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Biomedical subjects

R Engler

Publications and source records attributed to R Engler.

At least 55 records · Page 3Linked to original sources
PubMed1985

[Regulation of neoplasm-specific cathepsin B by cysteine-protease inhibitors present in cancerous exudates].

The Cathepsin B-like proteinase, a secretory form of lysosomal cathepsin B, is present in some cancerous exudates (i.e. pleural and ascitic fluids). It has been suggested that this enzyme may be involved in the invasive process, one of the most important aspects of cancer pathology. In the same fluids, two kinds of cysteine-proteinase inhibitors (C.P.I.'s) are found- HMr-CPI (90,000 daltons) and LMr-CPI's (11,000-13,000 daltons). The Cathepsin B-like enzyme is more strongly inhibited by the LMr-CPI's than by the HMr-CPI, the Ki values are 4.0 X 10(-9) M and 1.2 X 10(-7) M respectively. Theses results underline the similarity between this enzyme and the lysosomal Cathepsin B. On the other hand, the inhibitors could play a protective role against tumor invasion.

Ascitic Fluid↗
PubMed1984

Inhibition of human liver cathepsin L by alpha 2 cysteine-proteinase inhibitor and the low-Mr cysteine proteinase inhibitor from human serum.

The inhibition of human liver cathepsin L by two specific proteinase inhibitors present in human serum, namely alpha 2 cysteine-proteinase inhibitor and the low-Mr cysteine-proteinase inhibitor, was studied. Kinetic parameters, including inhibition constants (Ki) and rate constants for association and dissociation (k+1 and K-1), were determined. The values found are consistent with a possible physiological function of these inhibitors to control cathepsin L activity. Furthermore, a transfer of active proteinase from the complex with either cysteine-proteinase inhibitor species to alpha 2-macroglobulin was demonstrated in vitro. Given the rate of dissociation of both cathepsin-L-cysteine-proteinase inhibitor complexes, a function of transitory inhibitor can therefore be hypothesized for these proteins and might then provide an explanation of the clearance of lysosomal proteinases.

Binding Sites↗
PubMed1984

Long term production of acute-phase proteins by adult rat hepatocytes co-cultured with another liver cell type in serum-free medium.

Three acute-phase proteins, haptoglobin, alpha 2-macroglobulin and hemopexin, as well as albumin, have been measured daily in the hydrocortisone-supplemented serum-free medium of pure and mixed cultures of adult rat hepatocytes for 5 and 20 days respectively. Whereas plasma protein production rapidly declined in pure culture, it remained relatively stable when hepatocytes were co-cultured with rat liver epithelial cells. In the latter cultures, an early stimulation of albumin and alpha 2-macroglobulin secretion was observed. In addition, four other plasma proteins, fibrinogen, alpha 1-acute-phase protein, alpha 1-acid glycoprotein and alpha 1-antitrypsin were shown by immunodiffusion to still be produced by day 20 of co-culture. These results suggest that hepatocyte co-cultures represent a suitable model for studying the mechanism which controls synthesis of plasma proteins, including acute-phase proteins by liver cells.

Albumins↗
PubMed1984

Alpha 2 high molecular mass cysteine proteinase inhibitor: HMr alpha 2-CPI. An inhibitor of human liver cathepsin H as probed by kinetic study.

HMr alpha 2CPI was found to be an inhibitor of human liver cathepsin H by the measurement of the dissociation constant (Ki), the association rate constant (k1) and the dissociation rate constant (k-1) between the enzyme and the inhibitor. These data suggest that this protein-proteinase inhibitor can play a physiological role in the regulation of free cathepsin H.

Cathepsins↗
PubMed1984

Study of the evolution of acute phase reactants and of thromboxane and prostacyclin during calcium pyrophosphate-induced pleurisy in the rat.

By using a clearly defined model of acute inflammation in rats, CaPP-induced pleurisy, we compared the evolution of four APR levels (Hp, HpX, alpha 2M, SAP) at a local and peripheral site. At the same time we studied thromboxane and prostacyclin concentrations in pleural exudate. The levels of APR have shown a progressive increase up to 24 h. For alpha 2M, Hp, HpX the increase in serum concentration was more rapid than in exudate, whereas the evolution of SAP level was parallel in the intra and extra-vascular compartments. On the other hand the levels of albumin and transferrin which are not APR remained constant in serum and also in exudate from 6 h to 24 h. Thromboxane and prostacyclin levels reached a peak during the first two hours of the inflammatory reaction followed by a rapid decreased. These prostanoids may be considered as early and transient mediators of acute inflammation, whereas the acute phase proteins studied have a more prolonged role in the inflammatory reaction.

