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Biomedical subjects

C E Brown

Publications and source records attributed to C E Brown.

At least 19 recordsLinked to original sources

Experience-dependent regulation of synaptic zinc is impaired in the cortex of aged mice.

Zinc plays an important role in synaptic signaling in the mammalian cerebral cortex. Zinc is sequestered into presynaptic vesicles of subpopulations of glutamatergic neurons and is released by depolarization, in a calcium-dependent manner. As the majority of mechanisms that have been suggested to participate in experience-dependent alterations in synaptic strength in the cerebral cortex implicate signaling by glutamate, it stands to reason that zincergic signaling might also be crucial. Here we show that synaptic zinc is rapidly and dynamically modulated in relation to alterations in sensory input and that this response is highly age-dependent. Juvenile, adult, and aged mice were subjected to whisker removal and levels of staining for synaptic zinc in deprived and non-deprived cortical barrels were quantitatively assessed at post-deprivation times ranging from 3 h to 21 days. In the first 12 h, zinc levels increased slightly, but significantly, in all groups. At later time points, zinc levels increased robustly (23%) in the youngest group by 24 h and remained elevated through 7 days. By contrast, deprivation-induced changes in zinc staining in aged animals, achieved their maximal levels at 12 h (approximately 10%) and steadily declined thereafter. Adult animals revealed a biphasic, intermediate change with time. In all age groups, levels of zinc staining returned to baseline by 21 days after whisker plucking. However, only in juvenile and adult mice did we observe that the level of zinc staining in deprived barrel hollows, was correlated with the length of whiskers as they regrew. Our data suggest that alterations in the regulation of synaptic zinc may be involved with decrements of synaptic plasticity that accompany senescence.

Afferent Pathways↗

Determination of Cr3+, CrO42-, and Cr2O72- in environmental matrixes by high-performance liquid chromatography with diode-array detection (HPLC-DAD).

A high-performance liquid chromatographic method with diode array detection (HPLC-DAD), based on chelation with ammonium pyrrolidinedithiocarbamate (APDC), has been developed for the determination of chromium species. Determination of Cr3+, CrO42-, and Cr2O72- was performed for standards and synthetic environmental matrixes. This method is robust, rugged, and can be used for rapid routine determination of chromium species with high precision and reliability. Sample pretreatment is simple. The method is capable of discriminating not only between Cr(III) and Cr(VI) but also between the chemical forms of Cr(VI) - CrO42- and Cr2O72-. By analysis of numerous samples the method has been shown to be selective, sensitive, and free from matrix interference, which is crucial for the determination of chromium species in difficult-to-analyze environmental matrixes. This method has been validated by means of an interlaboratory study. Although different speciation techniques were used during this study, there was good agreement between results from the two laboratories. The method detection limits were 7 and 4 mg L(-1) for Cr3+ and Cr2O72-, respectively. Recoveries of the analytes from spiked samples were 98% and 100% for Cr3+ and Cr2O72-, respectively. Both were based on a 10-mL sample volume spiked with 0.4 mg L(-1) chromium.

Chromates↗

The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1.

It is well established that acetylation of histone and nonhistone proteins is intimately linked to transcriptional activation. However, loss of acetyltransferase activity has also been shown to cause silencing defects, implicating acetylation in gene silencing. The something about silencing (Sas) 2 protein of Saccharomyces cerevisiae, a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family, promotes silencing at HML and telomeres. Here we identify a ~450-kD SAS complex containing Sas2p, Sas4p, and the tf2f-related Sas5 protein. Mutations in the conserved acetyl-CoA binding motif of Sas2p are shown to disrupt the ability of Sas2p to mediate the silencing at HML and telomeres, providing evidence for an important role for the acetyltransferase activity of the SAS complex in silencing. Furthermore, the SAS complex is found to interact with chromatin assembly factor Asf1p, and asf1 mutants show silencing defects similar to mutants in the SAS complex. Thus, ASF1-dependent chromatin assembly may mediate the role of the SAS complex in silencing.

Acetyltransferases↗

Long-term fate and persistence of the spilled metula oil in a marine salt marsh environment degradation of petroleum biomarkers.

