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Biomedical subjects

E Matthew

Publications and source records attributed to E Matthew.

At least 19 recordsLinked to original sources
PubMed2003

Protection of lungs from hyperoxic injury: gene expression analysis of cyclosporin A therapy.

We have previously shown that cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), attenuates hyperoxia-induced reductions in murine lung compliance. CsA protected against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Gene expression studies were conducted to identify the gene expression patterns underlying the protective effects of CsA during hyperoxic lung injury. After 72 h of simultaneous treatment with >95% oxygen and CsA (50 mg x kg(-1) x day(-1)), RNA was isolated from murine lungs. RNA from treated and untreated lungs was reverse transcribed to cDNA, competitively hybridized, and used to probe 8,734 complimentary DNAs on the Incyte mouse GEM 1 array. Several known genes and expressed sequence tags (ESTs) showed increased (GenBank accession numbers: AA125385, AA241295, W87197, syntaxin, and cyclin G) or decreased [AA036517, AA267567, AA217009, W82577, uteroglobin, stromal cell-derived factor 1, and surfactant protein C (SP-C)] expression after hyperoxia. Hyperoxia-stimulated reductions in SP-C gene expression were confirmed through Northern blot analysis. The increase in gene expression of one expressed sequence tag (AA125385) with hyperoxia was reversed by CsA treatment. Sequence data demonstrated that this EST has high homology to murine cyclin B1. Western blot analysis did not demonstrate any changes in distal lung cyclin B1 expression after hyperoxia. Protein expression of cyclin B1 in the distal lung was observed in the endothelial cells, bronchiolar epithelial cells, and both the type I and type II alveolar epithelial cells. Further analysis of cyclin B1 may elucidate the protective actions of CsA in hyperoxic injury.

Animals↗
PubMed2001

A murine model of smoke inhalation.

The United States has one of the world's largest per capita fire death rates. House fires alone kill >9,000 Americans annually, and smoke inhalation is the leading cause of mortality from structural fires. Animal models are needed to develop therapies to combat this problem. We have developed a murine model of smoke inhalation through the design, construction, and use of a controlled-environment smoke chamber. There is a direct relationship between the quantity of wood combusted and mortality in mice. As with human victims, the primary cause of death from smoke inhalation is an elevated blood carboxyhemoglobin level. Lethal (78%) and sublethal (50%) carboxyhemoglobin levels were obtained in mice subjected to varying amounts of smoke. Mice exposed to wood smoke demonstrated more dramatic pathology than mice exposed to cotton or polyurethane smoke. A CD-1 model of wood smoke exposure was developed, demonstrating type II cell hypertrophy, cytoplasmic blebbing, cytoplasmic vacuolization, sloughing, hemorrhage, edema, macrophage infiltration, and lymphocyte infiltration. The bronchoalveolar lavage fluid of smoke-exposed mice demonstrated a significant increase in total cell counts compared with those in control mice. These findings are comparable to the lung tissue response observed in human victims of smoke inhalation.

Animals↗
PubMed1999

Cyclosporin A protects lung function from hyperoxic damage.

Cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), has been shown to play a role in exocytosis and neutrophil mobility. Hyperoxia (>95% oxygen for 72 h) causes lung injury and reduces lung compliance. This model is indicative of deficiencies in surfactant and elicits a vigorous immune response leading to further damage. We examined the effects of CsA on surfactant-secreting lung alveolar type II cells. CsA enhances ATP-stimulated increases in whole cell capacitance in the presence of 2 mM extracellular Ca2+. This measurement corresponds with increases in exocytosis. Because of its effect on the immune system and exocytosis from type II cells, CsA was examined for its protective effects against hyperoxia-induced lung damage in mice. We found that CsA (50 mg. kg-1. day-1) attenuated hyperoxia-induced reductions in lung compliance when administered before or during 72 h of >95% oxygen (P < 0.05). CsA (10 mg. kg-1. day-1) also had a protective effect against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Wet lung weight-to-dry lung weight ratios did not show any significant changes after hyperoxia or hyperoxia plus CsA (P < 0. 05). CsA may be useful to treat patients undergoing prolonged high-oxygen therapy and possibly other lung injuries.

Adenosine Triphosphate↗
PubMed1998

Brain mapping with single photon emission CT.

