PubMed Health⌕ Search

Biomedical subjects

D P Morris

Publications and source records attributed to D P Morris.

At least 19 recordsLinked to original sources
PubMed2004

Vibration characteristics and function of atelectatic segments in the tympanic membrane in fresh human cadaveric temporal bones.

Dimeric segments are commonly encountered in otological practice. They may be associated with a mild conductive hearing loss and often coexist with other tympanic membrane and middle ear abnormalities. Some otologists have advocated surgical management but the consequences of dimeric segment stiffening, shielding or excision and grafting on acoustic transfer to the stapes footplate has been poorly explored. In this study, laser Doppler vibrometry was used to measure vibrations at the tympanic membrane and the stapes footplate in the fresh cadaveric human temporal bone. The dimeric segment vibrates more than the adjacent, thicker normal tympanic membrane. Shielding or excision and grafting of the dimeric segment with thicker and stiffer materials has little effect on displacement at the stapes footplate.

Bone Conduction↗
PubMed2001

Phosphorylation of RNA polymerase II CTD fragments results in tight binding to the WW domain from the yeast prolyl isomerase Ess1.

The yeast prolyl isomerase, Ess1, has recently been shown to interact via its WW domain with the hyperphosphorylated form of the RNA polymerase II C-terminal domain (CTD). We have investigated folding of the Ess1 WW domain and its binding to peptides representing the CTD by circular dichroism and fluorescence. Ess1 WW folds and unfolds reversibly, but in the absence of ligand is only marginally stable with a melting temperature of 19 degrees C. The WW domain is stabilized by the addition of anionic ligands, namely, chloride, inorganic phosphate, phosphoserine, and phosphorylated CTD peptides. Dissociation constants were measured to be 70--100 microM for CTD peptides phosphorylated at one serine, and 16--21 microM for peptides with two or more phosphorylated serines. Weaker or no affinity was observed for nonphosphorylated CTD peptides. There is surprisingly little difference in the affinity for peptides phosphorylated at Ser 2 or Ser 5 of the consensus repeat, or for peptides with different patterns of multiple phosphorylation. The binding of Ess1 to phosphorylated CTD peptides is consistent with a model wherein the WW domain positions Ess1 to catalyze isomerization of the many pSer--Pro peptide bonds in the phosphorylated CTD. We suggest that cis/trans isomerization of prolyl peptide bonds plays a crucial role in CTD function during eukaryotic transcription.

Circular Dichroism↗
PubMed2001

Combined 'trache-stent': a useful option in the treatment of a complex case of subglottic stenosis.

The authors describe the adaptation of a Montgomery T-tube laryngo-tracheal stent to incorporate an uncuffed fenestrated Shiley tracheostomy tube in the management of a complex case of subglottic stenosis. The combined 'trache-stent' provided a secure, unobstructed airway and optimal phonation. The presence of a removable inner tube facilitated cleaning and reduced patient anxiety regarding the perceived risks of stent obstruction with dried secretions. The combined 'trache-stent' was upsized at four weeks with minimal evidence of local granulation formation. The device was removed entirely six weeks later after direct laryngoscopy reconfirmed the above findings. Almost two years later the patient retains a good voice and airway using a simple fenestrated tracheostomy tube and speaking valve. The subglottic area is stable and the patient has returned to full-time employment.

Attitude to Health↗
PubMed2001

Relapsing polychondritis associated with monoclonal gammopathy in a patient with myelodysplastic syndrome.

Relapsing polychondritis is a rare condition characterized by inflammation and subsequent degeneration of cartilages. Deformity of the pinna, nasal saddling and stridor due to involvement of the cartilages of the respiratory tract may lead to patients being referred to the otolaryngologist for initial assessment and further management. Recent observations have suggested that relapsing polychondritis may occur as a paraneoplastic phenomenon in cases of myelodysplasia. The case of a patient with relapsing polychondritis, myelodysplastic syndrome and a monoclonal gammopathy is presented. The authors highlight the apparent existence of this association and encourage otolaryngologists to consider such possible links when cases of relapsing polychondritis present to the outpatients department.

