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Biomedical subjects

D A Montgomery

Publications and source records attributed to D A Montgomery.

At least 19 recordsLinked to original sources
PubMed2001

Sampling methods for identifying differences in source reliability.

This study explored observer performance in using across-trial and within-trial variability information to weight sources based on reliability. Three trained observers performed a multi-element, visual signal-detection task under 3 block-type conditions: a fixed block condition and 2 random conditions. In the fixed block condition, the observers had both within- and across-trial variability information to identify differences in source reliability. The random conditions eliminated the across-trial information, leaving only within-trial variability information in 1 case and neither within- nor across-trial variability information in another case. There was a significant block-type effect. Observers could use differences in across-trial variability of individual sources to assign weights. Although there was a difference in the weights assigned to reliable and unreliable sources in the partial-random condition (in which within-trial variability information was available), only 1 participant showed a significant difference in the weight assignment relative to the full-random condition. Thus, altogether, observers were not very efficient at using within-trial variability to weight sources accordingly.

Analysis of Variance↗
PubMed1999

Inhibition of 3C protease from human rhinovirus strain 1B by peptidyl bromomethylketonehydrazides.

The gene coding for the 3C protease from human rhinovirus strain 1B was efficiently expressed in an Escherichia coli strain which also overexpressed the rare argU tRNA. The protease was isolated from inclusion bodies, refolded, and exhibited a kcat/Km = 3280 M-1 s-1 using an internally quenched peptidyl fluorogenic substrate. This continuous fluorogenic assay was used to measure the kinetics of 3C protease inhibition by several conventional peptidyl chloromethylketones as well as a novel series of compounds, the bromomethylketonehydrazides. Compounds containing the bromomethylketonehydrazide backbone and a glutamine-like side chain at the P1 position were potent, time-dependent inhibitors of rhinovirus 3C protease with kinact/Kinact values as high as 23,400 M-1 s-1. The inhibitory activity of compounds containing modified P1 side chains suggests that the interactions between the P1 carboxamide group and the 3C protease contributes at least 30-fold to the kinact/Kinact rate constants for bromomethylketonehydrazide inhibition of 3C protease. Electrospray ionization mass spectrometry measurements of the molecular weights of native and inhibited 3C protease have established an inhibitory mechanism involving formation of a covalent adduct between the enzyme and the inhibitor with the loss of a bromide ion from the bromomethylketonehydrazide. Tryptic digestion of bromomethylketonehydrazide-inhibited 3C protease established adduct formation to a peptide corresponding to residues 145-154, a region which contains the active site cysteine-148 residue. The bromomethylketonehydrazides were fairly weak inhibitors of chymotrypsin, human elastase, and cathepsin B and several of these compounds also showed evidence for inhibition of human rhinovirus 1B replication in cell culture.

3C Viral Proteases↗
PubMed1994

Effect of sequence delay on the discrimination of temporal patterns.

This experiment tested listeners' ability to discriminate between two temporal patterns as a function of the time interval between the pattern onsets. The listener's task was to decide whether two arrhythmic sequences of nine tones had the same or different temporal patterns; the patterns were defined by the time intervals between the tones. According to the temporal pattern correlation model [R. D. Sorkin, J. Acoust. Soc. Am. 87, 1695-1701 (1990)], listeners extract information about the series of time intervals in each sequence and then compute the correlation between the two series. In the present experiment, the tones in the second sequence were presented at a different frequency than the tones in the first sequence. In one condition, all time intervals in the second sequence were compressed or expanded by a factor that varied randomly over trials. Performance was very good when the sequences did not overlap in time, but was poor when the sequences overlapped. Performance was generally consistent with a discrimination mechanism that cannot process more than one pattern at a time.

Dichotic Listening Tests↗
PubMed1992

Characterization of DNA topoisomerase I from Candida albicans as a target for drug discovery.

Candida albicans is an opportunistic pathogen responsible for life-threatening infections in persons with impaired immune systems. Topoisomerase I is a potential target for novel antifungal agents; however, in order for this enzyme to be a therapeutically useful target, it needs to be demonstrated that the fungal and human topoisomerases differ sufficiently as to allow the fungal topoisomerase to be selectively targeted. To address this question, we isolated the topoisomerase I from C. albicans and compared its biochemical properties with those of the mammalian enzyme. Similar to other eukaryotic type I topoisomerases, the C. albicans type I topoisomerase has an apparent molecular mass of 102 kDa and covalently links to the 3' end of DNA, as shown after the reaction is interrupted by sodium dodecyl sulfate. Topoisomerase poisons such as camptothecin act by stabilizing the cleavage complex formed by the topoisomerase I and DNA. We observed that the C. albicans and mammalian type I topoisomerases differ in that the C. albicans cleavage complex is approximately 10-fold less sensitive to camptothecin than the mammalian cleavage complex is. In addition, we found that the antifungal agent eupolauridine can stabilize the cleavage complex formed by both the C. albicans and human topoisomerases and that the response of the C. albicans topoisomerase I to this drug is greater than that of the human enzyme. Thus, the topoisomerase I from C. albicans is sufficiently distinct from the human enzyme as to allow differential chemical targeting and will therefore make a good target for antifungal drug discovery.

