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Biomedical subjects

Matthew Jones

Publications and source records attributed to Matthew Jones.

At least 19 recordsLinked to original sources
PubMed2006

Neural dynamics for facial threat processing as revealed by gamma band synchronization using MEG.

Facial threat conveys important information about imminent environmental danger. The rapid detection of this information is critical for survival and social interaction. However, due to technical and methodological difficulties, the spatiotemporal profile for facial threat processing is unknown. By utilizing magnetoencephalography (MEG), a brain-imaging technique with superb temporal resolution and fairly good spatial resolution, Synthetic Aperture Magnetometry (SAM), a recently developed source analysis technique, and a sliding window analysis, we identified the spatiotemporal development of facial threat processing in the gamma frequency band. We also tested the dual-route hypothesis by LeDoux who proposed, based on animal research, that there are two routes to the amygdala: a quick subcortical route and a slower and cortical route. Direct evidence with humans supporting this model has been lacking. Moreover, it has been unclear whether the subcortical route responds specifically to fearful expressions or to threatening expressions in general. We found early event-related synchronizations (ERS) in response to fearful faces in the hypothalamus/thalamus area (10-20 ms) and then the amygdala (20-30 ms). This was even earlier than the ERS response seen to fearful faces in visual cortex (40-50 ms). These data support LeDoux's suggestion of a quick, subcortical thamalo-amygdala route. Moreover, this route was specific for fear expressions; the ERS response in the amygdala to angry expressions had a late onset (150-160 ms). The ERS onset in prefrontal cortex followed that seen within the amygdala (around 160-210 ms). This is consistent with its role in higher-level emotional/cognitive processing.

Adult↗
PubMed2006

Choosing the lesser of two evils, the better of two goods: specifying the roles of ventromedial prefrontal cortex and dorsal anterior cingulate in object choice.

The ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortices (ACd) are considered important for reward-based decision making. However, work distinguishing their individual functional contributions has only begun. One aspect of decision making that has received little attention is that making the right choice often translates to making the better choice. Thus, response choice often occurs in situations where both options are desirable (e.g., choosing between mousse au chocolat or crème caramel cheesecake from a menu) or, alternatively, in situations where both options are undesirable. Moreover, response choice is easier when the reinforcements associated with the objects are far apart, rather than close together, in value. We used functional magnetic resonance imaging to delineate the functional roles of the vmPFC and ACd by investigating these two aspects of decision making: (1) decision form (i.e., choosing between two objects to gain the greater reward or the lesser punishment), and (2) between-object reinforcement distance (i.e., the difference in reinforcements associated with the two objects). Blood oxygen level-dependent (BOLD) responses within the ACd and vmPFC were both related to decision form but differentially. Whereas ACd showed greater responses when deciding between objects to gain the lesser punishment, vmPFC showed greater responses when deciding between objects to gain the greater reward. Moreover, vmPFC was sensitive to reinforcement expectations associated with both the chosen and the forgone choice. In contrast, BOLD responses within ACd, but not vmPFC, related to between-object reinforcement distance, increasing as the distance between the reinforcements of the two objects decreased. These data are interpreted with reference to models of ACd and vmPFC functioning.

Adult↗
PubMed2006

Nontuberculous mycobacterial adenitis: effectiveness of chemotherapy following incomplete excision.

BACKGROUND: Management of lymphadenopathy caused by nontuberculous mycobacteria (NTM) is primarily surgical. Where this cannot achieve sufficient clearance of infected nodes, chemotherapy is often given. AIM: This study compared results of surgery alone with surgery followed by chemotherapy in instances where there was incomplete surgical removal of diseased tissue. METHODS: Chemotherapy comprised azithromycin 10 mg/kg and rifabutin 6 mg/kg both given once daily for 6 mo. Ninety-eight children with NTM infection were seen in the period 1990-2004. Sixty-eight cases with adenopathy where "time to healing" (discharge stopped and inflammation settled) was known were available to compare response to treatment. RESULTS: The median (range) "time to healing" in weeks for 43 patients who had surgery alone was: incision and drainage (I&D)/curettage 6 (1-72) (n = 10); excision 3 (1-28) (n = 22); and from the last operation of multiple (repeat) surgery 3 (1-40) (n = 11). For 25 patients who required chemotherapy in addition to surgery, the median (range) "time to healing" in weeks was I&D/curettage 10 (1-40) (n = 17), excision 14 (8-20) (n = 2) and multiple surgery 29 (2-88) (n = 6). CONCLUSION: In children with adenitis due to NTM, where surgical resection is followed by continued discharge and inflammation, chemotherapy should be considered before further surgery is undertaken.

Anti-Bacterial Agents↗
PubMed2006

An active headrest for personal audio.

