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Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

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

Fluorescent and photochemical properties of a single zinc finger conjugated to a fluorescent DNA-binding probe.

A single zinc finger derived from the DNA-binding domain of the glucocorticoid receptor (GR) has been tethered to the intercalating fluorophore thiazole orange, and the DNA recognition characteristics of the conjugate have been examined. DNA sequence specificity for the peptide-dye conjugate, determined by steady-state fluorescence measurements and photoactivated DNA cleavage experiments, reproduce the binding features of response element recognition found in the native GR. The thiazole orange is able to intercalate and fluoresce when the conjugate binds, at concentrations where little fluorescence is observed from either the conjugate alone or the conjugate mixed with DNA lacking the zinc finger target sequence. The conjugate preferentially targets a 5'-TGTTCT-3' sequence (the native glucocorticoid receptor element) with a dissociation constant of about 25 nM. Lower binding affinities (up to 10-fold) are observed for single site variants of this sequence, and much lower affinity (40-50-fold) is observed for binding to the estrogen response element (which differs from the glucocorticoid receptor element at two positions) as well as to nonspecific DNA. Footprinting reactions show a 4-6 base pair region that is protected by the zinc finger moiety. Photocleavage assays reveal a several base pair region flanking the recognition sequence where the tethered thiazole orange moiety is able to intercalate and subsequently cleave DNA upon visible light exposure. Thiazole orange is also shown to oxidize the 5'-G of remote GG sequences, depending on the details of the intervening DNA sequence. Small synthetic protein-dye conjugates such as this one are potentially useful for a variety of purposes including sequence-specific probes that work under physiological conditions (without melting and hybridization of DNA), sequence-specific photocleavage agents, and self-assembling components in electron and energy transfer systems that utilize DNA as a scaffold and/or photochemical medium.

Base Sequence↗
PubMed2000

Adsorptions of plasma proteins and their elutabilities from a polysiloxane surface studied by an on-line acoustic wave sensor.

Gold electrodes of thickness-shear mode acoustic wave sensors were modified with poly[(mercaptopropyl)methylsiloxane]. The flow-through adsorption of three major plasma proteins (human serum albumin, fibrinogen, and immunoglobulin G) was detected by acoustic network analysis. The elution of fibrinogen and albumin from coated and unmodified gold surfaces by sodium dodecyl sulfate was studied with respect to different adsorption times and protein concentrations. Both sequential and competitive adsorptions of the three proteins on polymer-modified surfaces of sensors were examined as were simultaneous adsorptions from binary and ternary mixtures. The experimental results confirm that the competitive behaviors of proteins in terms of adsorptive processes are explained by factors other than displacement phenomena.

Acoustics↗
PubMed2000

Defining hepatocellular chimerism in a liver failure patient bridged with hepatocyte infusion.

BACKGROUND: A practical method of monitoring engraftment by transplanted hepatocytes for the purpose of bridging human liver failure to native regeneration is described. METHODS: A previously healthy 37-year-old female with a 2-week history of a febrile illness presented with fulminant liver failure. Findings on admission included the following: illicit drug use, serum hepatitis B surface antigen positive, grade 1 encephalopathy, prothrombin time (pt) >100 sec, F7<1%, NH3 150 micromol/L, alanine aminotransferase 4079 U/L, total bilirubin level 11.4 mg/dl, and glucose 70 mg/dl (on IV D10). With immunosuppression, 8.8x10(8), 96% viable human hepatocytes were intraportally infused. Clinical chemistries, total sHLA class I, and ELISA to measure donor-specific sHLA-A1 and -B8 were recorded. Serial transjugular liver biopsies were performed and pooled for histological examination, DNA extraction, and HLA DNA typing. RESULTS: The patient fully recovered. At months 3 and 4 with donor biopsy specimen class I HLA DNA no longer detectable, immunosuppression was tapered off. The patient is clinically normal, serum hepatitis B surface antigen negative at 10 months of follow-up. CONCLUSIONS: Bridging liver failure with donor hepatocytes with HLA class I antigen disparate from recipients is clinically feasible, and allows for a marker, combined with serial graft histology, to safely wean immunosuppression when native liver regeneration succeeds.

