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Biomedical subjects

T Brock

Publications and source records attributed to T Brock.

15 recordsLinked to original sources
PubMed2005

[Epidemiology and management of stroke patients in emergency departments of the Centre region of France].

INTRODUCTION: Stroke is a leading cause of death and disability. Patients with suspected stroke are usually managed in emergency departments (ED). Stroke units must be created in our country, but only few French epidemiological data are available to define needs in stroke care. OBJECTIVE: A prospective study was planned to evaluate epidemiology and stroke care for patients with suspected stroke admitted in the 22 ED of our region in the center of France during a two-month period. METHODS: Patients with suspected stroke seen at the 22 ED were prospectively followed until discharge or one month after admission. Data on demographic characteristics, mode of transport, delay of arrival and imaging, clinical findings at arrival, department of admission, diagnosis, Rankin scale at day 7, in-hospital mortality, and outcome at a month were collected. A global statistical analysis and a comparison between rural and urban ED were performed. RESULTS: Five hundred and ninety-eight patients were included. Mean age was 75 years. Median admission delay was 4 hours and 52 minutes. Predominant mode of transport was a private ambulance. A CT scan was obtained in 91 p.cent of cases with a median delay of 2 hours and 30 minutes. Only a third of the patients were admitted in departments of Neurology. Final diagnosis was: ischemic stroke (61 p.cent), transient ischemic attack (16 p.cent), hemorrhagic stroke (10 p.cent), other vascular disease (3 p.cent), non vascular disease (10 p.cent). In-hospital mortality was 20 p.cent, factors significantly associated with death rate were elevated age and a Glasgow coma scale<10 at admission. Mean length of stay was 12 days for stroke patients. At one month, 63 percent of patients were discharged to their home, 28 percent were transferred to an institution or in a rehabilitation unit, and 15 percent were still hospitalized. Significant differences in stroke care were found between rural and urban ED. CONCLUSION: This prospective study provides epidemiological data for our region. Creation of stroke units and definition of acute stroke networks are necessary to improve stroke care.

Aged↗
PubMed2001

Vascular endothelial growth factor and basic fibroblast growth factor differentially modulate early postnatal coronary angiogenesis.

The roles of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF [FGF-2]) in early postnatal regulation of coronary angiogenesis were investigated by administering neutralizing antibodies to these growth factors between postnatal days 5 and 12. Immunohistochemistry and Western blotting both revealed decreases in VEGF protein in the hearts of rats treated with either antibody. In contrast, bFGF mRNA increased in both treated groups, whereas VEGF mRNA was unchanged. Using stereological assessment of perfusion-fixed hearts, we found that both anti-VEGF and anti-bFGF inhibited the rapid and marked capillary growth that occurs during this time period and that the effects of the two neutralizing antibodies are not additive. Arteriolar growth, as indicated by a lower length density, was inhibited by anti-bFGF, but not anti-VEGF. When both anti-VEGF and anti-bFGF were administered, arteriolar length density was not significantly lower, but the population of small arterioles (<15 microm) was markedly reduced, whereas the percentage of large arterioles (26 to 50 microm) more than doubled. Thus, inhibition of both growth factors negated or limited the formation of small arterioles and facilitated an expansion of the largest arterioles. These in vivo data are the first to document that during the early neonatal period, (1) both VEGF and bFGF modulate capillary growth, (2) bFGF facilitates arteriolar growth, and (3) the two growth factors interact to establish the normal hierarchy of the arteriolar tree.

Animals↗
PubMed1997

Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist.

Previously we reported the discovery of amidothiophenesulfonamides as endothelin receptor-A antagonists with high potency and selectivity. Replacement of an amide group in this class of compounds with an acetyl group maintained the in vitro binding affinity and in vivo activity while providing a compound with oral bioavailability and longer duration of action. The optimal compound discovered during these studies, 15q (TBC11251), binds competitively to human ETA receptors with a Ki of 0.43 +/- 0.03 nM and an IC50 of 1.4 nM (IC50 for ETB = 9800 nM). This compound inhibits ET-1-induced stimulation of phosphoinositide turnover with a Ki of 0.686 nM and a pA2 of 8.0. The compound has a serum half-life in the rat and the dog of 6-7 h and 60-100% oral bioavailability. This compound is one of the most selective ETA antagonists reported and therefore is suitable for additional pharmacological and clinical investigation of the role of ETA receptors in diseases.

Administration, Oral↗
PubMed1997

Odontogenic keratocysts of the midline maxillary region.