There is an increasing need for personal audio systems, which generate sounds that are clearly audible to one listener but are not audible to other listeners nearby. Of particular interest in this paper are listeners sitting in adjacent seats in aircraft or land vehicles. Although personal audio could then be achieved with headsets, it would be safer and more comfortable if loudspeakers in the seat headrests could be actively controlled to generate an acceptable level of acoustic isolation. In this paper a number of approaches to this problem are investigated, but the most successful involves a pair of loudspeakers on one side of the headrest, driven together to reproduce an audio signal for a listener in that seat and also to attenuate the pressures in the adjacent seat. The performance of this technique is investigated using simple analytic models and also with a practical implementation, tested in an anechoic chamber and a small room. It is found that significant attenuations, of between 5 and 25 dB, can be achieved in the crosstalk between the seats for frequencies up to about 2 kHz.

Acoustics↗
PubMed2005

Comparative study of erythritol and lactose monohydrate as carriers for inhalation: atomic force microscopy and in vitro correlation.

The adhesion of micronised salbutamol sulphate to two carrier excipients, lactose monohydrate and erythritol, was investigated using the atomic force microscope (AFM) colloid probe technique and correlated with their respective physico-mechanical properties and aerosolisation performance. The particle size, morphology and moisture sorption properties of the carriers were similar thereby allowing direct comparison of functionality. AFM force measurements (n = 1024 force curves) were obtained between salbutamol sulphate drug probes (n = 4) and the excipients, as 63-90 microm sieve fractions and atomically smooth crystals. In general, significant differences in drug adhesion to lactose monohydrate and erythritol were observed (ANOVA, p<0.05), with erythritol exhibiting relatively greater adhesiveness. A linear relationship between drug probe adhesion to lactose monohydrate and drug probe adhesion to erythritol was established with salbutamol sulphate-lactose monohydrate adhesion being 60-70% of that of the erythritol system. In vitro analysis suggested good correlation with the adhesion measurements. The aerosolisation of salbutamol sulphate from erythritol carrier particles was significantly less (ANOVA, p<0.05) than from lactose monohydrate, with a fine particle dose (<6.4 microm) of 41.9 +/- 7.4 microg and 24.9 +/- 3.1 microg for the lactose monohydrate and erythritol carriers, respectively (n = 3).

Administration, Inhalation↗
PubMed2005

Synthesis of 3-amino-1,2,4-benzothiadi- azine 1,1-dioxides via a tandem aza-Wittig/heterocumulene annulation.

[reaction: see text] Reaction of o-azidobenzenesulfonamides with polymer-supported triphenylphosphine affords the corresponding iminophosphoranes. Subsequent reaction with isocyanates gives 3-amino-1,2,4-benzothiadiazine 1,1-dioxides in high yields and purities. The reaction has been successfully applied to the synthesis of derivatives with various substituents at the 2- and 3-positions and in the benzenoid ring.

Azides↗
PubMed2005

Esophagogastric dissociation in the neurologically impaired: an alternative to fundoplication?

BACKGROUND/PURPOSE: Gastroesophageal reflux is common in children with severe neurological impairment. Fundoplication may produce symptomatic improvement but has a high failure rate. Esophagogastric dissociation (EGD) is an alternative procedure for treatment of gastroesophageal reflux. The aim of this study is to evaluate the results of EGD in our institution and compare them with a neurologically matched group of children who had Nissen fundoplication. METHODS: Twenty consecutive patients who had EGD were retrospectively evaluated and the results were compared with a neurologically matched group of 20 consecutive patients who had Nissen fundoplication. RESULTS: Twenty patients had EGD, 17 as a primary procedure. There was no operative mortality but 5 have died of other causes. Resolution of reflux-associated symptoms occurred in all patients. Of the 15 survivors, 5 remain on antireflux medication. Twenty patients had fundoplication. There was no operative mortality, but 8 patients have died of other causes. Failure occurred in 5 patients necessitating further surgery. Of the 10 unreoperated survivors, 6 remain on antireflux medication. CONCLUSIONS: Esophagogastric dissociation is an effective antireflux procedure when compared with fundoplication. It has a lower failure rate. We recommend EGD as a primary procedure in selected children with severe neurological impairment.

Adolescent↗
PubMed2004

Estimation of the treatment difference in multicenter trials.

The three fixed effects estimators of a treatment,difference are compared under conditions of random enrollment in a multicenter clinical trial. These comparisons are performed by assuming five different enrollment schemes. The estimators are compared via simulation using their expected mean squared errors. Unlike previous discussions of these three estimators, we take explicit account of the effect of centers that fail to enroll patients to one or both treatment arms. Within each center, we assume enrollment follows a Poisson process and consider the two situations in which the mean rate of this process is the same in every center and in which the mean rates are sampled from a gamma distribution. The effect of patient dropout is studied as well as the effect of increasing the number of centers. Simulations show that for many sound scenarios, the simpler estimator corresponding to the simplest model works better, even for the cases when data are generated by more complex models.

