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Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 91 records · Page 5Linked to original sources
PubMed2000

Comparison of the EQ-5D and SF-12 health surveys in a general population survey in Alberta, Canada.

OBJECTIVES: The purposes of this analysis were to evaluate the construct validity of the EQ-5D and compare responses on the EQ-5D with the Physical Component Summary (PCS-12) and Mental Component Summary (MCS-12) scores of the SF-12 Health Survey. METHODS: Data were collected via a survey instrument mailed to 4,200 randomly selected subjects in the province of Alberta, Canada. The instrument contained the EQ-5D and SF-12 health surveys, with additional questions eliciting clinical and demographic information from the respondents. RESULTS: 1,555 respondents returned mailed questionnaires; 606 questionnaires were returned undeliverable. The SF-12 summary scores were calculated for 1,380 respondents. Analysis of the EQ-5D responses by demographic variables found significant differences among categories of age, gender, and self-reported chronic medical conditions. Corresponding dimensions and summary scores were more strongly related (eg, mobility and PCS-12; F ratio = 598.3, P < 0.001) than dissimilar dimensions (eg, mobility and MCS-12; F ratio = 18.8, P < 0.001). The EQ-5D index scores were moderately correlated with SF-12 summary scores (r = 0.41 for MCS-12 and r = 0.68 for PCS-12). For subjects reporting no problems on the EQ-5D, PCS-12 and MCS-12 scores were significantly lower for people reporting medical problems or feelings of depression. CONCLUSIONS: The results of this investigation generally supported the validity of the EQ-5D. However, an important ceiling effect was observed for the EQ-5D in this sample. The combination of the EQ-5D and SF-12 provides relatively broad coverage of important health domains and scores for various purposes.

Activities of Daily Living↗
PubMed2000

Fat distribution and health in obesity.

Although independent associations of visceral fat with the insulin resistance syndrome were previously reported in obese women, the importance of truncal subcutaneous fat in this syndrome is controversial. The method by which the various fat depots are measured may be the reason for the underlying controversy. In the past five years, we have used various methods to measure visceral versus subcutaneous fat distribution in Caucasian (C) and African-American (AA) women and have related it to insulin sensitivity (SI) and to blood lipids, particularly fasting serum triglyceride levels (TG). Elevated TG levels in obese women were best predicted by an increased amount of visceral fat, whereas the amounts of truncal and peripheral subcutaneous fat did not have an impact on them. These results were confirmed, regardless of the method used to measure the fat depots. Insulin resistance (low SI) in obese women was predicted by both an increase of visceral and of upper-body (truncal) subcutaneous fat. However, measurements of the entire visceral and truncal subcutaneous fat volumes may be needed to confirm this latter association.

Absorptiometry, Photon↗
PubMed2000

Sequence analysis of TnphoA insertion sites in Vibrio cholerae mutants defective in rugose polysaccharide production.

Vibrio cholerae can switch from a smooth to a wrinkled or rugose colony phenotype characterized by the secretion of a polysaccharide that enables the bacteria to survive harsh environmental conditions. In order to understand the genetic basis of rugosity, we isolated TnphoA-induced stable, smooth mutants of two O1 El Tor rugose strains and mapped the insertion sites in several of the mutants using a modified Y-adapter PCR technique. One of the TnphoA insertions was mapped to the first gene of the vps region that was previously shown to encode the rugose polysaccharide biosynthesis cluster. Three insertions were mapped to a previously unknown hlyA-like gene, also in the vps region. Five other insertions were found in loci unlinked to the vps region: (i) in the epsD gene (encodes the "secretin" of the extracellular protein secretion apparatus), (ii) in a hydG-like gene (encodes a sigma(54)-dependent transcriptional activator similar to HydG involved in labile hydrogenase production in Escherichia coli, (iii) in a gene encoding malic acid transport protein upstream of a gene similar to yeiE of E. coli (encodes a protein with similarities to LysR-type transcriptional activators), (iv) in dxr (encodes 1-deoxy-D-xylulose 5-phosphate reductoisomerase), and (v) in the intergenic region of lpd and odp (encode enzymes involved in the pyruvate dehydrogenase complex formation). These data suggest the involvement of a complex regulatory network in rugose polysaccharide production and highlight the general utility of the Y-adapter PCR technique described here for rapid mapping of transposon insertion sites.