Aged↗
PubMed2001

"Bones of Contention". The donation of temporal bones for dissection after the organ-retention scandals.

It is essential for the Otologist in training to become familiar with the anatomy of the temporal bone. Generations of trainees have acquired this knowledge, together with basic surgical skills and techniques by dissection of cadaver temporal bones. In recent years, however, the supply of temporal bones for dissection has become a contentious issue in many British hospitals. Media and public attention has recently focused on issues surrounding the retention of human tissues following post-mortem examinations. In response, the Chief Medical Officer, the Royal College of Pathologists in the UK, the Faculty of Pathology of the Royal College of Physicians in Ireland, the British Medical Association, and other bodies have issued new guidelines that are of relevance to the Otolaryngologist. This paper gives details of some of the UK guidelines and where they can be accessed. A copy of the Royal College of Pathologists preferred post-mortem consent form is presented. The authors' experience in Manchester is discussed and details of an information leaflet on the subject of temporal bone donation are given. It is concluded that, with knowledge of the existing guidelines and good communication with other hospital colleagues, as well as families of the deceased, it is still possible legally to obtain temporal bones for dissection.

Education, Medical, Graduate↗
PubMed2000

The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II.

We showed previously that the WW domain of the prolyl isomerase, Ess1, can bind the phosphorylated carboxyl-terminal domain (phospho-CTD) of the largest subunit of RNA Polymerase II. Analysis of phospho-CTD binding by four other WW domain-containing Saccharomyces cerevisiae proteins indicates the splicing factor, Prp40, and the RNA polymerase II ubiquitin ligase, Rsp5, can also bind the phospho-CTD. The identification of Prp40 as a phospho-CTD binding protein represents the first demonstration of direct interaction between a documented splicing factor and the phospho-CTD. Domain dissection studies reveal that phospho-CTD binding occurs at multiple locations in Prp40, including sites in both the WW and FF domain regions. Because the conserved repeats of the CTD make it an ideal ligand for multi-site binding events, the implications of multi-site binding are discussed. Our data suggest a mechanism by which the phospho-CTD of elongating RNA polymerase II facilitates commitment complex formation by juxtaposing the 5' and 3' splice sites.

Amino Acid Sequence↗
PubMed2000

The application of computer-enhanced imaging to improve preoperative counselling and informed consent in children considering bone anchored auricular prosthesis surgery.

OBJECTIVES: Bone anchored auricular prostheses have become a valuable option in the treatment of congenital and acquired deformities of the pinna. However, preoperative counselling and informed consent remains a challenging issue. Until recently it has been difficult to provide the child with a realistic prediction of their own postoperative appearance. This is particularly relevant when a remnant pinna needs to be excised prior to the second stage. The potential for psychological repercussions and the possibility that remnant excision might compromise future autologous tissue reconstruction make it imperative that the decision to proceed with surgery is founded on the best possible information. METHODS: The authors describe the use of computer enhanced images using the Adobe Photoshop (Apple Mac. Inc.) software package to provide such a preview. This technique is used in the outpatient clinic as an adjunct to counselling provided by clinic staff and is reinforced by meeting children who have already enrolled on to the implant programme. Children are encouraged to follow the stages of their planned operation on the computer screen, providing an accurate insight into the physical consequences of surgery. RESULTS: Our experiences suggest that this approach has encouraged a better qualitative understanding of implant surgery which has helped to foster the on-going commitment that is required to maintain a long-lasting, trouble-free implant site. CONCLUSIONS: This application of the Adobe Photoshop package has strengthened our basis for a personal informed consent and has provided an opportunity to lessen the adverse psychological consequences of such irreversible surgery. It is commended for its simplicity as it employs established software to enhance photographic prints or slides taken from the child's clinical records.

Child↗
PubMed2000

Amyloidosis of Waldeyer's ring and larynx.

