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Biomedical subjects

K Carr

Publications and source records attributed to K Carr.

At least 19 recordsLinked to original sources
PubMed2001

Drought-induced guard cell signal transduction involves sphingosine-1-phosphate.

Stomata form pores on leaf surfaces that regulate the uptake of CO2 for photosynthesis and the loss of water vapour during transpiration. An increase in the cytosolic concentration of free calcium ions ([Ca2+]cyt) is a common intermediate in many of the pathways leading to either opening or closure of the stomatal pore. This observation has prompted investigations into how specificity is controlled in calcium-based signalling systems in plants. One possible explanation is that each stimulus generates a unique increase in [Ca2+]cyt, or 'calcium signature', that dictates the outcome of the final response. It has been suggested that the key to generating a calcium signature, and hence to understanding how specificity is controlled, is the ability to access differentially the cellular machinery controlling calcium influx and release from internal stores. Here we report that sphingosine-1-phosphate is a new calcium-mobilizing molecule in plants. We show that after drought treatment sphingosine-1-phosphate levels increase, and we present evidence that this molecule is involved in the signal-transduction pathway linking the perception of abscisic acid to reductions in guard cell turgor.

Abscisic Acid↗
PubMed2000

Microwave radiometric thermometry and its potential applicability to ablative therapy.

INTRODUCTION: [corrected] Current techniques for estimating catheter tip temperature in ablative therapy for cardiac arrhythmias rely on thermocouples or thermistors attached to or embedded in the tip electrode. These methods may reflect the electrode temperature rather than the tissue temperature during electrode cooling so that the highest temperature away from the ablation site may go undetected. A microwave radiometer is capable of detecting microwave radiation as a result of molecular motion. In this study, we evaluated microwave radiometric thermometry as a new technique to monitor temperature away from the electrode tip during ablative therapy utilizing a saline model. METHODS AND RESULTS: A microwave radiometer antenna and fluoroptic thermometer were inserted in a test tube with circulating room temperature saline kept constant at 23.5 degrees C while the surrounding saline bath was heated from 37 degrees C to 70 degrees C. For every degree rise in the warm saline bath placed either 5 mm or 8 mm from the radiometer antenna, the radiometer temperature changed 0.26 degrees C and 0.14 degrees C respectively while the fluoroptic temperature probe remained constant at 23.5 degrees C. The radiometer temperature was highly correlated with the warm saline bath temperature (R(2)=0.997 for warm saline 5 mm from the antenna, R(2)=0.991 for warm saline 8 mm from the antenna). CONCLUSIONS: Microwave radiometry can estimate distant temperatures by detecting microwave electromagnetic radiation. The sensitivity of the microwave radiometer is also distance-dependent. The microwave radiometer thus serves as a promising instrument for monitoring temperatures at depth away from the catheter-electrode tip in ablative therapy for cardiac arrhythmias.

Calibration↗
PubMed2000

Safety and efficacy of a steerable temperature monitoring microwave catheter system for ventricular myocardial ablation.

INTRODUCTION: Radiofrequency current delivered during cardiac ablation is limited by a rise in impedance secondary to coagulum formation on the ablation electrode. Microwave antennas continue to deliver energy despite the presence of coagulum; thus, temperature control of the ablation electrode may be even more important for microwave than for radiofrequency ablations to avoid thromboembolic risks. The purpose of this study was to test the safety and efficacy of an ablation system utilizing a feedback control system to maintain a fixed target temperature for creating lesions with multiple applications of microwave energy. METHODS AND RESULTS: Microwave ablation was assessed using an 8.5-French catheter at 2 to 4 sites in 11 dogs. Microwave energy delivery was performed for 60 seconds three times at the same site. Power was regulated using a feedback control mechanism to maintain a target temperature of 75 degrees C. Ambulatory ECG monitoring was performed before and after ablation to assess arrhythmia occurrence. After follow-up, the dogs were euthanized, and lesion dimensions measured after fixation. The mean power applied to achieve the target temperature of 75 degrees C was 9.3+/-44 W. The mean depth of the lesions was 8.8+/-4.2 mm. The mean volume of the lesions was 304+/-240 mm3. Forty-four percent of the lesions were transmural. No endocardial thrombus was found. Ventricular tachycardia was observed acutely but resolved after 1 week. CONCLUSION: Temperature feedback control systems for microwave ablation using a temperature-controlled system is feasible for myocardial ablation and creates uniform and large lesions; however, such large lesions can be acutely proarrhythmic.

