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Biomedical subjects

J S Carter

Publications and source records attributed to J S Carter.

At least 19 recordsLinked to original sources
PubMed2003

Integrating pharmacokinetics knowledge into a drug ontology: as an extension to support pharmacogenomics.

The newly developed U.S. Common Medication Information Infrastructure was used as a basis to capture and formally express the properties of drugs relevant to research and the clinical application of pharmacogenomics. Two associated taxonomies within the model, Mechanism of Action and Physiologic Effect, were enriched to accommodate pharmacogenomic use-cases; the 4,000 active ingredients in the VA NDF-RT drug file were related to the enhanced taxonomies. Pharmacokinetics were independently modeled for pharmacogenomics and tested against thirty-one high-profile drugs to demonstrate our approach.

Databases as Topic↗
PubMed2000

A colorimetric detection system for Calymmatobacterium granulomatis.

OBJECTIVE: To incorporate the first polymerase chain reaction (PCR) assay for Calymmatobacterium granulomatis into a colorimetric detection system for use in routine diagnostic laboratories. METHODS: A capture oligonucleotide specific for the Klebsiella phoE gene was covalently linked to tosyl activated magnetic beads. Biotinylated phoE PCR products obtained from 14 positive specimens from patients with donovanosis and isolates of Klebsiella pneumoniae, K rhinoscleromatis, and K ozaenae were cleaved with HaeIII for the purpose of differentiation, captured by the prepared beads, and subjected to standard EIA detection methodology. Eight samples from unrelated genital conditions underwent the same procedure. It was anticipated from the sequence data that the biotinylated fragment would be cleaved from the capture oligonucleotide target region in the three Klebsiella phoE products (that is, a negative colorimetric result) while the entire fragment of interest would remain intact in the positive C granulomatis phoE products (that is, a positive colorimetric result). RESULTS: All 14 positive specimens from patients with donovanosis gave strong colorimetric readings with this detection system. Isolates of K pneumoniae, K rhinoscleromatis, K ozaenae, and the eight specimens from unrelated genital conditions were negative. CONCLUSION: The successful development of a colorimetric detection system for C granulomatis incorporating two levels of specificity enables the molecular diagnosis of this condition to be undertaken by routine diagnostic laboratories. This should have an important role in the Australian government's campaign to eradicate donovanosis by 2003 though the test still needs to undergo trials and be validated using a larger number of samples from geographically diverse parts of the world in order to ascertain the generalisability of the methodology.

Calymmatobacterium↗
PubMed1999

4,5-Diaryloxazole inhibitors of cyclooxygenase-2 (COX-2).

A series of methysulfonyl or sulfonamido substituted 4,5-diaryloxazole were prepared and evaluated for their ability to inhibit the inducible form of cyclooxygenase (COX-2) in vitro and in vivo. Several unique substitution patterns were identified that led to potent and selective inhibitors of COX-2. In general, 2-trifluoromethly-4,5-diaryloxazoles substituted with a methylsulfonyl or sulfonamido group were particularly potent inhibitors. One of the more potent compounds with a selectivity for COX-2 of about 800 fold was 4b (SC-299). SC-299, a highly fluorescent molecule, may be useful for spectroscopic studies on preferential inhibitor binding to COX-2.

Animals↗
PubMed1999

Phylogenetic evidence for reclassification of Calymmatobacterium granulomatis as Klebsiella granulomatis comb. nov.

By sequencing a total of 2089 bp of the 16S rRNA and phoE genes it was demonstrated that Calymmatobacterium granulomatis (the causative organism of donovanosis) shows a high level of identity with Klebsiella species pathogenic to humans (Klebsiella pneumoniae, Klebsiella rhinoscleromatis). It is proposed that C. granulomatis should be reclassified as Klebsiella granulomatis comb. nov. An emended description of the genus Klebsiella is given.

Calymmatobacterium↗
PubMed1999

Knowledge, attitudes and behaviors related to physical activity among Native Americans with diabetes.

