Biomedical subjects

J Grimes

Publications and source records attributed to J Grimes.

At least 19 recordsLinked to original sources

PubMed2006

Liming poultry manures to decrease soluble phosphorus and suppress the bacteria population.

Stabilizing phosphorus (P) in poultry waste to reduce P losses from manured soils is important to protect surface waters, while pathogens in manures are an emerging issue. This study was conducted to evaluate CaO and Ca(OH)2 for killing manure bacterial populations (pathogens) and stabilizing P in poultry wastes and to investigate the influence on soils following amendment with the treated wastes. Layer manure and broiler litter varying in moisture content were treated with CaO and Ca(OH)2 at rates of 2.5, 5, 10, and 15% by weight. All treated wastes were analyzed for microbial plate counts, pH, and water-soluble phosphorus (WSP), while a few selected layer manures were analyzed by phosphorus X-ray absorption near edge structure (XANES). A loamy sand and a silt loam were amended with broiler litter and layer manure treated with CaO at rates of 0, 2.5, 5, 10, and 15% and soil WSP and pH were measured at times 1, 8, and 29 d. Liming reduced bacterial populations, with greater rates of lime leading to greater reductions; for example 10% CaO applied to 20% solids broiler litter reduced the plate counts from 793,000 to 6500 mL-1. Liming also reduced the WSP in the manures by over 90% in all cases where at least 10% CaO was added. Liming the manures also reduced WSP in soils immediately following application and raised soil pH. The liming process used successfully reduced plate counts and concerns about P losses in runoff following land application of these limed products due to decreased WSP.

Animals↗

PubMed2001

Evaluation of the effectiveness of an international diploma course in tropical medicine.

BACKGROUND: Numerous impediments to conducting continuing education (CE) courses in remote sites, particularly those courses that take place in developing countries, can include challenges associated with planning, infrastructure, and financial risk. This study reports the effectiveness of a course planned in the United States and executed in Peru, the Gorgas Course in clinical tropical medicine. METHODS: A survey was conducted of participants who had completed the Gorgas Course as recently as 6 months and as long as 3 years earlier. The questionnaire sought to determine each participant's reason for participation, whether the course was instrumental in the participant's reaching the personal goal associated with participation, and whether the participant considered the course to be worth the time and money spent to enable participation. RESULTS: Forty-nine participants responded to the questionnaire, all of whom indicated that the Gorgas Course enabled achievement of the personal goal associated with participation. Fully 100% of course participants stated that participation was worth the time and monetary expenditure, most often citing their having access to patients with tropical diseases and the personal enrichment of living overseas as reasons the course was worth its high cost. FINDINGS: It is logistically and financially feasible to conduct CE courses in developing countries, provided that the organization in the planning country has strong, pre-established relationships with the host institution(s). Continued collaboration between planning partners and frequent, rigorous course evaluations are necessary to enable an international CE course to become a stable, continuous academic offering.

Curriculum↗

PubMed2001

Examination of the short-term efficacy of a parent intervention to reduce college student drinking tendencies.

The research evaluated the efficacy of an intervention to reduce the onset and extent of binge drinking during the 1st year of college. The approach was on influencing the students before they start college, through their parents, during the critical time between high school graduation and the beginning of college. Specifically, parents were educated about binge drinking and how to convey information to their teens, and then encouraged to talk with their teens just before their teens embarked on their college education. Teens whose parents implemented the intervention materials were compared with a control sample during their 1st semester on drinking outcomes, perceptions about drinking activities, perceived parental and peer approval of drinking, and drinking-related consequences. As anticipated, teens in the treatment condition were significantly different (p < .05) on nearly all outcomes in the predicted directions (e.g., lower drinking tendencies, drinking consequences). The benefits of a parent-based intervention to prevent college drinking are discussed.

Adolescent↗

PubMed2000

Differences between women and men in adverse events and CD4+ responses to nucleoside analogue therapy for HIV infection. The Aids Clinical Trials Group 175 Team.

