Biomedical subjects

A Nichols

Publications and source records attributed to A Nichols.

At least 19 recordsLinked to original sources

PubMed2006

Plasma levels of tumour necrosis factor-alpha in patients with chronic periodontitis and type 2 diabetes.

OBJECTIVES: Studies suggest that elevated circulating tumour necrosis factor-alpha (TNF-alpha) may contribute to insulin resistance in patients with type 2 diabetes. The source of plasma TNF has been thought to be adipocytes associated with obesity, but inflammation and infection result in TNF-alpha production as well. METHODS: We studied 46 patients with type 2 diabetes and chronic periodontitis to determine the relationship between plasma TNF-alpha levels and clinical measures of periodontitis, gingival crevicular fluid (GCF) interleukin-1beta (IL-1beta), plasma endotoxin, serum glucose, and glycated haemoglobin (HbA1c). TNF-alpha levels were measured using a high sensitivity enzyme-linked immunosorbent assay. RESULTS: TNF-alpha showed a significant positive correlation with attachment loss (r=0.40, p=0.009), plasma endotoxin (r=0.33, p=0.03), and GCF IL-1beta (r=0.33, p=0.035), but not probing depth (r=0.28, p=0.07), bleeding on probing (r=0.30, p=0.053), plaque index (r=0.22, p=0.17), serum glucose, HbA1c (r=0.10, p=0.50), or body mass index (r=0.077, p=0.62). A dose-response relationship was observed between periodontitis severity and TNF-alpha (p=0.012). CONCLUSION: The finding that chronic periodontitis is associated with plasma TNF-alpha levels in subjects with type 2 diabetes supports the hypothesis that periodontal infection and inflammation may contribute to insulin resistance.

Blood Glucose↗

PubMed2006

Examining the influence of substrates and temperature on maximum specific growth rate of denitrifiers.

Facilities across North America are designing plants to meet stringent limits of technology (LOT) treatment for nitrogen removal (3-5 mg/L total effluent nitrogen). The anoxic capacity requirements for meeting LOT treatment are dependent on the growth rates of the denitrifying organisms. The Blue Plains Advanced Wastewater Treatment Plant (AWTP) is one of many facilities in the Chesapeake Bay region that is evaluating its ability to meet LOT treatment capability. The plant uses methanol as an external carbon source in a post-denitrification process. The process is very sensitive to denitrification in the winter. One approach to improve anoxic capacity utilization is to use an alternative substrate for denitrification in the winter to promote the growth of organisms that denitrify at higher rates. The aim of this study was to evaluate denitrification maximum specific growth rates for three substrates, acetate, corn syrup and methanol, at two temperatures (13 degrees C and 19 degrees C). These temperatures approximately reflect the minimum monthly and average annual wastewater temperature at the Blue Plains AWTP. The results suggest that the maximum specific growth rate (mu(max)) for corn syrup (1.3 d(-1)) and acetate (1.2 d(-1)) are higher than that for methanol (0.5d(-1)) at low temperature of 13 degrees C. A similar trend was observed at 19 degrees C.

Biomass↗

PubMed2005

Electric interactions through chirping behavior in the weakly electric fish, Apteronotus leptorhynchus.

The weakly electric fish Apteronotus leptorhynchus produces wave-like electric organ discharges distinguished by a high degree of regularity. Transient amplitude and frequency modulations ("chirps") can be evoked in males by stimulation with the electric field of a conspecific. During these interactions, the males examined in this study produced six types of chirps, including two novel ones. Stimulation of a test fish with a conspecific at various distances showed that two electrically interacting fish must be within 10 cm of each other to evoke chirping behavior in the neighboring fish. The chirp rate of all but one chirp type elicited by the neighboring fish was found to be negatively correlated with the absolute value of the frequency difference between the two interacting fish, but independent of the sign of this difference. Correlation analysis of the instantaneous rates of chirp occurrence revealed two modes of interactions characterized by reciprocal stimulation and reciprocal inhibition. Further analysis of the temporal relationship between the chirps generated by the two fish during electric interactions showed that the chirps generated by one individual follow the chirps of the other with a short latency of approximately 500-1,000 ms. We hypothesize that this "echo response" serves a communicatory function.