OBJECTIVE: Native Americans (NA) have higher diabetes morbidity and mortality compared to other ethnic groups. Although exercise plays an important role in diabetes management, little is known about exercise among Native Americans with diabetes. Our goal was to describe knowledge, attitudes and behaviors related to exercise in Native American participants in New Mexico. DESIGN: Bilingual community members administered a questionnaire to assess knowledge, stage of change (a measure of exercise readiness), and physical activity behavior. Hemoglobin A1c (HbA1c) was measured by DCA 2000 analyzer. Height and weight were measured to calculate body mass index (BMI). Average random blood glucose (RBS) levels and diabetes duration were assessed through chart audit. SETTING: Questionnaires were completed in offices in or near the communities. PARTICIPANTS: 514 Native Americans with diabetes were identified as potential participants, 40% (142 women, 64 men) participated. RESULTS: 37% of participants knew exercise lowers blood sugar. 82% reported they were in the preparation, action, or maintenance stage of change for exercise behavior. Seventy seven percent of this population did not meet the Surgeon General's recommendation for accumulating 30 minutes of leisure time endurance exercise on most days of the week. However, 67% of participants fell within the "high activity" category for all moderate and vigorous activities. Average age, BMI and HbA1c were 58.5 yrs., 30.5 kg/m2, 8.6%, respectively. CONCLUSIONS: Interventions to increase physical activity awareness and participation could improve diabetes management and overall health for Native Americans. When evaluating physical activity, researchers need to consider usual activities of daily living and leisure time activities specific to that population. Failure to do so would be ethnocentric and could lead to inappropriate conclusions.

Activities of Daily Living↗
PubMed1999

Diabetic amputations in the VA: are there opportunities for interventions?

Lower limb amputation (LLA) is a devastating complication experienced by some veterans with diabetes. The Veterans Affairs (VA) Healthcare system has identified the prevention of LLA as a priority goal. This study was designed to describe the sources of outpatient care received by veterans with diabetes who have undergone LLA, to determine whether these persons would have been impacted by a VA amputation prevention program. This study was also designed to describe prior amputation history, footwear history, and the pivotal events that led to these amputations. We found that the vast majority of these subjects identified the VA as their primary source of care, and thus would have been available for enrollment in a prevention program. Since over one-half of them had had a prior amputation, diabetics with a prior amputation should be particularly targeted for foot care interventions. Lastly, prescription of protective footwear has the potential to reduce the incidence of shoe-related ulcers and amputations.

Adult↗
PubMed1998

Adaptation of the Dartmouth COOP Charts for use among American Indian people with diabetes.

OBJECTIVE: To adapt the Dartmouth COOP Charts for use among American Indians with diabetes and to evaluate the operating characteristics of the adapted charts because measures of health status have not been evaluated for use among American Indians with diabetes. RESEARCH DESIGN AND METHODS: American Indian adults participated in focus group conferences to adapt and review the Dartmouth COOP Charts for use in American Indian communities. American Indian participants with diabetes were interviewed and administered the adapted charts. The operating characteristics of the charts were evaluated by measuring internal and external consistency, reliability, and acceptability. RESULTS: Some of the wording and pictures were considered to be offensive and culturally inappropriate in American Indian communities. The adapted charts showed internal consistency in a comparison of interchart variables. CONCLUSIONS: The adapted Dartmouth COOP Charts are more culturally acceptable than the original charts and appear to measure constructs adequately.

Adolescent↗
PubMed1997

Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib).

A series of sulfonamide-containing 1,5-diarylpyrazole derivatives were prepared and evaluated for their ability to block cyclooxygenase-2 (COX-2) in vitro and in vivo. Extensive structure-activity relationship (SAR) work was carried out within this series, and a number of potent and selective inhibitors of COX-2 were identified. Since an early structural lead (1f, SC-236) exhibited an unacceptably long plasma half-life, a number of pyrazole analogs containing potential metabolic sites were evaluated further in vivo in an effort to identify compounds with acceptable pharmacokinetic profiles. This work led to the identification of 1i (4-[5-(4-methylphenyl)-3-(trifluoromethyl)- H-pyrazol-1-yl]benzenesulfonamide, SC-58635, celecoxib), which is currently in phase III clinical trials for the treatment of rheumatoid arthritis and osteoarthritis.

Animals↗
PubMed1997

Temporal trends in diabetes mortality among American Indians and Hispanics in New Mexico: birth cohort and period effects.

Rates of diabetes mortality are disproportionately high among ethnic minorities in the United States. To describe ethnic trends and cohort effects in diabetes mortality in New Mexico, the authors examined the trends in mortality rates for non-Hispanic whites. Hispanics, and American Indians in the state during the period 1958-1994. Age-specific rates were examined graphically to qualitatively describe the contribution of calendar period and birth cohort effects to changes in the rates. The authors also fit age-period-cohort models to these data. Age-adjusted diabetes mortality rates for American Indians and Hispanics surpassed rates for non-Hispanic whites for all but the earliest two time periods. In the 1993-1994 period, the age-adjusted mortality rate for American Indians was 3.8 times higher for men and 5.6 times higher for women than for their non-Hispanic white counterparts. Rates for American Indian men and women increased sharply over the 37-year period, by 565% and 1,105%, respectively. Mortality rates increased among Hispanics over the period of study but less rapidly than did rates among American Indians. Graphical analyses of age-specific rates were consistent with birth cohort effects among both American Indians and Hispanics and also with a period effect among American Indians. Results from age-period-cohort models indicate a birth cohort effect starting with the 1912 cohort in American Indians and the 1902 cohort in Hispanics. A period effect was present during the 1960s in American Indians. American Indians have experienced an epidemic rise in diabetes mortality in New Mexico; if current trends continue, diabetes may become the leading cause of mortality among American Indians in the state.

