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Biomedical subjects

Thomas A Miller

Publications and source records attributed to Thomas A Miller.

36 records · Page 2Linked to original sources
PubMed2004

The spectrum of colovesical fistula and diagnostic paradigm.

BACKGROUND: Our experience with colovesical fistula (CVF) over a 12-year period was reviewed to clarify its clinical presentation and diagnostic confirmation. METHODS: Twelve patients with CVF were identified. Presenting symptoms, etiologic factors, diagnostic investigations, and subsequent treatment were reviewed. RESULTS: Underlying etiologies were diverticular disease (75%), colon cancer (16%), and bladder cancer (8%). Pneumaturia (77%) was the most common presentation, followed by urinary tract infections, dysuria and frequency (45%), fecaluria (36%), hematuria (22%), and orchitis (10%). The ability of various preoperative investigations to identify a CVF were: computed tomography (CT) (90%), barium enema (BE) (20%), and cystography (11%), whereas cystoscopy, intravenous pyelogram (IVP), and colonoscopy were nondiagnostic. All patients underwent single- or multiple-staged repair of the fistula. CONCLUSIONS: In patients with a suspected CVF, we recommend CT followed by a colonoscopy as a first-line investigation to rule out malignancy as a cause of CVF. Other modalities should only be used if the diagnosis is in doubt or additional information is needed to plan operative management.

Aged↗
PubMed2004

Electromyographic activity and strength during maximum isometric pronation and supination efforts in healthy adults.

There exists a lack of quantitative data in the literature related to the torque produced during axial forearm rotation and the electromyographic (EMG) activity of the muscles involved. Therefore, the purpose of this study was to compare the relative EMG activity of four forearm muscles during resisted forearm rotation. A custom-built device capable of measuring torque in the absence of grip was employed. Fourteen healthy volunteers performed maximum isometric voluntary contractions in five positions of axial forearm rotation for both pronation and supination. EMG data were collected simultaneously from the supinator, biceps, pronator quadratus (deep and superficial heads), and pronator teres muscles using fine-wire bipolar electrodes. Data were analyzed to determine the contributions of each muscle to pronation and supination torque over five positions of forearm rotation. In the absence of grip no significant difference was found between supination and pronation torque in neutral position. Supination torque generation was greater in the pronated forearm positions, and pronation torque was greater in the supinated positions (p<0.05). A root-mean-square EMG analysis verified the major contributions of the pronator teres and both heads of the pronator quadratus muscle to pronation torque, and supinator and biceps to supination torque. The deep head of the pronator quadratus was active during both pronation and supination, lending support to the theory that it may act primarily as a dynamic distal radioulnar joint stabilizer. This information may be helpful in upper extremity modeling, surgical treatments, and rehabilitation strategies.

Adult↗
PubMed2004

Aspirin-induced mucosal cell death in human gastric cells: evidence supporting an apoptotic mechanism.

This study was undertaken to define the role that apoptosis may play in inducing cellular injury and death in gastric mucosa exposed to aspirin. Apoptosis was characterized by DNA gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay, and DNA-histone-associated complex formation. A human gastric cell line (AGS) was exposed to physiologic concentrations (3 to 50 mM) of aspirin. Both time- and concentration-dependent effects on apoptosis were noted, which were effectively prevented by the caspase inhibitor z-VAD-fmk. Accordingly, the role of caspases in aspirin-induced apoptosis was also evaluated. Early activation of caspase-8 and caspase-9 was demonstrated, indicating a role for both receptor and mitochondrial pathways, respectively, in the apoptotic process. Corresponding activation of effector caspases-3, -6, and -7 was also evident, as was cleavage of PARP. We conclude that physiologically relevant concentrations of aspirin induces apoptosis in human gastric cells through a caspase-mediated mechanism.

