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Biomedical subjects

B Cercek

Publications and source records attributed to B Cercek.

At least 55 records · Page 3Linked to original sources
PubMed1996

Effect of External Ultrasound Frequency on Thrombus Disruption In Vitro.

Objectives: This in vitro study assesses the effect of different external ultrasound frequencies on the disruption of human thrombi. Background: Ultrasound energy has been shown to disrupt human thrombi in vitro. However, there have been no previous studies to assess the effect of a range of different ultrasound frequencies on the rate and extent of thrombus disruption. Methods: In vitro, we exposed 56, 1- to 3-hour-old human blood thrombi to continuous wave ultrasound (2.9 W/cm2) for 3 minutes. Seven different frequencies, ranging from 243 kHz to 25 kHz, were used. Results: There was a gradual increase in the total reduction of thrombus weight as well as the percent thrombus disruption with the use of lower ultrasound frequencies, reaching 99% at 25 kHz (p < 0.001) and 86% (p < 0.001) at 39 kHz, compared with 25% at 243 kHz. The average particle size of the disrupted thrombi was 3.26 µm (range 2.8-3.8). Conclusions: Our in vitro data with external ultrasound show that for a given power intensity of ultrasound, the extent and magnitude of thrombus disruption is progressively increased as frequencies decrease from 243 to 25 kHz. This might be related to the fact that larger acoustic bubbles are induced by lower frequency ultrasound, which gives rise to greater mechanical energy for thrombus disruption during bubble vibration and their collapse.

Journal Article↗
PubMed1996

Autocrine induction of DNA synthesis by mechanical injury of cultured smooth muscle cells. Potential role of FGF and PDGF.

To determine whether replication of arterial smooth muscle cells (SMCs) in response to mechanical injury would occur in the absence of serum and other cells, we created an in vitro model in which confluent, growth-arrested cultures of rat SMCs were injured by gentle pressure of a soft plastic tube and then kept in serum-free medium for up to 4 days. Replication of SMCs in and around the injury, as measured by tritiated thymidine incorporation, was noted within 24 hours and peaked at 48 hours after injury, whereas noninjured cells remained quiescent. An increased expression of platelet-derived growth factor (PDGF) A mRNA, noted 6 hours after injury, was followed by an increased PDGF AA immunoreactivity in SMCs in and around the zone of injury at 24 and 48 hours after injury. A PDGF A chain antisense oligonucleotide inhibited 87.0 +/- 4.0% (P < .005) of SMC replication in the injury zone, whereas the corresponding sense oligonucleotide reduced SMC replication by only 37.2%. An antibody to fibroblast growth factor (FGF) almost completely inhibited SMC replication in the injured zone, whereas an antibody to PDGF AA was without effect. Incubation of SMCs with FGF increased PDGF A mRNA levels in SMCs, and 5 mumol/L PDGF A antisense oligonucleotides reduced FGF-induced SMC replication by 62%. Taken together, these results demonstrate that injured rat SMCs in culture release FGF that activates DNA synthesis of neighboring SMCs both by a direct mechanism and by stimulating the production of PDGF AA.

Animals↗
PubMed1996

Active oxygen species and lysophosphatidylcholine are involved in oxidized low density lipoprotein activation of smooth muscle cell DNA synthesis.

It has recently been shown that oxidative modification of LDL enhances the mitogenic effect of LDL on smooth muscle cell (SMC) DNA synthesis. However, because of its complex chemical structure, the mitogenic components have not been well characterized. Exposure of LDL to the oxidant Cu2+ is followed by a rapid accumulation of peroxides that peaks after 8 to 12 hours and a conversion of the phospholipid phosphatidylcholine into lysophosphatidylcholine that continues for up to 48 hours. Most of the mitogenic activity is formed during the first 4 hours of oxidation. Both superoxide dismutase and catalase effectively inhibit the mitogenic activity of oxidized LDL, suggesting involvement of reactive oxygen intermediates. In the presence of 1% serum, low concentrations of hydrogen peroxide activated SMC DNA synthesis in a dose-dependent manner, with a maximal effect at a concentration of 200 mumol/L, whereas higher concentrations were inhibitory. Lysophosphatidylcholine also enhanced SMC DNA synthesis, with a maximal stimulation at a concentration of 10 mumol/L. Oxysterols, which also accumulate in oxidized LDL, effectively inhibited DNA synthesis. These results demonstrate that oxidation of LDL is associated with formation of several substances affecting the growth of SMCs. Among these substances, low levels of reactive oxygen intermediates and lysophosphatidylcholine stimulate DNA synthesis, whereas at a higher concentration they, as well as oxysterols, are inhibitory.

