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D Brewer

Publications and source records attributed to D Brewer.

At least 19 recordsLinked to original sources
PubMed2006

Chicken major histocompatibility complex class II molecules of the B haplotype present self and foreign peptides.

The chicken major histocompatibility complex (MHC), or B-complex, mediates genetic resistance and susceptibility to infectious disease. For example, the B19 haplotype is associated with susceptibility to Marek's disease. Here, we describe the sequencing and analysis of peptides presented by B19 MHC class II molecules. A B19/B19 B-cell line was used for the immunoaffinity purification of MHC class II molecules, which was followed by acid elution of the bound peptides. The eluted peptides were then analysed using tandem mass spectrometry. Thirty peptide sequences were obtained, ranging from 11 to 25 amino acids in length. Source protein cellular localization included the plasma membrane, cytosol and endosomal pathway. In addition, five peptides from the envelope glycoprotein of chicken syncytial virus (CSV) were identified. Chicken syncytial virus had been used as a helper virus along with reticuloendotheliosis virus strain T for transformation of B19/B19B cells. Alignment and analysis of the peptide sequence pool provided a putative peptide-binding motif for the B19 MHC class II.

Amino Acid Motifs↗
PubMed2003

Reconstructing gene networks: what are the limits?

To fully realize the benefits of high-throughput post-genomic technologies it is necessary to reconstruct and analyse the complicated network of interactions through which most genes operate. We briefly summarize the mathematical frameworks that can be used to model such networks, and the types of algorithms available for their reconstruction. We then focus on dynamic models, typically described using differential equations, and explain the two main reconstruction approaches in current use. We discuss the data requirements of these algorithms and ask how well they correspond to current microarray data.

Genes↗
PubMed2001

The integration of constructed wetlands into a treatment system for airport runoff.

A new surface runoff treatment system has been designed for London Heathrow Airport, which incorporates separate floating constructed wetlands or reedbeds and sub-surface flow constructed wetlands as major pollutant removal systems. The primary requirement of the newly developed treatment system is to control the concentrations of glycols following their use as de-icers and anti-icers within the airport. The ability of reedbeds to contribute to this treatment role was fully tested through pilot scale, on-site experiments over a 2 year period. The average reductions in runoff BOD concentrations achieved by pilot scale surface flow and sub-surface flow reedbeds were 30.9% and 32.9%, respectively. The corresponding average glycol removal efficiencies were 54.2% and 78.3%, following shock dosing inputs. These treatment performances are used to predict the required full scale constructed wetland surface areas needed to attain the desired effluent water quality. The treatment system also incorporates aeration, storage and, combined with reedbed technology, has been designed to reduce a mixed inlet BOD concentration of 240 mg/l to less than 40 mg/l for water temperatures varying between 6 degrees C and 20 degrees C.

Aircraft↗
PubMed2000

Evaluation of the metal binding properties of the histidine-rich antimicrobial peptides histatin 3 and 5 by electrospray ionization mass spectrometry.

Electrospray ionization mass spectrometry (ESI-MS) was used to investigate metal ion interactions with salivary peptides histatin 3 (H3) and histatin 5 (H5). Conformational changes of these peptides in the presence of metal ions were studied using circular dichroism spectroscopy. H3 and H5 formed high affinity complexes with Cu(2+) and Ni(2+) and, to a lesser extent, with Zn(2+). Both peptides show the potential for multiple binding sites for Cu(2+) and Ni(2+) and only a single strong binding site for Zn(2+). The binding of a third Cu(2+) ion to H3 seems to enable the binding of a fourth ion to H3. The binding of a second and third Ni(2+) ion to H5 has a similar effect in enabling the binding of a fourth ion. None of the metal ions examined stabilized a regular secondary structure for either peptide. Subtle changes in overall conformation are seen with the addition of Cu(2+) to both H3 and H5.

Amino Acid Sequence↗
PubMed1998

NMR studies of the antimicrobial salivary peptides histatin 3 and histatin 5 in aqueous and nonaqueous solutions.

