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Biomedical subjects

J F Collins

Publications and source records attributed to J F Collins.

At least 91 records · Page 5Linked to original sources

Mode-specific effects among three treatments for depression.

In the NIMH Treatment of Depression Collaborative Research Program (TDCRP), 250 depressed outpatients were randomly assigned to interpersonal psychotherapy, cognitive-behavioral therapy, imipramine plus clinical management, or pill placebo plus clinical management treatments. Although all treatments demonstrated significant symptom reduction with few differences in general outcomes, an important question concerned possible effects specific to each treatment. The therapies differ in rationale and procedures, suggesting that mode-specific effects may differ among treatments, each of which was precisely specified, applied appropriately, and shown to be discriminable. Outcome measures were selected for presumed sensitivity to the different treatments. Findings provided only scattered and relatively insubstantial support for mode-specific differences. None of the therapies produced consistent effects on measures related to its theoretical origins.

Adult↗

Personality disorders and treatment outcome in the NIMH Treatment of Depression Collaborative Research Program.

The authors investigated the relationship between personality disorders and treatment outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program, which involved 239 outpatients with major depressive disorder randomly assigned to one of four 16-week treatment conditions. Patients with personality disorders (74% of the sample) had a significantly worse outcome in social functioning than patients without personality disorders and were significantly more likely to have residual symptoms of depression. There were no significant differences in work functioning or in mean depression scores at treatment termination. Outcome was similar for patients in the different clusters of personality disorders.

Adult↗

Acute renal failure in a critical care unit.

We have reviewed all patients in a critical care unit who required dialysis for acute renal failure during a five year period from 1981-5. There were 45 patients, all of whom were severely ill, the majority requiring mechanical ventilation. Twenty-five were classified as surgical, including trauma, eighteen medical and two obstetric. The overall mortality rate was 53%. A wide range of variables were reviewed and it was found that only the number of failed organs was a significant predictor of mortality. Progressive multiple organ failure in turn was associated with ineradicable sepsis in the majority, although in 25% of deaths with multiple organ failure, sepsis was not proven. Patients without sepsis or multiple organ failure had excellent survival. Further reductions in the acute renal failure mortality rate will depend on better methods of prevention, diagnosis, and management of sepsis.

Acute Kidney Injury↗

National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments.

We investigated the effectiveness of two brief psychotherapies, interpersonal psychotherapy and cognitive behavior therapy, for the treatment of outpatients with major depression disorder diagnosed by Research Diagnostic Criteria. Two hundred fifty patients were randomly assigned to one of four 16-week treatment conditions: interpersonal psychotherapy, cognitive behavior therapy, imipramine hydrochloride plus clinical management (as a standard reference treatment), and placebo plus clinical management. Patients in all treatments showed significant reduction in depressive symptoms and improvement in functioning over the course of treatment. There was a consistent ordering of treatments at termination, with imipramine plus clinical management generally doing best, placebo plus clinical management worst, and the two psychotherapies in between but generally closer to imipramine plus clinical management. In analyses carried out on the total samples without regard to initial severity of illness (the primary analyses), there was no evidence of greater effectiveness of one of the psychotherapies as compared with the other and no evidence that either of the psychotherapies was significantly less effective than the standard reference treatment, imipramine plus clinical management. Comparing each of the psychotherapies with the placebo plus clinical management condition, there was limited evidence of the specific effectiveness of interpersonal psychotherapy and none for cognitive behavior therapy. Superior recovery rates were found for both interpersonal psychotherapy and imipramine plus clinical management, as compared with placebo plus clinical management. On mean scores, however, there were few significant differences in effectiveness among the four treatments in the primary analyses. Secondary analyses, in which patients were dichotomized on initial level of severity of depressive symptoms and impairment of functioning, helped to explain the relative lack of significant findings in the primary analyses. Significant differences among treatments were present only for the subgroup of patients who were more severely depressed and functionally impaired; here, there was some evidence of the effectiveness of interpersonal psychotherapy with these patients and strong evidence of the effectiveness of imipramine plus clinical management. In contrast, there were no significant differences among treatments, including placebo plus clinical management, for the less severely depressed and functionally impaired patients.

