Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 55 records · Page 3Linked to original sources

PubMed2001

Ex vivo purging by adenoviral p53 gene therapy does not affect NOD-SCID repopulating activity of human CD34+ cells.

Co-incubation of a replication-deficient, recombinant adenovirus carrying the wild-type p53 gene (rAd-p53) and hematopoietic stem cell (HSC) products from patients with breast cancer can significantly reduce tumor cell contamination. Whereas this approach provides a powerful tumor cell purging strategy, potential detrimental effects on the HSC population have not been investigated. The ability of human HSC to reconstitute hematopoiesis in severe combined immunodeficient (SCID) mice and to undergo secondary transplantation provides the only nonclinical measure of self-renewing, stem cell function. The objective of this study was to investigate whether co-incubation with rAd-p53 compromised the SCID repopulating activity (SRA) of HSC. Granulocyte colony-stimulating factor-mobilized human CD34+ cells were co-cultured with rAd-p53 at our targeted clinical dose, and the ability of these cells to establish multilineage hematopoiesis in sublethally irradiated, nonobese diabetic (NOD)-SCID mice was investigated. The persistence of human cells in the mice was investigated by flow cytometry, granulocyte-macrophage colony-forming unit assay, and polymerase chain reaction of human Alu sequences. Further, limiting dilution analysis provided a quantitative comparison between the SRA of CD34+ cells co-incubated with rAd-p53 and control CD34+ cells (no rAd-p53 co-incubation). We conclude that co-incubation with rAd-p53 has little effect on the SRA of HSC.

Adenoviridae↗

PubMed2001

Swallowing in myotonic muscular dystrophy: a videofluoroscopic study.

OBJECTIVES: (1) To determine how swallow function in patients with myotonic muscular dystrophy (MD) differs from that of healthy controls, (2) to identify the contributors to and predictors of improvement, and (3) to evaluate strategies that facilitate swallowing. DESIGN: Observational. SETTING: University medical center. PARTICIPANTS: Eighteen adults with myotonic MD (age range, 24-58 yr) and 60 healthy adult control subjects (age range, 18-73 yr). INTERVENTIONS: Swallow facilitation strategies. MAIN OUTCOME MEASURES: Between-group comparisons of mean bolus transit times, onsets of swallow gestures, and displacement measures obtained by dynamic lateral view videofluoroscopy. RESULTS: The MD patients' bolus transit times were significantly longer, and onsets of some swallow gestures were significantly delayed. Upper esophageal sphincter opening was prolonged (myotonic MD,.61 +/-.13s; control,.5 +/-.11s). Hyoid displacement was significantly less in men with myotonic MD (1.9 +/-.05 cm) than in male controls (2.4 +/-.68 cm); this difference was not observed between control and myotonic women. Of particular importance was the markedly reduced pharyngeal constriction found in the MD group. CONCLUSIONS: Weakness associated with the disease, as opposed to myotonia, was the most significant contributor to impairment. Persons at risk for aspiration may be identified by a measure of pharyngeal area. Selected strategies to facilitate pharyngeal clearing are worthwhile.

Adult↗

PubMed2001

Herpes zoster--predicting and minimizing the impact of post-herpetic neuralgia.

Herpes zoster results from reactivation of latent varicella-zoster virus in the dorsal root ganglia and is frequently associated with severe pain. Most patients suffer acute pain during the rash phase, and in many, prodromal pain or discomfort also precedes the rash. The pain of herpes zoster gradually resolves with time, but may persist after the acute disease as post-herpetic neuralgia for weeks, months or even years. Post-herpetic neuralgia, the most common complication of herpes zoster, often results in significant morbidity and healthcare resource usage. Early treatment with oral antivirals has been shown to accelerate the resolution of postherpetic neuralgia, with therapeutic effects particularly evident in the over-50 age group, where pain generally persists for longer. Progressively increasing life expectancy of the population translates to increasing numbers of cases of herpes zoster. The socio-economic gains associated with active management, including use of oral antivirals where indicated, to speed resolution of pain and post-herpetic neuralgia, readily justify additional cost.

Herpes Zoster↗

PubMed2001

Thiopental is a competitive inhibitor at the human alpha7 nicotinic acetylcholine receptor.

