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Biomedical subjects

L J Feldman

Publications and source records attributed to L J Feldman.

At least 37 records · Page 2Linked to original sources

Auxin metabolism in the root apical meristem.

Within the root meristem of flowering plants is a group of mitotically inactive cells designated the quiescent center (QC). Recent work links the quiescent state to high levels of the growth regulator auxin that accumulates in the QC via polar transport. This in turn results in elevated levels of the enzyme ascorbic acid oxidase (AAO), resulting in a reduction of ascorbic acid (AA) within the QC and mitotic quiescence. We present evidence for additional interactions between auxin, AAO, and AA, and report that, in vitro, AAO oxidatively decarboxylates auxin, suggesting a mechanism for regulating auxin levels within the QC. We also report that oxidative decarboxylation occurs at the root tip and that an intact root cap must be present for this metabolic event to occur. Finally, we consider how interaction between auxin and AAO may influence root development by regulating the formation of the QC.

Ascorbate Oxidase↗

Auxin and ETTIN in Arabidopsis gynoecium morphogenesis.

The phytohormone auxin has wide-ranging effects on growth and development. Genetic and physiological approaches implicate auxin flux in determination of floral organ number and patterning. This study uses a novel technique of transiently applying a polar auxin transport inhibitor, N-1-naphthylphthalamic acid (NPA), to developing Arabidopsis flowers to further characterize the role of auxin in organogenesis. NPA has marked effects on floral organ number as well as on regional specification in wild-type gynoecia, as defined by morphological and histological landmarks for regional boundaries, as well as tissue-specific reporter lines. NPA's effects on gynoecium patterning mimic the phenotype of mutations in ETTIN, a member of the auxin response factor family of transcription factors. In addition, application of different concentrations of NPA reveal an increased sensitivity of weak ettin alleles to disruptions in polar auxin transport. In contrast, the defects found in spatula gynoecia are partially rescued by treatment with NPA. A model is proposed suggesting an apical-basal gradient of auxin during gynoecium development. This model provides a mechanism linking ETTIN's putative transcriptional regulation of auxin-responsive genes to the establishment or elaboration of tissue patterning during gynoecial development.

Alleles↗

Relationship between resting 201Tl reverse redistribution, microvascular perfusion, and functional recovery in acute myocardial infarction.

UNLABELLED: 201TI reverse redistribution is a common finding early after reperfusion therapy for myocardial infarction. Its mechanism and clinical implications remain unclear. The aim of this study was to clarify the relationships between reverse redistribution, microvascular perfusion, and myocardial viability. METHODS: Resting, 10-min-postinjection, and redistribution 201TI data obtained for 33 patients 8 and 42 d after the onset of acute myocardial infarction were compared with echocardiographic wall motion measured acutely and on day 42. Microvascular perfusion was assessed by myocardial contrast echocardiography performed 10 min after restoration of complete patency of the infarct artery. RESULTS: Marked significant reverse redistribution was found on day 8 (absolute change, 7.5%+/-7.9% of the 10-min-postinjection defect size; P<5x0.000001) and significantly decreased on day 42 (2.7%+/-6.8%; P = 0.004 between days 8 and 42). The 10-min-postinjection defect size best predicted the final infarct size on day 42 and was closely related to microvascular perfusion. Patients with adequate reperfusion had a smaller postinjection defect on day 8 (21.1%+/-14.6%) and a larger reverse redistribution (10.2%+/-6.1%) than did patients with no reflow (35.3%+/-13% and 3.2%+/-9.2%, respectively; P<0.04 for both). CONCLUSION: Reverse redistribution was marked early after myocardial infarction in patients with complete patency of the infarct artery and decreased in subsequent weeks. Reverse redistribution was associated with restoration of adequate microvascular reperfusion and with myocardial salvage and viability. The early postinjection scans on day 8 were the relevant images for assessing myocardial salvage and predicting wall motion recovery.

Coronary Circulation↗

[The coronary atherosclerosis of the diabetic].

