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Biomedical subjects

Michael Thompson

Publications and source records attributed to Michael Thompson.

At least 37 records · Page 2Linked to original sources
PubMed2004

Role of CD38 in myometrial Ca2+ transients: modulation by progesterone.

Oxytocin-induced Ca(2+) transients play an important role in myometrial contractions. Here, using a knockout model, we found that the enzyme CD38, responsible for the synthesis of the second messenger cyclic ADP-ribose (cADPR), plays an important role in the oxytocin-induced Ca(2+) transients and contraction. We also observed that CD38 is necessary for TNF-alpha-increased agonist-stimulated Ca(2+) transients in human myometrial cells. We provide experimental evidence that the TNF-alpha effect is mediated by increased expression of the enzyme CD38. First, we observed that TNF-alpha increased oxytocin-induced Ca(2+) transients and CD38 expression in human myometrial cells. Moreover, using small interference RNA technology, we observed that TNF-alpha stimulation of agonist-induced Ca(2+) transients was abolished by blocking the expression of CD38. In control experiments, we observed that activation of the component of the TNF-alpha signaling pathway, NF-kappaB, was not affected by the treatments. Finally, we observed that the effects of TNF-alpha on CD38 cyclase and oxytocin-induced Ca(2+) transients are abolished by progesterone. In conclusion, we provide the first experimental evidence that CD38 is important for myometrial Ca(2+) transients and contraction. Moreover, CD38 is necessary for the TNF-alpha-mediated augmentation of agonist-induced Ca(2+) transients in myometrial cells. We propose that the balance between cytokines and placental steroids regulates the expression of CD38 in vivo and cell responsiveness to oxytocin.

ADP-ribosyl Cyclase↗
PubMed2004

BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice.

Faithful segregation of replicated chromosomes is essential for maintenance of genetic stability and seems to be monitored by several mitotic checkpoints. Various components of these checkpoints have been identified in mammals, but their physiological relevance is largely unknown. Here we show that mutant mice with low levels of the spindle assembly checkpoint protein BubR1 develop progressive aneuploidy along with a variety of progeroid features, including short lifespan, cachectic dwarfism, lordokyphosis, cataracts, loss of subcutaneous fat and impaired wound healing. Graded reduction of BubR1 expression in mouse embryonic fibroblasts causes increased aneuploidy and senescence. Male and female mutant mice have defects in meiotic chromosome segregation and are infertile. Natural aging of wild-type mice is marked by decreased expression of BubR1 in multiple tissues, including testis and ovary. These results suggest a role for BubR1 in regulating aging and infertility.

Aging↗
PubMed2004

Sub-micrometre imaging of metal surface corrosion by scanning Kelvin nanoprobe.

The detection of the initial changes in the surface microstructure and local chemical properties connected to the corrosion process is possible using a high-resolution scanning Kelvin nanoprobe. This technique provides the simultaneous imaging of the topographical features and potential distribution across a surface at the sub-micrometer level. Nanoprobe measurements performed on samples of Al, Cu, Fe, Ni, Ag and Pt before and after exposure to different corroding solutions reveal the significant changes that take place during the first stages of the corrosion process. The similarities of the images obtained subsequent to corrosion are reflective of surface fractal behavior.

Journal Article↗
PubMed2004

A pilot study of routine quality control of sampling by the SAD method, applied to packaged and bulk foods.

A recently proposed method of looking at sampling uncertainty has been tested by its application to the sampling and analysis of several types of food and an animal feedstuff. In this 'SAD' method, increments comprising the conventional sample (that is, collected in the fashion prescribed by the standard sampling protocol) are allocated to either of two equal sized 'splits', which are prepared and analysed separately. The absolute difference between the analytical results for the two splits (the split absolute difference, or SAD) is plotted on a one-sided control chart. A non-compliance indicates that the combined uncertainty of sampling or analysis is larger than expected and the result of the measurement (the mean of the two split results) is possibly not fit for purpose. In addition, the SAD results give rise to a rugged estimate the uncertainty associated with the sampling protocol, often a major part of the total measurement uncertainty.

Animals↗
PubMed2004

Superior analytical sensitivity of electromagnetic excitation compared to contact electrode instigation of transverse acoustic waves.

