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Biomedical subjects

D Montgomery

Publications and source records attributed to D Montgomery.

At least 19 recordsLinked to original sources
PubMed1999

Impact of vascular adaptation to chronic aortic regurgitation on left ventricular performance.

BACKGROUND: This investigation was designed to test the hypothesis that vascular adaptation occurs in patients with chronic aortic regurgitation to maintain left ventricular (LV) performance. METHODS AND RESULTS: Forty-five patients with chronic aortic regurgitation (mean age 50+/-14 years) were studied using a micromanometer LV catheter to obtain LV pressures and radionuclide ventriculography to obtain LV volumes during multiple loading conditions and right atrial pacing. These 45 patients were subgrouped according to their LV contractility (Ees) and ejection fraction values. Group I consisted of 24 patients with a normal Ees. Group IIa consisted of 10 patients with impaired Ees values (Ees <1.00 mm Hg/mL) but normal LV ejection fractions; Group IIb consisted of 11 patients with impaired contractility and reduced LV ejection fractions. The left ventricular-arterial coupling ratio, Ees/Ea, where Ea was calculated by dividing the LV end-systolic pressure by LV stroke volume, averaged 1.60+/-0.91 in Group I. It decreased to 0.91+/-0.27 in Group IIa (P<0.05 versus Group I), and it decreased further in Group IIb to 0.43+/-0.24 (P<0.001 versus Groups I and IIa). The LV ejection fractions were inversely related to the Ea values in both the normal and impaired contractility groups (r=-0.48, P<0.05 and r=-0.56, P<0.01, respectively), although the slopes of these relationships differed (P<0.05). The average LV work was maximal in Group IIa when the left ventricular-arterial coupling ratio was near 1.0 because of a significant decrease in total arterial elastance (P<0.01 versus Group I). In contrast, the decrease in the left ventricular-arterial coupling ratio in Group IIb was caused by an increase in total arterial elastance, effectively double loading the LV, contributing to a decrease in LV pump efficiency (P<0.01 versus Group IIa and P<0.001 versus Group I). CONCLUSIONS: Vascular adaptation may be heterogeneous in patients with chronic aortic regurgitation. In some, total arterial elastance decreases to maximize LV work and maintain LV performance, whereas in others, it increases, thereby double loading the LV, contributing to afterload excess and a deterioration in LV performance that is most prominent in those with impaired contractility.

Adaptation, Physiological↗
PubMed1999

Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding putative phosphate transport receptors.

Using culture filtrate Ag-specific mAbs generated from mycobacteria-infected H-2b haplotype mice, we have previously identified three genes in the Mycobacterium tuberculosis genome, encoding proteins homologous to the periplasmic ATP-binding cassette phosphate-binding receptor PstS of the phosphate-specific transport system of E. coli. To define the potential vaccinal properties of these phosphate-binding proteins, female C57BL/6 mice were injected i.m. with plasmid DNA encoding PstS-1, PstS-2, or PstS-3 proteins from M. tuberculosis and immunogenicity and protective efficacy against i.v. challenge with M. tuberculosis H37Rv was analyzed. Significant levels of highly Ag-specific Abs and Th1-type cytokines IL-2 and IFN-gamma could be detected following vaccination with each of the three genes. However, only mice vaccinated with PstS-3 DNA demonstrated significant and sustained reduction in bacterial CFU numbers in spleen and lungs for 3 mo after M. tuberculosis challenge, as compared with CFU counts in mice vaccinated with control DNA. Vaccination with PstS-2 DNA induced a modest reduction in CFU counts in spleen only, whereas vaccination with PstS-1 DNA was completely ineffective in reducing bacterial multiplication. In conclusion, our results indicate that DNA vaccination is a powerful and easy method for comparative screening of potentially protective Ags from M. tuberculosis and that the PstS-3 protein is a promising new subunit vaccine candidate.

ATP-Binding Cassette Transporters↗
PubMed1996

Comparison of responses of DNA topoisomerase I from Candida albicans and human cells to four new agents which stimulate topoisomerase-dependent DNA nicking.

