55, and 3.40%) was similar for cows fed control and DG, but greater for cows fed WDGS than DDGS. Milk fat yield was greater for cows fed DG than control and tended to be greater for cows fed WDGS than DDGS. Milk fat from cows fed DG, especially 20% DG, was more unsaturated and contained more cis-9, trans-11 conjugated linoleic acid than when fed the control diet. Milk protein percentage (3.05, 3.01, 3.02, 3.11, and 3.06%) was similar for cows fed control and DG but greater for cows fed WDGS than DDGS. Milk protein yield was greater for cows fed DG than control, tended to be greater for cows fed WDGS than DDGS, and tended to be greater for cows fed 20% DG than 10% DG. Milk urea nitrogen was similar for cows fed control and DG but greater for cows fed WDGS than DDGS and tended to be higher for cows fed 20% DG than 10% DG. Ruminal ammonia concentrations were greater for cows fed WDGS than DDGS. Overall, feeding DG improved feed efficiency (1.70, 1.79, 1.87, 1.84, and 1.92 kg of energy-corrected milk/kg of DMI) by increasing yields of milk, protein, and fat while tending to decrease DMI.

Ammonia↗
PubMed2005

Synaptic plasticity in the dy2J mouse model of laminin alpha2-deficient congenital muscular dystrophy.

Laminin alpha2-deficient congenital muscular dystrophy is a debilitating disease affecting both muscle and neural tissue as a result of mutations in the LAMA2 gene. It presents at or soon after birth with muscle weakness and is further characterised by clinical central nervous system involvement. Laminin alpha2 is part of the extracellular matrix, linked to the cellular cystoskeleton via dystroglycan which is an integral part of the dystrophin-glycoprotein complex (DGC). We examined both short- and long-term synaptic plasticity in the C57BL6J/dy(2J) mouse, an animal model of laminin alpha2 deficient congenital muscular dystrophy. Using a cerebellar slice preparation, we show that the pre-synaptically mediated paired-pulse facilitation (PPF) was no different between dy(2J) and littermate controls. Approximately half (7/12) the dy(2J) Purkinje cells displayed a blunted LTD compared to littermate controls, and one third (4/12) of dy(2J) Purkinje cells displayed LTP. This study demonstrates that a defective laminin alpha2 causes a disruption in long-term synaptic plasticity at the Purkinje cell-parallel fibre synapse.

Animals↗
PubMed2005

Intracellular trafficking of retroviral vectors: obstacles and advances.

Retroviruses are efficient vehicles for delivering transgenes in vivo. Their ability to integrate into the host genome, providing a permanent imprint of their genes in the host, is a key asset for gene therapy. Furthermore, the lentivirus subset of retroviruses can infect nondividing as well as dividing cells. This expands the cell types capable of gene therapy, driving the development of lentiviral vectors. However, the precise mechanisms used by different retroviruses to efficiently deliver their genes into cell nuclei remains largely unclear. Understanding these molecular mechanisms may reveal features to improve the efficacy of current retroviral vectors. Moreover, this knowledge may expose elements pliable to other gene therapy vehicles to improve their in vivo performance and circumvent the biosafety concerns of using retroviral vectors. Therefore, the mechanisms underlying the early trafficking of retroviral vectors in host cells are reviewed here, as understood from studying the native retroviruses. Events after virus entry up to nuclear delivery of the viral cDNA are discussed. Cellular obstacles faced by these retroviral vectors and how they advance beyond these barriers is emphasized.

Animals↗
PubMed2005

Generating genetic risk scores from intermediate phenotypes for use in association studies of clinically significant endpoints.

While previous results of genetic association studies for common, complex diseases (eg., coronary artery disease, CAD) have been disappointing, examination of multiple related genes within a physiologic pathway may provide improved resolution. This paper describes a method of calculating a genetic risk score (GRS) for a clinical endpoint by integrating data from many candidate genes and multiple intermediate phenotypes (IPs). First, the association of all single nucleotide polymorphisms (SNPs) to an IP is determined and regression beta-coefficients are used to calculate an IP-specific GRS for each individual, repeating this analysis for every IP. Next, the IPs are assessed by a second regression as predictors of the clinical endpoint. Each IP's individual GRS is then weighted by the regression beta-coefficients from the second step, creating a single, composite GRS. As an example, 3,172 patients undergoing coronary angiography were evaluated for 3 SNPs from the cholesterol metabolism pathway. Although these data provide only a preliminary example, the GRS method detected significant differences in CAD by GRS group, whereas separate genotypes did not. These results illustrate the potential of the GRS methodology for multigenic risk evaluation and suggest that such approaches deserve further examination in common, complex diseases such as CAD.