Algorithms↗
PubMed2003

Exploiting predisposition in the stereoselective synthesis of mono-, bi- and tetracyclic oxygen heterocycles: equilibration between, and trapping of, alternative di- and tetraacetals.

The desymmetrisation of 1,4-difuran-2-ylbutane-1,4-diol by Sharpless asymmetric oxidation gave the corresponding desymmetrised product in > 96% ee. However, the product existed as a mixture of two interconverting isomers, both of which were mixtures of anomers. The product could be trapped in high yield with a range of reagents to give stable adducts with embedded pyran-3-one, 1,6-dioxaspiro[4.5]decane or pyrano[3,2-b]pyran ring systems. The strategy was also applied in the interconversion between alternative tetracycles and, under acidic conditions, this process was thermodynamically controlled. The selectivity of the process was rationalised by molecular modelling using the HF/6-31G* parameter set.

Journal Article↗
PubMed2002

Initial sequencing and comparative analysis of the mouse genome.

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

Animals↗
PubMed2002

Phosphatidylinositol 3-kinase is essential for the proliferation of lymphoblastoid cells.

B-cell lymphoma, which is increasing world wide, includes such varied conditions as post-transplant lymphoproliferative disease (PTLD) and Burkitt's lymphoma. This study has characterized a role for the signalling molecule phosphatidylinositol 3-kinase, PI3K, in the regulation of growth and survival of immortalized B-lymphocytes. Burkitt's lymphoma cells die rapidly following inhibition of PI3K with LY294002, a chemical inhibitor. Furthermore, Epstein-Barr virus (EBV) immortalized B-cells, lymphoblastoid cell lines, which are a model of PTLD, do not die but are growth inhibited. This growth inhibition is due to an accumulation at G1 phase of the cell cycle and is paralleled by a loss of E2F transcriptional activity, which is essential for cell cycle entry. An active form of PI3K promotes E2F transcriptional activity in lymphoblastoid cell lines. Treatment of LCL with LY294002 causes a reduction of the expression of both cyclin D2 and cyclin D3, two key cyclins required for cell cycle progression but does not affect the expression of the EBV latent genes, EBNA2A or LMP-1. LY294002 also causes an increase in p27kip1, a cyclin dependent kinase inhibitor and results in the dephosphorylation of members of the pocket protein family. These data describe a mechanism by which PI3K plays a role in B-lymphocyte growth and suggests that a pathway from PI3K to D-type cyclin expression may provide diagnostic or treatment opportunities.

Cell Cycle Proteins↗
PubMed2002

Effect of sequence, timing of vascular anastomosis, and clamp removal on survival of microsurgical flaps.

The effects of the timing and order of clamp removal in microsurgical transplants were studied in rat groin skin flap and rat latissimus dorsi muscle flap models. Forty rats were divided into four groups. In Group 1, the arterial pedicle of the skin flap was anastomosed first, and the clamp was released after the anastomosis was completed. The venous pedicle was then repaired after inflow was restored. In Group 2, the venous pedicle of the skin flap was anastomosed first. The venous clamp was not released until completion of the arterial anastomosis. In Group 3, the arterial pedicle was anastomosed first in the muscle flap. The venous anastomosis was then performed after the arterial clamp was released. In Group 4, the venous pedicle was anastomosed first, and both clamps were released simultaneously. The blood perfusion of the skin flaps was examined after both clamps were released in Groups 1 and 2. The flap survival status was examined 5 days postoperatively for skin flaps and at 3 days for muscle flaps. Skin flaps in an additional six rats were harvested for histology. The results showed that the flap blood flow for Group 1 was statistically significantly higher than for Group 2 flaps in the first 20 min after reperfusion. There was no significant difference of flow between these two groups during the 30 to 90 min after reperfusion. The difference in survival rates for the four groups was not significant. Histology revealed extensive congestion in the flaps from Group 1 after completion anastomoses, but the congestion was significantly decreased at 3 hr following reperfusion. In conclusion, a brief venous stasis during anastomosis, after establishment of arterial inflow, is not detrimental to flap survival. The sequence of anastomosis will not affect outcome for either the cutaneous flap or the muscle flap models. Early flap perfusion was increased when the arterial anastomosis was performed first.

Analysis of Variance↗
PubMed2002

Combined feedback-feedforward active noise-reducing headset--the effect of the acoustics on broadband performance.

