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P Furst

Publications and source records attributed to P Furst.

15 recordsLinked to original sources
PubMed2001

Proteasome- and p38-dependent regulation of ERK3 expression.

Proteasome inhibition leads to accumulation of transcription factors, heat shock proteins, cyclins, and other proteasome substrate proteins by blocking their proteolytic degradation. An increase in gene transcription upon proteasome inhibition was found for a group of proteins, including p21(WAF1/CIP1), ubiquitin, and transcription factors. In this study, we have demonstrated selective up-regulation of extracellular signal-regulated kinase 3 (ERK3) mRNA and protein expression upon treatment with peptide-based proteasome inhibitors or lactacystin. ERK3 is a family member of the mitogen-activated protein kinases (also called ERK) that are key mediators of signal transduction from the cell surface to the nucleus. ERK3 up-regulation is independent of the p53, Bcl2, and caspase 3 status of cells. p38 pathway kinase inhibitors prevent proteasome-dependent ERK3 induction and enhance the antiproliferative effect of proteasome inhibitors. MCF-7 cells expressing ERK3 ectopically show increased resistance toward proteasome inhibition. The results indicate that ERK3 expression is a consequence of p38 pathway activation and most probably represents an intracellular defense or rescue mechanism against cell stress and damage induced by proteasome inhibition.

Cysteine Endopeptidases↗
PubMed1998

Glyceraldehyde-3-phosphate dehydrogenase, the putative target of the antiapoptotic compounds CGP 3466 and R-(-)-deprenyl.

R-(-)-Deprenyl (Selegiline) represents one of the drugs currently used for the treatment of Parkinson's disease. This compound was shown to protect neurons or glias from programmed cell death in a variety of models. The mechanism of action of neuroprotection as well as inhibition of apoptosis remains elusive. CGP 3466 is a structurally related analog of R-(-)-deprenyl that exhibits virtually no monoamine oxidase type B inhibiting activity but is neuroprotective in the picomolar concentration range. We showed specific binding of CGP 3466 to glyceraldehyde-3-phosphate dehydrogenase by affinity binding, by affinity labeling, and by means of BIAcore(R) technology. Apoptosis assays based on the human neuroblastoma cell line PAJU established the importance of this interaction for mediating drug-induced inhibition of programmed cell death.

Animals↗
PubMed1996

Influence of medium-chain triglyceride-based lipid emulsion on rat polymorphonuclear cell functions.

Intravenous lipid emulsions are used as energy and essential fatty acids sources. There are controversial reports postulating in vitro and in vivo inhibitory effects of long-chain triglycerides (LCT) upon the blood polymorphonuclear leukocytes (PMNL) functions. In the present study the in vivo and in vitro effects of LCT and a physical mixture of medium- and long-chain triglycerides (MCT/LCT) emulsions were investigated on select PMNL functions, i.e., chemotaxis, phagocytosis, and bacterial killing. Blood from 20 rats was incubated with LCT, MCT, MCT/LCT, and saline, respectively. MCT-containing emulsions exhibited an inhibitory effect on all PMNL functions investigated, whereas LCT exerted an effect on the phagocytic index only. The administration of a parenteral supply of LCT, MCT/LCT, and saline for 30 h followed by saline infusion for 14 h in discontinuous mode did not influence any of the investigated PMNL functions. Similarly, continuous infusion over 44 h at increasing infusion rates up to 1.5 mL/h did not affect the PMNL functions. The obvious difference between in vitro and in vivo response of the PMNL model emphasizes the necessity for continuous monitoring of in vivo conditions. Appropriate interpretation of the data requires continuous circumspection and consideration of trials in a clinical setting.

Animals↗
PubMed1996

The use of an intravenous fish oil emulsion enriched with omega-3 fatty acids in patients with cystic fibrosis.

