Biomedical subjects

B Cercek

Publications and source records attributed to B Cercek.

At least 19 recordsLinked to original sources

PubMed1992

Effects of hypophysectomy on vascular insulin-like growth factor-I gene expression after balloon denudation in rats.

Insulin-like growth factor-I (IGF-I) is a widely distributed mediator of the growth promoting effects of growth hormone (GH). We sought to determine whether the relationship between GH and IGF-I extends to the vascular system, where IGF-I is proposed to participate in the process of neointimal proliferation after balloon denudation. We show that in hypophysectomized rats basal aortic IGF-I mRNA is one-tenth that of normal rats and is increased after balloon denudation. The induction peaks at 7 days after balloon denudation at about 10-fold control levels, similar to normal rats. Treatment with GH restores basal IGF-I mRNA content to approximately half that of normal rats, without further increase in the relative magnitude of induction after balloon denudation. This local induction of IGF-I gene expression in the vessel wall following injury might explain why neointimal proliferation is not inhibited more profoundly after hypophysectomy.

Animals↗

PubMed1992

Regulation of insulin-like growth factor-I and its receptor in rat aorta after balloon denudation. Evidence for local bioactivity.

Local production of growth factors may play a major role in vascular repair after injury. We examined the regulation of insulin-like growth factor-I (IGF-I) and its specific membrane receptor in balloon-denuded rat aorta. Aortic IGF-I mRNA and radioimmunoassayable IGF-I content increased severalfold after balloon denudation with a peak at 7 d after injury. This coincided with a reciprocal 25% decrease in IGF-I receptor mRNA content and a 40% decrease in total 125I-IGF-I binding. Scatchard analysis indicated a single class of binding sites, with a decrease in receptor number at 7 d compared to control and no change in affinity. By in situ hybridization the predominant site of IGF-I expression in the normal and the denuded vessel wall was the medial smooth muscle cell. After denudation there was a relative decrease in IGF-I receptor mRNA in the medial cells as compared to the neointima, suggesting that the site of IGF-I action was predominantly in the medial layer. These data suggest that local expression and action of IGF-I are significant in the promotion of smooth muscle cell proliferation after arterial injury.

Animals↗

PubMed1992

Proliferating cell nuclear antigen immunohistochemistry in rat aorta after balloon denudation. Comparison with thymidine and bromodeoxyuridine labeling.

The authors compared detection of proliferating vascular smooth muscle cells (SMC) in vitro and in vivo with proliferating cell nuclear antigen (PCNA) immunohistochemistry and two established methods: [3H]thymidine autoradiography and bromodeoxyuridine immunohistochemistry. Labeling with [3H]thymidine and bromodeoxyuridine of rat vascular SMC in culture stained 11% +/- 2% and 11% +/- 1% of cells, and PCNA immunohistochemistry 22% +/- 2% of cells. Proliferation in the media of the denuded rat aortae was highest 3 days after denudation: 4.2%, 3.8%, and 4.7% of labeled cells with [3H]thymidine, bromodeoxyuridine, and PCNA, respectively. In the intima, proliferation was highest 7 days after denudation with 42% [3H]thymidine, 40% bromodeoxyuridine, and 46% PCNA-positive cells. With double labeling, all [3H]thymidine-positive cells were PCNA positive, whereas some cells were only positive for PCNA. The authors conclude that PCNA immunohistochemistry compares favorably with [3H]thymidine autoradiography, and bromodeoxyuridine immunohistochemistry.

Animals↗

PubMed1992

Cancer-associated SCM-recognition, immunedefense suppression, and serine protease protection peptide. Part I. Isolation, amino acid sequence, homology, and origin.