UNLABELLED: The nicotinic acetylcholine receptors (nAChRs) in the central nervous system may be a potential target for the anesthetic effects of thiopental. We evaluated the mechanism of action of thiopental on the human alpha7 nAChR by using 2-electrode voltage clamp methodology. Concentration response curves for agonist were prepared in the presence of 25-250 microM of thiopental. Inhibition by the S- and R-thiopental enantiomers was compared with inhibition by racemic thiopental. We found that thiopental acts as a competitive inhibitor at the human alpha7 nAChR. Inhibition is independent of membrane potential and the K(i(apparent)) is 13 microM of thiopental. The clinical 50% effective concentration for thiopental in humans is 25 microM. Thus, with a K(i(apparent)) of 13 microM, inhibition of the human alpha7 nAChR is within a clinically relevant range. The S- and R-enantiomers of thiopental cause inhibition indistinguishable from the inhibition caused by racemic thiopental. This discordance makes it unlikely that the alpha7 nAChR plays a role in loss of righting reflex induced by thiopental in mice, although nicotinic inhibition by thiopental may mediate other anesthetic effects and side effects. IMPLICATIONS: The receptors for nicotine in the brain may be involved in the mechanism of general anesthetics. We have shown that a human receptor for nicotine is inhibited by the anesthetic barbiturate thiopental, at concentrations used clinically. The nicotinic receptor thus may mediate some of the actions of this drug.

Anesthetics, Intravenous↗

PubMed2001

Linear and volumetric wear of tibial inserts in posterior cruciate-retaining knee arthroplasties.

Linear and volumetric wear was measured in 33 tibial polyethylene inserts from three different cruciate-retaining knee systems retrieved at the time of revision surgery. Wear patterns also were evaluated and classified. Eccentric and asymmetric wear patterns were seen in 78% of inserts with flat articulating geometry versus 12% in inserts with curved anteroposterior geometry. The mean linear wear rate was .35 mm/year (range, .05-1.68 mm/year) and the mean volumetric wear rate was 794 mm3/year (range, 24-4088 mm3/year). Linear and volumetric wear rates showed a negative correlation with the length of implantation. Linear wear rates also showed a negative correlation with patient weight.

Arthroplasty, Replacement, Knee↗

PubMed2001

Clinical manifestations of early syphilis by HIV status and gender: results of the syphilis and HIV study.

BACKGROUND: Despite reports of unusual clinical presentations and therapeutic responses among HIV-infected patients with syphilis, syphilis has not been regarded as a serious opportunistic infection that predictably progresses among most HIV-coinfected patients. GOAL: To define and describe differences in the presentation and response to treatment of early syphilis among HIV-infected and HIV-uninfected patients, to describe any differences by gender, and to determine if clinical presentation of central nervous system involvement predicted serologic failure. DESIGN: A prospective, multicenter, randomized, controlled trial of enhanced versus standard therapy to compare the benefit of enhanced therapy, the clinical importance of central nervous system involvement, and the clinical manifestations of early syphilis infection among HIV-infected and HIV-uninfected patients. RESULTS: The median number of ulcers was significantly greater among HIV-infected and HIV-uninfected patients, as was the percent of HIV-infected patients with multiple ulcers. Among patients diagnosed with secondary syphilis, a higher percentage of HIV-infected patients presented with genital ulcers [13/53 (25%)] than did HIV-uninfected patients [27/200 (14%)]. No differences between HIV-infected and HIV-uninfected patients were detected for other secondary syphilis manifestations. Although women presented more frequently with secondary syphilis than did men, no other gender differences in clinical manifestations were noted. Neurologic complaints were reported most frequently among patients with secondary syphilis [103/248 patients (42%)] compared with patients with primary syphilis [32/136 (24%)] and early latent syphilis [48/ 142, (34%)] (P < 0.05), but no differences in neurologic complaints were apparent by HIV status or CSF abnormalities. No neurologic complaints were significantly associated with serologic treatment failures at 6 months. CONCLUSIONS: Overall, HIV infection had a small effect on the clinical manifestations of primary and secondary syphilis. Compared with HIV-uninfected patients, HIV-infected patients with primary syphilis tended to present more frequently with multiple ulcers, and HIV-infected patients with secondary syphilis presented with concomitant genitals ulcers more frequently.

Adult↗

PubMed2001

Candidate disease resistance genes in sunflower cloned using conserved nucleotide-binding site motifs: genetic mapping and linkage to the downy mildew resistance gene Pl1.