OBJECTIVE: To prospectively examine differences in baseline characteristics and study outcomes between HIV-infected women and men during a clinical trial of nucleoside analogue therapy. METHODS: ACTG 175 randomized HIV-infected patients with CD4+ counts between 200 and 500 cells/mm3 to one of four nucleoside analogue regimens: zidovudine (ZDV), didanosine (ddI), ZDV + ddI, or ZDV + zalcitabine (ddC). Differences in time to first dose modification, voluntary withdrawal, development of toxicity and symptomatology, and AIDS progression were compared by gender. RESULTS: The study included 438 women and 2029 men. Baseline values of HIV RNA plasma concentrations were significantly lower for women (0.3 log10) than men in a subset of patients in whom assays were taken and this difference persisted after adjustment for CD4+ count. Women reported reducing dosage and discontinue ddI-containing regimens more frequently than men did; adjustment for weight did not completely explain this difference. Women were at lower risk than men for progression to a study endpoint (19% of women versus 24% of men; p <.0001). Among those antiretroviral-naive study subjects receiving ZDV, men were four times more likely to progress to a study endpoint than women. CONCLUSIONS: Differences in pretreatment characteristics and on study experiences were demonstrated between women and men enrolled in this clinical trial. The suggestion of a gender difference in response to ZDV monotherapy by antiretroviral-naive study subjects and the lower baseline values for HIV RNA in women compared with those in men provides evidence for gender differences in the relationship between virus replication, CD4+ decline, and responses to nucleoside analogue therapy.

Adult↗

PubMed2000

Evaluation of tendon-to-bone reattachment: a rabbit model.

Two different tendon-to-bone reattachment methods were compared to assess tensile strength and histologic repair. After sharp dissection, rabbit Achilles tendons were reattached to the calcaneus by one of two methods: to abraded cortical bone (group 1) or into a cancellous bone tunnel (group 2). After surgery, each rabbit had its long-leg hip spica-cast in plantar flexion for 3 weeks. The rabbits' tendon-bone junctions were harvested 1, 2, 4, 6, and 12 weeks after surgery. Three rabbits were used for each repair method at each point in time: 2 for strength testing and 1 for histologic analysis. After this preliminary study, tensile strength was tested with another 14 rabbits 2 weeks after surgery. At each advancing point in time, in both groups, increasing tendon-bone strength was found. Ultimate tensile strength was equivalent for test rabbits (both methods after 6 weeks) and control rabbits. There was no significant difference between methods at any point in time. Blinded pathologic evaluation reported similar healing with both methods over time. With both methods, healing occurred with Sharpey fibers attached to the superficial cortex, with tendon resorption occurring in the bone tunnel. The simple method of cortical reattachment was shown to be equal to the more complex bone-tunnel reattachment.

Achilles Tendon↗

PubMed1999

CoREST: a functional corepressor required for regulation of neural-specific gene expression.

Several genes encoding proteins critical to the neuronal phenotype, such as the brain type II sodium channel gene, are expressed to high levels only in neurons. This cell specificity is due, in part, to long-term repression in nonneural cells mediated by the repressor protein REST/NRSF (RE1 silencing transcription factor/neural-restrictive silencing factor). We show here that CoREST, a newly identified human protein, functions as a corepressor for REST. A single zinc finger motif in REST is required for CoREST interaction. Mutations of the motif that disrupt binding also abrogate repression. When fused to a Gal4 DNA-binding domain, CoREST functions as a repressor. CoREST is present in cell lines that express REST, and the proteins are found in the same immunocomplex. CoREST contains two SANT (SW13/ADA2/NCoR/TFIIIB B) domains, a structural feature of the nuclear receptor and silencing mediator for retinoid and thyroid human receptors (SMRT)-extended corepressors that mediate inducible repression by steroid hormone receptors. Together, REST and CoREST mediate repression of the type II sodium channel promoter in nonneural cells, and the REST/CoREST complex may mediate long-term repression essential to maintenance of cell identity.

Amino Acid Sequence↗

PubMed1999

Alpha7 nicotinic receptor mediated protection against ethanol-induced cytotoxicity in PC12 cells.

Ethanol caused a concentration-dependent loss of PC12 cells over a 24 h interval, accompanied by an increase in intracellular calcium. The specific alpha7 nicotinic receptor partial agonist DMXB attenuated both of these ethanol-induced actions at a concentration (3 microM) found previously to protect against apoptotic and necrotic cell loss. The alpha7 nicotinic receptor antagonist methylylaconitine blocked the neuroprotective action of DMXB when applied with but not 30 min after the agonist. These results indicate that activation of alpha7 nicotinic receptors may be therapeutically useful in preventing ethanol-neurotoxicity.

