Search PubMed⌕ Search

Biomedical subjects

R Engler

Publications and source records attributed to R Engler.

At least 37 records · Page 2Linked to original sources
PubMed1989

The glycosylation state of the precursors of the cathepsin B-like proteinase from human malignant ascitic fluid: possible implication in the secretory pathway of these proenzymes.

We have investigated the structure of the carbohydrate moiety of the precursors of the cathepsin B-like proteinase (PCBt). The largest precursor has an apparent molecular size (Mr) of 45-47 Kd and it contains 3 N-linked oligosaccharide chains which were Endo beta N acetylglucosaminidase H (Endo H)-resistant forms. On the other hand, these chains were sequentially removed by Endo beta N acetylglucosaminidase F (Endo F). Both results indicate a complex type structure for these oligosaccharides. As usual in these cases, sialic acids were also found. In the deglycosylated state, PCBt has a Mr value of 36 Kd closely related to the 35.9 Kd Mr for human Pro CB, deduced from the cDNa sequence. These findings may explain the extracellular location of PCBt in malignancy: complex oligosaccharides are in most cases associated with secretory or membrane bound glycoproteins. On the contrary, mannose-rich types are involved in the lysosomal routage.

Adenocarcinoma↗
PubMed1989

Tear protein analyses in 30 patients before and after penetrating keratoplasty.

The precise study of tears can afford good help in the preoperative and postoperative management of keratoplasties. Such studies may be performed with a laser nephelometer, a very comfortable and practical equipment for quantitative protein analysis, which enables one to analyze tears much more precisely than the break-up time and the Schirmer tests. Raised albumin and IgG values were demonstrated, indicating increased permeability of the blood-tear barrier, in the group with postoperatively reduced visual acuity, and lower values in the group with unchanged or increased visual acuity. Unfortunately, no statistically significant exclusive common laboratory findings for clinical signs of slight or severe rejection were found.

Albumins↗
PubMed1989

A decision scheme for coronary angiography after acute myocardial infarction.

It is important to select patients in the convalescent phase of acute myocardial infarction in whom knowledge of coronary anatomy may identify those potentially suitable for intervention aimed at improving prognosis. However, differing guidelines have been proposed, and by applying some of these guidelines to our large database of patients after acute myocardial infarction, several problem areas were identified. These include lack of considering patients with resting ischemia beyond day 5 of hospitalization, management of patients with reduced ventricular function or patients not exercise tested, and the role of coronary angiography in the elderly. Based on this experience and further analysis in 1,848 patients surviving beyond day 5 of hospitalization, a modified decision scheme for coronary angiography was developed and then tested in a second population (n = 780). In the new scheme, patients over 75 years of age are considered individually. Those under 75 years of age with severe resting ischemia in the hospital at any time beyond the first 24 hours (18% mortality between day 6 and year 1), and hospital survivors with a history of previous myocardial infarction and clinical or radiographic signs of left ventricular failure in the hospital (25% 1-year mortality after discharge), are recommended for coronary angiography. Among the remaining patients, some will perform an exercise test, and those with an ischemic response or poor workload (11% 1-year mortality) are also assigned to coronary angiography. When an exercise test is not performed, a resting radionuclide left ventricular ejection fraction is recommended, and coronary angiography is considered if the value lies between 0.20 and 0.44 (12% 1-year mortality). This relatively simple scheme does not make general recommendations in the elderly, considers patients with in-hospital left ventricular failure or reduced left ventricular function or both, and approaches the problem of patients who do not perform an exercise test. This general approach would avoid early coronary angiography in patients with an average 1-year mortality risk after discharge of 3% and recommend coronary angiography in those at increased risk (average mortality rate, 16%) who make up about 55% of this population under 75 years of age.

Aged↗
PubMed1989

Differing circadian patterns of symptom onset in subgroups of patients with acute myocardial infarction.