DNA topoisomerase I is a potential target for therapeutic antifungal agents predicted to have a fungicidal mode of action. This report describes four agents with varying degrees of selectivity for the fungal topoisomerase I compared to the human enzyme: 5-hydroxy-1H-indole-3-acetic acid (5-HIAA), quinizarin, dibenzo-p-dioxin-2-carboxylic acid and 7-amino-4-hydroxy-2-naphthalenesulfonic acid. Taken together with the response of topoisomerase to camptothecin and aminocatechol, these data suggest that there are sufficient structural differences between the topoisomerase I from Candida albicans and human cells to allow selective targeting of the fungal topoisomerase I over its human counterpart.

Anthraquinones↗
PubMed1996

A computational model of visual hallucinations in migraine.

Cortical spreading depression is a wave of electrical and biochemical changes that spreads across the cerebral cortex. It has been hypothesized to be an important underlying cause of the visual disturbances occurring during the migraine aura, but this is difficult to test in animals or humans. We created a computational model of cortical spreading depression and found that during the wave of biochemical changes the spatial pattern of neural activity broke up into irregular patterns of lines and small patches of highly activated elements. The corresponding visual disturbances that would be produced by these patterns of neural activity resemble the hallucinations reported during the migraine aura, providing strong support for the cortical spreading depression hypothesis of migraine. The model also makes the testable prediction that these hallucinations move at an exponentially increasing speed across the visual field.

Animals↗
PubMed1996

The use of high doses of adrenaline in paediatric cardiac resuscitation.

Adrenaline has been used in cardiac resuscitation for many years, yet until recently its mechanism of action and optimal dosage remained poorly investigated or understood. Recent guidelines suggest the use of higher doses of adrenaline at an early stage in paediatric resuscitation. This paper examines the use of adrenaline in paediatric resuscitation and studies the arguments in favour of using higher doses than previously accepted.

Adrenergic Agonists↗
PubMed1996

Novel triterpene sulfates from Fusarium compactum using a rhinovirus 3C protease inhibitor screen.

Two novel triterpene sulfates have been isolated from Fusarium compactum by bioactivity-directed fractionation using an assay which measures the inhibition of proteolytic activity of rhinovirus 3C protease on a fluorogenic peptide substrate. The compounds were purified by countercurrent and reverse phase chromatographies. NMR, MS, UV and IR studies revealed two triterpene sulfates, uncommon metabolites of terrestrial fungi.

Cholestenes↗
PubMed1995

Identification of the aminocatechol A-3253 as an in vitro poison of DNA topoisomerase I from Candida albicans.

The aminocatechol A-3253 is active against several pathogenic fungi, including Candida albicans, Cryptococcus albidus, and Aspergillus niger. A-3253 interferes with both the in vitro biosynthesis of (1,3)-beta-glucan and the activity of topoisomerases I isolated from Candida spp. It is likely that one or more of the enzymes involved in glucan biosynthesis rather than topoisomerase I is the primary intracellular target of A-3253, since a strain of Saccharomyces cerevisiae lacking topoisomerase I is as susceptible to A-3253 as cells containing wild-type levels of topoisomerase I. However, the interaction of A-3253 with topoisomerase I in vitro is of interest since the Candida topoisomerase is more susceptible to A-3253 than is the topoisomerase I isolated from human HeLa cells. A-3253 is both a reversible inhibitor of topoisomerase I catalysis and a reversible poison of topoisomerase I, and in both reactions the fungal topoisomerase I is more susceptible than the human topoisomerase I to A-3253. In contrast, an earlier study found that the human topoisomerase I is more susceptible than the fungal topoisomerase to camptothecin (J. M. Fostel, D. A. Montgomery, and L. L. Shen, Antimicrob. Agents Chemother. 36:2131-2138, 1992). Taken together with the response to camptothecin, the greater susceptibility of the Candida topoisomerase I to A-3253 suggests that there are structural differences between the human and fungal type I topoisomerases which can likely be exploited to allow for the development of antifungal agents which act against the fungal topoisomerase and which have minimal activity against the human enzyme.

Antifungal Agents↗
PubMed1995

Residents' formal knowledge acquisition and preferred learning styles.