Diabetes mellitus is one of the main risk factors of coronary atherosclerosis. The relative risk of cardiovascular disease is 2 to 4 times higher in type II diabetes than in the general population. The number of cases, especially type II, is increasing, especially as the definition of diabetes has been changed recently by the specialist scientific societies (American Diabetic Association, World Health organisation and ALFEDIAM) to include all patients with fasting glucose levels > or = 7 mmol/L on two occasions. Therefore, in the next 25 years, the number of diabetic patients will probably double, not only because of this new definition but also because of the combined effects of an ageing population, dietary changes (with an increase in obesity) and a progressively more sedentary and urbanized life-style in the so-called "emerging" countries.

Angioplasty, Balloon, Coronary↗

The role of amyloplasts during gravity perception in gynophores of the peanut plant (Arachis hypogaea).

Gravitropic perception and response are essential for the completion of the reproductive life cycle of the peanut plant (Arachis hypogaea L.). The developing seeds are buried in the soil by a specialized organ, the gynophore, allowing the fruit to mature underground. Controversy exists about the site of graviperception in the gynophore: previous workers suggested that the intercalary meristem was the zone where gravity was perceived. Taking the starch statolith hypothesis for graviperception as a framework, we explored the possibility that the starch-grain filled plastids (amyloplasts) in the starch sheath of the gynophore may be acting as gravisensors. We show that these amyloplasts sediment readily with respect to the gravity vector within 30 min of reorientation, and before there is a measurable gravitropic response. Gynophore explants were incubated with gibberellic acid and kinetin, in darkness, to remove starch from the amyloplasts. Destarching the gynophores did not inhibit overall growth of the organ, but reduced the gravitropic response curvature by 82% compared to water-treated controls. In addition, gynophores placed on a rotating clinostat (without hormone treatment) also showed a reduced gravitropic response. In conclusion, the evidence presented in this work strongly suggests that the amyloplasts of the starch sheath are responsible for gravitropic perception in the peanut gynophore. A model for graviperception in the gynophore is presented.

Arachis↗

Auxin redistributes upwards in graviresponding gynophores of the peanut plant.

The peanut (Arachis hypogaea L.) produces flowers aerially, but buries the recently fertilized ovules into the soil, where fruit and seed development occur. The young seeds are carried down into the soil at the tip of a specialized organ called the gynophore. Although the gynophore has a typical shoot anatomy, it responds positively to gravity like a root. In this study, we explore the role of the plant growth regulator indole-3-acetic acid (IAA) in the growth and the gravitropic response of the peanut gynophore. With an immunolocalization technique using an IAA monoclonal antibody, we localized IAA within the tissues of vertically oriented and gravistimulated gynophores. We found that in vertically oriented gynophores, IAA labeling occurs in the periphery of the gynophore, in the entire cortex and epidermis. Within 20 min of horizontal reorientation, the IAA signal gradually increases in the upper cortex/ epidermis and diminishes in the lower cortex/epidermis. At 1.5 h after gravistimulation, all of the IAA immunolocalization signal is detected in the upper cortex and epidermis--none is detected in the lower side. Growth rate measurements also indicate that after 1-2 h of reorientation, the growth rate maximum on the upper side corresponds temporally and spatially to the growth rate minimum on the lower side. Experiments using radioactively labeled IAA corroborate an upper-side redistribution of this hormone upon horizontal reorientation. These results are analyzed with respect to the current theories of plant gravitropic response, and a model for a possible gravity-induced IAA redistribution from the lower to the upper side of the peanut gynophore is proposed.

Arachis↗

Elevated cardiac troponin I predicts a high-risk angiographic anatomy of the culprit lesion in unstable angina.