Aniline Compounds↗

PubMed1999

Examination of cognitive variables relevant to sunscreen use.

The present study is an examination of the underlying psychological variables relevant to a sun-damage preventive behavior, sunscreen use. The focus of the research was to examine cognitive predictors of sunscreen use, utilizing a decision theoretic framework. Two hundred thirty subjects were recruited from psychology classes and administered questionnaires assessing sunscreen behavioral tendencies, attitudes toward sunscreen use, and internal- and external-based cognitions relevant toward sunscreen use. In contrast to previous work that had examined only one or two of these predictor variables in isolation, the present study evaluated the relative impact of these variables on sunscreen use tendencies. The findings revealed evidence of a multivariate model (using structural equation modeling; LISREL VIII) relating perceived need for, perceived efficacy of, perceived consequences of, and social normative influences on sunscreen use. The findings are discussed with respect to improving the effectiveness of short-term education efforts to increase sunscreen use.

Adult↗

PubMed1999

Virus crystallography.

Virus crystallography can provide atomic resolution structures for intact isometric virus particles and components thereof. The methodology is illustrated by reference to a particularly complex example, the core of the bluetongue virus (700 A).

Bluetongue virus↗

PubMed1998

Effect of HIV-specific immune-based therapy in subjects infected with HIV-1 subtype E in Thailand.

OBJECTIVE: To examine the effect of treatment with an inactivated, gp120-depleted, HIV-1 immunogen (Remune) in 30 Thai subjects infected with HIV-1 subtype E. DESIGN: Sixty-week open-label study. METHODS: Thirty HIV-positive volunteers with CD4 cell counts > or = 300 x 10(6)/l were given intramuscular injections of Remune into the triceps muscle on day 1 and then at weeks 4, 8, 12, 24, 36, 48 and 60. RESULTS: Treatment with Remune was well-tolerated and augmented HIV-1-specific immune responses. Furthermore, subjects had a significant increase in CD4 cell count (P < 0.0001), CD4 cell percentage (P < 0.0001), CD8 cell percentage (P < 0.0001), and body weight (P < 0.0001) compared with pretreatment levels. Fourteen subjects with detectable viral load at day 1 showed a decrease at week 60 (P=0.04). Retrospective Western blot analysis showed 23 subjects with increased intensity of antibody bands and 15 patients showed development of new reactivities to HIV proteins, especially towards p17 and p15. CONCLUSION: These results indicate that HIV-specific immune-based therapeutic approaches such as Remune should be further examined in countries with different clades of HIV-1 and where access to antiviral drug therapies is limited.

AIDS Vaccines↗

PubMed1998

Structural studies of orbivirus particles.

We are using crystallographic methods to investigate the structure of AHSV and BTV. Our initial approach was to investigate the structure of the major protein component of the viral core, VP7(T13). This trimeric protein has been studied in several crystal forms from both orbiviruses and reveals a structure made up of conserved domains, capable of conformational changes and possessing a cleavage site. Further crystallographic analyses of native particles have provided a picture of the VP7(T13) and VP3(T2) layers of the BTV core. The VP7(T13) layer consists of 260 trimers arranged rather symmetrically and possessing very similar structures, thereby following the rules of quasi equivalence. The VP3(T2) layer is thin and contains 120 copies of 100 kDa protein arranged as 60 approximate dimers. This type of icosahedral construction has not been observed before and appears to contain a genome which is highly ordered. We anticipate that all of these features will be common to AHSV.

African Horse Sickness Virus↗

PubMed1997

The crystal structure of plasma gelsolin: implications for actin severing, capping, and nucleation.

The structure of gelsolin has been determined by crystallography and comprises six structurally related domains that, in a Ca2+-free environment, pack together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur. We propose that binding Ca2+ can release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently. Domain shifts are proposed in response to Ca2+ as bases for models of how gelsolin acts to sever, cap, or nucleate F-actin filaments. The structure also invites discussion of polyphosphoinositide binding to segment 2 and suggests how mutation at Asp-187 could initiate a series of events that lead to deposition of amyloid plaques, as observed in victims of familial amyloidosis (Finnish type).