Amyloidosis of the upper aerodigestive tract is relatively rare. A case of localized amyloidosis involving all components of Waldeyer's ring with added laryngeal involvement is described. This has not been previously reported. A literature review of this conditions is presented.

Amyloidosis↗
PubMed1999

Phospho-carboxyl-terminal domain binding and the role of a prolyl isomerase in pre-mRNA 3'-End formation.

A phospho-carboxyl-terminal domain (CTD) affinity column created with yeast CTD kinase I and the CTD of RNA polymerase II was used to identify Ess1/Pin1 as a phospho-CTD-binding protein. Ess1/Pin1 is a peptidyl prolyl isomerase involved in both mitotic regulation and pre-mRNA 3'-end formation. Like native Ess1, a GSTEss1 fusion protein associates specifically with the phosphorylated but not with the unphosphorylated CTD. Further, hyperphosphorylated RNA polymerase II appears to be the dominant Ess1 binding protein in total yeast extracts. We demonstrate that phospho-CTD binding is mediated by the small WW domain of Ess1 rather than the isomerase domain. These findings suggest a mechanism in which the WW domain binds the phosphorylated CTD of elongating RNA polymerase II and the isomerase domain reconfigures the CTD though isomerization of proline residues perhaps by a processive mechanism. This process may be linked to a variety of pre-mRNA maturation events that use the phosphorylated CTD, including the coupled processes of pre-mRNA 3'-end formation and transcription termination.

Chromatography, Affinity↗
PubMed1999

The implant-site split-skin graft technique for the bone-anchored hearing aid.

We describe the technique of implant-site split-skin grafting for the bone-anchored hearing aid (BAHA). Twenty-five patients have undergone this procedure (20 adults and five children) since 1993 with a minimum follow-up of 1 year. Fifteen adults were operated upon as single stage surgery, all other cases (including all children) were performed in two stages. In four patients (16%) significant early graft inflammation was encountered which settled with outpatient treatment. In one the abutment had to be temporarily removed to allow the graft to settle. All patients now have a stable graft site. This surgical technique is straightforward and a separate graft donor site is avoided. It would appear this technique results in a stable BAHA graft site with low associated morbidity.

Adolescent↗
PubMed1998

Protonation of the neutral repeats of the RNA polymerase II CTD.

The CTD (carboxy-terminal repeat domain) of the largest subunit of RNA Polymerase II in most eukaryotes consists of from 26 to 52 seven amino acid repeats, the consensus sequence of which is YSPTSPS. Even though this consensus repeat does not contain residues that are normally protonated under the conditions used for positive ion electrospray mass spectrometry, we find that the CTD acquires about one proton per repeat when analyzed by this procedure. We have termed this phenomenon superprotonation. Superprotonation is apparently a property of the consensus sequence as the repeat peptide, (YSPTSPS)4, is superprotonated whereas other proteins and the repeat peptides (YSPTSPK)4, (YSPTSPR)4 and (YSPTAPR)4 are not. The highly conserved nature of the contiguous consensus repeats in organisms ranging from yeast to mammals implies that the functionally significant behavior of the domain is easily perturbed. We propose that CTD superprotonation is a manifestation of a unique biophysical property that will influence and could be the basis for consensus repeat function in vivo.

Amino Acid Sequence↗
PubMed1998

Bones of contention. The supply of temporal bones for dissection: the legalities, problems and solutions.

Temporal bone dissection is considered to be an important aspect of the otological training of the Specialist Registrar with dissection skills being formally assessed in the Intercollegiate Fellowship Examination. However the procurement of cadaveric specimens suitable for dissection may be fraught with difficulties. The authors take an historical perspective to clarify the existing legal issues and outline the means available to improve supply.

Autopsy↗
PubMed1997

Factor IX activation by factor XIa proceeds without release of a free intermediate.

