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Biomedical subjects

D M Harris

Publications and source records attributed to D M Harris.

At least 19 recordsLinked to original sources
PubMed2003

Effects of cyclo (his-pro) plus zinc on glucose metabolism in genetically diabetic obese mice.

AIMS: The specific objective of this study was to determine acute and long-term effects of cyclo (his-pro) (CHP) plus zinc and l-histidine (CZH) treatment on glucose metabolism in genetically obese (ob/ob), type 2 diabetic mice. METHODS: Acute effects of 0.3 mg of CHP plus 10 mg of zinc and 0.5 mg of l-histidine/kg body weight (BW) on fed blood glucose concentrations and 3-h average of above fasting blood glucose concentrations (TAFGCs), an index of oral glucose tolerance test, in lean and ob/ob mice were determined. To evaluate long-term effects of CZH on TAFGCs, lean and ob/ob mice were treated with drinking water containing increasing doses of CHP (0, 0.5, 1.0 or 1.5 mg/l) plus 10 mg zinc and 0.5 mg of l-histidine/l for 3 weeks. During the treatment period, fed blood glucose concentrations, BW and food and water intake were determined. At the end of the treatment, fasting blood glucose concentrations, TAFGC and fed plasma insulin concentrations were determined. RESULTS: Blood glucose concentrations significantly decreased when CZH was administered acutely via gastric gavage in food-deprived ob/ob mice. Similarly, 1.0 mg/l CHP treatment of mice with fixed amounts of 10 mg zinc and 0.5 mg l-histidine/l was optimal to decrease fed blood glucose and plasma insulin concentrations during a 3-week treatment period in ob/ob mice. TAFGC values in these mice also improved most significantly with the same combination of CHP, zinc and l-histidine used to test for fed blood glucose and plasma insulin levels. Fasting blood glucose concentrations and BW gains also decreased in ob/ob mice treated with 1.0 mg of CHP/l plus the same amount of zinc and l-histidine used in the above experiments. No effects of CZH treatment in lean mice were observed. CONCLUSIONS: CZH is effective in decreasing blood glucose concentrations in genetically obese (ob/ob), type 2 diabetic mice. These data support our working hypothesis that CZH may be an important anti-hyperglycaemic agent.

Animals↗
PubMed2002

Effects of arachidonic acid plus zinc on glucose disposal in genetically diabetic (ob/ob) mice.

AIM: The present study is designed to determine whether arachidonic acid (AA) plus zinc improves clinical signs of diabetes in genetically diabetic ob/ob mice. METHODS: In the first study, effects of acute administration of AA plus zinc on glucose disposal were determined in ob/ob and lean mice (n = 6 each). In the second study, ob/ob and lean mice were treated with increasing doses of AA plus zinc for 2 weeks (n = 5 each). Postprandial and fasting blood glucose concentrations, three-hour-area-average above fasting glucose concentration (TAFGC), water and food intake, body weight and plasma insulin concentrations were measured. RESULTS: Acute administration of AA plus zinc significantly increased glucose disposal in ob/ob mice. In the second study, postprandial and fasting blood glucose concentrations, TAFGC, and water and food intake in ob/ob mice treated with AA plus zinc for 2 weeks were significantly decreased compared with those in mice given no AA. Plasma insulin concentrations in both lean and ob/ob mice were not changed by AA treatment in drinking water. CONCLUSIONS: AA plus zinc in drinking water is effective in decreasing blood glucose levels in obese mice. These results indicate that use of these compounds should be considered as a dietary supplement to control hyperglycaemia in patients with type II diabetes.

Animals↗
PubMed2002

Stimulation of amylase release by Orexin is mediated by Orexin 2 receptor in AR42J cells.