Circadian variation of the onset of acute myocardial infarction has been noted in many studies and may carry important pathophysiologic implications. However, only a few previous studies have attempted subgroup analyses. In 4,796 patients with documented acute myocardial infarction, the time of symptom onset was recorded. As in other studies, the peak of onset occurred in the morning from 6:01 AM to 12:00 noon, and 28% of the population (1.16 times the average percentage for the other time periods) experienced symptom onset in that period (p less than 0.001). There was a second, lower peak (25%) in the evening between 6:01 PM and 12:00 midnight, which was also observed in some previous studies. We sought to determine whether or not the presence of subgroups with specific clinical characteristics would exhibit different patterns and thereby contribute to these peaks in the overall population. In patients with a history of congestive heart failure (n = 606) or with non-Q wave infarction (n = 832), a pronounced peak (29%) occurred only in the evening. Two nearly equal peaks were observed in patients older than 70 years of age (n = 1,422), smokers (n = 2,057), diabetics (n = 767), women (n = 1,213), and patients taking beta-blocking drugs (n = 847). Finally, in patients with a previous myocardial infarction (n = 1,104), no peaks were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1989

Central nervous system side effects of beta-adrenergic blocking agents with high and low lipid solubility.

beta-adrenergic blocking agents have undesirable effects believed to be mediated through the central nervous system (CNS). If these effects are due to direct CNS action, less lipid soluble agents ought to have fewer effects. Accordingly, several formal psychological tests of items such as mood, motivation, and anxiety were used in a double-blinded crossover study in 17 hypertensive subjects taking equipotent beta blocking agents with high (propranolol) and low (atenolol) lipid solubility. Patients had less negative effects (p less than 0.05) on 12 of 21 items evaluated with atenolol compared to propranolol while peripheral beta blockade [beta 1, exercise heart rate (HR), and blood pressure (BP)] was equivalent. These results suggest that the mental changes which accompany beta blockade therapy are mediated directly in the CNS and that less soluble drugs can be expected to have fewer CNS effects.

Adult↗
PubMed1988

Influence on prognosis and morbidity of left ventricular ejection fraction with and without signs of left ventricular failure after acute myocardial infarction.

The left ventricular (LV) ejection fraction (EF) is known to be an independent predictor of late prognosis after acute myocardial infarction. Despite a previous report that early heart failure (evidenced only by advanced pulmonary rales in the hospital) can predict prognosis in the absence of severe depression of the LVEF at hospital discharge, the potentially strong influence of various measures of in-hospital heart failure on the predictive ability of LVEF has not been generally appreciated. Accordingly, in 972 patients with acute myocardial infarction the effect on late mortality of the presence or absence in-hospital of both clinical and radiographic signs of LV failure in subgroups of patients with normal, moderately or severely depressed LVEF was examined and measured close to hospital discharge. Patients were divided into 3 groups according to LVEF: group I LVEF less than or equal to 40, n = 265; group II LVEF 0.41 to 0.50, n = 241 and group III LVEF greater than or equal to 0.51, n = 466. When clinical signs of LV failure were present at any time during the coronary care unit period, the 1-year mortality rate after hospital discharge in groups I, II and III was 26, 19 and 8%, compared with 12% (p less than 0.01), 6% (p less than 0.01) and 3% (p less than 0.02), respectively, when signs of LV failure were absent.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Late clinical outcome in patients with early ventricular fibrillation after myocardial infarction.

