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Biomedical subjects

M E Ritchie

Publications and source records attributed to M E Ritchie.

17 recordsLinked to original sources
PubMed2001

Effects of macrophyte species richness on wetland ecosystem functioning and services.

Wetlands provide many important ecosystem services to human society, which may depend on how plant diversity influences biomass production and nutrient retention. Vascular aquatic plant diversity may not necessarily enhance wetland ecosystem functioning, however, because competition among these plant species can be strong, often resulting in the local dominance of a single species. Here we have manipulated the species richness of rooted, submerged aquatic plant (macrophyte) communities in experimental wetland mesocosms. We found higher algal and total plant (algal plus macrophyte) biomass, as well as lower loss of total phosphorus, in mesocosms with a greater richness of macrophyte species. Greater plant biomass resulted from a sampling effect; that is, the increased chance in species mixtures that algal production would be facilitated by the presence of a less competitive species-in this case, crisped pondweed. Lower losses of total phosphorus resulted from the greater chance in species mixtures of a high algal biomass and the presence of sago pondweed, which physically filter particulate phosphorus from the water. These indirect and direct effects of macrophyte species richness on algal production, total plant biomass and phosphorus loss suggest that management practices that maintain macrophyte diversity may enhance the functioning and associated services of wetland ecosystems.

Biomass↗
PubMed2001

Refractory no-reflow successfully treated with local infusion of high-dose adenosine and verapamil--a case report.

No-reflow is an unpredictable complication following percutaneous coronary intervention. No-reflow is associated with myocardial ischemia and infarction and increased mortality. A case of refractory no-reflow is described that was rapidly and successfully treated with multiple infusions of high doses of verapamil and adenosine applied directly at the site of no-reflow through a perfusion catheter.

Adenosine↗
PubMed2000

Incidence of thrombocytopenia following coronary stent placement using abciximab plus clopidogrel or ticlopidine.

The incidence of thrombocytopenia with ticlopidine and clopidogrel when used in conjunction with abciximab has not been systematically addressed. We evaluated the rate of thrombocytopenia in patients undergoing intracoronary stent implantation receiving bolus plus infusion of abciximab and either ticlopidine or clopidogrel. We noted an incidence of 24% with the combination of 300-mg clopidogrel and abciximab. Other doses of ticlopidine (250 and 500 mg) and clopidogrel (75 mg) did not result in a statistically significant increase in thrombocytopenia over that of the 2.5%-5.2% reported incidence with abciximab alone. Length of hospital stay was 2.3 vs. 6.4 days in those developing thrombocytopenia (P = 0.06). Four (25%) developed thrombocytopenia requiring blood transfusion. Eight (50%) had no sequelae. The combination of 300-mg clopidogrel and abciximab results in a significant increase in the incidence of thrombocytopenia. This is an important clinical observation that merits further study.

Abciximab↗
PubMed1999

Spatial scaling laws yield a synthetic theory of biodiversity.

Ecologists still search for common principles that predict well-known responses of biological diversity to different factors. Such factors include the number of available niches in space, productivity, area, species' body size and habitat fragmentation. Here we show that all these patterns can arise from simple constraints on how organisms acquire resources in space. We use spatial scaling laws to describe how species of different sizes find food in patches of varying size and resource concentration. We then derive a mathematical rule for the minimum similarity in size of species that share these resources. This packing rule yields a theory of species diversity that predicts relations between diversity and productivity more effectively than previous models. Size and diversity patterns for locally coexisting East African grazing mammals and North American savanna plants strongly support these predictions. The theory also predicts relations between diversity and area and between diversity and habitat fragmentation. Thus, spatial scaling laws provide potentially unifying first principles that may explain many important patterns of species diversity.

Africa, Eastern↗
PubMed1999

Characterization of MAP kinase and PKC isoform and effect of ACE inhibition in hypertrophy in vivo.