PURPOSE: To investigate the feasibility of performing brain mapping studies by using cortical activation paradigms and single photon emission computed tomography (SPECT) and to evaluate methods of analysis. MATERIALS AND METHODS: Twenty healthy volunteers underwent technetium-99m bicisate SPECT under baseline conditions and during either full-field or right hemifield visual stimulation with a black and white reversing checkerboard pattern. Changes in regional cerebral perfusion were measured by using regions of interest (ROIs) and statistical parametric mapping. RESULTS: ROI analysis identified statistically significant increases in perfusion in the occipital cortex with full-field visual stimulation (mean +/- standard error of the mean percentage change from baseline: left, 8.0 +/- 1.5; right, 6.6 +/- 2.4). With right hemifield visual stimulation, perfusion was significantly increased only in the left occipital cortex (left, 5.2 +/- 1.5; right, -0.2 +/- 1.9). Statistical parametric mapping showed areas of activation (more than 100 voxel clusters showed significant change from baseline at a threshold value of P < or = .005 or z > or = 2.58) in the left primary visual cortex (right hemifield visual stimulation) and in both right and left primary visual areas (full-field visual stimulation). CONCLUSION: Brain mapping studies were preformed with Tc-99m bicisate SPECT, and activation-induced changes were visualized and measured. These methods can be applied to develop improved methods of diagnosis and assessment of treatment outcome in patients with neuropsychiatric disorders.

Adult↗
PubMed1996

Regional cerebral blood flow changes after light therapy in seasonal affective disorder.

There is considerable evidence to indicate that depressive disorders may be associated with changes in regional cerebral blood flow (rCBF), and that successful treatment may reverse these changes. We studied patients with seasonal affective disorder (SAD) using 99Tcm-hexamethylpropylene amine oxime (99TCm-HMPAO) single photon emission tomography (SPET) to examine the effect of light therapy on rCBF. Ten depressed patients (8 females, 2 males) with a mean (+/- S.D.) age of 33.5 +/- 11.3 years underwent 99TCm-HMPAO SPET studies before and after light therapy. The treatment response was evaluated using the Structured Interview Guide for the Hamilton Depression Rating Scale-Seasonal Affective Disorders Version (SIGH-SAD). A patient was considered responsive to light therapy if the post-treatment SIGH-SAD score was reduced by 60% or more in comparison to the pre-treatment score (responders, n = 5; non-responders, n = 5). Pre- and post-treatment SIGH-SAD scores and SPET data were compared in each patient. An improvement in depressive symptoms after light therapy was associated with an increase in rCBF in the frontal and cingulate regions as well as the thalamus. Such changes were not seen in non-responsive subjects.

Adult↗
PubMed1995

Benzodiazepine receptors mediate regional blood flow changes in the living human brain.

We studied the effects of a high-affinity gamma-aminobutyric acid (GABA)-benzodiazepine-receptor agonist (lorazepam) and an antagonist (flumazenil) in humans, using H2(15)O positron-emission tomography. Administration of lorazepam to healthy volunteers caused time- and dose-dependent reductions in regional cerebral blood flow and self-reported alterations in behavioral/mood parameters. Flumazenil administration reversed these changes. These observations indicated that benzodiazepine-induced effects on regional cerebral blood flow and mood/behavior are mediated at some level through GABA-benzodiazepine receptors, although the specific mechanism remains unclear. The approach described here provides a method for quantifying GABA-benzodiazepine-receptor-mediated neurotransmission in the living human brain and may be useful for studying the role of these receptors in a variety of neuropsychiatric disorders.

Adult↗
PubMed1993

Changes in the glucose-6-phosphatase complex in hepatomas.

Hepatomas tend to have a decreased glucose-6-phosphatase activity. We have observed phenotypic stability for this change in Morris hepatomas transplanted in rats. To determine if this decrease is selective for translocase functions or the hydrolase activity associated with glucose-6-phosphatase, we have compared activities in liver and hepatomas with glucose-6-phosphate or mannose-6-phosphate as substrates and with intact or histone-disrupted microsomes. In five out of seven subcutaneously transplanted rat hepatoma lines, the microsomal mannose-6-phosphatase activity was lower than in preparations from liver of normal or tumor-bearing rats. With liver microsomes and with most hepatoma microsomes, preincubation with calf thymus histones caused a greater increase in mannose-6-phosphatase than in glucose-6-phosphatase activity. In studies with liver and hepatoma microsomes there were similar increases in mannose-6-phosphatase activity with total calf thymus histones and arginine-rich histones. A smaller increase was seen with lysine-rich histones. The effect of polylysine was similar to the action of lysine-rich histones. There was only a small effect with protamine at the same concentration (1 mg/ml). Rat liver or hepatoma H1 histones gave only about half the activation seen with core nucleosomal histones. Our data suggested that microsomes of rat hepatomas tend to have decreased translocase and hydrolase functions of glucose-6-phosphatase relative to activities in untransformed liver.

Animals↗
PubMed1993

Metabolic and cognitive changes in hereditary ataxia.