The isolation of a cancer-associated, SCM-recognition, immunedefense-suppressing, and serine protease-protecting (CRISPP) peptide from the blood plasma of cancer patients is described. The amino acid sequences were determined on preparations from 12 different cancers. The peptide is composed in 9 cancers of 29 and in 3 cancers of 35 amino acid residues with molecular weights of 3410 and 4007 Da, respectively. A consensus, synthetic 29 amino acid CRISPP peptide (CRISPPs) has the same cancer SCM-recognition (CR) activity and SCM-response modifying effects as the natural peptide. The "cancer SCM-recognition epitope" of the CRISPP peptide was determined. Anti-CRISPPs antibodies were raised and used in immunoassays to confirm the presence of the CRISPP peptides in cancer blood plasmas, in supernatants of cancer cell growth media and in cultured human cancer cells. The amino terminal end sequences of peptides isolated from growth media of cultured breast and colon cancer cells corresponded to amino acid sequences of CRISPP peptides isolated from cancer blood plasmas of subjects with the respective cancers. The CRISPP peptides are between 83 to 100% homologous to the alpha 1-protease inhibitor amino acid sequence located at the carboxy terminal end between residues 358 and 393. The genetic origin of the CRISPP peptides and their selective advantage to cancer cell survival are discussed.

Adult↗

PubMed1991

Growth factors in pathogenesis of coronary arterial restenosis.

Restenosis occurs in 25% to 55% of patients within 6 months of successful angioplasty. The major histologic component of the restenotic lesion is intimal hyperplasia, which is almost certainly driven by growth factors. After vascular injury, smooth muscle cells proliferate, reaching a maximum rate at day 2. Smooth muscle cell proliferation diminishes as the vessel surface is re-endothelialized at about day 7, and by week 4 the smooth muscle cell mitotic rate returns to baseline of less than 1% per day. The events of the histologic evolution of arterial injury can be used to create a hypothetical paradigm for the role of growth factors in restenosis. Restenosis might logically be prevented by an inhibitory intervention at any of the various steps in the healing process.

Animals↗

PubMed1991

Complicated acute myocardial infarction. Heart failure, shock, mechanical complications.

In-hospital mortality in patients with acute myocardial infarction is predominantly related to heart failure or shock and mechanical complications (acute mitral regurgitation, ventricular septal rupture, and free wall rupture). Heart failure and shock are primarily the consequences of contractile dysfunction of the left ventricle. Use of inotropic agents and assist devices are temporizing measures; early reperfusion with salvage of ischemic interventricular septum or free wall, resulting in severe mitral insufficiency, left to right shunt, and acute tamponade, respectively, necessitates immediate diagnosis and surgical intervention.

Acute Disease↗

PubMed1990

Critically ischemic myocardium in clinically stable patients following thrombolytic therapy for acute myocardial infarction: potential implications for early coronary angioplasty in selected patients.

The utility of post-thrombolysis, rest-redistribution thallium (TI)-201 scintigraphy was studied in 32 patients with a first myocardial infarction who were clinically stable following reperfusion. Day 1 scintigraphy obtained 5 +/- 4 hours (range 1 to 16) after thrombolysis revealed an average perfusion defect of 6.5 +/- 2.6 segments (range 1 to 11). There was a total of 208 abnormal segments, 137 of which were nonreversible at 4 hours, 50 of which were fully or partially reversible, and 21 of which had a reverse redistribution pattern. Repeat TI-201 scintigraphy on day 10 revealed significantly smaller perfusion defects of 4.9 +/- 2.4 segments (range 0 to 9) with improvement predominantly of the day 1 reversible segments, and the improvement in segmental perfusion correlated with better regional left ventricular function. Twenty-nine (58%) of the 50 reversible segments normalized by day 10, and 11 (22%) improved, whereas only 16 (12%) of 137 nonreversible segments had normalized by day 10, only 9 had (6%) improved and 112 (82%) were unchanged (p less than 0.001 reversible versus nonreversible). There was no significant change in segments with a pattern of reverse redistribution. The improvement of reversible segments was greater in the 16 patients who underwent coronary angioplasty (PTCA) during the interval between the two scintigrams than in the 16 who did not. All 24 reversible segments in the PTCA group improved or normalized by day 10 compared with 16 (62%) of 26 reversible segments in the No PTCA group (p less than 0.001). Furthermore, 8 of the 10 reversible segments in the No PTCA group that did not improve actually deteriorated and became nonreversible by day 10. The minor improvement of nonreversible segments was not related to PTCA. Consistent with the findings in individual segments, the 19 patients with a reversible component on the day 1 TI-201 scintigram had significantly greater improvement in perfusion defect by day 10 than the 13 patients without a reversible component (37 +/- 33% versus 7 +/- 22% decrease in perfusion defect severity, p less than 0.05), and this improvement was greatest in the 10 patients with a reversible component who underwent PTCA. In contrast, PTCA had no impact on the perfusion defect in the 13 patients without a reversible component. Our data suggest that following thrombolytic therapy for acute myocardial infarction, viable myocardium in the reperfused zone may remain ischemic, as manifested by a reversible pattern of TI-201 redistribution at rest, and thus may be in jeopardy of gradual progression to necrosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1990