INTRODUCTION AND AIMS: Orexins have been demonstrated to have mainly central physiological functions, including regulation of food and water intake, sleep, and arousal. However, little is known about their direct peripheral effects, if any. As a first step toward understanding the role of Orexin in non-neuronal tissues or cells, we initiated studies to examine expression of Orexin receptors (OXR) in an established pancreatic tumor cell line AR42J. Secondly, we wanted to determine whether Orexins, in various molecular forms, are active to stimulate any known pancreatic cell functions in AR42J cells. METHODOLOGY: Reverse transcription-PCR analysis was performed to identify the presence of specific Orexin receptor subtypes. Intracellular calcium mobilization and cAMP levels were measured following stimulation by Orexin A and B peptides, their respective C-terminal decapeptide fragments, and hypocretin-2-gly (glycine-extended Orexin B). Release of alpha-amylase was measured in conditioned media after acute stimulation with the set of Orexin peptides for 30 minutes. Cell proliferation was determined by H-thymidine incorporation after 24 hours following treatment with Orexins under serum-free condition. RESULTS: RT-PCR and sequencing results showed that Orexin receptor subtype 2 (OX2R) was the main form expressed in AR42J cells. Orexins stimulated dose-dependent increases in intracellular calcium mobilization with EC50 0.05 nM for Orexin A and 0.1 nM for Orexin B but were unable to stimulate any significant cAMP accumulation or DNA synthesis even at micromolar concentrations. Both Orexin-A and -B, but not hypocretin-2-gly, also stimulated dose-dependent increases in amylase release in the AR42J cells. Orexin-A and -B carboxyl-terminal decapeptides elicited significant but much lower calcium and amylase responses. CONCLUSION: Our data demonstrate that OX2R mediates Ca -dependent amylase release in AR42J cells, suggesting that Orexins may have secretory functions in pancreatic tumor cells.

Amino Acid Sequence↗
PubMed2002

Control of foot and mouth disease: lessons from the experience of the outbreak in Great Britain in 2001.

An epidemic of foot and mouth disease occurred on an unprecedented scale in Great Britain in 2001. This was characterised by widespread dissemination of disease in sheep due to infection being present but unreported for at least three weeks before the first case was identified. As envisaged by the contingency plans, existing procedures dealt rapidly with disease in many parts of the country where outbreaks were reported. Elsewhere, the scale and speed of disease spread was so great that veterinary resources had to be supplemented on the operational front by a large influx of military and administrative support. At the time of writing (June 2002), the United Kingdom Government has already identified a number of key lessons, and will learn further from this experience and from the findings of inquiries, how a future outbreak of this unprecedented nature and extent could be handled. Lessons identified so far relate to the improvement of contingency plans, the wider impact on rural businesses and communities, reassessing the possible use of emergency vaccination, the availability of serological capacity, better animal identification and movement controls, carcass disposal, communications, data handling and management information. The authors present the initial lessons learned and which formed the basis of official submissions to the inquiries. Further lessons will be learned from the findings of those inquiries.

Animals↗
PubMed2001

Synergistic antidiabetic activities of zinc, cyclo (his-pro), and arachidonic acid.

Previous studies have already shown that prostate extract (PE) has antidiabetic activity when given to animals and humans. In this study, we explore whether this antidiabetic activity is related to the high concentrations of zinc, cyclo (his-pro) (CHP), and the prostaglandin precursor, arachidonic acid (AA), in prostate tissue. When streptozotocin-induced diabetic rats were given drinking water containing 10 mg/L zinc and 100 mg/L PE for 3 weeks, fasting blood glucose levels and glucose clearance rates, but not plasma insulin levels, were significantly lower than at pretreatment. In subsequent experiments, blood glucose levels in rats given PE for 3 weeks were significantly lower than in rats given distilled water or 10 mg/L zinc alone. However, in rats given 100 mg/L CHP with zinc, blood glucose levels were also lower than in rats given PE alone. Time-course studies in diabetic rats given drinking water containing 20 mg/L Zn, 20 mg/L L-histidine, and 10 mg/L CHP showed that blood glucose levels dropped 209 +/- 53 mg/dL in 1 day and stayed low for 2 weeks. When CHP was replaced with 100 mg AA/L, blood glucose levels dropped 230 +/- 64 mg/dL in 5 days, but returned to the original values 11 days later. Growth rate improved and water consumption decreased significantly in CHP- and AA-treated diabetic rats. High intake of L-histidine and testosterone increased blood glucose concentrations in diabetic rats. To determine optimal dosages of CHP and AA, we gave rats drinking water containing 10 mg/L Zn and 0.5 mg/L L-histidine with various concentrations of CHP or AA. The most effective doses for reducing blood glucose levels were 0.32 mg CHP/kg/day and 11 mg AA/kg/day. These data suggest that the active antidiabetic ingredients in the PE are CHP, zinc, and AA or its precursors.

Animals↗
PubMed1999

Eyelid resurfacing.