The effects of parenteral nutrition supplemented with a lipid emulsion enriched with the omega-3 fatty acids (FA), eicosapentaenoate (20:5n-3) and docosahexaenoate (22:6n-3), derived from fish oil were compared to a standard lipid emulsion containing omega-6 FA in patients with cystic fibrosis (CF). Patients were randomized to receive either Omegavenous 10%, which contains fish oil (IFO), or Liposyn III 10% (control) daily for 1 mo at a dose of 150 mg/kg. There were no observed allergic or toxic reactions, no abnormalities in liver function tests or coagulation parameters. To assess the bioavailability of the lipid administered, measurement of plasma free fatty acid (FFA) levels were made of the essential FA. There were no adverse changes in plasma levels of the omega-6 FA (18:2n-6, 18:3n-6, 20:3n-6, and 20:4n-6), and plasma levels of the omega-3 FA (20:5n-3 and 22:6n-3) increased significantly during the 1-mo study. There were no significant changes in plasma FFA profiles of the essential FA for the patients receiving the control lipid. The effect of treatment on pulmonary function was also investigated. There were no significant changes in FVC, FEV1, PEFR, FEV1/ FVC, or FEF25-75 (absolute value or percentage) over the 4 weeks of study in the group receiving IFO or control. This preliminary investigation suggests that intravenous administration of fish oils enriched with long chain omega-3 FA to patients with CF is safe and bioavailable.

Adolescent↗
PubMed1996

More on metformin.

Explore the source record for details and available documents.

Drug Interactions↗
PubMed1989

Energy production, intracellular amino acid pools, and protein synthesis in chronic renal disease.

Intracellular glycolytic regulating enzyme activities, pyruvate kinase (PK) and phosphofructokinase (PFK), adenylate kinase (AK), energy charge (Ech), free amino acids (ICAA), and protein synthesis (PS) were measured in polymorphonuclear leukocytes--used as a cell model--in 62 adults and 12 children with chronic renal failure, and 66 normal adults and 21 children as comparison controls. In normal subjects, children had significantly lower enzyme activities and cell amino acid levels but similar Ech and higher PS than adults. ICAA concentrations were significantly higher than plasma amino acid concentrations (PAA) in both groups, and the PAA were not correlated with, nor indicative of, the ICAA concentrations. The variance (R2) in PS could be largely accounted for by a combination ("set") of six ICAA, as determined by multivariate analysis. The sets differed in children vs adults, suggesting that different proteins were being synthesized. In the uremic patients, reduced PF, PFK, Ech, most ICAAs and PS were indicative of cellular malnutrition. For the uremic adults, the abnormalities in cell metabolism were modified by therapy--nondialyzed uremics being worst, CAPD patients best and approximately normal, and hemodialyzed intermediate. The uremic CAPD children had reduced, PK, PFK, AK, most ICAA, and PS. Ech was increased. Cellular malnutrition in children with chronic renal failure may contribute to their poor growth.

Adolescent↗
PubMed1985

Muscle and plasma amino acids during semi-starvation in normal subjects: hypocaloric glucose vs. amino acid infusions.

Normal subjects were fed hypocaloric amounts of amino acids or glucose for 3 days to separate the effects of these nutrients from those of trauma on muscle and plasma amino acids. Intracellular and plasma levels of Val, Leu and Ile were increased in both groups but were increased to a greater extent when amino acids were infused. Intracellular free glutamine concentration in muscle tissue was not significantly altered. Some of the trauma induced changes in amino acids can be replicated by maintaining normal subjects on hypocaloric amino acids; the decrease in glutamine concentration seen with trauma is not a function of hypocaloric nutrition.

Journal Article↗
PubMed1980

Muscle and plasma amino acids after injury: hypocaloric glucose vs. amino acid infusion.

This study examines the effect of three different hypocaloric diets on the patterns of muscle and plasma amino acids in patients undergoing total hip replacement. Group I (seven patients) received 90 g/day of glucose, Group II (seven patients) received 70 g/day of amino acids, Group III (eight patients) received both 90 g of glucose and 70 grams of amino acids per day. Utilizing the percutaneous biopsy technique of Bergström, free amino acid patterns in muscle and plasma were analyzed pre- and postoperatively (day 4). The postoperative pattern of amino acids was characterized by elevated levels in muscle and plasma of the branched chain amino acids, phenylalanine, tyrosine and methionine. There was a marked decrease in muscle glutamine and smaller decreases in the basic amino acids in both muscle and plasma. Muscle:plasma concentration ratios increased for the neutral amino acids, decreased for glutamine and the basic amino acids and were unchanged for the acidic amino acids. The patterns seen after hip replacement are almost identical to those seen after colectomy or accidental injury. There was little effect of diet on amino acid concentrations in muscle. In plasma, concentrations of leucine, isoleucine, valine and proline were higher in Group II in the absence of glucose intake, than in the other groups. Lysine was lower in Group I with no amino acid intake than in the other groups. Thus, there is a unique amino acid pattern associated with operative trauma which is relatively unaffected by hypocaloric, intravenous nutrition.

Amino Acids↗
PubMed1980

Muscle and plasma amino acids following injury. Influence of intercurrent infection.