Conformational studies of the salivary peptides histatin 3 (H3) and histatin 5 (H5) were performed by NMR and circular dichroism (CD) in aqueous and nonaqueous solutions. Histatin 5 has no defined structure in H2O but adopts a more helical conformation in dimethyl sulfoxide and aqueous trifluoroethanol. This is in agreement with the CD analysis, which shows no secondary structure in H2O but increasing helical content in the presence of trifluoroethanol. CD analysis shows that H3 has less propensity to form a helical structure than H5 in similar conditions. The NMR analysis of H3 in H2O at pH 7.4 reveals that its conformational mobility is less than that of H5 as indicated by the observation of backbone cross peaks alphaN (i, i + 1) and NN (i, i + 1) and the slow exchanging amide protons in the C-terminus. However, H3 remains essentially unordered as suggested by the lack of longer range nuclear Overhauser effects (NOEs) in the NOESY spectrum. H3 becomes much more ordered in a mixture of 50:50 H2O-dimethyl sulfoxide as indicated by the numerous NOEs, including several side chain to side chain and side chain to backbone connectivities. Our data suggest that in these conditions H3 contains a turn in the region of K13 to K17 and possibly a 3(10) helix at the C-terminus. This study demonstrates that H3 and H5 are both conformationally mobile and that each adopt different types of conformations in aqueous and nonaqueous solutions.

Amino Acid Sequence↗
PubMed1998

Should low-molecular-weight heparins replace unfractionated heparin as the agent of choice for adults with deep venous thrombosis?

BACKGROUND: Several low-molecular-weight heparins (LMWHs) are now approved for use in the United States for the prophylaxis of venous thromboembolism. They are used in Europe for the treatment of deep venous thrombosis (DVT) and pulmonary embolism. This review examines the evidence addressing the question "Should LMWHs replace unfractionated heparin (UFH) in the treatment of adults with DVT?" METHODS: We performed a MEDLINE search using the key words "low-molecular-weight heparin" from the years 1990 to 1998, and the results were assessed using the JAMA Users' Guides to the Medical Literature system. RESULTS: Low-molecular-weight heparins are at least as safe and effective as unfractionated heparin in the treatment of patients with DVT. They are probably more effective and safer. They are more convenient to use and are associated with lower overall costs. CONCLUSIONS: Based on efficacy, safety, convenience, and cost, LMWHs are clearly superior to UFH in the treatment of DVT in primary care. Studies that confirm an expected improvement in patient-oriented outcomes (e.g., mortality and quality of life) need to be done.

Adult↗
PubMed1997

Traumatic intrapericardial diaphragmatic hernia diagnosed by echocardiography.

Emergency Department echocardiography revealed an intrapericardial hollow viscus in an 80-year-old auto crash victim. This proved to be stomach herniated through a ruptured diaphragm. Echocardiography and ultrasonography are very valuable diagnostic procedures currently available to the trauma surgeon to rule out diaphragmatic injury early in the trauma room.

Aged↗
PubMed1997

Histidine-rich human salivary peptides are inhibitors of proprotein convertases furin and PC7 but act as substrates for PC1.

A 32 amino acid peptide called histatin-3 (H3; 22% His) and its N-terminal 24 amino acid fragment histatin-5 (H5, 33% His), are found in human saliva and possess powerful antimicrobial properties. These His-rich peptides have been synthesized by Fmoc-based solid-phase chemistry. Their sequences are: DSHAKRHHGYKRKFHEKHHSHRGYRSNYLYDN (H3) and DSHAKRHHGYKRKFHEKHHSHRGY (H5). In addition, we also prepared two H5 and one H3 mutants. The H5 mutants were: DH5 (all amino acids in D configuration) and H5F (where all His are replaced by Phe at positions 3, 7, 8, 15, 18, 19, 21). The 9-24 segment of H3 with all the His at positions 15,18,19,21 replaced by Tyr was also prepared (delta 1-8 H3Y). The behavior of these five peptides was examined with three proprotein convertases (PC's) which possess cleavage specificity directed towards single and pairs of basic residues. These were: human (h)PC1, an endocrine and neural convertase, hfurin and rat (r)PC7, two widely expressed enzymes. All are serine endoproteases belonging to the kexin/subtilisin family. Our in vitro study revealed that H3 behaves as a substrate for PC1, being cleaved by this endoprotease primarily at a site carboxy terminal to the single Arg25 residue (HRGYR decrease SN). On prolonged incubation some minor cleavage was also observed C-terminal to the first LysArg6 pairs of basic amino acids namely at: HAKR decrease HH, which contains a P4 as well as P'1 and P'2 His residues. The second potential site YKRK12-FH which does not have a P4 basic residues is not cleaved, even upon incubation with excess protease. PC1 only poorly cleaves H5 at the same site mentioned above for H3, i.e., at HAKR decrease HH. As expected, neither the D-amino acid analogue (DH5), nor the Phe and Tyr mutant analogues of the long and short histatins, respectively, are cleaved at all. In contrast to the above findings for hPC1, the convertase hfurin did not cleave any of the five synthetic peptides. Instead, H3 and H5 were found to be moderately potent inhibitors of the furin-mediated cleavage of the pentapeptide pGlu-Arg-Thr-Lys-Arg-MCA fluorogenic substrate. This inhibition was reversible and competitive, with an estimated inhibition constant Ki of 1.98 microM for H3 and 2.98 microM for H5. The other analogs exhibited only a moderate to weak inhibition of furin, suggesting that substitution of all His by aromatic residues (Phe or Tyr) drastically reduces their inhibitory potency. When tested against rPC7, H3 exhibited almost identical inhibition profile with a measured Ki of 2.4 microM. The partial sequence identity of H3 to the inhibitory pro-peptide of furin and PC7 provides a rationale for our observation.