Apoptosis↗
PubMed2003

An unusual dinuclear ruthenium(III) complex with a conjugated bridging ligand derived from cleavage of a 1,4-dihydro-1,2,4,5-tetrazine ring. Synthesis, structure, and UV-vis-NIR spectroelectrochemical characterization of a five-membered redox chain incorporating two mixed-valence states.

Reaction of [Ru(acac)(2)(CH(3)CN)(2)] with 3,6-bis(3,5-dimethylpyrazol-1-yl)-1,4-dihydro-1,2,4,5-tetrazine (H(2)L) results in formation of an unexpected dinuclear complex [(acac)(2)Ru(III)(L(1))Ru(III)(acac)(2)] (1) in which the bridging ligand [L(1)](2)(-) contains an (-)HN[bond]C[double bond]N[bond]N[double bond]C[bond]NH(-) unit arising from two-electron reduction of the 1,4-dihydro-1,2,4,5-tetrazine component of H(2)L. The crystal structure of complex 1 confirms the oxidation assignment of the metal ions as Ru(III) and clearly shows the consequent arrangement of double and single bonds in the bridging ligand, which acts as a bis-bidentate chelate having two pyrazolyl/amido chelating sites. Cyclic voltammetry of the complex shows the presence of four reversible one-electron redox couples, assigned as two Ru(III)/Ru(IV) couples (oxidations with respect to the starting material) and two Ru(II)/Ru(III) couples (reductions with respect to the starting material). The separation between the two Ru(III)/Ru(IV) couples (Delta E(1/2) = 700 mV) is much larger than that between the two Ru(II)/Ru(III) couples (Delta E(1/2) = 350 mV) across the same bridging pathway, because of the better ability of the dianionic bridging ligand to delocalize an added hole (in the oxidized mixed-valence state) than an added electron (in the reduced mixed-valence state), implying some ligand-centered character for the oxidations. UV-vis-NIR spectroelectrochemical measurements were performed in all five oxidation states; the Ru(II)-Ru(III) mixed-valence state of [1](-) has a strong IVCT transition at 2360 nm whose parameters give an electronic coupling constant of V(ab) approximately 1100 cm(-1), characteristic of a strongly interacting but localized (class II) mixed-valence state. In the Ru(III)-Ru(IV) mixed-valence state [1](+), no low-energy IVCT could be detected despite the strong electronic interaction, possibly because it is in the visible region and obscured by LMCT bands.

Journal Article↗
PubMed2003

Apoptosis is a major mechanism of deoxycholate-induced gastric mucosal cell death.

This study was undertaken to determine whether necrosis or apoptosis was the predominant mechanism responsible for gastric mucosal cellular death using the cell line known as AGS cells. Cells were exposed to various concentrations of deoxycholate (DC; 50-500 muM) for periods ranging from 30 min to 24 h. Lactic dehydrogenase (LDH) activity was used as a marker for necrotic cell death, whereas apoptosis was characterized by 4',6-diamidino-2 phenylindole staining, DNA gel electrophoresis, terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and DNA-histone-associated complex formation. When cells were bathed in Hank's balanced salt solution, DC-induced necrosis was the predominant mechanism of cell death. In contrast, when cells were bathed in Ham's F-12 solution (a more physiologically relevant medium), no evidence of cytotoxicity (by LDH assay) was discernible when cells were exposed to DC (50-300 muM) for periods as long as 8 h; instead, clear evidence of apoptosis was noted that was time and dose dependent. When cells were exposed for 24 h to these DC concentrations, cytotoxicity was also present, indicating necrosis as well. Furthermore, acidification of the ambient environment also evoked a necrotic response when exposed to DC. We demonstrated that apoptosis induced by DC shows early activation of caspase-3 that is dependent on both receptor and mitochondrial pathways. Our results indicate that physiological concentrations of DC (50-300 muM) primarily induce cellular death through an apoptotic process. Only after prolonged exposure to DC or acidification of the bathing solution does necrosis also occur.