BACKGROUND: This study assessed the relation between the angiographic appearance of the culprit lesion and cardiac troponin I (cTnI) or C-reactive protein (CRP) elevations within the first 24 hours in unstable angina. Intracoronary thrombus or a complex morphology, is frequently observed on angiography in patients with unstable angina and is associated with a higher rate of spontaneous or coronary angioplasty-related complications. Biochemical parameters related to myocardial injury (eg, cTnI) or to systemic inflammation (eg, CRP) are known prognostic markers for clinical outcome and may help in angiographic risk stratification to provide new adjunctive therapy. METHODS AND RESULTS: We studied 100 patients admitted for unstable angina with angiographically proven coronary artery disease (with normal creatine kinase [CK] and CK-MB mass). Serum concentrations of cTnI (N < 0.4 ng/mL) and CRP (N < 3 mg/L) were measured at admission and 12 and 24 hours later. Multivariate analysis showed that elevated cTnI (>/=0.4 ng/mL) within 24 hours (35 patients) was an independent predictor of an angiographic appearance of the culprit lesion carrying a high risk of major cardiac events in the outcome and whether angioplasty is attempted (coronary thrombus, occlusion, or type C lesions; odds ratio 4.1, 1. 6 to 10.5). cTnI levels at admission and CRP at 0, 12, and 24 hours were not predictive of high-risk angiographic anatomy. CONCLUSIONS: In patients with unstable angina and angiographically proven coronary artery disease, increased cTnI within 24 hours of admission but not increased CRP is associated with an angiographic appearance of the culprit lesion carrying a high risk of complication, especially in the event of angioplasty.

Angina, Unstable↗

Gravitaxis in Chlamydomonas reinhardtii: characterization using video microscopy and computer analysis.

We characterized the gravitactic behavior of Chlamydomonas reinhardtii, a unicellular green alga, using a computer-analysis system in order to study directional swimming. The effects of the calcium-channel inhibitors gadolinium and diltiazem on graviorientation and swimming speed were examined. In addition, we studied directional swimming in the ptx1 strain of C. reinhardtii, a flagellar dominance mutant. Results indicate that Chlamydomonas reorients for gravitactic swimming through a mechanism different from the calcium-mediated pathway believed to be involved in gravity transduction in higher plants. We suggest that calcium-mediated gravitaxis originated in an organism that was more evolutionarily advanced than Chlamydomonas.

Animals↗

Heterogeneity of prognosis in patient subsets treated by primary coronary angioplasty during acute myocardial infarction.

Among 377 patients consecutively treated with primary coronary angioplasty for acute myocardial infarction, in-hospital mortality was higher in patients ineligible than in patients eligible for thrombolysis (14.4% vs 7.8%, p <0.05). It remained dismal (75.9%) in patients with cardiogenic shock, but was similar in lytic-eligible patients and in those who were ineligible because of an increased bleeding risk (7.8% vs 7.2%, p = NS), and was zero in patients with nondiagnostic electrocardiograms.

Age Factors↗

Effects of poloxamer 407 on transfection time and percutaneous adenovirus-mediated gene transfer in native and stented vessels.

UNLABELLED: Reduction in transfection time and the ability to perform gene transfer in conjunction with endovascular stent implantation constitute two important challenges for percutaneous adenovirus-mediated gene transfer to vessel walls. Studies have suggested that the use of biocompatible polyol poloxamer 407 could be useful. We first evaluated the use of poloxamer 407 for percutaneous gene transfer in nonstented rabbit iliac arteries. A 200-microl mixture of Ad-RSVbetagal or Ad-CMVLuc in either phosphate-buffered saline (PBS) or 20% poloxamer was delivered. After 3 days, gene transfection was evaluated by X-Gal staining or measurement of luciferase activity. Poloxamer use resulted in a 3- to 15-fold increase in the percentage of transfected cells (X-Gal, p = 0.001) and a 16-fold increase in protein product (luciferase activity, p = 0.03), and allowed a decrease in transfection time from 30 to 5 min with minimal reduction in transfection efficiency. We then evaluated the feasibility of percutaneous gene transfer, using Ad-RSVbetagal diluted in pure PBS or 20% poloxamer, in conjunction with stent implantation. Gene delivery was performed either immediately before (pre-) or after (post-) stent implantation. When adenoviruses were diluted in PBS, gene transfer had a low efficiency (prestent, 0.3%; poststent, 0.2%; NS). With poloxamer, the efficacy was much higher (p = 0.0001) and similar "pre" (2.2%) or "post" (1.7%) stent delivery (NS). CONCLUSIONS: (1) The use of poloxamer, rather than PBS, as a vehicle increases the efficacy of percutaneous adenovirus-mediated gene transfer and reduces transfection time; (2) gene transfer performed during stent implantation with poloxamer is feasible and achieves a significant level of gene expression. Thus percutaneous gene delivery is applicable to conventional stents and could present an attractive method by which to achieve local biological effects in a stent environment.