Adult↗
PubMed2000

Pentafluorinated probes for the X-ray photoelectron spectroscopic study of immobilized bifunctional silanes.

Bifunctional silanes constitute valuable linking agents for attachment of biomolecules at high levels of surface population density through the formation of thioether or disulfide bonds. Three such compounds, 1-((trifluoroacetyl)-thio)-11-(trichlorosilyl)undecane, 1-bromo-11-(trichlorosilyl)undecane, and 1-((bromoacetyl)oxy)-11-(trichlorosilyl)undecane, are discussed in terms of their surface chemistry on silicon wafers. To examine the electrophilic and nucleophilic generation of sulfur-containing linkages, three new probes, N'-(pentafluorophenyl)iodoacetohydrazide, N'-(pentafluorophenyl)-3-(2-pyridylthio)propriono-hydrazide, and N'-(pentafluorophenyl)mercaptoacetohydrazide, are introduced with respect to their reactions with silanized surfaces (studied by X-ray photoelectron spectroscopy). Thiol-functionalized surfaces obtained by silanization act as nucleophiles toward the probes. In air, low yields of conjugation are exhibited which are attributed to the unavailability of thiol groups because of intramolecular disulfide group formation instigated by oxygen or by disulfide exchange with the proprionyl probe. The behavior of electrophilic silanized surfaces toward the mercaptoacetyl-containing probe is governed by the nature of the leaving group and by steric factors.

Alkanes↗
PubMed2000

Risk factors for suicide attempts among African American women.

The aim of this study was to examine psychological and interpersonal risk factors for suicidal behavior in low income, African American women; 285 African American women who reported being in a relationship with a partner in the past year were studied, 148 presented to the hospital following a suicide attempt, and 137 presented for general medical care. Cases were compared to controls with respect to psychological symptoms, alcohol and drug abuse, family violence (intimate partner abuse, childhood trauma), relationship discord, and social support. Psychological risk factors for suicide attempts at the univariate level included psychological distress [Crude Odds Ratio (COR) = 6.5], post traumatic stress disorder (PTSD) symptoms (COR = 3.8), hopelessness (COR = 7.7), and drug abuse (COR = 4.2). Interpersonal risk factors at the univariate level included relationship discord (COR = 4.0), physical partner abuse (COR = 2.5), nonphysical partner abuse (COR = 2.8), childhood maltreatment (COR = 3.2), and low levels of social support (COR = 2.6). A multivariate logistic regression model identified four variables that were strongly and independently associated with an increased risk for suicide attempts: psychological distress, hopelessness, drug abuse, and relationship discord. The model predicted suicide attempt status correctly 77% of the time. The results reveal that African American women who report high levels of psychological distress, hopelessness, drug use, and relationship discord should be assessed carefully for suicidal ideation and referred for appropriate mental health care.

Adaptation, Psychological↗
PubMed2000

Continuous infusion of cyclosporin A postinjury significantly ameliorates cortical damage following traumatic brain injury.

Traumatic brain injury (TBI) results in the rapid necrosis of cortical tissue at the site of injury. In the ensuing hours and days, secondary injury exacerbates the original damage resulting in significant neurological dysfunction. Recent reports from our lab demonstrate that a bolus injection of the immunosuppressant cyclosporin A (CsA) is neuroprotective following TBI. CsA transiently inhibits the opening of the mitochondrial permeability transition pore and maintains calcium homeostasis in isolated mitochondria. The present study utilized a unilateral controlled cortical impact model of TBI to assess whether the neuroprotective effects of CsA could be extended by chronic infusion. Adult rats were subjected to a moderate (2 mm) cortical deformation and the extent of cortical damage was assessed using modern stereological techniques. Animals were administrated a 20 mg/kg intraperitoneal bolus of CsA or vehicle 15 min postinjury and osmotic minipumps were implanted subcutaneously to deliver CsA (4.5 or 10 mg/kg/day) or vehicle. All animals receiving CsA demonstrated a significant reduction in lesion volume, with the highest dose offering the most neuroprotection (74% reduction in lesion volume). These results extend our previous findings and demonstrate that chronic infusion of CsA is neuroprotective following TBI. These findings also suggest that the mechanisms responsible for tissue necrosis following TBI are amenable to manipulation.