Three coastal sites, heavily oiled from the 1974 Metula oil spill in the Strait of Magellan [two are salt marshes (East and West) and the third, an intertidal asphalt pavement], were examined during May 1998. Complete 'total oil analyses' were performed on the oil samples collected from these sites. Chemical fingerprinting data reveal, except for those samples from the East Marsh untreated plots which were only lightly to moderately weathered, that the spilled oil has undergone significant alteration in chemical composition after 24 years. There are no fundamental differences between the heavily weathered West Marsh and treated East Marsh samples. However, the effect of experimental filling action conducted in 1993 has been to substantially promote plant recolonization. The asphalt pavement samples indicate extremely high degradation of oil hydrocarbons, evidenced by a complete loss of n-alkanes from n-C8 to n-C41 and by depletion of greater than 98% of the alkylated polycyclic aromatic hydrocarbon homologues. Even the most refractory biomarker compounds showed some degree of biodegradation. The biomarkers were generally degraded in the declining order of importance as follows: diasteranes>C27 steranes>tricyclic terpanes>pentacyclic terpanes>norhapanes approximately C29-alphabetabeta-steranes.

Oils↗

Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit.

Promoter-specific recruitment of histone acetyltransferase activity is often critical for transcriptional activation. We present a detailed study of the interaction between the histone acetyltransferase complexes SAGA and NuA4, and transcription activators. We demonstrate by affinity chromatography and photo-cross-linking label transfer that acidic activators directly interact with Tra1p, a shared subunit of SAGA and NuA4. Mutations within the COOH-terminus of Tra1p disrupted its interaction with activators and resulted in gene-specific transcriptional defects that correlated with lowered promoter-specific histone acetylation. These data demonstrate that the essential Tra1 protein serves as a common target for activators in both SAGA and NuA4 acetyltransferases.

Acetylation↗

An immunohistochemical study of osteoprotegerin in the human dental pulp.

This study investigated the expression of osteoprotegerin (OPG) in healthy and inflamed dental pulps. Histological sections 7 microm thick of 47 teeth, either caries-free or affected by gross caries, were used. Sections were stained with hematoxylin-eosin, and other sections of the same specimen were subjected to the avidin-biotin peroxidase complex immunohistochemical procedure for detection of OPG. The study focused on the coronal pulp that was divided into peripheral and central regions. In the peripheral pulp healthy and inflamed specimens showed high OPG immunoreactivity of the odontoblastic layer. When no inflammation was present in the central pulp OPG immunoreactivity was light. Fibroblasts and endothelial cells showed immunoreactivity ranging from none to intense. When inflammation was present in the central pulp the chronic inflammatory cells showed intense immunoreactivity.

Chi-Square Distribution↗

Relationships of cortisol, perceived stress, genitourinary infections, and fetal fibronectin to gestational age at birth.

The authors investigated the role of stress and cortisol with patients having preterm labor (PTL) and preterm birth (PTB). The relationships of maternal cortisol, perceived stress, fetal fibronectin (fFN), and genitourinary infections to PTL and PTB were studied. A prospective, longitudinal, observational study (n = 78) was conducted in a private practice in central Texas. Subjects had 4 blood draws for cortisol measurements grouped by 15-19, 20-22, 23-26, 27-30, and 31-35 weeks of gestation. Subjects had 2 vaginal swabs forfFN, chlamydia, and bacterial vaginosis screens at 23-26 and 27-30 weeks with assessment of psychosocial stress at 23-26 and 31-35 weeks. Statistical analysis was by analysis of variance, Pearson correlations, Fisher exact test, and logistic regression. There were no significant differences between the PTB, PTL, and term groups on cortisol levels at any of the gestational periods. Cortisol concentrations at any gestational stage did not correlate with gestational age at birth. A relationship of cortisol to race was observed when comparing Caucasians to other ethnic groups. A correlation (r = 0.42, P < 0.001) between the change in Perceived Stress Scale (PSS) score and gestational age was observed. The greater the decrease in PSS scores, the longer was the gestational age. A significant increase in cortisol at 19-21 weeks (P < 0.04), 23-26 weeks (P < 0.05), and 31-35 weeks (P < 0.01) was observed in patients having genitourinary infection. PTL was also significantly increased in subjects having positive genitourinary infections at either 23-26 weeks or 27-30 weeks (P < 0.01). The sensitivity of fFN to predict PTL collected at 27-30 weeks was 40%, specificity 86%, positive predictive value 55%, and negative predictive value 83%. These results indicate that cortisol is a poor predictor of either PTL or PTB. A decrease in perceived stress during the 2nd trimester was associated with an increase in length of gestation, suggesting the possibility of stress reduction as an appropriate intervention for lengthening gestational age.