Coronary Disease↗
PubMed2005

Evaluation of recirculating sand filter in a cold climate.

Approximately 30% of Minnesota's residents rely on onsite technologies for their wastewater treatment. There is a growing need for 'alternative' technologies to aid in treatment for difficult sites and sensitive environmental areas. Recirculating sand filters (RSFs) have been used since the 1970s for small communities with flows > 20,000 L per day, but use for small flow application (< 5,000 L/d) has been growing due to its small land use requirement. A research site was developed in southern Minnesota in 1995 to test alternative technologies, including two RSFs. In addition, in 1998, two RSFs were added to existing residential soil treatment systems that were having problems because of inadequate separation and fill soil conditions. All RSFs in this study used 0.6 metres of coarse sand for treatment, were loaded at approximately 204 L per day per square metre (5 gallons per square foot per day) and a recirculation rate of 5:1. All RSFs have effectively reduced Biochemical Oxygen Demand (BOD5), Total Suspended Solids (TSS), Fecal Coliform (FC) and Nutrients (nitrogen and phosphorus). These systems are able to achieve secondary effluent treatment levels for BOD5 and TSS. The median FC reduction was 90% with a value of 5.7 E4 cfu/100 mL, indicating additional treatment is necessary to protect health and the environment. The RSFs consistently removed 25% or more total phosphorus (TP) and 40% or more total nitrogen (TN). The RSFs did not show significantly decreased performance during the winter months. Two of the RSFs receiving rather high strength domestic waste were able to reduce a greater percentage of total nitrogen, indicated that the addition of carbon from the high strength waste is a benefit resulting in greater TN removal.

Cold Temperature↗
PubMed2002

Assessing the water resources of Scotland--perspectives, progress and problems.

This paper reviews historical progress in the assessment of rainfall, evaporation, runoff and groundwater resources in Scotland and, within the same water-balance framework, considers recent advances in quantifying the major hydrological fluxes, with particular reference to river flows. The contributions of hydrological models and digital cartography are considered against a background of changing information needs and the likelihood that the long term stability which has characterised water resource variability in the past may not, continue in the future. The complementary roles of modelling and hydrometric monitoring networks are considered and the need for greater integration, and an increased strategic dimension to network design and evolution is discussed.

Conservation of Natural Resources↗
PubMed2002

Brain function in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the second most commonly occurring genetically inherited disease in humans. It is an X-linked condition that affects approximately one in 3300 live male births. It is caused by the absence or disruption of the protein dystrophin, which is found in a variety of tissues, most notably skeletal muscle and neurones in particular regions of the CNS. Clinically DMD is characterized by a severe pathology of the skeletal musculature that results in the premature death of the individual. An important aspect of DMD that has received less attention is the role played by the absence or disruption of dystrophin on CNS function. In this review we concentrate on insights into this role gained from investigation of boys with DMD and the genetically most relevant animal model of DMD, the dystrophin-deficient mdx mouse. Behavioural studies have shown that DMD boys have a cognitive impairment and a lower IQ (average 85), whilst the mdx mice display an impairment in passive avoidance reflex and in short-term memory. In DMD boys, there is evidence of disordered CNS architecture, abnormalities in dendrites and loss of neurones, all associated with neurones that normally express dystrophin. In the mdx mouse, there have been reports of a 50% decrease in neurone number and neural shrinkage in regions of the cerebral cortex and brainstem. Histological evidence shows that the density of GABA(A) channel clusters is reduced in mdx Purkinje cells and hippocampal CA1 neurones. At the biochemical level, in DMD boys the bioenergetics of the CNS is abnormal and there is an increase in the levels of choline-containing compounds, indicative of CNS pathology. The mdx mice also display abnormal bioenergetics, with an increased level of inorganic phosphate and increased levels of choline-containing compounds. Functionally, DMD boys have EEG abnormalities and there is some preliminary evidence that synaptic function is affected adversely by the absence of dystrophin. Electrophysiological studies of mdx mice have shown that hippocampal neurones have an increased susceptibility to hypoxia. These recent findings on the role of dystrophin in the CNS have implications for the clinical management of boys with DMD.