Animals↗
PubMed1998

Anxiety proneness linked to epistatic loci in genome scan of human personality traits.

A genome-wide scan between normal human personality traits and a set of genetic markers at an average interval of 13 centimorgans was carried out in 758 pairs of siblings in 177 nuclear families of alcoholics. Personality traits were measured by the Tridimensional Personality Questionnaire. We detected significant linkage between the trait Harm Avoidance, a measure of anxiety proneness, and a locus on chromosome 8p21-23 that explained 38% of the trait variance. There was significant evidence of epistasis between the locus on 8p and others on chromosomes 18p, 20p, and 21q. These oligogenic interactions explained most of the variance in Harm Avoidance. There was suggestive evidence of epistasis in other personality traits. These results confirm the important influence of epistasis on human personality suggested by twin and adoption studies.

Anxiety↗
PubMed1998

Genome-wide search for genes affecting the risk for alcohol dependence.

Alcohol dependence is a leading cause of morbidity and premature death. Several lines of evidence suggest a substantial genetic component to the risk for alcoholism: sibs of alcoholic probands have a 3-8 fold increased risk of also developing alcoholism, and twin heritability estimates of 50-60% are reported by contemporary studies of twins. We report on the results of a six-center collaborative study to identify susceptibility loci for alcohol dependence. A genome-wide screen examined 291 markers in 987 individuals from 105 families. Two-point and multipoint nonparametric linkage analyses were performed to detect susceptibility loci for alcohol dependence. Multipoint methods provided the strongest suggestions of linkage with susceptibility loci for alcohol dependence on chromosomes 1 and 7, and more modest evidence for a locus on chromosome 2. In addition, there was suggestive evidence for a protective locus on chromosome 4 near the alcohol dehydrogenase genes, for which protective effects have been reported in Asian populations.

Adolescent↗
PubMed1997

Initial genomic scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 3, 5, 15, 16, 17, and 22.

As part of the four-center NIMH Genetics Initiative on Bipolar Disorder we carried out a genomic scan of chromosomes 3, 5, 15, 16,17, and 22. Genotyping was performed on a set of 540 DNAs from 97 families, enriched for affected relative pairs and parents where available. We report here the results of the initial 74 markers that have been typed on this set of DNAs. The average distance between markers (theta) was 12.3 cM. Nonparametric analysis of excess allele sharing among affected sibling pairs used the SIBPAL program of the S.A.G.E. package to test three hierarchical models of affected status. D16S2619 gave some evidence of linkage to bipolar disorder, with P = 0.006 for Model II (in which bipolar 1, bipolar 2 and schizoaffective-bipolar type individuals are considered affected). Nearby markers also showed increased allele sharing. A second interesting region was toward the telomere of chromosome 5q, where D5S1456 and nearby markers showed increased allele sharing; for D5S1456, P = 0.05, 0.015 and 0.008 as the models of affected status become more broad. MOD score analysis also supported the possible presence of a susceptibility locus in this region of chromosome 5. A pair of adjacent markers on chromosome 3, D3S2405 and D3S3038, showed a modest increased allele sharing in the broad model. Several isolated markers had excess allele sharing at the P < 0.05 level under a single model. D15S217 showed a MOD score of 2.37 (P < 0.025). Multipoint analysis flagged the region of chromosome 22 around D22S533 as the most interesting. Thus, several regions showed modest evidence for linkage to bipolar disorder in this initial genomic scan of these chromosomes, including broad regions near previous reports of possible linkage.

Alleles↗
PubMed1997

Alcohol use after liver transplantation in alcoholics: a clinical cohort follow-up study.