Induction of insulin-like growth factor I messenger RNA in rat aorta after balloon denudation.

Insulin-like growth factor I (IGF-I) is a widely distributed mitogen that mediates the growth-promoting effects of platelet-derived growth factor in mesenchymal cells. We show that rat aortic IGF-I messenger RNA (mRNA) is induced 24 hours after deendothelialization, at a time when smooth muscle cell proliferation within the intima is still not apparent. After 7 days, IGF-I mRNA induction peaks at about ninefold control levels and then falls to about threefold 14 days after denudation when smooth muscle cell proliferation is at its peak. We also show that, of the 5' untranslated IGF-I mRNA transcripts, only the class C transcript is expressed and regulated in aortic tissue. In contrast, treatment of rats with supraphysiological doses of growth hormone, the major endocrine regulator of IGF-I gene expression, elicited only twofold induction of aortic IGF-I mRNA. Our findings suggest that IGF-I may be an important autocrine or paracrine regulator of smooth muscle cell proliferation and that it may be significant in determining the cellular response to arterial wall injury.

Animals↗

PubMed1989

Selective decrease in lysis of old thrombi after rapid administration of tissue-type plasminogen activator.

The safety of thrombolytic therapy of acute myocardial infarction could be improved if a method were developed to dissolve fresh occlusive coronary thrombus without simultaneously dissolving hemostatic thrombi outside the coronary arteries. This study is based on the assumption that, in a patient with evolving acute myocardial infarction, hemostatic thrombi are likely to be older than the thrombus responsible for occlusion of the coronary artery. It explored whether the relative rates of lysis of fresh and old thrombi could be influenced by the rapidity of recombinant tissue-type plasminogen activator (rt-PA) administration. In each of 17 dogs, two 1 h and two 24 h old thrombi were produced by inserting copper coils into both jugular and both femoral veins. After 24 h and 1 h, respectively, the coils with the thrombi were removed, weighed and inserted into the adjacent carotid and femoral arteries. A 1 mg/kg body weight dose of rt-PA was given either over 180 or over 30 min. The coils were removed and weights of the residual thrombi determined at the end of the 180 min infusion (Group I), at the end of the 30 min infusion (Group IIA) and 45 min after the 30 min infusion (Group IIB). The 24 h old thrombi were lysed significantly less than the 1 h old thrombi in all three experimental groups: 53.9 +/- 4.8% (mean +/- SE) versus 86.1 +/- 2.5% in Group I (p less than 0.001), 16.6 +/- 3.5% versus 65.2 +/- 6.0% in Group IIA (p less than 0.001) and 21.6 +/- 5.4% versus 91.7 +/- 1.7% in Group IIB (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Usefulness of a rapid initial increase in plasma creatine kinase activity as a marker of reperfusion during thrombolytic therapy for acute myocardial infarction.