Adolescent↗

Tissue reactions after subcutaneous and intraosseous implantation of mineral trioxide aggregate and ethoxybenzoic acid cement.

Biocompatibility of mineral trioxide aggregate and ethoxybenzoic acid cement was investigated by subcutaneous and intraosseous implantation of the materials in rats. Tissue reactions were studied at 15, 30, and 60 days after implantation. Subcutaneous implantation of mineral trioxide aggregate initially elicited severe reactions with coagulation necrosis and dystrophic calcification; the reactions, however, subsided to mostly moderate with time. Subcutaneous implantation of ethoxybenzoic acid cement initially elicited mostly moderate reactions that subsided to mild in time. Osteogenesis was not observed with either material upon subcutaneous implantation indicating that neither material is osteoinductive. Reactions to intraosseous implants of both materials were less intense than with subcutaneous implantation. Osteogenesis occurred in association with intraosseous implants indicating that both materials are osteoconductive.

Aluminum Compounds↗

On the physics of the infant feeding bottle and middle ear sequela: ear disease in infants can be associated with bottle feeding.

BACKGROUND: When using conventional feeding bottles, negative pressure is generated in the oral cavity, as well as, in the bottle when fluid is removed by sucking. The negative pressure inside the bottle causes the infant to suck excessively and the intraoral negative pressure may subsequently be transmitted to the middle ear via the eustachian tube. METHODS: in seven infants, simultaneous pressure recordings were performed in the feeding vessel and the middle ear using three types of feeding bottles. RESULTS: with conventional non-ventilated and under-ventilated bottles a negative pressure formed while the infant sucked and negative intratympanic pressure was frequently generated. CONCLUSIONS: it is suggested that this sequence of events may lead to secretory otitis and it's accompanying consequences. In contrast, a fully ventilated bottle showed positive pressure throughout the feeding procedure, which is similar to normal breast-feeding, and negative pressure changes were not recorded in the middle ear.

Bottle Feeding↗

The many HATs of transcription coactivators.

Histone acetylation is closely linked to gene transcription. The identification of histone acetyltransferases (HATs) and the large multiprotein complexes in which they reside has yielded important insights into how these enzymes regulate transcription. The demonstration that HAT complexes interact with sequence-specific activator proteins illustrates how these complexes target specific genes. In addition to histones, some HATs can acetylate non-histone proteins suggesting multiple roles for these enzymes.

Acetyltransferases↗

The admid system: generation of recombinant adenoviruses by Tn7-mediated transposition in E. coli.

A new system has been developed for generating recombinant adenoviruses by Tn7-mediated transposition in E. coli. Low copy number E. coli plasmids containing a full-length adenoviral genome with lacZattTn7 replacing E1 have been constructed. The adenovirus plasmid or admid, as well as high copy number progenitors, were stably maintained in E. coli strain DH10B. Several transfer vectors containing a mammalian expression cassette flanked by Tn7R and Tn7L were used as donors to transpose the mini-Tn7 into the E1 region of the adenoviral genome. Transposed recombinant admids are readily identified by their beta-galactosidase phenotype. Transfection of admid DNA into producer cells resulted in the efficient production of infectious adenovirus. This easy-to-use, efficient system generates pure, clonal stocks of recombinant adenovirus without successive rounds of plaque purification.

Adenoviridae↗

Dominant-negative polo-like kinase 1 induces mitotic catastrophe independent of cdc25C function.