Adult↗

xerB, an Escherichia coli gene required for plasmid ColE1 site-specific recombination, is identical to pepA, encoding aminopeptidase A, a protein with substantial similarity to bovine lens leucine aminopeptidase.

The heritable stability of ColE1 is dependent on a site-specific recombination system which acts to resolve plasmid multimers into monomers. This plasmid stabilizing recombination system requires the presence in cis of the ColE1 cer region, plus at least two trans-acting factors encoded by the xerA and xerB genes of Escherichia coli. The xerB gene has been cloned and sequenced and found to encode a polypeptide with a calculated mol. wt of 55.3 kd. The predicted amino acid sequence of this protein exhibits striking similarity to that of bovine lens leucine aminopeptidase (53 kd). The biological significance of this similarity is corroborated by genetic and biochemical evidence which suggests that xerB is identical to the E.coli and S.typhimurium pepA genes that encode aminopeptidase A.

Amino Acid Sequence↗

Analysis of the nucleotide sequence of the Streptomyces glaucescens tcmI genes provides key information about the enzymology of polyketide antibiotic biosynthesis.

Key information about the biosynthesis of polyketide metabolites has been uncovered by sequence analysis of the tetracenomycin C polyketide synthase genes (tcml) from Streptomyces glaucescens GLA.0. The sequence data revealed the presence of three complete open reading frames (ORFs). ORF1 and ORF2 appear to be translationally coupled and would encode proteins containing 426 and 405 amino acids, respectively. The two deduced proteins are homologous to known beta-ketoacyl synthases. ORF3 begins 70 nucleotides after the stop codon of ORF2 and would code for an 83 amino acid protein with a strong resemblance to known bacterial, animal and plant acyl-carrier proteins (ACP). The presence of an ACP gene within the tcm gene cluster suggests that different ACPs are used in fatty acid and polyketide biosynthesis in Streptomyces. We conclude from these data and earlier information that polyketide biosynthesis in S. glaucescens, and most likely in other bacteria, involves a multienzyme complex consisting of at least five types of enzymes: acylCoA transferases that load the acyl and 2-carboxyacyl precursors onto the ACP; a beta-ketoacyl synthase that, along with the acylated ACP, forms the poly-beta-ketoacyl intermediates; a poly-beta-ketone cyclase that forms carbocyclic structures from the latter intermediates; a beta-ketoacyl oxidoreductase that forms beta-hydroxyacyl intermediates or reduces ketone groups in fully formed polyketides; and a thioesterase that releases the assembled polyketide from the enzyme.

Amino Acid Sequence↗

Time course of carbamazepine autoinduction. The VA Cooperative Study No.118 Group.

We sequentially determined carbamazepine clearance values in 17 patients at the end of weeks 1, 2, 4, 8, and 12 of monotherapy. There were no significant differences among these clearance values. In 11 of 17 patients, week 1 clearance accurately predicted week 12 carbamazepine serum concentration (within +/- 33%). Our data indicate that carbamazepine autoinduction was completed within the first 1 or 2 weeks of monotherapy. Serum concentration values obtained after 1 week of monotherapy, using our dosing regimen, can be used to predict directly the dosing rate needed to obtain a specific serum concentration in most patients.

Adult↗

Segments of bacteriophage lambda (orf 221) and phi 80 are homologous to genes coding for mammalian protein phosphatases.

The amino acid sequences of mammalian protein phosphatase 1 and 2A were compared pairwise with every sequence in the National Biomedical Research Foundation protein sequence database using an exhaustive searching programme [Coulson et al., Comp. J. 30 (1987) 420-424]. The N-terminal half of the protein encoded by an open reading frame, orf 221, in bacteriophage lambda (nt 43,224-43,886 in the map of Daniels et al. [in Hendrix et al. (Eds.), Lambda II. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, 1983, pp. 519-676] shows 35% identity to either protein phosphatase 1 or 2A in this region. If conservative replacements are included the overall homology rises to 49%. A gene in phi 80 also shows 35% identity with the mammalian protein phosphatases. The results indicate that orf 221 of phage lambda and the homologous phi 80 gene may encode protein phosphatases. The possible roles of protein phosphorylation in the propagation of bacteriophage are discussed.