Cells, Cultured↗
PubMed1996

Effect of immunization with homologous LDL and oxidized LDL on early atherosclerosis in hypercholesterolemic rabbits.

Although the existence of an immune response against modified lipoproteins in atherosclerosis has been observed in experimental animals as well as in humans, the precise pathophysiological relevance of these findings remains unclear. In this study we determined the effect of an immunization with homologous LDL and copper-oxidized LDL on the formation of atherosclerotic plaque in hypercholesterolemic rabbits. Immunizations were performed at the start of a cholesterol-rich diet and 3 weeks later. After 16 weeks, antibodies against oxidized LDL had developed in rabbits given hypercholesterolemic diet alone, but the titers were increased by twofold in rabbits immunized with oxidized LDL as well as in rabbits immunized with LDL, suggesting that the LDL had also become oxidized during the preparation and/or immunization procedure. Immunization with LDL and oxidized LDL reduced atherosclerotic lesions in the proximal aorta by 74% (P < .05) and 48% (P = NS), respectively. The cellular composition of the lesions was not affected by the immunizations. These results support the hypothesis that an immune response against modified LDL has a protective effect against the development of early atherosclerotic lesions.

Animals↗
PubMed1996

Regulated expression of the ets-1 transcription factor in vascular smooth muscle cells in vivo and in vitro.

Ets-1 regulates the transcription of several genes encoding extracellular matrix proteins (ie, osteopontin and tenascin) as well as enzymes involved in degradation and remodeling of the extracellular matrix (ie, stromelysin and urokinase plasminogen activator). In the present study, we investigated the regulation of c-ets-1 in cultured rat vascular smooth muscle cells as well as in the arterial wall after balloon injury in vivo. Serum-starved smooth muscle cells exposed to serum for various time points express a major c-ets-1 mRNA transcript of 5.3 kb and minor bands of 4.0 and 2.5 kb with a peak at 2 hours after stimulation. These effects were concentration dependent. Western blotting revealed an increase in 55- and 40-kD immunoreactive ets-1 proteins in cells treated with serum for 2 hours, and binding to an oligonucleotide containing the ets-1 consensus cis-acting motif was demonstrated by electrophoretic mobility shift assay. Ets-1 mRNA abundance was induced with a peak at 2 hours after stimulation with platelet-derived growth factor-BB and with angiotensin II. There was a distinct increase of ets-1 immunoreactivity in the inner layer of the media 2 hours after balloon catheter injury of rat arteries, which declined after 6 hours and returned to the basal level 1 day after vessel wall damage. Arterial c-ets-1 mRNA content was induced with an identical time course. These findings suggest that c-ets-1 may be of importance in the mitogenic signaling pathway of smooth muscle cells grown in culture. In addition, ets-1 may play a role in the activation of smooth muscle cells in vivo after mechanical injury of the vessel wall. Because the ets-1 transcription factor activates the gene expression of a number of mRNA species involved in matrix deposition and degradation, these data are compatible with a role for ets-1 in vascular remodeling and/or cell migration.

Animals↗
PubMed1995

Incomplete recanalization as an important determinant of Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolytic therapy for acute myocardial infarction. TEAM Investigators. Thrombolytic Trial of Eminase in Acute Myocardial Infarction.

