PubMed Health⌕ Search

Biomedical subjects

A Nies

Publications and source records attributed to A Nies.

At least 19 recordsLinked to original sources
PubMed1999

Export pumps for anionic conjugates encoded by MRP genes.

Several members of the multidrug resistance protein (MRP) family mediate the ATP-dependent transport of amphiphilic anions across membranes. The substrate specificity of recombinant human MRP1 has been most extensively defined by use of inside-out membrane vesicles. Substrates include the glutathione S-conjugate leukotriene C4, 17 beta-glucuronosyl estradiol, glucuronosyl bilirubin, glutathione disulfide, in addition to the fluorescent lipophilic anion Fluo-3. These substances are also substrates for the apical isoform MRP2, also termed canalicular multispecific organic anion transporter, cMOAT, which shares only 49% amino acid sequence identity with MRP1. The K(m) of leukotriene C4 for MRP2 is 10-fold higher than for MRP1, and the K(m) of 17 beta-glucuronosyl estradiol is 4.8-fold higher for MRP2 than for recombinant human MRP1. Human as well as rat MRP2 confer multidrug resistance to polarized MDCKII cells permanently expressing the recombinant glycoprotein in their apical plasma membrane. Resistance of cells transfected with human and rat MRP2 to etoposide was enhanced 5-fold and 3.8-fold, and resistance to vincristine was enhanced 2.3-fold and 6.0-fold, respectively. Conjugate-transporting members of the MRP family with a related sequence and a similar function have been detected recently. In addition to several MRP isoforms (MRP1-6) and orthologs in mammals (human, rat, rabbit, mouse), MRP family members have been identified in the nematode Caenorhabditis elegans, in the yeast Saccharomyces cerevisiae, and in the plant Arabidopsis thaliana. These conjugate export pumps of the MRP family play a widespread role in detoxification, drug resistance, and, because of the role in the export of glutathione disulfide by MRP1 and MRP2, in the defense against oxidative stress.

ATP-Binding Cassette Transporters↗
PubMed1994

The effect of age on the beta-adrenergic lipolytic response in healthy humans.

We evaluated the effect of age on the lipolytic response to intravenous infusion of isoproterenol in 12 elderly (age, > 60 years) and 12 young (age, 21 to 34 years) volunteers to examine if there is alteration in innervated beta-adrenergic responsiveness in tissues other than the heart. Lipolysis was evaluated by measuring the plasma concentrations of free fatty acids and glycerol. We also measured the plasma concentration of isoproterenol during infusion so that we could calculate comparable plasma isoproterenol concentrations to lipolytic responses in the two age groups. Our data show that, at equivalent infusion rates of isoproterenol, the two age groups achieved equivalent isoproterenol concentrations. The elderly had a higher concentration of free fatty acids but equivalent concentrations of glycerol as compared with the young subjects at equivalent isoproterenol plasma concentrations. However, our data were complicated by the fact that at the higher infusion rates of isoproterenol, the elderly showed a greater sympathetic stimulation than the young subjects as measured by plasma norepinephrine concentrations. Nonetheless, our data could not show that the elderly subjects were more resistant to beta-adrenergic receptor-mediated stimulated lipolysis. Thus innervated beta-adrenergic receptor hyporesponsiveness caused by aging may not necessarily extend to all organ systems.

Adult↗
PubMed1990

Nucleotide sequence and expression of a plasmid-encoded chromate resistance determinant from Alcaligenes eutrophus.

The nucleotide sequence of the 2.6-kilobase pair (kb) EcoRI fragment encoding chromate resistance (Chrr) on plasmid pMOL28 in Alcaligenes eutrophus was determined. Three open reading frames were assigned to three polypeptides which were expressed from this determinant in Escherichia coli under the control of a phage T7 transcription promoter. When the roles of the polypeptides and open reading frames were analyzed with deletion derivatives of the 2.6-kilobase fragment, the membrane-bound ChrA (401 amino acids) and ChrB (196 amino acids) polypeptides were essential for inducible chromate resistance and reduced accumulation of chromate, while the third open reading frame was not needed.

Alcaligenes↗
PubMed1989

Expression and nucleotide sequence of a plasmid-determined divalent cation efflux system from Alcaligenes eutrophus.

Resistance to cobalt, zinc, and cadmium specified by the czc determinant on plasmid pMOL30 in Alcaligenes eutrophus results from a cation efflux system. Five membrane-bound polypeptides that were expressed in Escherichia coli from this determinant under the control of a phage T7 promoter were assigned to four open reading frames identified in the nucleotide sequence of the 6881-base-pair fragment containing the czc putative operon. The contributions of the polypeptides to the cation efflux system were analyzed with deletion derivatives of the 6.9-kilobase fragment, constructed, and expressed in E. coli under the control of the phage T7 promoter and in A. eutrophus under the control of the lac promoter.

Alcaligenes↗
PubMed1989

Cloning and expression of plasmid genes encoding resistances to chromate and cobalt in Alcaligenes eutrophus.