Protein kinase C (PKC) and mitogen-activated protein (MAP) kinase activation appear important in conferring hypertrophy in vitro. However, the response of PKC and MAP kinase to stimuli known to induce hypertrophy in vivo has not been determined. We recently demonstrated that pressure-overload hypertrophy induced a transiently transfected gene driven by an hypertrophy responsive enhancer (HRE) through a marked increase in binding activity of its interacting nuclear factor (HRF). These data suggested that the HRE/HRF could serve as a target for evaluating the signal transduction events responsible for hypertrophy in vivo. Accordingly, we characterized MAP kinase and PKC isoform activation, injected HRE driven reporter gene expression, and HRF binding activity in rat hearts subjected to ascending aortic clipping or sham operation in the presence of the angiotensin-converting enzyme (ACE) inhibitor fosinopril, hydralazine, or no treatment. Analyses showed that PKC-epsilon and MAP kinase were acutely activated following ascending aortic ligature and that fosinopril significantly inhibited but did not completely abrogate PKC-epsilon and MAP kinase activation. However, fosinopril completely prevented pressure overload-mediated induction of HRE containing constructs and obviated increased HRF binding activity. These results suggest a direct relationship between ACE activity and HRE/HRF-mediated gene activation and imply that PKC-epsilon and MAP kinase may be involved in transducing this signal.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Nuclear factor-kappaB is selectively and markedly activated in humans with unstable angina pectoris.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) resides inactive in the cytoplasm of lymphocytes, monocytes, endothelial cells, and smooth muscle cells, where, after stimulation, it transcriptionally activates interleukins, interferon, tumor necrosis factor-alpha, and adhesion molecules. Because acute inflammation may play a role in coronary artery plaque rupture, it was hypothesized that NF-kappaB activation correlated with coronary artery disease (CAD) activity. METHODS AND RESULTS: Evidence of NF-kappaB activation in the circulation of 102 consecutive patients without an acute myocardial infarction who were undergoing cardiac catheterization was determined. Of these, 19 had unstable angina (USA) and were within 24 hours of the last episode of chest pain. The remaining 83 were being evaluated for stable angina (53), valvular heart disease (8), atypical chest pain (12), or congestive heart failure (10). Evidence of NF-kappaB activation was determined by electromobility shift assays (EMSAs) with the NF-kappaB binding-site-specific probe and nuclear proteins isolated from the buffy coat of blood obtained at the beginning of the procedure. Specificity of this DNA-protein interaction was confirmed by competition and supershift EMSAs. Analyses showed that 17 of 19 patients with USA had marked activation of NF-kappaB. Despite a significant number of patients with severe CAD (69%), only 2 of the 83 without USA showed marked NF-kappaB activation. A lack of NF-kappaB activation was not due to a lack of functional cell/protein because NF-kappaB was appropriately activated by lipopolysaccharide ex vivo in all patients. NF-kappaB activation was not a nonspecific response of all transcription factors because neither Sp1 or Oct1 was activated in patients with activated NF-kappaB. There was no relationship between drugs used, hemodynamic status, or other clinical characteristics and state of NF-kappaB activation. CONCLUSIONS: These data show that NF-kappaB is specifically and significantly activated in unstable angina pectoris and is not affected by severity of CAD or medical therapy. Furthermore, because NF-kappaB is activated before a clinical event, it may be mechanistically involved in the plaque disruption that produces acute coronary artery syndromes.

Angina, Unstable↗
PubMed1998

Use of transesophageal echocardiography to detect unsuspected massive pulmonary emboli.

This report describes three patients in whom unsuspected large central pulmonary emboli were identified by transesophageal echocardiography. We discuss the utility and limitations of transesophageal echocardiography in diagnosing pulmonary emboli and its potential beneficial impact on the management of patients in the intensive care unit, particularly those with unexplained hypotension.

Adult↗
PubMed1998

Ergonovine-testing-directed therapy and long-term outcome of sudden-death survivors with no apparent heart disease.

