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J M Andersen

Publications and source records attributed to J M Andersen.

36 records · Page 2Linked to original sources
PubMed1981

Rates of sterol synthesis and uptake in the major organs of the rat in vivo.

This study was undertaken to determine the rates of sterol synthesis and uptake in the major organs of the female rat in vivo. At the mid-dark phase of the light cycle, control animals, animals in which hepatic sterol synthesis had been selectively inhibited by chylomicron infusion and animals in which the small intestine and liver had been surgically removed, were administered [(3)H]water, and the content of (3)H-labeled digitonin-precipitable sterols ([(3)H]-DPS) in different organs was measured 1 hr later. In control animals, the highest content of [(3)H]DPS was found in the liver (2279 nmol/hr per g), adrenal gland (1222), ovary (791), and small bowel (529): the content of newly synthesized sterols was much lower in 13 other tissues. By selectively inhibiting sterol synthesis in the liver or by surgically removing the small intestine and liver, it was determined that of the total amount of [(3)H]DPS synthesized in the whole animal about 50% had occurred in the liver, 24% in the small bowel, 8% in the skin, and 18% in the remaining tissues of the carcass combined. By analyzing the relationship between the content of [(3)H]DPS in blood and in each organ, it was further possible to determine how much [(3)H]DPS was synthesized and how much was taken up from the blood in each tissue. The highest rate of uptake was found in the adrenal gland where only 4% of the tissue content of [(3)H]DPS came from local synthesis. Low rates of synthesis relative to the rates of uptake, were also found in the spleen (6%), lung (17%), and kidney (26%). In contrast, in other organs there was little uptake of [(3)H]DPS from blood so that >75% of the [(3)H]DPS present in brain and muscle, for example, was due to local synthesis. Lowering the circulating levels of plasma cholesterol markedly increased the synthesis of [(3)H]DPS in tissues like adrenal gland, spleen, and kidney that were dependent upon plasma cholesterol as the major source of tissue sterols, but not in tissues such as muscle and brain. These studies have quantitated the importance of each major organ to total body synthesis and have delineated the rates of movement of [(3)H]DPS between major tissue compartments of the rat.-Turley, S. D., J. M. Andersen, and J. M. Dietschy. Rates of sterol synthesis and uptake in the major organs of the rat in vivo.

Animals↗
PubMed1981

Hypertension associated with protamine sulfate administration.

A case of protamine-associated hypertension in a 76-year-old Caucasian woman with chronic renal failure (CRF) undergoing hemodialysis is reported. Four dialysis runs during March 1977 are described in this report; all involved the i.v. administration of heparin sodium (2500-5000 units) during the five-hour procedures. Protamine sulfate (25-50 mg) was given i.v. at the end of each procedure to neutralize excess heparin. In three of the four dialyses, the patient became short of breath, hypertensive, and tachycardic, usually for less than 10 minutes. In the last of these runs, the patient first became hypotensive and then hypertensive, and was incontinent of urine and feces. Treatment in each case consisted of elevation of the head of the bed and oxygen administration. During the forth dialysis, no adverse reaction occurred. Possible explanations of this phenomenon are discussed, including hypersensitivity to protamine sulfate products and the action of protamine on platelets resulting in serotonin or histamine release. In dialyses where the patient became hypertensive, more protamine on platelets resulting in serotonin or histamine release. In dialyses where the patient became hypertensive, more protamine sulfate was given than was needed to neutralize the heparin. In the run where symptoms were most severe, the patient received only 2500 units of heparin but was given 50 mg protamine sulfate. It is concluded that this reaction occurred as a result of administering excess protamine sulfate, which then acted on platelets. The platelets released either histamine or serotonin, which mediated rapid changes in blood pressure, heart rate, and breathing pattern.

Aged↗
PubMed1979

Low and high density lipoproteins and chylomicrons as regulators of rate of cholesterol synthesis in rat liver in vivo.

The steady-state levels of plasma cholesterol carried in high and low density lipoproteins and in chylomicrons were varied over a wide range by use of a constant-infusion technique. After 40 hr, the rates of hepatic cholesterol synthesis and levels of hepatic cholesterol esters were measured and were related to the plasma level of each of the lipoprotein fractions. From the rates of infusion and the steady-state plasma levels attained, the whole animal clearance rates for cholesterol carried in low density and high density lipoproteins and in chylomicrons were calculated to be 0.53, 0.61, and 42.6 ml/hr, respectively. Hepatic cholesterol ester content increased by 0.8 mug/g for each 1.0 mg/dl increase in the steady-state level of plasma low density lipoprotein cholesterol and by 1.4 mug/g for a similar elevation in plasma high density lipoprotein cholesterol. In contrast, the increase in ester content was 300-fold greater when chylomicrons were infused (330 mug/g). The rate of hepatic cholesterol synthesis was inhibited by a factor of 0.004 and 0.007, respectively, per 1.0 mg/dl increase in the steady-state level of plasma cholesterol carried in either low density or high density lipoprotein but the inhibition was by a factor of 0.255, 50-fold greater, when chylomicrons were infused. Thus, in the steady state, cholesterol carried in either low density or high density lipoproteins is apparently taken up by the liver and regulates the rate of hepatic cholesterol synthesis; however, cholesterol carried in chylomicrons is at least 50-fold more effective in this regard. This marked difference can be attributed to the much higher rates of transport of chylomicron cholesterol into the hepatocyte than of cholesterol carried in either low density or high density plasma lipoproteins.

Animals↗
PubMed1979

Absolute rates of cholesterol synthesis in extrahepatic tissues measured with 3H-labeled water and 14C-labeled substrates.

