PubMed Health⌕ Search

Biomedical subjects

M Oratz

Publications and source records attributed to M Oratz.

At least 37 records · Page 2Linked to original sources
PubMed1980

Spermine stimulation of CCl4 depressed protein synthesis in rabbits.

CCl4, 2.5 ml/kg body weight, was administered via a gastric tube to fed rabbits 2 hr before the livers were removed and perfused. Electron microscope studies of the liver showed that CCl4 caused a decrease in the rough endoplasmic reticulum and an increase in the smooth reticulum. The reticulum was dilated and vesiculated with few attached ribosomes. Sucrose gradient analysis of the endoplasmic reticulum bound polysomes showed them to be considerably disaggreated, and albumin synthesis and 14C-incorporation into proteins secreted into the perfusate were decreased. These effects were partially reversed when these livers were perfused with either 1 mM spermine of 10 mM arginine. Perfusion with both arginine and spermine increased endoplasmic reticulum bound polysome aggregation to about 92% of control and albumin synthesis increased from a low of 3.3 mg/100 g wet liver weight to 8.2 mg/hr or 37% of control. 14C-Incorporation into total hepatic protein and secretory proteins increased as well. The combination of spermine and arginine was more effective in stimulating albumin synthesis than either agent alone. The ability of spermine to partially reverse a specific toxic effect of carbon tetracholoride, namely polysome disaggregation, and to stimulate protein production is noted.

Albumins↗
PubMed1978

Synthesis of myosin heavy and light chains in the afterloaded guinea pig right ventricle.

Increased afterload causes increased cardiac myosin synthesis and ultimately leads to hypertrophy. Since the latter is associated with altered myosin ATPase activity, it was of interest to study the synthesis of myosin subunits in the acute response to this stress. An in vitro guinea pig heart preparation was used which allowed application of afterload to the right ventricle with unaltered coronary flow, and also permitted measurement of synthesis of myosin heavy chains (HC) and combined light chains (LC) by continuous perfusion with labelled amino acids (3H-lysine and/or 3H-phenylalanine) of constant specific activity. Isolation of 3H-labelled HC and LC with heterologous unlabelled carrier was possible because of identical mobilities of HC's and LC's from unlabelled lamb carrier myosin and 3H-labelled guinea pig myosin. This permitted study of comparative synthesis of the HC and LC in small samples as the single guinea pig right ventricle (100--150 mg) and avoided errors inherent in pooling hearts or in measurement of turnover in the nonsteady state. After 3 h or perfusion, the ratio of synthesis of HC/LC was 2 : 1 in controls. This ratio increased significantly to 3 : 1 in after load. It is possible that the disproportionate increase in HC synthesis may lead to stoichiometric problems in myosin assembly which ultimately effect altered myosin ATPase activity.

Animals↗
PubMed1978

Effect of hydrostatic pressure on isolated cardiac nuclei: Stimulation of RNA polymerase II activity.

RNA polymerase activity was measured in isolated cardiac nuclei subjected to hydrostatic pressure. After 20 min of pressure, Mn2+ stimulated RNA polymerase II activity was increased. The response to pressure was inhibited by low concentrations of alpha-amanitin (1.1 microgram.cm-3) an inhibitor of polymerase II activity. The data show that pressure applied to isolated nuclei stimulates RNA polymerase II activity, forming mRNA, and suggests that direct application of pressure to cardiac nuclei may be the stimulus which triggers the augmented protein synthesis seen in pressure overload.

Amanitins↗
PubMed1978

Hepatic extraction of long- and short-acting narcotics in the isolated perfused rabbit liver.

Hepatic extraction of the long-acting narcotic, methadone, was compared to that of the short-acting narcotics, morphine, diacetylmorphine, and meperidine, using an isolated perfused rabbit liver preparation. Methadone was avidly extracted from portal venous blood (86.1 +/- 0.81%) in a single pass through the liver after a bolus injection (1.5 mg) into a nonrecirculating perfusion system. Hepatic extraction of methadone was independent of rate of hepatic blood flow (0.59 to 1.53 ml per g of liver per min) but was altered by increasing the total amount of methadone injected. After a bolus injection of 15.0 and 75.0 mg, the proportions of methadone extracted were reduced to 75 and 56%, respectively. The hepatic extraction of morphine (1.5 mg) was 25%, of diacetylmorphine (1.5 mg) 59%, and of meperidine (1.5 mg) 66% in a single pass, all significantly lower (P less than 0.01) than that of methadone. Subcellular fractionation of whole liver homogenates after a single pass of drug showed that methadone and its metabolites were localized primarily in the fractions containing nuclei, mitochondria, microsomes, and other membranes, whereas morphine was primarily localized in the supernatant cytosol. Unchanged methadone was shown to be slowly released from the liver into hepatic effluent blood along with small amounts of the inactive pyrrolidine and pyrroline metabolites (identified by gas chromatography and mass spectrometry). These findings suggest that the liver may serve not only as a site of biotransformation of methadone, but also as a major reservoir for storage and subsequent release of unchanged compound.

