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R G Johnson

Publications and source records attributed to R G Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Lack of beneficial effects of growth hormone treatment in conscious dogs during development of heart failure.

The effects of chronic treatment with growth hormone (porcine GH, 0.56 mg.kg-1.day-1 s.c.) were examined in dogs with heart failure induced by rapid ventricular pacing (240 beats/min) for 4 wk. Fourteen conscious dogs were studied 2-3 wk after surgical instrumentation with catheters in the descending aorta and left atrium, a pressure gauge in the left ventricle (LV), a flow probe around the ascending aorta, pacing leads on the ventricular free wall and left atrium, and ultrasonic crystals on the opposing anterior and posterior endomyocardium of the LV. GH treatment for 4 wk significantly increased both body weight and plasma insulin-like growth factor 1 (IGF-1) compared with vehicle-treated dogs (P < 0.01, +2.0 +/- 0.5 vs. +0.3 +/- 1.1 kg; 1,043 +/- 218 vs. 241 +/- 64 ng/ml, respectively). However, the changes in resting LV systolic (i.e., both isovolumic and ejection phases) and diastolic function (i.e., isovolumic relaxation time constant tau) and the systemic vascular resistance were similar for the GH- and vehicle-treated groups during the development of heart failure. LV contractile reserve, assessed with step infusion of isoproterenol or dobutamine challenge, was markedly attenuated after heart failure, but there were no differences between the GH- and vehicle-treated groups. During the progression of heart failure, the increases in plasma atrial natriuretic peptide correlated (P < 0.01) directly with left atrial pressure and inversely with LV circumferential fiber shortening. However, GH treatment did not substantially modify these relationships. In addition, renal function and myocardial ultrastructure at the advanced stage of heart failure also showed similar changes for the GH- and vehicle-treated groups. We conclude that in conscious dogs during the development of congestive heart failure produced by rapid ventricular pacing, GH at a dose that increases body weight and plasma IGF-1 levels does not affect LV performance or systemic vascular dynamics.

Adrenergic beta-Agonists↗
PubMed1998

The "H" graft: an alternative approach for performing minimally invasive direct coronary artery bypass.

OBJECTIVES: Minimally invasive direct coronary artery bypass permits arterial revascularization without cardiopulmonary bypass, potentially decreasing associated morbidity. The procedure is, however, technically challenging and associated with significant postoperative pain resulting from retraction through the small incision. METHODS AND PATIENT SELECTION: From December 1996 to April 1997, eight patients underwent grafting of the left anterior descending coronary artery by use of a short segment of right inferior epigastric artery attached proximally to the side of an in situ left internal thoracic artery. We have termed this procedure the "H" graft MIDCAB. RESULTS: No patients required intraoperative conversion to conventional bypass. No postoperative deaths or myocardial infarctions occurred. Six patients with normal renal function underwent postoperative angiography that demonstrated graft patency with rapid filling of the left anterior descending coronary in each case. Postoperatively clinical signs of acute ischemia were resolved or a normal exercise tolerance test was obtained in all patients. The median postoperative length of stay was 3 days. Rib spreading and chest wall retraction were not required in any procedure. CONCLUSIONS: The "H" graft procedure is an attractive alternative to standard minimally invasive bypass because of greater technical simplicity, the avoidance of internal thoracic artery harvest, and excellent visualization with no chest wall retraction.

Coronary Artery Bypass↗
PubMed1998

5-Hydroxytryptamine2 receptors modulate auditory filtering in the rat.