BACKGROUND AND OBJECTIVE: Laser resurfacing of eyelids was examined in a series of experiments designed to measure beam parameters, surface temperatures, ablation characteristics, thermal damage, tissue responses and clinical outcomes. These data were collected for the purpose of developing a logical basis for clinical dosimetry. STUDY DESIGN: All experiments were conducted with similar short-pulse CO(2) lasers (TruPulse, Albuquerque, NM) where the beam had been carefully characterized and calibrated. The chronological sequence examined begins with the photophysical laser/tissue interactions during the first few microsec of irradiation and ends with an evaluation of the efficacy of wrinkle reduction nine months after treatment. RESULTS: Eyelid tissue removed by the first and second passes consisted mostly of epidermis with about 38 microm of thermal damage into the papillary dermis. Erythema resolved within four weeks and most patients experienced 70-100% wrinkle reduction by nine months. CONCLUSION: A layer of contracted dermal scar tissue that replaced the thermally challenged zone in the dermis is identified as the substrate for wrinkle reduction. The data support the following dosimetry for periorbital wrinkle reduction: One pass 4-6 J/cm(2) (350-500 mJ into a 3 x 3 mm spot). A second treatment after 9-12 months may be more beneficial than a second pass.

Animals↗
PubMed1999

Regulation of cholecystokinin-mediated amylase secretion by leptin in rat pancreatic acinar tumor cell line AR42J.

Expression of the long form of the leptin receptor, the isoform that is considered to have full signaling capability, has been reported in the central nervous system and several peripheral cell types. However, only a few cell lines have been shown to express the long form of the receptor. AR42J, a cell line derived from azaserine-treated rat pancreas, is a common model for pancreatic acinar cell secretion. In this study, the presence of leptin-receptor variants and leptin action was evaluated in this cell line. Messenger RNAs for both the long and a short form of the leptin receptor were detected by reverse transcription-polymerase chain reaction (RT-PCR) in AR42J cells, and authenticity of the receptor was confirmed by DNA sequencing. Competitive binding studies demonstrated that binding of radiolabeled leptin was specific and did not cross-react with cholecystokinin (CCK). Biologic effects of leptin on amylase release and intracellular calcium mobilization were further assessed in the presence and the absence of CCK, a known pancreatic secretagogue. Although leptin alone (< or =200 ng/ml) did not affect basal amylase release, it inhibited amylase release stimulated by 1 nM CCK by 48%. Leptin alone had no significant effect on calcium mobilization. However, pretreatment of leptin (10 and 100 ng/ml) enhanced calcium responses stimulated by CCK. These data demonstrate that the rat pancreatic tumor cell line AR42J expresses a functional form of the leptin receptor that modulates the action of CCK in calcium mobilization and amylase release.

Amylases↗
PubMed1999

The Arabidopsis homolog of yeast TAP42 and mammalian alpha4 binds to the catalytic subunit of protein phosphatase 2A and is induced by chilling.

Type 2A serine/threonine protein phosphatases (PP2A) have been implicated as important mediators of a number of plant growth and developmental processes. In an effort to identify plant PP2A substrates and/or regulators, we performed a yeast two-hybrid screen using an Arabidopsis PP2A catalytic subunit cDNA as bait. All true positives identified by this screen were derived from the same gene, which we have named TAP46 (2A phosphatase associated protein of 46 kD). The TAP46 gene appears to be a single-copy gene and is expressed in all Arabidopsis organs. Transcripts derived from this gene are induced by chilling treatment but not by heat or anaerobic stress. Immunoprecipitation assays using antibodies generated to a peptide spanning amino acids 356 to 366 of TAP46 indicate that TAP46 is associated with a type 2A protein phosphatase in vivo. A search of the database identified TAP46 as a homolog of Saccharomyces cerevisiae TAP42 and mammalian alpha4. These two proteins are known to bind to the catalytic subunit of PP2A and to function in the target-of-rapamycin signaling pathway. Our results identify TAP46 as a plant PP2A-associated protein, with a possible function in the chilling response, and suggest that a target-of-rapamycin-like signaling pathway may exist in plants.

Adaptor Proteins, Signal Transducing↗
PubMed1998

A rapid assay of endotoxin in whole blood using autologous neutrophil dependent chemiluminescence.

A rapid (30 min) whole blood assay for the detection of lipopolysaccharide (LPS) is described. This chemiluminescent (CL) assay utilizes the CR1 and CR3 receptor-induced oxidant production of polymorphonuclear leucocytes as a detection platform. The differential priming of neutrophils in whole blood by LPS-antibody complexes allows the specificity of the assay to be achieved. Oxidant released in response to complement opsonized zymosan results in luminol oxidation and subsequent light emission. This is dependent on heat labile putative complement proteins in the plasma. The assay consists of a control which measures baseline whole blood neutrophil oxidant production. The test assay contains murine monoclonal IgM antibody against the Lipid A epitope of LPS and measures the enhanced chemiluminescent response of the neutrophils in the presence of LPS-antibody complexes. Maximal sensitivity of the CL assay is dependent upon optimal antigen-antibody equivalence and duration of pre-incubation with the whole blood sample. The quantification of LPS is possible by inclusion of a positive control containing a maximally reactive LPS dose (800 pg/ml Escherichia coli 055:B5 LPS at an antibody concentration of 0.8 microg/assay). The CL assay is insensitive to variations in patient neutrophil concentration over a minimum range of 0.5 to 20 x 10(9) cells/l. The CL assay is widely reactive with the LPS of many strains of gram negative bacteria but not with the cell wall products of gram positive bacteria or Candida and Aspergillus. In comparison to acid extraction chromogenic LAL, the CL assay demonstrates superior recovery precision and accuracy in in vitro studies. This was reproducible over a wide range of LPS concentrations (0.017-1.6 EU/ml or 20-2000 pg/ml). This assay may be a clinically useful tool for the diagnosis of infection or endotoxin in patients.