Resistances to chromate and cobalt were cloned on a 30-kilobase-pair (kb) DNA region from the large Alcaligenes eutrophus plasmid pMOL28 into the broad-host-range mobilizable cosmid vector pVK102. A restriction nuclease map of the 30-kb region was generated. The resistances expressed from the hybrid plasmids after transfer back into A. eutrophus were inducible and conferred the same degree of resistance as the parent plasmid pMOL28. Resistances were expressed in metal-sensitive Alcaligenes strains and related bacteria but not in Escherichia coli. Resistance to chromate was further localized on a 2.6-kb EcoRI fragment, and resistance to cobalt was localized on an adjoining 8.5-kb PstI-EcoRI fragment. When the 2.6-kb EcoRI fragment was expressed in E. coli under the control of a bacteriophage T7 promoter, three polypeptides with molecular masses of 31,500, 21,000, and 14,500 daltons were visible on autoradiograms. The 31,500- and 21,000-dalton polypeptides were membrane bound; the 14,500-dalton polypeptide was soluble.

Alcaligenes↗
PubMed1985

Response to phenelzine among depressed patients with features of hysteroid dysphoria.

A 21-item questionnaire eliciting features of hysteroid dysphoria was administered to 51 depressed outpatients. Of the 47 patients who completed a 6-week double-blind study comparing the efficacy of amitriptyline and phenelzine, 14 had questionnaire scores greater than or equal to 13 (high score) and 33 had scores less than 13 (low score). Nine of nine high-score patients responded to phenelzine; only three of five high-score patients responded to amitriptyline. Low-score patients responded equally well to either drug (79% improved). These findings suggest that some depressed patients have features of hysteroid dysphoria and that these patients respond preferentially to phenelzine.

Adult↗
PubMed1984

Dexamethasone suppression test in recently detoxified alcoholics: clinical implications.

An overnight dexamethasone suppression test (DST) was performed on 66 nondepressed primary alcoholics, a mean of 20.79 +/- 11.5 days after last alcohol intake. The Beck Depression Inventory (BDI) was given concurrently. Only 6% of the subjects were nonsuppressors. There was no correlation between cortisol levels at 17 and 24 hours postdexamethasone and the age of the subjects or duration of abstinence. There was a low level correlation between cortisol values at 24 hours and the BDI scores. Review of published data indicates that the DST may be abnormal in alcoholics in the first 2 weeks of abstinence, probably a result of abnormal liver function and withdrawal phenomena. DST response of alcoholics resembles that of normal controls after more than 2 weeks of abstinence. Alcoholics with clinical features of depression and an abnormal DST after 2 weeks of abstinence may be candidates for antidepressant therapy or electroconvulsive therapy.

Adult↗
PubMed1984

Differential response patterns to MAO inhibitors and tricyclics.

The concept of atypical depression is reviewed and data comparing the clinical effects of monoamine oxidase inhibitors and tricyclic antidepressants are presented. Monoamine oxidase inhibitors are indicated for treatment of syndromes of panic and generalized anxiety with or without supervening atypical depression. The two classes of drugs have contrasting effects on adrenergic metabolism which may be related to the superior antianxiety and antipanic effects of monoamine oxidase inhibitors.

Adult↗
PubMed1983

Abuse potential of halazepam and of diazepam in patients recently treated for acute alcohol withdrawal.

Thirty men recently treated for alcohol withdrawal were enrolled in a three-way crossover double-blind study with a balanced incomplete block design. Patients received single doses of three of the following: halazepam, 320 mg; halazepam, 160 mg; diazepam, 40 mg; diazepam, 20 mg; and placebo. The doses of the drugs were approximately equivalent in anxiolytic effect. Patients rated themselves at baseline, 30 min after, and 1, 2, 3, 4, 6, and 8 hr after drug on the following: euphoria, sedation, "drug-liking," "feeling the drug," and drug identification. By 30 min both diazepam groups reported increases in euphoria, sedation, and feeling and liking the drug; halazepam groups reported little subjective change at 30 min, and at 1 hr subjective effects did not differ from placebo on any scale. At 2 and 3 hr, both halazepam doses induced subjective effects on several scales, but peak effects were lower than peak effects of high diazepam doses. Unlike diazepam, the higher halazepam dose did not appear to induce greater effects than the lower dose. At peak, more of the diazepam group correctly identified the drug than those in the halazepam groups. More in the halazepam groups identified it as placebo than either diazepam group. To the degree that abuse potential is related to peak intensity and to time of onset of those subjective effects described as pleasant or likable, halazepam should have a lower potential for abuse than diazepam.

Adult↗
PubMed1983

Plasma levels of catecholamines and dihydroxyphenylglycol during antidepressant drug treatment.

Plasma norepinephrine, epinephrine, and 3,4-dihydroxyphenylglycol levels were measured in depressed outpatients treated in a double-blind controlled clinical trial with 150 mg/day of amitriptyline or 60 mg/day of phenelzine for 6 weeks. Both antidepressant drug treatments were associated with a significant decline in plasma dihydroxyphenylglycol concentrations, which was more pronounced with phenelzine. Plasma norepinephrine levels also declined during phenelzine but not amitriptyline treatment, and the posttreatment values correlated with clinical improvement with the monoamine oxidase inhibiting drug. Reductions in norepinephrine and dihydroxyphenylglycol correlated highly with the degree of platelet monoamine oxidase inhibition. Mechanisms of these antidepressant drug effects on amine metabolism and their implications are discussed.