Disease resistance gene candidates (RGCs) belonging to the nucleotide-binding site (NBS) superfamily have been cloned from numerous crop plants using highly conserved DNA sequence motifs. The aims of this research were to (i) isolate genomic DNA clones for RGCs in cultivated sunflower (Helianthus annuus L.) and (ii) map RGC markers and Pl1, a gene for resistance to downy mildew (Plasmopara halstedii (Farl.) Berl. & de Toni) race 1. Degenerate oligonucleotide primers targeted to conserved NBS DNA sequence motifs were used to amplify RGC fragments from sunflower genomic DNA. PCR products were cloned, sequenced, and assigned to 11 groups. RFLP analyses mapped six RGC loci to three linkage groups. One of the RGCs (Ha-4W2) was linked to Pl1, a downy mildew resistance gene. A cleaved amplified polymorphic sequence (CAPS) marker was developed for Ha-4W2 using gene-specific oligonucleotide primers. Downy mildew susceptible lines (HA89 and HA372) lacked a 276-bp Tsp5091 restriction fragment that was present in downy mildew resistant lines (HA370, 335, 336, 337, 338, and 339). HA370 x HA372 F2 progeny were genotyped for the Ha-4W2 CAPS marker and phenotyped for resistance to downy mildew race 1. The CAPS marker was linked to but did not completely cosegregate with Pl1 on linkage group 8. Ha-4W2 was found to comprise a gene family with at least five members. Although genetic markers for Ha-4W2 have utility for marker-assisted selection, the RGC detected by the CAPS marker has been ruled out as a candidate gene for Pl1. Three of the RGC probes were monomorphic between HA370 and HA372 and still need to be mapped and screened for linkage to disease resistance loci.

Base Sequence↗

PubMed2001

Verbal instruction for correcting errors versus such instructions plus videotape replay on learning the overhand throw.

The influence of two methods of providing information to women, ages 19 to 22 years who were novices and learning the overhand throw with the nondominant arm, was examined. One group received verbal information on correcting errors, and a second group received the same information immediately prior to viewing a videotaped replay of a just completed throw. Performance was assessed quantitatively with respect to outcome (distance thrown) and qualitatively with respect to throwing form as measured on a 7-point rating scale by judges with a working knowledge of the overhand throw and with respect to throwing mechanics rated by a panel of experts in biomechanics using a scale of Leme and Shambes. Although the treatments led to better learning and performance, there was no significant difference between groups for distance thrown on the Leme and Shambes scale in Sessions 1-6 of 10 trials each on Session 7. The mean rating also indicated increased scores for both groups and better retention at posttest by the group receiving only verbal corrections. These results suggest that information provided by adding videotaped replay may be redundant and unnecessary for those in Sessions 1-6.

Adult↗

PubMed2001

Shoulder range of motion characteristics in collegiate baseball players.

BACKGROUND: To determine range of motion and capsular characteristics of dominant and nondominant shoulders in baseball players. Our hypothesis was that there is a significant difference between dominant and nondominant range of motion in collegiate baseball players with unoperated and without shoulder pain. METHODS DESIGN: prospective, range of motion measurements during regular season. SETTING: two collegiate baseball teams in Houston. PARTICIPANTS: 15 pitchers and 23 position players. MAIN OUTCOME MEASURES: shoulder range of motion was evaluated by goniometric technique in all baseball players. Horizontal adduction (cross body reach test) and active internal rotation (reach behind back) in standing position and external rotation and internal rotation in supine lying position were measured for each player. RESULTS: Average external rotation with the arm in 90 degrees of abduction was significantly greater and average internal rotation was less in the dominant shoulder than in the nondominant shoulders, both in pitchers and position players. There was no statistical difference in shoulder horizontal adduction. Both dominant and nondominant shoulders of pitchers had greater average range of motion in horizontal adduction and external rotation at 90 degrees of abduction and less average internal rotation than those of position players. Although there was a significant difference in active internal rotation as cm between dominant and nondominant shoulders both in both groups, no difference was found between pitchers and position players. CONCLUSIONS: Differences in the range of motion in the throwing shoulder of baseball players exist involved in overhead throwing motions and should be considered in rehabilitation of the upper extremity after injury and in the prevention of injury for pitchers and position players.

Adolescent↗

PubMed2001

Effectiveness and tolerability of melatonin and zolpidem for the alleviation of jet lag.