Quartz disks incorporated into an electrolyte flow-through configuration have been excited by both direct electrode contact and electromagnetic fields to generate propagating transverse acoustic waves in to the fluid. The conventional thickness-mode device was operated at the first harmonic (9 MHz) whereas the EM excited structure functioned successfully at 453 MHz (nominal 49th harmonic). The nature of signals produced by the two devices and potential contributions to noise are evaluated. A comparison of the response of the higher frequency sensor to the introduction of the protein neutravidin to the system reveals at least a seven times higher signal-to-noise ratio than is the result for the conventional bulk-acoustic wave structure. This increase in sensitivity coupled with the possibilities for tuning the frequency of the electromagnetic device and its potential for non-contact excitation offer significant advantages in terms of analytical sensor technology.

Journal Article↗
PubMed2004

Surgical volume and long-term survival following surgery for colorectal cancer in the Veterans Affairs Health-Care System.

OBJECTIVE: The objective of this study was to examine the relationship between hospital surgical volume and long-term survival in patients with a new diagnosis of colorectal cancer who underwent surgical resection during fiscal years 1991-2000 in the Veterans Affairs (VA) health-care system. METHODS: This research was a cohort study of patients admitted to all VA hospitals with a new diagnosis of colorectal cancer who underwent surgical resection between October 1990 and September 2000 and followed through September 2001. Overall 5-yr cumulative survival was calculated from Kaplan-Meier estimates, while adjusted risk of death was estimated using a Cox proportional hazards model. Adjustment was made for differences in patient characteristics including comorbidity, receipt of therapy, and year of surgery. RESULTS: We identified 34,888 individuals with a new diagnosis of colorectal cancer in VA hospitals during fiscal years 1991-2000, of whom 22,633 (65%) underwent surgical resection. The majority (98.5%) were men, the mean age was 68 yr, and the two largest race/ethnic groups were whites (75%) and blacks (17%). The 5-yr cumulative survival was greater among those who received surgery in high surgical volume hospitals as defined by 25 or more procedures per year (52.1%) than among those who received surgery in low volume hospitals (48.3%). After adjusting for differences in patient characteristics, comorbidity, receipt of adjuvant therapy, and year of surgery, we found 7% and 11% increases in 5-yr survival for patients with colon and rectal cancers, respectively, who underwent surgical resection in high volume hospitals compared with those who had surgery in low volume hospitals. CONCLUSIONS: Greater hospital surgical volume is an independent predictor of prolonged long-term survival following surgery for both colon and rectal cancer in the VA health-care system. The volume-long-term mortality relationship is greater for rectal than for colon cancer patients, perhaps reflecting the fact that surgery for rectal cancer is more technically demanding. Future studies are needed to discover what aspects of clinical management explain these differences.

Aged↗
PubMed2004

Biosensors for the detection of bacteria.

This review will consider the role of biosensors towards the detection of infectious bacteria, although non-infectious ones will be considered where necessary. Recently, there has been a heightened interest in developing rapid and reliable methods of detection. This is especially true for detection of organisms involved in bioterrorism, food poisoning, and clinical problems such as antibiotic resistance. Biosensors can assist in achieving these goals, and sensors using several of the different types of transduction modes are discussed: electrochemical, high frequency (surface acoustic wave), and optical. The paper concludes with a discussion of three areas that may make a great impact in the next few years: integrated (lab-on-a-chip) systems, molecular beacons, and aptamers.

Bacteria↗
PubMed2003

Protein microarray scanning in label-free format by Kelvin nanoprobe.

Surface-immobilized protein species deposited in the microarray format have been detected by time-of-flight secondary ion mass spectrometry and by scanning Kelvin nanoprobe. The former method was used to examine the nature of protein deposition on amine-coated glass slides and gold substrates in preparation for Kelvin measurements. Both gallium and SF(5)(+) ion sources were employed to produce positive and negative ion spectra of amino acids and polypeptides. Scanning Kelvin technology has been used to detect antibody-antigen interactions in a label-free protocol through measurement of the surface potential of the biochemical pair on indium tin oxide, amine-treated slides and gold substrates. The results show that good inter-spot reproducibility can be achieved and that deposited areas can be examined for homogeneity at 100 nm resolution. This work represents the first report on surface potential detection in protein microarray technology.

Mass Spectrometry↗
PubMed2003

Kinetic characterization of TAR RNA-Tat peptide and neomycin interactions by acoustic wave biosensor.

