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Biomedical subjects

D A Mitchell

Publications and source records attributed to D A Mitchell.

At least 19 recordsLinked to original sources
PubMed2005

Anatomical variability of omohyoid and its relevance in oropharyngeal cancer.

AIMS: To define the reproducibility of the position of omohyoid muscle. SETTING: A regional Maxillofacial surgical oncological service. MATERIAL AND PATIENTS: Thirty dissections of cadavers and consecutive series of 88 patients who had had neck dissections, either prophylactic or therapeutic, as part of their oncological management. METHOD: Measurement of the upper border of omohyoid muscle relative to the clavicle and the internal jugular vein (mm). RESULTS: The position of omohyoid muscle in relation to the clavicle and internal jugular vein varied considerably and by inference the nodal yield at level IV is also likely to vary. CONCLUSION: The wide variability of the position of omohyoid muscle is likely to have implications for the surgical management of oral and oropharyngeal cancer.

Adult↗
PubMed2003

Bridging the gap--vocational trainee to senior house officer: a new induction course.

OBJECTIVES: The objectives of this course were: to develop an induction course for vocational trainees taking up first SHO posts; to enable new dental SHOs to have enhanced skills from the beginning of the post; to create safe practitioners capable of performing SHO duties; and to assess whether such a course is perceived to be beneficial by the SHOs, their educational supervisors and professional colleagues from medicine, dentistry and nursing. DESIGN: A 5-day intensive, interactive course was developed and directed by a consultant maxillofacial surgeon, with contributions from a range of professional colleagues to teach appropriate knowledge, skills and attitudes. SUBJECTS: Trainees completing the VT programme; due to commence SHO posts in the Yorkshire Region. EVALUATION METHOD: Detailed daily and end of course questionnaires were completed. A post course; in-work evaluation was sought from the trainees, educational supervisors and a range of professional colleagues about the validity of the course. RESULTS: Daily and end of course evaluations were positive about the perceived importance and relevance of the course. After 6 weeks in post the SHOs continued to place high value on the course as a preparation for hospital practice. Feedback from the supervisors and colleagues indicated that the SHOs were performing well, but the influence of the course on performance could not be determined in this study. CONCLUSION: It was possible to design and deliver an appropriate induction course, which appeared to meet most of the needs of new dental SHOs. Feedback indicated the need for modification of some aspects of the course.

Attitude of Health Personnel↗
PubMed2001

Structural basis for selective recognition of oligosaccharides by DC-SIGN and DC-SIGNR.

Dendritic cell specific intracellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin (DC-SIGN), a C-type lectin present on the surface of dendritic cells, mediates the initial interaction of dendritic cells with T cells by binding to ICAM-3. DC-SIGN and DC-SIGNR, a related receptor found on the endothelium of liver sinusoids, placental capillaries, and lymph nodes, bind to oligosaccharides that are present on the envelope of human immunodeficiency virus (HIV), an interaction that strongly promotes viral infection of T cells. Crystal structures of carbohydrate-recognition domains of DC-SIGN and of DC-SIGNR bound to oligosaccharide, in combination with binding studies, reveal that these receptors selectively recognize endogenous high-mannose oligosaccharides and may represent a new avenue for developing HIV prophylactics.

Acetylglucosamine↗
PubMed2001

Residence time distributions of gas flowing through rotating drum bioreactors.

Residence time distribution studies of gas through a rotating drum bioreactor for solid-state fermentation were performed using carbon monoxide as a tracer gas. The exit concentration as a function of time differed considerably from profiles expected for plug flow, plug flow with axial dispersion, and continuous stirred tank reactor (CSTR) models. The data were then fitted by least-squares analysis to mathematical models describing a central plug flow region surrounded by either one dead region (a three-parameter model) or two dead regions (a five-parameter model). Model parameters were the dispersion coefficient in the central plug flow region, the volumes of the dead regions, and the exchange rates between the different regions. The superficial velocity of the gas through the reactor has a large effect on parameter values. Increased superficial velocity tends to decrease dead region volumes, interregion transfer rates, and axial dispersion. The significant deviation from CSTR, plug flow, and plug flow with axial dispersion of the residence time distribution of gas within small-scale reactors can lead to underestimation of the calculation of mass and heat transfer coefficients and hence has implications for reactor design and scale-up.

Air↗
PubMed2001

A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands.

