Inhibition of the metalloproteinase domain of mouse TACE.
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ADAM Proteins↗
Biomedical subjects
B J Smith
Publications and source records attributed to B J Smith.
Gas chromatographic-mass spectrometric analysis of hydroxylamine for monitoring the metabolic hydrolysis of metalloprotease inhibitors in rat and human liver microsomes.
A gas chromatographic-mass spectrometric (GC-MS) method was developed for the analysis of hydroxylamine (HA) in supernatants obtained from liver microsomes. HA monitoring was used to determine the metabolic hydrolysis of two hydroxamic acid-based matrix metalloprotease inhibitors in rat and human liver microsomes. The hydrolysis of the hydroxamic acids to their corresponding carboxylic acids releases HA as a common metabolic product. HA was derivatized to acetone oxime by addition of acetone to the liver microsomal supernatant, followed by direct injection of the supernatant into the GC-MS, with detection of the oxime by selected-ion-monitoring. The method is simple, reproducible, and sensitive for the determination of the hydrolysis of hydroxamic acid compounds, where hydrolysis is the major metabolic pathway. The methodology can be used for rank ordering and selecting hydroxamic acid analogs based on their susceptibility to hydrolysis.
Animals↗
Specific detection of Xylella fastidiosa Pierce's disease strains.
Pierce's disease (PD, Xylella fastidiosa) of grapevine is the primary pathogen limiting vinifera grape production in Florida and other regions of the southeastern United States. Quick and accurate detection of PD strains is essential for PD studies and control. A unique random amplified polymorphic DNA (PD1-1-2) was isolated from a PD strain from Florida. Fragment PD1-1-2 was cloned, sequenced, and found to be 1005 bp in length. PCR primers were designed to utilize these sequence data for PD strain detection. One primer set (XF176f-XF954r) amplified a 779-bp DNA fragment from 34 PD strains including seven pathotypes of X. fastidiosa, but not from strains of Xanthomonas campestris pv. campestris, Xan. vesicatoria or Escherichia coli. A second primer set (XF176f and XF686r) amplified a 511-bp fragment specific to 98 PD strains, but not from strains of citrus variegated chlorosis, mulberry leaf scorch, oak leaf scorch, periwinkle wilt, phony peach, or plum leaf scald. Sequence analysis indicated that RAPD fragment PD1-1-2 contains a Ser-tRNA gene. The PD-specific region includes a TaqI restriction site (TCGA) and is 150 bp downstream of the Ser-tRNA gene.
Base Sequence↗
The novel-response procedure in humans.
The novel-response drug discrimination procedure is one of several three-choice procedures developed to address interpretational difficulties that can occur under standard two-response procedures. The novel-response procedure is unique among three-choice discrimination procedures by using instructions, rather than explicit training procedures. With the novel-response procedure, participants are trained under a standard two-response (drug vs. placebo) discrimination, and then instructed that in the presence of a drug stimulus unlike either of the training drugs, responses should be made on the novel-response alternative. Several studies have assessed the utility of the novel-response procedure by comparing effects under a standard two-response and the novel-response procedure in participants trained to discriminate triazolam from placebo. Results indicate that the novel-response procedure can increase the selectivity of both placebo- and drug-appropriate responding, and in this way, allows for finer distinctions to be made among sedatives than a standard two-response procedure.
Anti-Anxiety Agents↗
Tilapia (Oreochromis niloticus) dosed with azathioprine display immune effects similar to those seen in mammals, including apoptosis.