BACKGROUND: Many family practice residency programs use the Myers-Briggs Type Indicator (MBTI) in their educational programs. Our purpose was to study the relationship between learning style, as determined by MBTI personality preferences, and residents' cognitive knowledge acquisition, measured by in-service training examination (ISTE) scores during the first and third years of residency. METHODS: We evaluated 36 residents using both their first- and third-year ISTE composite scores and their MBTI scores. ISTE scores were analyzed according to the MBTI personality factors. We used the Wilcoxon Rank-Sum Test to determine the association between the improvement in residents' ISTE scores between the first- and third-year examinations and preferred learning styles. RESULTS: Significant differences were found on the composite ISTE scores for the thinking/feeling and judgment/perception scales. Feelers increased ISTE scores more than thinkers (P = .031); judgers increased ISTE scores more than perceivers (P = .04). CONCLUSIONS: Results do not support the literature or current MBTI learning theory. Intuitive residents demonstrated no advantage over sensing residents. Residents using feeling/judgment as their preferred learning style acquired more knowledge over 3 years than their thinking/perceiving counterparts, as measured by ISTE scores.

Adult↗
PubMed1994

Modeling cortical spreading depression.

Cortical spreading depression is a wave of electrical silence and biochemical changes that spreads across the cerebral cortex. Recently there has been a growing recognition that it may be an important pathophysiological event in a number of neurological disorders. In this paper, we describe a reaction-diffusion model of the extracellular potassium changes that are a central part of this process. Simulations with the model show that an appropriate stimulus evokes a moving wave of increased potassium with many similarities to that seen experimentally. The resultant model is a useful computational tool for future study of the effects of spreading depression on the cortex.

Computer Simulation↗
PubMed1993

Thermodynamic and structural analysis of the folding/unfolding transitions of the Escherichia coli molecular chaperone DnaK.

The thermal unfolding of the Escherichia coli 70 kDa heat shock protein, DnaK, exhibits three well defined transitions. At pH 7.6, these transitions are centered at 45.2, 58.0 and 73.3 degrees C. High sensitivity calorimetric scans as a function of pH indicate that the folding/unfolding behavior is well described by a four-state model which includes a delta H, tm and delta Cp for each state. Calorimetric scans of a 44 kDa N-terminal proteolytic fragment show a major transition centered at 47.5 degrees C (N1) and a minor transition at 79.4 degrees C (N2). A calorimetric scan of a 23 kDa C-terminal proteolytic fragment exhibits a low temperature peak at 58.5 degrees C (C1) and a high temperature peak at 70.6 degrees C (C2). Deconvolution analysis of the low temperature peak reveals that it is actually composed of two transitions of roughly equal delta H centered at 50.4 degrees C (C1a) and 58.2 degrees C(C1b). These experiments have allowed us to assign the transitions of the intact protein as follows. The low temperature transition of DnaK can be assigned to the N-terminal region on the basis of the similarity between the delta H and tm values for the low temperature transition and those obtained for the N1 transition of the isolated N-terminal fragment. This assignment is also supported by measurements of the intrinsic fluorescence emission as a function of temperature. DnaK contains a single tryptophan localized at residue 102 in the N-terminal domain of the protein. Additionally, calorimetric scans show that the tm of the low temperature transition increases by 9.2 degrees C in the presence of excess ADP, which is known to bind to the N-terminal domain. The middle transition can be assigned to the C1a and C1b transitions of the C-terminal fragment on the basis of the similarity of delta H and tm. In the intact protein C1a and C1b form a single cooperative unit; however, the cooperative interactions between these folding/unfolding domains are disrupted in the isolated fragment. The high temperature transition of the intact protein is composed of contributions from both the N-terminal and C-terminal regions of the protein. These studies have allowed us to develop a quantitative model of the folding/unfolding behavior of DnaK.

Bacterial Proteins↗
PubMed1993

Targeted delivery of peptide epitopes to class I major histocompatibility molecules by a modified Pseudomonas exotoxin.

