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Biomedical subjects

M Gates

Publications and source records attributed to M Gates.

At least 19 recordsLinked to original sources

The role of age at asthma diagnosis in the development of triggers of asthma episodes.

This study examined the relationship of age at asthma diagnosis to the subsequent impacts of 12 common asthma triggers, which we classified as either mainly physically based or strongly psychosocially mediated. The physically based triggers were air pollution, cigarette smoke, high humidity, high/low environmental temperature, allergy problems, respiratory infection, physical activity, and nighttime hours; the psychosocially mediated triggers were stress or worry, anger, excitement, and laughter. Data were collected with questionnaires from families with asthmatic children (n=115), 2 to 20 years of age, as part of a larger study of biological and psychosocial factors in asthma and other illnesses. Using parents' reports, we classified the children as early-diagnosed (before age 2) or later-diagnosed (at or after 2) for asthma and compared these groups, separated by gender, in 2 x 2 multivariate analyses. The impacts of all four psychosocially mediated triggers on asthma attacks were significantly greater for the later-diagnosed children than the early-diagnosed children. No age of diagnosis differences were found for any of the physically based triggers, and no gender or interaction effects were found for either type of trigger.

Age Factors↗

Pharmacological effects of AMPA receptor potentiators LY392098 and LY404187 on rat neuronal AMPA receptors in vitro.

The present study describes the pharmacological activity of two novel positive allosteric modulators at AMPA receptors in acutely isolated rat cerebellar Purkinje neurons and cultured rat hippocampal neurons. Currents elicited by application of glutamate (100 microM) to isolated cerebellar Purkinje neurons were potentiated by LY392098, LY404187, cyclothiazide, CX516 and aniracetam. The rank order of potency was LY404187> LY392098> cyclothiazide > CX516> aniracetam. LY392098 displayed a higher maximal efficacy than the other compounds examined. AMPA-activated inward currents in cultured rat hippocampal neurons were potentiated by LY392098, LY404187 and cyclothiazide in a reversible and concentration-dependent manner although considerable heterogeneity in the magnitude of response from cell to cell was observed. LY392098 was ineffective in potentiating AMPA receptor responses when dialyzed via the intracellular solution. The selectivity profiles of the two novel AMPA receptor potentiators were examined. LY392098 or LY404187 had minimal activity on NMDA receptor responses, on voltage-gated calcium channel currents in cultured hippocampal neurons and on GluR5 kainate receptor currents in acutely isolated rat dorsal root ganglion neurons.

Allosteric Regulation↗

Kainate receptors are involved in synaptic plasticity.

The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are three classes of ionotropic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate receptors; critical roles in synaptic plasticity have been identified for two of these. Thus, at many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors. Here, to determine whether kainate receptors are involved in synaptic plasticity, we have used a new antagonist, LY382884 ((3S, 4aR, 6S, 8aR)-6-((4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydro isoquinoline-3-carboxylic acid), which antagonizes kainate receptors at concentrations that do not affect AMPA or NMDA receptors. We find that LY382884 is a selective antagonist at neuronal kainate receptors containing the GluR5 subunit. It has no effect on long-term potentiation (LTP) that is dependent on NMDA receptors but prevents the induction of mossy fibre LTP, which is independent of NMDA receptors. Thus, kainate receptors can act as the induction trigger for long-term changes in synaptic transmission.

Animals↗

Assessment of pulmonary lesions with 18F-fluorodeoxyglucose positron imaging using coincidence mode gamma cameras.

