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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 145 records · Page 8Linked to original sources
PubMed2000

Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (Membrane type 1)-MMP-dependent activation of pro-MMP-2.

The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been shown to be a key enzyme in tumor angiogenesis and metastasis. MT1-MMP hydrolyzes a variety of extracellular matrix components and is a physiological activator of pro-MMP-2, another MMP involved in malignancy. Pro-MMP-2 activation by MT1-MMP involves the formation of an MT1-MMP.tissue inhibitors of metalloproteinases 2 (TIMP-2). pro-MMP-2 complex on the cell surface that promotes the hydrolysis of pro-MMP-2 by a neighboring TIMP-2-free MT1-MMP. The MT1-MMP. TIMP-2 complex also serves to reduce the intermolecular autocatalytic turnover of MT1-MMP, resulting in accumulation of active MT1-MMP (57 kDa) on the cell surface. Evidence shown here in Timp2-null cells demonstrates that pro-MMP-2 activation by MT1-MMP requires TIMP-2. In contrast, a C-terminally deleted TIMP-2 (Delta-TIMP-2), unable to form ternary complex, had no effect. However, Delta-TIMP-2 and certain synthetic MMP inhibitors, which inhibit MT1-MMP autocatalysis, can act synergistically with TIMP-2 in the promotion of pro-MMP-2 activation by MT1-MMP. In contrast, TIMP-4, an efficient MT1-MMP inhibitor, had no synergistic effect. These studies suggest that under certain conditions the pericellular activity of MT1-MMP in the presence of TIMP-2 can be modulated by synthetic and natural (TIMP-4) MMP inhibitors.

Animals↗
PubMed2000

Mott transition, antiferromagnetism, and unconventional superconductivity in layered organic superconductors.

The phase diagram of the organic superconductor kappa-(ET)2Cu[N(CN)2]Cl has been accurately measured from 1H NMR and ac susceptibility techniques under helium gas pressure. The domains of stability of antiferromagnetic and superconducting orders in the pressure vs temperature plane have been determined. Both phases overlap through a first-order boundary that separates two regions of inhomogeneous phase coexistence. The boundary curve merges with the first-order line of the metal-insulator transition which ends with a critical point at higher temperature. The whole phase diagram features a point-like region where metallic, insulating, antiferromagnetic, and non-s-wave superconducting phases all meet.

Journal Article↗
PubMed2000

Analysis of habituated embryogenic lines in Asparagus officinalis L.: growth characteristics, hormone content and ploidy level of calli and regenerated plants.

Habituated asparagus embryogenic lines derived from eleven genotypes were maintained on hormone-free medium and grew actively through secondary embryogenesis. Secondary embryos were of single cell origin and emerged from the transversal division of some epidermal or subepidermal cotyledonary cells of primary embryos. The intensity of secondary embryogenesis was found to be variable between embryogenic lines. Plants regenerated from three of these lines have been previously demonstrated to carry a mutation whose phenotype was the direct appearance of somatic embryos on apices or nodes cultured on hormone-free medium. Habituated lines of embryogenic calli and various tissues of embryogenic mutant and wild type plants were analysed for their hormonal content in ABA, IAA, iP, Z and their metabolites ABA-GE, iPA, iMP, ZR. No significant difference was found between different embryogenic lines, except the level of iPA, or between cladophyll or apex cultures of mutant and wild type plants. Flow cytometry analyses indicated only 34% of the embryogenic lines were diploid, most of the others being tetraploid, but 62% of regenerated plants from these lines were diploid. This indicated the process of maturation and conversion selected diploid embryos in the embryogenic lines.

Journal Article↗
PubMed2000

The developmental transition to flowering represses ascorbate peroxidase activity and induces enzymatic lipid peroxidation in leaf tissue in Arabidopsis thaliana.

