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Biomedical subjects

J A Weinstein

Publications and source records attributed to J A Weinstein.

9 recordsLinked to original sources
PubMed1991

Ethanol induces a1-protease inhibitor mRNA in Hep 3B cells.

Ethanol alters many metabolic processes within the liver. Both ethanol abuse and the inability to mount an acute phase response (APR) have been associated with an increased morbidity and mortality in critically ill patients. To determine if ethanol influences the hepatic APR, relative amounts of two different human acute phase protein mRNA's were examined in the human hepatoma cell line Hep 3B before and after exposure to ethanol. Hep 3B cells were treated with one or more of the following: ethanol ((E) 150 mM); interleukin-1 beta ((IL-1) 200 units/ml); or interleukin-6 ((IL-6) 50 units/ml). After a 12-20 hr incubation relative amounts of mRNA for a1-protease inhibitor (PI) or beta fibrinogen were determined by Northern blot hybridization. Both ethanol and IL-6 were found to induce a1-PI mRNA. Fibrinogen mRNA was induced by IL-6 but not by ethanol, and no induction of PI or fibrinogen mRNA was found with IL-1. This suggests that under certain conditions, ethanol may influence acute phase protein metabolism. To our knowledge, this is the first description of an ethanol induced alteration of acute phase protein mRNA.

Carcinoma, Hepatocellular↗
PubMed1988

A controlled trial of esmolol for the induction of deliberate hypotension.

Twenty-five patients scheduled for lumbar fusion or cerebrovascular surgery were enrolled in an open label treatment controlled study comparing blood pressure and heart rate responses during deliberate hypotension with either esmolol or nitroprusside during steady-state N2O/isoflurane anesthesia. The first 5 patients were empirically assigned to the esmolol group; the remaining 20 patients were randomized to receive either esmolol or nitroprusside. The target of 15% reduction in mean arterial pressure (MAP) from baseline determined during anesthesia was attained with esmolol 195 +/- 10 micrograms/kg/min (mean +/- SEM) for the group (n = 15) or nitroprusside 1.9 +/- 0.3 micrograms/kg/min for the nitroprusside group (n = 10). Nitroprusside use was associated with a 15.9 +/- 5.3% increase in heart rate compared to a 12.1 +/- 2.2% decrease in the esmolol group (p = 0.0001 between groups). Upon termination of the hypotensive infusions, nitroprusside patients had a MAP increase of 13.9 +/- 5.5% above baseline (p less than 0.05 compared to prehypotension) while the 7.4 +/- 3.5% increase in the esmolol group was not statistically significant. Although 30% of nitroprusside patients overshot their baseline MAP by more than 25%, no esmolol patients had this degree of rebound. One esmolol patient had a brief period of atrial premature contractions. No patient in either group suffered any adverse reaction to hypotension. It is concluded that in moderate doses esmolol is a safe and effective hypotensive agent during isoflurane anesthesia, with no reflex tachycardia and no significant potential for rebound hypertension. A MAP reduction of 30% from preanesthesia baseline was readily obtained with this combination.

Adrenergic beta-Antagonists↗
PubMed1988

Pharmacodynamics of vecuronium and atracurium in the obese surgical patient.

The effect of obesity on the duration of action of the nondepolarizing muscle relaxants atracurium and vecuronium was studied in 28 neurosurgical patients. In obese patients given vecuronium (0.1 mg/kg), the time to go from 5 to 25% of recovery of twitch response was statistically significantly longer (14.6 +/- 7 minutes, mean +/- SD) than it was in nonobese control patients (6.9 +/- 2 minutes). Similarly, with vecuronium times for recovery from 25 to 75% were longer (33 +/- 15 minutes) in obese patients than in control patients (13.2 +/- 2 minutes), as was time to 75% recovery, 82 +/- 30 minutes in obese patients, 50 +/- 9 minutes in controls. In contrast, obese patients given atracurium (0.5 mg/kg) exhibited no difference in recovery indexes or recovery times when compared to control patients of normal weight. The prolonged duration of action of vecuronium in obese patients is most likely related to impaired hepatic clearance and/or an overdose effect with recovery occurring during the distribution phase. That the duration of action of atracurium is not prolonged in the obese is believed due to this relaxant's not depending on organ function for elimination.

Adult↗
PubMed1987

Interleukin-1 and the acute-phase response: induction of mouse liver serum amyloid A mRNA by murine recombinant interleukin-1.

Traumatic tissue injury of infection provokes a systemic inflammatory response, termed the acute-phase response, which is accompanied by hepatic synthesis of certain plasma proteins. Increased levels of serum amyloid A (SAA), C-reactive protein (CRP), and fibrinogen have been observed during the acute-phase response. One possible mediator of the acute-phase response is interleukin-1, a pro-inflammatory monokine released in response to traumatic tissue injury or infection. There is evidence that partially purified macrophage supernatants containing interleukin-1 activity stimulate hepatocyte secretion of SAA, CRP, and fibrinogen. The effect of interleukin-1 on mouse liver serum amyloid A mRNA levels was investigated. The acute-phase response was induced in mice by intraperitoneal injection of interleukin-1 obtained from cloned murine recombinant DNA. We monitored SAA mRNA levels using DNA/RNA dot blot hybridization. Interleukin-1 stimulated a dose-dependent increase in SAA mRNA levels compared to unstimulated controls. In contrast, mRNA levels for apolipoprotein E (a constitutive hepatic protein not produced as part of the acute-phase response) were unchanged under identical conditions. Interleukin-1 also induced SAA mRNA in an endotoxin-resistant strain of mice (C3H/HeJ), indicating that this stimulation was not due to endotoxin contamination since endotoxin alone was unable to induce SAA mRNA in these mice. These results indicate that recombinant interleukin-1, when injected intraperitoneally into mice, induced specific production of SAA mRNA and hence one phase of the acute-phase response.