The outcome of patients with Thrombolysis in Myocardial Infarction (TIMI) trial grade 2 flow is worse than that of patients with TIMI grade 3 flow after thrombolytic therapy for acute myocardial infarction. It is unclear whether TIMI grade 2 flow represents incomplete recanalization of the culprit lesion or poor distal runoff. The Thrombolytic Trial of Eminase (anistreplase) in Acute Myocardial Infarction (TEAM)-2 and TEAM-3 were randomized trials comparing anistreplase with streptokinase (TEAM-2, n = 370) or with alteplase (tissue plasminogen activator) (TEAM-3, n = 325). We compared the minimal luminal diameter of the culprit lesion in patients with TIMI grade 2 flow with that in patients with TIMI grade 3 flow both 90 minutes (TEAM-2) and 1 day (TEAM-3) after thrombolysis. Patients with TIMI grade 2 flow had a lower residual luminal diameter in the culprit lesion than patients with TIMI grade 3 flow (TEAM-2, 0.58 +/- 0.03 vs 0.79 +/- 0.02 mm, p = 0.0001; TEAM-3, 0.88 +/- 0.04 vs 1.17 +/- 0.03 mm, p = 0.0001, for patients with TIMI grades 2 and 3 flow). Residual percent stenosis was correspondingly higher in patients with TIMI grade 2 flow. At the early angiogram, 66% of patients with TIMI grade 2 flow, but only 35% of those with TIMI grade 3 flow, had a minimal luminal diameter of 0.6 mm (positive predictive value 87%, negative predictive value 35%). Incomplete recanalization of the culprit lesion may thus be an important determinant of TIMI grade 2 flow after thrombolysis. Whether more complete thrombolysis or rescue angioplasty improves outcome in these patients deserves evaluation.

Analysis of Variance↗
PubMed1995

VCL, an antagonist of the platelet GP1b receptor, markedly inhibits platelet adhesion and intimal thickening after balloon injury in the rat.

BACKGROUND: Arterial injury is immediately followed by platelet adhesion at the site of injury, a process that requires the interaction of subendothelial von Willebrand factor with the platelet GP1b receptor. VCL, a recombinant von Willebrand factor GP1b binding domain, inhibits platelet binding to von Willebrand factor. The aim of this study was to determine whether VCL inhibits platelet adhesion at the site of arterial injury and affects neointimal thickening after injury in rats. METHODS AND RESULTS: Sprague-Dawley rats were randomized to receive VCL, 4 mg/kg bolus followed by a continuous infusion of 2 mg.kg-1.h-1 for 72 hours, or an identical volume of saline. Balloon injury of the femoral artery was performed 15 minutes after the initial bolus injection of VCL. Scanning electron microscopy performed 1 and 3 days after injury indicated that VCL-treated rats had > 80% reduction in the number of platelets adherent to the vessel wall at the site of injury compared with controls (P < .003). Histological examination at day 14 showed that, compared with controls, VCL-treated rats had a 60% reduction in the intima-media ratio (0.21 +/- 0.03 versus 0.53 +/- 0.06, P = .001) and a reduced luminal area stenosis (12 +/- 3% versus 38 +/- 10%, P = .04). At 28 days after injury, there was no rebound of neointimal thickening in VCL-treated rats (intima-media ratio, 0.19 +/- 0.04; luminal stenosis, 17 +/- 5%). The difference between VCL-treated rats and control rats persisted but was attenuated (intima-media ratio, 0.19 +/- 0.04 versus 0.28 +/- 0.1, P = .162; luminal stenosis, 17 +/- 5% versus 31 +/- 5%, P = .058) as neointimal thickening regressed in untreated rats. With the use of proliferating cell nuclear antigen immunohistochemistry on day 3, VCL had no effect on smooth muscle cell (SMC) proliferation. CONCLUSIONS: Antagonism of the platelet GP1b receptor by VCL profoundly decreased platelet deposition at the site of balloon injury in the rat femoral artery. This effect was associated with a persistent reduction in neointimal thickening. The lack of effect of VCL on SMC proliferation suggests that the decrease in neointimal thickening may have been mediated through inhibition of SMC migration and/or modulation of the extracellular matrix.