Alkaline Phosphatase↗
PubMed2000

Phylogeny of Vibrio cholerae based on recA sequence.

We sequenced a 705-bp fragment of the recA gene from 113 Vibrio cholerae strains and closely related species. One hundred eighty-seven nucleotides were phylogenetically informative, 55 were phylogenetically uninformative, and 463 were invariant. Not unexpectedly, Vibrio parahaemolyticus and Vibrio vulnificus strains formed out-groups; we also identified isolates which resembled V. cholerae biochemically but which did not cluster with V. cholerae. In many instances, V. cholerae serogroup designations did not correlate with phylogeny, as reflected by recA sequence divergence. This observation is consistent with the idea that there is horizontal transfer of O-antigen biosynthesis genes among V. cholerae strains.

Base Sequence↗
PubMed2000

Mutations in the extracellular protein secretion pathway genes (eps) interfere with rugose polysaccharide production in and motility of Vibrio cholerae.

Vibrio cholerae is the causal organism of the diarrheal disease cholera. The rugose variant of V. cholerae is associated with the secretion of an exopolysaccharide. The rugose polysaccharide has been shown to confer increased resistance to a variety of agents, such as chlorine, bioacids, and oxidative and osmotic stresses. It also promotes biofilm formation, thereby increasing the survival of the bacteria in the aquatic environments. Here we show that the extracellular protein secretion system (gene designated eps) is involved directly or indirectly in the production of rugose polysaccharide. A TnphoA insertion in epsD gene of the eps operon abolished the production of rugose polysaccharide, reduced the secretion of cholera toxin and hemolysin, and resulted in a nonmotile phenotype. We have constructed defined mutations of the epsD and epsE genes that affected these phenotypes and complemented these defects by plasmid clones of the respective wild-type genes. These results suggest a major role for the eps system in pathogenesis and environmental survival of V. cholerae.

Alkaline Phosphatase↗
PubMed2000

Cryptic genetic diversity in Dientamoeba fragilis.

Uncertainty surrounding the role of Dientamoeba fragilis in human disease could be due in part to the existence of pathogenic and nonpathogenic variants. Evidence for two genetically distinct forms was obtained using PCR-restriction fragment length polymorphism analysis of ribosomal genes. Future studies in humans will need to take D. fragilis diversity into account.

Animals↗
PubMed2000

Forskolin-induced apical membrane insertion of virally expressed, epitope-tagged CFTR in polarized MDCK cells.

Channel gating of the cystic fibrosis transmembrane conductance regulator (CFTR) is activated in response to cAMP stimulation. In addition, CFTR activation may also involve rapid insertion of a subapical pool of CFTR into the plasma membrane (PM). However, this issue has been controversial, in part because of the difficulty in distinguishing cell surface vs. intracellular CFTR. Recently, a fully functional, epitope-tagged form of CFTR (M2-901/CFTR) that can be detected immunologically in nonpermeabilized cells was characterized (Howard M, Duvall MD, Devor DC, Dong J-Y, Henze K, and Frizzell RA. Am J Physiol Cell Physiol 269: C1565-C1576, 1995; and Schultz BD, Takahashi A, Liu C, Frizzell RA, and Howard M. Am J Physiol Cell Physiol 273: C2080-C2089, 1997). We have developed replication-defective recombinant adenoviruses that express M2-901/CFTR and used them to probe cell surface CFTR in forskolin (FSK)-stimulated polarized Madin-Darby canine kidney (MDCK) cells. Virally expressed M2-901/CFTR was functional and was readily detected on the apical surface of FSK-stimulated polarized MDCK cells. Interestingly, at low multiplicity of infection, we observed FSK-stimulated insertion of M2901/CFTR into the apical PM, whereas at higher M2-901/CFTR expression levels, no increase in surface expression was detected using indirect immunofluorescence. Immunoelectron microscopy of unstimulated and FSK-stimulated cells confirmed the M2-901/CFTR redistribution to the PM upon FSK stimulation and demonstrates that the apically inserted M2-901/CFTR originates from a population of subapical vesicles. Our observations may reconcile previous conflicting reports regarding the effect of cAMP stimulation on CFTR trafficking.