This study evaluates a new nonangiographic marker of reperfusion--a rapid initial increase in plasma creatine kinase (CK) and CK-MB activity--in 50 patients receiving intracoronary streptokinase. Blood for CK and CK-MB activity was sampled at 30-minute intervals and angiography performed at 15-minute intervals or earlier if there were clinical signs suggestive of reperfusion. An absolute first-hour increase in CK activity of 480 +/- 345 IU/liter (range 54 to 1,440 IU/liter), or a relative first-hour increase of 34 +/- 18% (range 13 to 67% of the peak rise), or an absolute first-hour increase in CK-MB activity of 48 +/- 36 IU/liter (range 10 to 144 IU/liter) or a relative first-hour increase of 27 +/- 13% (range 13 to 57%) was found in patients immediately after reperfusion with Thrombolysis In Myocardial Infarction (TIMI) grade 3 perfusion of the artery of infarction. The onset of rapid increase in CK and CK-MB activity closely reflected the time of angiographic documentation of reperfusion. In contrast, in the absence of reperfusion, the absolute rate of increase in CK activity measured in the last hour of the 2 1/2-hour period beginning with the start of treatment was only 15 +/- 9 IU/liter on the average (range 2 to 30 IU/liter) and the relative rate of rise was 3 +/- 2% on the average (range 1 to 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation↗

PubMed1987

Efficacy of a two-hour infusion of 150-mg tissue plasminogen activator in acute myocardial infarction.

Forty-two patients with acute myocardial infarction received 150-mg recombinant human tissue-type plasminogen activator (rt-PA) at 2.3 +/- 1.2 hours after the onset of chest pain. After a 40 U/kg bolus of heparin, rt-PA was given as a 10-mg bolus followed by a 2-hour continuous infusion of 90 mg in the first hour and 50 mg in the second hour. Nonangiographic signs of reperfusion occurred during treatment (41 +/- 21 minutes) in 35 patients and in 1 other patient about 30 minutes after rt-PA. Three patients had discordant nonangiographic signs of reperfusion, 2 patients had no evidence of reperfusion and 1 patient in cardiogenic shock died before completion of the rt-PA infusion and before reperfusion status could be ascertained. Clinical signs of early reocclusion occurred in 4 of the 36 patients with evidence of reperfusion, 3 of whom were retreated with rt-PA with clinical success in 2. Coronary angiography 10 +/- 8 hours later revealed a patent artery of infarction in 35 patients: 32 with nonangiographic signs of sustained reperfusion, both patients with successfully treated reocclusion and 1 of 3 patients with discordant signs of reperfusion. Angiography revealed evidence of partial reperfusion in the remaining 2 patients with discordant signs, and an occluded artery was found in both patients without any evidence of reperfusion and in both patients with clinical signs of persistent reocclusion. Hemorrhagic complications occurred in 9 patients, 7 were related to procedural trauma and 2 patients required a blood transfusion. Four patients died, each of a cardiac cause: 3 in hospital and 1 at home.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Ancrod enhances the thrombolytic effect of streptokinase and urokinase.

Since thrombi continue to incorporate fibrin during lysis we tested the effect of pretreatment with ancrod, a defibrinating agent from Malaysian pit viper venom, on thrombolysis with urokinase and streptokinase. Thrombi were induced by copper-coils in the carotid arteries of the dogs, weighed after 1 hour and inserted into the femoral arteries of the same animals. They were then exposed for 15 min to iv boluses of streptokinase 10,000 U/kg, urokinase 10,000 U/kg and urokinase 25,000 U/kg with or without pretreatment with ancrod. Ancrod depleted fibrinogen within 5 min and enhanced the lytic effect of streptokinase from 25 +/- 8% to 59 +/- 13% (p less than .05), urokinase 10,000 U/kg from 16 +/- 11% to 66 +/- 18% (p less than .01) and urokinase 25,000 U/kg from 27 +/- 17% to 85 +/- 8% (p less than .001) of the initial thrombus weight. Ancrod itself did not activate plasminogen to plasmin. We conclude that ancrod enhances thrombolysis probably by depleting fibrinogen and preventing new fibrin incorporation into the thrombus during lysis.

Ancrod↗

PubMed1987

Time course and characteristics of ventricular arrhythmias after reperfusion in acute myocardial infarction.