Fourteen subjects (affected, n = 7; at risk, n = 7) from one well-known kindred with adult onset autosomal dominant olivopontocerebellar atrophy (OPCA), were studied with [18F]-2-deoxy-D-glucose (FDG) positron emission tomography (PET), magnetic resonance imaging (MRI), cognitive testing and scored neurological examination, and compared with normal controls. The neurological examination, MRI and cognitive tests showed no significant differences between at risk and normal control subjects. Mild cognitive deficits were seen in affected subjects; the degree of cognitive change appeared to relate to the severity of the illness. MRI demonstrated cerebellar and brainstem atrophy in all affected subjects. PET studies showed higher global metabolic rates (mean [SD]) in at risk subjects (10.5 [1.5] mg per min per 100 g) as compared to affected (9.0 [0.8] mg per min per 100 g) and normal control subjects (9.1 [1.5] mg per min per 100 g). Normalized (region/global average) regional metabolic rates were reduced in cerebellar hemispheres and vermis, and in frontal and prefrontal areas of affected subjects in comparison to at risk and normal control subjects. These findings indicate that functional changes in some forms of autosomal dominant hereditary cerebellar ataxia may extend beyond the cerebellum and brainstem to involve other parts of the neuraxis.

Adult↗
PubMed1993

Neuropeptides in dissociated cell cultures of mammalian spinal cord and dorsal root ganglion.

Immunohistochemical studies of leucine-enkephalin, somatostatin, vasoactive intestinal polypeptide and neurotensin were carried out in dissociated cell co-cultures of embryonic mouse spinal cord and dorsal root ganglion, using the peroxidase-antiperoxidase technique. Leucine-enkephalin immunoreactivity exceeded that of the other peptides in these coculture preparations. Leucine-enkephalin, substance P and somatostatin were also studied in spinal cord cultures (without dorsal root ganglia) and in dorsal root ganglia cultures (without spinal cord). Each of these peptides was present in only a small percentage (< 10%) of perikarya and processes in spinal cord cultures. No leucine-enkephalin immunoreactivity was seen in dorsal root ganglion cultures; a considerable proportion of the processes were immunoreactive for substance P or somatostatin. These observations suggest that co-cultures of spinal cord and dorsal root ganglia can provide a simplified in vitro "model" of the nervous system for the study of peptidergic interactions.

Animals↗
PubMed1993

Growth hormone and prolactin in temporal lobe epilepsy.

Growth hormone and prolactin levels were measured sequentially during wakefulness and sleep, in seven patients with unilateral temporal lobe epilepsy who underwent telemetric EEG monitoring (10-24 h), and in three additional patients studied while temporal structures were stimulated with implanted electrodes during pre-surgical evaluation. The results indicated that growth hormone/prolactin release patterns were not significantly affected by selective unilateral stimulation of deep temporal structures, or, when sleep patterns were normal, by epileptic activity confined to one temporal lobe.

Adolescent↗
PubMed1993

Reproducibility of resting cerebral blood flow measurements with H2(15)O positron emission tomography in humans.

Two consecutive measurements of resting CBF were carried out in normal volunteers (n = 25) using H2(15)O positron emission tomography. Absolute whole-brain blood flow (WBBF; ml 100 g-1 min-1, mean +/- SD) for the first (40.3 +/- 6.4) and second (39.3 +/- 6.5) measurements was not significantly different (mean % difference 2.3 +/- 8.7). Analysis of regions of interest showed no significant differences in absolute regional CBF (rCBF) and normalized (rCBF/WBBF) rCBF. Left-right differences were also not significant. These data demonstrate the reproducibility of resting CBF measurements in normal humans.

Adult↗
PubMed1987

Oral antimicrobial therapy for adults with osteomyelitis or septic arthritis.

We conducted a retrospective review of 21 adult patients with osteomyelitis and septic arthritis who were treated with high doses of oral antimicrobial agents, usually after an initial course of intravenous therapy. The mean duration of parenteral and oral therapy was 3.6 days and 43.0 days, respectively. Absorption of oral antibiotics was assessed by determining the trough serum bactericidal titers for the infecting organism; whenever feasible, the dosages were adjusted to achieve trough titers greater than or equal to 1:8. The follow-up period ranged from six to 66 months (mean, 42.4 months). Eighteen of 21 patients had no clinical signs of recurrence after initial therapy. One patient with an infected joint prosthesis developed recurrent infection, and two patients had recurrences accompanied by sequestra. The mean duration of hospitalization was 13.4 days, and the mean duration of outpatient treatment was 31.9 days.

Administration, Oral↗
PubMed1984

Benzodiazepines: rat pinealocyte binding sites and augmentation of norepinephrine-stimulated N-acetyltransferase activity.