Amino Acid Sequence↗

Sialyltransferase-1 in a human malignant glioma cell line. Kinetic characteristics and effect of human interferon-beta.

Sialyltransferase-1 activity was studied in cultured 12-18 human glioma cells. The apparent Km and Vmax with variable LacCer concentrations were 32 microM and 197 pmoles/mg protein/hr and with variable CMP-NeuAc concentrations were 172 microM and 877 pmoles/mg protein/hr., respectively. The pH optimum towards exogenous LacCer was 6.0 and towards endogenous acceptors was 6.2. The optimum protein:detergent ratio was 1:1. Human beta interferon (1000 units/ml medium) increased sialyltransferase-1 activity only slightly on a protein basis but increased it 47% on a per cell basis. These results demonstrate that one of the biochemical effects of beta-interferon on 12-18 human glioma cells is to stimulate ganglioside synthesis.

Cell Line↗

Can categorization of patient background problems be used to determine early termination in a clinical trial?

Many patients entering a long-term clinical study are unable to remain active in the trial (taking medication as prescribed and attending clinic as scheduled) for up to 6 years. We studied a group of 622 patients entering an antiepileptic drug study with maximum possible follow-up period of 6 years. A centralized case validation system was used in this VA Epilepsy Cooperative Study to note problems in patients entering the study. The categories established for pre-entry case status were associated with events occurring during the course of the study that led to noncompletion of the study. The data were reviewed to determine whether pre-entry status can be used to suggest the likelihood that an individual patient will remain in the study to completion or become a non-drug-related loss. Over one-half of all losses were related to failure to return to clinic. Medical problems (18%), medication noncompliance (14%), and psychiatric problems (12%) accounted for the remainder of losses. Pre-entry issues often were the same reason for early loss. However, many patients with problems known at entry were maintained in the study when targeted for extra support. We found some groups of patients had considerably more early terminations whereas others had less loss to the trial than we predicted originally. Thus, case categorization at entry can be used to estimate the likelihood of early termination from a clinical trial.

Actuarial Analysis↗

The significance of protein sequence similarities.

A general method of assessing the significance of scored best local alignments, particularly suited to protein sequence comparisons, is described. The method establishes the parameters describing the distribution of the best results from any search program, provided that the set is sufficiently large and the majority of the alignments arise from unrelated sequences. The expected frequency of occurrence of any score can then be calculated, together with the number of standard deviations above expectation. These provide sensible measures of significance without additional search operations. However the biological significance of any alignment or set of alignments does not solely depend on the improbability of the alignment, but on all relevant factors known to the biologist.

Algorithms↗

Histological response and antigen transmission in the lymph nodes of athymic nu/nu mice inoculated with Crohn's disease tissue filtrates.

Lymph node histology and antigen transmission in the nu/nu mouse in response to animal inoculation with Crohn's disease tissue filtrates were re-evaluated. We found that a hyperplastic lymph node response in nu/nu mice occurred with Crohn's disease (CD), ulcerative colitis (UC), or other intestinal disease (OID) tissue inoculations. In addition, antigen transmission to lymph nodes as detected by indirect immunofluorescence using CD sera was observed in all inoculation groups. The immunofluorescent reaction also occurred independently of lymph node histology. Thus, we confirm that CD sera recognize an antigen(s) expressed in lymph nodes of athymic mice inoculated with CD tissue filtrates. The antibody (or antibodies) in CD sera was not specific for this 'CD antigen or antigens', however, as tested in the nu/nu mouse system, because the CD sera antibodies also recognised antigens in UC inoculated and OID inoculated animals.

Animals↗

Effect of parathyroid hormone on random migration of human polymorphonuclear leukocytes.