Whether ventricular fibrillation occurring within 48 h after acute myocardial infarction is associated with particular clinical features and poor prognosis, especially in patients with anterior myocardial infarction, is still debated. Therefore, clinical variables and in-hospital and 1 year mortality rates were analyzed in 2,088 patients, aged 18 to 95 years (mean +/- SD 64 +/- 12), admitted to the hospital with acute myocardial infarction between 1979 and mid 1984. One hundred forty-seven patients (7%) had at least one episode of ventricular fibrillation occurring within 48 h of hospital admission. Of these, 25% died during their initial hospitalization compared with 13% of patients without early ventricular fibrillation (p less than 0.001). In greater than 50% of patients with early ventricular fibrillation, the immediate cause of death was left ventricular failure or cardiogenic shock. In contrast, the 1 year mortality rate after hospital discharge was not significantly greater in patients with than in those without early ventricular fibrillation (15 versus 11%, respectively), particularly in the subgroup of patients with anterior myocardial infarction in which the mortality rate tended to be lower in patients with early ventricular fibrillation (8 versus 14%, respectively). Similar mortality results were found when only primary (not associated with left ventricular failure) ventricular fibrillation was analyzed. The left ventricular ejection fraction and the incidence of complex ventricular arrhythmias from 24 h ambulatory electrocardiographic monitoring obtained at hospital discharge were not different in survivors with or without early ventricular fibrillation (0.45 +/- 0.13 versus 0.49 +/- 0.14 and 41 versus 41%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1988

Glycosylation of chicken haptoglobin: isolation and characterization of three molecular variants and studies of their distribution in hen plasma before and after turpentine-induced inflammation.

Chicken haptoglobin (Hp), a hemoglobin-binding protein isolated from chicken plasma, is composed of three molecular variants that react differently with concanavalin A (ConA). These glycosylation variants of chicken Hp have been isolated by affinity chromatography using Sepharose-bound ConA. They differ in their molecular weight, as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Analysis of the glycopeptides obtained after pronase digestion of these variants yielded two types of structures: one, reactive with ConA, corresponded to a biantennary N-linked carbohydrate unit and one, unreactive with ConA, corresponded to a triantennary unit. The strongly ConA-reactive Hp variant bears only two biantennary units and the nonreactive Hp variant bears only two triantennary units; the weakly reactive Hp variant bears equal amounts of both units. The distribution of Hp glycosylation variant does not show any significant difference when obtained from the plasma of laying hens before and after turpentine-induced inflammation.

Animals↗
PubMed1988

[Proteins of the inflammatory reaction. Regulatory functions].

There is a very important modification of the plasma protein equilibrium during an inflammatory reaction. Most of the proteins, except the immunoglobulins, have their biosynthesis or catabolic rate modified. The plasma concentration of these proteins may be increased, decreased or equal to the normal values. Clinically, the term "Acute Phase Protein" APP is reserved for the proteins whose plasma concentration is at least 50 per cent higher than normal values. These APP are: alpha-1 acid-glycoprotein, alpha-1 proteinase inhibitor, alpha-1 antichymotrypsin, haptoglobin, ceruloplasmin, fibrinogen, C-reactive protein, serum amyloid A protein. Interleukin-1 induces the APP's hepatic biosynthesis. The APP and, more generally, a lot of plasma proteins play a role during inflammatory reaction. They have some real functions of metabolic regulators. The functions result from the interaction of these proteins with ligands of various origins which give "protein-ligands" complexes. These complexes are cleared by the RES or by the hepatocyte. The results are protease inhibition, neutralization of toxic molecules such as hemoglobin or the superoxide anion, clearance of cell membranes and chromatin. The interaction of plasma proteins and particularly the APP's with different ligands issued from the inflammatory site, is an example of physiopathological self regulation.

Acute-Phase Proteins↗
PubMed1988

Purification and characterization of two different precursor forms of the cathepsin B-like proteinase from human malignant ascitic fluid.

We have purified two different precursors of a cathepsin B-like proteinase (PCBT) from malignant ascitic fluid. The molecular mass of these proteins were 45-47 kDa and 36 kDa, respectively. This report is the first which shows cathepsin-B precursors as purified proteins. By using sheep immunoglobulins directed against denatured lysosomal cathepsin B, we have found that both precursors, together with the 33-kDa pepsin generated cathepsin B-like proteinase, reacted in immunoblotting: the three components are thus cathepsin B-related. These antibodies allow us the show that during pepsin activation the 45-47 kDa precursor is converted to the 33-kDa cathepsin B-like proteinase together with the 36-kDa PCBT. We have also prepared sheep immunoglobulins directed against the 36-kDa precursor. The generation of the cathepsin B-like proteinase by pepsin digestion of purified precursors followed a time and dose dependent process. This latter result argues for activation through peptide bond cleavages.