Adult↗
PubMed1982

Cardiovascular effects of phenelzine and amitriptyline in depressed outpatients.

Blood pressure and ECG changes were monitored in depressed outpatients treated for 6 weeks with amitriptyline, 150 mg/day, or phenelzine, 60 mg/day, as part of an ongoing double-blind study. Phenelzine produced significant decreases in blood pressure and a significant increase in orthostatic fall in pressure. Amitriptyline produced little overall change in blood pressure. The degree of MAO inhibition in phenelzine-treated patients was significantly correlated with blood pressure. Tricyclic plasma concentrations were also related to some blood pressure measures. Reported dizziness/faintness did not correlate with blood pressure changes in either group. Amitriptyline significantly increased heart rate, while phenelzine produced slowing. Amitriptyline was associated with significant prolongation of QRS and QTc but not PR intervals. Phenelzine produced significant shortening of the QTc interval.

Adult↗
PubMed1980

Phenelzine and amitriptyline in the treatment of depression. A comparison of present and past studies.

We present the results of a direct comparison of pheneizine sulfate and amitriptyline hydrochloride therapy in 105 depressed patients. We believe this is the first definitive double-blind controlled clinical trial of a monoamine oxidase inhibitor and a tricyclic antidepressant in the outpatient setting. The results show both antidepressants to be effective, with the similarities between the two exceeding the differences. Both drugs had marked antidepressant and antianziety effects. Phenelzine tended to exert a stronger antianxiety action; amitriptyline was more effective in reversing weight loss and improving sleep. The incidence of two side effects, sedation and orthostatic hypotension, was almost identical. Dry mouth was more prevalent with amitriptyline. We discuss the indications for the differential clinical use of both drugs in depressed outpatients.

Adult↗
PubMed1980

Demographic, biologic, and other variables affecting monoamine oxidase activity.

Monoamine oxidase (MAO) activity has been shown to be influenced by a variety of demographic, biologic, and other variables. Human platelet, plasma, and brain enzyme activities correlate with age and are higher in women. Brain catecholamines tend to decrease with age. The acute effects of ethanol on platelet MAO do not appear to be significant, but chronic ethanol ingestion could influence enzyme activity through a variety of possible mechanisms. Numerous drugs and hormones have been shown to alter platelet and tissue MAO. Heterogeneity of platelet size, density, age, and enzyme activity complicates the study of MAO in clinical populations. Newer platelet isolation techniques may diminish the variability due to platelet sampling. Studies of platelet MAO activity in schizophrenia require that careful attention be given to controlling for variables possibly influencing the blood enzyme activity, such as prior neuroleptic treatment. The limited studies of brain MAO activity in man fail to demonstrate differences between patients with schizophrenia and normal controls.

Adult↗
PubMed1979

Plasma tricyclic drug levels in amitriptyline-treated depressed patients.

In a double-blind phenelzine controlled clinical trial, 49 depressed outpatients were treated with a fixed dose of amitriptyline (AMI) 150 mg/day for 6 weeks. No significant relationships were found between steady-state plasma levels of AMI and its metabolite, nortriptyline, at 4 weeks and therapeutic response at 6 weeks or side effects. In the patient subgroup with more severe endogenous symptoms, there was a general trend for a weak positive association between AMI plasma levels and clinical improvement. Plasma tricyclic determinations appear to have little if any predictive value for antidepressant effect in outpatients treated with AMI.

Adult↗
PubMed1978

Clinical pharmacology of phenelzine.

There is renewed interest in the clinical pharmacology of phenelzine sulfate and other monoamine oxidase (MAO) inhibitors. Newer clinical and analytic techniques recently have been applied to investigations of this class of drugs in man. The results show that drugs such as phenelzine are effective in nonendogenous depression and phobic disorders. Clinical response to phenelzine is related to platelet MAO inhibition and dosage per unit body weight. High percent MAO inhibition in platelets at two weeks is associated with greater improvement after a six-week course of treatment. Our data show that a safe, effective phenelzine dose in 1 mg/kg body weight per day. These results have delineated the pharmacologic and therapeutic effects of phenelzine and support a continuing role for MAO inhibitors in psychopharmacology.

Acetylation↗
PubMed1978

Use of MAOI antidepressants.

The monoamine oxidase inhibitors (MAOIs) exert significant antidepressant, antianxiety and antiphobic effects. They are safe, provided the patients are carefully selected for treatment and are given instructions on incompatible foods and drugs that must be avoided. The MAOIs represent effective alternatives to the tricyclic antidepressants. Phenelzine is an excellent agent for treating ambulatory patients with neurotic depression and those with agoraphobia and social phobias.

Adjustment Disorders↗