Adenoviridae↗
PubMed2000

Sickle cell disease telemedicine network for rural outreach.

The Medical College of Georgia (MCG) Sickle Cell Center in Augusta, Georgia, USA, provides consultation and (in some cases) primary-care services to more than 1000 patients with sickle cell disease (SCD). Three SCD telemedicine clinic sites were established in rural areas of middle and southern Georgia, based on clinical need; a fourth site had been proposed. Over a 36-month study period, 77 telemedicine SCD clinics were held. There was a mean of 6.1 (SD 2.5) encounters per clinic and 466 total encounters among 128 SCD patients. By using telemedicine, the productivity of the MCG adult sickle cell clinic increased from 1413 to 1889 encounters a year, with an increase in rural outreach activity from 271 to 745 encounters a year. This was accomplished with the addition of a single physician assistant during the last 12 months of the study period; otherwise provider staffing was unchanged. A formal cost-benefit analysis now needs to be carried out.

Adolescent↗
PubMed2000

Health-related quality of life for adults with cystic fibrosis: a regression approach to assessing the impact of recombinant human DNase.

STUDY OBJECTIVES: To examine the general health-related quality of life (HRQOL) of adults with cystic fibrosis (CF) using available generic instruments, and to determine important predictors of change in HRQOL, including therapy with recombinant human Dnase (rhDNase). DESIGN: Prospective, observational study. PATIENTS: Fifty-nine adults with CE. INTERVENTION: The Medical Outcomes Study Short-Form 36 (SF-36) and the EuroQol (EQ-5D) were mailed to patients; follow-up surveys were mailed 1 year later. MEASUREMENTS AND MAIN RESULTS: Multivariate regression analyses assessed the relationships between clinical and demographic variables and change in health status. The 39 respondents reported lower HRQOL scores compared with general population norms for generic instruments. Regression analyses indicated that age (p=0.010), percentage predicted forced expiratory volume in 1 second (p=0.005), hospital admission (p=0.023), and rhDNase therapy (p=0.026) were positively associated 1998 EQ-5D index scores, whereas body mass index was negatively associated (p=0.025) with 1998 EQ-5D index scores after controlling for baseline 1997 scores. The size of the regression coefficients indicated that only 1997 scores and hospital admission in the year were quantitatively importantly associated with 1998 scores. Baseline HRQOL assessments showed that adults with CF reported important decrements in health status and functioning. An interesting relationship between functional status and total household income was observed. CONCLUSION: Although a statistically significant association between rhDNase and 1-year change in HRQOL was found on multivariate regression analysis, the magnitude of this relationship may not be clinically important.

Adult↗
PubMed2000

Gender differences in labetalol kinetics: importance of determining stereoisomer kinetics for racemic drugs.

STUDY OBJECTIVE: To evaluate the impact of gender on labetalol kinetics. DESIGN: Part of a randomized, crossover study. SETTING: Academic medical center. PATIENTS: Nineteen hypertensive patients (14 men, 5 women; 6 blacks, 13 whites). INTERVENTIONS: Participants had labetalol dosages titrated to a specific antihypertensive response, then underwent ambulatory blood pressure monitoring (ABPM) and a pharmacokinetic study. Labetalol plasma concentrations were measured by high-performance liquid chromatography (HPLC) and labetalol stereoisomer ratios were determined in a single plasma sample by chiral HPLC, both with fluorescence detection. MEASUREMENTS AND MAIN RESULTS: Labetalol concentrations were 80% higher in women (area under the concentration-time curve [AUC]/dose x 1000: 6.79 +/- 2.11 in women vs 3.82 +/- 1.37 hr/L in men, p<0.05), yet both genders had a similar antihypertensive response by 24-hour ABPM. Dose-corrected AUC (AUC/dose x 1000) for labetalol's stereoisomers in women and men, respectively, were S,R-labetalol 7.55 +/- 1.47 and 4.83 +/- 1.54 hr/L (p<0.05), S,S-labetalol 8.23 +/- 2.93 and 4.65 +/- 1.78 hr/L (p<0.05), R,S-labetalol 6.99 +/- 3.30 and 4.25 +/- 2.35 hr/L (p=0.11), and R,R-labetalol 3.91 +/- 2.57 and 3.55 +/- 3.08 hr/L (NS). CONCLUSION: The higher labetalol concentration in women than in men was explained largely by differences in inactive and alpha1-blocking stereoisomers. However, concentrations were similar between genders for the beta-blocking stereoisomer (R,R-labetalol), possibly explaining the similarity in antihypertensive response to the drug. This study highlights the importance of determining stereoisomer kinetics for agents administered as racemates, particularly when relating concentrations to pharmacologic response.