The time course and characteristics of ventricular arrhythmias were studied in 45 consecutive patients with acute myocardial infarction who received intravenous streptokinase and underwent 24-hour Holter monitoring both after admission and before discharge 8 +/- 3 days later. In 41 of the 45 patients, thrombolytic treatment resulted in reperfusion as determined by characteristic clinical signs, i.e., rapid relief of pain associated with rapid resolution of ST-segment elevation and simultaneous abrupt increase in serum creatine kinase-MB activity. During the first 24 hours after reperfusion, the prevalence of ventricular premature complexes (VPCs) and couplets was nearly 100%, with an average frequency of 67 VPCs (range 1 to 1,336, median 44) and 6 couplets per hour per patient (range 1 to 97, median 4). Ninety percent of patients had an average of 8 runs of accelerated idioventricular rhythm per hour per patient (range 1 to 226, median 5) and 23% of the patients had an average of 2 runs of ventricular tachycardia per hour per patient (range 1 to 22, median 2) during the first 24 hours after reperfusion. The frequency of arrhythmias began to decrease 8 to 12 hours after reperfusion. Except for VPCs, ventricular arrhythmias were rare during the predischarge Holter study. Arrhythmias after reperfusion did not produce clinical symptoms and did not degenerate into ventricular fibrillation even though the patients were not receiving antiarrhythmic therapy. In the 4 patients without signs of reperfusion, the prevalence and frequency of all ventricular arrhythmias during the 24 hours after treatment was lower than in patients with reperfusion, and none had an accelerated idioventricular rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Complexes, Premature↗

PubMed1987

Mortality and morbidity rates of patients older and younger than 75 years with acute myocardial infarction treated with intravenous streptokinase.

The influence of patient age on mortality risk and on the incidence of serious hemorrhagic complications after treatment of acute myocardial infarction (AMI) with intravenous streptokinase (SK) and heparin was examined in 120 consecutive patients. No upper age limit was set for patient inclusion. The mortality rate increased abruptly in patients aged 75 years or older such that the 24 patients in that age group had a 10-fold higher in-hospital mortality rate (33% vs 3%) and 1-year mortality rate (42% vs 4%) than the 96 patients younger than 75 years. This increased mortality rate in the elderly patients was related to a 2-fold higher incidence of major hemorrhagic complications (24% vs 11%) and an increased incidence of anterior AMI, healed prior AMI, multiple-vessel coronary artery disease and extensive myocardial necrosis estimated by peak creatine kinase-MB. Hemorrhagic complications were more frequent in women than in men and in patients with diabetes mellitus or systemic hypertension; all of these conditions were more prevalent in patients aged 75 years and older than in those younger than 75 years. In contrast, the incidence of hemorrhagic complications in nondiabetic elderly men (1 of 12) was similar to the incidence of bleeding in the patients younger than 75 years. Based on our data and those from other studies reporting no reduction in mortality in elderly patients with AMI who are treated with intravenous SK, it is recommended that patients aged 75 years or older should not be routinely treated with intravenous SK.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1987

Inferior ST segment changes during acute anterior myocardial infarction: a marker of the presence or absence of concomitant inferior wall ischemia.

The significance of inferior ST segment changes during acute anterior myocardial infarction was studied in 60 patients with acute anterior infarction who had angiographic visualization of the entire distribution of the left anterior descending artery after thrombolytic therapy with streptokinase. In 34 patients (Group 1) this artery supplied the anterior wall of the left ventricle up to or including the apex but did not reach the inferior wall; in 16 patients (Group 2) it continued beyond the apex onto the inferior wall of the left ventricle; and in 10 patients with prior inferior infarction (Group 3) it partially supplied the inferior wall of the left ventricle through collateral channels to an occluded right or dominant circumflex coronary artery. Consistent with this anatomy, evidence of inferior wall ischemia was significantly more frequent in Groups 2 and 3 than in Group 1 by thallium-201 scintigraphy (91 versus 7%) and by contrast left ventriculography (91 versus 13%). There was no difference in the magnitude of precordial ST segment elevation among the three groups but the inferior ST segment depression was significantly smaller in Groups 2 and 3 with concomitant inferior wall ischemia than in Group 1 (aVF: -0.5 +/- 0.7; -0.5 +/- 1.0; -1.8 +/- 0.8 mm, respectively; p less than 0.001) with 10 of the 26 patients in Groups 2 and 3 having an elevated or isoelectric ST segment in aVF compared with none of the 34 patients in Group 1 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Early atrial fibrillation during evolving myocardial infarction: a consequence of impaired left atrial perfusion.