Acute-Phase Proteins↗
PubMed1984

The systolic arterial pressure/end-systolic volume relationship in patients with severe left ventricular dysfunction.

Performance of the intact left ventricle is well-defined by the end-systolic pressure/end-systolic volume relationship that appears independent of preload and afterload. To determine whether noninvasive measurements of this relationship could distinguish normal from abnormal subjects, we evaluated the relationship between arterial systolic pressure (determined by cuff sphygnomanometry) and radionuclide estimates of end-systolic volume in 12 normal subjects and 24 patients with severe left ventricular dysfunction. Data were acquired at rest, after atropine injection, and then during at least three increments of arterial pressure (average total increase approximately 45 mm Hg) using phenylephrine. The relationship between peak-systolic pressure (SP) and end-systolic volume (ESV) was found to be linear in all subjects (r greater than or equal to 0.91). The slope of this line was steeper in normal subjects than in myopathic patients (73 +/- 21.7 vs 20.8 +/- 8.7 mm Hg/volume unit/m2, P less than 0.001) and the zero pressure intercept also was greater (49.8 +/- 30 mm Hg vs 27.1 +/- 44.2 mm Hg, P less than 0.01). Similarly, resting ejection fraction (EF) was greater in the normals (0.71 +/- 0.88 vs 0.21 +/- 0.07% P less than 0.001) and end-diastolic volume (EDV) was smaller (4.14 +/- 0.88 vs 6.58 +/- 0.65 volume units, P less than 0.01). Systolic pressure/end-systolic volume relationship determined by these noninvasive methods was linear in both patients with severely reduced cardiac function and normal control subjects, clearly distinguishing normal from severely impaired left ventricles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

In vitro studies on some parameters of the binding of the rat hemopexin--heme complex with the hepatic membrane receptor.

The binding of [125I]Hpx--heme with the rat hepatic plasma membrane receptor was studied at 37 degrees C as well as different parameters such as plasma membrane concentration, calcium dependence, optimal pH and specific binding. A Scatchard plot revealed the existence of one binding for [125I]Hpx--heme on the isolated liver plasma membrane with a Kd = 3.2 X 10(-8) M.

Animals↗
PubMed1983

Evolutionary changes in acute-phase proteins in alcoholic hepatocellular diseases.

We studied the pattern of acute-phase proteins (orosomucoid, C-reactive protein, and haptoglobin) in hepatocellular deficiency due to chronic alcohol consumption, characterized by a decrease in serum transferrin concentration. We found that their patterns could vary independently of hepatocellular deficiency, but depend on the progression of hepatic disease. The most useful protein for discriminating the stage of inflammatory reaction is orosomucoid. In moderate hepatocellular deficiency, acute-phase proteins are increased independently of the decrease in transferrin, whereas in severe hepatocellular deficiency the acute-phase proteins are also decreased. Thus, it is possible to distinguish the two stages of hepatocellular deficiency by following changes in the concentration of orosomucoid.

Acute Disease↗
PubMed1982

[Increased activity of adenine phosphoribosyl transferase in a child trisomic for 16q22.2 to 16qter due to malsegregation of a t(16;21) (q22.2;q22;2)pat].

Two cousins with trisomy for the distal third of 16q due to a familial translocation, t(16;21)(q22.2;q22.2), are reported. The APRT gene locus could be assigned to 16q22.2 to 16qter. The phenotypic similarities of the first patient, who had trisomy 16q22.3 to 16qter and monosomy 21q22.3, to six other patients with partial trisomy 16q reported in literature allows the delineation of a syndrome due to trisomy 16qter. In the second patient, with trisomy 16q22.3 to 16qter and trisomy 21pter to 21q22.2, similar features are present, but in association with the classical symptoms of trisomy 21.

Adenine Phosphoribosyltransferase↗
PubMed1982

Clinical assessment and follow-up of functional capacity in patients with chronic congestive cardiomyopathy.