Animal Communication↗

PubMed2004

Change of place, change of pace, change of status: rural community training for junior doctors, does it influence choices of training and career?

INTRODUCTION: The Rural and Remote Area Placement Program (RRAPP) began in April 2000 to provide a rural community practice training term for junior doctors and to increase the opportunities for junior doctors to experience training outside the hospital setting. Recent research into the community-based training and experience for junior doctors in Australia suggests that such experience contributes to their decision-making about future training and career. METHODS: A structured national survey was undertaken of all 107 junior doctors who had participated in RRAPP prior to October 2003 and included semi-structured interviews of 54 participants from prior to October 2002. RESULTS: Data indicated that rural and community experience influenced the choice of further rural and general practice training and also provided a useful setting for junior doctors to reflect on, and confirm, future training plans. This study provided evidence of the positive influence of RRAPP on the career choices of junior doctors, with greater than 70% of participants confirming RRAPP's influence on their plans. This study also provided insight into the process of these career decisions. Decision-making was precipitated by taking junior doctors 'outside their comfort zone' of the tertiary hospital and providing a different perspective on both the present and the future. CONCLUSION: In addition to the contrast in setting and the expansion of knowledge about rural community practice, RRAPP junior doctors identified the change of place, the change of pace, and the change of status as instrumental in their decision-making about future training and careers.

Journal Article↗

PubMed2003

[Successful management of abdominal stab wounds with clinical evaluation: experiences of an South-African trauma unit with 496 consecutive patients].

BACKGROUND: Up to 80% of all operations performed in South African trauma units are due to penetrating injuries. This study will evaluate our own clinical guidelines for the management of penetrating abdominal injuries. METHODS: Absolute indication for operation in patients with penetrating abdominal injuries have been: haemodynamic instability, evisceration of bowels or organs, peritonitis, free air under the diaphragm on plain abdominal x-rays, the evidence of fresh blood on rectal examination or in the stomach. No ultrasonography or CT scanning has been performed. RESULTS: 496 patients were included in this study. In 248 (50%) patients an operation has been performed. 50 (20%) of them were initially selected for abdominal observation. In 230 (93%) patients, peritoneal penetration was diagnosed during laparotomy. In 18 (7%) patients the laparotomy was negative and in 24 (10%) non-therapeutic.6 (2%) patients died. Specifically 93.2% (CI 90.2-96.2%), positive prediction 92.7% (89.5%-95.7%). CONCLUSION: The clinical evaluation of patients with abdominal stab wounds is a safe method to detect possible fatal injuries in hospitals without unlimited access to ultrasonography and CT scanning. 80% of all patients with a selective conservative approach needed no operation.

Abdominal Injuries↗

PubMed2001

Abnormal regulation of DDB2 gene expression in xeroderma pigmentosum group E strains.

A damage-specific DNA binding protein (DDB) activity is absent from a subset (DDB(-)) of cells from individuals initially classified as group E of xeroderma pigmentosum (XP), a hereditary, photosensitive disease with a high incidence of skin malignancies. In these cases, mutations have been identified in the DDB2 gene (DDB2(-)) that codes for the small subunit, p48, of the DDB heterodimer. In four DDB2(- )strains, neither p48 nor DDB activity were observed before or after UV-irradiation, despite an unusually strong up-regulation of DDB2 mRNA levels after UV-irradiation. In a fifth strain, XP82TO, p48 was detectable and both DDB2 mRNA and p48 levels were more up-regulated after UV-irradiation than in normal primary cells. Moreover, DDB activity also became apparent after irradiation. XP82TO showed very mild clinical manifestations compared with the other DDB(-) patients. These results, coupled with our findings that most, if not all DDB(+) cells classified as XP-E were misclassified, suggests a direct correlation between DDB2 levels and the XP-E phenotype.