Polo-like kinase 1 (PLK1), which has been shown to have a critical role in mitosis, is one possible target for cancer therapeutic intervention. PLK1, at least in Xenopus, starts the mitotic cascade by phosphorylating and activating cdc25C phosphatase. Also, loss of PLK1 function has been shown to induce mitotic catastrophe in a HeLa cervical carcinoma cell line but not in normal Hs68 fibroblasts. We wanted to understand whether the selective mitotic catastrophe in HeLa cells could be extended to other tumor types, and, if so, whether it could be attributable to a tumor-specific loss of dependence on PLK1 for cdc25C activation. When PLK1 function was blocked through adenovirus delivery of a dominant-negative gene, we observed tumor-selective apoptosis in most tumor cell lines. In some lines, dominant-negative PLK1 induced a mitotic catastrophe similar to that published in HeLa cells (K. E. Mundt et al., Biochem. Biophys Res. Commun., 239: 377-385, 1997). Normal human mammary epithelial cells, although arrested in mitosis, appeared to escape the loss of centrosome maturation and mitotic catastrophe seen in tumor lines. Mitotic phosphorylation of cdc25C and activation of cdk1 was blocked by dominant-negative PLK1 in human mammary epithelial cells as well as in the tumor lines regardless of whether they underwent mitotic catastrophe. These data strongly argue that the mitotic catastrophe is not attributable to a lack of dependence for PLK1 in activating cdc25C.

Adenoviridae↗

Puerperal septic pelvic thrombophlebitis: incidence and response to heparin therapy.

OBJECTIVE: Before the availability of modern imaging studies the diagnosis of septic pelvic thrombophlebitis causing prolonged puerperal fever was difficult to confirm without surgical exploration. With the use of computed tomography infection-related pelvic phlebitis can now be confirmed, and this study was designed to determine its incidence after delivery. We also designed a randomized clinical trial to evaluate the efficacy of heparin added to antimicrobial therapy for treatment of women with septic phlebitis. STUDY DESIGN: We studied women who had pelvic infection and fever that persisted after 5 days despite adequate antimicrobial therapy with clindamycin, gentamicin, and ampicillin. After giving consent study participants underwent abdominopelvic computed tomographic imaging. Women with pelvic thrombophlebitis were randomly assigned to 1 of 2 management schemes that included continuation of antimicrobial therapy, either alone or with the addition of heparin, until the temperature was </=37.5 degrees C for 48 hours. RESULTS: During the 3-year study period 44,922 women were delivered at Parkland Hospital; among these 8535 (19%) were delivered by the cesarean route. There were 69 women who met criteria for prolonged infection, and 15 (22%) of these were found to have septic pelvic thrombophlebitis. Four had infection after vaginal delivery and 11 had been delivered by the cesarean route. Of 14 women randomly assigned to therapy, 8 were assigned to receive continued antimicrobial therapy without the addition of heparin and the other 6 were assigned to receive heparin therapy in addition to the antimicrobial agents. According to an intent-to-treat analysis there was no significant difference between the responses of women with pelvic infection who were and were not given heparin therapy. Specifically, women not given heparin were febrile for 140 +/- 39 hours compared with 134 +/- 65 hours for women who received heparin (P =.83). Duration of hospitalization was also similar between the 2 groups at 10.6 +/- 1.9 days for those with thrombosis who were given antimicrobial agents alone and 11.3 +/- 1.2 days for women who also received heparin (P >.5). The 54 women with persistent fever but without computed tomographic evidence of septic pelvic thrombophlebitis were hospitalized for a mean of 12.0 +/- 4.1 days, compared with 10.9 +/- 2.9 days for women in whom thrombosis was diagnosed (P =.14). These women were followed up for >/=3 months post partum and none showed evidence of reinfection, embolic episodes, or postphlebitic syndrome. CONCLUSIONS: The overall incidence of septic pelvic thrombophlebitis was 1:3000 deliveries. The incidence was about 1:9000 after vaginal delivery and 1:800 after cesarean section. Women given heparin in addition to antimicrobial therapy for septic thrombophlebitis did not have better outcomes than did those for whom antimicrobial therapy alone was continued. These results also do not support the common empiric practice of heparin treatment for women with persistent postpartum infection.

