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Biomedical subjects

H Tucker

Publications and source records attributed to H Tucker.

At least 19 recordsLinked to original sources
PubMed1992

Novel inhibitors of prolyl 4-hydroxylase. 2. 5-Amide substituted pyridine-2-carboxylic acids.

A series of 5-[(arylcarbonyl)amino]- and 5-(arylcarbamoyl)pyridine-2-carboxylic acids has been prepared and tested for activity as inhibitors of the enzyme prolyl 4-hydroxylase (EC 1.14.11.2). All the analogues prepared were inhibitors of the enzyme in vitro, the best compounds being equipotent with the known inhibitor pyridine-2,5-dicarboxylic acid (9). Like 9 these amidic analogues were not active in a cultured embryonic chick tendon cell model, considered to be a predictor of in vivo activity. The activity of the amides is not consistent with the model described for the mode of action of 9 with the enzyme and aspects of this are discussed.

Amides↗
PubMed1990

Structure and polymorphic map of human lipoprotein lipase gene.

Lipoprotein lipase (LPL) catalyzes the key step for the removal of triacylglycerol-rich lipoproteins from the circulation. In this paper, we report the cloning and structure of the normal human LPL gene, which was isolated in three overlapping lambda phage clones that span about 35 kilo bases (kb) of the genetic locus. The peptide coding region of the gene is approx. 23 kb in length and contains nine exons with intron sizes ranging from 0.7 to 8.7 kb. The entire 3' untranslated region is in the tenth exon. Specific sequences in this region support the hypothesis that two mRNA species found for human LPL are generated by differential utilization of polyadenylation signals. The first exon occurs in the 5' untranslated region and the region coding for the signal peptide. The second exon includes the protein domain coding for the N-linked glycosylation site that is required for the expression of enzyme activity. The fourth exon contains the region that was proposed as a lipid binding domain, the sixth for one putative heparin binding domain, and the eighth codes for a domain containing another N-linked glycosylation site. These results suggest that the unique structural and functional domains are confined to specific exons. The PvuII polymorphic site was located within the intron between exon 6 and 7 and the HindIII polymorphic site to the 3' flanking region. The location of these polymorphic sites suggests that the PvuII restriction fragment length polymorphism (RFLP) associated with lipase deficiency in a few Japanese kindred may be a linkage marker for a functional defect of LPL, while the HindIII RFLP associated with hypertriglyceridemia may be important for gene regulation of LPL.

Amino Acid Sequence↗
PubMed1989

Excitation thresholds for nerve pedicles: a preliminary report.

Ongoing interest in the rehabilitation of paralyzed musculature in the head and neck has focused on the electronic stimulation of nerve-muscle pedicles that have been reimplanted into the incapacitated effector(s). Despite visual and histochemical evidence of reinnervation, it is still not known whether the excitability of a nerve-muscle pedicle (or for that matter a direct nerve implant) is equivalent to or better than that of reinnervated or normal muscle. Such information is necessary for the eventual construction of an implantable stimulator. Eighteen rabbits were anesthetized with intramuscular xylazine and ketamine and the ansa hypoglossi nerve was cut on one side. A crossover nerve-muscle pedicle was brought in from the opposite sternothyroid muscle to the sternohyoid in nine animals; the other nine received a direct nerve implant. After a minimum neurotization period of 3 months and reexploration, an electrical stimulator capable of delivering square wave pulses of variable amplitude and width was used to determine the thresholds of contraction of the nerve pedicles, an intact motor nerve of similar size, a normal muscle, and the reinnervated strap in 16 evaluable rabbits. Strength duration curves were established. The data indicate that thresholds for nerve pedicles are equivalent to those of normal nerves and are significantly lower than those of muscle.

Animals↗
PubMed1988

Resolution of the nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3'- (trifluoromethyl)-propionanilide and the determination of the absolute configuration of the active enantiomer.

The nonsteroidal antiandrogen 4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2- hydroxy-2-methyl-3'-(trifluoromethyl)-propionanilide (1) (ICI 176334) has been resolved by chromatographic separation of the diastereomeric (R)-camphanyl esters of the precursor thioether 2 followed by hydrolysis and oxidation of the isolated enantiomers. In addition, an asymmetric synthesis of (S)-3-bromo-2-hydroxy-2-methylpropanoic acid (11) and subsequent conversion into the (S)-sulfone 6a has established that the more potent enantiomer of 1 has the R absolute configuration.

Androgen Antagonists↗
PubMed1988

Nonsteroidal antiandrogens. Synthesis and structure-activity relationships of 3-substituted derivatives of 2-hydroxypropionanilides.

A series of 3-(substituted thio)-2-hydroxypropionanilides and some corresponding sulfones and sulfoxides of general structure 7, in which R' is methyl or trifluoromethyl, were prepared and tested for antiandrogen activity. Members of the trifluoromethyl series (7, R' = CF3) generally exhibited partial androgen agonist activity whereas the members of the methyl series (7, R' = CH3) were pure antagonists. Lead optimization in the methyl series has led to the discovery of novel, potent antiandrogens, which are peripherally selective. One of these, (RS)-4'-cyano-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-3'- (trifluoromethyl)propionanilide, 40 (ICI 176334), is being developed currently for the treatment of androgen-responsive benign and malignant disease.