Coronary artery vasospasm, the most common cause of sudden death in patients with structurally normal hearts, is not well recognized. We describe 2 survivors of sudden death with ergonovine-inducible coronary artery vasospasm successfully treated long term with calcium channel blockers. Of the reported (17 worldwide) patients with documented vasospasm-mediated sudden cardiac death treated with calcium blockers, none have had a recurrent event. This is substantially less than the 6-month sudden-death rate of 18 % of untreated vasospasm. We advocate that ergonovine provocative testing of sudden-death survivors with structurally normal hearts, followed by appropriate therapy with calcium channel blockers, be the standard approach for these highly treatable patients.

Adult↗
PubMed1998

Pseudo-pseudoaneurysm of the left ventricle.

Left ventricular pseudoaneurysms are an uncommon complication of myocardial infarction and need urgent surgical repair. Though it is critical that they be accurately identified, pseudoaneurysms are occasionally misdiagnosed. We report an abnormality which may be mislabeled a pseudoaneurysm which we term a pseudo-pseudoaneurysm. The approach to accurate diagnosis of pseudoaneurysms is discussed.

Aged↗
PubMed1997

bFGF induces BCK promoter-driven expression in muscle via increased binding of a nuclear protein.

Changes in gene expression occurring during skeletal muscle differentiation are exemplified by downregulation of brain creatine kinase (BCK) and induction of muscle creatine kinase (MCK). Although both are transcriptionally regulated, there appears to be no transcription factor-element overlap, suggesting that their coordinate expression results from culture medium-related influences. Basic fibroblast growth factor (bFGF) prevents myogenesis and represses MCK expression by inhibiting transcriptional activation. It was hypothesized that bFGF similarly influenced BCK by inducing its expression. Accordingly, BCK promoter constructs were transiently transfected into C2C12 cells and, after a switch to differentiation medium, were treated with bFGF, bFGF plus herbimycin, adenosine 3',5'-cyclic monophosphate (cAMP), or phorbol 12-myristate 13-acetate (PMA). Analyses demonstrated that bFGF responsiveness was contained within a 33-base pair element. Electromobility shift assays showed that bFGF induction increased the abundance of the nuclear factor binding the element. Both effects were prevented by herbimycin. Neither cAMP nor PMA specifically induced the construct containing the bFGF-responsive element. The induced factor required phosphorylation to bind, implying that bFGF-mediated increases in binding may be due to transcription factor phosphorylation.

Animals↗
PubMed1996

Characterization of human B creatine kinase gene regulation in the heart in vitro and in vivo.

During cardiogenesis, genes indicative of the adult phenotype are transcriptionally activated while genes characteristic of the embryonic phenotype are down-regulated. The regulation of embryonic genes such as the brain isoform of creatine kinase (BCK) during cardiac development has not been characterized. Accordingly, the transcriptional regulation of BCK in the developing heart was determined. In vitro and in vivo promoter analyses of the human BCK gene identified an element between +25 and +57 that functioned as an enhancer. Electromobility shift assays using adult and neonatal nuclear extracts identified a specific complex binding this element, the abundance of which correlated with the developmental level of endogenous cardiac BCK expression. Mutations at +47 and +53 led to a loss of activity in transfected cells and obviated binding in electromobility shift assays. These data show that a nuclear factor in cardiocytes interacts with an enhancer element (+25 and +57), via nucleotides +47 and +53, to drive BCK expression in the heart and suggest that developmental BCK expression is via abundance of this factor. The nuclear factor has not been identified but as described previously binding sites are not present in the enhancer, it is either a known factor interacting with a new recognition site or a new factor.

Aging↗
PubMed1996

Human B creatine kinase gene expression in C2C12 cells is regulated by protein interactions involving the first exon.