Actins↗

PubMed1997

Structure-affinity relationships and stereospecificity of several homologous series of local anesthetics for the beta2-adrenergic receptor.

UNLABELLED: Local anesthetics inhibit binding of ligands to beta2-adrenergic receptors (beta2ARs), and, as a consequence, inhibit intracellular cAMP production. We hypothesized that among homologous local anesthetics, their avidity at inhibiting binding of tritiated dihydroalprenolol (3H-DHA) to beta2ARs would increase with increasing length of alkyl substituents and would demonstrate stereospecificity. Specific binding of 3H-DHA to human beta2ARs was assayed in the presence of six different members of the 1-alkyl-2,6-pipecoloxylidide class of local anesthetics (including mepivacaine, ropivacaine, and bupivacaine), the R(+) and S(-) bupivacaine enantiomers, lidocaine, prilocaine, etidocaine, procaine, and tetracaine. Avidity of binding to beta2ARs increased with increasing length of the alkyl chain (pKi values = 2.4, 3.6, 4.3, 4.1, 4.1, 5.9 for the methyl [mepivacaine], ethyl, S(-)propyl [ropivacaine], butyl [bupivacaine], pentyl, and octyl derivatives, respectively). We found no evidence for bupivacaine stereospecificity (pKi values = 4.3 and 4.9 for the S(-) and R(+) isomers, respectively). Other amide and ester local anesthetics also showed increasing potency with increasing length of alkyl substituents (pKi values = 3.6, 3.8, and 4.3 for lidocaine, prilocaine, and etidocaine; 4.2 and 5.6 for procaine and tetracaine, respectively). The correlation between increased inhibition of beta2AR binding and alkyl chain length resembles the correlation between local anesthetic potency at nerve block and increased alkyl chain length. The lack of clear stereospecificity is consistent with the relatively low potency these agents demonstrate at inhibition of beta2AR binding. Finally, the relatively potent inhibition of beta2ARs by etidocaine, tetracaine, and bupivacaine suggests that their propensity for cardiovascular depression after accidental intravenous overdose could result from beta2AR or beta1AR blockade and inhibition of cAMP production. IMPLICATIONS: Local anesthetics demonstrate a rank order of avidity for displacing ligands from beta2-adrenergic receptors such that larger molecules displace ligands at lower concentrations than smaller local anesthetic molecules. This relationship between molecular size and receptor avidity could explain the greater propensity for cardiovascular toxicity of relatively large local anesthetics such as bupivacaine.

Adrenergic beta-2 Receptor Antagonists↗

PubMed1996

Improving accelerometer-based rate adaptive pacing by means of second-generation signal processing.

Accelerometer-based rate adaptive pacing has gained widespread clinical use. Limitations exist for the distinction between walking upstairs and downstairs. It was the aim of this study to evaluate a new signal processing algorithm for more physiological rate adaptation. A custom-made pacemaker incorporating an accelerometer was randomly fixed to the left or right chest of 16 pacemaker patients (7 females, age: 64 +/- 11 years), 18 elderly study participants (6 females, age: 62 +/- 11 years), and 15 students (7 females age: 23 +/- 2 years). Study participants walked on level ground, upstairs and downstairs at five different step rates (72, 84, 96, 108, and 120 steps/min) controlled by an acoustic quartz metronome. The accelerometer signals, recorded on a portable data recorder, were analyzed with respect to frequency content, peak average of the mean acceleration, and morphology characteristics of the acceleration signal above and below zero baseline. By calculating the quotient of the signal's duration above and below zero baseline, a reliable discrimination between walking upstairs and downstairs was possible. A correction of the Leaky integrator signal by the new quotient yielded a more adequate rate adaptation to walking up and downstairs to represent at the patient's daily life activities. A more physiological rate adaptation can be achieved when using not only the accelerometer signal's amplitude, but applying additionally the morphology criterium of the acceleration signal's content in the positive and negative direction.

Acceleration↗

PubMed1996

Crystal structure of the top domain of African horse sickness virus VP7: comparisons with bluetongue virus VP7.