Cytotoxic T lymphocytes (CTLs) expressing the CD8 surface marker recognize peptides in association with major histocompatibility complex (MHC) class I molecules. Although most peptides expressed on MHC class I molecules are derived from self- or virally encoded proteins, delivery of exogenous proteins to the cytosol can result in their being processed for presentation to CTLs on MHC class I molecules. We describe two fusion proteins (PEMa and PENP), consisting of the binding and translocating domains of Pseudomonas exotoxin A (PE), fused to peptide epitopes from influenza A matrix protein and nucleoprotein, respectively. These fusion proteins were internalized and processed by MHC class I-positive target cells, resulting in sensitization of target cells for lysis by peptide-specific CTLs. A point mutation known to interfere with intoxication by wild-type PE also reduced the ability of PEMa to sensitize target cells. Fusion of peptide or polypeptide epitopes with PE provides a potential means of eliciting CTLs without the use of self-replicating agents, as well as a useful probe for studying MHC class I-restricted antigen processing.

ADP Ribose Transferases↗
PubMed1993

Validation of 24-hour recalls assisted by food records in third-grade children. The CATCH Collaborative Group.

OBJECTIVE: The objective of the study was to validate the use of 24-hour recalls assisted by food records as a dietary assessment tool for use with third-grade children. DESIGN: Trained staff observed children during mealtime at school, and parents observed and recorded what children ate in their presence. The following day children participated in a 24-hour recall interview. Children's ability to recall what they consumed during a 24-hour period was compared with observational data collected during the same period. SETTING: All data were collected in elementary school settings at four sites involved in the Child and Adolescent Trial for Cardiovascular Health. SUBJECTS: The sample of 49 children was self-selected, based on parents' willingness to observe and record their child's food intake. MAIN OUTCOME MEASURES: Recalled and observed data for energy and nutrient levels were compared using mean energy and nutrient analysis and quartile classification. In addition, recalled and observed foods were compared by meal type and estimation of portion size. STATISTICAL ANALYSIS PERFORMED: Paired t tests, Pearson and Spearman correlations, and classification analysis were used to compare recalled and observed data. RESULTS: Comparison of observed and recalled food intakes showed no significant differences in percentage of energy from total fat, saturated fat, monounsaturated fat, and polyunsaturated fat or in the amount of sodium consumed, although there were differences in energy intakes. Spearman rank order correlations between recalled and observed nutrients ranged from .45 to .79. A 77.9% agreement was found across all meals in the food items children recalled having consumed compared with those adults actually observed them consuming. CONCLUSIONS: We conclude that the 24-hour recall assisted by food records is a valid method for assessing the dietary intake of children as young as 8 years old for the purpose of group comparison.

Age Factors↗
PubMed1993

Comparison of temperature measurements by an aural infrared thermometer with measurements by traditional rectal and axillary techniques.

OBJECTIVE: To compare temperatures obtained with glass-mercury axillary and aural infrared thermometers with temperatures obtained with glass-mercury rectal thermometers. DESIGN: Blind comparison with criterion standard. SETTING: Well-baby nursery at a private teaching hospital. PATIENTS: Convenience sampling of 200 term newborn infants. INTERVENTION: Temperatures were measured simultaneously with glass-mercury rectal and axillary thermometers for a 3-minute period by one investigator. In a blinded fashion, a second investigator obtained three aural temperatures by using two tympanic membrane thermometers. One tympanic membrane reported infants' rectal-equivalent temperatures, and a second reported oral equivalent temperatures. RESULTS: Temperatures obtained with glass-mercury rectal and axillary thermometers for the population were similar (37 degrees +/- 0.4 degree C vs 36.8 degrees +/- 0.3 degrees C, respectively), but 25% of measurements at these two sites differed by > 0.3 degree C. Oral-equivalent tympanic membrane temperatures were more accurate than rectal-equivalent temperatures in predicting an infant's glass-mercury axillary and rectal temperatures (75% of oral-equivalent temperatures vs fewer than 50% of rectal-equivalent temperatures were within 0.3 degree C of either glass-mercury rectal or axillary measurements). CONCLUSIONS: Temperatures obtained with glass-mercury axillary and rectal thermometers are similar in most cases. However, temperatures obtained with tympanic membrane thermometers either in the rectal-equivalent mode or in the oral-equivalent mode did not accurately reflect an infant's rectal or axillary temperature. We believe that tympanic membrane temperatures should not be substituted for rectal or axillary temperatures in assessments of newborn infants.

Axilla↗