Sensory processing deficits are a hallmark of schizophrenia and can be demonstrated by recording auditory evoked potentials (AEPs) elicited in response to closely paired click stimuli. In nonschizophrenic humans, as well as in rats, the amplitude of the response to the second click is reduced (filtered) compared with the first. In contrast, schizophrenics, or rats treated with amphetamine, generate AEPs that have smaller amplitudes and show little or no reduction in the response to the second click. We sought to evaluate the role of 5-hydroxytryptamine2 5-HT2 receptors in auditory filtering. Male Sprague-Dawley rats were implanted with a skull screw electrode to permit chronic recording of AEPs from a point approximating human vertex. During subsequent recording sessions, pairs of clicks (a conditioning click followed by a test click) were presented 500 msec apart. Parameters of N40, a dominant midlatency component of the AEP, were examined to evaluate the effects of a 5-HT2 receptor agonist, (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI), and a 5-HT2 receptor antagonist, ketanserin. Systemic administration of ketanserin reduced sensory filtering in a dose-dependent manner. Conversely, DOI significantly improved filtering. In addition, DOI dose-dependently antagonized the disruption of filtering induced by administration of amphetamine (1.83 mg/kg i.p.). Taken together, these results indicate an important role for 5-HT2 receptors in the modulation of auditory filtering.

Amphetamine↗
PubMed1997

Minimally invasive direct coronary artery bypass: our experience with 32 patients.

From January 1996 to May 1997, minimally invasive direct coronary artery bypass (MIDCAB) through a small anterior thoracotomy without cardiopulmonary bypass was completed in 31 of 32 patients (Male: Female=1.9:1, mean age=64.6 years, 11 (34.4%)>70 years). Twenty, five, and seven patients had one, two, and three vessel disease respectively. Twelve patients presented with unstable angina, seven had prior myocardial infarction, one had a pre-operative intra-aortic balloon pump, and four had prior coronary artery bypass grafting (CABG). Eight were diabetic, five had chronic obstructive pulmonary disease, and one was morbidly obese. Our newly developed coronary artery immobilizing and occluding device facilitated the coronary anastomosis. There were no post-procedure deaths, no peri-operative myocardial infarctions, and no strokes. One patient required intra-operative conversion to conventional CABG for an intramyocardial target vessel. Two patients had conversion after post-operative angiogram demonstrated incorrect target identification and early graft occlusion. Four patients had limited access graft revision (two kinks, one graft injury, and one haemorrhage). Thirty-one of the 32 patients were followed from 0.5 to 16 months and 30 reported no post-operative cardiac events (one required PTCA to another vessel). We conclude that MIDCAB is safe and effective.

Adult↗
PubMed1997

[3H]8-OH-DPAT labels a 5-HT site coupled to inhibition of phosphoinositide hydrolysis in the dorsal raphe.

The present study was undertaken to compare the properties of the [3H]8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) binding site in the dorsal raphe nucleus with the hippocampal 5-HT1A receptor. In both tissues inclusion of 1 mM Mg2+ enhanced specific [3H]8-OH-DPAT binding, while 1 mM GTP decreased radioligand binding. [3H]8-OH-DPAT appears to bind to a single population of binding sites in both the hippocampus and the dorsal raphe nucleus, although the K(d) for the radioligand at the dorsal raphe site was five times that observed at the hippocampal 5-HT1A receptor. Similarly, although 5-HT and selective 5-HT1A receptor ligands displayed high affinity for the [3H]8-OH-DPAT binding site in the dorsal raphe nucleus, the affinity at the dorsal raphe site was less than that observed at the hippocampal 5-HT1A receptor. 8-OH-DPAT inhibited forskolin-stimulated adenylyl cyclase activity in the hippocampus, but did not alter enzyme activity in the dorsal raphe nucleus. Conversely, 8-OH-DPAT inhibited the accumulation of [3H]inositol phosphates in the dorsal raphe nucleus, but not in the hippocampus. An inhibition of phosphoinositide hydrolysis in the dorsal raphe nucleus also was found with the putative 5-HT1A receptor selective ligands, flesinoxan and gepirone. However, addition of another putative 5HT1A receptor selective ligand, buspirone, did not alter the generation of [3H]inositol phosphates, but blocked the inhibitory effect of 8-OH-DPAT on phosphoinositide hydrolysis. These studies demonstrate that the 8-OH-DPAT binding site in the dorsal raphe nucleus displays a binding profile which is similar to the hippocampal 5-HT1A receptor, but unlike this 5-HT1A receptor the binding site in the dorsal raphe nucleus is negatively coupled to phosphoinositide turnover.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1997