Amino Acid Sequence↗
PubMed1995

Postoperative morbidity and mortality following resection of the colon and rectum for cancer.

PURPOSE: The aim of this study was to report the prevalence of postoperative complications and mortality of patients with colorectal cancer when treated by conventional surgery. METHODS: Morbidity and mortality following open resection for colorectal cancer were analyzed in 1,846 patients whose clinical, operative, and pathology data were prospectively documented over a 20-year period. RESULTS: Mortality following elective resection of the left and right colon was low, whereas overall morbidity was high (37.2 percent). Respiratory and cardiac complications were especially common. Incidence of clinically significant leakage was similar following right (0.5 percent) or left (1.1 percent) hemicolectomy. Incidence of anastomotic leakage was significantly higher after emergency right hemicolectomy (4.3 percent). Overall morbidity following excision of the rectum was high (40.2 percent). Respiratory and cardiac complications predominated. Incidence of clinically significant anastomotic leakage following anterior resection was low (2.9 percent). Over the years, there has been a decline in the number of patients with tumor demonstrated histologically in a line of resection, suggesting an improved local surgical clearance. CONCLUSIONS: These results following conventional surgery may be useful when evaluating new techniques.

Adenocarcinoma↗
PubMed1995

Physiological characteristics of the supported singing voice. A preliminary study.

The purpose of this study was to develop a definition of the supported singing voice based on physiological characteristics by comparing the subjects' concepts of a supported voice with objective measurements of their supported and unsupported voice. This preliminary report presents findings based on data from eight classically trained singers. Subjects answered questions about their concepts of the characteristics of the supported singing voice and how it is produced. Samples of the supported and unsupported singing voice produced at low, medium, and high pitches at a comfortable loudness level were collected for acoustic, spectral, airflow, electroglottographic, air volume, and stroboscopic analyses. Significant differences between the supported and unsupported voice were found for sound pressure level (SPL), peak airflow, subglottal pressure (Ps), glottal open time, and frequency of the fourth formant (F4). Mean flow and F2 frequency differences were sex and pitch related. Males adjusted laryngeal configuration to produce supported voice, whereas glottal configuration differences were greater in females. Breathing patterns were variable and not significantly different between supported and unsupported voice. Subjects in this study believe that the supported singing voice is resonant, clear, and easy to manage and is produced by correct breath management. Results of data analysis show that the supported singing voice has different spectral characteristics from and higher SPL, peak airflow, and Ps than the unsupported voice. Singers adjust laryngeal and/or glottal configuration to account for these changes, but no significant differences in breathing activity were found.

Acoustics↗
PubMed1995

Endoscopic microsuture repair of vocal fold defects.

The presence of a nonvibratory segment of vocal folds after microlaryngeal surgery is often a cause of poor voice result. The etiology of a nonvibratory segment is due to full thickness epithelial defect followed by secondary wound closure and scar contracture. To reduce scar contracture and nonvibratory segment of the vocal folds, primary repair with a 6-0 chromic endo-knot suture technique was used to close defects and approximate microflaps of the vocal folds. This was done in 18 patients with epithelial defects after resection of benign vocal fold lesions. The pathologic findings included severe polypoid degeneration (n = 7), fusiform laryngeal polyps (n = 5), sulcus vocalis (n = 2), cyst (n = 2), and keratosis (n = 2). Voice was improved in all patients after surgery. Comparison of vocal fold vibration before and after surgery showed improvements in configuration, amplitude, and mucosal wave. Vocal folds that were sutured all had good vibratory characteristics; none had a nonvibrating segment at the site of suture placement. Voice and healing after microsuture technique were near normal by Day 10 and return of mucosal wave was often complete by Day 14. Endoscopic microsuture closure of microflaps of the vocal folds edge is safe and affords the surgeon an opportunity for primary repair with improved functional result.