Cells, Cultured↗

PubMed2001

Overexpression of plasminogen activator inhibitor type 2 in basal keratinocytes enhances papilloma formation in transgenic mice.

The serpin plasminogen activator inhibitor (PAI) type 2 is expressed in differentiated epidermal keratinocytes. To explore its role in this tissue, we studied the impact of PAI-2 overexpression on epidermal differentiation and skin carcinogenesis. A mouse PAI-2-encoding transgene was targeted to basal epidermis and hair follicles under the control of the bovine keratin type 5 gene promoter. Two mouse lines were established, one of which strongly expressed the transgene and produced elevated levels of PAI-2 in the epidermis. Although it had no manifest impact on cellularity or differentiation of skin or hair follicles, PAI-2 overexpression rendered the mice highly susceptible to skin carcinogenesis induced by a single application of 7,12-dimethylbenz(a)anthracene (initiation) followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate [TPA (promotion)]. In transgenic mice, papillomas could be observed after 3 weeks of promotion; after 8 weeks, 94% (31 of 33) of transgenic mice had developed readily visible papillomas, whereas only 35% (7 of 20) of control mice (transgene-negative littermates) had barely detectable lesions. After 11 weeks, all but 1 (32 of 33) of the transgenic mice had papillomas as compared with only 65% (13 of 20) of control mice. After 11 weeks of promotion, application of TPA was terminated. In control mice, papillomas regressed and eventually disappeared; in transgenic mice, there was continued growth of papillomas, some of which further progressed to carcinomas. In contrast to massive apoptosis in regressing papillomas of control mice, only a few apoptotic cells were detected in transgenic papillomas after the cessation of TPA application. The effect of PAI-2 on papilloma formation did not appear to involve inhibition of the secreted protease urokinase-type plasminogen activator (uPA): PAI-2 accumulated predominantly in cells, and PAI-2 overexpression failed to alleviate a phenotype induced by uPA secretion, as demonstrated by a double transgenic strategy. In addition, in situ hybridization revealed that uPA mRNA is not expressed concomitantly with PAI-2 in developing papillomas. We conclude that overexpression of PAI-2 promotes the development and progression of epidermal papillomas in a manner that does not involve inhibition of its extracellular target protease, uPA, but appears to be related to an inhibition of apoptosis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Spectroscopic analysis of the tribological behavior of a model boundary layer lubricant.

Highly ordered alkanethiol self-assembled monolayers (SAMs) on gold substrates are suitable models of boundary layer lubricants and may be used in actual nanoscale device applications. Here, such monolayers were studied by spectroscopic methods as a function of tribological wear (rubbing) using a pin-on-disk microtribometer. The coefficient of friction (COF) (ratio of the frictional force to the load) was measured with the tribometer, and reflectance infrared spectra and X-ray photoelectron spectra were obtained as the monolayer film failed and the COF changed. The results show that it is possible to correlate disorder in the monolayer film with tribological failure of the film, and that continued rubbing produces a chemical change in the monolayer film. Disorder in the monolayer is distinct from the influence of wear in the underlying gold substrate. Aged SAMs, having sulfonate rather than thiol headgroups and initially less well ordered, behave differently to the well-ordered freshly prepared SAMs. Interestingly, they show a lower COF over many more cycles of exposure to the rubbing pin. The impact of the mechanism of film failure in boundary layer lubrication is discussed.

Journal Article↗

PubMed2001

Regionalisation of rural medical training in far north Queensland: a learning experience for medical educators and managers.