Decreased myogenic reactivity in skeletal muscle arterioles after hypothermic cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is associated with a generalized defect in the intrinsic control of vascular smooth muscle. To determine if myogenic reactivity of skeletal muscle arterioles was altered by CPB, sheep (n = 7) were placed on hypothermic CPB (27 degrees C) for 90 min and hearts were arrested by cold blood cardioplegia ([K+] = 25 mM) for 60 min. Arterioles (70-180 microns) were isolated from the gracilis muscle before (control) and 15 min after CPB. In vitro arteriolar responses were studied with video-microscopy. Myogenic reactivity was examined to stepwise increases in intraluminal pressure from 10 to 100 mm Hg. Mean arterial pressure was decreased from 80 +/- 15 prior to CPB to 55 +/- 4 mm Hg (P < 0.01) 15 min after CPB. Myogenic contraction was observed in control vessels and was markedly attenuated by the protein kinase C inhibitor staurosporine (P < 0.01). CPB decreased myogenic contraction and shifted the pressure-diameter relation upward, suggesting a decrease in the intrinsic tone (both P < 0.05 vs control). CPB reduced contractile responses to the alpha 1-adrenoceptor agonist phenylephrine from -43 +/- 7% to -23 +/- 5% (P < 0.01) and the protein kinase C activator 12-deoxyphorbol 13-isobutyrate 20-acetate (phorbol ester) from -64 +/- 6% to -38 +/- 16% (P < 0.01). CPB-associated decrease in myogenic reactivity of skeletal muscle arterioles is likely due to alterations in protein kinase C and/or downstream signal transduction. This may account in part for reduction in systemic vascular resistance and hypotension associated with CPB.

Adrenergic alpha-Agonists↗
PubMed1997

Predictors of CABG within one year of successful PTCA: a retrospective, case-control study.

BACKGROUND: We previously have established characteristics predictive of the need for coronary artery bypass grafting (CABG) over many years after successful percutaneous transluminal coronary angioplasty (PTCA). In this study, we examined the factors associated with the need for CABG within 1 year of successful PTCA, and the recent impact of newer, catheter-based technologies. METHODS: From January 1982 through December 1995, 234 patients underwent CABG within 1 year of a successful "index" PTCA at our hospital. Emergency operations within 12 hours of index PTCA were excluded. These cases were matched with 234 controls who underwent a successful index PTCA but did not require a subsequent CABG during the next year. Cases were matched by the date of their index PTCA, and 1-year follow-up was complete for all patients. RESULTS: Before index PTCA there were no differences between the groups in terms of age, sex, diabetes, prior myocardial infarction, ejection fraction, duration of anginal symptoms, hypertension, hyperlipidemia, family history, or obesity (all nonsignificant). At index PTCA the cases had a greater mean number of lesions measuring 70% or greater compared with the controls (2.8 versus 1.8, respectively; p < 0.0001). The cases were more likely to have critical (70% or greater) proximal left anterior descending artery, proximal first obtuse marginal artery, and right posterior descending artery stenoses. The use of stents or atherectomy devices was not significantly more common among the controls (21% of controls versus 17.1% of cases; p = 0.35). Complete revascularization was achieved in significantly fewer of the cases than the controls (91 versus 156, respectively; p < 0.0001). The cases underwent CABG at a mean of 3 months (86% within 6 months) after PTCA. Among those who had a diagnostic catheterization, 52% of the patients had both restenosis of a dilated lesion and progression of other disease. Only 5 of 75 patients who had restenosis of a dilated lesion had a stent or an atherectomy device used at index PTCA. Of note, 13% (30 of 234) required an emergency operation, with an overall operative mortality rate of 3% (7 of 234). CONCLUSIONS: Although the likelihood of local restenosis is decreased by newer interventional techniques, the need for CABG within 1 year after successful PTCA is not diminished. The number of critical lesions and their location are the best predictors of the need for early CABG. If early post-PTCA CABG is to be avoided, patients who cannot be completely revascularized by PTCA should be revascularized by CABG.