BACKGROUND: The aim of this study was to compare the effectiveness and tolerability of a chronobiotic (melatonin) with a hypnotic (zolpidem) and the combination of both substances to alleviate jet lag symptoms associated with eastward travel. METHODS: This double-blind, randomized, placebo-controlled study is based on 137 volunteers flying from Switzerland to the American continent and back (6-9 time zones). The participants either received melatonin 5 mg (n = 35), zolpidem 10 mg (n = 34), a combination thereof (n = 29) or placebo (n = 39) on the eastbound flight back to Switzerland and once daily at bedtime on 4 consecutive days after the flight. The test battery included daily sleep logs, symptoms questionnaires, and the Profile of Mood States (POMS). Also, on the last treatment day, Visual Analog Scales (VAS) were completed to assess overall jet lag ratings and treatment effectiveness. Baseline data were collected on 4 consecutive days 2 wk after the flight. During post-flight treatment and baseline, motor activity was assessed in a subgroup of 49 subjects using wrist-worn ambulatory monitors. RESULTS: The self-rated sleep quality was significantly improved by zolpidem, especially during the night flight. Subjects taking zolpidem reported significantly less jet lag and zolpidem was rated as the most effective jet lag medication. However, zolpidem and the combination melatonin/zolpidem were less well tolerated than melatonin alone; adverse event reports included nausea, vomiting, amnesia and somnambulia to the point of incapacitation. Confusion, morning sleepiness and nausea were highest in the combination group. CONCLUSIONS: All active treatments led to a decrease of jet lag severity with zolpidem being the most effective treatment, particularly in facilitating sleep on night flights. Potential individual adverse reactions to this hypnotic have to be considered.

Adolescent↗

PubMed2001

Advocacy groups dismayed by lack of funding in president's budget.

HIV/AIDS advocates have expressed dismay, if not surprise, over the proposed funding for domestic HIV programs outlined in the budget submitted in the spring by President George W. Bush. Despite the reality of rising drug costs and increasing numbers of newly infected Americans, the Ryan White CARE Program was flat-funded in the proposal. Other programs fared no better, except for research and international HIV funding.

Budgets↗

PubMed2001

Prioritization of professional issues by Idaho Dental Hygienists.

PURPOSE: The Idaho Dental Hygienists' Association (IDHA) and other constituents use surveys to establish the goals of the association and better represent members. This study was conducted to assess dental hygienists' opinions about professional issues related to dental hygiene practice and legislative activities in Idaho. METHODS: In 1998, a questionnaire was mailed to all active Idaho dental hygiene licensees (N = 652). The coded questionnaire contained two sections. Section I included items on demographic and employment characteristics, and Section II included items on legislative and professional issues. Respondents were asked to rank 14 professional issues by selecting the top five concerns about dental hygiene practice in Idaho. Research questions asked included: 1) Do entry-level baccalaureate degrees in dental hygiene affect the ranking of professional concerns of Idaho dental hygienists? 2) Does being a member of the American Dental Hygienists' Association (ADHA) affect Idaho dental hygienists' ranking of professional concerns? Data were analyzed using frequency distributions and nonparametric tests of association. RESULTS: A 74% (N = 431) response rate was obtained after two mailings. Three professional issues were ranked as important concerns by at least 50% of respondents. They were 1) the "national trend to reduce entry-level education for dental hygienists," 2) "dental assistants performing dental hygiene services," and 3) "legalizing self-regulation." CONCLUSIONS: It is incumbent upon constituent dental hygienists' associations to obtain and utilize information from members for strategic planning and legislative efforts. A statewide membership study clearly can provide direction. Idaho dental hygienists are concerned about maintaining quality education programs, reducing illegal practices, and regulating themselves. Also, the state association and regulatory agencies need to take an active role to assure that dentists, dental hygienists, and dental assistants are educated about state laws.

Adult↗

PubMed2000

Coordinate up-regulation of hypoxia inducible factor (HIF)-1alpha and HIF-1 target genes during multi-stage epidermal carcinogenesis and wound healing.

Both carcinogenesis and wound healing proceed through stages of proliferation and tissue remodeling. Here, using either a model of multistage epidermal carcinogenesis in K14-HPV16 transgenic mice or creation of full-thickness back wounds in nontransgenic mice, we determined patterns of expression of hypoxia inducible factor (HIF)-1alpha, and three targets of the heterodimeric transcription factor HIF-1, glucose transporter (GLUT)-1, phosphoglycerate kinase (PGK)-1, and vascular endothelial growth factor (VEGF) in skin. Neither HIF-1alpha, GLUT-1, PGK-1, nor VEGF mRNA was detectable in unwounded nontransgenic skin. In epidermal carcinogenesis, HIF-1alpha, GLUT-1, PGK-1, and VEGF mRNAs were just detectable in early-stage hyperplasia, markedly increased in high-grade epidermal chest dysplasias, and further increased in invasive squamous carcinomas. In neoplastic skin, HIF-1alpha, GLUT-1, and PGK-1 mRNAs localized in the basal and immediate suprabasal epidermal layers, whereas VEGF mRNA was predominantly expressed in the more superior spinous and granular epidermal layers. Immediately after wounding, HIF-1alpha, GLUT-1, and PGK-1 mRNAs were detectable in basal keratinocytes at the wound edge. Expression of all three genes increased to maximum levels in reepithelializing basal keratinocytes and then diminished to near undetectable levels after wound epithelialization. Although VEGF mRNA similarly increased and decreased during wound healing, its expression pattern was more punctate; the most intense hybridization signals were detected in the upper spinous and granular layers of reepithelializing keratinocytes and in dermal cells morphologically similar to macrophages. These data suggest stage-specific and spatio-temporal control of HIF-1alpha and HIF-1 target gene expression in both multistage epithelial carcinogenesis and wound healing.