Angioplasty, Balloon↗
PubMed1995

How do smokers differ from nonsmokers in their response to thrombolysis? (the TIMI-4 trial)

Smokers with acute myocardial infarction appear to have a better outcome after thrombolysis than do nonsmokers. To identify factors that could contribute to this curious finding, we analyzed data from the Thrombolysis in Myocardial Infarction (TIMI-4) trial, in which 382 patients with acute myocardial infarction were randomized to tissue plasminogen activator, anistreplase, or both. Coronary angiography was performed 90 minutes and 18 to 36 hours after randomization, a myocardial perfusion scan was performed at 18 to 36 hours and before discharge, and a radionuclide ventriculogram was obtained before discharge. Angiographic and clinical outcome variables were determined in current smokers, ex-smokers, and nonsmokers, and regression analysis was used to correct for differences in baseline characteristics. The in-hospital mortality of current smokers was lower than that of ex-smokers and nonsmokers: 2.3% versus 5.2% versus 7.0%, respectively (p = 0.04 by paired comparison, current vs nonsmokers). Ninety minutes after randomization, the incidence of TIMI grade 3 flow was significantly higher in smokers than in ex-smokers and nonsmokers (55% vs 43% and 45%, p = 0.02); this difference was no longer observed at the second angiogram, nor did smokers differ from nonsmokers with respect to residual stenosis, thrombus grade, infarct size, ejection fraction, or recurrent ischemia. Because a strong inverse relation exists between TIMI grade 3 flow at 90 minutes and mortality, our findings suggest that the lower mortality of current smokers after thrombolytic therapy may be related to a higher incidence of early, complete reperfusion.

Double-Blind Method↗
PubMed1995

Thrombolytic Therapy for Acute Myocardial Infarction in Patients with Prior Coronary Bypass Surgery: Results from the Thrombolysis in Myocardial Infarction (TIMI) 4 Trial.

Little data exist on the value of intravenous thrombolysis for acute myocardial infarction in patients with previous coronary bypass surgery. The Thrombolysis In Myocardial Infarction (TIMI) 4 trial was a randomized study comparing tissue plasminogen activator, anistreplase, or a combination in patients with evolving myocardial infarction; patients with previous coronary bypass surgery were not excluded. Coronary angiography was performed 90 minutes and 18-36 hours after randomization, a myocardial perfusion scan was performed at 18-36 hours and predischarge, and a radionuclide ventriculogram was obtained predischarge. Angiographic and clinical outcome variables were determined in patients with and without a history of coronary bypass surgery. A total of 416 patients were randomized and 13 of them had previous bypass surgery; of these, 6 had an occluded vein graft as the infarct-related vessel. The incidence of TIMI grade 3 flow at 90 minutes was lower in patients with previous coronary surgery as compared with controls (42% vs. 49%), and overall patency was significantly lower (50% vs. 77%, p = 0.04). This trend persisted at 18-36 hours after randomization. Furthermore, patients with previous coronary surgery had more thrombus in their infarct-related arteries, especially with occlusion of a vein graft (83% vs. 32%, p = 0.04) and higher rates of recurrent ischemia (15% vs. 8%) and recurrent infarction (23% vs. 5%, p = 0.03) than controls. Thus, in patients with previous coronary bypass surgery intravenous thrombolysis yields results that are inferior to those achieved in patients without such a history and alternative methods of reperfusion should be considered.

Journal Article↗
PubMed1995

Balloon catheterization induced arterial expression of embryonic fibronectins.

Fibronectins (FNs) comprise a family of adhesive extracellular matrix proteins that arise by alternative splicing in three regions: V (IIICS), EIIIA (ED-A), and EIIIB (ED-B). FNs bearing the EIIIA and EIIIB segments are prevalent during embryogenesis, expressed to lesser degrees in normal adult tissues, and may be locally reexpressed at adult tissue injury. RNase mapping shows that normal rat arteries express low levels of FNs that are predominantly EIIIA- and EIIIB-. Following balloon injury, arterial walls produce increased total levels of FN transcripts that preferentially include both the EIIIA and EIIIB segments. However, despite inducing increased total FN mRNA, balloon injury does not alter the relative composition of V120+, V95+, AND V0 spliced forms. In situ hybridization reveals that as early as 4 days after injury medial cells express increased total FN mRNA, and by 7 days substantial neointimal and focal medial synthesis of EIIIA+, EIIIB+, and V120+ FNs occurs; macrophages do not significantly contribute to this observed vascular FN synthesis. Consistent with the mRNA data, immunofluorescence microscopic analysis reveals increased deposition of EIIIB+ and V+ FN protein forms in injured arterial walls, particularly within the neointima. Our results suggest that local synthesis of specific FN isoforms is important to the neointimal formation that ensues after balloon injury.