Androgen Antagonists↗
PubMed1987

ICI 176,334: a novel non-steroidal, peripherally selective antiandrogen.

Pure antiandrogens, like flutamide, antagonize androgen action both peripherally and centrally at the hypothalamic-pituitary axis, which leads to an increase in LH and testosterone secretion. A new non-steroidal antiandrogen ICI 176,334 [2RS)-4'-cyano-3-(4-fluorophenylsulphonyl)-2-hydroxy-2-methyl-3'- trifluoromethyl)propion-anilide) has now been discovered which causes regression of the accessory sex organs but does not increase serum concentrations of LH and androgens. ICI 176,334 binds to rat prostate androgen receptors with an affinity around fourfold that of hydroxyflutamide. When administered s.c. concurrently with testosterone propionate (200 micrograms/kg) for 7 days to immature castrated rats, ICI 176,334 (10 mg/kg) significantly (P less than 0.001) inhibited growth of the seminal vesicles and ventral prostate gland. Oral administration of ICI 176,334 at doses of 1, 5 and 25 mg/kg for 14 days to adult rats caused a dose-related reduction in accessory sex organ weights but had no effect on the testes. None of these doses caused a significant increase in serum LH and testosterone. Flutamide was around fourfold less potent and significantly increased serum LH and testosterone at the higher doses. ICI 176,334 was well tolerated. ICI 176,334 should, therefore, prove useful for the treatment of androgen-responsive benign and malignant diseases.

Androgen Antagonists↗
PubMed1985

Accurate diagnosis of early ectopic pregnancy.

Commonly used preoperative diagnostic procedures were analyzed for their ability to predict the presence of early ectopic pregnancy. Patients presenting to the emergency room with acute onset of pelvic pain were evaluated with culdocentesis, pelvic ultrasonography, and qualitative serum and urine pregnancy testing. Clinical examination and urine pregnancy testing were found to be poor predictors of either the presence or absence of an early ectopic pregnancy. The combination of a sensitive serum human chorionic gonadotropin (hCG) determination and pelvic ultrasonography accurately predicted ectopic pregnancy in 93% of proved cases. This predicted accuracy was superior to that of culdocentesis alone or in combinations of culdocentesis and ultrasound or qualitative serum pregnancy testing.

Adult↗
PubMed1978

beta-Adrenergic blocking agents. 18. 1-(Aryloxy)-3-(arylthioalkylamino)propan-2-ols and 1-substituted alkylthioamino-3-(aryloxy)propan-2-ols.

The synthesis is described of a seris of derivaties of 1-(aryloxy)-3-(arylthioalkylamiho)propan-2-ols and 1-(alkylthioamino)- and 1-(aralkylamino)-3-(aryloxy)propan-2-ols. These compounds were investigated for their beta-adrenoreceptor blocking properties and their selectivity of action for the cardiac beta1 receptor. The structure-activity relationships are discussed with particular reference to the effects of the sulfur, sulfoxide, and sulfone groups on beta-adrenoreceptor blocking potency and selectivity.

Adrenergic beta-Antagonists↗
PubMed1978

Assessing the psychological effects of an exercise training programme for patients following myocardial infarction: a pilot study.

During a study investigating physiological and other effects of an exercise programme for coronary patients, a questionnaire was administered. Preliminary analysis had suggested some improvement in the patients' morale, but in view of the possible relevance of a number of psychological variables it was decided to carry out further analysis on the available data. The coefficient of discrimination was computed for 32 patients. For 19 patients correlations were computed between scores on subjective fitness, symptoms, anxiety, interest in sex, if at work, age, weight, and workload achieved at a given heart rate. The questionnaire appeared to have satisfactorily high internal and external validity. Patients with a high 'morale' score tended to achieve a greater increase in workload over the course. Although cause and effect cannot be unequivocally assigned, the association is felt to be important, and research is continuing.

Anxiety↗
PubMed1977

beta-Adrenergic blocking agents. 17. 1-Phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols.

The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed.

Adrenergic beta-Antagonists↗
PubMed1977

Endobronchial control of bronchopleural fistulae.

This report describes a proposed solution to the problem of high-flow bronchopleural fistulae in the adult respiratory distress syndrome. Animal studies and clinical application demonstrate the efficacy of this treatment.

Adult↗
PubMed1973

Exercise programme after myocardial infarction.

Fifty-nine men with known coronary disease entered an exercise rehabilitation programme. Forty-nine had sustained recent myocardial infarctions, nine had had past myocardial infarcts, and one had had a recent internal mammary implant for severe angina. Each class lasted about 45 minutes and they were held twice weekly; the course for each patient was three months. Sixteen patients dropped out from the course, only three for reasons obviously medical. No deaths or cardiac arrests occurred during the programme. Extrasystoles and angina were detected in a minority of patients and did not constitute reasons for failure to complete the course. The main aim of the study was to show that such a programme is feasible in a district general hospital. Improvement in the morale of patients was impressive and the incidence of return to work high.

Adult↗