PURPOSE: This article compares the demographic features of the anterior midline maxillary odontogenic keratocyst with those in other regions. MATERIALS AND METHODS: The data on 18 cases of anterior midline maxillary odontogenic keratocyst were reviewed. RESULTS: Thirteen of the cases were in men (72.2%), and 16 of the patients (88.9%) were past the age of 60 years. The mean age of the patients was 69.9 years, which is much higher than for odontogenic keratocysts in other locations. The most common clinical diagnoses were periapical cyst and nasopalatine duct cyst. CONCLUSION: It is important to include odontogenic keratocyst in the differential diagnosis of anterior midline maxillary radiolucencies, especially when they occur in older individuals.

Adult↗
PubMed1996

Translocation of cytosolic phospholipase A2 to the nuclear envelope elicits topographically localized phospholipid hydrolysis.

Cytosolic phospholipase A2 (cPLA2) is a good candidate for mediating the agonist-stimulated release of arachidonic acid (AA) from membrane phospholipids. This enzyme undergoes a Ca(2+)-dependent translocation from the cytosol to a membrane site in a variety of cell types, and this site has recently been identified as the nuclear envelope in leucocytes. The functional correlate of this finding has not yet been established. The present study was therefore undertaken to determine whether translocation of cPLA2 to the nuclear envelope was associated with localized phospholipid hydrolysis at this site. Rat alveolar epithelial cells, previously shown to contain cPLA2, were prelabelled with [3H]AA and stimulated with the model agonist, ionophore A23187. Ionophore-induced AA release exhibited characteristics typical of a cPLA2-mediated response, in that it was Ca(2+)-dependent, sn-2 AA-selective, and inhibited by arachidonyl trifluoromethyl ketone. As determined by indirect immunofluorescence microscopic analysis as well as subcellular fractionation with immunoblotting, ionophore treatment resulted in a translocation of cPLA2 protein from the cytoplasm to the nuclear envelope. To determine whether the nuclear membrane was indeed the source of released AA, prelabelled cells were incubated in the presence or absence of A23187, after which the phospholipid radioactivity was quantified in nuclear and non-nuclear membrane fractions. [3H]AA was distributed in both nuclear and non-nuclear membrane phospholipids. Following A23187 stimulation, the loss of [3H]AA from nuclear membrane phospholipids accounted for 88.1 +/- 5.8% of the total loss from phospholipids and for 92.9 +/- 2.3% of the total [3H]AA released into the medium. These results demonstrate for the first time that agonist-stimulated translocation of cPLA2 to the nuclear envelope is associated with phospholipid hydrolysis which is preferentially localized to that site.

Animals↗
PubMed1995

Liver transplantation: dentistry is an essential part of the team.

Liver transplantation has become a commonplace procedure, with more than 3,000 livers being transplanted annually. Patient demand remains much greater than availability of donor organs, resulting in many deaths per year. Due to the nature of hepatic function, unique concern exists regarding susceptibility to infection and rejection during the post-transplant period, placing great importance on vigilant oral health maintenance. Patients are severely immunocompromised and must be well educated and treated pretransplant and for the rest of their post-transplant lives; however, even though patients are on waiting lists for matching donor livers for an adequate amount of time to provide definitive dental treatment, this is not a major priority on the protocols of some transplant centers. This paper addresses these concerns and illustrates a patient who presented shortly post-transplant with severe dental problems requiring immediate definitive treatment. As these patients may present in any office, general dentists should be aware of the unique concerns involving their assessment, education, treatment and maintenance.

Adult↗
PubMed1993

Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology.

Hypervascularity, focal necrosis, persistent cerebral edema, and rapid cellular proliferation are key histopathologic features of glioblastoma multiforme (GBM), the most common and malignant of human brain tumors. By immunoperoxidase and immunofluorescence, we definitively have demonstrated the presence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFr) in five out of five human glioma cell lines (U-251MG, U-105MG, D-65MG, D-54MG, and CH-235MG) and in eight human GBM tumor surgical specimens. In vitro experiments with glioma cell lines revealed a consistent and reliable relation between EGFr activation and VEGF production; namely, EGF (1-20 ng/ml) stimulation of glioma cells resulted in a 25-125% increase in secretion of bioactive VEGF. Conditioned media (CM) prepared from EGF-stimulated glioma cell lines produced significant increases in cytosolic free intracellular concentrations of Ca2+ ([Ca2+]i) in human umbilical vein endothelial cells (HUVECs). Neither EGF alone or CM from glioma cultures prepared in the absence of EGF induced [Ca2+]i increases in HUVECs. Preincubation of glioma CM with A4.6.1, a monoclonal antibody to VEGF, completely abolished VEGF-mediated [Ca2+]i transients in HUVECs. Likewise, induction by glioma-derived CM of von Willebrand factor release from HUVECs was completely blocked by A4.6.1 pretreatment. These observations provide a key link in understanding the basic cellular pathophysiology of GBM tumor angiogenesis, increased vascular permeability, and cellular proliferation. Specifically, EGF activation of EGFr expressed on glioma cells leads to enhanced secretion of VEGF by glioma cells. VEGF released by glioma cells in situ most likely accounts for pathognomonic histopathologic and clinical features of GBM tumors in patients, including striking tumor angiogenesis, increased cerebral edema and hypercoagulability manifesting as focal tumor necrosis, deep vein thrombosis, or pulmonary embolism.