Endoscopy↗
PubMed1994

Aerodynamic and stroboscopic findings before and after microlaryngeal phonosurgery.

Acoustic, aerodynamic, and laryngo-video-stroboscopy (LVS) studies were done on 50 patients before and after microlaryngeal surgery for benign vocal fold lesions. Perceptual pre- and postratings were also obtained. After microlaryngeal surgery, statistically significant differences between pre- and posttreatment conditions included postoperative findings of (a) a lowering of mean flow rate, (b) an increase in glottal efficiency, and (c) an increase in maximum sound pressure level. There was no significant improvement in maximum phonation time. Stroboscopy findings showed changes of glottal configuration, linearity of the vocal fold edge, amplitude of vocal fold vibration, excursion of the mucosal wave, and periodicity. Acceptable perceptual voice quality appeared to depend on a straight vocal fold edge, good vibratory amplitude, and good mucosal wave. Improved understanding of vocal function after phonosurgery should help us refine surgical principles and techniques. The combined use of LVS and phonatory function measures is advocated.

Glottis↗
PubMed1994

Diagnosis and treatment of persistent dysphonia after laryngeal surgery: a retrospective analysis of 62 patients.

Sixty-two patients with persistent or recurrent dysphonia after laryngeal surgery underwent interdisciplinary voice evaluation, laryngostroboscopy, and objective measurements of vocal function. The causes of persistent dysphonia were attributed to vocal fold scarring (n = 22), residual mass lesion (n = 8), residual inflammation (n = 13), recurrent mass (n = 4), and hyperfunctional voice disorder (n = 7). Laryngoscopy often showed excessive ventricular compression and anterior-to-posterior laryngeal compression. Ventricular dysphonia was often a compensatory gesture in response to poorly mobile vocal fold membranes. Stroboscopy was able to document a number of abnormalities which included abnormalities of laryngeal configuration, vibratory asymmetry, reduction of amplitude, and mucosal wave. Using a diversified approach consisting of medical therapy, voice therapy, and repeat surgery, better vocal function was able to be restored in the majority of patients. An interdisciplinary approach to the dysphonic patient after laryngeal surgery was most useful in defining the pathology and refining a treatment rehabilitation program.

Adult↗
PubMed1992

Dysphonia in the aging: physiology versus disease.

A chart review from 151 dysphonic patients over the age of 60 was done to define aging related voice disorders. Overwhelmingly, patients suffered from dysphonia due to disease processes associated with aging rather than to physiologic aging alone. These include: 1. central neurological disorders affecting laryngeal function (e.g., stroke, Parkinson's disease, essential tremor, Alzheimer's disease); 2. benign vocal fold lesions (e.g., Reinke's edema, benign and dysplastic epithelial lesions); 3. inflammatory disorders (e.g., laryngitis sicca, medication effect); 4. laryngeal neoplasia; and 5. laryngeal paralysis. Typical laryngeal findings of vocal fold bowing and breathiness consistent with presbylarynges were present in only six patients. Presbylarynges is not a common disorder and should be a diagnosis of exclusion made only after careful medical and speech evaluation.

Aged↗
PubMed1991

Functional staging for vocal cord paralysis.

Phonatory function can be reliably tested after vocal paralysis. After a review of 116 cases, 55 patients underwent objective testing. The clinical history of vocal ability and aspiration were found to be significantly correlated with measurements of phonatory mean flow rate (MFR), maximum phonation time (MPT), and maximum decibel output (SPL). A four-stage classification system, based on clinical and objective measurements, has been formulated. In stage I, measures of vocal parameters approached those of normals with MFR = 155 cc/sec, MPT = 12 sec, and SPL = 92 dB. Patients with stage IV disability have high MFR (480 cc/sec), but low MPTs (less than 3 sec) and low SPL values (76 dB). Factors such as sex, age, weight loss, and the presence of malignancy affect the degree of vocal function deficit. Post-therapy recordings indicated an improvement in vocal function by an increase in MPT and SPL, with a decrease in MFR. Measurements of MFR, PT, and SPL are good objective indicators available to the clinician. Functional staging can be applied to assessment and treatment of vocal cord paralysis.

Adult↗