Alkaloids↗
PubMed1992

DNA topoisomerases from pathogenic fungi: targets for the discovery of antifungal drugs.

DNA topoisomerases, a class of enzymes that change the topological structure of DNA, have been shown to be the target of many therapeutic agents, including antibacterial agents (quinolones) and anticancer agents. These drugs inhibit the enzyme in a unique way so that the enzyme is converted into a cellular poison. Candida albicans and Aspergillus niger are two major opportunistic fungal pathogens. Our results show that these fungi have high levels of both type I and type II topoisomerases (with a minimum of 5 x 10(5) ATP-independent relaxation units and 2 x 10(5) P-4 unknotting units per liter of wild-type C. albicans). The ATP-dependent type II topoisomerase (termed C. albicans topoisomerase II) was purified by approximately 2,000-fold from C. albicans cells by using a simple isolation scheme that consists of three column procedures: hydroxylapatite, phosphocellulose, and heparin-agarose chromatographies. The responses of the Candida and the calf thymus topoisomerase II to some known topoisomerase II inhibitors were measured. Etoposide and 4'-(9-acridinylamino)methanesulfon-m-anisidide, compounds known to inhibit catalysis and to enhance DNA breakage by mammalian topoisomerase II, and A-80198, an etoposide derivative, enhanced cleavage by both enzymes at similar concentrations of these compounds, with the response of the calf thymus topoisomerase II from slightly to fourfold higher in magnitude than the response of the Candida enzyme in the same concentration range. In contrast, A-75272 (a cytotoxic tricyclic quinolone) shows a slightly stronger DNA cleavage enhancement effect with the Candida enzyme than with the mammalian counterpart. The abundance of the enzyme in cells and the different drug responses of the host enzyme and the fungal enzyme suggest that the fungal topoisomerase may serve as a target for the discovery of effective and safe antifungal agents.

Animals↗
PubMed1991

Effect of time compression and expansion on the discrimination of tonal patterns.

This experiment tested how well human listeners can discriminate between temporal patterns that are compressed or expanded in time. The listener's task was to determine whether two arrhythmic, tonal sequences had the same or different temporal patterns. According to the pattern correlation model [R. D. Sorkin, J. Acoust. Soc. Am. 87, 1695-1701 (1990)], listeners perform this task by computing the correlation between the pattern of time intervals marked by the tones in each sequence. Listener performance dropped when one of the sequences was compressed or expanded in time. In order for the model to describe the observed performance, it was necessary to postulate an internal noise component that was proportional to the magnitude of the difference between the sequence transformations.

Adult↗
PubMed1991

Nutrition information needs during cardiac rehabilitation: perceptions of the cardiac patient and spouse.

A survey instrument, which was developed from personal interviews with participants in a cardiac rehabilitation program, was administered at two hospital-based Phase II cardiac rehabilitation programs. Thirty-five patients (28 men, 7 women) and 29 spouses (5 men, 24 women) responded to survey items designed to investigate how subjects perceived themselves dealing with the cardiac diet, what questions they were asking, and how answers to those questions would help them. Subjects in the patient group (which was 80% male) most frequently asked questions dealing with compliance and the diet's benefits. Subjects in the spouse group (which was 83% female) most frequently asked questions relating to food selection. Participants indicated that having their questions answered would help them make decisions, be motivated, feel in control, and plan. Participants' overall attitude toward the diet was positive because patients were willing to make changes in their diet; however, more than half the sample thought food labels were difficult to understand and grocery shopping was difficult. We conclude that nutrition education programs that address individual needs and uses for nutrition information could enhance the learning process in group settings such as cardiac rehabilitation programs.

Adult↗
PubMed1988

Synthesis and in-vitro cytotoxic activity of phenyl-amino-4-(p-toluenesulfinyl)-trans-1,5-hexadiene.

A novel anticancer drug, 1-phenyl-3-phenylamino-4-(p-toluenesulfinyl-trans-1,5-hexadiene has been synthesized and found to have in-vitro cytotoxicity against P388 (LD50 = 15 micrograms/ml) and L1210 (LD50 = 19 micrograms/ml) murine leukemia cells in culture. The LD50 compared favorably with that for doxorubicin. The compound was more cytotoxic to P388 tumor cells than to normal mouse splenocytes. The compound inhibited the uptake of both tritiated thymidine (42% inhibition) and tritiated uridine (24% inhibition) after 3 h of incubation when used at 5 micrograms/ml. No effect on uptake of tritiated leucine was observed during this time period. The compound was cytotoxic to normal mouse splenocytes which had been stimulated to divide by the mitogen concanavalin A. No effect was found on normal, non-dividing splenocytes. These results suggest that this novel compound is cytotoxic to leukemic cells or other rapidly dividing cells through inhibition of DNA and/or RNA synthesis.

