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Biomedical subjects

M C Davis

Publications and source records attributed to M C Davis.

At least 19 recordsLinked to original sources
PubMed2001

Rational design and synthesis of novel 2,5-disubstituted cis- and trans-piperidine derivatives exhibiting differential activity for the dopamine transporter.

Herein, we report the rational design and synthesis of novel 2,5-disubstituted piperidine derivatives in the cis and trans isomeric forms. Out of these two isomers, the cis-isomer, 7a, was found to exhibit the most potent activity and selectivity for the dopamine transporter. These novel derivatives represent conformationally constrained version of piperidine analogue of GBR compounds.

Benzhydryl Compounds↗
PubMed2001

Total synthesis of SR 121463 A, a highly potent and selective vasopressin v(2) receptor antagonist.

SR 121463 A, 1, is a promising nonpeptide prototype for potent and selective antagonism of the vasopressin V(2) receptor subtype and, thus, a candidate for control of the clinically debilitating condition of hyponatremia and its associated syndromes. In the present work, we present a novel and stereoselective synthesis that stems from the preparation of three key intermediates: the substituted benzenesulfonyl chloride 2, the N-protected oxindole 3, and protected dibromide 4. The synthesis of 1 has been achieved in good overall yield, each step proceeding in greater than 80% yield. In addition, intermediate 2 and the syn isomer of 1 were prepared with complete control of stereochemistry. The latter reduction appears to proceed by lithium cation mediated chelation control. Molecular mechanics calculations with the MM3* and MMFF force fields underscore geometric and energetic aspects of the reaction.

Antidiuretic Hormone Receptor Antagonists↗
PubMed2001

The identification and characterization of hydrazinyl urea-based antibacterial agents through combinatorial chemistry.

An effort to identify novel inhibitors of peptidoglycan synthesis with antibacterial activity resulted in the discovery of a series of biaryl urea-based antibacterial agents through isolation of a by-product from a mixture-based combinatorial library of semi-carbazones and subsequent parallel synthesis efforts. The compounds were shown to possess broad spectrum antibacterial activity against gram-positive drug resistant pathogens, and showed apparent specificity for disruption of the bacterial cell wall biosynthesis pathway.

Anti-Bacterial Agents↗
PubMed2001

Vulnerability to stress among women in chronic pain from fibromyalgia and osteoarthritis.

In two investigations, we studied vulnerability to the negative effects of stress among women in chronic pain from 2 types of musculoskeletal illnesses, fibromyalgia syndrome (FMS) and osteoarthritis (OA). In Study 1, there were 101 female participants 50 to 78 years old: 50 had FMS, 29 had OA knee pain and were scheduled for knee surgery, and 22 had OA but were not planning surgery. Cross-sectional analyses showed that the three groups were comparable on demographic variables, personality attributes, negative affect, active coping, and perceived social support. As expected, FMS and OA surgery women reported similar levels of bodily pain, and both groups scored higher than OA nonsurgery women. However, women with FMS reported poorer emotional and physical health, lower positive affect, a poorer quality social milieu, and more frequent use of avoidant coping with pain than did both groups of women with OA. Moreover, the perception and use of social support were closely tied to perceived social stress only among the FMS group. In Study 2, we experimentally manipulated negative mood and stress in 41 women 37 to 74 years old: 20 women had FMS, and 21 women had OA. Participantsfrom each group were randomly assigned to either a negative mood induction or a neutral mood (control) condition, and then all participants discussed a stressful interpersonal eventfor 30 min. Stress-related increases in pain were exacerbated by negative mood induction among women with FMS but not women with OA, and pain during stress was associated with decreases in positive affect in women with FMS but not women with OA. These findings suggest that among women with chronic pain, those with FMS may be particularly vulnerable to the negative effects of social stress. They have fewer positive affective resources, use less effective pain-coping strategies, and have more constrained social networks than their counterparts with OA, particularly those who experience similar levels ofpain. They also seem to experience more prolonged stress-related increases in pain under certain circumstances, all of which may contribute to a lowering of positive affect and increased stress reactivity over time.

Adaptation, Psychological↗
PubMed2001

DNA polymerases as engines for biotechnology.

This review examines the DNA polymerases, a class of enzymes that has been an essential tool for molecular biology research. Several families of DNA polymerases have been defined based on amino acid sequence comparisons, and new enzymes are continually being discovered, driving the expansion of the current classifications. Structural similarities among the enzymes are examined, as well as the functions of the various subunits and enzyme domains. The natural variety of polymerase activities has been harnessed for applications such as amplification, labeling, and detection of DNA sequences. In addition, enhancements to DNA polymerases by genetic engineering will be described, such as enzymes specifically designed for DNA sequencing by improving the incorporation of dideoxynucleotide terminators. Reverse transcription, the ability to use RNA as a template for DNA synthesis, is described for the application of making cDNA. We believe that new and unanticipated applications will emerge as new polymerases and mutated polymerases are created and characterized.

Biotechnology↗
PubMed2000

The role of stressful events in the relationship between positive and negative affects: evidence from field and experimental studies.