Animals↗
PubMed1978

Alcohol, amino acids, and albumin synthesis. III. Effects of ethanol, acetaldehyde, and 4-methylpyrazole.

The effects of ethanol, 4-methylpyrazole (4-MP), and acetaldehyde on albumin and urea synthesis, and on polysome aggregation were studied in isolated perfused rabbit livers. Fed or fasted males served as donors and the perfusate contained ethanol, 200 mg per 100 ml, with and without 1.5 mM 4-MP; or acetaldehyde, 2 mg per 100 ml, with and without 1.5 mM 4-MP. The results indicate that in livers from fed donors ethanol depressed albumin and urea synthesis and bound polysomes were disaggregated. Perfusion with acetaldehyde caused a similar decrease in albumin and urea synthesis, but did not cause polysome disaggregation. The addition of 4-MP to the ethanol perfusates did not enhance albumin or urea synthesis but did prevent polysome disaggregation. When the donor was fasted, the addition of 4-MP to the ethanol perfusates restored urea synthesis and polysome aggregation to fasted control levels. In the livers from fasted donors, acetaldehyde did not lower albumin or urea synthesis and had no effect on polysome aggregation. The results indicate that the hepatic responses to ethanol and acetaldehyde are different if the livers are derived from fed or fasted donors, and it is not possible to ascribe the toxic effects of acetaldehyde or ethanol on albumin and urea synthesis to either agent, per se.

Acetaldehyde↗
PubMed1976

Alcohol, amino acids, and albumin synthesis. II. Alcohol inhibition of albumin synthesis reversed by arginine and spermine.

The effects of alcohol and spermine on albumin synthesis and polysome aggregation were studied in the isolated perfused rabbit liver system. Fed or fasted males served as donors and the perfusate contained, singly or in combination, alcohol, 200 mg per 100 ml, spermine, 1 mM, and arginine, 10 mM. The results indicate that in the presence of alcohol, using a liver from a fed donor, albumin synthesis is depressed from 16 to 6 mg per 100 g of wet liver weight per hr and the bound polysome is disaggregated. Spermine partially reaggregates the bound polysome and a combination of spermine and arginine augments albumin synthesis to the control rate. When the donor is fasted, and alcohol is present in the perfusate, the addition of spermine results in aggregated bound and free polysome patterns, whereas the combination of arginine and spermine is necessary to restimulate albumin synthesis. The results indicate that spermine plays an important role in the integrity of the polysome system and that arginine and spermine appears synergistic in maintaining albumin synthesis.

Albumins↗
PubMed1976

The stimulation of albumin sythesis by methadone.

Elevated levels of serum albumin have been noted in patients on chronic methadone maintenance and in heroin addicts. This observation was investigated in rabbits maintained on daily methadone 4 mg per kg of body weight after a period of 3 months on increasing dosage to assure drug tolerance. Albumin distribution and metabolism were measured with tested lots of 125I rabbit albumin. Studies were made before and again after the attainment of the methadone maintenance state. Albumin distribution was altered markedly with a shift of intravascular albumin to extravascular sites. Associated with this change, the serum albumin level rose by an average of 0.5 g per 100 ml. Albumin degradation increased by 32% from 248 to 327 mg per kg per day. The total exchangeable albumin pool increased 35%, or 3.6 g. Since the exchangeable albumin pool increased in the face of an increment in albumin degradation, albumin synthesis must have increased even further to account for this change. Although the specific factors responsible for these alterations in albumin metabolism and distribution are not known at present, to date, this hyperalbuminemic hypercatabolic state is not produceable in any other clinical or experimental situation.

Animals↗
PubMed1975

Effects of ethanol on protein synthesis.

Cardiac: Cardiac protein synthesis is influenced by the state of nutrition with reduction of cardiac size in starvation. Ethanol per se may not affect this synthesis directly, but the metabolite of ethanol, acetaldehyde, profoundly decreases normal protein synthesis in the heart in vitro. The interference with the synthetic process may play a role in the ultimate cardiomyopathies of malnutrition and alcoholism. Hepatic: In vivo albumin synthesis is sensitive to environment, oncotic pressure, normal balance, nutrition, as well as toxins and state of health. Thus, to study the acute effects of alcohol alone, it was necessary to employ the isolated perfused liver. Fasting reduced albumin synthesis 50%, with loss of RNA and a disaggregation of the endoplasmic membrane bound polysome. Tryptophan, arginine and ornithine added to the perfusate at a final concentration of 10 mM reversed these findings. Alcohol likewise reduced albumin synthesis; disaggregates the bound polysome without a marked loss of RNA. Ornithine, arginine and tryptophan are able to reverse this loss in albumin synthesizing capacity. The combination of fasting and alcohol, while not lowering albumin synthesis below that seen with either stress alone, prevents the recovery from either stress.

Acetaldehyde↗
PubMed1975

The effect of pressure or flow stress on right ventricular protein synthesis in the face of constant and restricted coronary perfusion.