Angioplasty, Balloon, Coronary↗
PubMed1997

Cardiopulmonary bypass alters vasomotor regulation of the skeletal muscle microcirculation.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with alterations in the regulation of organ perfusion and vascular permeability. The purpose of this study was to examine the effects of hypothermic CPB on the regulation of the skeletal muscle microcirculation and the modulating influence of the priming solution. METHODS: Sheep were placed on hypothermic CPB with a prime of either Pentastarch hydroxylethyl starch (HS) solution (n = 7), a solution in which HS is conjugated with deferoxamine (n = 7), or Ringer's lactate solution (n = 7). Sheep were placed on hypothermic CPB (27 degrees C) for 90 minutes while the heart was protected with cold blood cardioplegia. Sheep were then separated from CPB and perfused for an additional 3 hours off CPB. Hemodynamics and total water content were measured. RESULTS: In vitro relaxation responses of gracilis muscle arterioles (70 to 180 microns) to the endothelium-dependent agent acetylcholine, the endothelium-independent cyclic GMP-mediated vasodilator sodium nitroprusside, the beta-adrenergic agonist isoproterenol, and the adenylate cyclase activator forskolin were studied. No statistically significant hemodynamic differences were observed between groups. However, weight gain was significantly less when the priming solution was HS or HS-deferoxamine compared to when Ringer's lactate was used. Skeletal muscle arteriolar relaxations to the endothelium-dependent vasodilator acetylcholine and the beta-adrenergic agonist isoproterenol were impaired after CPB in the HS and Ringer's lactate groups. Acetylcholine response was preserved in the HS-deferoxamine group, whereas the response to isoproterenol remained impaired. The responses to sodium nitroprusside and forskolin were similar in all groups. CONCLUSIONS: Skeletal muscle microvascular endothelium-dependent relaxation and beta-adrenergic relaxation are reduced after CPB using either a crystalloid or HS prime. Skeletal muscle microvascular endothelial dysfunction may be attributable to oxygen-derived free radical-mediated injury, whereas altered beta-adrenergic regulation is attributable to mechanisms other than the generation of oxygen-derived free radicals during CPB.

Acetylcholine↗
PubMed1997

Rats reared in social isolation show schizophrenia-like changes in auditory gating.

Central sensory filtering processes can be demonstrated using a paired stimulus paradigm. Normal humans show a diminished vertex-recorded midlatency auditory-evoked potential to the second of paired clicks (0.5 s apart), a phenomenon termed auditory gating. Schizophrenics routinely fail to suppress the response to the second stimulus; thus, they do not gate. Previous animal studies of auditory gating have used psychotomimetic drug administration to induce a schizophrenia-like loss. However, a nonpharmacologic model of deficient gating would be advantageous. Isolation rearing of weanling rats produces impaired prepulse startle inhibition similar to that observed in schizophrenics. The present studied examined the effects of rearing status upon auditory gating. Male Sprague-Dawley rats raised in social isolation (ISO) were compared to socially raised rats (SOC). Across 10 baseline recording sessions, SOC rats showed substantial gating, while ISO rats failed to gate. Abnormal auditory gating is transiently normalized by nicotine, but not haloperidol, in schizophrenics. ISO rats given nicotine bitartrate showed gating in the normal range for 60 min. By contrast, haloperidol failed to normalize gating in ISO rats. Thus, isolation rearing of weanling rats appears to produce a stable schizophrenia-like gating deficiency that shows the same pattern of response to pharmacological interventions.

Acoustic Stimulation↗
PubMed1997

Cutaneous closure after cardiac operations: a controlled, randomized, prospective comparison of intradermal versus staple closures.