Leaf senescence in many plant species is associated with increased oxidative damage to cellular macromolecules by reactive oxygen species (ROS). Since ROS levels and their damage products in many plants are known to increase during senescence, it is possible that these changes are due to a decline in the levels of certain antioxidant enzymes. Using specific assays, we find that the developmental transition to bolting and flowering is associated with up to a 5-fold decline in ascorbate peroxidase activity and an increase in chloroplastid superoxide dismutase. As expected, these changes are associated with a measured increase in lipid peroxidation products. By HPLC separation of the products, we identified the different positional isomers and find that stereospecific lipid peroxidation occurs after the bolting transition. The product distribution suggests that enzyme-mediated lipid peroxidation, via a lipoxygenase, is responsible for the observed increase. Surprisingly, though consistent with the known induction of antioxidant defenses by hydrogen peroxide, the activity of APX rebounds with further development (reproduction and seed setting) and this increase (up to 5-fold) is associated with declines in lipid peroxidation and with the onset of visible senescence symptoms. Thus, in Arabidopsis, ROS increases are associated with the developmental transition to flowering, perhaps due to programmed declines in APX activity, and apparently lead to the oxidative activation of lipoxygenase and subsequent lipid peroxidation. The reactivation of APX at later stages appears to help reduce the lipid peroxidation rate, although the senescence program continues unabated.

Journal Article↗
PubMed2000

Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy.

Granulocyte colony-stimulating factor (G-CSF) has had a major impact on management of "severe chronic neutropenia," a collective term referring to congenital, idiopathic, or cyclic neutropenia. Almost all patients respond to G-CSF with increased neutrophils, reduced infections, and improved survival. Some responders with congenital neutropenia have developed myelodysplastic syndrome and acute myeloblastic leukemia (MDS/AML), which raises the question of the role of G-CSF in pathogenesis. The Severe Chronic Neutropenia International Registry (SCNIR), Seattle, WA, has data on 696 neutropenic patients, including 352 patients with congenital neutropenia, treated with G-CSF from 1987 to present. Treatment and patient demographic data were analyzed. The 352 congenital patients were observed for a mean of 6 years (range, 0.1-11 years) while being treated. Of these patients, 31 developed MDS/AML, for a crude rate of malignant transformation of nearly 9%. None of the 344 patients with idiopathic or cyclic neutropenia developed MDS/AML. Transformation was associated with acquired marrow cytogenetic clonal changes: 18 patients developed a partial or complete loss of chromosome 7, and 9 patients manifested abnormalities of chromosome 21 (usually trisomy 21). For each yearly treatment interval, the annual rate of MDS/AML development was less than 2%. No significant relationships between age at onset of MDS/AML and patient gender, G-CSF dose, or treatment duration were found (P >.15). In addition to the 31 patients who developed MDS/AML, the SCNIR also has data on 9 additional neutropenic patients whose bone marrow studies show cytogenetic clonal changes but the patients are without transformation to MDS/AML. Although our data does not support a cause-and-effect relationship between development of MDS/AML and G-CSF therapy or other patient demographics, we cannot exclude a direct contribution of G-CSF in the pathogenesis of MDS/AML. This issue is unclear because MDS/AML was not seen in cyclic or idiopathic neutropenia. Improved survival of congenital neutropenia patients receiving G-CSF therapy may allow time for the expression of the leukemic predisposition that characterizes the natural history of these disorders. However, other factors related to G-CSF may also be operative in the setting of congenital neutropenia. (Blood. 2000;96:429-436)

Adolescent↗
PubMed2000

Carvedilol affects the physiological and behavioral response to smoked cocaine in humans.

The noradrenergic system is implicated in mediating some of the physiological effects of cocaine. The purpose of this study was to investigate whether treatment with an adrenergic blocker, carvedilol, which would be expected to attenuate the physiological effects of cocaine, would also attenuate the subjective and behavioral response to cocaine in humans. Twelve crack cocaine users participated in this double-blind, placebo-controlled outpatient study. Acute treatment with 50 mg of oral carvedilol attenuated the smoked cocaine-induced increases in heart rate, systolic and diastolic blood pressure. The number of cocaine self-administrations was lower under 25 mg carvedilol treatment condition compared with 50 mg carvedilol or placebo treatment conditions. The subjective responses to smoked cocaine deliveries were not affected by carvedilol treatment. These results suggest that acute treatment with carvedilol attenuates the physiological effects of smoked cocaine. The effects of carvedilol on cocaine self-administration need to be studied further.