The kinetics of binding of short Tat peptides and an aminoglycoside molecule to the human immunodeficiency virus-type 1(HIV-1) TAR RNA and to a bulge mutant analogue (MTAR) is studied in a biosensor format by monitoring the time course of the response in a series resonance frequency, using an acoustic wave biosensor. Association and dissociation rate constants are evaluated by fitting the experimental data to a simple 1:1 (Langmuir) model. Kinetic rate and equilibrium dissociation constants show that MTAR-peptide complexes are subject to a higher dissociation rate and are less stable compared to the corresponding TAR-peptide complexes. In addition, longer peptides display enhanced discrimination ability than a shorter peptide according to the equilibrium dissociation constants evaluated using this technique. K(D) values for TAR-Tat vs. MTAR-Tat complexes are 2.6 vs. 3.8 microM for Tat-12, 0.87 vs. 4.3 microM for Tat-18 and 0.93 vs. 1.6 microM for Tat-20. The equilibrium dissociation constant for TAR-neomycin complex is 12.4 microM and it is comparable to the values obtained from non-biosensor type assays. These findings are in parallel with those cited in the literature and the results from this study underline the potential of the acoustic wave sensor for detailed biophysical analysis of nucleic acid-ligand binding.

Acoustics↗
PubMed2003

The role of cyclic-ADP-ribose-signaling pathway in oxytocin-induced Ca2+ transients in human myometrium cells.

Human myometrial contraction plays a fundamental role in labor. Dysfunction of uterine contraction is an important cause of labor progression failure. Although the mechanisms controlling uterine contraction are not completely understood, intracellular Ca2+ mobilization plays an important role during uterine contraction. Several mechanisms of intracellular Ca2+ mobilization are present in smooth muscle, but in the human uterus, only 1,4,5-trisphosphate-induced Ca2+ release has been studied extensively. Ryanodine receptor channels are present in myometrium. We determined the role of the cyclic ADP-ribose (cADPR)-signaling pathway in oxytocin-induced intracellular Ca2+ [(Ca2+)i] transients in human myometrial cells. We found that oxytocin-induced Ca2+ transient is dependent on several sources of Ca2+, including extracellular Ca2+ and intracellular Ca2+ stores. In addition, we found that both the 1,4,5-trisphosphate- and the cADPR-induced Ca2+ releasing systems are important for the induction of [Ca2+]i transients by oxytocin in human myometrial cells. Furthermore, we investigated TNFalpha regulation of oxytocin-induced [Ca2+]i transients, CD38 cyclase activity, and CD38 expression in human myometrial cells. We found that oxytocin-induced [Ca2+]i transients were significantly increased by 50 ng/ml TNF. Similarly, CD38 mRNA levels, CD38 expression, and cyclase activity were increased by TNFalpha, thus increasing cADPR levels. We propose that a complex interaction between multiple signaling pathways is important for the development of intracellular Ca2+ transients induced by oxytocin and that TNFalpha may contribute for the myometrium preparation for labor by regulating the cADPR-signaling pathway. The observation that the cADPR-signaling pathway is important for the development of intracellular Ca2+ transients in human myometrial cells raises the possibility that this signaling pathway could serve as a target for the development of new therapeutic strategies for abnormal myometrial contraction observed during pregnancy.

ADP-ribosyl Cyclase↗
PubMed2003

Binding affinity and inhibitory potency of neomycin and streptomycin on the Tat peptide interaction with HIV-1 TAR RNA detected by on-line acoustic wave sensor.

The binding of two aminoglycoside antibiotics, neomycin and streptomycin, to a segment of the transactivation responsive region (TAR) RNA of the human immunodeficiency virus, and their inhibitory potency to disrupt the interaction of the RNA with a regulatory Tat protein-derived peptide, have been studied using a flow-through acoustic wave detector system. Binding affinity is directly correlated with the inhibitory potency of these molecules and the acoustic wave detection system shows that neomycin exhibits at least a ten-fold greater affinity for TAR RNA and that it is also a more potent inhibitor than streptomycin. These results are in agreement with previous studies. However, unlike the time-consuming batch-based assays, use of the flow-through format offers considerable potential for the rapid screening of the chemistry of relatively small-molecule-nucleic acid binding events.

Acoustics↗
PubMed2003

Environmental enrichment decreases nicotine-induced hyperactivity in rats.

RATIONALE: Previous research has determined that rats reared in an enriched condition (EC) are more sensitive to the effects of acute systemic amphetamine than rats raised in an impoverished condition (IC). OBJECTIVES: The present experiments examined the effect of environmental enrichment on locomotor activity following repeated injections of nicotine. Experiment 1 assessed differences in locomotor activity in EC and IC rats and experiment 2 assessed differences between EC rats and rats housed in pairs without novel objects or daily handling (social condition; SC) to determine whether enrichment causes changes beyond that of social contact alone. METHODS: In experiment 1, EC and IC rats were treated with saline, 0.2 mg/kg or 0.8 mg/kg nicotine, and locomotor activity was assessed for 60 min. Nicotine-induced activity was measured every 48 h for a total of eight sessions. All rats were challenged with 0.8 mg/kg nicotine on session 9. In experiment 2, EC and SC rats were treated with saline or 0.2 mg/kg nicotine, and locomotor activity was assessed using the same regimen as in experiment 1. RESULTS: In experiment 1, EC rats exhibited less sensitivity than IC rats to the psychostimulant effect of nicotine upon both acute and repeated administration. On the nicotine challenge session (session 9), EC rats were again less sensitive to the hyperactive effects of nicotine. In experiment 2, EC rats were also less sensitive than SC rats to nicotine-induced hyperactivity across repeated injections. CONCLUSIONS: These results suggest that environmental enrichment during development reduces the stimulant effect of nicotine.