OBJECTIVE: To determine the difference in wound complication and infection rates between suture and staple closure techniques applied to clean incisions in coronary bypass patients. BACKGROUND: The true incidence of postoperative wound complications, and their correlation with closure techniques, has been obscured by study designs incorporating small numbers, retrospective short follow-up, uncontrolled host factors, and narrowly defined complications. METHODS: Sternal and leg wounds were studied prospectively, each patient serving as his or her own control. Two hundred forty-two patients with sternal and saphenous vein harvest wounds had half of each wound closed with staples and the other half with intradermal sutures (484 sternal and 516 leg segments). Wound complications were defined as drainage, erythema, separation, necrosis, seroma, or infection. Infections were identified in the subset having purulent drainage, antibiotic therapy, or debridement. Wounds were examined at discharge, at 1 week after discharge, and at 3 to 4 weeks after operation. Patient preferences for closure type were assessed 3 to 4 weeks after operation. RESULTS: Neither leg nor sternal wounds had a statistically significant difference in infection rate according to closure method (leg sutured = 9.3% vs. leg stapled = 8.9%; p = 0.99, and sternal sutured = 0.4% vs. sternal stapled = 2.5%; p = 0.128). There was, however, a greater complication rate in stapled segments (leg stapled = 46.9% vs. leg sutured = 32.6%; p = 0.001, and sternal stapled = 14.9% vs. sternal sutured = 3.7%; p = 0.00005). Sutures were favored over staples among patients who expressed a preference (sternal = 75.6%, leg = 74.6%). CONCLUSIONS: With the host factors controlled by pairing staples and sutures in each patient, we demonstrated a similar incidence of infection but a significantly lower incidence of total wound complications with intradermal suture closure than with staple closure.

Aged↗
PubMed1997

Inhibitory effects of 12-O-tetradecanoylphorbol-13-acetate on dye leakage from single Novikoff cells and on dye transfer between reaggregated cell pairs.

The inhibitory effects of 12-O-tetradeconylphorbol-13-acetate (TPA) on the Lucifer Yellow leakage in single (nondissociated and dissociated) Novikoff cells in the presence of ethyleneglycotetraacetic acid (EGTA) and transfer between reaggregated cell pairs were investigated. Under treatment with TPA, single Novikoff cells showed inhibition of the dye leakage in the presence of EGTA, especially after 60-min treatment. There were only slight differences between nondissociated and dissociated cells in these experiments. The dye transfer in reaggregated cell pairs were significantly inhibited after 30-min treatment with TPA. In pretreatment with TPA during the recovery period of reaggregation the dye transfer in cell pairs was completely blocked. It was suggested that TPA blocks the assembly of gap junction, while it had no remarkable effect on gating mechanism of the hemichannels.

Animals↗
PubMed1996

Effects of pentastarch-deferoxamine conjugate on lung injury after cardiopulmonary bypass.

BACKGROUND: Oxygen-derived free radicals have been implicated in the pathogenesis of lung injury and endothelial dysfunction after cardiopulmonary bypass (CPB). We examined the effects of priming the CPB pump with a low-molecular-weight hydroxyethyl starch pentastarch (PS) solution, PS conjugated to the iron chelator deferoxamine (DFO), or lactated Ringer's solution alone (LR) on lung injury parameters and skeletal microvessel relaxation responses. METHODS AND RESULTS: Sheep were placed on hypothermic CPB with a prime of PS (n = 8), PS-DFO (n = 8), or LR (n = 8). A 60-minute period of cardioplegia-ischemia was followed by rewarming, separation from CPB, and 2 hours of post-CPB monitoring. Hemodynamics, oxygenation, pulmonary lymph flow, lymph protein clearance, and total body weight were measured. Right and left atrial blood samples were obtained simultaneously for white blood cell and platelet counts. No statistically significant hemodynamic or oxygenation differences were found between groups. Lymph flow was increased after CPB but significantly more in the LR group (264.6 +/- 45%, P < .05) compared with PS-DFO (126.6 +/- 22%) or PS (120.9 +/- 25%). Increases in lymph protein clearance and weight gain were significantly less with PS and PS-DFO compared with LR (P < .05). CONCLUSIONS: The oncotic agent PS ameliorates lung derangements seen after CPB compared with that seen with an LR prime, and no significant additional pulmonary benefit was demonstrated with PS conjugated to the oxygen-derived free radical scavenger DFO.

Animals↗
PubMed1996

Gap junction formation between cultured embryonic lens cells is inhibited by antibody to N-cadherin.