Acids↗
PubMed2003

Regulation of neuregulin/ErbB signaling by contractile activity in skeletal muscle.

Putative roles of neuregulin (NRG) and the ErbB receptors in skeletal muscle biology include myogenesis, ACh receptor expression, and glucose transport. To date, however, the physiological regulation of NRG/ErbB signaling has not been examined. We tested the hypothesis that contractile activity in vivo induces NRG/ErbB activation. Rat hindlimb muscle contraction was elicited with a single bout of electrical stimulation (RX) or treadmill running (EX). Western blot and immunofluorescence confirmed the expression of multiple NRG isoforms and the ErbB2, ErbB3, and ErbB4 receptors in adult skeletal muscle. Both RX and EX significantly increased phosphorylation of all NRG receptors. Furthermore, contraction induced a shift in the expression profile of NRG, consistent with proteolytic processing of a transmembrane isoform. Thus two distinct modes of exercise activated processing of NRG with concomitant stimulation of ErbB2, ErbB3, and ErbB4 signaling in vivo. To our knowledge, this is the first demonstration of physiological regulation of NRG/ErbB signaling in any organ and implicates this pathway in the metabolic and proliferative responses of skeletal muscle to exercise.

Animals↗
PubMed2003

Wolbachia infections of the whitefly Bemisia tabaci.

We report the first systematic survey for the presence of Wolbachia endosymbionts in aphids and whiteflies, particularly different populations and biotypes of Bemisia tabaci. Additional agriculturally important species included were predator species, leafhoppers, and lepidopterans. We used a polymerase chain reaction (PCR)-based detection assay with ribosomal 16S rDNA and Wolbachia cell surface protein (wsp) gene primers. Wolbachia were detected in a number of whitefly populations and species, whitefly predators, and one leafhopper species; however, none of the aphid species tested were found infected. Single, double, and triple infections were detected in some of the B. tabaci populations. PCR and phylogenetic analysis of wsp gene sequences indicated that all Wolbachia strains found belong to group B. Topologies of the optimal tree derived by maximum likelihood (ML) and a ML tree in which Wolbachia sequences from B. tabaci are constrained to be monophyletic are significantly different. Our results indicate that there have been at least four independent Wolbachia infection events in B. tabaci. The importance of the presence of Wolbachia infections in B. tabaci is discussed.

Animals↗
PubMed2003

Ring A-seco mosquito larvicidal limonoids from Turraea wakefieldii.

Five novel limonoids, 1-5, were isolated from the root bark of Turraea wakefieldii and were characterized as tecleaninoid derivatives. This is the first report of the natural occurrence of tecleanin-type limonoids with a five-membered-ring A-seco structure for which we propose the name neotecleanins. The relative stereochemical structures of compounds 1-5 were established on the basis of NMR spectroscopy. The absolute stereochemical structure of 5 was confirmed by X-ray diffraction methods. In mosquito larvicidal assays, compounds 1, 2 and 4 showed dose-dependent larvicidal activity against larvae of Anopheles gambiae s.s.

Animals↗
PubMed2003

Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt.

We have found that neuregulin-1beta (NRG-1beta) is expressed in the cardiac microvascular endothelium, and promotes the growth and survival of cardiac myocytes in culture through the activation of erbB2 and erbB4 receptor tyrosine kinases. In this study, we examined the role of NRG-1/erbB signaling in protection of cardiac myocytes from anthracycline-induced apoptosis in vitro to determine the coupling between erbB receptor subtypes and cytoprotective signaling. Treatment of neonatal rat ventricular myocytes with NRG-1beta inhibited daunorubicin-induced apoptosis as shown by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling staining for DNA fragmentation as well as flow cytometric quantification of apoptotic myocytes. Daunorubicin-induced activation of caspase-3 in cardiomyocytes was similarly inhibited by NRG-1beta. The phosphoinositol-3-kinase (PI3-kinase) inhibitor wortmannin prevented the effects of NRG-1beta on daunorubicin-induced apoptosis and activation of caspase-3. NRG-1beta treatment induced rapid activation of Akt/PKB that was inhibited by wortmannin, and adenoviral-mediated overexpression of a dominant-negative Akt prevented the protective effect of NRG-1beta. Akt activation by NRG-1beta was prevented by the tyrphostin AG1478, which we show inhibits erbB4 activation by NRG-1beta. In contrast, the erbB2-specific tyrphostin AG879 had no effect on NRG-1beta activation of Akt. Myocyte treatment with an activating antibody to erbB2 caused phosphorylation of erbB2, and led to activation of Erk but not Akt. Treatment with the erbB2 antibody had no effect on anthracycline-induced apoptosis. Thus, NRG-1beta protects against anthracycline-induced apoptosis via erbB4-dependent activation of the PI3-kinase/Akt pathway.