Ascitic Fluid↗
PubMed1988

Alpha-1-acid glycoprotein concentrations and protein binding of propranolol in Sprague-Dawley and Dark Agouti rat strains treated by phenobarbital.

Propranolol binding to rat serum samples was studied after 7 days of phenobarbital (PB) administration to induce alpha-1-acid glycoprotein (AAG). In male Sprague-Dawley rats, serum AAG concentrations and the bound/free propranolol ratio (B/F) were increased slightly after enzyme-inducing drug administration (mean +/- S.D.): from 0.30 +/- 0.04 to 0.49 +/- 0.05 g/l for AAG and from 6.79 +/- 1.24 to 8.81 to 1.31 for B/F. In male DA (Dark Agouti) rats, the same parameters increased greatly: from 0.20 +/- 0.01 to 1.38 +/- 0.13 g/l for AAF and from 8.75 +/- 1.01 to 27.15 +/- 3.28 for B/F. PB concentrations determined on the same serum samples were similar in both rat strains. Female DA rats also were responsive to PB administration. Propranolol binding to DA rat serum from the treated group was characterized by an increase in high-affinity binding site concentrations. The binding of propranolol to isolated rat AAG at various concentrations (0.2-1 g/l), alone or associated with rat serum albumin at a constant concentration (36 g/l), also was studied. Propranolol binding capacities to rat AAG were increased 2.4 times by the presence of albumin and consequently B/F values for both proteins agreed with values obtained with serum samples. These results indicate that increased propranolol binding to rat serum induced by PB administration is probably a direct consequence of increased concentrations of AAG. The high sensitivity of DA rats to PB suggests that this strain should be used preferentially for the study of the effect of cytochrome P-450 inducers on AAG metabolism and cationic drug binding.

Animals↗
PubMed1987

Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia.

During acute myocardial ischemia, granulocytes accumulate and obstruct the microcirculation. Granulocytes remain plugged in individual myocardial capillaries on reperfusion and are the major cause of the no-reflow phenomenon. During 3 h of ischemia, the granulocyte content of myocardium measured by 111In labeling increases from 1.0 X 10(6) to 1.5 X 10(6) cells/g, and after 5 min of reperfusion increases to 2.4 X 10(6) cells/g. The effects of granulocytes during 1 h of acute ischemia were determined by comparing agranulocytic to whole blood perfusion. With whole blood collateral flow decreased, water content increased (edema), ventricular fibrillation was common, and 27% of capillaries had no-reflow, whereas in the absence of granulocytes, collateral flow increased, there was no edema, arrhythmias were rare, and the no-reflow phenomenon was completely prevented. It is unfortunate that the inflammatory signals triggered by ischemia remain active on acute reperfusion, limit tissue salvage, and perhaps cause reperfusion injury. Several activating stimuli for granulocytes are known, but what inhibits them? Adenosine is known to inhibit superoxide radical formation by granulocytes, and 5-amino-4-imidazole carboxamide-riboside (AICA-riboside) augments adenosine release from energy-deprived cells. In dogs subjected to 1 h of ischemia, AICA-riboside pretreatment augmented adenosine release by nearly 10-fold, which was accompanied by a significant increase in collateral blood flow and decreased arrhythmias. We propose a new hypothesis: adenosine acts as a natural antiinflammatory autacoid during transient injury linking the ability to catabolize ATP (an indicator of viability) to granulocyte inhibition, thus preventing premature activation of the inflammatory response to cell death. Granulocytes are active participants in acute myocardial ischemia and means to prevent their activation, remove them from the reperfusate, or inhibit them will be necessary for optimum reperfusion salvage.

Adenosine↗
PubMed1987

Granulocytes cause reperfusion ventricular dysfunction after 15-minute ischemia in the dog.