Adult↗
PubMed2000

Using focus groups to identify barriers to drug use in patients with congestive heart failure.

STUDY OBJECTIVE: To explore barriers to adherence to drug therapy identified by patients with congestive heart failure (CHF). SETTING: University-associated heart failure clinic and a family practice clinic. PATIENTS: Twenty-six patients with CHF. INTERVENTION: Four focus group sessions. MEASUREMENTS AND MAIN RESULTS: Participants were asked to describe how their lives changed as a result of developing CHF and the challenges they face when taking drugs for the condition. In the second half of each session, participants were asked for their opinions regarding various teaching and memory aids for improving adherence with therapy. They recognized the value of these aids and often created their own when health care professionals did not supply them. Transcripts were reviewed and comments grouped to identify patient-perceived barriers to adherence. The disease placed significant limitations on lifestyle. Furosemide had dramatic effects on daily activities, and some patients altered the dosing schedule to accommodate their plans. Influences on adherence were generalized into five themes: confidence in health care providers; their own knowledge regarding the disease and drugs used to treat it; previous experience with drugs; support from family and friends; and ease of communication with health care professionals. CONCLUSION: Focus groups are an effective and efficient method to explore patients opinions of barriers to drug therapy adherence. Such information can have a direct impact on management of patients with CHF. Information gathered in this study will be used to construct a survey to measure barriers to drug adherence and design interventions to improve adherence.

Aged↗
PubMed2000

Seasonal occurrence of postharvest dried fruit insects and their parasitoids in a culled fig warehouse.

Parasitoids of dried-fruit insects were surveyed at a culled fig warehouse in Fresno, CA. Three parasitoids of pyralid larvae were found: Habrobracon hebetor (Say), Venturia canescens (Gravenhorst), and at least one species in the genus Goniozus Förster. Two parasitoids of pyralid pupae also were noted: Mesostenus gracilis (Cresson) and a new species of Psilochalcis Keifer. The latter is a new host association. Several beetle parasitoids were present, including Anisopteromalus calandrae (Howard), three species of Cephalonomia Westwood, Laelius centratus (Say), and Cerchysiella utilis Noyes. C. utilis, a parasitoid of driedfruit beetle, Carpophilus hemipterus (L.), is a new record for California. Most activity by parasitoids (detected by yellow flight traps) occurred directly above the fig mass. Pyralid parasitoids exhibited two peaks of seasonal activity; one in late summer through early fall, shortly after new figs were brought into the warehouse, and one in the spring. H. hebetor generally attacked older host larvae, whereas V. canescens equally attacked older and younger larvae, indicating that these two parasitoids may coexist by exploiting different portions of the host population. H. hebetor was active throughout the winter, suggesting that winter release of H. hebetor could be used to control diapausing pyralid populations in dried fruit and nut storage areas.

Animals↗
PubMed2000

Predictability of the effects of race or ethnicity on pharmacokinetics of drugs.