Adult↗
PubMed1996

Non-insulin-dependent diabetes mellitus in minorities in the United States.

PURPOSE: To review the available information on prevalence, complications, and mortality of non-insulin-dependent diabetes mellitus and primary and secondary prevention activities in black persons, Hispanic persons, Native Americans, and Asians and Pacific Islanders in the United States. DATA SOURCE: MEDLINE search from 1976 to 1994 through the PlusNet search system. STUDY SELECTION: Use of the key words non-insulin-dependent diabetes mellitus, the names of each specific minority group, socioeconomic status, acculturation, genetics, diet, complications, mortality, treatment, and intervention (lifestyle or medication) produced 290 unduplicated articles. Additional articles cited in the original articles were also included. DATA EXTRACTION: Risk factors, incidence, prevalence, complications, and mortality of non-insulin-dependent diabetes mellitus. DATA SYNTHESIS: All minorities, except natives of Alaska, have a prevalence of non-insulin-dependent diabetes mellitus that is two to six times greater than that of white persons. Most studies show an increased prevalence of nephropathy that can be as much as six times higher than that of white persons. Retinopathy has variably higher rates in black persons, Hispanic persons, and Native Americans. Amputations are done more frequently among black persons than among white persons (9.0 per 1000 compared with 6.3 per 1000), and Pima Indians have 3.7 times more amputations than do white persons. Diabetes-related mortality is higher for minorities than for white persons, and the rate is increasing. The relative importance of genetic heritage, diet, exercise, socioeconomic status, culture, language, and access to health care in the prevalence, incidence, and mortality of diabetes is not clear. Studies of interventions in minority populations are in progress. CONCLUSION: Diabetes should be treated as a public health problem for minority populations.

Black or African American↗
PubMed1996

Rapid HbA1c testing in a community setting.

OBJECTIVE: To determine whether the DCA 2000 analyzer provides valid and reliable HbA1c results when used under field conditions and operated by nonmedical personnel. This study was part of a community diabetes education program, the Native American Diabetes Project, in which HbA1c was measured as an indicator of average glycemic control. RESEARCH DESIGN AND METHODS: Two study samples were taken, the first in the spring of 1994 and the second in the spring of 1995. Seven community members in 1994 and six new community members in 1995 were trained over 2 days, using standard protocol, to operate the DCA 2000 HbA1c analyzer and to collect two capillary blood samples from participants in the Native American Diabetes Project. Duplicate DCA 2000 HbA1c measurements performed by the community workers were compared with measurements from a high-performance liquid chromatography (HPLC) system. Validity and reliability measures were calculated. RESULTS: Of the participants, 43 were studied in 1994 and 14 in 1995. Comparison of the mean DCA 2000 results with those of HPLC showed high validity, with the absolute relative difference between the mean DCA 2000 and the external reference of HPLC (magnitude of mean DCA 2000-HPLC magnitude of /HPLC) as 4.0 and 2.0% for 1994 and 1995, respectively. The Pearson correlation coefficients (r) between these two measures were 0.968 and 0.996 for 1994 and 1995, respectively. While the 1994 data appeared to have less validity for values > 10%, they included only one value with a 60-min warm-up of the DCA analyzer. The 1995 data, all collected after a 60-min warm-up, had good correlation throughout the range of values. The within-run reliability was excellent, with an intraclass correlation coefficient of reliability of 0.959 and 0.975 for paired samples, for 1994 and 1995 respectively. The mean coefficient of variation for these paired measures was 3.0% in 1994 and 2.8% in 1995. Both validity and reliability were improved by changing the warm-up period of the DCA 2000 analyzer from 5 to 60 min. All correlation coefficients were statistically significant (P < 0.0001). CONCLUSIONS: The DCA 2000 gave valid and reliable HbA1c results when operated in a community setting by nonmedical personnel. Extending the warm-up period of the device to 60 min slightly improved the validity and reliability of the test.

Blood Chemical Analysis↗
PubMed1994

Identification of residues in monoclonal antibody NC10.8 that bind to the sweetener N-(p-cyanophenyl)-N'-(diphenylmethyl)guanidinoacetic acid by using radioligand binding, absorption and fluorescence spectroscopy, computer-aided molecular modeling, and site-directed mutagenesis.

