Plasminogen activators and plasminogen activator inhibitors in neural development.
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Animals↗
Biomedical subjects
G Friedman
Publications and source records attributed to G Friedman.
Regulation of lipoprotein lipase by dibutyryl cAMP, cholera toxin, Hepes and heparin in F1 heart-cell cultures.
Regulation of lipoprotein lipase was studied in mesenchymal rat heart-cell cultures. Treatment of the cultures with dibutyryl cyclic AMP or with cholera toxin resulted in an increase in LPL activity and a comparable increase in LPL mRNA. When the cells were exposed to 100 mM Hepes for 24 h, total enzyme activity rose 2-fold and LPL mRNA increased 2.4-fold. After 72 h, there was a 3-fold increase in LPL mRNA and a 4-fold rise in cellular LPL activity, while medium activity increased 20-fold. Exposure of the cultures to heparin for 24 h resulted in a 3.2-fold increase in total activity and a 36-fold increase in medium activity. This increase was not accompanied by any rise in LPL mRNA. Addition of actinomycin D to control dishes for 24 h resulted in a 33% reduction in LPL mRNA and a 43% reduction in enzyme activity. These values were 71% and 56%, respectively, in Hepes-treated cells, indicating that no stabilization of LPL mRNA occurred under these conditions. It can be concluded that in mesenchymal rat heart-cells in culture cAMP and cholera toxin upregulate lipoprotein lipase at the level of transcription. The increase in LPL activity after 24 h exposure to Hepes could be compatible with transcriptional regulation, while exposure to heparin is not accompanied by a change in LPL mRNA.
Animals↗
Recombinant human interleukin-1 suppresses lipoprotein lipase activity, but not expression of lipoprotein lipase mRNA in mesenchymal rat heart cell cultures.
The effect of human recombinant interleukin-1 (IL-1) on the regulation of lipoprotein lipase (LPL) was studied in rat heart mesenchymal cell cultures. A time-dependent reduction in enzyme activity occurred with a 30% fall after 1 h. The suppression of enzyme activity was accompanied by a commensurate reduction in enzyme mass. The reduction in LPL activity was most prominent in the heparin releasable pool; IL-1 treatment resulted in a 7.2-8.3-fold decrease in the functional compartment and a 2.5-2.8-fold decrease in residual cellular activity. The effect of IL-1 could be prevented by the addition of the IL-1 inhibitor. However, in contradistinction to the effect of tumor necrosis factor (TNF), there was no change in LPL mRNA in cultures treated with IL-1. The present results show that the regulation of LPL in mesenchymal heart cell cultures by IL-1 occurs posttranscriptionally, as has been shown in 3T3 cells. The more pronounced effect on LPL activity in the functional pool suggests that IL-1 treatment might have influenced also the processing and/or transport of the enzyme to the cell surface.
Animals↗
Complications of diagnostic cardiac catheterization requiring surgical intervention.
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Adult↗
The expression of lipoprotein lipase activity and mRNA in mesenchymal rat heart cell cultures is modulated by bFGF.
The effect of basic fibroblast growth factor (FGF) on lipoprotein lipase (LPL) production was studied in mesenchymal rat heart cell cultures. Addition of FGF to culture medium containing 20% serum resulted in a 3-fold increase in LPL activity. The minimal effective dose of FGF was 10 ng/ml and the increase occurred after exposure for 48 h. Addition of FGF was effective during the first week in culture, when enzyme activity was increasing, but not after 11 days when the cultures were superconfluent and the enzyme activity was high. Addition of FGF to serum-poor medium was able to replace serum required to sustain LPL activity. In FGF-treated cultures, more LPL activity was present in the functional pool, but not in the medium, than in the controls. The increase in enzymic activity was accompanied by an increase in enzyme mass and in LPL mRNA.
Animals↗
Apolipoprotein E is secreted by cultured lipocytes of the rat liver.