Adult↗

Histone acetyltransferase complexes and their link to transcription.

Early studies revealing the relationship between the state of histone acetylation and gene transcription were largely indirect. Increasing information regarding the enzymes that catalyze transcription linked acetylation is beginning to clarify this issue. This review attempts to relate previous data regarding the distribution of histone acetylation within different chromatin regions with recent data regarding the substrate specificity, subunit composition, and recruitment of the known histone acetyltransferase complexes.

Acetyltransferases↗

Effect of in-line bacteriological filters on numbers of heterotrophic bacteria in water emitted from non-autoclavable dental air-water syringes.

PURPOSE: To determine the effect of in-line bacteriological filters on the heterotrophic bacterial count of water from non-autoclavable dental air-water syringes. MATERIALS AND METHODS: In-line bacteriological filters were placed in the waterlines of non-autoclavable dental air-water syringes. Filters were placed either as close as possible to the air-water syringe or at a distance of approximately 6 feet (1.8 meters) from the air-water syringe. After routine flushing of water lines and air-water syringes, water samples were collected aseptically. Samples were diluted, plated on NWRI agar, and incubated, and numbers of heterotrophic bacteria per ml were determined. RESULTS: Filtration substantially reduced heterotrophic contamination of air-water syringe water when the filter was placed immediately adjacent to the air-water syringe. However, there was no beneficial effect when the filter was at a distance from the air-water syringe. Furthermore, filtered water containing no detectable heterotrophic bacteria was re-contaminated upon passage through the non-autoclavable air-water syringe.

Colony Count, Microbial↗

NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint.

The transcription factor NF-kappaB is a pivotal regulator of inflammatory responses. While the activation of NF-kappaB in the arthritic joint has been associated with rheumatoid arthritis (RA), its significance is poorly understood. Here, we examine the role of NF-kappaB in animal models of RA. We demonstrate that in vitro, NF-kappaB controlled expression of numerous inflammatory molecules in synoviocytes and protected cells against tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) cytotoxicity. Similar to that observed in human RA, NF-kappaB was found to be activated in the synovium of rats with streptococcal cell wall (SCW)-induced arthritis. In vivo suppression of NF-kappaB by either proteasomal inhibitors or intraarticular adenoviral gene transfer of super-repressor IkappaBalpha profoundly enhanced apoptosis in the synovium of rats with SCW- and pristane-induced arthritis. This indicated that the activation of NF-kappaB protected the cells in the synovium against apoptosis and thus provided the potential link between inflammation and hyperplasia. Intraarticular administration of NF-kB decoys prevented the recurrence of SCW arthritis in treated joints. Unexpectedly, the severity of arthritis also was inhibited significantly in the contralateral, untreated joints, indicating beneficial systemic effects of local suppression of NF-kappaB. These results establish a mechanism regulating apoptosis in the arthritic joint and indicate the feasibility of therapeutic approaches to RA based on the specific suppression of NF-kappaB.

Animals↗

The research basis for prevention of preterm delivery in twin gestations.

The purpose of this review is to explore interventions to improve the preterm delivery (PTD) rate in twin gestations. The increased mortality rate of twin gestations is strongly associated with low birth weight and PTD. Current evidence-based interventions such as specialized, comprehensive care by a consistent provider (such as an advanced practice nurse) should be implemented. Research is still needed for improved early detection and interventions to decrease risk factors for PTD. Nursing research is challenged to further develop interventions to improve perinatal outcomes in twin gestations and to decrease the burdens of premature delivery for our nation.

Journal Article↗

Biocompatibility of two apatite cements.

Biocompatibility and osteogenic potential of two calcium phosphate cements (G-5 and G-6) and Super-EBA were investigated by subcutaneous and intraosseous implantation in 90 rats. Reactions were studied microscopically at 15, 30, and 60 days after implantation. Super-EBA was well tolerated by both soft and hard tissues. G-5 was highly biocompatible with resorption and bone replacement at intraosseous implantation sites. G-6 promoted moderate inflammation and a foreign body giant cell response over the 60-day study period. None of the materials elicited osteogenesis or dystrophic calcification at the subcutaneous implantation sites.

Animals↗