Acute-Phase Reaction↗
PubMed1978

Initiation factor eIF-4B (IF-M3)-dependent recognition and translation of capped versus uncapped eukaryotic mRNAs.

Translation of capped and uncapped eukaryotic mRNAs is stimulated by addition of eIF-4B to an mRNA-dependent reticulocyte lysate system. m7G5 ppp inhibits translation of capped but not uncapped mRNAs and reduces translation of capped vaccinia mRNA to the level obtained with uncapped vaccinia mRNA. Exogenous eIF-4B but no other initiation factor reverses inhibition of protein synthesis by m7G5'ppp. Both capped and uncapped mRNAs interact directly with eIF-4B to form a stable complex, which can be detected by a simple nitrocellulose filter binding assay. However, addition of a 5'-cap to beta-eliminated globin mRNA or satellite tobacco necrosis virus RNA (normally uncapped) increased binding affinity of these mRNAs for eIF-4B and causes binding of these mRNAs to become sensitive to inhibition by m7G5'ppp. These results indicate that the role of the mRNA 5'-cap in translation is related specifically to the function of eIF-4B in forming a complex with mRNA (prior to association of mRNA with the 40 S ribosomal subunit) and that both cap and non-cap sequences participate in this process.

Animals↗
PubMed1977

Studies on the mechanism for entry of vesicular stomatitis virus glycoprotein G mRNA into membrane-bound polyribosome complexes.

Glycoprotein mRNA (G mRNA) of vesicular stomatitis virus is synthesized in the cytosol fraction of infected HeLa cells. Shortly after synthesis, this mRNA associates with 40S ribosomal subunits and subsequently forms 80S monosomes in the cytosol fraction. The bulk of labeled G mRNA is then found in polysomes associated with the membrane, without first appearing in the subunit or monomer pool of the membrane-bound fraction. Inhibition of the initiation of protein synthesis by pactamycin or muconomycin A blocks entry of newly synthesized G m RNA into membrane-bound polysomes. Under these circumstances, labeled G mRNA accumulates into the cytosol. Inhibition of the elongation of protein synthesis by cucloheximide, however, allows entry of 60 percent of newly synthesized G mRNA into membrane-bound polysomes. Furthermore, prelabeled G mRNA associated with membrane-bound polysomes is released from the membrane fraction in vivo by pactamycin or mucomycon A and in vitro by 1mM puromycin - 0.5 M KCI. This release is not due to nonspecific effects of the drugs. These results demonstrate that association of G mRNA with membrane-bound polysomes is dependent upon polysome formation and initiation of protein synthesis. Therefore, direct association of the 3' end of G mRNA with the membrane does not appear to be the initial event in the formation of membrane-bound polysomes.

Anti-Bacterial Agents↗
PubMed1976

Evidence for role of m7G5'-phosphate group in recognition of eukaryotic mRNA by initiation factor IF-M3.

7-methylguanosine 5'-monophosphate inhibits protein synthesis in a fractionated, messenger-dependent, reticulocyte cell-free system. This compound also inhibits binding of histone mRNA to reticulocyte ribosomes as well as interaction of VSV mRNA and histone mRNA but not EMC virus RNA with purified initiation factor IF-M3. These studies provide evidence that the role of 7-methylguanosine in the mechanism for initiation of eukaryotic mRNA translation may be related to specific recognition of mRNA by initiation factor IF-M3.

Animals↗
PubMedDate not supplied

Accelerated recovery from doxacurium-induced neuromuscular blockade in patients receiving chronic anticonvulsant therapy.

STUDY OBJECTIVE: To determine whether a drug interaction exists between doxacurium and anticonvulsants. DESIGN: Open-label controlled study. SETTING: Inpatient neuroanesthesiology service at a university medical center. PATIENTS: Three groups of nine patients each, consisting of those chronically receiving carbamazepine, phenytoin, or no anticonvulsant therapy. INTERVENTION: Intravenous administration of doxacurium 60 micrograms/kg during anesthesia with nitrous oxide (N2O), fentanyl, and droperidol. MEASUREMENTS AND MAIN RESULTS: The adductor pollicis mechanical response to single 0.2-millisecond supramaximal pulses delivered to the ulnar nerve at 0.15 Hz was recorded. Patients receiving phenytoin or carbamazepine recovered neuromuscular function more quickly than did the control group. The times from doxacurium injection to 50% recovery of mechanomyographic response, for example, were as follows: control group, 161 +/- 55 minutes (mean +/- SD); phenytoin group, 76 +/- 31 minutes; and carbamazepine group, 66 +/- 27 minutes (p less than 0.05). The time for recovery from 75% to 25% blockade (recovery index) was decreased by 53% in the phenytoin group and by 67% in the carbamazepine group as compared with the control group (41.0 +/- 18.0 minutes and 28.6 +/- 8.6 minutes vs 86.4 +/- 45.2 minutes, respectively). CONCLUSION: Chronic treatment with anticonvulsants results in more rapid recovery from neuromuscular blockade produced by doxacurium.

Adult↗