Antibodies, Bacterial↗
PubMed1997

Differential expression of three Arabidopsis genes encoding the B' regulatory subunit of protein phosphatase 2A.

Numerous plant processes ranging from signal transduction to metabolism appear to be mediated, in part, by type 2A protein serine/threonine phosphatases (PP2A). In an effort to identify factors that control the activity of this enzyme in plants, we have isolated and characterized DNA sequences encoding the B' regulatory subunit of PP2A from Arabidopsis thaliana. Specifically, we used PCR to amplify a segment of Arabidopsis cDNA that encodes a conserved section of the B' polypeptide. This PCR fragment was subsequently used as a probe to screen an Arabidopsis cDNA library and cDNA clones derived from three distinct genes were identified. The AtB' alpha and AtB' beta genes encode highly similar 57-kDa B' regulatory subunits while the third gene, AtB' gamma, encodes a more divergent 59-kDa B' protein. A comparison of the three Arabidopsis B' polypeptides to those of yeast and animals shows the core region of this protein to be the most conserved while the amino and carboxy termini vary both in length and sequence. Genomic Southern blots indicate that at most the Arabidopsis genome contains five genes encoding the B' regulatory subunit. The three genes identified in this study are expressed in all Arabidopsis organs, albeit at varying levels. In addition, mRNAs derived from the three genes accumulate differentially in response to heat shock. Our results indicate that the activity of plant PP2A might be regulated by a B' type regulatory subunit similar to those found in animals and yeast, and suggest possible roles for B'-containing PP2A complexes within plant cells.

Amino Acid Sequence↗
PubMed1997

Laser ablation as a function of the primary absorber in dentin.

BACKGROUND AND OBJECTIVE: Infrared transmission spectra of dentin reveal a broad absorption band between 6.0 and 7.0 microns composed of absorption peaks of water, collagen and carbonated hydroxyapatite. The nearly constant absorption and the existence of absorption peaks of different tissue components were used to investigate ablation as a function of the primary absorber. STUDY DESIGN/MATERIALS AND METHODS: Laser ablation of dentin as a function of fluence was studied in the wavelength range between 6.0 and 7.5 microns using the Vanderbilt Free-Electron Laser (FEL). Depth and volume of the ablation crater were determined with a silicon replica method and subsequent confocal laser topometry. SEM investigations were performed on the irradiated surfaces. For the description of the experimental data an ablation model is developed. RESULTS: At all applied wavelengths we found a linear increase of ablation depth as a function of fluence above a threshold fluence. The lower absorption of dentin at 7.5 microns compared to the absorption at 6.0, 6.5 and 7.0 microns results in a greater ablation threshold. At 6.0, 6.5 and 7.0 microns wavelengths the ablation thresholds are comparable. The experimental data are in good agreement with an ablation model using a mean absorption coefficient of the target material. No thermal cracking is observed after ablation in dentin. The post ablative surface structure at 6.0 and 7.0 microns looks similar whereas at 7.5 microns the surface reveals a greater roughness. CONCLUSION: The ablation efficiency and threshold depend on the mean absorption but do not depend upon the chemical identity of the primary absorber in dentin. Calculations show that heat conduction during the laser pulse leads to a thermal equalization between the heated microstructures and surrounding tissue resulting in an ablation with little dependence on the primary absorber.

Absorption↗
PubMed1997

Multi-unit mapping of acoustic stimuli in gerbil inferior colliculus.