Azathioprine, an anti-neoplastic drug and therapeutic immunosuppressant, was administered intraperitoneally at 10.0 and 50.0 mg/kg to 3-6-month-old tilapia (Oreochromis niloticus). Consistent alterations in immune cellular parameters of the blood, pronephros (hematopoietic kidney) and spleen were observed. Peripheral blood total cellularity decreased as the azathioprine dose increased, to approximately half that of the control. Differential analysis of white blood cells indicated a decline in lymphocyte number, in particular, with increased dosage of azathioprine. Pronephric total cellularity was depressed in fish receiving the 10.0 or 50.0 mg/kg dose. In contrast, both splenic weight and splenic total cellularity increased proportionately with the increase in the drug dosage. Histopathologic examination of the spleens showed normal patterns for both control and 10.0 mg/kg dose groups. At 50.0 mg/kg, spleens were characterized by marked expansion of the white pulp, although lymphocytes were rare. Melanomacrophage centers at the higher dose were also larger and more numerous than in the control group. Evaluation of splenic and pronephric leukocytes with apoptotic markers showed an increase in apoptotic cells in the pronephros with increasing drug dose. These changes in fish are consistent with those seen in humans and laboratory rodents dosed with azathioprine, suggesting that fish may be potentially useful as preliminary models for detecting immunosuppressive compounds.
Animals↗
Developing an effective program to complete ictal SPECT in the epilepsy monitoring unit.
With the availability of more stable radiopharmaceuticals, the ictal single photon emission computed tomography (SPECT) perfusion study has emerged as a useful noninvasive functional neuroimaging tool in the presurgical evaluation of patients with medically intractable partial epilepsy. The purpose of this study was to determine whether the development of a program using trained electroencephalography (EEG) technologists to perform ictal injections in the epilepsy monitoring unit enabled a more efficient delivery of radiopharmaceuticals and therefore a higher specificity and sensitivity of outcome. All patients admitted to the epilepsy monitoring unit for prolonged video/EEG monitoring as part of the presurgical evaluation were eligible for completion of an ictal SPECT study using a three-way needle-free apparatus. Over a 19-month period, 85 (77%)) of 110 eligible patients were successfully injected during typical partial seizures. Various factors were analyzed including latency of ictal injection (27.3+/-20.8 [S.D.] s), radiopharmaceutical wastage (40% dose utilization), radiation safety parameters (1.6% contamination rate), and preliminary data of localizing value. Our results show that ictal SPECT can be a safe, noninvasive procedure completed on a routine basis in the epilepsy monitoring unit when appropriately trained support staff are utilized as part of a structured multidisciplinary program.
Adult↗
Morbidity and infection in combined subdural grid and strip electrode investigation for intractable epilepsy.
The coverage of large surface areas of the brain for electrographic monitoring purposes necessitates a craniotomy to achieve comprehensive sampling. We undertook a review and prospective analysis over 3 years of 38 patients undergoing craniotomy for electrode implantation. The indication for invasive monitoring was to determine candidacy for resective surgery in patients whose seizure focus was not well localized by scalp electroencephalography and other noninvasive testing. Prophylactic cultures from the epidural space were obtained at electrode removal. There were five positive epidural cultures. All five patients went on to seizure-free status. Two positive cultures occurred in patients without obvious infection and who were not treated with antibiotics. Other complications included individual cases of atrial fibrillation, pulmonary edema, postoperative fever, and epidural hematoma. There was no mortality or permanent neurologic morbidity related to craniotomy for electrode placement. There was a 7.9% rate of clinical infection per patient and a 5.7% rate per craniotomy side. This study has identified several factors that significantly correlate with positive epidural culture results: > 100 electrodes, more than ten cables, more than 14 days of implantation, and more than one cable exit site.
Adolescent↗
Skin care management practices for premature infants.
OBJECTIVE: To describe current skin care practices for preterm infants in neonatal intensive care units in the United States. We hypothesized that there would be little consensus among facilities. STUDY DESIGN: Neonatal intensive care units (n = 823) listed in the 1996 United States Neonatologists Directory (American Academy of Pediatrics, Section on Perinatal Pediatrics) were sent a 28-question survey dealing with many aspects of neonatal skin care along with descriptive data about their neonatal intensive care unit. Descriptive data analysis was performed. RESULTS: A total of 305 surveys were returned (37% return rate); of these, 241 of the respondents reported admitting infants weighing < or = 1000 gm. Some neonatal skin care practices showed wide consensus (> 70%) (e.g., scrub procedure for staff; use of a skin barrier under tapes/adhesives), whereas other practices showed little consensus (< 30%) (e.g., routine surveillance cultures; use of Aquaphor). CONCLUSION: Consensus on skin care practices was not found among neonatal intensive care units. Data from this survey can be used to develop studies to examine whether certain skin care management practices can improve neonatal outcomes.