Analysis of Variance↗
PubMed2003

Can CK-MB and cTn-I be detected in the peripheral circulation within the first 10 min of acute coronary ischemia?

There are approximately 4 million patients hospitalized with suspected acute coronary syndromes (ACS) annually. However, the current standard tools for assessing ACS in the Emergency Department are felt to have insufficient sensitivity and specificity. Animal studies have demonstrated that CK-MB and troponin-I are released in a biphasic pattern with an initial transient release which peaks and falls within the first 10 min of ischemia. We hypothesize that transient elevations of CK-MB and troponin-I can be detected in the peripheral circulation within the first 10 min of ischemia in a human model of brief coronary ischemia. We also present results from our pilot study that failed to confirm this hypothesis; however, this pilot studied was insufficiently powered to detect potentially clinically important results.

Creatine Kinase↗
PubMed2003

Antineoplastic agents 500. Narcistatin.

An efficient procedure was found for synthetic conversion of the sparingly soluble anticancer isocarbostyril narciclasine (1), a component of various Narcissus species, to a cyclic phosphate designated narcistatin (3b). The reaction between narciclasine, tetrabutylammonium dihydrogen phosphate, and p-toluenesulfonic acid in pyridine afforded pyridinium narcistatin (3a) in reasonable yields. Transformation of narcistatin (3a) to, for example, the water-soluble prodrug sodium narcistatin (3d) was easily achieved by cation exchange chromatography. Narcistatin (3b) and 15 salt derivatives were evaluated against a panel of human cancer cell lines, and the range (0.1-0.01) of GI(50) values in micro g/mL was found to parallel that shown by the parent narciclasine.

Alkaloids↗
PubMed2003

Imaging TOF-SIMS analysis of oligonucleotide microarrays.

Single strand thiolated oligonucleotide (25-mer) was printed onto chemically modified glass and silicon surfaces. Confirmation of the level of attachment attained in each case was effected through detection by conventional confocal fluorescence microscopy. Both positive-ion and negative ion imaging time-of-flight mass spectra were recorded for the visualization of micro-patterned oligonucleotide arrays. This represents the first report of such detection by this form of mass spectrometry on glass. Ultimately, we are interested in the possibility that imaging time-of-flight secondary ion mass spectrometry can discern the orientation and conformation of DNA strands present on the surface of a substrate.

Humans↗
PubMed2003

Analytical measurements in small pulmonary vessels.

Micro-sensors and ultra small devices, the latter often discussed in the context of the field of nanotechnology, have attracted burgeoning interest in recent years. Michael Thompson in consultation with Flavio Coceani of Scuola Superiore di Studi Universitari e di Perfezionamento Sant'Anna, Pisa, Italy, outlines the background and challenge represented by the design of sensors required for the quantitative determination of NO and CO in very small pulmonary vessels. The solution to this problem will require a highly interdisciplinary research effort involving micro-electronic or -optical fabrication, physiology, chemometrics and surface chemistry.

Animals↗
PubMed2002

RNA-peptide binding and the effect of inhibitor and RNA mutation studied by on-line acoustic wave sensor.

Acoustic wave devices of the transverse shear-wave type are becoming increasingly important in the study of biochemical binding events at the solid-liquid interface in real time. The operation of the sensor is based on the principle that perturbations occurring at the solid-liquid interface result in changes in the propagating characteristics of the acoustic wave. The binding of the human immunodeficiency virus-type 1 Tat protein to the transactivation-responsive RNA element has been studied using this sensor. Variable acoustic signals in terms of frequency and motional resistance changes are obtained when surface-immobilized RNA is challenged by different peptide fragments derived from Tat protein. The effect of peptide concentration and mutation in addition to the inhibition of RNA-peptide binding by neomycin has been investigated. The results of this study suggest that acoustic physics offers considerable potential for the screening of small-molecule interactions with nucleic acids.

Acoustic Stimulation↗