Active noise-reducing headsets that employ analog feedback control and provide good broadband attenuation are commercially available for a wide range of applications. Recent studies have explored the integration of an adaptive digital feedforward controller with the analog feedback controller to provide additional attenuation of periodic noise components. This paper presents an experimental study of such a combined control system, but with both feedback- and feedforward controllers attenuating broadband noise. Good performance is demonstrated in a reverberant sound field, while under direct sound-field conditions the attenuation performance of the feedforward controller is shown to be dependent on head position. The paper concludes with an analysis of the forward path delay showing how the passive attenuation mechanism improves broadband performance.

Computers↗
PubMed2002

The lytic cycle of Epstein-Barr virus is associated with decreased expression of cell surface major histocompatibility complex class I and class II molecules.

Human herpesviruses utilize an impressive range of strategies to evade the immune system during their lytic replicative cycle, including reducing the expression of cell surface major histocompatibility complex (MHC) and immunostimulatory molecules required for recognition and lysis by virus-specific cytotoxic T cells. Study of possible immune evasion strategies by Epstein-Barr virus (EBV) in lytically infected cells has been hampered by the lack of an appropriate permissive culture model. Using two-color immunofluorescence staining of cell surface antigens and EBV-encoded lytic cycle antigens, we examined EBV-transformed B-cell lines in which a small subpopulation of cells had spontaneously entered the lytic cycle. Cells in the lytic cycle showed a four- to fivefold decrease in cell surface expression of MHC class I molecules relative to that in latently infected cells. Expression of MHC class II molecules, CD40, and CD54 was reduced by 40 to 50% on cells in the lytic cycle, while no decrease was observed in cell surface expression of CD19, CD80, and CD86. Downregulation of MHC class I expression was found to be an early-lytic-cycle event, since it was observed when progress through late lytic cycle was blocked by treatment with acyclovir. The immediate-early transactivator of the EBV lytic cycle, BZLF1, did not directly affect expression of MHC class I molecules. However, BZLF1 completely inhibited the upregulation of MHC class I expression mediated by the EBV cell-transforming protein, LMP1. This novel function of BZLF1 elucidates the paradox of how MHC class I expression can be downregulated when LMP1, which upregulates MHC class I expression in latent infection, remains expressed in the lytic cycle.

Antigen Presentation↗
PubMed2002

Evaluation of four once-daily aminoglycoside dosing nomograms.

STUDY OBJECTIVE: To evaluate the accuracy of four once-daily aminoglycoside dosing nomograms in producing the desired gentamicin peak concentration (Cmax) target of 20 microg/ml in patients with varying degrees of renal function. DESIGN: Retrospective analysis using prospectively collected pharmacokinetic data. SETTING: Rural teaching hospital. PATIENTS: Ninety patients receiving intravenous gentamicin divided into three groups (30 patients each) determined by estimated renal function: group 1, creatinine clearance (Cl(cr),) 60 ml/minute or greater; group 2, Cl(cr) 40-59 ml/minute; group 3, Cl(cr) 20-39 ml/minute. Intervention. Serum gentamicin concentrations were collected for a 2-point (two consecutive infusions and one predose and one postdose concentration sampled during steady state) or 3-point (single infusion and one predose and two postdose concentrations at least 1.5 estimated half-lives apart) pharmacokinetic study for determination of patient-specific pharmacokinetic parameters (elimination rate constant, volume of distribution at steady state, and clearance) after 30-minute infusions of gentamicin 2.8 +/- 1.6 mg/kg. MEASUREMENTS AND RESULTS: The four nomograms evaluated were from Hartford Hospital, Barnes-Jewish Hospital, University of Rochester, and the Sanford Guide. With a pharmacokinetic analysis program and the patient-specific pharmacokinetic parameters, Cmax and minimum concentration (Cmin) were determined with use of the recommended doses and dosing intervals of the four nomograms. Also, the gentamicin dose and interval needed to achieve a Cmax and Cmin of 20 microg/ml and 0.2 microg/ml, respectively, were determined. Dosing was based on total body weight unless that weight was more than 25% of ideal body weight, in which case, an adjusted body weight was used. In general, the recommended dosages and resultant Cmax produced by the nomograms were significantly less (p < 0.05) than the dosage and Cmax actually needed to achieve a Cmax:minimum inhibitory concentration (MIC) ratio of 10 or greater for bacteria with an MIC of 2 microg/ml. CONCLUSION: Once-daily aminoglycoside dosing using the four nomograms resulted in inaccurate dosing, and because of the large variability in human pharmacokinetics, dosing nomograms such as these should be abandoned in favor of individualizing dosages with therapeutic drug monitoring.

Adult↗