Body Temperature Regulation↗
Ultrastructural morphology of the gill of the hybrid striped bass (Morone saxatilis x M. chrysops).
The fine structure of the principal cell types found in the gill filaments and secondary, respiratory lamellae of the hybrid striped bass (Morone saxatilis x M. chrysops) was studied by transmission electron microscopy. Most of the cell types generally resembled those observed at this level of resolution in other euryhyaline, teleostean species, and the mucus cells, epithelial cells, and cartilage cells were non-distinctive. Pillar cells were atypically flattened within the lamellae. The extensive cytoplasmic tubular system of the chloride cells was more densely distributed and was less branched than reported for many other teleosts. The vascular endothelial cells of the marginal, lamellar blood vessels were particularly striking because of their prominent, electron-dense cytoplasmic granules. Although the physiological function and chemical composition of these granules remain obscure, their presence suggests an important role of secretion into the vascular lumen. These gill data from normal specimens of this sport and commercial, hybrid species constitute a useful basis for interpreting gill changes in diseased striped bass.
Animals↗
Asthma and chronic obstructive airway diseases are associated with osteoporosis and fractures: a literature review.
The objective was to assess the association between asthma and/or chronic obstructive airway diseases (COAD), and osteoporosis, and appraise treatments of osteoporosis in these patients. MEDLINE and Excerpta Medica were searched for original research with control groups which tested the above association. One cohort and nine cross-section studies of bone density in patients with asthma and/or COAD were retrieved. These demonstrated clinically important bone density reductions of up to 29% in subjects, dependent upon daily oral corticosteroids, by a variety of measurement techniques, at various bone sites. Bone density reduction has also been less consistently reported in the absence of oral corticosteroids, suggesting that other factors including high-dose inhaled corticosteroids may have a role. Fracture studies. Three studies in oral corticosteroid-dependent asthmatics demonstrated a vertebral fracture prevalence up to 56%, and annual vertebral fracture incidence of up to 42%. The strength of the available evidence is limited, but suggests that patients with asthma and/or COAD are at increased risk of osteoporosis. The evidence of the association between osteoporosis and inhaled corticosteroids is much more limited than for oral corticosteroids. Bisphosphonates are promising agents to maintain and/or promote bone mass in this patient group.
Administration, Inhalation↗
Efficient site specific removal of a C-terminal FLAG fusion from a Fab' using copper(II) ion catalysed protein cleavage.
The peptide sequence (N)DKTH(C) was investigated as a site for efficient, specific cleavage of a fusion protein by cupric ions using a humanised gamma1 Fab' as a model protein. The native upper hinge (N)DKTH(C) sequence was mutated to create a site resistant to cleavage by cupric ions and a (N)DKTH(C) sequence introduced between the hinge and a C-terminal FLAG peptide. Incubation of Fab' with Cu2+ at 62 degrees C at alkaline pHs resulted in removal of the FLAG peptide with efficiencies of up to 86%. Cleavage conditions did not detrimentally affect the Fab' protein. Use of the (N)DKTH(C) sequence along with cupric ions may provide a cost-effective method for large scale proteolytic cleavage of fusion proteins.
Amino Acids↗
Cohen's paradox.
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Air Pollutants, Radioactive↗
Detection of event-related potentials for development of a direct brain interface.