Regional ventricular dysfunction (the stunned myocardium) persists for several hours after 15 minutes of ischemia and reperfusion in the dog. Superoxide-radical-induced damage appears to be one of the mechanisms of this injury. We tested whether granulocytes were a direct source of injury in the stunned myocardium in the 15-minute ischemia dog model. Regional function during agranulocytic extracorporeal coronary perfusion (using Leukopak filters) with ischemia and reperfusion was compared with function during a second period of ischemia and reperfusion after removal of the filters (granulocytopenia). Flow reduction and reperfusion flow, preload, afterload, and inotropic stimulation were the same during agranulocytic and granulocytopenic perfusion. During agranulocytic perfusion, stunning did not occur (greater than 100% of preischemic function during reperfusion), but when the filters were removed and about 10% of the normal granulocyte count was present, stunning occurred with only 76% return of function at 60 minutes of reperfusion (p less than 0.01). A second series of studied animals with extracorporeal perfusion and granulocyte replete perfusion all had less than 75% return of regional function, indicating that the agranulocytic perfusion and not the extracorporeal aspects of the experiment prevented stunning. We conclude that granulocytes are the direct source of the injury in stunned myocardium and apparently the main source of superoxide in the 15-minute ischemia dog model. Other possible granulocyte-related mechanisms of reperfusion injury include capillary no-reflow, causing microvascular ischemia and degranulation leading to enzyme-induced damage.

Agranulocytosis↗
PubMed1986

Comparison of the efficacy and safety of esmolol, a short-acting beta blocker, with placebo in the treatment of supraventricular tachyarrhythmias. The Esmolol vs Placebo Multicenter Study Group.

The efficacy and safety of esmolol, a short-acting intravenous beta-adrenergic-blocking agent, and placebo were compared in patients with supraventricular tachyarrhythmias (heart rate greater than 120 bpm) in a multicenter, double-blind, partial-crossover study. Seventy-one patients were randomized to receive either esmolol (n = 36) or placebo (n = 35) as initial treatment. Therapeutic failures were crossed over to the other study medication. Therapeutic response was defined as greater than or equal to 20% reduction in heart rate, heart rate less than 100 bpm, or conversion to normal sinus rhythm. The therapeutic response to esmolol during the initial treatment period (72%) was similar to that obtained when esmolol was given as a second agent. The average esmolol dosage producing a therapeutic response was 97.5 micrograms/kg/min. Four patients (6%) converted to normal sinus rhythm during esmolol infusion. In the majority of patients (80%), therapeutic response was lost within 30 minutes following discontinuation of esmolol infusion, a finding indicative of rapid reversal of beta-adrenoceptor blockade. The most prevalent adverse effect during esmolol infusion was hypotension which occurred in eight patients (12%). Hypotension and associated symptoms resolved within 30 minutes after discontinuation of esmolol infusion, which is consistent with the short duration of action of esmolol (elimination half-life of 9.2 minutes).

Adrenergic beta-Antagonists↗
PubMed1986

Inhibition of the cathepsin B like proteinase by a low molecular weight cysteine-proteinase inhibitor from ascitic fluid and plasma alpha 2 macroglobulin.

The cathepsin B like proteinase present in ascitic fluid of a patient with neoplasia has been purified and characterized after pepsin activation. From this fluid we have prepared the low molecular weight (LMW) cysteine-proteinase inhibitors. Three major inhibitor forms were found with isoelectric points of 7.4, 5.4, and 5.1, respectively. The interaction of the enzyme with the former inhibitor was studied because this inhibitor was the most abundant. The Ki value was found to be 4.3 X 10(-8) M. Two molecules of this proteinase were bound by one molecule of plasma alpha 2 macroglobulin (alpha 2M). The LMW inhibitor was able to bind to the enzyme entrapped in alpha 2M and reduced its endopeptidase activity on benzyloxycarbonyl-L-phenylalanyl-L-arginine-4-methyl-7-coumarylamide. These results may have a physiological significance in the regulation of the enzyme which, among other extracellular hydrolases, probably plays an important role in tumor invasion.

Ascites↗