Cardiac stress produced by hypertension or excess volume loading results in different types of hypertrophy. Elevated left ventricular pressure rapidly results in increased myocardial protein synthesis in vivo and in vitro, but such rapid alterations are not consistently seen in volume loading. The difference in response is difficult to clarify since it is not possible to effect alterations in left ventricular pressure or perfusion without profoundly affecting coronary perfusion. The present study describes cardiac protein synthesis in the right ventricle of the young guinea pig heart in vitro by utilizing a perfusion model in which the right ventricle could be stressed by elevations of pressure or volume loading in the presence of constant and restricted coronary perfusion. With coronary flow maintained at 4 ml/min per heart equivalent to 25 ml/min/g dry wt, an increase in right ventricular pressure from normal levels of 3 mm Hg to 11 mm Hg resulted in a 60 percent increase of myocardial incorporation of (14C)lysine into protein. However, with further increases of right ventricular pressure to 22 mm Hg, protein synthesis dropped back to normal levels. The falloff in protein synthesis was not due to decreased contractility, alterations in intracellular lysine pool specific activity, or alterations in distribution of coronary flow. a 60 percent increase in coronary perfusion was again associated with a similar response of protein synthesis to progressive elevations of pressure despite a rise in the ATP levels and a fall in lactate production. Thus, a deficiency of O2 did not entirely explain the decline of protein synthesis with maximal pressures. At all levels of coronary perfusion, volume loading for 3 h did not result in increased protein incorporation of (14C)lysine. The studies support a relationship between ventricular pressure and protein synthesis unrelated to coronary flow per se. A pressure receptor triggering protein synthesis within the ventricular wall is postulated. Such a relationship is not apparent in short-term volume loading in vitro.

Adenosine Triphosphate↗
PubMed1975

Pressure versus flow stress: the response of cardiac protein synthesis.

Cardiac stress produced by hypertension or excess volume loading results in different types of hypertrophy. Elevated left ventricular pressure rapidly results in increased myocardial protein synthesis in vivo and in vitro, but such rapid alterations are not consistently seen in volume loading. The difference in response is difficult to clarify since it is not possible to effect alterations in left ventricular pressure or perfusion without profoundly affecting coronary perfusion. The present study describes cardiac protein synthesis in the right ventricle of the young guinea pig heart in vitro utilizing a perfusion model in which the right ventricle could be stressed by elevations of pressure or volume loading in the presence of constant and restricted coronary perfusion. With coronary flow maintained at 25 ml/min/g dry wt, an increase in right ventricular pressure from normal levels of 3 mm Hg to 11 mm Hg resulted in a 60% increase of myocardial incorporation of lysine-14 C into protein. However, with further increases of right ventricular pressure to 22 mm Hg, protein synthesis dropped back to normal levels. The fall-off in protein synthesis was not due to decreased contractility, alterations in intracellular lysine pool specific activity, or alterations in total coronary flow or pressure. A 60% increase in coronary perfusion was associated with a similar response of protein synthesis to progressive elevations of pressure. Since the ATP levels rose and lactate production fell, a deficiency of O2 did not entirely explain the decline of protein synthesis with maximal pressures. At all levels of coronary perfusion, volume loading for 3 hr did not result in increased protein incorporation of lysine-14 C. The studies indicate a relationship between ventricular pressure and protein synthesis unrelated to coronary flow per se and suggest a pressure receptor triggering protein synthesis within the ventricular wall. Such a relationship is not apparent in short term volume loading in vitro.

Adenosine Triphosphate↗
PubMed1975

Alcoholic cardiomyopathy: the effect of ethanol and acetaldehyde on cardiac protein synthesis.

The occurrence of cardiomy opathy in chronic alcoholics is well known, but the causes are as yet unclear (Mitchell and Cohen, 1970). Metabolic effects of ethanol, such as accumulation of triglycerides despite a decrease in fatty acid extraction (Regan et al., 1966; 1969), have been suggested as a cause of ultimate impairment of myofibrillar function. The suggestion has also been made that the detrimental effects of ethanol may actually be an acetaldehyde effect, mediated through the release of norepinephrine causing chronic chronotropic and inotropic effects which may often play a role in the development of the myopathy (James and Bear, 1967). It has been reported that acute exposure to alcohol decreases to one-third that of the control the capacity of the liver to synthesize albumin (Rothschild et al., 1971). In view of the rapid inhibitory effect, it was felt to be of interest to study the effect of alcohol in the perfused heart to see whether myocardial protein synthesis was similarly inhibited. In addition, since alcohol is apparently not metabolized by the heart (Gailis and Verdy, 1971; Lochner, Cowley, and Brink, 1969). The effect of a primary metabolite, acetaldehyde (James and Bear, 1967), synthesized in liver was also studied. The results indicated that acute exposure to levels of alcohol which decreased albumin synthesis in the perfused liver had no effect on protein synthesis in the perfused heart. However, acetaldehyde, at levels that produce a marked chronotropic and inotropic effect, markedly inhibited protein synthesis of total cardiac protein. To further define the inhibition of protein synthesis by acetaldehyde, the effects of ethanol and acetaldehyde on cardiac micorsomes were also studied in cell-free systems. Some of these data were reported previously (Schreiber et al., 1972; 1974).

Acetaldehyde↗