Seven of 214 patients (3%) with acute myocardial infarction (120 inferior and 94 anterior) developed atrial fibrillation within 3 hr of the onset of chest pain. All seven patients had an inferior infarction and in all seven the left circumflex artery was occluded proximal to the origin of its left atrial circumflex branch. In five patients this occlusion was acute and was the cause of inferior infarction and in the remaining two patients the occlusion was old and the inferior infarction was due to an acute occlusion of the right coronary artery that also supplied extensive collaterals to the previously occluded left circumflex artery. All seven patients also had impaired perfusion to the atrioventricular nodal artery, as evidenced by total occlusion proximal to its origin or by stenosis proximal to its origin associated with second- or third-degree atrioventricular block. In contrast, early atrial fibrillation did not occur in any of the 18 patients with inferior myocardial infarction due to acute occlusion of the distal left circumflex artery or in any of the five patients with inferior infarction due to acute occlusion of the proximal left circumflex artery if perfusion to the atrioventricular nodal artery was not impaired. Early atrial fibrillation did not occur in any of the 90 patients with inferior infarction due to acute occlusion of the right coronary artery, including 12 patients with occlusion proximal to the sinus nodal artery, but without coexistent occlusion of the left circumflex artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1987

Effects of ascorbate ions on intracellular fluorescein emission polarization spectra in cancer and normal proliferating cells.

Ascorbate ions induced a polarization peak in the intracellular fluorescein fluorescence polarization spectra of asynchronous populations of a variety of cancer cell types from human and animal biopsy material or in cells grown in vivo and/or in vitro. The appearance of this polarization peak at 510 nm on excitation at 470 nm (P510 peak) indicates the transition of mitochondria from the condensed (active) into orthodox (resting) conformation. In contrast, no effects of ascorbate ions were observed in the polarization spectra of various normal cell lines. This apparent differential response seems to be caused by the effects of ascorbate ions on several steps of the altered energy metabolism in cancer cells. It appeared not to be due to a defective mechanism responsible for the conformational changes in the mitochondria. In YMDR cells resistant to the antitumor drug methylene-dimethanesulphonate (MDMS), HeLa cells pretreated with colcemid, and YMDS cells pretreated with cytochalasin B, the transition of mitochondria into orthodox conformation could not be induced by ascorbate ions. Thus, it is possible that tumors also pretreated with other drugs become resistant to growth inhibitory effects of ascorbate ions. Induction of the fluorescein emission polarization peak at 510 nm in cells from biopsies or from in vitro-induced malignancies could be used as an additional criterion for malignant transformation.

2,4-Dinitrophenol↗

PubMed1986

Usefulness of residual plasma fibrinogen after intravenous streptokinase for predicting delay or failure of reperfusion in acute myocardial infarction.

The relation between the level of residual plasma fibrinogen and coronary artery reperfusion after 750,000 IU of intravenous (i.v.) streptokinase (SK) was examined in 76 patients with acute myocardial infarction. Both the frequency and rapidity of reperfusion were greater in the 53 patients in whom the residual fibrinogen level was 50 mg/dl or less (low fibrinogen) than in the 23 patients in whom it was more than 50 mg/dl (high fibrinogen). Reperfusion occurred in all 53 patients in the low-fibrinogen group, compared with only 15 patients in the high-fibrinogen group (p less than 0.001). The interval from initiation of SK to clinical signs of reperfusion was 50 +/- 34 minutes in the low-fibrinogen group and 110 +/- 54 minutes in the high-fibrinogen group (p less than 0.001). A high fibrinogen level occurred in 58% of patients who weighed more than 85 kg and in 25% of patients who weighed 85 kg or less (p less than 0.05). No patient who weighed 60 kg or less had a high fibrinogen level. The high-fibrinogen group also had a greater incidence of a high anti-SK antibody titer: 8 of 13 patients (62%) tested, compared with none of the 8 patients tested in the low-fibrinogen group (p less than 0.01). Our data indicate that a high residual fibrinogen level after administration of i.v. SK identifies patients in whom SK is relatively ineffective, probably because of inadequate dosage of inactivation of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation↗