Three studies are presented that examine the effects of stress on the relationship between positive and negative affective states. In the first study, recently bereaved and disabled older adults were compared to matched control groups without these recent stressors. Negative affect was inversely correlated with positive affect to a significantly greater extent for the highly stressed groups compared with controls. In a second study, older adults were exposed to a laboratory stressor, and their positive and negative affective reactions recorded. Immediately following a speech stressor task, the inverse correlation between positive and negative affect was significantly greater than in pre- and postassessments of affects. The third study was an attempt to replicate and extend the findings from Study 2 with a mid-aged sample of women. The speech stressor had the same effects as in Study 2. A second stressor, which induced pain through immersion of an arm into cold water, had no effects on the correlation between affective states. Alternative explanations for these effects and the implications for cognitive interventions are discussed.

Adult↗
PubMed1999

Oral contraceptive use and hemodynamic, lipid, and fibrinogen responses to smoking and stress in women.

The effects of acute smoking and oral contraceptive (OC) use on cardiovascular, lipid, and fibrinogen stress responses were examined in 52 female smokers and nonsmokers, half of whom were using OCs. Women smoked or sham-smoked a cigarette and then performed 2 stressful tasks. Stress elicited increases in total and low-density lipoprotein cholesterol, and in triglycerides among women who smoked, and in fibrinogen among all women. Smokers who used OCs had greater blood pressure increases to smoking and to stress than did smokers who did not use OCs. OC use was also associated with enhanced total peripheral resistance stress responses among women who smoked and cardiac output stress responses among women who sham-smoked. Results suggest that OC use moderates cardiovascular reactivity in smokers but not nonsmokers, enhancing vascular responsivity to smoking combined with stress and myocardial responsivity to stress alone.

Adolescent↗
PubMed1999

Association of negative and positive social ties with fibrinogen levels in young women.

The associations between positive and negative aspects of social relationships and fibrinogen, a risk factor for coronary heart disease (CHD), were examined in young, healthy women recruited from the community (n = 46) and from a college campus (n = 42). For community women, the perception that individuals in their social networks frequently undermined them was related to higher fibrinogen, independent of perceived frequency of support. For college women, fibrinogen was elevated among women with frequent undermining only when they also reported infrequent support. After controlling for other risk factors, the associations between social ties and fibrinogen remained significant in both samples. These results indicate that positive and negative social ties are associated with fibrinogen levels and suggest that social relationships may affect CHD risk in part through their influence on fibrinogen.

Adult↗
PubMed1999

Body fat distribution and hemodynamic stress responses in premenopausal obese women: a preliminary study.

To examine the relationship between body fat distribution and hemodynamic stress responses, cardiovascular responses to a speech task and a forehead cold pressor task were evaluated with 24 premenopausal women classified a priori as either centrally or peripherally obese. Results showed that women with central adiposity exhibited greater stress-related increases in diastolic blood pressure and total peripheral resistance, whereas women with peripheral adiposity exhibited greater stress-related increases in cardiac output. Depression, self-consciousness, hostility, and mood scores did not explain significant variance in the stress response differences between regional adiposity groups. The findings suggest that central adiposity may increase the risk of cardiovascular disease in women at least in part by enhancing vascular responses to stress.

Adipose Tissue↗
PubMed1998

Antimycobacterial activity of substituted isosteres of pyridine- and pyrazinecarboxylic acids.

Pyrazines and pyridines substituted with alkylated tetrazoles, esterified vinylogous carboxylic acids, and ketosulfides were synthesized as precursors of antimycobacterial agents which, after penetration of the mycobacterial cell wall, could be biotransformed by esterases or peroxidase-catalases. The expected products are tetrazoles, a vinylogous carboxylic acid, and CH-acidic ketosulfoxides, isosteres of pyrazinoic and nicotinic acids, which should inhibit mycobacterial growth when released inside the bacterial cell. The growth inhibitory activity of the synthesized compounds against the H37Rv strain of Mycobacterium tuberculosis was determined to assess the viability of this concept. It was shown that all of the compounds designed as lipophilic precursors were more active than the unmodified polar isosteres of pyrazinoic and nicotinic acids.

Antitubercular Agents↗
PubMed1998

MR teleradiology network serving remote imaging centers.

The operational experience of a commercial teleradiology practice utilizing a wide-area ISDN network linking six imaging centers located in two states will be reviewed. Open magnet designs were chosen to complement existing high-field units available in each community. Image data was first acquired than transmitted without compression at 128 Kbytes/s to a central reading site located in McLean, Virginia for interpretation by a team of radiologists. Average transmission time was 6-8 minutes. System design allows optimal utilization of radiologists expertise in imaging interpretation while reserving the on-site patient management responsibilities such as gadolinium contrast injections and sedation to a nonradiologists physician and/or nurse practitioner. Over 15,000 teleradiology readings have been rendered via this network by January 1998.

Adult↗
PubMed1998

Use of combinatorial library screening to identify inhibitors of a bacterial two-component signal transduction kinase.