This study was undertaken to develop techniques for measuring absolute rates of sterol synthesis in extrahepatic tissues in vitro and to estimate the magnitude of the errors inherent in the use of various 14C-labeled substrates for such measurements. Initial studies showed that significant errors were introduced when rates of synthesis were estimated using [3H]water since about 20 nmol of water were bound to each mg of tissue cholesterol isolated as the digitonide. This source of error could be eliminated by subtracting apparent incorporation rates obtained at 0 degrees C from those obtained at 37 degrees C or by regenerating and drying the free sterol. In a second set of experiments, the H/C incorporation ratio in cholesterol was determined in the liver by measuring the absolute rates of hydrogen and acetyl CoA flux into sterols. The ratio of 0.69 +/- 0.03 was found to be independent of the rate of hepatic cholesterol synthesis, the rate of hepatic acetyl CoA generation, or the source of the acetyl CoA. In a third set of studies, rates of incorporation of [3H]water or 14C-labeled acetate, octanoate, and glucose into digitonin-precipitable sterols were simultaneously measured in nine different extrahepatic tissues. Assuming that the H/C ratio measured in the liver also applied to these tissues, the [3H]water incorporation rates were multipled by the reciprocal of the H/C ratio to give the absolute rates of sterol synthesis in each tissue. When these were compared to the incorporation rates determined with the 14C-labeled substrates the magnitude of the errors in the rates of sterol synthesis obtained with these substrates in each tissue could be assessed. Only [14C]octanoate gave synthesis rates approaching 100% of those obtained with [3H]water and this occurred only in the intestine and kidney; in the other extrahepatic tissues this substrate gave rates of 6--66+ of the absolute rates. Rates of [14C]acetate incorporation in sterols varied from 4 to 62% of the [3H]water incorporation rates while those obtained with [14C]glucose were only 2--88% of the true rates. These studies document the large and highly variable errors inherent in estimating rates of sterol synthesis in extrahepatic tissues using 14C-labeled substrates under in vitro conditions.

Acetates↗
PubMed1977

Rate constants for the uptake of cholesterol from various intestinal and serum lipoprotein fractions by the liver of the rat in vivo.

The increase in the mass of cholesterol esters in the liver was used to estimate hepatic net uptake rates of cholesterol from various serum and intestinal lipoprotein fractions. Initial uptake rates equalled essentially zero for high density serum lipoproteins and for large chylomicrons while administration of both low density serum lipoproteins and smaller chylomicrons produced a significant increase in hepatic cholesterol ester levels. The rate of uptake of both serum lipoprotein fractions did not change over a 5 h interval after injection: in contrast, the rates of uptake of the intestinal fractions increased 10-25-fold during this interval. Circulation of large chylomicrons in functionally eviscerated rats markedly increased the rate of hepatic cholesterol uptake when these metabolized lipoproteins were reinjected into recipient animals. Uptake of cholesterol from intestinal lipoproteins was essentially a linear function of the amount of chylomicrons administered to the animals and was independent of the level of circulating serum cholesterol and the rate of hepatic cholesterogenesis. These observations are consistent with the view that the liver is capable of taking up cholesterol from chylomicron remnants and, at significantly lower rate, low density serum lipoproteins.

Animals↗
PubMed1976

Cholesterogenesis: derepression in extrahepatic tissues with 4-aminopyrazolo (3,4-d) pyrimidine.

Administration of 4-aminopyrazolo [3,4-d] pyrimidine decreased serum cholesterol levels in the rat to less than 5 milligrams per deciliter. Coincident with this change, there was a 2.1 - to 16.0-fold increase in the rate of sterol synthesis in seven extrahepatic tissues. This suggests that cholesterol carried in serum lipoproteins plays a major role in regulating sterol synthesis in many extrahepatic tissues.

Adenine↗
PubMedDate not supplied

pH effects on ciliomotility and morphology of respiratory mucosa.

Tracheal cilia of cows exposed, in vitro, for 20 hours to different acidities and alkalinities of sulfuric acid and sodium hydroxide, respectively, showed ciliomotility at pH values as low as 4.9, while the epithelial cells began to be expelled from the mucosa at pH 6.7, initiating a reduction of ciliary function around this pH value. In alkaline reactions, ciliostasis occurred at pH 9.76. Destroyed cilia were found above pH 10.15, while they were morphologically unchanged at pH values as low as 4.0, the lowest value examined. The first symptoms, however, of adverse effects were intracellular edema and the simultaneous occurrence of cellular polyps in both acid and alkaline reactions at pH 6.7 and 9.5, respectively. The results indicate that the early effects of air pollutants are better demonstrated by transmission electron microscopy studies than by, e.g., studies of ciliomotility.

Animals↗
PubMedDate not supplied

Primidone-induced catatonic schizophrenia.

The authors report the case of a severely retarded, 19-year-old female (treated with primidone 250 mg tid since age 12) who was admitted with visual and auditory hallucinations. After four days of continuing hallucinations, she went into classic catatonic schizophrenia. Upon examination, her primidone serum level was found to be well above the normal therapeutic range. The primidone dosage was decreased, and symptoms subsided as serum levels returned to normal.

Adult↗
PubMedDate not supplied

Serum sickness associated with 6-mercaptopurine in a patient with Crohn's disease.

A 43-year-old man with a 19-year history of Crohn's disease experienced serum sickness with acute lobular panniculitis and vasculitis within 2 weeks of initiating 6-mercaptopurine therapy. He had no history of extraintestinal manifestations of Crohn's disease or drug allergy. Symptoms included disabling joint pain, proteinuria, fever, rash, and malaise. To our knowledge, this adverse drug reaction has not been described in association with 6-mercaptopurine.

Adult↗