The study presented here is part of an ongoing effort to develop a direct brain interface based on detection of event-related potentials (ERPs). In a study presented in a companion article, averaged ERP templates were identified from electrocorticograms recorded during repetition of voluntary motor actions. Here the authors report on the detection of individual motor ERPs within the electrocorticogram using cross-correlation. An averaged ERP template was created from the first half of each electrocorticogram and then cross-correlated with the continuous electrocorticogram from the second half. Points where the cross-correlation value exceeded an experimentally determined detection threshold were considered to be detection points. A detection point was considered to be a valid "hit" if it occurred between 1 second before and 0.25 second after the recorded time of a voluntary action. The difference between the hit and false-positive percentages (HF-difference) was used as a metric of detection accuracy. HF-differences greater than 90 were found for 5 of 15 subjects, HF-differences greater than 75 were found for 8 of 15 subjects, and HF-differences greater than 50 were found for 12 of 15 subjects. The three other subjects with HF-differences less than 50 had electrode locations not well suited for recording movement-related ERPs. Recordings from sensorimotor and supplementary motor areas produced the highest yield of channels with HF-difference greater than 50; however, a number of channels with good performance were found in other areas as well. The results demonstrate the likely prospect of using ERP detection as the basis of a single-switch direct brain interface and that furthermore, there is a good possibility of obtaining multiple control channels using this approach.
Analysis of Variance↗
The effect of a respiratory home nurse intervention in patients with chronic obstructive pulmonary disease (COPD).
BACKGROUND: Chronic obstructive pulmomary disease (COPD) is associated with substantial mortality, morbidity, and costs to the health care system. With the increasing interest in outreach care programmes it is important to evaluate their impact upon patients and health services, for conditions such as COPD. AIM: To determine the effectiveness of an outreach respiratory nurse in a shared care approach, with collaboration between general practitioners and hospital services, in the management of patients with severe COPD. METHODS: Patients with severe COPD attending The Queen Elizabeth Hospital, Adelaide participated in a randomised controlled trial of a home based nursing intervention (HBNI) over 12 months with outcome measures including mortality rate, hospital service utilisation, FEV1 and health related quality of life (HRQL) using a modified Dartmouth Primary Care Co-operative Quality of Life questionnaire. RESULTS: There were 48 subjects in each study arm, with no differences in mortality rate (eight deaths in the HBNI group and seven in the control group), hospital admissions, length of stay, number of outpatient and Emergency Service visits. The study had inadequate follow-up of FEV1 and HRQL within the control group. Within the HBNI group, a small improvement in HRQL (in three of ten indices measured) was demonstrated, despite a deterioration in FEV1 (11% reduction, p=0.04) compared to baseline. Quality of life of HBNI subjects' carers did not change. CONCLUSION: An increased level of care given by an outreach respiratory nurse in a shared care approach for patients with severe COPD produced small improvements in HRQL but did not result in the prevention of deaths or reduced health care utilisation.
Aged↗
Industry, air quality, cigarette smoke and rates of respiratory illness in Port Adelaide.
OBJECTIVES: To examine the prevalence of self-reported asthma, bronchitis/emphysema, wheezing, night cough and smoking in Port Adelaide; to explore the relationship of the disorders to the presence of industry, tobacco smoke, indoor appliances and air quality. METHODS: Prevalence data from a 1995 survey of Port Adelaide residents were compared with data from the 1995 National Health Survey and the 1995 South Australian Health Omnibus Survey. These data were then compared across three geographic areas in Port Adelaide, one being highly industrialised. Their relation to tobacco smoke and the presence of unflued gas appliances were examined. Finally, outdoor gaseous air pollutants were examined across the three areas. RESULTS: Males in Port Adelaide had higher rates of asthma and bronchitis/emphysema than nationally. Asthma was significantly higher for children aged 5-14 years and for adults aged 25-44 years. Bronchitis/emphysema was significantly higher for males aged 25-64. The highly industrial area had a higher rate of asthma (OR 1.85, 95% CI 1.07-3.22) in males that appeared unrelated to smoking or ambient gaseous pollutants. Smoking in Port Adelaide was significantly higher than in the general population, and was significantly associated with wheeze, night cough and bronchitis/emphysema. The presence of unflued gas heaters at home was significantly associated with asthma prevalence in males (OR 3.27, 95% CI 1.40-7.64). CONCLUSIONS: Respiratory disease appeared to be independently related to an area of high industry, smoking and presence of unflued gas appliances in Port Adelaide.
Adolescent↗
Thrombolysis in acute myocardial infarction: analysis of studies comparing accelerated t-PA and streptokinase.