The International Conference on Harmonization has put forth a tripartite guideline addressing mechanisms by which regulatory agencies might be able to accept foreign clinical data. A major issue is the effect of ethnicity on the drug's pharmacokinetics, pharmacodynamics and/or safety. The purpose of this review was to determine whether the effects of ethnicity on pharmacokinetics are predictable. We also evaluated whether the premise that only pharmacokinetic processes which are biologically or biochemically mediated are likely to exhibit ethnic differences was supported by the literature. Bioavailability is determined by absorption, gut metabolism/transport and hepatic first pass metabolism. Absorption is usually a passive process and, as would be expected, no examples of ethnic differences in passive absorption were found in the literature. Direct evaluation of ethnic differences in gut metabolism/transport or hepatic first pass metabolism is largely lacking, although some studies suggest such differences exist. These differences would also be expected based on known ethnic differences in hepatic clearance of drugs. Ethnic differences in plasma protein-binding to the two major drug-binding proteins, alpha1-acid glycoprotein (AGP) and albumin, have been studied in several populations. Based on these studies, ethnic differences in plasma protein-binding for drugs which bind exclusively to albumin (e.g. acids) are uncommon. Conversely, ethnic differences in plasma protein-binding of drugs to AGP appear to be very common, with the studies consistently showing Caucasians have higher binding (lower plasma free fractions) than other ethnic groups. This difference appears, in all cases, to be explained by racial differences in plasma AGP concentration. Hepatic metabolism is the most common pharmacokinetic parameter for which there are ethnic differences. Differences have been documented in both oxidative and conjugative metabolism. Ethnic differences in hepatic metabolism are unpredictable by race (e.g. one racial group is not consistently higher or lower than another group) and specific enzyme (e.g. studies with different CYP3A4 substrates have yielded different results). Ethnic differences in renal tubular secretion have been documented, but also appear to be unpredictable, while differences in the passive processes of renal elimination, filtration and reabsorption, have not been observed. The literature supports the premise that pharmacokinetic processes which are active (e.g. involve a protein) are the ones with the potential for differences between ethnic groups while passive pharmacokinetic processes do not exhibit such differences. Based on the available literature, the drugs most likely to exhibit ethnic differences in their pharmacokinetics are those that undergo significant gut metabolism/transport and/or hepatic first pass metabolism; are highly bound to plasma proteins (especially AGP); or have hepatic metabolism as a major route of elimination.

Ethnicity↗
PubMed2000

CYP1A2 and CYP2D6 4-hydroxylate propranolol and both reactions exhibit racial differences.

We have previously shown racial differences in propranolol kinetics, with the largest differences appearing to be in its 4-hydroxylation. The purpose of this study was to identify and confirm the cytochrome P450 enzymes (CYP) with propranolol 4-hydroxylase activity, describe their enzyme kinetics, and determine whether there were racial differences in their catalytic activity. Eleven human recombinant, expressed CYPs were screened, but only CYP1A2 and CYP2D6 possessed propranolol 4-hydroxylase activity. Subsequent studies were conducted in human liver microsomes, including correlation, inhibition, enzyme kinetics, and racial comparison studies. Significant correlations were noted between propranolol 4-hydroxylation and ethoxyresorufin-O-deethylation (marker of CYP1A2 activity), with marked improvement in the correlations when CYP2D6-mediated propranolol 4-hydroxylation was inhibited with quinidine. Inhibition studies showed that quinidine inhibited approximately 55% of propranolol 4-hydroxylation and furaphylline (CYP1A2-selective inhibitor) inhibited about 45% of propranolol 4-hydroxylation. Median (range) parameter estimates of (S)-4-hydroxypropranolol [(S)-HOP] formation were a V(max) value of 307 (165-2397) and 721 (84-1975) pmol/mg of protein/60 min for CYP1A2 and CYP2D6, respectively, and a K(m) value of 21.2 (8.9-77.5) and 8.5 (5.9-31.9) microM for CYP1A2 and CYP2D6, respectively. CYP1A2- and CYP2D6-mediated propranolol 4-hydroxylation was about 70 and 100% higher (P <.05 for both), respectively, in African-Americans compared with Caucasians. In summary, we found that both CYP1A2 and CYP2D6 catalyze formation of 4-hydroxypropranolol and that both enzymes exhibited racial differences in this reaction. The observed racial differences in drug metabolism may have relevance to drug efficacy, toxicity, or carcinogen activation for CYP1A2 or CYP2D6 substrates.