Adenoviridae↗
PubMed2003

Conversion of cholic acid to methyl 3alpha-carbethoxy-12alpha-acetoxy-6-oxo-5beta-chol-7-en-24-oate.

A new and efficient method for preparation of a 7-en-6-one derivative of cholic acid is described. Acetylation of the known methyl 3alpha-carbethoxy-12alpha-hydroxy-7-oxo-5beta-cholan-24-oate (3) at 12 position and reduction of its 7-oxo group yield the 12alpha-acetoxy-7alpha-hydroxy derivative 5. Dehydration of the 7alpha-hydroxy group in 5 followed by allylic oxidation provide methyl 3alpha-carbethoxy-12alpha-acetoxy-6-oxo-5beta-chol-7-en-24-oate (7) in good yield.

Chemistry, Organic↗
PubMed2002

Modulation of anthracycline-induced myofibrillar disarray in rat ventricular myocytes by neuregulin-1beta and anti-erbB2: potential mechanism for trastuzumab-induced cardiotoxicity.

BACKGROUND: There is an increased incidence of heart failure in patients treated concurrently with anthracyclines and the chemotherapeutic anti-erbB2 agent trastuzumab (Herceptin). On the basis of our previous studies with recombinant neuregulin-1beta (NRG-1beta), a ligand for the erbB2 receptor tyrosine kinase, we hypothesized that activation of erbB2 by anti-erbB2 versus NRG-1 would cause differential effects on myocyte intracellular signaling as well as anthracycline-induced myofibrillar injury and might potentially account for the clinical toxicity of trastuzumab in the setting of concurrent anthracycline therapy. METHODS AND RESULTS: We tested this hypothesis using adult rat ventricular myocytes (ARVMs) in culture, assessing myofibrillar structure by immunostaining for myomesin and filamentous actin. Activation of erbB2, extracellular signal-regulated kinase 1/2 (Erk1/2), and Akt was assessed by use of antibodies to phosphorylated activated receptor or kinase detected by immunoblot. ARVMs treated with doxorubicin (0.1 to 0.5 micromol/L) showed a concentration-dependent increase in myofilament disarray. NRG-1beta (10 ng/mL) activated erbB2, Erk1/2, and Akt in ARVMs and significantly reduced anthracycline-induced disarray. In contrast to NRG-1beta, anti-erbB2 (1 microg/mL) caused rapid phosphorylation of erbB2 but not Erk1/2 or Akt, with downregulation of erbB2 by 24 hours. Concomitant treatment of myocytes with anti-erbB2 and doxorubicin caused a significant increase in myofibrillar disarray versus doxorubicin alone. CONCLUSIONS: NRG-1beta/erbB signaling regulates anthracycline-induced myofilament injury. The increased susceptibility of myofilaments to doxorubicin in the presence of antibody to erbB2 may explain the contractile dysfunction seen in patients receiving concurrent trastuzumab and anthracyclines.

Actin Cytoskeleton↗
PubMed2002

Transformed bacterial symbionts re-introduced to and detected in host gut.