Intercellular communication mediated by gap junctions is important for tissue homeostasis in the avascular lens, and extensive areas of gap junctions form between fiber cells during fiber cell differentiation and lens development. We examined the role of the calcium-dependent cell adhesion molecule, N-cadherin, in the process of gap junction formation between fiber cells. Lentoids, multicellular structures with characteristics of differentiated fiber cells, were isolated from embryonic chick lens cultures and subsequently paired to provide an in vitro model of fiber cell interactions. Gap junction formation between cells of paired lentoids was monitored by observing the lentoid-to-lentoid transfer of fluorescent dyes, either calcein or Lucifer yellow, over a time course of up to 48 hr. Dye transfer between lentoids was inhibited upon the addition to the medium of Fab fragments (100-622 microgram/ml) of a monoclonal antibody specific for N-cadherin, and also by the reduction of extracellular calcium in the incubation medium. However, the addition of Fab fragments (100-1500 microgram/ml) of an antibody to a fiber-cell-specific integral membrane protein, MIP, did not change the time course nor extent of dye transfer between lentoids. Our results, using cultured embryonic cells, extend those from previous studies with cell lines and transfected cells. We conclude that cadherin interactions facilitate the formation of gap junctions between embryonic lens fiber cells, by the stabilization of membrane appositions and/or by the generation of an intracellular signal(s).

Animals↗
PubMed1996

Dissociation of phospholamban regulation of cardiac sarcoplasmic reticulum Ca2+ATPase by quercetin.

Quercetin had a biphasic effect on Ca2+ uptake and calcium-stimulated ATP hydrolysis in isolated cardiac sarcoplasmic reticulum (SR). Stimulation of Ca2+ATPase was observed at low quercetin concentrations (<25 microM) followed by inhibition at higher concentrations. The effects were dependent upon the SR protein concentration, the MgATP concentration, and intact phospholamban regulation of cardiac Ca2+ATPase. Only the inhibitory effects at higher quercetin concentrations were observed in skeletal muscle SR which lacks phospholamban and in cardiac SR treated to remove phospholamban regulation. Stimulation was additive with monoclonal antibody 1D11 (directed against phospholamban) at submaximal antibody concentrations; however, the maximal antibody and quercetin stimulation were identical. Quercetin increased the calcium sensitivity of the Ca2+ATPase like that observed with phosphorylation of phospholamban or treatment with monoclonal antibody 1D11. In addition, low concentrations of quercetin increased the steady-state formation of phosphoenzyme from ATP or Pi, but higher quercetin decreased phosphoenzyme levels. Quercetin, even under stimulatory conditions, was a competitive inhibitor of ATP, but appears to relieve the Ca2+ATPase from phospholamban inhibition, thereby, producing an activation. The subsequent inhibitory action of higher quercetin concentrations results from competition of quercetin with the nucleotide binding site of the Ca2+ATPase. The data suggest that quercetin interacts with the nucleotide binding site to mask phospholamban's inhibition of the SR Ca2+ATPase and suggests that phospholamban may interact at or near the nucleotide binding site.

Animals↗
PubMed1996

Lipid differentiation in MP26 junction enriched membranes of bovine lens fiber cells.

The present study was undertaken to address the question whether lipid differentiation occurs in junctional domains which could imply a functional requirement for specific lipids in junctional structures. Junction enriched membranes were isolated from bovine lens fiber cells using Tris and urea treatment, and the presence of junctional structures was ascertained by electron microscopy. Enrichment in major intrinsic protein (MIP, MP26) was monitored by SDS polyacrylamide gel electrophoresis. Junctional lipids were extracted by a modified Folch procedure, to quantitatively recover cholesterol, and lipid classes were analyzed. While 99.5% of total lens protein was solubilized in the course of junction isolation, 43.9% of cell phospholipids (PL) and 64.1% of cell cholesterol (Chol) were conserved. Cholesterol was by far the predominant lipid in the junction enriched lens fiber cell membranes (833 nmol/mg protein) and was more abundant than all phospholipids combined (682 nmol/mg protein). In isolating the junctional membranes, cholesterol levels increased 144-fold, and average phospholipid levels increased 99-fold, which resulted in an increase in Chol/PL ratio from 0.84 to 1.22. Different phospholipids showed substantially different degrees of enrichment with highest enrichments seen for the phosphatidylethanolamine fraction (152-fold) and sphingomyelin (101-fold). Thus, the phospholipids of the junction enriched membranes consisted mainly of ethanolamine glycerophospholipids (37.3%) and sphingomyelin (28.6%), with lesser amounts of choline glycerophospholipids (23.5%) and phosphatidylserine (9.2%) present. Our data suggest that the MP26 junction enriched membranes of bovine lens fiber cells contain differentiated lipid domains, and that cholesterol, ethanolamine glycerophospholipids and sphingomyelin are the prevalent boundary lipids of the major intrinsic protein in these domains.