Animals↗

PubMed2000

Event-related potential (ERP) studies of memory encoding and retrieval: a selective review.

As event-related brain potential (ERP) researchers have increased the number of recording sites, they have gained further insights into the electrical activity in the neural networks underlying explicit memory. A review of the results of such ERP mapping studies suggests that there is good correspondence between ERP results and those from brain imaging studies that map hemodynamic changes. This concordance is important because the combination of the high temporal resolution of ERPs with the high spatial resolution of hemodynamic imaging methods will provide a greatly increased understanding of the spatio-temporal dynamics of the brain networks that encode and retrieve explicit memories.

Brain↗

PubMed2000

Requirement for p38alpha in erythropoietin expression: a role for stress kinases in erythropoiesis.

Activity of the p38alpha MAP kinase is stimulated by various stresses and hematopoietic growth factors. A role for p38alpha in mouse development and physiology was investigated by targeted disruption of the p38alpha locus. Whereas some p38alpha(-/-) embryos die between embryonic days 11.5 and 12.5, those that develop past this stage have normal morphology but are anemic owing to failed definitive erythropoiesis, caused by diminished erythropoietin (Epo) gene expression. As p38alpha-deficient hematopoietic stem cells reconstitute lethally irradiated hosts, p38alpha function is not required downstream of Epo receptor. Inhibition of p38 activity also interferes with stabilization of Epo mRNA in human hepatoma cells undergoing hypoxic stress. The p38alpha MAP kinase plays a critical role linking developmental and stress-induced erythropoiesis through regulation of Epo expression.

Anemia↗

PubMed2000

Optimization of a precision-cut trout liver tissue slice assay as a screen for vitellogenin induction: comparison of slice incubation techniques.

An in vitro male rainbow trout liver slice assay has been developed for long-term incubation of precision-cut slices for the detection of vitellogenin (VTG) protein induction in response to xenobiotic chemicals. The assay was optimized to allow 72 h of incubation of slices to maximize detection of VTG, while maintaining slice viability. Two methods of incubation frequently used with rat liver slices were compared: (1) slices were submerged in media (11 degrees C) and cultured in 12-well plates (PL) with continuous shaking; or (2) slices were floated onto titanium screens, placed into glass vials, and held under dynamic organ culture (DOC) conditions (11 degrees C). Slices (200 µm) in modified L-15 media were exposed to 1.0 µM 17beta-estradiol (E2) or diethylstilbestrol (DES). Protein from media and slice was sampled for Western blot analysis, using a polyclonal antibody to detect appearance of VTG protein. Maximum VTG was seen at 72 h, with detectable protein at 24 and 48 h in slices and media following PL incubation. In contrast, slices incubated in DOC showed little detectable VTG above background levels after 72 h. This difference was not attributable to protein loss to vial or plate surfaces. Standard viability assays did not reveal any differences between slices incubated in PL or DOC. However, histopathological examination revealed earlier and more severe vacuolization in slices incubated in DOC. Significantly more E2 uptake and conversion to water-soluble metabolites was noted in PL, compared with DOC, as well as more production of VTG in response to DES and E2, correlated with less histologic change. The in vitro assay described allows tissue-level assessment of estrogenicity in aquatic organisms, and will be useful for assessing not only comparative species receptor binding and transactivation, but also the role of tissue-specific activation factors in the estrogenic response of fish.

Journal Article↗

PubMed2000

Consultant appraisals. With due respect.

Consensus is needed on which management competencies should be included in doctors' appraisals. One trust employed management consultants to find out the views of senior doctors, managers, directors and patients. Common themes included concern for standards, effective use of information, openness, integrity and insight. The results will be used to guide future recruitment.

Clinical Competence↗

PubMed2000

Prescribing costs. Braking point.

A joint hospital, health authority and PCG initiative to improve prescribing has produced significant savings in the PCG involved. The venture included the appointment of a medicines management pharmacist to work with practices, and a survey to ascertain GPs' prescribing needs. GPs considered the most important issues to be developing local disease management guidelines, education and repeat prescribing. Guidelines on dyspepsia management have resulted in a 4.9 per cent reduction in the cost of prescribing gastrointestinal drugs. Antibiotic prescribing has also fallen.

Anti-Bacterial Agents↗