Animals↗
PubMed2000

Mutual help groups, perceived status benefits, and well-being: a test with adult children of alcoholics with personal substance abuse problems.

A field experiment was conducted to examine the potential effects of mutual help group participation on perceived status benefits, depression, and substance use among adult children of alcoholics (ACOAs) with personal substance abuse problems. Participants were randomly assigned to attend either ACOA-specific mutual help group meetings or substance abuse education classes during the initial month that they were enrolled in a residential treatment program for low-income substance abusers. Analyses were based on assessments made at baseline, a 1-month posttest, and a 6-month follow-up. Results indicated that participation in the mutual help group promoted perceived status benefits, which in turn led to reductions in depression and substance use. These findings have clear implications for consumers of ACOA groups and can inform research on the social psychological underpinnings of different types of mutual help groups.

Adult↗
PubMed2000

The effect of repeated professional supragingival plaque removal on the composition of the supra- and subgingival microbiota.

BACKGROUND, AIMS: The purpose of the present investigation was to determine the effect of weekly professionally administered supragingival plaque removal on the composition of the supra and subgingival microbiota. METHODS: 18 adult subjects with periodontitis who had been treated and were in a maintenance phase of therapy were clinically and microbiologically monitored at baseline, 3, 6 and 12 months. After the baseline visit, the subjects received scaling and root planing followed by professional supragingival plaque removal every week for 3 months. Clinical measures of plaque accumulation, bleeding on probing (BOP), gingival redness, suppuration, pocket depth and attachment level were made at 6 sites per tooth at each visit. Separate supra (N = 1804) and subgingival (N = 1804) plaque samples were taken from the mesial aspect of all teeth excluding third molars in each subject at each time point and evaluated for their content of 40 bacterial taxa using checkerboard DNA-DNA hybridization. Significance of changes in mean counts, prevalence and proportions of bacterial species over time in both supra and subgingival samples were determined using the Quade test and adjusted for multiple comparisons. RESULTS: Mean % of sites exhibiting plaque, gingival redness and BOP were significantly reduced during the course of the study. Significant decreases in mean counts were observed in both supra and subgingival samples. Mean total DNA probe counts (x10(5), +/-SEM) at baseline, 3, 6 and 12 months were: 133+/-19, 95+/-25, 66+/-6, 41+/-6 (p<0.001) for supragingival samples and 105+/-22, 40+/-10, 19+/-4, 13+/-3 (p<0.001) for subgingival samples. Mean counts of 22 of 40 and 34 of 40 species tested were significantly reduced in the supra and subgingival samples respectively over the monitoring period. For example, mean counts of Porphyromonas gingivalis x10(5) at baseline, 3, 6 and 12 months in the subgingival plaque samples were 2.0+/-0.4, 0.5+/-0.2, 0.6+/-0.3, 0.3+/-0.1 (p<0.001); Bacteroides forsythus 2.0+/-0.6, 0.4+/-0.1, 0.4+/-0.2, 0.1+/-0.2 (p<0.001); Treponema denticola 3.4+/-1.1, 0.8+/-0.3, 0.4+/-0.2, 0.3+/-0.3 (p<0.01). Similar reductions were seen in supragingival plaque samples. While counts were markedly reduced by professional plaque removal, the proportion and prevalence of the 40 test species were marginally affected. CONCLUSIONS: Weekly professional supragingival plaque removal profoundly diminished counts of both supra- and subgingival species creating a microbial profile comparable to that observed in periodontal health. This profile was maintained at the final monitoring visit, 9 months after completion of therapy.

Adult↗
PubMed2000

Surface immobilized biochemical macromolecules studied by scanning Kelvin microprobe.