Derangements in leukocyte function occur in patients with primary hyperparathyroidism and in those with uremia, which is a state of secondary hyperparathyroidism, suggesting that parathyroid hormone (PTH) may affect leukocyte function. We examined the interaction between PTH and random migration of human polymorphonuclear leukocytes (PMNL) utilizing a modified Boyden chamber. Intact 1-84 PTH but not its amino-terminal (1-34 PTH) or its carboxy-terminal (53-84 PTH) fragments produced marked and significant (p less than 0.01) stimulation of random migration in a dose-dependent manner. Inactivation of 1-84 PTH abolished its effect and other peptide hormones (calcitonin, glucagon, insulin and vasopressin) did not stimulate migration of PMNL. The effect of PTH on migration was not due to action of the hormone on chemotaxis. PTH did not enhance cAMP or cGMP production by PMNL. The stimulation of PMNL motility by PTH was independent of calcium concentration in media, was not mimicked by calcium ionophore and was not blocked by verapamil. Quinidine also produced significant (p less than 0.01) increase in random migration of PMNL and this effect was not additive to that of PTH. Prolonged exposure to PTH (16-20 h) was associated with significant inhibition of random migration of PMNL. The migration of PMNL from patients with advanced renal failure was significantly (p less than 0.01) reduced and there was a significant (p less than 0.01) inverse relationship between random migration of PMNL and serum levels of PTH. Also PTH produced only modest stimulation of random migration of PMNL in most patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Migration Inhibition↗

Aspects of compliance: taking drugs and keeping clinic appointments.

Treatment of epilepsy depends on adherence to a drug regimen as prescribed and periodic assessment of progress. Typical problems of compliance to medication and adherence to follow-up in long-term epilepsy treatment in a clinical trial were analyzed. Zero drug levels, subtherapeutic levels, variable levels and delayed dose were measures of non-compliance to the drug regimen. Missed visits and non-drug-related dropouts from the study marked non-adherence. Data from 622 patients participating in a multicenter evaluation of the efficacy and toxicity of carbamazepine, phenobarbital, phenytoin and primidone, showed generally good compliance. Only 5% of patients had zero drug levels or greater than or equal to 24 h since prior dose at 2 or more visits. Good adherence to the protocol was demonstrated by 93% attendance as scheduled. The support structure of the study and the availability of a study assistant helped many patients to prevent potential problems and convert patients into excellent adherers.

Adolescent↗

DL-2-[3,4-3H]amino-4-phosphonobutyrate binding sites in the rat hippocampus: distribution and possible physiological role.

Binding sites for the novel, glutamate-like radioligand DL-2-[3,4-3H]amino-4-phosphonobutyrate (DL-[3H]APB) on rat hippocampal synaptic membranes were identified and characterised. The existence of a single, saturable population of binding sites was demonstrated. These appeared to be indistinguishable, in terms of their pharmacological profile and ionic dependence, from those described previously in the striatum and whole brain. The distribution of these sites was also examined using a number of discrete neuronal lesions. A majority of sites (approx. 55%) were located on dentate gyrus granule cells. Smaller populations appeared to be situated on perforant path terminals and on pyramidal cells. However, L-APB was found to be ineffective as an inhibitor of basal and potassium evoked D-[3H]aspartate release from hippocampal slices. A presynaptic location can therefore presumably be ruled out. The likely postsynaptic location of DL-[3H]APB-binding sites in the hippocampus suggests that this site may be involved in synaptic neurotransmission. This possibility is discussed with regard to electrophysiological data concerning the synaptic pharmacology of neuronal connections within the hippocampus.

Amino Acids↗

The haemolytic uraemic syndrome and prostatic carcinoma.

We report on three episodes of acute renal failure due to the haemolytic uraemic syndrome in two elderly men with disseminated prostatic carcinoma. Two of the three episodes were treated with plasmapheresis and antiplatelet agents and all three episodes resolved before treatment for the prostatic carcinoma was undertaken. There are only two previous reports in the literature of untreated malignancy presenting with the haemolytic uraemic syndrome, one of which was a case of prostatic carcinoma.

Adenocarcinoma↗