While the activation of muscle specific genes is well characterized, the mechanism mediating the regulation during muscle development of embryonic genes is poorly understood. To begin to investigate this area, the transcriptional regulation of the human brain creatine kinase (BCK) gene was characterized during in vitro myogenesis of C2C12 muscle cells. Initial analyses identified the first exon as important for high level expression in general and for the decrease in expression in response to C2C12 differentiation. In vivo competition confirmed the functional importance of the first exon. Electrophoretic mobility shift assays using portions of the exon showed that two separate proteins bound to sequences +1 to +27 and +25 to +57, respectively. The +1 to +27 interacting factor is present in skeletal but not cardiac muscle and thus may function as a skeletal muscle determining factor. The +25 to +57 interacting factor functions as a positive effector in myoblasts. This region also imparts the differentiation dependent decrease in expression via either modification of the myoblast factor or due to the presence of an additional factor. Site directed mutagenesis show that base pair +26 is critical for appropriate down regulation of BCK.

Animals↗
PubMed1995

Characterization of 5' end of human thromboxane receptor gene. Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets.

Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction. To determine if platelet thromboxane receptors are under transcriptional control, we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene. The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA. A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site. The thromboxane receptor gene has neither a TATA nor a CAAT consensus site. Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells. Thromboxane receptor promoter activity, as assessed by CAT expression, was relatively weak but was significantly enhanced by phorbol ester treatment. Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site. These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements. These findings strongly suggest that the mechanism for previously described upregulation of platelet thromboxane receptors after acute myocardial infarction is increased thromboxane receptor gene transcription in platelet-progenitor cells.

Base Sequence↗
PubMed1992

The human M creatine kinase gene enhancer contains multiple functional interacting domains.

Cis-elements (-933 to -641) upstream of the human M creatine kinase gene cap site contain an enhancer that confers developmental and tissue-specific expression to the chloramphenicol acetyltransferase gene in C2C12 myogenic cells transfected in culture. Division of the enhancer at -770 into a 5' fragment that includes the MyoD binding sites (-933 to -770) and a 3' fragment that includes the MEF-2 binding site (-770 to -641) resulted in two subfragments that showed minimal activity but in combination interacted in a position- and orientation-independent fashion to enhance activity of the SV40 promoter in transient transfection experiments. A 5' enhancer construct (-877 to -832) including only one (the low affinity) MyoD binding site was active when present in multiple copies. In contrast, a 3' enhancer construct (-749 to -732) including the MEF-2 binding site was inactive even when present in multiple copies. However, if the 5' construct was extended to include the high-affinity MyoD binding site (-877 to -803) the 5' and 3' constructs interacted in a position- and orientation-independent fashion to activate the SV40 promoter. Thus, the human M creatine kinase enhancer comprises multiple functional interacting domains.

3T3 Cells↗
PubMed1991

Multiple positive and negative elements regulate human brain creatine kinase gene expression.

We characterized the developmental expression of the brain creatine kinase (BCK) gene in the C2C12 myogenic cell line with the use of isoenzyme, Western blot, and Northern blot analyses. The results show that both BCK subunit protein and mRNA are upregulated early in myogenesis, and then downregulated in fully differentiated myotubes. To characterize the transcriptional regulatory mechanisms, a chimeric construct containing 1.2 kilobase pairs of 5'-flanking DNA from the human BCK gene placed upstream of the chloramphenicol acetyltransferase gene in the promoterless plasmid pSVOCAT was transiently transfected into C2C12 cells. In myoblasts and differentiating myotubes, the time course of expression of the constructs paralleled that of endogenous BCK mRNA. Additional constructs prepared by deleting 5'-flanking DNA were also transfected into C2C12 cells. All constructs were preferentially expressed in myoblasts relative to myotubes with absolute levels of expression increasing with deletion of 5'-flanking DNA. In nonmyogenic cells expression of the plasmids also increased with deletion of 5'-flanking DNA. An element from -1150 to -388 was isolated and found to be capable of suppressing expression of the BCK promoter and of heterologous promoters independent of orientation and position and hence to function as a silencer. Thus, BCK expression is mediated by sequences contained in the 5'-flanking DNA, including negative elements active in both C2C12 cells and nonmyogenic cells and elements that mediate the developmental expression of the BCK gene in C2C12 myogenic cells.

3T3 Cells↗