The need for an appropriate, dedicated vertically-integrated training pathway for rural doctors, provided by regional consortia of educational organisations, has been clearly identified by Rural Doctors Association of Queensland (RDAQ) and The Australian College of Rural and Remote Medicine (ACRRM) as a key strategy to resolve rural medical workforce issues. The opportunity to put the ideas into action is now here with rural doctors responding to the challenge of managing more reform in general practice all over Australia. In Far North Queensland, the ongoing reform of general practice education has been challenging, with many lessons learned by both educators and managers. This paper describes the management of change, and outlines key principles and characteristics of a successful regional rural medical training system, building on the lessons learned from the Rural and Remote Area Placement Program (RRAP) and other projects.

Cooperative Behavior↗

PubMed2001

Protein kinase epsilon dampens the secretory response of model intestinal epithelia during ischemia.

BACKGROUND: Luminal fluid sequestration and diarrhea are early manifestations of mesenteric ischemia. This can be modeled in vitro with the use of T84 intestinal epithelia, where ischemia induces Cl(-) secretion with adenosine-mediated autocrine feedback. Protein kinase C (PKC) regulates epithelial transport and, in some organ systems, is involved in the response to ischemic stress. The purpose of this study was to define the role of PKC on epithelial transport during ischemia. METHODS: By voltage-current clamp, short-circuit current (Isc) equals Cl(-) secretion. Ischemic conditions were simulated with the use of a well-established chemical hypoxia protocol. RESULTS: Chemical hypoxia briskly activated Isc. Gö6850, an antagonist of novel and conventional PKC isoforms, markedly enhanced the ischemia-induced Isc response, although Gö6976 (which inhibits only conventional isoforms) had no effect. Rottlerin, a specific inhibitor of PKC delta, did not attenuate ischemic Isc. Both phorbol 12-myristate, 13-acetate and bryostatin-1, which selectively activate PKC epsilon in T84 cells, markedly attenuated the Isc response to ischemia. Both agents also inhibited the Isc response to exogenous adenosine. CONCLUSIONS: PKC (likely the novel epsilon isoform) in intestinal epithelia modulates ischemia-induced alterations in ion transport. Inhibition of PKC epsilon exaggerates the secretory response that is induced by ischemia and by authentic adenosine; conversely, augmented activation of PKC epsilon inhibits secretion. Manipulation of PKC epsilon could limit luminal fluid sequestration during mesenteric ischemia.

Biological Transport↗

PubMed2000

Urokinase-type plasminogen activator and its receptor synergize to promote pathogenic proteolysis.

Urokinase-type plasminogen activator (uPA) is a potent catalyst of extracellular proteolysis, which also binds to a high-affinity plasma membrane receptor (uPAR). Binding of uPA may influence pericellular proteolysis and/or activate intracellular signal transduction. Transgenic mice overexpressing either uPA or uPAR in basal epidermis and hair follicles had no detectable cutaneous alterations. In contrast, bi-transgenic mice overexpressing both uPA and uPAR, obtained by crossing the two transgenic lines, developed extensive alopecia induced by involution of hair follicles, epidermal thickening and sub-epidermal blisters. The phenotype was due to uPA catalytic activity since combined overexpression of uPAR and uPAR-binding but catalytically inactive uPA in the same tissue was not detrimental in another bi-transgenic line. It was accompanied by increased plasmin-generating capacity, up-regulation and activation of matrix metalloproteinases type-2 and -9, and cleavage of uPAR. Thus, combined overexpression of uPA and uPAR acts in synergy to promote pathogenic extracellular proteolysis.

Animals↗

PubMed2000

Substrate recognition domains within extracellular signal-regulated kinase mediate binding and catalytic activation of mitogen-activated protein kinase phosphatase-3.

