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Biomedical subjects

A Nies

Publications and source records attributed to A Nies.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

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

Monoamine metabolism in human brain.

Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.

Adolescent

Relationship between age and tricyclic antidepressant plasma levels.

Older depressed patients treated with imipramine or amitriptyline developed higher steady-state plasma levels of imipramine, desipramine, and amitriptyline. In imipramine-treated patients this finding was associated with a decreased rate of drug elimination from plasma. These findings provide at least a partial explanation for the increased susceptibility of the older patient to tricyclic antidepressant side effects and also provide a pharmacological rationale for use of lower dosages in this age group.

Administration, Oral

A comparison of standard alternating current and low-energy brief-pulse electrotherapy.

This study compares a low-energy brief-pulse stimulus (LEBS) with a conventional a-c sine wave stimulus in terms of electrical paramenters, efficiency in producing seizures, and clinical outcome on a variety of standard behavioral measures. The results show the LEBS to require equal voltage, less current, and only one-half the total energy to produce clinically manifest convulsions. There was no apparent difference between methods on any outcome measure. The Halstead-Reitan Neuropsychological Test Battery showed as many patients impaired prior to ECT as following treatment. Implications for ECT practices are discussed.

Depression

A multiple-dose, controlled study of phenelzine in depression-anxiety states.

In a double-blind, controlled experiment, 62 outpatients with symptoms of depression with anxiety were selected for treatment with phenelzine sulfate, 60 mg daily, phenelzine sulfate, 30 mg daily, or placebo for six weeks. Forty-nine patients (79%) completed the experiment. Phenelzine sulfate, 60 mg daily, was significantly more effective than placebo in relieving symptoms of both depression and anxiety. Phenelzine sulfate, 30 mg daily, did not differ from the placebo. Only phenelzine sulfate, 60 mg daily, resulted in a median inhibition of platelet monoamine oxidase that exceded 80%. The results confirm a previous study that found phenelzine to be effective in the treatment of outpatients with depressive-anxiety states. Drug dosage is an important variable influencing clinical outcome in this patient group.

Adult

Genetics of monoamine oxidase.

Evidence for the genetic control of human MAO is now well established. The relationships of MAO activities to neuropsychiatric disorders or response to psychopharmacologic treatments are relatively unstudied. Preliminary findings from our own studies suggest that (1) blood MAO activity is a polygenically controlled trait; (2) there may be a subgroup of depressed patients with high MAO activity who are more severe symptomatically and more resistant to treatment, and (3) that men with atypical and mixed depressions respond more favorably than women to treatment with an MAO inhibitory drug.

Adult