The baculovirus-expressed core protein VP7 of African horse sickness virus serotype 4 (AHSV-4) has been purified to homogeneity and crystallized in the presence of 2.8 M urea. The X-ray structure has been solved to a 2.3-Angstroms (1 Angstrom = 0.1 nm) resolution with an Rfactor of 19.8%. The structure of AHSV VP7 reveals that during crystallization, the two-domain protein is cleaved and only the top domain remains. A similar problem was encountered previously with bluetongue virus (BTV) VP7 (whose structure has been reported), showing that the connections between the top and the bottom domains are rather weak for these two distinct orbiviruses. The top domains of both BTV and AHSV VP7 are trimeric and structurally very similar. The electron density maps show that they both possess an extra electron density feature along their molecular threefold axes, which is most likely due to an unidentified ion. The characteristics of the molecular surface of BTV and AHSV VP7 suggest why AHSV VP7 is much less soluble than BTV VP7 and indicate the possibility of attachment to the cell via attachment of an Arg-Gly-Asp (RGD) motif in the top domain of VP7 to a cellular integrin for both of these orbiviruses.

African Horse Sickness Virus↗

PubMed1995

The crystal structure of bluetongue virus VP7.

Bluetongue virus (BTV), a representative of the orbivirus genus of the Reoviridae, is considerably larger (at 80 nm across), and structurally more complex, than any virus for which we have comprehensive structural information. Orbiviruses infect mammalian hosts through insect vectors and cause economically important diseases of domesticated animals. They possess a segmented double-stranded RNA genome within a capsid composed of four major types of polypeptide chains. An outer layer of VP2 and VP5 is removed as the virus enters the target cell, to leave an intact core within the cell. This core is 70 nm across and composed of 780 copies of VP7 (M(r) 38K) that, as trimers, form 260 'bristly' capsomeres clothing an inner scaffold constructed from VP3 (M(r) 103K). We report here the crystal structure of VP7 from BTV serotype 10, which reveals a molecular architecture not seen previously in viral structural proteins. Each subunit consists of two domains, one a beta-sandwich, the other a bundle of alpha-helices, and a short carboxy-terminal arm which might tie trimers together during capsid formation. A concentration of methionine residues at the core of the molecule could provide plasticity, relieving structural mismatches during assembly.

Amino Acid Sequence↗

PubMed1995

Expression of carbonic anhydrase II (CA II) promoter-reporter fusion genes in multiple tissues of transgenic mice does not replicate normal patterns of expression indicating complexity of CA II regulation in vivo.

Although the proximal, 5' 115 bp of the human carbonic anhydrase II (CA II) gene was sufficient for expression of a reporter gene in some transfected cell lines, we found previously that 1100 bp of this promoter (or 500 bp of the mouse CA II promoter) was not sufficient for expression in transgenic mice. We have now studied the expression of linked reporter genes in mice transgenic for either (1) 11 kb of the human 5' promoter or (2) 8 kb of the human 5' promoter with mouse sequences from the first exon, part of the first intron (since a CpG island spans this region), and the 3' sequences of the gene. Expression was found in both cases, but the tissue specificity was not appropriate for CA II. Although there was a difference in the sensitivity of the assays used, the first construct led to expression in many tissues, while the second construct was expressed only in spleen. These findings indicate considerable complexity of DNA control regions for in vivo CA II expression.

Animals↗

PubMed1994

Female pseudohermaphroditism with multiple caudal anomalies: absence of Y-specific DNA sequences as pathogenetic factors.

46,XX female pseudohermaphrodites have been previously described with nearly complete masculinization of the external genitalia and no apparent source of testosterone. Multiple malformations of internal genital, urinary, and gastrointestinal tracts are associated. We have evaluated four such infants with female pseudohermaphroditism and multiple caudal anomalies. Three cases had apparently normal chromosomes (46,XX); one had a 46,XX,del(10)(q25.3-->qter) chromosome constitution. The chromosome breakpoint is in the region of PAX2, a developmentally important paired box gene which is expressed in urogenital tissue. Using the polymerase chain reaction, we screened for the presence of multiple Y specific sequences, including SRY (sex determining region, Y chromosome), that could explain masculinization of the external genitalia. All were negative for Y centromeric sequences, ZFY (Zinc finger Y), and SRY. Furthermore, there was no evidence for adrenal or other sources of testosterone. We suggest that the masculinization in these cases is the result of abnormal expression of genes which would normally be regulated by testosterone.

Abnormalities, Multiple↗