Adrenergic Antagonists↗
PubMed2000

A genetic analysis of crystal growth.

The regulation of crystal morphology by proteins is often observed in biology. It is a central feature in the formation of hard tissues such as bones, teeth and mollusc shells. We have developed a genetic system in the bacterium Escherichia coli to study the protein-mediated control of crystal growth. We have used the crystallization of gold as a model system and found polypeptides that control the morphology of the resulting gold crystals. Analysis of the crystallization process influenced by these polypeptides indicates they act catalytically by an acid mechanism. Our results suggest that the concepts and methods of microbial genetics are general and can be applied to substances not commonly found in biological systems.

Acids↗
PubMed2000

Implications of the Tribolium Deformed mutant phenotype for the evolution of Hox gene function.

Among insects, the genetic regulation of regional identities in the postoral head or gnathal segments (mandibular, maxillary, and labial) is best understood in the fly Drosophila melanogaster. In part, normal gnathal development depends on Deformed (Dfd) and Sex combs reduced (Scr), genes in the split Drosophila homeotic complex. The gnathal segments of Dfd and Scr mutant larvae are abnormal but not homeotically transformed. In the red flour beetle, Tribolium castaneum, we have isolated loss-of-function mutations of the Deformed ortholog. Mutant larvae display a strong transformation of mandibular appendages to antennae. The maxillary appendages, normally composed of an endite and a telopodite, develop only the telopodite in mutant larvae. We previously reported that mutations in the beetle Scr and Antennapedia orthologs cause the labial and thoracic appendages, respectively, to be transformed to antennae. Moreover, a deficiency of most of the beetle homeotic complex causes all gnathal (as well as thoracic and abdominal) segments to develop antennae. These and other observations are consistent with the hypothesis that ancestral insect homeotic gene functions have been modified considerably during the evolution of the highly specialized maggot head. One of the ancestral homeobox genes that arose close to the root of the Eumetazoa appears to have given rise to Dfd, Scr, and the Antennapedia homeobox-class homeotic genes. Evidence from both Tribolium and Drosophila suggests that this ancestral gene served to repress anterior development as well as confer a trunk-specific identity.

Amino Acid Sequence↗
PubMed2000

Effects of transcendental meditation on symptoms and electrocardiographic changes in patients with cardiac syndrome X.

Chest pain with normal coronary angiograms is often associated with chronic sympathetic activation, anxiety, and depression, and is resistant to conventional antianginal treatment. The practice of transcendental meditation, a standard relaxation method for 3 months twice daily, significantly improved exercise tolerance, angina episodes, and quality of life in 9 women; the positive findings in this study warrant further research.

Aged↗
PubMed2000

Does succinate oxidation yield FADH(2) or ubiquinol?

Most textbooks still show the oxidation of succinate in the tricarboxylic acid (TCA) cycle resulting in the reduction of FADH(2). Such a presentation does not reflect the reaction catalysed by the enzyme in vivo or in vitro, does not simplify the treatment of the reaction, and is unnecessarily misleading and confusing.

Journal Article↗
PubMed2000

Correlation of histologic 2-dimensional reconstruction and confocal scanning laser microscopic imaging of choroidal neovascularization in eyes with age-related maculopathy.

OBJECTIVE: To topographically localize vascular channels, macrophages, and retinal pigment epithelium and other components of choroidal neovascularization (CNV) associated with age-related maculopathy. METHODS: Two postmortem eyes with age-related maculopathy and CNV were evaluated. The formalin-fixed CNV complex was excised and processed for confocal scanning laser microscopy including immunostaining for factor VIII-related antigen and incubation with Ig fluorescein isothiocyanate. After confocal microscopy, the specimens were serial step sectioned, stained, and 2-dimensional topographic reconstructions were made. The confocal images were compared with the 2-dimensional reconstructions. RESULTS: Both specimens contained central disciform scars surrounded by areas of intact retinal pigment epithelium. The first specimen was more atrophic and contained fewer choroidal neovascular channels than the second specimen. The topographic arrangement of the CNV and retinal pigment epithelial changes in the confocal images corresponded with the 2-dimensional reconstructions. Macrophages were concentrated around areas of vascularization. CONCLUSION: Confocal scanning laser microscopy of excised CNV simulates fluorescein angiography and topographic localization of the components of CNV provides insight into the pathogenesis of CNV.