Studies of [3H]diazepam binding to intact rat pineal cells were carried out in tissue culture preparations. The binding was saturable, reversible and proportional to the number of cells used. Scatchard analysis resulted in a linear plot [Kd = 23 nM, maximum binding sites (Bmax) = 1.56 pmol/mg of protein for cells in monolayer culture; Kd = 7 nM, Bmax = 1.3 pmol/mg of protein for cells in suspension culture]. Inhibition constants (Ki) for clonazepam (500 nM), flunitrazepam (38 nM) and Ro-5-4864 (5 nM) indicated that the binding sites were probably of the "peripheral" type. In addition, the effects of diazepam on norepinephrine-stimulated N-acetyltransferase (NAT) activity were studied in organ culture and dissociated cell culture. Diazepam (10-50 microM) both prolonged and increased the magnitude of the norepinephrine-induced increase in NAT activity but did not affect the initial rate of rise of enzyme activity. The effect was dose-dependent and was also seen with clonazepam, flunitrazepam and Ro-5-4864, but not with Ro-15-1788. Diazepam, by itself, at these concentrations, had no effect on NAT, but enzyme activity was increased by higher concentrations (0.1-1 mM). Although a relationship between the [3H]diazepam binding sites described here and the effect of benzodiazepines on NAT cannot be established from these studies, the data suggest that the benzodiazepines may alter melatonin levels through their action on NAT.

Acetyltransferases↗
PubMed1982

Substance P-like immunoreactivity in neurons in dissociated cell cultures of mammalian spinal cord and dorsal root ganglia.

Dissociated cell cultures prepared from fetal mouse spinal cords and dorsal root ganglia were stained for endogenous substance P using the peroxidase-antiperoxidase technique. Substance P-like immunoreactivity was localized within a small percentage of rounded or multipolar neuronal somata and in varicose processes. The substance P-positive multipolar neurons were derived from spinal cord, while the small rounded neurons were possibly of spinal cord and/or sensory ganglion origin. Large dorsal root ganglion neurons were unreactive. These results are consistent with in vivo findings and indicate the feasibility of electrophysiologic studies in culture to analyze the synaptic connections between substance P neurons and their target cells.

Animals↗
PubMed1981

Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells.

We found that two markers of differentiation, tyrosinase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) activity and melanin synthesis, are induced by diazepam in B16/C3 mouse melanoma cells. We also demonstrated high-affinity binding sites for [3H]diazepam in these cells by radioreceptor assay, and we visualized binding to the cell surface by fluorescence microscopy with a benzodiazepine analog conjugated to a fluorescein-labeled protein. Our studies also showed that there are differences between the binding characteristics in intact cells and in membrane fractions prepared from these cells. Scatchard analysis of the binding data from membrane fractions gave a linear plot (Kd = 9.1 X 10(-8) M). With intact cells, a curvilinear Scatchard plot was obtained. This was resolved into two components defining binding sites with affinity constants of 1.7 X 10(-9) M and 4.6 X 10(-7) M. Thus, it appears that [3H]diazepam binding in intact cells is more complex than in isolated membranes. Several related benzodiazepines, including flunitrazepam, Ro-5-4864, nitrazepam, oxazepam, lorazepam, Ro-5-3072, chlordiazepoxide, and clonazepam also induced melanogenesis. When these compounds were tested for their ability to inhibit [3H]diazepam binding, flunitrazepam, diazepam, and Ro-5-4864 were found to be the most effective inhibitors. These three compounds were also the most potent in inducing melanogenesis. Our results suggest that the benzodiazepines modulate cell differentiation. The presence of high-affinity binding sites in this homogeneous, easily grown cell line may provide a useful model for studies on the mechanism of action of these compounds.

Benzodiazepines↗
PubMed1980

Seizures following intracranial surgery: incidence in the first post-operative week.

Consecutive craniotomies (118) drawn from major hospitals, and performed for disorders other than epilepsy or acute trauma were reviewed. The final diagnosis included tumor (70), subdural hematoma (13), aneurysm (10), arteriovenous malformation (7), and miscellaneous lesions (18). Eighty-seven (73.7%) patients had not experienced seizures prior to neurosurgery, 11 of these (12.6%) had a seizure within the first week, in six the attack occurred within 24 hours, and of these three had further attacks. In contrast, of the 31 patients (26.3%) that had one or more seizures prior to operation, 11 patients (35.5%) had seizures within the first week. In ten patients seizures occurred within the first 24 hours and of these seven had one or more recurrences later in the week. Anticonvulsant drugs were administered to 72 patients before operation, including all those with a history of seizures, but loading doses were not utilized to ensure therapeutic levels. In patients with predisposing factors to postoperative seizures, anticonvulsant drugs should be administered before or immediately following craniotomy in adequate dosage to rapidly achieve and maintain effective plasma levels. Phenytoin, owing to its minimal sedative effects is the drug of choice. A loading dose of 18 milligrams per kilogram can be safely administered as an admixture to an intravenous infusion of 0.9% saline with careful monitoring of cardiopulmonary function.

Adult↗