Adult↗
PubMed2001

Novel cardiac troponin T mutation as a cause of familial dilated cardiomyopathy.

BACKGROUND: Familial dilated cardiomyopathy (FDCM) and hypertrophic cardiomyopathy (FHCM) are the 2 most common forms of primary cardiac muscle diseases. Studies indicate that mutations in sarcomeric proteins are responsible for FHCM and suggest that mutations in cytoskeletal proteins cause FDCM. Evidence is evolving, however, that such conclusions are premature. METHODS AND RESULTS: A novel missense mutation in the cardiac troponin T gene was identified by direct sequencing and confirmed by endonuclease restriction analysis in a large family with FDCM that we had previously mapped to chromosome 1q32. The mutation substitutes tryptophan for a highly conserved amino acid, arginine, at amino acid residue 141 (Arg141Trp). The mutation occurs within the tropomyosin-binding domain of cardiac troponin T and alters the charge of the residue. This mutation cosegregates with the disease, being present in all 14 living affected individuals. The mutation was not found in 100 normal control subjects. Clinical features were congestive heart failure with premature deaths. The age of onset and severity of the disease are highly variable, with incomplete penetrance. Because 15 mutations in troponin T are known to cause FHCM, 219 probands with FHCM were screened, and none had the mutation. CONCLUSIONS: Thus, the novel cardiac troponin T mutation Arg141Trp is responsible for FDCM in our family. Because several mutations in troponin T have already been recognized to be responsible for FHCM, it appears that the phenotype, whether it be hypertrophy or dilatation, is determined by the specific mutation rather than the gene.

Adult↗
PubMed2001

Chemical and on-line electrochemical reduction of metalloproteins with high-resolution electrospray ionization mass spectrometry detection.

The observation of the reduced forms of several metal-containing proteins using electrospray ionization (ESI) is reported for the first time. High-resolution mass analysis using Fourier transform ion cyclotron resonance mass spectrometry allows the oxidized and reduced forms of the proteins to be distinguished. The metalloproteins are reduced both chemically and electrochemically. Under normal sample handling conditions, the proteins that are reduced in solution appear in their oxidized form in their ESI mass spectra. Rigorous exclusion of oxygen from the solution of the reduced protein allows the observation of the reduced form in the gas phase. The metal centers investigated include heme and non-heme iron proteins, copper, and a manganese-substituted iron-sulfur cluster of the form [3FeMn-4S]. The electrochemical method is shown to provide several advantages over chemical reduction. The oxidation state of the metal center is stable with respect to electrospray ionization in both positive and negative ionization modes.

Electrochemistry↗
PubMed2001

Usefulness of in-hospital prescription of statin agents after angiographic diagnosis of coronary artery disease in improving continued compliance and reduced mortality.

Despite well-documented clinical benefit of the use of statins in patients with coronary artery disease (CAD) and even mild lipid elevations, studies have documented the presence of a significant "treatment gap" between those patients in whom treatment is indicated and those patients who actually receive it. It has been proposed that a prescription for statin therapy given to indicated patients at the time of initial angiographic diagnosis of CAD has the potential to improve long-term medication compliance, but this requires further evaluation. We prospectively followed 600 patients with angiographically demonstrated CAD (diameter stenosis > or = 70%) who met the National Cholesterol Education Project (NCEP) guidelines for statin therapy for an average of 3.0 years (range 2.0 to 4.6). Patients were an average of 65 years of age, 78% were men, 77% presented initially with acute ischemic syndrome, and 64 (10.7%) died during follow-up. Overall, 105 patients (18%) were discharged from the initial hospitalization with a statin prescription. At long-term follow-up, the number of patients taking statins had increased to 47%. However, long-term statin compliance was significantly higher among patients initially discharged with a statin prescription than those who were not (77% vs 40%; p < 0.0001). Additionally, those patients discharged with a statin prescription had significantly reduced mortality rate at long-term follow-up (5.7% vs 11.7%; p = 0.05). Cox hazard regression analysis, controlling for all known clinical baseline variables, confirmed the absence of a prehospital discharge statin prescription to be an independent predictor of increased mortality (hazard ratio 2.4) with a statistical trend (p = 0.06). Thus, this study demonstrates that after angiographic diagnosis of CAD, prescription of appropriate statin therapy at the time of hospital discharge improves long-term statin compliance and may significantly enhance survival.