Aged↗
PubMed2000

Effects of improvement in aerobic power on resting insulin and glucose concentrations in children.

In this study we determined the influence of improving aerobic power (VO(2max)) on basal plasma levels of insulin and glucose of 11- to 14-year-old children, while accounting for body fat, gender, pubertal status, and leisure-time physical activity (LTPA) levels. Blood samples were obtained from 349 children after an overnight fast and analyzed for plasma insulin and glucose. Height, mass, body mass index (BMI), and sum of skinfolds (Sigma triceps + subscapular sites) were measured. LTPA levels and pubertal status were estimated from questionnaires, and VO(2max) was predicted from a cycle ergometry test. Regardless of gender, insulin levels were significantly correlated (P = 0.0001) to BMI, skinfolds, pubertal stage, and predicted VO(2max), but were not related to LTPA levels. Fasting glucose levels were not correlated to measures of adiposity or exercise (LTPA score, VO(2max)) for females; however, BMI and skinfolds were correlated for males (P < 0.006). The children then took part in an 8-week aerobic exercise program. The 60 children whose VO(2max) improved (>/=3 ml x kg(-1) x min(-1)) had a greater reduction in circulating insulin than the 204 children whose VO(2max) did not increase -16 (41) vs -1 (63) pmol x l(-1); P = 0.028. The greatest change occurred in those children with the highest initial resting insulin levels. Plasma glucose levels were slightly reduced only in those children with the highest insulin levels whose VO(2max) improved (P < 0.0506). The results of this study indicate that in children, adiposity has the most significant influence on fasting insulin levels; however, increasing VO(2max) via exercise can lower insulin levels in those children with initially high levels of the hormone. In addition, LTPA does not appear to be associated with fasting insulin status, unless it is sufficient to increase VO(2max).

Adolescent↗
PubMed2000

Comparative gene mapping workshop: progress in agriculturally important animals.

Following the successful Comparative Mapping Workshop held at Fraser Island, Australia in 1995, HUGO organized a second workshop of 41 invited participants, held at Toulouse, France on May 3 and 4, 1999. The aim of the conference was to focus on recent developments in genome mapping in a variety of vertebrate species, with particular emphasis on progress in farm animals (cattle, pigs, chickens, sheep, horses, goats, and deer). In addition, representatives from important experimental mammalian and vertebrate organisms (e.g. mice, rats, dogs, fugu, and marsupials) also participated in the meeting. After a rapid overview of developments in the construction and comparison of genome maps in a wide variety of species, discussion focused on how comparative genomics will play a vital role in the genetic dissection of multigenic traits and the characterization of agriculturally important loci in agricultural species. Acceleration of gene discovery with heterologous ESTs (Expressed Sequence Tags) or collections of ESTs was discussed. Recent developments in the construction of cDNA libraries and the efficiency of tools such as whole genome radiation hybrids (RH) and large fragment clone libraries (YACs and in particular BACs) were discussed. Proposed criteria to improve the identification of homologous genes between species and recommendations for nomenclatures were identified. Particular emphasis was placed on how the integration of biological databases could help the scientific community.

Agriculture↗
PubMed2000

Human chorionic gonadotropin as a predictor of outcome in assisted reproductive technology pregnancies.