The purposes of this study were to determine among a cohort of long-term alcoholic survivors after liver transplantation (1) the incidence of alcohol use, (2) its effect on allograft integrity and extrahepatic health, and (3) the validity of the pretransplant alcohol prognosis screening process. Retrospective clinical cohort study of all alcoholic patients undergoing orthotopic liver transplantation at a single center from February 1987 until January 1991 with follow-up through December 1994, giving a median duration of follow-up of 63 months (range, 6-89 months). Multidisciplinary liver transplantation program at a tertiary-care academic medical center. Fifty alcoholic, long-term liver transplant recipients. The frequency of alcohol relapse, defined as any alcohol use in the period after transplantation, was determined by two questionnaire studies and by clinical follow-up. Allograft integrity was assessed by coded review of serial percutaneous allograft biopsies. Potential systemic effects of alcohol relapse were assessed by chart review. The alcohol prognosis screening process was evaluated by retrospectively comparing pretransplant estimates of putative indicators of alcoholism prognosis in posttransplant alcohol users and abstainers. Thirty-three recipients (66%) consistently denied any alcohol use throughout the duration of posttransplant follow-up, whereas 17 (34%) were identified as having consumed alcohol at least once since the transplant. There were no significant differences at the time of evaluation between abstainers and alcohol users in age, sex distribution, severity of liver dysfunction, median duration of abstinence, or University of Michigan alcoholism prognosis score. The median interval from transplantation to alcohol relapse was 17 months, with a range of 3 to 45 months. Recurrent alcohol use was associated with significant medical complications sufficient to require admission to the hospital in 6 patients. One patient died of graft dysfunction, noncompliance with immunosuppressant medications, and presumed graft rejection while drinking. Mild or progressive hepatitis, which was the most common abnormality in posttransplant liver biopsy findings, was equally distributed between both alcohol users and abstainers and sometimes occurred in the absence of antibody to hepatitis C virus antibodies. There was a similar frequency of biopsy-proven acute cellular rejection in alcohol users and abstainers. Typical histological features of alcoholic liver injury were present in posttransplant biopsies from 1 alcohol user only. Alcohol use by alcoholics is uncommon in the first 5 years after liver transplantation, and alcohol-associated liver injury is unusual. Mild nonspecific hepatitis is common in both alcohol users and nonusers alike. Among a small subset of alcoholic transplant recipients, drinking behavior after liver transplantation is associated with considerable morbidity, requiring hospital admissions and occasionally leading to graft loss and death.

Alcohol Drinking↗
PubMed1997

Analysis of chondroitin sulfate in lumbar intervertebral discs at two different stages of degeneration as assessed by discogram.

Previous studies have presented evidence that an underlying cause of intervertebral disc degeneration is related to changes in the sulfation of the proteoglycans. The sulfation of the chondroitin in cadaveric lumbar intervertebral discs, at two different stages of degeneration as assessed by discogram, were analyzed. Fourteen of 28 lumbar discs were graded 2 and the other 14 were graded 4 (i.e., more degenerated). From each disc, six regional segments were carefully isolated. Proteoglycans were solubilized from the disc tissue with 4 M GuHCl. Chondroitin sulfate chains were analyzed by diethylaminoethyl (DEAE)-Sephacel and high-performance liquid chromatography (HPLC) anion exchange chromatography. The major differences in sulfation of the chondroitin between grade 2 and grade 4 discs only occurred in the posterior central annulus and nucleus segments. The chondroitin in the posterior central nucleus segments of the grade 2 and grade 4 intervertebral discs were undersulfated as compared with the other segments, and the differences between these segments and the others were more accentuated in the grade 4 discs than in grade 2 discs.

Cadaver↗
PubMed1996

Haloperidol antagonism of cue-elicited cocaine craving.

BACKGROUND: Studies of cocaine-dependent subjects have shown that re-exposure to environmental cues previously associated with cocaine use produces a strong conditioned response characterised by autonomic hyperarousal and increases in subjective measures of cocaine craving. METHODS: To evaluate the role of dopamine release by such cues, 20 cocaine-dependent inpatients were randomised in a single-dose, crossover, placebo-controlled design, to haloperidol (4 mg by mouth) and placebo. Plasma homovanillic acid (HVA, a dopamine metabolite), adrenocorticotropic hormone (ACTH), and cortisol were assayed before and after cue exposure. Craving and anxiety were measured before and after cues with visual analogue scales for desire to use cocaine now and for mood changes. FINDINGS: Cocaine cues significantly increased anxiety, ACTH, cortisol, and HVA. Increases in anxiety and craving resulting from cue exposure were significantly antagonised by pretreatment with haloperidol. INTERPRETATION: It has long been hypothesised that increases in extracellular concentrations of dopamine mediate the acute reinforcing effects of cocaine. Our data suggest that dopamine release may also mediate some of the conditioned responses to cocaine cues.