Hepatic lipocytes, the retinoid-storing cells of the liver, share several characteristics with vascular smooth muscle cells. To determine whether they also share the characteristic of apolipoprotein E secretion, we have compared the relative mRNA expression and protein secretion of apolipoprotein E, apolipoprotein A-I, and apolipoprotein A-IV in early primary cultures of lipocytes, hepatocytes, and Kupffer cells. Expression of apolipoprotein mRNAs was detected using the polymerase chain reaction and oligonucleotide primers specific for apolipoprotein E, apolipoprotein A-I, and apolipoprotein A-IV. Cellular mRNA concentrations were compared by dot blot analysis, and apolipoprotein secretion was assessed by immunoblot analysis of culture media. Apolipoprotein E mRNA was found in all three cell types, whereas apolipoprotein A-I and A-IV mRNAs were detected only in hepatocytes. Hepatocyte, lipocyte, and Kupffer cell media all contained a Mr approximately 36,000 protein identified by an antibody specific for rat apolipoprotein E. The relative concentration of apolipoprotein E mRNA per microgram of total cellular RNA in lipocytes, hepatocytes, and Kupffer cells was 1.0, 3.0, and 1.6, respectively. The relative secretion of apolipoprotein E per cell was also lowest in lipocytes, being twofold greater in hepatocytes and 1.4-fold greater in Kupffer cells. The secretion of apolipoprotein E by lipocytes is not only an additional smooth muscle cell-like characteristic of the hepatic lipocyte, but also raises the possibility of retinol mobilization upon apolipoprotein secretion.
Animals↗
Diet and the irritable bowel syndrome.
Food intake plays a key role in triggering or perpetuating symptoms in patients with IBS. Evaluation of the impact of diet in the individual patient requires a precise dietary history and a 7-day prospective dietary analysis, which should include the quality and quantity of food consumed, chronologic sequence and nature of symptoms, and the frequency and consistency of bowel movements. The caloric density of the meal, total fat intake, the quantity and quality of lactose-containing foods, sorbitol, fructose, and the nature and quantity of soluble and insoluble fiber intake must be noted. Patients with reflux esophageal symptoms should eliminate foods that decrease LES pressure, such as chocolate, peppermint, alcohol, and coffee. Direct esophageal mucosal irritants such as tomatoes, citrus juices, sharp condiments, and alcohol should be limited. Gastric emptying is slowed with the ingestion of fats and soluble fiber. Small bowel motility is slowed by soluble fiber and fatty foods. Gaseous syndromes may be reduced by avoidance of smoking, chewing gum, excessive liquid intake, and carbonated drinks. The reduced intake of large amounts of lactose-containing foods, sorbitol, and fructose may limit postprandial bloating. Flatus production can be lowered by reducing fermentable carbohydrates such as beans, cabbage, lentils, brussel sprouts, and legumes. Soluble and insoluble fiber ingestion will reduce sigmoidal intraluminal pressures and overcome spastic constipation when given in progressive graded doses. Effective dietary manipulations remain a key factor in reducing symptoms in IBS.
Colonic Diseases, Functional↗
Treatment of the irritable bowel syndrome.
Individualization of treatment for patients with IBS is predicated on a thorough analysis of the patient's symptoms, consideration of the reasons for seeking health care, evaluation of symptom-precipitating factors, elimination of confounding features, and the absolute knowledge of the absence of organic illness. Collecting and codifying appropriate historical data allow the physician to educate the patient with respect to the origin of his symptoms, and to enlist the patient as a partner in his future health care. There is no single, universally accepted therapeutic agent available for the treatment of the IBS patient. As a result, treatment is directed at reducing the frequency and intensity of triggering factors as well as ameliorating the symptoms when they arise. Symptoms evoked by psychologic factors may be effectively reduced by psychotherapy or hypnotherapy. Situational anxiety may be treated for brief periods by using antianxiety agents such as diazepam, chlordiazepoxide, buspirone, or similar agents. Depressive reactions may be reduced with suitable doses of antidepressant agents such as amitriptyline. Smooth muscle hyperreactivity may be dulled with small amounts of selected anticholinergics, which are usually most effective in reducing meal-induced discomfort. Peppermint oil may be of additional benefit. Gas-related symptoms require elimination of contributory dietary factors, such as lactose-containing foods, sorbitol, or fructose, as well as certain oligosaccharides. Simethecone, charcoal, or beanase may be helpful. Functional constipation is best treated with graded doses of insoluble or soluble fiber. Diarrheal episodes may be reduced with either loperamide or diphenoxylate. Careful, continued follow-up assessment of therapeutic endeavors, a sincere interest in the patient's concerns, and surveillance for intercurrent organic illness are the cornerstones of complete ongoing care.
Antidepressive Agents↗
Cellular metabolism of human plasma intermediate-density lipoprotein (IDL).