UNLABELLED: Accurate assessment of lung carcinoma remains a significant clinical problem, often leading to surgical procedures without curative potential. PET with 18F-fluorodeoxyglucose (FDG) has shown promise in differentiating benign from malignant lesions and in staging the extent of disease, resulting in improved treatment at a significant cost savings. This multicenter prospective study used dual-detector coincidence imaging with FDG to categorize pulmonary lesions as benign or malignant. The goal of this study was to determine the sensitivity and specificity of dual-detector coincidence imaging of FDG in patients with pulmonary lesions who were scheduled to have a diagnostic procedure for histopathologic confirmation. METHODS: A total of 96 patients with pulmonary lesions with a lesion size ranging from 1 to 7 cm with a mean of 3.44 cm based on their chest radiograph or CT scan were studied using FDG scans with a dual-detector coincidence detection system. An additional 24 patients were entered as control subjects. The studies of 120 subjects were interpreted in random order by three physicians experienced in the use of FDG in patients with lung cancer. Surgical pathology was used as the standard for identifying malignant lesions. RESULTS: There was 94% agreement between the readers in the independent interpretation of the FDG studies. In the 96 patients with pulmonary lesions, FDG studies were 97% sensitive and 80% specific in identifying proven malignant lesions. CONCLUSION: The results of this prospective study provide evidence that dual-detector coincidence imaging with FDG provides an accurate, sensitive and specific means of diagnosing malignancy in patients with pulmonary lesions.

Case-Control Studies↗

Cloning of two loci for synapse protein Snap25 in zebrafish: comparison of paralogous linkage groups suggests loss of one locus in the mammalian lineage.

Synaptosome-associated protein of 25 kDa (Snap25) is an intracellular protein that is defined as a target receptor for synapse vesicles prior to neurotransmitter release. Snap25 is highly conserved, with 61% identity between human and Drosophila melanogaster. Whereas mammals and chicken have a single locus for Snap25, the tetraploid goldfish has at least three loci. We report that the zebrafish has two loci with 91% amino acid identity to each other. The alternative splicing of exon 5 arose before the gene duplication. The expression patterns of the two loci are virtually identical in adult zebrafish. The two zebrafish snap25 loci are located in paralogous linkage groups that seem to correspond to human chromosome 20, which harbors the SNAP locus, and human chromosome 14. Because no additional Snap25 homologue has been reported for any mammal or chicken, snap25.2 may have been lost in the amniote or even tetrapod lineage.

Amino Acid Sequence↗

Incorporation of mouse neural progenitors transplanted into the rat embryonic forebrain is developmentally regulated and dependent on regional and adhesive properties.

During development, telencephalic neural progenitors acquire positional specification and give rise to distinct structures such as the striatum and cortex. Here, we examine, in vivo, the influence of developmental stage, cell-surface molecules and regional differences along the dorso-ventral and antero-posterior axes on the selective incorporation of neural progenitors derived from different regions of the developing brain, utilizing a cross-species in utero transplantation paradigm. Striatal progenitors derived from the embryonic day (E) 12-14 mouse lateral ganglionic eminence (LGE) were observed consistently to incorporate into the developing striatum as early as 24-48 h following intraventricular injection into the E15-17 rat host. By removing cell-surface molecules from the LGE progenitors, the pattern of incorporation was remarkably different with no preferential striatal incorporation. Cortical progenitors with intact cell-surface molecules, by contrast, displayed little telencephalic (including striatal) incorporation as compared with precursors from the LGE. However, both progenitors from cortex and LGE incorporated widely into diencephalic and mesencephalic structures. The capacity for integration of precursors derived from the LGE and cortex gradually decreased during development of the host and was minimal in the postnatal day (P) 1 host. Unlike the telencephalic precursors, the vast majority of progenitors derived from the midbrain and cerebellar primordium (with cell-surface molecules intact) incorporated into diencephalic and midbrain nuclei with only a few cells observed in the telencephalon. These results demonstrate that incorporation of neural progenitors across the ventricular wall in the embryonic host is strictly developmentally regulated, dependent on their position along the antero-posterior axes and in the case of progenitors from the LGE is mediated by cell-surface molecules expressed on the transplanted cells.

Animals↗

Mapping of mhc class I and class II regions to different linkage groups in the zebrafish, Danio rerio.