Adolescent↗
PubMed1996

Outcome of the contralateral hip following total hip arthroplasty for osteoarthritis.

One thousand one hundred and sixteen patients who underwent unilateral total hip arthroplasty osteoarthritis between 1970 and 1980 were examined for development, progression, and total hip arthroplasty in the contralateral joint. At the time of the original surgery, 452 patients were diagnosed with bilateral osteoarthritis and 664 had a normal contralateral hip. The probability of osteoarthritis progressing in the contralateral joint is 78.6% at 10 years, with the chance of arthroplasty being 53.8%. The probability of a hip diagnosed as normal developing osteoarthritis is 36.5% at 10 years, with an 8.3% chance of requiring total hip arthroplasty.

Adult↗
PubMed1996

Tibial shaft fracture following tibial tubercle osteotomy.

Tibial tubercle osteotomy has been reported to be an excellent exposure for a very stiff primary or revision knee requiring total knee arthroplasty. In 1993, the Center for Hip and Knee Surgery performed 657 primary and 16 revision total knee arthroplasties, using tibial tubercle osteotomy in 9 cases, 2 of which sustained tibial shaft fractures, because of which the Center's experience is reviewed.

Aged↗
PubMed1995

Expression of CD60 on multiple cell lineages in inflammatory synovitis.

BACKGROUND: CD60 is a recently described T cell subset marker that is expressed on the surface of most T lymphocytes in synovial tissue and fluid and on a smaller proportion of peripheral T cells. Activation of T lymphocytes can be triggered through CD60. CD60 is also expressed by neuroectodermally derived cells in thymic epithelium and in skin. EXPERIMENTAL DESIGN: Immunohistologic analysis of CD60 expression in synovium and thymus was performed using formalin-fixed tissue samples. Nonlymphoid cell lines grown from similar tissues were analyzed by flow cytometry. RESULTS: CD60 was readily identified in formalin-fixed, paraffin-embedded tissues. Simultaneous examination of CD60 distribution and cell morphology demonstrated that, in addition to its presence on T cells, CD60 was also expressed by a variety of nonlymphoid cells in synovium, including synovial lining cells, vascular endothelium, and dendritic-appearing cells deep within synovial tissue. Synovial tissue expression of CD60 was similar in rheumatoid arthritis and in other forms of inflammatory arthritis. In addition, it was strongly expressed by giant cells in pigmented villonodular synovitis. Surface expression of CD60 was detected by flow cytometry on cultured synoviocytes and on other CD60+ nonlymphoid cells, thus excluding adsorption of CD60 shed by T cells as a sufficient explanation of the immunohistologic findings. CONCLUSIONS: These results define the T cell-activating CD60 determinant as a broadly distributed Ag within synovial tissue, with a possible functional role in the activation of a variety of cellular populations. CD60 may also be a marker for previously undescribed cell subsets in the synovial compartment, possibly including a cell population of neuroectodermal origin.

Adult↗
PubMed1995

The effect of heterotopic bone formation on prosthetic loosening after total hip replacement.

Seven hundred thirty-two total hip replacements performed from 1970 to 1980 were evaluated for the degree of heterotopic bone formation postoperatively and its effect on long-term mechanical loosening. There were 231 Charnley total hip replacements, of which 152 had no heterotopic bone formation, 58 had Grade 1 formation, and 21 had Grade 2 or 3 formation. Among the 123 Mueller total hip replacements, 98 had no heterotopic bone formation, 19 had Grade 1 formation, and 6 had Grade 2 or 3 formation. For the 378 T-28 total hip replacements, there were 305 with no heterotopic bone formation, 59 with Grade 1 formation, and 14 with Grade 2 or 3 formation. Survival analyses using the definition of failure as loosening, fracture, or revision of the acetabulum or femoral components were constructed. There was no correlation between mechanical loosening, fracture, or revision of the total hip replacement and any degree of heterotopic bone formation.

Arthritis, Rheumatoid↗