The cellular metabolism of human plasma intermediate-density lipoprotein (IDL) was investigated in cultured human skin fibroblasts and hepG-2 cell in the absence and presence of exogenous recombinant or plasmatic apo E-3. IDL (d 1.006-1.019 g/ml) and LDL (d 1.019-1.063 g/ml) were prepared by centrifugation from the plasma of apo E-3/3 or 4/3 normolipidemic human subjects. Without added apo E-3, IDL binding and cell association are similar or slightly reduced while their degradation is one third to one half. This results in degradation to binding ratios for IDL that are half those for LDL. Exogenous apo E-3 enhances binding, association and degradation of IDL by 50-150%, but the degradation to binding ratio remains low. Exogenous apo E-3 also increased the ability of IDL but not LDL, to down-regulate the incorporation of [14C]acetate to sterol by the cells. The optimal concentration of apo E-3 is 4 micrograms protein/10 micrograms IDL protein and at that concentration appreciable amounts of the apo E are found associated with the lipoprotein. Apo E-2 has no effect on the cellular metabolism of IDL and apo E-3 is not effective in receptor-negative human fibroblasts. Monoclonal antibodies that block apo E binding to B,E (LDL) receptor (1D7) abolish the cellular metabolism of IDL while antibodies against B-100 (4G3) are ineffective. In competitive binding experiments, IDL is slightly more effective than LDL in displacing 125I-LDL from receptors in hepG-2 cells and appreciably more effective than LDL when tested against 125I-IDL. Apo E-3 increases the capacity of IDL to compete with either 125I-LDL or 125I-IDL. Addition of apo E-3 also increases the binding affinity of IDL to hepG-2 receptors, with Kd values of 2.50, 0.93 micrograms protein/ml, respectively. The study demonstrates the essential role that functional apo E molecules play in the interaction of human IDL with cellular receptors. Yet, in spite of presence of apo E in IDL (2-3 molecules/particle) and enrichment of IDL with apo E-3 (to 4-5 molecules/particle) the proteolytic degradation of the lipoprotein by specific cellular receptor is similar to LDL.
Antibodies, Monoclonal↗
Interaction of lipoprotein lipase with subendothelial extracellular matrix.
We have analyzed the binding of lipoprotein lipase (LPL) to the subendothelial extracellular matrix produced by cultured endothelial cells. Binding was linear up to a concentration of 0.5 microgram/ml (10 nM) enzyme used in this study, and equilibrium was achieved after 2 h of incubation with bovine 125I-LPL at 4 degrees C. Heparin and heparan sulfate effectively inhibited the binding of LPL to extracellular-matrix-coated plates; chondroitin sulfate had no effect, while high concentrations of dermatan sulfate or keratan sulfate inhibited binding of LPL to extracellular matrix by only 40%. Basic fibroblast growth factor (bFGF) did not affect LPL binding, while antithrombin-III (AT-III) caused up to a 50% inhibition of enzyme binding to extracellular matrix. alpha-Thrombin. 5.10(-6) M, and its esterolytically inactive derivative, DIP-alpha-thrombin, effectively inhibited binding of LPL to extracellular-matrix-coated plates. alpha-Thrombin was also able to release the extracellular-matrix-bound LPL in an active form. Extracellular-matrix-bound LPL detached into medium containing triolein emulsion and/or serum, and was catalytically active after being released. Extracellular-matrix-bound LPL lost 30% of its activity following incubation at 37 degrees C for 4 h. in contrast to soluble LPL which lost 75% of its activity. It is plausible to conclude from these data that in vivo the subendothelial basement membrane, similarly to extracellular matrix, sequesters and stabilizers LPL secreted into the subendothelial space by non-endothelial cells, and thus may play an important role in determining the route of LPL from its site of synthesis to its site of action.
Animals↗
Lethal hypoglycemia and hypothermia induced by administration of low doses of tumor necrosis factor to adrenalectomized rats.