Aged↗
PubMed2001

Prospective study of pathogen burden and risk of myocardial infarction or death.

BACKGROUND: We previously demonstrated that the risk of coronary artery disease (CAD) increased in relation to the number of pathogens (the "pathogen burden") in a cross-sectional study. In the present prospective study with a different patient cohort, we evaluated the effect of pathogen burden on the risk of myocardial infarction (MI) or death among CAD patients. METHODS AND RESULTS: IgG antibodies to cytomegalovirus (CMV), hepatitis A virus (HAV), herpes simplex virus type 1 (HSV1), HSV type 2 (HSV2), Chlamydia pneumoniae and Helicobacter pylori, and C-reactive protein (CRP) levels were tested in baseline blood samples from 890 patients who had significant CAD on angiography. The mean follow-up period was 3 years. The baseline prevalence of antibodies directed against CMV, HAV, HSV1, or HSV2, but not C pneumoniae and H pylori, was significantly higher among patients who subsequently developed MI or death than among control subjects. After adjustment for traditional risk factors, number of diseased vessels, and clinical presentation, relative hazards (95% confidence limits) for MI or death were 2.0 (1. 4 to 3.2) for CMV, 1.6 (1.1 to 2.3) for HAV, and 1.5 (1.0 to 2.2) for HSV2. Increasing pathogen burden was significantly associated with increasing risk of MI or death in a dose-response fashion. Adjusted relative hazards of MI or death associated with pathogen burden were significant among individuals with low or high CRP levels. CONCLUSIONS: The results suggest that infection plays an important role in incident MI or death and that the risk posed by infection is independently related to the pathogen burden.

Adult↗
PubMed2001

The role of nitric oxide in diaphragmatic dysfunction in endotoxemic rats.

In this study we examined the role of nitric oxide (NO) from inducible nitric oxide synthase (iNOS) and adenosine triphosphate (ATP) depletion, using aminoguanidine and 3-aminobenzamide, on diaphragm contractility in a rat model of sepsis. Intraperitoneal lipopolysaccharide (LPS) injection was used to induce septicemia in rats. The LPS treatment caused a decrease in maximal absolute force produced by the diaphragm muscle stimulated at 100 HZ, and the force-frequency curves were right-shifted with a decrease in force at 2, 5 and 15 HZ. LPS administration also made the diaphragm muscle strips more fatigable than controls. The decrease in force in LPS-treated animals was not due to an induction of pathological levels of i NOS. Increased fatigability did not appear to be due to a depletion of ATP through poly-adenosine-diphosphate-ribose polymerase (PARP) activation. This study does not support the hypothesis that the decrease in diaphragm muscle force as a result of sepsis is due to an induction of pathological levels of nitric oxide or ATP depletion.

Adenosine Triphosphate↗
PubMed2001

Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma.

The benefits of bisphosphonate therapy for multiple myeloma bone disease have been clearly documented. However, the effects of bisphosphonates on the osteoclast stimulatory activity (OSA) that is present in the marrow of patients with multiple myeloma, even before the bone disease is detectable, are unknown. Therefore, we examined the effects of ibandronate (IB) treatment prior to the development of bone disease in a murine model of human myeloma. Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH-77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous injections of IB started before or at different times after tumor injection as follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7; group 4 on day +14 after IB administration; and group 5 (control) received no IB. Mice were sacrificed after they developed paraplegia. The onset of paraplegia was delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The number of lytic lesions and the bone surface area of resorption (mm(2)) were significantly decreased in groups 1, 2, and 3, which were treated early with IB, when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as measured by the capacity of bone marrow plasma from ARH-77 mice to induce osteoclast (OCL) formation in human bone marrow cultures, was decreased proportionally to the length of IB treatment. Group 1 had the lowest OSA compared with the other groups (p = 0.003). However, all mice eventually developed paraplegia, and at time of sacrifice, tumor burden was not grossly different among the groups. Interestingly, macroscopic abdominal tumors were more frequent in mice treated with IB. These data demonstrate that early treatment of ARH-77 mice with IB prior to development of myeloma bone disease decreases OSA and possibly retards the development of lytic lesions, but not eventual tumor burden.