Alternative Splicing↗
PubMed1995

A DNA probe study on the origin of the cancer recognition, immunedefense suppression and serine protease protection peptide.

A quantitative "two DNA probe" dot blot hybridization assay, using chemiluminescence detection, was used to distinguish between the mRNA and DNA coding for the cancer recognition, immunedefense suppression, and serine protease protection (CRISPP) peptide, and the partially homologous C-terminal end sequence of the alpha1-PI. In cancer cells, there is up to 2.4 times more mRNA and up to 6.3 times more DNA coding for the CRISPP peptide than for the homologous alpha1-PI in their normal cell counterparts. This corroborates results of the "two antibody" immunoassay, which showed that cancer cells produce the CRISPP, peptide in addition to alpha1-PI molecules. The amplified transcription of the CRISPP peptide DNA could be the result of derepression and/or translocation of an inherited, or acquired, heritable damage to the DNA in the exon V of the alpha1-PI gene. Expression of the CRISPP peptide mRNA and DNA is SV40 transformed cells could indicate that a viral transduction causes the amplified transcription of a mutated exon V of the alpha1-PI gene and/or loss of a specific suppressor gene. The CRISPP peptide with its multiple, cancer-promoting biological effects may qualify as a product of a novel, as yet unidentified, oncogene. The detection of the CRISPP peptide DNA regions, using the two DNA probe, or some other suitable methods, might be a useful adjunct in cancer diagnosis of biopsies and/or in predictive diagnosis of familial cancers.

Base Sequence↗
PubMed1995

Effect of the cancer recognition, immunedefense suppression, and serine protease protection peptide on DNA synthesis in rat hepatocytes and human lymphocytes.

The cancer recognition, immunedefense suppression, and protease protection (CRISPP) peptide produced by cancer cells enhanced DNA synthesis in primary cultures of rat hepatocytes and in human peripheral blood lymphocytes. In 72-h hepatocyte cultures, increasing doses of the CRISPP peptide increased DNA synthesis, as judged by 3H-thymidine incorporation, from 35.2% above the peak incorporation value observed when the hepatocytes are induced to undergo DNA synthesis by 10 ng/ml of EGF when 0.01 ng/ml of the CRISPPS peptide is used to 130.5% at 100 ng/ml of the peptide. The CRISPPS peptide also enhanced DNA synthesis in PHA stimulated human peripheral blood lymphocytes (HPBL) in 72-h cultures. A bell-shaped concentration dependence was observed in HPBL, with a maximum increase in 3H-thymidine uptake of 248% at 1 ng/ml of the CRISPPS peptide. The effect decreased to 26% at 100 ng/ml. The difference in the concentration dependence between hepatocytes and HPBL could be due to specific cell types and culture conditions, and/or to differences in the biochemical pathways leading to DNA synthesis as induced by EGF and PHA. Since the CRISPP peptide protects serine proteases against inhibition by the alpha 1-protease inhibitor, different biochemical pathways might require participation and/or timing of limited proteolytic controls to a different extent. In both cases, the protective effect of the CRISPP peptide could amplify and/or prolong the activities of the intracellular proteases involved in the mitogenic processes.

Animals↗
PubMed1994

Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits.