An increased sensitivity of adrenalectomized (Adex) rats to intravenous (IV) injection of recombinant human tumor necrosis factor (rHuTNF) was manifested by a marked increase in the rate of mortality. The rats that died exhibited severe hypoglycemia and hypothermia. Administration of 2.5 or 10 micrograms/100 g body weight (3% or 12%) of the lethal dose in sham-operated rats (90 micrograms/100 g body weight) rHuTNF caused a mortality rate of 50% or 100%, respectively, within 4 hours of its injection. Pre-administration of dexamethasone or intermittent glucose infusion protected the animals from the lethal effect of rHuTNF. Indomethacin did not change the mortality rate in rHuTNF-treated Adex rats, but prevented it in sham-operated rats. The rats that died exhibited a marked decrease in body temperature, but only Adex rats developed hypoglycemia after low doses of TNF. Pretreatment with dexamethasone prevented the hypothermia in both Adex and sham-operated rats, while indomethacin was effective only in sham-operated rats and did not prevent the hypothermia or the hypoglycemia in Adex rats. In the surviving rHuTNF-treated Adex rats, a rapid increase in body temperature occurred, blood glucose decreased to 30 mg/dL, serum insulin concentration decreased to 6 microU/mL, liver glycogen content was reduced by 98%, and a significant reduction in liver phosphoeonolpyruvate carboxykinase (PEPCK) and liver microsomal glucose-6-phosphatase activities was observed. Repeated administration of glucose IV to rHuTNF-treated Adex rats caused an increase in blood glucose and insulin concentrations, and some repletion in liver glycogen content. Injection of rHuTNF, 2.5 to 10 micrograms/100 g body weight, to sham-operated rats caused a significant but slower increase in body temperature.(ABSTRACT TRUNCATED AT 250 WORDS)
Adrenal Medulla↗
Smoking depresses adipose lipoprotein lipase response to oral glucose.
Adipose tissue lipoprotein lipase was studied in smokers (n = 17) aged 18-47 years and compared with enzyme activity in non-smokers of comparable age (n = 8) and a second time in some of the subjects 5-9 weeks after cessation of smoking (n = 7). Serum cotinine levels served to validate the smoking status of the subjects. Fasting enzyme activity was similar in smokers and non-smokers, when expressed per 10(6) cells, but was significantly increased when normalized for cell size. When lipoprotein lipase was determined in the same individual 4 h after an oral glucose load, a significant decrease (P less than 0.002) occurred in the smokers, while enzyme activity rose in the nonsmokers (P less than 0.02). A tendency for enzyme activity to rise after oral glucose was seen in ex-smokers, which did not reach statistical significance. Even though the mean serum insulin and glucose levels did not differ in the three groups of subjects, the per cent decrease in lipoprotein lipase after oral glucose in smokers was negatively correlated with insulin release into serum in the same subject, i.e., the greater the insulin release, the less the decrease in lipoprotein lipase activity. We would like to propose that the lower body weight in smokers is related to the paradoxical response of adipose tissue lipoprotein lipase to carbohydrate and that the reversal of this behaviour contributes to the weight gain often observed after cessation of smoking.
Adipose Tissue↗
Septic arthritis of the sternoclavicular joint in healthy adults.
Septic arthritis of the sternoclavicular joint (SCJ) is a rare disorder, and is usually associated with predisposing factors such as contiguous foci of infection, heroin addiction, rheumatoid arthritis and diabetes mellitus. Three cases in previously healthy adults are reported here. The aetiology, clinical manifestations and treatment are briefly reviewed. The considerable difficulty in diagnosing this disorder in adults is emphasized. In summary, diagnosis of septic arthritis of the SCJ in adults requires a high index of suspicion, and must be considered not only in patients with predisposing factors, but also in previously healthy adults.
Adult↗
Superinduction of the human gene encoding low density lipoprotein receptor.
Expression of human LDL receptor mRNA and protein is induced in human glioblastoma-astrocytoma cells upon transfer into lipoprotein-deficient medium, a mode of induction likely to be physiological. The presence of cycloheximide (CHX) leads to up to 7.5-fold superinduction of LDL receptor mRNA within 4 hr and, upon removal of this inhibitor, to superinduction of LDL receptor protein as well. The extent of superinduction of LDL receptor mRNA reaches over 40-fold beyond the level expressed in medium containing regular serum. Despite its extensive superinduction, LDL receptor mRNA decays rapidly in the presence of CHX. Stabilization of LDL receptor mRNA is thus unlikely to account for the observed superinduction. These results show that normally the LDL receptor gene is expressed to only a small fraction of its full potential.
Cell Line↗
Prolonged reversible acute renal failure in focal glomerulonephritis with severe nephrotic syndrome in an elderly patient.
A clinical report of a 67-year-old woman who developed reversible acute renal failure due to focal glomerulonephritis with severe nephrotic syndrome is presented. The patient required four weeks' dialysis treatment but recovered completely. The role of temporary dialysis and diuretics on the clinical course and the reversibility of the process in old age is discussed.