Mitogen-activated protein (MAP) kinase phosphatase-3 (MKP-3) is a dual specificity phosphatase that inactivates extracellular signal-regulated kinase (ERK) MAP kinases. This reflects tight and specific binding between ERK and the MKP-3 amino terminus with consequent phosphatase activation and dephosphorylation of the bound MAP kinase. We have used a series of p38/ERK chimeric molecules to identify domains within ERK necessary for binding and catalytic activation of MKP-3. These studies demonstrate that ERK kinase subdomains V-XI are necessary and sufficient for binding and catalytic activation of MKP-3. These domains constitute the major COOH-terminal structural lobe of ERK. p38/ERK chimeras possessing these regions display increased sensitivity to inactivation by MKP-3. These data also reveal an overlap between ERK domains interacting with MKP-3 and those known to confer substrate specificity on the ERK MAP kinase. Consistent with this, we show that peptides representing docking sites within the target substrates Elk-1 and p90(rsk) inhibit ERK-dependent activation of MKP-3. In addition, abolition of ERK-dependent phosphatase activation following mutation of a putative kinase interaction motif (KIM) within the MKP-3 NH(2) terminus suggests that key sites of contact for the ERK COOH-terminal structural lobe include residues localized between the Cdc25 homology domains (CH2) found conserved between members of the DSP gene family.

Amino Acid Sequence↗

PubMed2000

Dual specificity phosphatases: a gene family for control of MAP kinase function.

Mitogen-activated protein (MAP) kinases are important players in signal transduction pathways activated by a range of stimuli and mediate a number of physiological and pathological changes in cell function. MAP kinase activation requires phosphorylation on a threonine and tyrosine residue located within the activation loop of kinase subdomain VIII. This process is reversible even in the continued presence of activating stimuli, indicating that protein phosphatases provide an important mechanism for MAP kinase control. Dual specificity phosphatases (DSPs) are an emerging subclass of the protein tyrosine phosphatase (PTP) gene superfamily, which appears to be selective for dephosphorylating the critical phosphothreonine and phosphotyrosine residues within MAP kinases. Some DSPs are localized to different subcellular compartments and moreover, certain family members appear highly selective for inactivating distinct MAP kinase isoforms. This enzymatic specificity is due in part to powerful catalytic activation of the DSP phosphatase after tight binding of its amino-terminal to the target MAP kinase. DSP gene expression is induced strongly by various growth factors and/or cellular stresses, providing a sophisticated transcriptional mechanism for targeted inactivation of selected MAP kinase activities.

Amino Acid Sequence↗

PubMed2000

An ideal combination.

Explore the source record for details and available documents.

Education, Nursing, Graduate↗

PubMed1999

Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis.

Here we report that in staurosporine-induced apoptosis of HeLa cells, Bid, a BH3 domain containing protein, translocates from the cytosol to mitochondria. This event is associated with a change in conformation of Bax which leads to the unmasking of its NH2-terminal domain and is accompanied by the release of cytochrome c from mitochondria. A similar finding is reported for cerebellar granule cells undergoing apoptosis induced by serum and potassium deprivation. The Bax-conformational change is prevented by Bcl-2 and Bcl-xL but not by caspase inhibitors. Using isolated mitochondria and various BH3 mutants of Bid, we demonstrate that direct binding of Bid to Bax is a prerequisite for Bax structural change and cytochrome c release. Bcl-xL can inhibit the effect of Bid by interacting directly with Bax. Moreover, using mitochondria from Bax-deficient tumor cell lines, we show that Bid- induced release of cytochrome c is negligible when Bid is added alone, but dramatically increased when Bid and Bax are added together. Taken together, our results suggest that, during certain types of apoptosis, Bid translocates to mitochondria and binds to Bax, leading to a change in conformation of Bax and to cytochrome c release from mitochondria.

Animals↗

PubMed1999

Conformational preferences in a benzodiazepine series of potent nonpeptide fibrinogen receptor antagonists.