The measurement of work function is a particularly effective method for the characterization of surfaces because of the sensitivity of the parameter to interfacial structure, modification and overall chemistry. Accordingly, techniques for the analysis of work function offer a powerful tool for monitoring surface chemical changes, especially for situations involving the immobilization of new moieties at the interface. In the present paper, we describe the performance of a new, modified scanning Kelvin microprobe which is capable of the tandem measurement of contact potential and surface topography with resolutions of 1 mV and 10 nm, respectively. The lateral resolution is 1 micron. The instrument has been applied to the study of substrates modified by the attachment of biochemical macromolecules such as oligonucleotides and DNA. This preliminary work confirms the great potential of the technique in the study of biocompatibility, macromolecular structure and microarray devices.

Algorithms↗
PubMed2000

Repetitive cortical spreading depression in a gyrencephalic feline brain: inhibition by the novel benzoylamino-benzopyran SB-220453.

Transient cortical depolarization is implicated in the pathology of migraine. SB-220453 is a potent anti-convulsant which inhibits neurogenic inflammation and cortical spreading depression (SD)-evoked nitric oxide release via a novel but unknown mechanism. This study further investigates the effects of SB-220453 on generation and propagation of repetitive SD in the anaesthetized cat. Vehicle or SB-220453 1, 3 or 10 mg/kg was administered intraperitoneally 90 min prior to induction of SD in the suprasylvian gyrus (SG). Changes in d.c. potential were recorded in the SG and the adjacent marginal gyrus (MG). In vehicle-treated animals (n = 7), a brief exposure (6 min) to KCl induced a median (25-75% range) number of five (four to six) and three (two to four) depolarizations over a duration of 55 min (32-59 min) and 51 min (34-58 min) in the SG and MG, respectively. SB-220453 produced dose-related inhibition of the number of events and period of repetitive SD activity. SB-220453 also reduced SD-induced repetitive pial vasodilatation but had no effect on resting haemodynamics. However, when SD events were observed in the presence of SB-220453, it had no effect on metabolic coupling. These results show that SB-220453 produces marked inhibition of repetitive SD in the anaesthetized cat. SB-220453 may therefore have therapeutic potential in treatment of SD-like activity in migraine.

Analgesics↗
PubMed2000

A randomised, double-blind comparison of subarachnoid and epidural diamorphine for elective caesarean section using a combined spinal-epidural technique.

We have compared the quality of analgesia and incidence of side-effects from subarachnoid and epidural diamorphine for caesarean section, as part of a combined spinal-epidural technique. Sixty patients were studied in a randomised, double-blind, double-dummy assessment. The doses of diamorphine reflect current practice in our hospital and are close to optimal. All patients received 13.25 mg subarachnoid bupivacaine and 37.5 mg epidural bupivacaine. In addition, patients in group 1 received 0.3 mg subarachnoid diamorphine and patients in group 2 received 3 mg epidural diamorphine. All patients were premedicated with ranitidine 150 mg and metoclopramide 10 mg and after surgery received diclofenac regularly and co-dydramol as needed. The duration and quality of analgesia, assessed by verbal rating score, was the same in the two groups. The incidence and severity of pruritus were higher (P< 0.005) in group 1. Postoperative nausea and vomiting were uncommon; 83% of patients in group 1 and 77% in group 2 had none. Subarachnoid and epidural diamorphine provided similar quality analgesia with a low incidence of emetic symptoms. However, pruritus was more common and more severe after subarachnoid diamorphine.

Clinical Trial↗
PubMed2000

Metabolism of levormeloxifene, a selective oestrogen receptor modulator, in the Sprague-Dawley rat, Cynomolgus monkey and postmenopausal woman.

1. The metabolic fate of levormeloxifene in the Sprague-Dawley rat, Cynomolgus monkey and postmenopausal volunteer has been investigated. 2. Two doses of [14C]levormeloxifene, 0.7 and 50 mg/kg, were given to the male and female rat and monkey, and a single 20-mg dose to the postmenopausal volunteer. 3. The primary route of excretion in all three species was the faeces. Metabolism was similar in all three species, with demethylation forming the major metabolite in the rat and postmenopausal volunteer. One of the major metabolites in the monkey involved an oxidative ring opening of a pyrrole ring. 4. The main site of metabolism of levormeloxifene is the liver and the majority of the drug and its metabolites is excreted via the faecal route. Metabolic pathways appear to be similar in the three species studied.

Administration, Oral↗