Animals↗
PubMed2001

Hamstrings vs. patella tendon for anterior cruciate ligament reconstruction: a randomised controlled trial.

A randomised controlled trial was performed to evaluate early outcome for two types of anterior cruciate ligament reconstruction. Sixty patients undergoing cruciate reconstruction were randomized into two groups. Group PT underwent reconstruction using a patella tendon autograft, whereas Group (SG) had a semitendinosus/gracilis autograft (SG). IKDC, Lysholm, and Tegner scores, KT1000 values and muscle strength were recorded pre-operatively, at 6 months and 1 year follow up. The functional scores, activity level, muscle strength and anterior tibial translation improved in both groups. No significant difference between groups was found for any measurement at 6 months and 1 year despite adequate study power. The study indicates that the 1 year results for either technique are equally favourable.

Analysis of Variance↗
PubMed2001

Comparison of dilated cardiomyopathy and coronary artery disease in patients with life-threatening ventricular arrhythmias: Differences in presentation and outcome in the AVID registry.

BACKGROUND: The etiology of structural heart disease in patients with life-threatening arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) may define clinical characteristics at presentation, may require that different therapies be administered, and may cause different mortality outcomes. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) registry, baseline clinical characteristics, treatments instituted, and ultimate mortality outcomes from the National Death Index were obtained on 3117 patients seen at participating institutions with VT/VF, irrespective of participation in the randomized trial. By use of these data, 2268 patients with coronary artery disease (CAD) were compared with 334 patients with dilated nonischemic cardiomyopathy (DCM). RESULTS: The CAD group was 7 years older and had a higher percentage of males. DCM patients were more likely to be African American, have severely compromised left ventricular function (52% vs 39%), and have a history of congestive heart failure symptoms (62% vs 44%). Patients with CAD were more likely to be treated with b-blockers and calcium channel blockers and less likely to be treated with angiotensin-converting enzyme inhibitors. Patients with DCM were more likely to be treated with diuretics, warfarin, and an implantable cardioverter defibrillator for VT/VF (54% vs 48% for CAD); the use of other antiarrhythmic therapies did not differ between the 2 groups. Two-year survival was not significantly different between the groups (76.6% [95% CI 74.6%-78.7%] vs 78.2% [95% CI 73.6%-82.9%]). CONCLUSIONS: In AVID registry patients with VT/VF, demographic and clinical characteristics were different between patients with CAD and those with DCM. Despite these differences, overall survival was similar in these 2 groups.

Anti-Arrhythmia Agents↗
PubMed2001

Endoluminal aortic grafting with renal and superior mesenteric artery incorporation by graft fenestration.

PURPOSE: To explore the use of juxta- and suprarenal aortic segments for endograft fixation in abdominal aortic aneurysm (AAA) patients and to develop methods of graft implantation that use endograft fenestrations to preserve renal and visceral vessel perfusion. METHODS: From August 1998 to May 2000, 13 AAA patients with unsuitable infrarenal aortic necks were treated with custom-designed endovascular grafts employing the juxta- and suprarenal aortic segments for proximal sealing. Flow to 33 renal and superior mesenteric arteries was maintained via graft fenestrations that were aligned by use of radiopaque graft markers. The fenestration-orifice interface for renal arteries was secured with modified balloon-expandable stents. RESULTS: All fenestrated grafts were deployed as planned, and all target vessels (33/33) were preserved. Two patients did not receive any stents, one being the first in the series and another who had incorporation of a renal accessory artery only. Without the use of transgraft stenting, 5 renal arteries would have been occluded by the endograft or poorly perfused. Procedural success was 100%. No conversion to open operation or graft-related complications occurred. There was no primary endoleak in any patient by angiographic criteria. Two patients required additional surgical procedures related to access vessels. Periprocedural mortality at 30 days was nil. Follow-up ranging from 3 to 24 months on all patients has not demonstrated any proximal or distal endoleaks. One stented renal vessel has occluded; all other arteries remain patent at last examination. CONCLUSIONS: This study has demonstrated the ability to successfully place a multifenestrated endoluminal graft in an aortic aneurysm using juxta- and suprarenal aortic segments to obtain a satisfactory seal. Stenting of the fenestration-renal ostium junction has helped to maintain renal patency.

Aortic Aneurysm, Abdominal↗