The presumption that the results of left ventricular systolic function tests performed at rest are related to the symptoms of chronic congestive heart failure or to exercise capacity is unproved. Thirty-three patients with chronic congestive cardiomyopathy underwent serial exercise tests, determinations of ejection fraction and systolic time intervals, echocardiograms, assessment of symptom score, chest roentgenogram, and physical examination over a mean ( +/- standard deviation) of 24.8 +/- 14.1 months. Maximal exercise performance achieved correlation with symptoms (r = 0.66) but not with indexes of left ventricular function. Edema, elevated jugular venous pressure, rales and radiologic evidence of pulmonary venous hypertension were more common in patients with severe limitation of exercise capacity. in 17 patients whose functional capacity changed during the follow-up period, congruent changes in left ventricular function measured at rest were not consistently observed. Thus the findings on history, physical examination and radiologic examination correlate with exercise capacity, but indexes of left ventricular performance at rest do not and therefore are of limited use in assessing treatment. The clinical course of patients with chronic congestive cardiomyopathy can be followed up safely, effectively and economically by simple clinical observations. Serial laboratory testing of left ventricular function can be reserved for specific indications, research and patients with valvular heart disease.

Adult↗
PubMed1982

Inhibition of cathepsin L and B by haptoglobin, the haptoglobin-hemoglobin complex, and asialohaptoglobin. "In vitro" studies in the rat.

In broadening our research on the inhibition of cathepsin B (EC 3.4.22.1) by rat haptoglobin, we have used the haptoglobin-hemoglobin complex and asialohaptoglobin. The inhibition of cathepsin L (EC 3.4.22.15), another lysosomal thiol proteinase, by haptoglobin and its related molecules has also been investigated. With azocasein as substrate, both enzymes were inhibited by both haptoglobin and its related molecules. When azocasein was used as a substrate, the apparent Michaelis constant (Km, app.) for cathepsin L was 1 X 10(-5) +/- 0.4 X 10(-5) M. When haptoglobin was added, the apparent inhibition constant (Ki, app) was 3 X 10(-8) +/- 2.5 X 10(-8) M. The results suggest that rat haptoglobin specifically inhibits lysosomal thiol proteinases and that it has a regulatory role in tissue proteolysis associated with the inflammatory reaction. On the other hand, these properties would seem to be peculiar to the systems rat haptoglobin-rat liver cathepsin B or L.

Animals↗
PubMed1982

Changes in control of renin release in congestive heart failure in dogs: response to acute and chronic vasodilator therapy.

Neural control of renin secretion is an important physiologic mechanism, but alterations in the central nervous system feedback and control of renin release in heart failure have not been investigated. Accordingly we studied conscious dogs after volume overload (arteriovenous fistula) or chronic myocardial infarction. Acute infusion of nitroprusside was used to test the renin response to arterial hypotension and decreased central blood volume. Hydralazine and prazosin administration were used to test the response to chronic vasodilator administration. After 4 weeks of volume overload or 3 weeks after myocardial infarction, the renin response to a graded hypotensive stimulus was blunted. After 7 days of hydralazine or prazosin administration, plasma renin activity remained elevated and blood volume increased from baseline values. Our results indicate a decrease in the neural feedback control of renin release after chronic volume overload or myocardial infarction. However, chronic vasodilator administration still resulted in sustained augmented renin secretion and an increase in blood volume.

Animals↗
PubMed1982

[Increased activity of adenine phosphoribosyl transferase in a child trisomic for 16q22.2 to 16qter due to malsegregation of a t(16;21) (q22.2;q22;2)pat (author's transl)].

Two cousins with trisomy for the distal third of 16q due to a familial translocation, t(16;21)(q22.2;q22-2), are reported. The APRT gene locus could be assigned to 16q22.2 to 16qter. The phenotypic similarities of the first patient, who had trisomy 16q22.3 to 16qter and monosomy 21q22.3, to six other patients with partial trisomy 16q reported in literature allows the delineation of a syndrome due to trisomy 16qter. In the second patient, with trisomy 16q22.3 to 16qter and trisomy 21pter to 21q22.2 similar features are present but in association with the classical symptoms of trisomy 21.

Adenine Phosphoribosyltransferase↗