BACKGROUND: Several epidemiological studies have shown an inverse relation between high-density lipoprotein (HDL) cholesterol levels and coronary heart disease. Recently, observational studies have suggested a similar inverse relation between HDL and restenosis after coronary balloon angioplasty. Despite these observations, it is unclear whether this inverse relation reflects a direct vascular protective effect of HDL or apolipoprotein (apo) A-I, the major apolipoprotein component of HDL. Therefore, to determine whether HDL directly influences neointima formation, we investigated the effect of recombinant apo A-I Milano (apo A-I M), a mutant of human apo A-I with Arg-173 to Cys substitution, on intimal thickening after balloon injury in cholesterol-fed rabbits. METHODS AND RESULTS: Cholesterol feeding was initiated 18 days before injury and continued until the time of death. Eight rabbits received intravenous injections of 40 mg of apo A-I M linked to a phospholipid carrier on alternate days, beginning 5 days before and continuing for 5 days after balloon injury of femoral and iliac arteries. Eight rabbits received the carrier alone, and four received neither apo A-I M nor the carrier. Three weeks after balloon injury, apo A-I M-treated rabbits had significantly reduced intimal thickness compared with the two control groups (mean +/- SD): 0.49 +/- 0.29 versus 1.14 +/- 0.38 mm2 and 1.69 +/- 0.43 mm2, P < .002 by ANOVA). The intima-to-media ratio was also significantly reduced by apo A-I M (0.7 +/- 0.2 versus 1.5 +/- 0.5 and 2.1 +/- 0.1, P < .002 by ANOVA) compared with the two controls. The fraction of intimal lesion covered by macrophages, as identified by immunohistochemistry using macrophage-specific monoclonal antibody, was significantly less in apo A-I M-treated rabbits compared with carrier-treated animals (25.3 +/- 17% versus 59.4 +/- 12.3%, P < .005). Aortic cholesterol content, measured in an additional 10 rabbits, did not differ significantly between apo A-I M-treated animals (n = 5) and carrier-treated controls (n = 5). CONCLUSIONS: Apo A-I M significantly reduced intimal thickening and macrophage content after balloon injury in cholesterol-fed rabbits without a change in arterial total cholesterol content. Although the precise mechanism of action remains to be defined, these findings are consistent with a direct vascular effect of apo A-I, which could have potential therapeutic implications.

Animals↗
PubMed1994

Mechanical stimuli induce vascular parathyroid hormone-related protein gene expression in vivo and in vitro.

PTH-related peptide (PTHrP), the factor mediating the syndrome of humoral hypercalcemia of malignancy, is also expressed in smooth muscle cells (SMC) of the urinary bladder and uterus in response to mechanical distention and fetal occupancy, respectively. Vascular SMC also produce PTHrP, and its expression is induced by serum and vasoconstrictors, such as angiotensin-II. To determine whether mechanical distension affected vascular PTHrP gene expression, the abdominal aorta of adult male rats was balloon-distended, and aortae were collected at various times after the intervention. PTHrP mRNA was determined by competitive reverse transcriptase-polymerase chain reaction, using sequential dilutions of a cloned internally truncated PTHrP RNA fragment as standard. The molar concentration of PTHrP mRNA was obtained by extrapolating at a standard/wild-type band intensity ratio of 1:1. Aortic PTHrP mRNA was induced from a basal level of 19, to 22, 46, 36, 13, 12, 22, and 20 attamoles/mg total RNA 1, 2, 12, 24, and 48 h and 7 and 48 days after balloon distension, respectively. To determine whether mechanical events directly regulate vascular PTHrP gene expression, primary rat aortic SMC were plated and placed on a rocking device at 20 oscillations/min to create a gentle flowing motion of the culture medium. Rocking induced PTHrP mRNA of SMC exposed to either serum-free medium or 10% serum by 2.5-and 4.0-fold at 4 h, and 2.9- and 3.7-fold at 24 h, respectively. These effects were oscillation rate dependent, potentiated by angiotensin-II, and specific, as similar changes were not observed in alpha-actin mRNA content. Flow motion-induced PTHrP mRNA at 24 h was partially decreased by 10(-6) M colchicine (which inhibits microtubule assembly), but not by cytochalasin-E (which disrupts actin polymerization). As PTHrP is a known vasorelaxant, we propose that mechanical events induce the release of PTHrP by SMC, possibly to serve as a compliance factor or an agent for vascular remodeling.

Alkaloids↗
PubMed1993

Enhancement of thrombolysis by external ultrasound.

The purpose of our study was to assess the efficacy of external ultrasound to enhance in vitro thrombolysis with urokinase or streptokinase. One-hour-, 1-day-, 4-day-, and 6-day-old human blood thrombi (n = 366) were incubated in normal saline solution with three different concentrations of streptokinase (50, 250, and 2000 mu/ml) or urokinase (200, 2000, and 5000 mu/ml). Thrombi were exposed to pulsed ultrasound of 1 MHz at 1.0, 1.5 and 2.2 W/cm2 at different exposure times. The combination of ultrasound (2.2 W/cm2, 30 min) and urokinase or streptokinase enhanced lysis rate by an average of 25% compared with lysis with thrombolytic agents alone (p < 0.05). The enhancement was greater at higher ultrasound power outputs (2.2 W/cm2 > 1.5 W/cm2 > 1.0 W/cm2). At higher-power outputs there was no increase of temperature in the solution containing the thrombus. The extent of lysis was higher with longer ultrasound exposure time and with fresh thrombi. These data suggest that use of external ultrasound has the potential to increase both efficacy and rate of thrombolysis.