OBJECTIVE: To determine whether serum hCG and progesterone levels obtained 16 days after ovulation are reliable predictors of pregnancy outcome. DESIGN: A retrospective study. SETTING: The data were obtained from two integrated Adelaide-based clinics: the Queen Elizabeth Hospital and Wakefield Clinic. PATIENT(S): Women who have achieved a pregnancy through ART treatment. MAIN OUTCOME MEASURE(S): Analysis of data using logistic regression (STATA v.5.0) to predict a binary outcome: ongoing pregnancy or miscarriage. Ongoing pregnancy was defined as progression to >20 weeks' gestation. Miscarriage included spontaneous abortion, biochemical and ectopic pregnancies, and blighted ovum. RESULT(S): Human chorionic gonadotropin was found to be the main determinant of ongoing pregnancy. Age and progesterone had minor effects, whereas stimulation, luteal support, and treatment types were nonpredictive. Low hCG levels between 25 and 50 IU/L are associated with a low probability of ongoing pregnancy (<35%), whereas levels of >500 IU/L predict a >95% chance of ongoing pregnancy. CONCLUSION(S): A single serum hCG level 16 days after ovulation provides a useful predictor of pregnancy outcome.

Abortion, Spontaneous↗
PubMed2000

Is there a relationship between serum S-100beta protein and neuropsychologic dysfunction after cardiopulmonary bypass?

OBJECTIVES: Over the past decade, the glial protein S-100beta has been used to detect cerebral injury in a number of clinical settings including cardiac surgery. Previous investigations suggest that S-100beta is capable of identifying patients with cerebral dysfunction after cardiopulmonary bypass. Whether detection of elevated levels S-100beta reflects long-term cognitive impairment remains to be shown. The present study evaluated whether perioperative release of S-100beta after coronary artery operations with cardiopulmonary bypass could predict early or late neuropsychologic impairment. METHODS: A total of 100 patients undergoing elective coronary bypass without a previous history of neurologic events were prospectively studied. To exclude noncerebral sources of S-100beta, we did not use cardiotomy suction or retransfusion of shed mediastinal blood. Serial perioperative measurements of S-100beta were performed with the use of a new sensitive immunoluminometric assay up to 8 hours after the operation. Patients underwent cognitive testing on a battery of 11 tests before the operation, before discharge from the hospital, and 3 months later. RESULTS: No significant correlation was found between S-100beta release and neuropsychologic measures either 5 days or 3 months after the operation. CONCLUSION: Despite using a sensitive immunoluminometric assay of S-100beta, we found no evidence to support the suggestion that early release of S-100beta may reflect long-term neurologic injury capable of producing cognitive impairment.

Anesthesia, General↗
PubMed2000

Effects of labetalol treatment on the physiological and subjective response to smoked cocaine.

Adrenergic receptors mediate some of the physiological and possibly behavioral effects of cocaine. The purpose of this study was to investigate the effect of treatment with a peripherally acting adrenergic blocking drug labetalol on the cardiovascular and subjective response to repeated deliveries of smoked cocaine. In this double-blind, placebo-controlled, crossover study, 12 cocaine users were treated with a single 100 or 200 mg dose of labetalol, or placebo in each of three experimental sessions. Starting 2 h after the medication treatment, subjects received three doses of 0.4 mg/kg smoked cocaine, 30 min apart. Labetalol treatment significantly attenuated the cocaine-induced increases in heart rate and systolic blood pressure. This effect of labetalol on the cardiovascular response did not decrease with repeated cocaine deliveries. The subjective response to smoked cocaine deliveries was not affected by labetalol treatment. These results suggest that labetalol effectively attenuates the systolic blood pressure and heart rate increases induced by repeated doses of smoked cocaine, but does not alter subjective effects.

Adrenergic Antagonists↗
PubMed2000

Genital tract electrical burns during hysteroscopic endometrial ablation: report of 13 cases in the United States and Canada.

We investigated 13 alleged thermal injuries to the genital tract of women undergoing hysteroscopic endometrial ablation. Possible mechanisms proposed to explain these injuries are hot-weighted speculum, povidone-iodine scrub solution, inadequate rinsing of Cidex sterilizing solution, and electrical burns. The history, nature, and distribution, as well as experimental evidence strongly support the hypothesis that these injuries are electrical due to capacitive coupled currents induced onto the sheath of the resectoscope, and/or stray currents generated by arcing or direct coupling from defective electrode insulation to the telescope, electrifying the entire resectoscope.

Adult↗