DC-SIGN and DC-SIGNR are cell-surface receptors that mediate cell-cell interactions within the immune system by binding to intercellular adhesion molecule-3. The receptor polypeptides share 77% amino acid sequence identity and are type II transmembrane proteins. The extracellular domain of each comprises seven 23-residue tandem repeats and a C-terminal C-type carbohydrate-recognition domain (CRD). Cross-linking, equilibrium ultracentrifugation, and circular dichroism studies of soluble recombinant fragments of DC-SIGN and DC-SIGNR have been used to show that the extracellular domain of each receptor is a tetramer stabilized by an alpha-helical stalk. Both DC-SIGN and DC-SIGNR bind ligands bearing mannose and related sugars through the CRDs. The CRDs of DC-SIGN and DC-SIGNR bind Man(9)GlcNAc(2) oligosaccharide 130- and 17-fold more tightly than mannose, and affinity for a glycopeptide bearing two such oligosaccharides is increased by a further factor of 5- to 25-fold. These results indicate that the CRDs contain extended or secondary oligosaccharide binding sites that accommodate mammalian-type glycan structures. When the CRDs are clustered in the tetrameric extracellular domain, their arrangement provides a means of amplifying specificity for multiple glycans on host molecules targeted by DC-SIGN and DC-SIGNR. Binding to clustered oligosaccharides may also explain the interaction of these receptors with the gp120 envelope protein of human immunodeficiency virus-1, which contributes to virus infection.

Amino Acid Sequence↗
PubMed2001

The phosphotyrosyl phosphatase activator, Ncs1p (Rrd1p), functions with Cla4p to regulate the G(2)/M transition in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae p21-activated kinases, Ste20p and Cla4p, have individual functions but appear to share an essential function(s) as well because a strain lacking both kinases is inviable. To learn more about the shared function, we sought new mutations that were lethal in the absence of CLA4. This approach led to the identification of at least 10 complementation groups designated NCS (need CLA4 to survive). As for ste20 cla4-75 mutants, most ncs cla4-75 double mutants were defective for septin localization during budding. One group, NCS1/RRD1 (YIL153w), did not confer this defect, however, and we investigated its function further. ncs1Delta cla4Delta cells arrested with elongated buds and short mitotic spindles. The morphological defects and lethality were suppressed by mutations that abrogate the cell cycle morphogenetic checkpoint, CDC28Y19F or swe1Delta. The connection to the cell cycle may be direct, as we detected a Cla4p-Cdc28p complex. NCS1 encodes a protein with significant similarity to a mammalian phosphotyrosyl phosphatase activator (PTPA) regulatory subunit for type 2A protein phosphatases (PP2As). Genetic and biochemical evidence suggested that the phosphatase Sit4p is a target for Ncs1p. First, CLA4 and SIT4 were synthetically lethal. Second, Ncs1p and its yeast paralog, Noh1p (Rrd2p), bound to the catalytic domain of Sit4p in vitro, and Ncs1p could be immunoprecipitated with Sit4p but not with another PP2A (Pph21p) from yeast cell extracts. Strains lacking both NCS1 and NOH1 were inviable and arrested as unbudded cells, implying that PTPA function is required for proper G(1) progression.

CDC28 Protein Kinase, S cerevisiae↗
PubMed2000

Two-phase model of the kinetics of growth of Rhizopus oligosporus in membrane culture.

An empirical model was developed to describe a growth profile occurring in solid-state fermentation (SSF), namely that consisting of an initial period of rapid acceleration followed by an extended period of deceleration. This kinetic profile is not adequately described by the logistic model. The empirical model is based on the concept of active and nonactive hyphal segments. Exponential and deceleration growth phases are modeled. The model parameters can be determined directly from the dry-weight profile and they depend on the growth medium present. The model suggests that, at the instant the culture enters the deceleration phase, there is a 71% to 86% decrease in the number of actively extending hyphal tips and that, during the deceleration phase, there is an exponential decay in the number of active hyphal segments, with a first-order decay constant of 0.042 to 0.072 h(-1).

Biomass↗
PubMed2000

Mathematical modeling as a tool to investigate the design and operation of the zymotis packed-bed bioreactor for solid-state fermentation.

Zymotis bioreactors for solid-state fermentation (SSF) are packed-bed bioreactors with internal cooling plates. This design has potential to overcome the problem of heat removal, which is one of the main challenges in SSF. In ordinary packed-bed bioreactors, which lack internal plates, large axial temperature gradients arise, leading to poor microbial growth in the end of the bed near the air outlet. The Zymotis design is suitable for SSF processes in which the substrate bed must be maintained static, but little is known about how to design and operate Zymotis bioreactors. We use a two-dimensional heat transfer model, describing the growth of Aspergillus niger on a starchy substrate, to provide guidelines for the optimum design and operation of Zymotis bioreactors. As for ordinary packed-beds, the superficial velocity of the process air is a key variable. However, the Zymotis design introduces other important variables, namely, the spacing between the internal cooling plates and the temperature of the cooling water. High productivities can be achieved at large scale, but only if small spacings between the cooling plates are used, and if the cooling water temperature is varied during the fermentation in response to bed temperatures.