Bacterial resistance to antibiotics is emerging as a major concern to the medical community. The appearance of several antibiotic-resistant strains, including multidrug-resistant Staphylococcus aureus, raises the prospect that infections by these bacteria could soon become untreatable with currently available antibiotics. In order to address this problem, increased emphasis is being placed on the discovery of novel classes of antibacterial agents that inhibit novel molecular targets using sources of compounds not yet exploited for antibiotic drug discovery. Novel classes of compounds can now be rapidly investigated using combinatorial chemistry approaches. This report describes the identification of novel antibacterial compounds from a combinatorial library of N-acetylated, C-amidated D-amino acid hexapeptides. This library of compounds was screened for inhibitors of CheA, a member of the bacterial two-component signal transduction kinase family. Several peptides with apparent IC50 values in the low micromolar range were identified. In addition to inhibiting CheA, these peptides inhibited mammalian protein kinase C (from rat brain) with comparable potency. Finally, these peptides were also found to have significant antibacterial properties, although the true mechanism by which they exhibited inhibition of bacterial growth remains uncertain.

Amino Acids↗
PubMed1997

Effect of prior nicotine treatment on drug induced changes in serum LH concentrations in rats.

The effect of daily injections of nicotine on drug induced changes in LH secretion was investigated in male rats. Daily administration of nicotine for 7 days resulted in decreased basal serum LH concentrations. Nicotine treatment blocked naloxone induced LH release and reduced LHRH induced increases in serum LH. Clonidine induced increases in serum LH were not altered by nicotine treatment and haloperidol treatment did not alter nicotine induced decreases in serum LH. In an acute study nicotine blocked LH secretion induced by the long acting opioid antagonist naltrexone. Collectively these results indicate that opioidergic neurons are involved in the reduction in serum LH that occurs following nicotine. They also indicate that chronic nicotine treatment can reduce the pituitary gland response to LHRH.

Adrenergic alpha-Agonists↗
PubMed1997

Teleradiology in rural imaging centres.

An economic analysis of a private commercial magnetic resonance (MR) imaging service was carried out. At an expected case-load of 2000 per year, a mid-field MR unit was predicted to cost $470 per case using teleradiology and $544 per case using film and a courier service. Routine and emergency MR services were provided to two communities in Maryland. In a two-year study period, 8083 teleradiology examinations were performed. Digital images were acquired and transmitted without data compression via ISDN at 128 kbit/s to a central diagnostic workstation for interpretation by a team of radiologists. The average transmission time for a typical case of 50 images was 6-8 min. Preliminary interpretations were normally available within 2 h and the final transcribed reports were usually faxed to the physicians' offices within 24 h. The results of a survey indicated that the system was well received by both referring physicians and patients. Costs per case in practice were similar to those predicted.

Feasibility Studies↗
PubMed1997

Thermo Sequenase DNA polymerase and T. acidophilum pyrophosphatase: new thermostable enzymes for DNA sequencing.

A combination of thermostable enzymes has been developed that produces higher quality cycle sequences. Thermo Sequenase DNA polymerase is a thermostable enzyme engineered to catalyze the incorporation of ddNTPs with an efficiency several thousandfold better than other thermostable DNA polymerases. Since the enzyme also catalyzes pyrophosphorolysis at dideoxy termini, a thermostable inorganic pyrophosphatase is needed to remove the pyrophosphate produced during sequencing reactions. Thermoplasma acidophilum inorganic pyrophosphatase (TAP) is thermostable and effective for converting pyrophosphate to orthophosphate. The use of the combination of Thermo Sequenase polymerase and TAP for cycle sequencing yields sequence data with uniform band intensities, allowing the determination of longer, more accurate sequence reads. Uniform band intensities also facilitate interpretation of sequence anomalies and the presence of mixed templates. Sequencing PCR products of DNA amplified from heterozygous diploid individuals results in signals of equal intensity from each allele.

Cloning, Molecular↗
PubMed1996

Family behavior, adaptation, and treatment adherence of pediatric nephrology patients.

In this exploratory study we investigated the relationships among family behavior variables (e.g., family expressiveness), adaptive functioning skills, maladaptive behavior, and adherence to treatment in pediatric renal failure patients. The study included 22 pediatric outpatients with renal failure who had not yet received dialysis or transplantation (RF) and their parents, and 12 pediatric outpatients with kidney transplants (TX) and their parents. For the RF patients, significant correlations were found between some of their adaptive functioning skills and measures of their medication adherence, diet adherence, and clinic appointment adherence; however, for the TX patients significant correlations were found only between some of their adaptive functioning skills and measures of their medication adherence. For the RF patients only, some measures of their family behavior were significantly correlated with measures of their medication adherence and diet adherence. Additionally, some measures of the RF patients' family behavior were significantly related to their communication skills, socialization skills, overall adaptive functioning skills, and maladaptive behavior. For the TX patients, only their socialization skill level was significantly correlated with one measure of their family behavior. It is concluded that facilitation of adaptive and physical functioning among renal pediatric patients likely requires multidimensional training and/or counselling interventions with the children and their families, and that some of the content and/or emphasis of this training likely needs to differ for RF patients versus TX patients.

Adaptation, Psychological↗