Aniline Compounds↗
PubMed1986

Natural history of diabetes presenting age 40-69 years: a prospective study of the influence of intensive dietary therapy.

Two hundred and twenty-three newly-diagnosed symptomatic diabetic patients with onset age 40-69 years enrolled in a prospective study of intensive dietary management of diabetes were observed for a period of six years and the data obtained is analysed. The variables studied were weight and fasting levels of plasma glucose and insulin, and of serum total cholesterol and triglyceride. These tests were monitored throughout the study and in addition the oral glucose tolerance test was analysed at entry to the study, after six months intensive dietary management and again after 72 months. Blood pressure, electrocardiogram and the presence of posterior tibial artery pulsation were recorded at entry to the study and at 36 months and 72 months. Approximately 80 per cent of the patients were managed solely by dietary restriction for the entire six years, but 25 patients received oral hypoglycaemic drugs and 26 required insulin treatment. Weight, and fasting glucose and triglyceride values fell in the first few months of intensive dietary management. Analysis of possible risk factors in survivors and patients dead at six years showed no significant differences, apart from a higher mean age at diagnosis in those who died. During the six years of intensive dietary management the mortality from all causes in these diabetic patients was no greater than that for the general population of Northern Ireland.

Adult↗
PubMed1982

Cushing's syndrome in pregnancy--treatment with metyrapone.

A 23-year-old female presented with severe Cushing's syndrome in the 23rd week of pregnancy. Investigations showed plasma cortisol 770 nmol/l (08.00 h) and 850 nmol/l (23.00 h); plasma ACTH was 10 ng/l (08.00 h) and 27 ng/l (23.00 h); urinary free cortisol excretion was 2460 nmol/24 h. Dexamethasone 2 mg 6-hourly for 48 h suppressed the 08.00 h plasma cortisol only to 680 nmol/l. Abdominal C.T. scan showed a right adrenal adenoma. The patient was treated with metyrapone and a good clinical improvement ensued. Plasma cortisol was reduced to 300-500 nmol/l. Depsite ultrasonographic evidence of normal fetal growth, urinary oestriol excretion was markedly deficient. Prior to the spontaneous onset of labour, there was a marked rise in plasma cortisol despite continuous metyrapone treatment. A normal female infant was born at 37 weeks' gestation. The maternal adrenal adenoma was subsequently removed. The deficiency of oestriol synthesis during the pregnancy may be explained by metyrapone-induced inhibition of C19-hydroxylation.

Adenoma↗
PubMed1980

Dietary management of maturity-onset diabetes.

Dietary management of maturity-onset diabetes is a basic medical concept. It is difficult to study scientifically because of variable eating habits and the impossibility of rigorous measurement. The non-insulin-requiring diabetic patient is often managed by the family doctor, who may not have access to dietetic assistance, and assessment of the success of simple but careful dietary measures is infrequent. We have taken a special interest in this group of patients, and find that most maturity-onset diabetic patients can be satisfactorily managed on diet only. In a group of 58 such patients there was a significant fall in mean weight and fasting plasma glucose and triglyceride concentrations after six months, which persisted for up to three years. This achievement was chiefly due to those patients who were graded as "good" in their dietary adherence, but less good dieting still achieved weight loss, though plasma glucose and triglyceride concentrations did not fall so low. The clinical dietitian has played a central part in this study.

Adult↗
PubMed1980

Antithrombin III activity and other coagulation changes in proliferative diabetic retinopathy.

Antithrombin III, factor VIII, fibrinogen and fibrinolytic activity were measured in two groups of long-standing insulin-dependent diabetic subjects (24 with proliferative retinopathy, 24 without detectable retinopathy) and 24 non-diabetic controls. Mean antithrombin III (+/- 1 SD) was 115.9 (+/- 15.1), 109.8 (+/- 18.1) and 101.4% (+/- 12.5), respectively, in the retinopathy, non-retinopathy and control groups. Statistical significance was obtained when comparing the retinopathy and control groups (p < 0.001) and when comparing all 48 diabetics collectively with controls (p < 0.01). Mean factor VIII coagulant activity was 137.5 (+/- 37.0), 126.2 (+/- 58.2) and 97.0% (+/- 38.7), respectively, in the three groups. Again the differences between all diabetics and controls (p < 0.01) were statistically significant. Similar increases were observed for other modalities of factor VIII activity. Fibrinolytic activity was significantly increased in both diabetic groups but fibrinogen levels, although increased, were not statistically different from levels in controls. It is suggested that the observed changes are more likely to be secondary to the development of retinopathy and that the increase in antithrombin III activity is due to an increase in alpha 2-macroglobulin.

Adult↗