Brain Neoplasms↗
PubMed1991

P300 from auditory and somatosensory stimuli: probability and inter-stimulus interval.

The P300 (P3) event-related brain potential (ERP) was elicited with auditory and somatosensory stimuli using an easy discrimination task in two experiments. Experiment 1 manipulated target stimulus probability (0.20 vs. 0.80). Experiment 2 manipulated inter-stimulus interval (2 s vs. 6 s) for both stimulus modalities in different conditions while keeping target probability constant. Probability and inter-stimulus interval had similar effects for auditory and somatosensory stimuli, with lower probability and longer inter-stimulus intervals producing larger P3 amplitudes. No statistically reliable differences in scalp distribution between modalities were obtained, with both modalities producing maximal amplitudes at Pz. The results suggest that auditory and somatosensory stimuli when used in a relatively easy discrimination task yield the same overall P3 values.

Acoustic Stimulation↗
PubMed1990

Augmented desensitization to epidermal growth factor (EGF) immediate actions: a novel mechanism for altered EGF growth response in mutant A431 cells.

Epidermal growth factor (EGF) may either stimulate or inhibit cell growth. To elucidate the mechanism of these varied effects, we compared EGF action in parental A431 cells in which cell growth is inhibited, and clone 15, a mutant of these cells resistant to EGF growth inhibition. In both lines, EGF receptor was present in similar concentrations and underwent tyrosine phosphorylation to the same extent. Likewise, in both lines, acute exposure to EGF stimulated an increase in free cytoplasmic [Ca2+], as well as a similar increase in phosphorylation of lipocortin 1, a major substrate for the EGF receptor kinase whose phosphorylation is calcium-dependent. On the other hand, pretreatment of clone 15 cells with EGF for 72 h abolished EGF-induced phosphorylation of lipocortin 1 and led to a loss of the increase in cytoplasmic free [Ca2+], whereas no such desensitization was seen in the parental A431 cells. These data indicate a link between EGF-induced increase in cytoplasmic calcium, lipocortin phosphorylation, and cell growth and suggest that differences in mechanisms of desensitization to these immediate actions of EGF may lead to altered growth response to this hormone.

Annexins↗
PubMed1978

Role of cyclic AMP in rat aortic microsomal phosphorylation and calcium uptake.

The role of adenosine 3',5'-monophosphate (cyclic AMP)-dependent membrane phosphorylation in the regulation of microsomal calcium transport in rat aortic smooth muscle was studied. Cyclic AMP-dependent protein kinase augmented the phosphorylation of serine residues in a microsomal protein component with a molecular weight of about 44,000 (determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis) and the majority of 32P incorporation was in serine residue(s). The phosphorylated protein had stability characteristics of a phosphoester. The phosphorylated substrate was not extracted from the trichloroacetic acid (TCA) precipitate with organic solvents or by suspension in hot TCA; and the demonstrated hydroxylamine insensitivity suggested that the substrate was not lipid or nucleic acid. Intrinsic phosphoprotein phosphatase cleaved the labeled phosphate from the cyclic AMP-stimulated microsomes in the first 5 min of incubation. Microsomes phosphorylated in the presence of 1 micron cyclic AMP or 1 micron cyclic AMP plus 0.1 mg/ml protein kinase exhibited enhanced calcium uptake. We suggest that reversible phosphorylation of microsomal membranes may play an important role in the regulation of aortic microsomal calcium transport by cyclic AMP.

Animals↗
PubMedDate not supplied

High-volume enzyme immunoassay test system for sulfamethazine in swine.

A high-volume enzyme immunoassay (EIA) system for slaughterhouse screening of sulfamethazine in swine plasma/serum has been developed. The system includes a robotic sample processor that performs most of the liquid handling requirements in the assay. The assay gives good correlation with the widely used thin layer chromatographic method for determination of sulfamethazine in serum and plasma (r = 0.826). Inter- and intra-assay coefficients of variation are less than 10%. Approximately 2,400 serum/plasma samples can be analyzed in a normal working day (8 h) with this system.

Animals↗