Aryl Hydrocarbon Hydroxylases↗
PubMed2000

Effects of COER-verapamil on circadian pattern of forearm vascular resistance and blood pressure.

Controlled-onset extended-release verapamil (COER-V) is designed so drug concentrations rise sharply in the early morning to coincide with the peak incidence of cardiovascular events. The primary objective of this study was to compare the diurnal pattern of forearm vascular resistance (FVR) between hypertensives and normotensives and to determine the effect of COER-V on FVR's diurnal pattern. The authors also studied the effects of COER-V on 24-hour ambulatory blood pressure (ABP) and the early morning blood pressure rise. Baseline 24-hour ABP was recorded, and FVR was determined by venous occlusion plethysmography at 7 a.m., 2 p.m., and 9 p.m. in 23 untreated hypertensives; FVR was also determined in 10 matched, normotensive controls. Plethysmography studies and 24-hour ABP were repeated and S- and R-verapamil concentrations determined over 24 hours by HPLC following > or = 4 weeks of therapy. The diurnal pattern of FVR differed between hypertensives and normotensives, with normotensives exhibiting an FVR decline between 2 p.m. and 9 p.m., while FVR rose at 9 p.m. in hypertensives. COER-V appeared to minimize the diurnal variation in FVR in hypertensives, although there were no significant differences at any single time point (baseline 7 a.m.: 58 +/- 24; 2 p.m.: 48 +/- 13; and 9 p.m.: 55 +/- 19 vs. COER-V at 7 a.m.: 51 +/- 23; 2 p.m.: 51 +/- 17; and 9 p.m.: 54 +/- 17 mmHg/ml/min/100 g). COER-V effectively reduced ABP throughout the 24-hour period (p < 0.05). No significant differences were found in the slopes of the early morning rise in BP or change in morning trough-to-peak BP at baseline and on the drug. The data suggest that hypertension alters the normal diurnal pattern in FVR and that COER-V minimizes the diurnal variation in this parameter. In addition, the authors conclude that COER-V is an effective antihypertensive that lowers BP throughout a 24-hour period, but it does not blunt the early morning rate of BP rise despite peak S-verapamil concentrations in the early morning.

Adult↗
PubMed2000

Aging in America: challenges and strategies for health care delivery.

This article delineates the current and future trends related to aging in the United States. The demographic and economic forces outlined are ones that will clearly challenge health services leaders and policy-makers in the coming decades. Various policy interventions and strategies currently underway to address the needs of the aging population are described. Shifts in caregiving patterns, the delivery of long-term care services, economics, choices in living arrangements, and managed care programs for the elderly are a few of the issues presented in this article. Health and human services for the elderly will undergo a profound change as the health system continues to adapt itself to the demands of an aging society.

Aged↗
PubMed1999

Conformation of a rigid tetrasaccharide epitope in the capsular polysaccharide of Vibrio cholerae O139.

A newly reported strain of Vibrio cholerae, known as strain O139 Bengal, is the first instance of an encapsulated strain that has caused epidemic cholera. The O-antigenic capsule is the critical antigen for protective immunity. Since mapping of the antigenic epitopes will assist in the development of a protein conjugate vaccine based on the capsular polysaccharide, we have undertaken a study of the three-dimensional conformation of the polysaccharide. It contains six residues in the repeating subunit with the unusual feature of a 4,6 cyclic phosphate on a beta-galactopyranoside. A structural epitope composed of four of the residues is somewhat similar to the Lewis(b) blood group tetrasaccharide. Polysaccharide samples enriched in (13)C have been prepared by growth of the bacteria in (13)C-enriched medium. Multidimensional heteronuclear NMR and molecular modeling studies are reported, which show that the O139 tetrasaccharide adopts a compact and tightly folded conformation that is relatively rigid and similar to the Le(b) conformation. The cyclic phosphate on the beta-galactopyranoside residue is in contact with the colitose residue linked to the beta-GlcNAc.

Carbohydrate Conformation↗