Combined Modality Therapy↗
PubMed1993

Angiographic validation of bedside markers of reperfusion.

OBJECTIVES: We sought to validate with coronary angiography several primary and ancillary markers of reperfusion. BACKGROUND: The availability of bedside markers of reperfusion is of major importance in the thrombolytic therapy of acute myocardial infarction. However, the reliability of current markers is still controversial. METHODS: Changes in chest pain, ST segment elevation and heart rate and rhythm were assessed every 5 to 10 min for up to 3 h after initiation of recombinant tissue-type plasminogen activator therapy in 82 patients with acute myocardial infarction. Coronary angiography was performed within 24 h. RESULTS: At angiography, 69 of the 82 patients had a patent infarct-related artery with Thrombolysis in Myocardial Infarction trial (TIMI) grade 3 flow and a rapid and progressive decrease in chest pain and ST elevation. The pain resolved in 24 +/- 23 min (range 3 to 50). The ST elevation decreased by > or = 50% within 16 +/- 14 min (range 5 to 41). Accelerated idioventricular rhythm developed in 49% of patients and sinus bradycardia in 23%; conduction abnormalities and atrial fibrillation resolved. All markers appeared in close temporal proximity to the onset of an abrupt increase in plasma creatine kinase (CK) and CK-MB isoenzyme activity, a previously validated marker of the time of reperfusion. Before its final resolution, ST elevation transiently decreased and increased in 58% of patients. Comparison of one pretreatment and one posttreatment electrocardiogram significantly reduced the reliability of ST segment change as a marker of reperfusion. In 13 of 82 patients, the infarct-related artery demonstrated TIMI grade < or = 2 flow; in 9, pain and ST elevation did not lessen and CK and CK-MB activity showed no abrupt increase. The remaining four patients initially demonstrated a decrease in pain and ST elevation; however, within 3 h and before angiography, the recurrence of pain and ST elevation suggested reocclusion. CONCLUSIONS: A rapid and progressive decrease in pain and ST elevation is a reliable marker of reperfusion with TIMI grade 3 flow. Because ST elevation and pain often fluctuate before undergoing final resolution with reperfusion, frequent or continuous monitoring of ST elevation is essential for reliable recognition of the fact and time of reperfusion. Accelerated idioventricular rhythm and episodes of sudden sinus bradycardia, although specific to reperfusion, do not occur in all patients with reperfusion.

Aged↗
PubMed1993

Cancer-associated SCM-recognition, immunedefense suppression, and serine protease protection peptide. Part II. Immunedefense suppressive effects of the CRISPPs peptide.

The cancer SCM-recognition, immunedefense suppression, and serine protease protection (CRISPP) peptide, a product of a hereditary or acquired heritable alpha 1-PI gene DNA mutation in cancer cells, is a potent suppressor of the natural killer (NK) and lymphokine activated killer (LAK) cytotoxicity against cancer cells. The "NK suppression epitope" encompasses amino acid residues 8 to 29 of the 29 amino acid sequence of the CRISPPs peptide. The NK suppression is peptide dose and incubation time dependent. The formation of conjugates between effector and target cells is not affected by the peptide, but the release of interleukin-2 (IL-2) and of tumor necrosis factor-alpha (TNF alpha) from lymphocytes is significantly decreased after treatment of lymphocytes with the CRISPPs peptide. The suppression of NK and LAK activity of lymphocytes by the CRISPPs peptide cannot be removed by washing, nor can it be reversed by subsequent treatment with recombinant interleukin-2 (rIL-2). However, autologous cell-free blood plasma, especially plasma ultrafiltrates of molecular weights higher than 100 kDa, can restore up to 83% of the NK activity. Scavenging of the CRISPPs peptide with anti-CRISPPs antibodies prevents the suppression of NK cytotoxicity. The relevance of CRISPP peptides for adoptive immunotherapy is discussed.

Cytotoxicity, Immunologic↗