Factor IX activation by factor XIa is thought to proceed through the singly-cleaved free intermediate, factor IX alpha. However, we observed no intermediate development during factor IX activation by factor XIa when using a low substrate to enzyme ratio (44:1 mol/mol). This result can be explained by one of two mechanisms: (1) factor XIa-catalyzed activation proceeds via a singly-cleaved free intermediate with a much higher efficiency of cleavage than factor IX zymogen, or (2) the reaction occurs without free intermediate generation, whereby factor XIa makes both proteolytic cleavages in a single substrate molecule before releasing the final product (processive mechanism). We compared the factor XIa cleavage rates of free factor IX alpha and factor IXa alpha with that of factor IX zymogen. In contrast to the requirements of mechanism (1), the cleavage rate constants of factor IX zymogen, factor IX alpha, and factor IXa alpha were similar: 0.38 +/- 0.02 s(-1), 0.34 +/- 0.05 s(-1), and 0.27 +/- 0.01 s(-1), respectively. It seems likely that factor XIa-generated intermediates observed under some reaction conditions are produced through the occasional failure of a processive mechanism. Indeed, in reactions using a high substrate to enzyme ratio (1900:1 mol/mol), we observed some factor IX alpha development; however, the pattern of intermediate and product development over time was inconsistent with a mechanism involving an obligate intermediate. Rather, it corresponded to behavior expected from a processive mechanism undergoing a consistent low failure. We conclude that factor XIa-catalyzed activation of factor IX proceeds via a processive mechanism without release of a free intermediate.

Antibodies, Monoclonal↗
PubMed1997

Assaying CTD kinases in vitro and phosphorylation-modulated properties of RNA polymerase II in vivo.

The functional properties of RNA polymerase II are modulated by hyperphosphorylation of its unique C-terminal repeat domain (CTD). A number of enzymes with CTD kinase activity have been identified, and correlations between CTD phosphorylation and RNA polymerase II function have been made. Here we describe methods for assaying CTD kinases and for characterizing them enzymologically. In addition we present approaches for studying phosphorylation-mediated behavior of chromosome-associated RNA polymerase II by using CTD-directed, phosphorylation state-sensitive antibodies and in situ localization techniques. The methods described here should, in conjunction with genetic approaches, contribute to elucidating the physiological roles of CTD kinases.

Animals↗
PubMed1995

Processive post-translational modification. Vitamin K-dependent carboxylation of a peptide substrate.

Mass spectrometry has been used to demonstrate that vitamin K-dependent carboxylation is a processive post-translational modification (i.e. multiple carboxylations occur during a single association between enzyme and substrate). Purified vitamin K-dependent carboxylase can carboxylate as many as 12 glutamate residues in FIXQ/S, a peptide substrate based on amino acids -18 to 41 of the human blood clotting enzyme factor IX. Mass spectrometry was used to determine the number of gamma-carboxyl groups added to FIXQ/S by the carboxylase during an in vitro reaction. Despite the fact that most substrate molecules in a reaction were uncarboxylated, almost all carboxylated FIXQ/S molecules were carboxylated many times. This observation can only be explained by two types of mechanisms. In a processive mechanism, multiple carboxylations could occur during a single substrate binding event. Alternatively, a distributive mechanism could result in the observed behavior if the initial carboxylation event results in a substrate that is additionally carboxylated far more efficiently than the uncarboxylated FIXQ/S. Kinetic experiments and arguments were used to show that the vitamin K-dependent carboxylase is not distributive but rather is one of the first well documented examples of an enzyme that catalyzes a processive post-translation modification.

Amino Acid Sequence↗
PubMed1995

Thrombosed posterior-inferior cerebellar artery aneurysm: a rare cerebellopontine angle tumour.

A case report of a thrombosed posterior-inferior cerebellar artery aneurysm is described. The tumour masqueraded as a vestibular schwannoma on imaging but the presenting features were unusual, the facial pain and weakness predominating despite well preserved hearing. This is an example of a rare cerebellopontine angle tumour and highlights the need for suspicion when lesions present atypically.

Aneurysm↗