Animals↗
PubMed1996

Expression of zebrafish connexin43.4 in the notochord and tail bud of wild-type and mutant no tail embryos.

Communication via gap junctions provides a mechanism for the cell-cell transfer and coordination of developmental signals. The spatial restriction of gap junctions may also serve to organize cells into domains of coordinated behavior. To investigate the role of gap junctions during embryogenesis, we have characterized the expression of a member of the gap junction gene family, zebrafish connexin43.4, a homolog of connexin45 in chicken and mammals. Expression of connexin43.4 was induced in the early gastrula, coincident with the first definitive assignments of axial cell fate and the onset of the cell movements comprising convergence and extension in zebrafish. In situ hybridization and immunohistochemistry revealed that during gastrulation connexin43.4 mRNA and protein were progressively enriched in the germ ring and in the notochord primordia on the dorsal side of the embryo. Later in development connexin43.4 expression was detected in the notochord, the paraxial mesoderm, and the tail bud but was not observed after the differentiation of these tissues. In no tail mutant embryos which are defective in tail formation and proper morphogenesis of the notochord, connexin43.4 expression was absent during gastrulation from the caudal embryonic shield and notochord primordia. During somite stages in no tail embryos, connexin43.4 expression remained absent in the notochordal precursor cells and was lost in the tail bud. Thus, the no tail gene product, a transcription factor, was required for the expression of connexin43.4 in both the notochord and tail bud during morphogenesis. By microinjection of mRNA coding for a connexin43.4/green fluorescent protein fusion in the 1-cell zebrafish embryo, we showed that connexin43.4 is capable of assembling into structures reminiscent of gap junctions. The progressively restricted, developmental expression of the zebrafish connexin43.4 gene suggests that this gap junctional protein participates in the coordination of gastrulation and the formation of the notochord and tail.

Animals↗
PubMed1996

Neointimal thickening after severe coronary artery injury is limited by a short-term administration of a factor Xa inhibitor. Results in a porcine model.

BACKGROUND: Fibrin- and platelet-rich thrombus formations occur as the initial event after percutaneous transluminal coronary angioplasty. We therefore tested the hypothesis that short-term administration of the recombinant tick anticoagulant peptide (rTAP), a factor Xa inhibitor, would reduce the thickness of neointima at 28 days after injury in a porcine coronary balloon angioplasty model. METHODS AND RESULTS: Continuous intravenous infusion of rTAP (average dose, 194 micrograms . kg-1 . min-1) or placebo (vehicle only) was given to the study pigs for 60 hours. The goal of anticoagulation was to maintain the activated clotting time at 200 seconds. A central venous catheter was inserted 2 days before the procedure. On the day of coronary injury, the animals were administered boluses of rTAP (6.5 mg) and then underwent injury with an oversized metallic coil by standard methods in the right, circumflex, or left anterior descending coronary artery. No significant difference in vascular injury between rTAP and vehicle control was observed after euthanasia at 28 days. Significantly less neointimal thickening occurred in the rTAP-treated animals (thickness, mean +/-SD: 0.30 +/-0.08 mm) compared with the control (0.48 +/- 0.12 mm, P< .001). CONCLUSIONS: The specific factor Xa inhibitor rTAP, when given in fully anticoagulant doses for a short duration after coronary artery injury in the porcine model, resulted in a long-term decrease in neointimal thickness. These results implicate thrombin generation in neointimal formation and suggest that administration of a potent antithrombotic for several days immediately after the procedure may influence the long-term outcome of the coronary injury with a decrease in neointimal formation.

Angioplasty, Balloon, Coronary↗