Acute Kidney Injury↗
Mechanism of the hypertriglyceridemia induced by tumor necrosis factor administration to rats.
4 h after intravenous injection of recombinant HuTNF-alpha to fed rats, an increase in heart, diaphragm, and plasma lipoprotein lipase activity was observed. At the same time, a 40-60% decrease in enzymic activity in epididymal fat pad and kidney and 40% decrease in hepatic lipase activity in liver had occurred. Similar results were obtained 20 h after injection of recombinant HuTNF-alpha into fasted rats. Pretreatment with Indomethacin did not affect the changes in tissue lipoprotein lipase activity observed following recombinant HuTNF-alpha administration. Serum triacylglycerol concentration increased by 2- and 6-fold; 4 and 20 h after recombinant HuTNF-alpha administration. Disappearance of 14C-labeled triacylglycerol from the circulation after injection of small chylomicrons, biosynthetically labeled in their triacylglycerol and cholesterol moieties, was lower in TNF-treated than in control rats. However, the clearance rate of triacylglycerol was the same or even higher in recombinant HuTNF-alpha treated rats (assuming that 14C-labeled chylomicron triacylglycerol represents the serum triacylglycerol pool). The livers of recombinant HuTNF-alpha-treated rats and controls contained similar amounts of 14C-labeled lipids, but less [3H]cholesterol, suggesting that in recombinant HuTNF-alpha-treated rats, the liver took up chylomicron remnant particles enriched with triacylglycerol. Separation of the d less than 1.04 g/ml fraction of serum obtained from control and recombinant HuTNF-alpha treated rats by zonal ultracentrifugation revealed that in recombinant HuTNF-alpha-treated rats the lipoprotein particles were less lipolyzed than in controls. The secretion rate of [3H]triacylglycerol into the serum was determined 90 min after injection of [3H]palmitate albumin complex and Triton WR 1339. In recombinant HuTNF-alpha-treated rats, the secretion of [3H]triacylglycerol into plasma was 48% higher than in controls. It is suggested that the increase in lipoprotein lipase activity of heart and diaphragm resulted from an indirect effect of TNF. It is concluded that the increase in serum triacylglycerol in the recombinant HuTNF-alpha-treated rats is due mainly to an increased secretion of triacylglycerol by the liver. Impaired lipolysis, probably due to a fall in hepatic lipase could also contribute to the rise in plasma triacylglycerol.
Animals↗
Nutritional therapy of irritable bowel syndrome.
Nutritional factors relative to IBS include diagnostic and therapeutic considerations. Etiologically, foods do not cause IBS. A small percentage of patients with childhood allergic diatheses, usually in association with atopic dermatitis and asthma, may be intolerant to one or more of wheat, corn, dairy products, coffee, tea, or citrus fruits. Diagnostically, many patients labeled as IBS subjects are in fact intolerant to the ingestion of lactose-containing foods, sorbitol, fructose, or combinations of fructose and sorbitol. A precise dietary history will characterize this group. Taken in its broadest context, IBS involves the entire hollow tract inclusive of esophagus, stomach, small bowel, and colon. The symptomatic presentation relative to the hollow organ involved allows the selection of dietary manipulations that may help to reduce symptoms. Gastroesophageal reflux, a consequence of low LES pressure in some IBS patients, may be treated with the elimination of fatty foods, alcohol, chocolate, and peppermint. Delayed gastric emptying may be helped by the elimination of fatty foods and reduction of soluble fiber. Aberrant small bowel motor function may be ameliorated by reduction of lactose, sorbitol, and fructose and the addition of soluble fiber. Gas syndromes may be improved by reduced intake of beans, cabbage, lentils, legumes, apples, grapes, and raisins. Colonic motor dysfunction may be overcome by the gradual addition of combinations of soluble and insoluble fiber-containing foods and supplements. The selective use of activated charcoal and simethicone may be helpful.
Colonic Diseases, Functional↗
Irritable bowel syndrome: I. A practical approach. ACG Committee of FDA-Related Matters. American College of Gastroenterology.
An overview of current concepts of the irritable bowel syndrome has been presented. The definition, symptomatology, epidemiology, diagnosis, physical examination, and appropriate evaluation have been discussed. The role of emotional factors as triggering mechanisms has been analyzed. Succeeding papers will deal with clinical and experimental findings related to motor dysfunction in this disorder, nutritional factors related to the irritable syndrome, and a final paper discussing appropriate therapeutic approaches in IBS.
Colonic Diseases, Functional↗