Adenoviruses, Human↗

Hospital outcome after bailout coronary stenting in patients with acute myocardial infarction.

We evaluated the outcome of bailout coronary stenting in acute myocardial infarction. Fifty patients (35 men, mean age 60 plusmn; 12) with acute myocardial infarction consecutively underwent bailout stenting after primary and rescue coronary angioplasty (n=41 and 9, respectively). Cardiogenic shock was present in six patients, and 17 others had contraindications to thrombolysis. Stent implantation was successful in 49/50 patients. The antithrombotic regimen combined heparin, aspirin, and ticlopidine. One patient had symptomatic stent closure. Predischarge angiography in 41/44 survivors showed widely patent stents in 40/41 patients. Six patients (4 of whom had been admitted with cardiogenic shock) died in the hospital. During acute myocardial infarction, bailout stenting can achieve high TIMI grade 3 coronary patency (here, 92%), and low acute stent closure rates (here, 2%). However, in-hospital mortality remained high, at nearly 10%, mainly due to the severe risk profile in this patient subset.

Adult↗

Pre-treatment with elastase improves the efficiency of percutaneous adenovirus-mediated gene transfer to the arterial media.

The endothelium and internal elastic lamina (IEL) appear to be the main barriers to adenovirus-mediated gene transfer to medial smooth muscle cells (SMC). The present randomized study tested whether controlled incubation with elastase enhanced the efficiency of catheter-based gene transfer to medial SMC by adenoviral vectors. After an initial safety dose ranging study, rabbits underwent balloon abrasion of the iliac endothelium followed by local incubation of either elastase (2 x 10(-7) IU over 5 min) or saline using a double balloon catheter (DBC). Then, adenoviral vectors (5 x 10(9) p.f.u.) carrying Cmv-Luc or RSV-beta gal reporter genes were instilled for 30 min. Three days later, the number of medial SMC expressing lacZ was increased in the elastase-treated arteries compared with saline-treated arteries (7.2 +/- 2.5 versus 2.3 +/- 0.9 cells per section, P = 0.003). Likewise, the amount of luciferase protein product was increased (70 +/- 32 versus 36 +/- 15 pg luciferase/mg tissue, P = 0.03). No vessel enlargement, light or electron microscopic evidence of injury or inflammation was seen in elastase-treated arteries up to 7 weeks. Preincubation with elastase increased transduction efficiency of catheter-based gene delivery of replication-defective adenoviral vectors to rabbit iliac arteries without detectable arterial damage.

Adenoviridae↗

Photoinduction of flower identity in vegetatively biased primordia.

Far-red light and long photoperiods promote flowering in Arabidopsis. We report here that when 30-day-old vegetative plants were induced with a continuous light treatment enriched in far-red light, flowers developed directly from previously initiated primordia. Specifically, plants induced with our continuous incandescent-enriched (CI) treatment produced an average of two primary-axis nodes with a leaf/flower phenotype, indicating that approximately two leaf/paraclade primordia per plant produced an individual flower from tissue that typically would differentiate into a paraclade (secondary inflorescence). Assays for APETALA1::beta-glucuronidase activity during the CI photoinduction treatment indicated that the floral meristem identity gene APETALA1 was transcriptionally activated in primordia with a leaf/paraclade bias and in primordia committed to leaf/paraclade development. APETALA1::beta-glucuronidase activity levels were initially highest in young primordia but were not correlated strictly with primordium fate. These results indicate that primordium fate can be modified after primordium initiation and that developing primordia respond quantitatively to floral induction signals.

Arabidopsis↗

Growth rates and auxin effects in graviresponding gynophores of the peanut, Arachis hypogaea (Fabaceae).

The gynophore of the peanut plant (Arachis hypogaea) is a specialized organ that carries and buries the fertilized ovules into the soil in order for seed and fruit development to occur underground. The rates of growth of vertically and horizontally oriented gynophores were measured using a time-lapse video imaging system. We found that the region of maximum extension growth due to elongation (termed the Central Elongation Zone) is located on average at 2-5 mm from the tip. In the first 0-4 h after horizontal reorientation (gravistimulation), new zones of growth emerge on the upper surface, while the elongation zone of the lower side decreases in size and magnitude. Four to six hours after reorientation the zones of maximum growth are almost equal in size and location on the upper and lower sides. The growth rate and the gravitropic response decreased dramatically, upon the excision of the ovule region (terminal 1.5 mm), but a gravitropic growth response could be restored by applying the auxin indole-3-acetic acid exogenously to the excised tip. The addition of napthylphthalamic acid (an auxin transport inhibitor) at the ovule region allowed some growth to occur, but the gynophores do not respond normally to gravity, upon horizontal reorientation. We discuss the role of auxin in the gravitropic response of the gynophore.