Aspergillus niger↗
PubMed2000

Approach to designing rotating drum bioreactors for solid-state fermentation on the basis of dimensionless design factors.

The development of large-scale solid-state fermentation (SSF) processes is hampered by the lack of simple tools for the design of SSF bioreactors. The use of semifundamental mathematical models to design and operate SSF bioreactors can be complex. In this work, dimensionless design factors are used to predict the effects of scale and of operational variables on the performance of rotating drum bioreactors. The dimensionless design factor (DDF) is a ratio of the rate of heat generation to the rate of heat removal at the time of peak heat production. It can be used to predict maximum temperatures reached within the substrate bed for given operational variables. Alternatively, given the maximum temperature that can be tolerated during the fermentation, it can be used to explore the combinations of operating variables that prevent that temperature from being exceeded. Comparison of the predictions of the DDF approach with literature data for operation of rotating drums suggests that the DDF is a useful tool. The DDF approach was used to explore the consequences of three scale-up strategies on the required air flow rates and maximum temperatures achieved in the substrate bed as the bioreactor size was increased on the basis of geometric similarity. The first of these strategies was to maintain the superficial flow rate of the process air through the drum constant. The second was to maintain the ratio of volumes of air per volume of bioreactor constant. The third strategy was to adjust the air flow rate with increase in scale in such a manner as to maintain constant the maximum temperature attained in the substrate bed during the fermentation.

Air Movements↗
PubMed2000

Biochemical engineering aspects of solid state bioprocessing.

Despite centuries of use and renewed interest over the last 20 years in solid-state fermentation (SSF) technology, and despite its good potential for a range of products, there are currently relatively few large-scale commercial applications. This situation can be attributed to the complexity of the system: Macroscale and microscale heat and mass transfer limitations are intrinsic to the system, and it is only over the last decade or so that we have begun to understand them. This review presents the current state of understanding of biochemical engineering aspects of SSF processing, including not only the fermentation itself, but also the auxiliary steps of substrate and inoculum preparation and downstream processing and waste disposal. The fermentation step has received most research attention. Significant advances have been made over the last decade in understanding how the performance of SSF bioreactors can be controlled either by the intraparticle processes of enzyme and oxygen diffusion or by the macroscale heat transfer processes of conduction, convection, and evaporation. Mathematical modeling has played an important role in suggesting how SSF bioreactors should be designed and operated. However, these models have been developed on the basis of laboratory-scale data and there is an urgent need to test these models with data obtained in large-scale bioreactors.

Animals↗
PubMed2000

RNA transfected dendritic cells as cancer vaccines.

Immunization with dendritic cells loaded with tumor antigens could represent a powerful method of inducing antitumor immunity. Studies from several laboratories have shown that immunization with dendritic cells pulsed with specific antigens prime cytotoxic T-cells and engender tumor immunity. This review will focus on the use of dendritic cells transfected with RNA as cancer vaccines, with emphasis on the potential advantages of using RNA. The majority of cancer patients who lack an identified tumor antigen and/or cannot provide sufficient tumor tissue for antigen preparation will be excluded from treatment with cancer vaccines based on using either specific tumor antigens or mixtures of tumor-derived antigens in the form of peptides or proteins isolated from tumor cells. Vaccination with the mRNA content of tumor cells would extend the scope of vaccination to this group of patients as well because RNA can be amplified from very few cancer cells.

Animals↗
PubMed1999

Response of Rhizopus oligosporus to temporal temperature profiles in a model solid-state fermentation system.

Membrane overcultures of Rhizopus oligosporus were shifted from 37 to 50 degrees C for 10 h and then returned to 37 degrees C, mimicking the temporal temperature profiles which typically occur in SSF due to heat transfer limitations. Analysis with a modified two-phase growth model suggests that the temperature upshift causes a 48% decrease in the number of actively extending hyphal tips, and that the first order death rate constant of tips increases from 0. 059 to 0.073 h(-1). The fungus did not immediately recover when the temperature was returned to 37 degrees C. The model assumed that the specific growth rate constant microgram(g) was not affected by the increase of temperature, although contradictory data was obtained from radial growth rate experiments.

Cell Division↗