OBJECTIVES: To compare outcomes from accelerated alteplase (recombinant tissue plasminogen activator, t-PA) and streptokinase use in acute myocardial infarction. METHODS: Review of available studies identified by Medline and other literature searches that met the criteria of being a prospective, randomised clinical trial enrolling over 1000 patients with acute myocardial infarction. The studies had to contain an intervention arm comprising accelerated infusion t-PA, or an intervention arm comprising streptokinase provided accelerated t-PA that was compared in the same trial. Interventions compared were streptokinase 1.5 million units given over one hour compared with accelerated t-PA infusion, with concomitant use of aspirin and heparin, and main outcome measure of 30 day mortality. RESULTS: Four studies met prespecified criteria, these being the GUSTO I, GUSTO IIb Angioplasty Substudy, GUSTO III, and COBALT trials. There was a total study population of 64,387 patients of whom 20,251 received streptokinase, 19,474 received t-PA, with others receiving different treatment. Pooled data show that accelerated t-PA produces a marginal 30 day mortality advantage compared with streptokinase (6.6% v 7.3%, p = 0.02, Bonferroni adjusted p = 0.12, that is borderline significance, relative risk 0.918, 95% confidence interval 0.854 to 0.986). Any benefit is attributable entirely to patients recruited in the United States in the GUSTO I study. There is an increased incidence of stroke with t-PA. CONCLUSIONS: The data do not consistently show a 30 day mortality benefit from using t-PA compared with streptokinase in acute myocardial infarction, but do show increased risk of stroke. Streptokinase can be considered the thrombolytic agent of choice.
Female↗
Comparing single and cumulative dosing procedures in human triazolam discriminators.
This study evaluated a cumulative dosing procedure for drug discrimination with human participants. Four participants learned to discriminate triazolam (0.35 mg/70 kg) from placebo. A crossover design was used to compare the results under a single dosing procedure with results obtained under a cumulative dosing procedure. Under the single dosing procedure, a dose of triazolam (0, 0.05, 0.15, or 0.35 mg/70 kg) or secobarbital (0, 25, 75, or 175 mg/70 kg) was administered 45 min before assessment. Determining each dose-effect curve thus required four sessions. Under the cumulative dosing procedure, four doses of triazolam (0, 0.05, 0.10, and 0.20 mg/70 kg) or secobarbital (0, 25, 50, and 100 mg/70 kg) were administered approximately 55 min apart, producing a complete dose-effect curve in one four-trial session. Regardless of procedure, triazolam and secobarbital produced discriminative stimulus and self-reported effects similar to previous single dosing studies in humans. Shifts to the right in cumulative dose-effect curves compared to single dose-effect curves occurred on several self-report measures. When qualitative stimulus functions rather than quantitative functions are of interest, application of cumulative dosing may increase efficiency in human drug discrimination.
Adult↗
The influence of an expert system for test ordering and interpretation on laboratory investigations.
BACKGROUND: The Laboratory Advisory System (LAS) is an expert system interface that works interactively with clinicians to assist them with test selection and result interpretation throughout the laboratory investigation of a patient. METHODS: To study the influence of the LAS on laboratory investigations, a repeated-measures experiment using clinical vignettes was conducted. To collect baseline data on how laboratory investigations are currently conducted, clinicians investigated one-half of the vignettes using a conventional (noncomputer) approach. To determine the influence of the LAS on clinicians' behavior, the other half of the vignettes were investigated using the LAS. RESULTS: Clinicians using the LAS (compared with conventional practice) ordered fewer laboratory tests during the diagnostic process (mean, 17.8 vs 32.7), completed the diagnostic workup with fewer sample collections (mean, 5.8 vs 7.5), generated lower laboratory costs (mean, $194 vs $232), shortened the time required to reach a diagnosis (mean, 1 day vs 3.2 days), showed closer adherence to established clinical practice guidelines, and exhibited a more uniform and diagnostically successful investigation. CONCLUSION: The LAS enhances the outcome of the investigation and improves laboratory utilization.
Clinical Laboratory Information Systems↗