Previously, we reported the direct design of highly potent nonpeptide 3-oxo-1,4-benzodiazepine fibrinogen receptor antagonists from a constrained, RGD-containing cyclic semipeptide. The critical features incorporated into the design of these nonpeptides were the exocyclic amide at the 8-position which overlaid the Arg carbonyl, the phenyl ring which maintained an extended Gly conformation, and the diazepine ring which mimicked the gamma-turn at Asp. In this paper, we investigate conformational preferences of the 8-substituted benzodiazepine analogues by examining structural modifications to both the exocyclic amide and the seven-membered diazepine ring and by studying the conformation of the benzodiazepine ring using molecular modeling, X-ray crystallography, and NMR. We found that the directionality of the amide at the 8-position had little effect on activity and the (E)-olefin analogue retained significant potency, indicating that the trans orientation of the amide, and not the carbonyl or NH groups, made the largest contribution to the observed activity. For the diazepine ring, with the exception of the closely analogous 3-oxo-2-benzazepine ring system described previously, all of the modifications led to a significant reduction in activity compared to the potent 3-oxo-1, 4-benzodiazepine parent ring system, implicating this particular type of ring system as a desirable structural feature for high potency. Energy minimizations of a number of the modified analogues revealed that none could adopt the same low-energy conformation as the one shared by the active (S)-isomer of the 3-oxo-1, 4-benzodiazepines and 3-oxo-2-benzazepines. The overall data suggest that the features contributing to the observed high potency in this series are the orientation of the 3-4 amide and the conformational constraint imposed by the seven-membered ring, both of which position the key acidic and basic groups in the proper spatial relationship.

Benzodiazepines↗

PubMed1999

Cristobalite in volcanic ash of the soufriere hills volcano, montserrat, british west indies

Crystalline silica (mostly cristobalite) was produced by vapor-phase crystallization and devitrification in the andesite lava dome of the Soufriere Hills volcano, Montserrat. The sub-10-micrometer fraction of ash generated by pyroclastic flows formed by lava dome collapse contains 10 to 24 weight percent crystalline silica, an enrichment of 2 to 5 relative to the magma caused by selective crushing of the groundmass. The sub-10-micrometer fraction of ash generated by explosive eruptions has much lower contents (3 to 6 percent) of crystalline silica. High levels of cristobalite in respirable ash raise concerns about adverse health effects of long-term human exposure to ash from lava dome eruptions.

Journal Article↗

PubMed1999

Predator Avoidance of Transgenic Channel Catfish Containing Salmonid Growth Hormone Genes.

Transgenic channel catfish (Ictalurus punctatus) containing salmonid growth hormone genes can grow 33% faster than normal channel catfish under aquaculture conditions. However, before transgenic catfish are released and utilized by the private sector, their genetic impact on the natural environment must be examined. Predator avoidance is one of the major fitness traits determining potential environmental risk. To determine the predator avoidance ability and growth performance of transgenic catfish in a natural habitat, various densities of transgenic and nontransgenic channel catfish were communally stocked in 0.04-ha earthen ponds without supplemental feeding. Largemouth bass (Micropterus salmoides) and green sunfish (Lepomis cyanellus) were stocked as predators. Nontransgenic fry had better predator avoidance than transgenic channel catfish when data were pooled (p <.01). When data were not pooled, nontransgenic catfish had better predator avoidance in six trials and transgenic individuals had better predator avoidance in four trials. There was no difference in predator avoidance in three trials. Overall predator avoidance was also better for nontransgenic individuals (p <.01) when the fish were evaluated as 3.5-g fingerlings, more clearly than as fry, as transgenic individuals were more vulnerable in 3 of 4 trials at this life stage. There was no significant difference in growth performance between transgenic and nontransgenic channel catfish in ponds without supplemental feeding. These findings indicate that transgenic channel catfish could be used for commercial aquaculture without affecting the natural environment. Although transgenic channel catfish may be released to nature by accident, any ecological effect would be unlikely because the increased susceptibility of transgenic channel catfish to predators would most likely decrease or eliminate the transgenic genotype.

Journal Article↗