Arachis↗

Light-regulated root gravitropism: a role for, and characterization of, a calcium/calmodulin-dependent protein kinase homolog.

Roots of many species grow downward (orthogravitropism) only when illuminated. Previous work suggests that this is a calcium-regulated response and that both calmodulin and calcium/calmodulin-dependent kinases participate in transducing gravity and light stimuli. A genomic sequence has been obtained for a calcium/calmodulin-dependent kinase homolog (MCK1) expressed in root caps, the site of perception for both light and gravity. This homolog consists of 7265 base pairs and contains 11 exons and 10 introns. Since MCK1 is expressed constitutively in both light and dark, it is unlikely that the light directly affects MCK1 expression, though the activity of the protein may be affected by light. In cultivars showing light-regulated gravitropism, we hypothesize that MCK1, or a homolog, functions in establishing the auxin asymmetry necessary for orthogravitropism.

Base Sequence↗

The Dispatch catheter as a delivery tool for arterial gene transfer.

OBJECTIVE: Most currently available percutaneous delivery methods for arterial gene therapy are limited by the need for a long incubation period, which may lead to unacceptable tissue ischemia, especially in the coronary vasculature. Conversely, shorter incubation times may result in inefficient gene transfer, especially in atheromatous arteries. A new local delivery autoperfusion multichamber catheter is now available which permits local delivery in the coronary arterial system without inducing myocardial ischemia. The present study aimed at evaluating the performance of this catheter for achieving arterial gene transfer using replication-defective adenoviral vectors in normal and atheromatous arteries. METHODS: A replication-defective adenoviral vector carrying a nuclear-targeted beta-galactosidase reporter gene (Ad-RSV beta gal, 5.10(9) plaque-forming units [pfu]) was delivered to the iliac arteries of normal (n = 7) and atheromatous (1% cholesterol diet + arterial abrasion) (n = 6) rabbits, via a multichamber autoperfusion balloon catheter (Dispatch, SciMed). Duration of gene delivery was 60 min. RESULTS: Three days later, marked expression of the reporter gene was detected by histochemistry in the endothelium at the delivery site (percentage of transfected cells: 16 +/- 8% / artery (range 11-25%). There was a low transduction rate in medial smooth muscle cells 0.7 +/- 0.4%/artery (range 0.3-1.1%). In atheromatous arteries, transduction was consistently achieved in the superficial layers of the neointima but was lower (1.1 +/- 0.5%/artery, range 0.3-1.7%). Transgene expression was detected by histochemistry in the liver of 3/13 animals, suggesting that there is a substantial risk of systemic dissemination of the viral vectors. CONCLUSION: Efficient arterial gene delivery to endothelial and superficial smooth muscle cells is feasible using local delivery of adenoviral vectors via the Dispatch autoperfusion catheter, in both normal and atheromatous arteries. This perfusion catheter may be a useful tool for coronary artery gene transfer.

Adenoviruses, Human↗

Optimal techniques for arterial gene transfer.

Cardiovascular gene therapy is becoming a clinical reality due to improved vectors, delivery systems and careful experimental validation studies. Nearly all cardiovascular diseases are amenable to gene therapy, but the optimal combination of vector, delivery system and therapeutic gene is likely to be unique to each application. Currently, the most efficient vectors available are replication-defective adenoviral vectors, but transgene expression is limited in time due to a strong immune response. Conversely, non-viral vectors or plasmid DNA may be used safely but have very limited efficiency. Percutaneous, catheter-based delivery is feasible for most applications. The ultimate issues that will decide of the future of gene therapy are safety of the transfer and delivery techniques as well as cost/effectiveness comparisons with alternative therapies, including local delivery of drugs, proteins and/or mechanical devices.

Arteries↗