The mammalian major histocompatibility complex (Mhc) consists of three closely linked regions, I, II, and III, occupying a single chromosomal segment. The class I loci in region I and the class II loci in region II are related in their structure, function, and evolution. Region III, which is intercalated between regions I and II, contains loci unrelated to the class I and II loci, and to one another. There are indications that a similar Mhc organization exists in birds and amphibians. Here, we demonstrate that in the zebrafish (Danio rerio), a representative of the teleost fishes, the class II loci are divided between two linkage groups which are distinct from the linkage group containing the class I loci. The beta2-microglobulin-encoding gene is loosely linked to one of the class II loci. The gene coding for complement factor B, which is one of the region III genes in mammals, is linked neither to the class I nor to the class II loci in the zebrafish. These results, combined with preliminary data suggesting that the class I and class II regions in another order of teleost fish are also in different linkage groups, indicate that close linkage of the two regions is not necessary either for regulation of expression or for co-evolution of the class I and class II loci. They also raise the question of whether linkage of the class I and class II loci in tetrapods is a primitive or derived character.

Animals↗

X-ray microanalysis and mapping: measuring uptake and intracellular distribution of labeled molecules.

X-ray microanalysis is a useful technique for elemental analysis of tissues and cells. This technique utilizes x-rays generated in ultra-thin cryosections of tissue by the electron beam in an electron microscope. The x-rays are characteristic of the various elements, and can be used to measure quantitatively the elemental distribution at subcellular levels. An important application of this x-ray microanalysis and mapping technique is the study of uptake and intracellular distribution of molecules containing an element not normally present in the tissue. It is useful for tissues and samples in which the cell population is not homogeneous. Mapping permits elemental distributions to be measured throughout the sample, not just at selected sites. Maps created are not only for the element of interest but also for other specified elements present. Using an x-ray imaging system and cisplatin as a model, we have been able to demonstrate the feasibility of studying the cellular and subcellular distribution of cisplatin, a molecule containing platinum atom.

Animals↗

A genetic linkage map for the zebrafish.

To facilitate molecular genetic analysis of vertebrate development, haploid genetics was used to construct a recombination map for the zebrafish Danio (Brachydanio) rerio. The map consists of 401 random amplified polymorphic DNAs (RAPDs) and 13 simple sequence repeats spaced at an average interval of 5.8 centimorgans. Strategies that exploit the advantages of haploid genetics and RAPD markers were developed that quickly mapped lethal and visible mutations and that placed cloned genes on the map. This map is useful for the position-based cloning of mutant genes, the characterization of chromosome rearrangements, and the investigation of evolution in vertebrate genomes.

Animals↗

The impact of Medicaid adoption of the Medicare fee schedule.

In this article, the authors simulate the effects on Federal and State Medicaid expenditures of increasing Medicaid fees to Medicare fee schedule (MFS) levels. Strict adoption of the MFS by the States would increase total Medicaid spending by approximately 4 percent, $2.5 to $2.9 billion. Because Medicaid fees vary across States, so does the impact of adopting the MFS. Medicaid spending would increase significantly in some wealthy States with large Medicaid populations and in a few small, relatively poor States. Some States currently pay more than the MFS for obstetrical services. If these fees continued at higher levels for obstetrical care, total Medicaid spending would increase by $3.5 to $4.0 billion.

Adult↗

How do Medicare physician fees compare with private payers?

Under the new fee schedule, Medicare physician fees are 76 percent of private fees. Consistent with the intent of payment reform, Medicare physician fees more closely approximate private fees for visits (93 percent) than for surgery (51 percent) and in rural areas as compared with large metropolitan areas. Variation in private fees across the country is considerably greater than it is for Medicare fees. Consequently, Medicare fees are most generous in areas that compare least favorably with the private market because private fees in these areas are well above average. These results shed light on the impact of the fee schedule and on the implications of using Medicare payment methods as part of a broad-based health reform.

Data Interpretation, Statistical↗