The present study was undertaken to determine intracellular amino acid patterns in patients with multiple trauma, whether or not complicated by sepsis and during convalescence. A percutaneous muscle biopsy was performed three to four days following major accidental injury in ten patients and analyzed for muscle free amino acids. Venous blood was drawn at the time of the biopsy and analyzed for plasma free amino acids. Five patients developed sepsis and a repeat biopsy was performed on days 8 to 11. In five of the patients a biopsy was performed during the late convalescent period (anabolic phase). A marked depletion of nonessential amino acids in muscle occurred in both injury and sepsis due to a decrease (50%) in glutamine, which was equally marked in both states. The essential amino acids in muscle increased in injury. During sepsis, a further increase was observed with a return toward normal in the convalescent period. In injury, the most marked rise was in the branched-chain amino acids, phenylalanine, tryosine and methionine. With sepsis, a further rise in muscle branched-chain amino acids, phenylalanine and tryosine occurred, while plasma levels remain unchanged. During convalescence, muscle glutamine, arginine, histidine and plasma branched-chain amino acids were below normal, whereas muscle phenylalanine and methionine were elevated. The muscle free amino acid pattern observed after major trauma was essentially the same as earlier described following elective operation. This suggests a common response of intracellular amino acids irrespective of the degree of injury, and may indicate that the pump settings which regulate amino acid transport follow the "all or none" rule. The high intracellular levels of branched-chain amino acids in sepsis suggest that the energy deficit of this state is due to an impairment of substrate use rather than intracellular availability. The high concentrations of the aromatic amino acids and methionine may be due to altered liver function. During the late convalescent period (anabolic phase) the low levels of certain key amino acids suggests inadequate nutrition. The difficulties in nourishing the injured or septic patient are well recognized. The period following these catabolic states may be an important period for the application of an optimal, aggressive nutritional regimen.

Abdomen, Acute↗
PubMedDate not supplied

Chemical analytic approaches to the definition of uremic toxins.

In this preliminary research we have started a systematic study of substances present in uremic but non in normal serum. Methylguanidine has been examined by the new single method of ion pair extraction and has been found in higher concentration in uremic plasma than in normal, but in lower concentration than previously described with less selective method and used in experimental animal intoxication. We did not find a correlation of Methylguanidine concentration and uremic symptoms and complications as pericarditis, neuropathy and uremic coma. Using the high spead gel filtration method comparative analyses of uremic and normal fluids and many substances have been registered a 9 peak serie. Peak 7 seem to be the most interesting. It is less prominent in normal plasma, increases in uremic patients and decreases after dietary treatment, peritoneal dialysis and hemodialysis. Furthermore it is formed by middle molecular weight substances (approximately 1300).

Chromatography, Gel↗
PubMedDate not supplied

Branched-chain amino acids and respiratory pattern and function in the neonate.

Branched-chain amino acids (BCAA) increase respiratory drive in adults and improve diaphragmatic function in vitro. This study was designed to examine the effects of increased amounts of BCAA in intravenous nutrition on respiratory function and episodes of apnea in premature infants. An open cross-over design was used, with each patient serving as his own control. Ten premature infants, 34 weeks' gestation or less, were observed. Mean gestational age was 30.6 weeks (range 27 to 33 weeks), mean birth weight was 1487 gm +/- 300 gm, and the age at study was 5 to 33 days. For three consecutive 24-hour periods, the infants received routine total parenteral nutrition (TPN) (30% BCAA), enriched TPN (53% BCAA), and routine TPN (30% BCAA). Pulmonary function, apnea frequency, blood chemistry, and amino acid pattern were measured. Enriched TPN resulted in significant increases in all infants in dynamic compliance, from 2.41 +/- 1.07 to 4.55 +/- 2.78 ml/cm H2O (p < 0.025), and in specific dynamic compliance from 1.67 +/- 0.64 to 3.1 +/- 1.51 ml/cm H2O/kg (p < 0.005). Total pulmonary resistance decreased from 40.3 +/- 23.3 to 24.0 +/- 20.9 cm H2O/L/sec (p < 0.05), and peak-to-peak pressure decreased from 5.96 +/- 0.93 to 4.09 +/- 2.34 cm H2O (p < 0.05). All values returned to baseline with resumption of the routine TPN. In four infants with significant apnea, the average number of episodes of apnea decreased from 58 during standard TPN to 11 with the enriched solution infusion during matched 12-hour periods (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