Strains of Enterobacter agglomerans and Klebsiella pneumoniae isolated from Rhagoletis completa Cresson were engineered to express transgenic fluorescent proteins (ECFP, DsRed). These bacteria were introduced into flies by feeding the flies a sucrose solution in which the bacteria were suspended. The transgenic and heterologous marker protein was expressed and visible in the bacteria after they were ingested by WHF and while they were in the fly gut. We describe the plasmids used to transform these bacteria and demonstrate expression of heterologous proteins from the transforming plasmids and discuss the implications for future pest control strategies.

Animals↗
PubMed2002

Transformation of Enterobacter gergoviae isolated from pink bollworm (Lepidoptera: Gelechiidae) gut with Bacillus thuringiensis toxin.

Production of molecules with toxic activity by genetically transformed symbiotic bacteria of pest insects may serve as a powerful approach to biological control. The symbiont, Enterobacter gergoviae, isolated from the gut of the pink bollworm (PBW), has been transformed to express Cyt1A, a cytolytic protein toxin lethal to mosquito and black fly larvae, as a model system. These transgenic bacteria might be used to spread genes encoding insecticidal proteins to populations of agricultural insects or as replacement for chemical insecticides such as malathion used in bait formulation to control specific insect pests, because of extreme public pressure against organophosphate pesticide spraying.

Animals↗
PubMed2002

Gastric surgery.

Most significant research relating to gastric surgery in the past year has centered on surgery for gastroesophageal reflux disease (GERD). Antireflux surgery has become more popular with advanced laparoscopic technology. Two previously accepted surgical principles have been challenged by current studies: the importance of division of the short gastrics and the dictum that partial fundoplication is preferred for patients at risk for dysphagia. Additionally, risk factors for postoperative dysphagia have been identified, allowing for better patient selection and education. Further study on the cause of GERD has shown a positive correlation between pathologic gastroesophageal reflux and those with hiatal hernia or disordered esophageal peristalsis, although cause or effect has not yet been established. Literature relating to bariatric surgery has confirmed the safety and efficacy of the laparoscopic Roux-en-Y gastric bypass, and several papers address the appropriateness of prophylactic cholecystectomy in these patients. The role of laparoscopic surgery for treatment of perforated peptic ulcer disease has now been validated, with subsequent eradication of Helicobacter pylori infection. The relationship of H. pylori infection to acutely bleeding ulcers is less clear. Indications for ulcer surgery are predominantly limited now to perforation and bleeding because of the availability of effective acid-reducing medications and recognition of the role of H. pylori infection.

Journal Article↗
PubMed2002

Evaluation of rehabilitation outcomes in older patients with hip fractures.

OBJECTIVE: This study evaluated functional outcomes in patients with hip fracture after inpatient rehabilitation. DESIGN: The physical and cognitive functioning of 100 patients with hip fracture were determined by using the FIM instrument. The Montebello rehabilitation factor score was used to reflect rehabilitative outcome. Follow-up data were collected from 44 patients by using a telephone FIM interview. RESULTS: Discharge total FIM scores improved. The Montebello rehabilitation factor score for rehabilitation efficacy and efficiency scores both demonstrated improvement for patient function during inpatient rehabilitation. The mean motor FIM domain scores for transfer mobility and locomotion were lower at discharge compared with the domains of self-care and sphincter control. A subgroup of 44 patients showed no change in mean motor FIM domain scores. CONCLUSIONS: Inpatient rehabilitation improves overall functional independence as measured by the FIM instrument. Relative change, as measured by the Montebello rehabilitation factor score, indicated that rehabilitation outcome for locomotion was not maximized, despite exhibiting large absolute gains during inpatient rehabilitation. The improvements demonstrated at discharge were maintained at follow-up for a subgroup of 44 patients. Improved locomotion skills and maximizing ability to transfer independently are areas in which inpatient rehabilitation may be targeted to improve function in the future.

Aged↗