Multi-unit peristimulus time (MU-PST) histograms were recorded in the gerbil inferior colliculus (IC) in response to tone burst stimuli. Histograms were collected every 100 microns as the recording electrode was advanced along the tonotopic axis of the central nucleus of the IC. Space/time maps of neural activity were constructed from these data. In most of our sample the pattern of response changed systematically as the stimulating frequency was increased in octave steps. At low frequencies (< 500 Hz) the pattern of response was broadly distributed spatially and phase-locked to the stimulus frequency. At higher frequencies (> 1 kHz) the pattern of response was more localized and showed no evidence of phase locking. The location of the maximum response to tones from 1 to 32 kHz moved ventrally along the tonotopic axis at an approximate rate of 230 microns/stimulus octave. The patterns of response were localized near stimulus threshold and spread over a larger region as level increased. This method of collecting and displaying multi-unit response maps provides an overview of ensemble activity that allows concurrent observation of spatial and temporal variations in activity patterns. The quantitative analysis of components of MU-PST Maps are consistent with trends illustrated with single-unit tuning and level functions. This perspective of IC activity suggests potential processing mechanisms that are congruent with single-unit reconstructions.

Acoustic Stimulation↗
PubMed1997

Physician and plan effects on satisfaction of Medicaid managed care patients with their health care and providers.

As many Medicaid patients move into managed care, it is important that physicians competing to serve these patients understand the factors that lead to patient satisfaction. This study uses survey data from 7,313 Oregon Medicaid managed care patients to create a model describing how provider effects and health plan effects relate to patients' satisfaction with their medical care and provider. Path analysis was used to test the explanatory power and strength of relationships in the model. Perceived technical and interpersonal physician quality and health plan rating were most strongly linked with these patients' satisfaction with their care and provider.

Analysis of Variance↗
PubMed1995

Selective impairment of the retrieval of people's names: a case of category specificity.

Recent cases of 'proper names anomia' have been interpreted as arising from a category-specific recall deficit that is mediated either by the effects of 'uniqueness', or 'meaningfulness'. However, an alternative account is suggested by the report of a patient whose difficulties in naming familiar people arise from a selective learning impairment. The current case study presents data that are inconsistent with a learning interpretation of difficulties in naming people. We conclude that a dissociation exists between selective deficits affecting the learning and recall of people's names.

Aged↗
PubMed1995

I recognize your face but I can't remember your name: is it because names are unique?

Burton & Bruce (1992), and Cohen (1990a), offer alternative accounts of the differences in 'normal' and neurologically impaired subjects' abilities to recall people's names and other pieces of biographical information. Cohen claims that the principal difference between names and other biographical information is in their relative meaningfulness, while Burton & Bruce argue that uniqueness is the crucial variable. As yet existing empirical evidence cannot be explained within the framework of either of these accounts, although the Burton & Bruce (1992) proposal has the advantage of being implemented as an interactive activation model. This paper describes the case of a patient who, following a stroke, retained the ability to access 'unique' semantic information for familiar people she is no longer able to name. It is argued that this pattern of performance provides difficulties for the Burton & Bruce model. However, it can be accounted for by Cohen's account, and a modified version of Burton & Bruce's model (Bruce, Burton & Walker, 1994).

Aged↗
PubMed1995

Effect of somatotropin treatment on lipogenesis, lipolysis, and related cellular mechanisms in adipose tissue of lactating cows.

The effect of bST on the metabolism of lipid in adipose tissue was studied using tissue biopsies from lactating cows treated with bST for 8 d. Cows responded to treatment by increasing daily milk yield by 10.9 kg, although net energy intake was not changed. Thus, net energy balance was changed from highly positive to slightly negative (+7.7 to -1.1 Mcal/d). Consistent with these changes in net energy balance, lipogenesis rates were dramatically reduced (97%) in adipose tissue from bST-treated cows. Activities of acetyl-coenzyme A carboxylase (initial and total) and fatty acid synthase were also dramatically decreased. Therefore, for cows in positive energy balance, reduced lipid synthesis in adipose tissue represents a major mechanism whereby bST alters nutrient partitioning to support greater milk synthesis. Treatment with bST had no effect on beta-adrenergic-stimulated lipolysis in adipose tissue explants incubated in vitro with adenosine deaminase. However, bST treatment reduced the ability of adenosine to inhibit lipolysis in adipose tissue, which involved changes in both sensitivity and responsiveness to adenosine. Therefore, the enhanced lipolytic response to catecholamine in vivo with bST treatment relates to relief in the adenosine inhibitory signaling cascade rather than to a direct effect on the stimulatory signaling pathway.

Adipose Tissue↗
PubMed1994

A hospital study of ice-making machines: their bacteriology, design, usage and upkeep.

Ice-making machines have occasionally been implicated in nosocomial infection. We have examined the ice-making machines in our hospital both bacteriologically and for their general state of cleanliness and repair. Results were variable but, in most cases few organisms of significance were found. Some design features are considered and recommendations for the purchase, maintenance, cleaning and use of these machines are included.

Cross Infection↗