The interactive residues for mouse mAb NC10.8, which binds a superpotent guanidinium sweetener N-(p-cyanophenyl)-N'-(diphenylmethyl)guanidinoacetic acid with high affinity (Kd = 5 nM), were examined by using radioligand competitive binding, photoaffinity labeling, absorption and fluorescence spectroscopy, computer-aided molecular modeling, and site-directed mutagenesis. Competitive ligand analogue binding data revealed important structural features and a pH sensitivity for ligand binding. Spectroscopy of the sweetener-mAb complex revealed ligand-induced fluorescence quenching and the presence of a charge-transfer band. Site-directed mutagenesis of L:96W abolished the ligand-induced fluorescence quenching and reduced Ab affinity. The apparent Kd increased from 5 nM to more than 200 nM after such modification. A theoretical model of the Fv region was generated with use of a knowledge-based algorithm, and this model was used to identify the locations of key residues in the complementarity determining regions. These experimental and theoretical studies support the prediction that the sweetener ligand coordinates with the following residues: L:34H contacts the cyanophenyl ring, L:27DR forms a salt bridge with the acetic acid moiety, L:96W forms a pi-pi interaction with the cyanophenyl ring, and H:95E contacts the positively charged aryl nitrogen. These studies are important to our understanding of Ab-ligand specificity and may also shed light on the important chemical motifs responsible for elevated levels of sweetness potency in organic compounds.

Acetates↗
PubMed1993

Effect of phosphoramidon (endothelin converting enzyme inhibitor) and BQ-123 (endothelin receptor subtype A antagonist) on blood pressure in hypertensive rats.

We reported previously that the endothelin converting enzyme (ECE) inhibitor phosphoramidon lowers mean arterial pressure (MAP) when infused in conscious, spontaneously hypertensive rats (SHRs). In this study we determined the dose-response relationship for this action in SHRs and in a high-renin hypertensive model, the renal artery-ligated rat. We also determined whether the ETA receptor antagonist BQ-123 (cyclo [D-Trp-D-Asp-Pro-D-Val-Leu]) might lower MAP in hypertensive rats. Phosphoramidon lowered MAP by 9 +/- 4, 31 +/- 4, and 40 +/- 4 mm Hg after 5 h when infused in SHRs at 10, 20, and 40 mg/kg/h. This lowering of MAP was associated with dose-related inhibition of the pressor response to a bolus intravenous injection of big ET (1-39) at 1 nmol/kg. BQ-123 also lowered MAP in SHRs (by 25 +/- 3 mm Hg), but only at a very high dose (50 mg/kg/h for 5 h). At this dose, BQ-123 blocked the pressor response to a bolus intravenous injection of ET-1 (1 nmol/kg), but the blockade was incomplete. Phosphoramidon infused in conscious, renal hypertensive rats lowered MAP by 31 +/- 9, 46 +/- 8, and 54 +/- 1 mm Hg after 5 h at 10, 20, and 40 mg/kg/h, respectively. This lowering of MAP was associated with blockade of the pressor response to big ET (1-39). BQ-123 did not lower MAP in renal hypertensive rats when infused at 30 mg/kg/h for 5 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Effect of endothelinA-receptor antagonist BQ-123 and phosphoramidon on cerebral vasospasm.

The present study was designed to determine whether an endothelinA (ETA)-receptor antagonist BQ-123 (cyclo[Dtrp, Dasp, pro-D-Val-Leu]) or an ET-converting enzyme inhibitor phosphoramidon may prevent development of cerebral vasospasm after subarachnoid hemorrhage (SAH). A "double hemorrhage" canine model of the disease was used (n = 17 dogs), and the degree of vasospasm of the basilar artery was assessed by angiography. Mongrel dogs of either sex were divided into three experimental groups: animals treated with daily intracisternal injections of BQ-123 (10(-4) M; n = 6) or phosphoramidon (2 x 10(-4) M; n = 6) and control animals treated with saline solution (n = 5). Diameter of basilar arteries in animals treated with saline solution was reduced by SAH to 56 +/- 7% of control diameter. BQ-123 and phosphoramidon did not significantly affect SAH-induced vasospasm (diameters were 62 +/- 0% and 56 +/- 10% of control diameters for BQ-123 and phosphoramidon, respectively). In contrast, in isolated canine basilar arteries BQ-123 (10(-5) M) selectively inhibited concentration-dependent contractions to ET-1 (10(-11)-3 x 10(-8) M; n = 5). Levels of immunoreactive ET in plasma and cerebrospinal fluid were not affected by development of vasospasm. These results suggest that intracisternal injections of ETA-receptor antagonist or phosphoramidon cannot prevent SAH-induced cerebral vasospasm and that ET-1 may not be the major mediator responsible for the decrease in cerebral arterial diameter associated with SAH.

Amino Acid Sequence↗