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Biomedical subjects

M D Ryan

Publications and source records attributed to M D Ryan.

At least 19 recordsLinked to original sources

The epidemiology of fractures and fracture-dislocations of the cervical spine.

A total of 717 fractures and fracture-dislocations of the cervical spine occurred in 657 patients in a 13-year period. Injury was commonest in the third decade of life. The levels most frequently injured were the second, fifth, and sixth. Injuries of the first and second cervical vertebrae commonly occurred together, and injuries involving the upper and lower cervical spine in the same individual occurred in 9 per cent of patients with fractures of C1 and C2. Odontoid fractures were the most frequent fractures in patients over 70 years of age, and formed the majority of fractures in patients over 80 years of age. It is recommended that if a fracture of the upper cervical spine is seen on radiographs, another fracture in the upper or lower cervical spine should be excluded. Patients aged 70 years and above who complain of neck pain after trauma should be suspected of having an odontoid fracture, until proven otherwise.

Adult

The management of an old fused hip after the occurrence of paraplegia.

Two patients are reported who suffered traumatic paraplegia, and had a long-standing fused hip joint. Both required an excision (Girdlestone) arthroplasty to allow them to sit and one, who made a late but substantial neurological recovery, eventually underwent a total hip replacement. Both suffered thromboembolic and urinary complications. These may not have occurred if the procedures had been carried out earlier. Early mobilisation of the hip joint is recommended in these circumstances.

Adult

Spinal manifestations of Paget's disease.

This paper reviews the syndromes which affect the spinal column as a result of Paget's disease. These are back pain, spinal canal stenosis, paraplegia or paraparesis, sarcomatous transformation, intradiscal invasion, and extramedullary haemopoesis.

Back Pain

Neurological deterioration after reduction of cervical subluxation. Mechanical compression by disc tissue.

We report three patients with neurological deterioration after the reduction of cervical spine dislocation. In each case compression of the spinal cord by disc material was demonstrated by magnetic resonance imaging and recovery occurred following removal of the compressing disc. A separate radiological study suggested that disproportionate narrowing of the disc space implies disc extrusion; reduction of a dislocation showing this sign may produce or exacerbate neurological deterioration.

Adult

Depo-Medrol and myelographic arachnoiditis.

OBJECTIVE: This study was undertaken to see if patients who had a radiological diagnosis of arachnoiditis attributed to methylprednisolone acetate (Depo-Medrol, Upjohn Pty Limited) had the clinical syndrome of arachnoiditis. DESIGN: An attempt was made to review all patients, reported by Roche in 1984 with a radiological diagnosis of corticosteroid-induced arachnoiditis, by taking a detailed history and performing a physical examination. SETTING: The Department of Orthopaedics and Traumatic Surgery, The University of Sydney, The Royal North Shore Hospital, Sydney. RESULTS: Of the 18 patients reported by Roche 15 were located and participated in this study. The clinical syndrome of arachnoiditis was defined as a constant burning pain in the back and legs, impotence, marked limitation of spinal motion, alteration of sensation and power in the legs, and a need for regular analgesia. Three of the 15 patients had the clinical syndrome of arachnoiditis. The grade of radiological change was unrelated to the severity of symptoms. The details of doses and precise sites of administration were unavailable for the severely affected individuals. CONCLUSIONS: The absence of any other apparent cause for their symptoms implies that Depo-Medrol should not be used in or about the thecal sac.

Adult

Cleavage of foot-and-mouth disease virus polyprotein is mediated by residues located within a 19 amino acid sequence.

The 2A region of the foot-and-mouth disease virus (FMDV) polyprotein is only 16 amino acids in length. During synthesis of the FMDV polyprotein a primary proteolytic processing event occurs between the 2A and 2B regions of the polyprotein. The activity responsible for this cleavage is not known but it is thought that either an unidentified virus-encoded proteinase may be responsible, or that 2A acts as a substrate for a host cell proteinase. A series of recombinant FMDV polyproteins has been constructed in which sequences to the N- or C-terminal side of the 2A region have been deleted. Analysis of the processing of these polyproteins shows that a 19 amino acid sequence spanning 2A is sufficient to mediate polyprotein cleavage at a site immediately C-terminal to 2A, whereas deletions extending into the 2A region prevent cleavage.

Amino Acid Sequence

Polyacetal rod fixation of fractures in osteoporotic bone. A preliminary report.

Intramedullary rods manufactured from polyacetal were used to fix diaphyseal fractures in osteoporotic bone. They are pliable and can be introduced without further damage to such bone. Their low elastic modulus induces abundant callus. They can be locked with cortical bone screws without the need of jigs or radiographic control. Nine femoral and five tibial fractures were fixed in 10 patients, all with osteoporosis; 13 united primarily; one required bone grafting. No implant broke; however, no ambulant patient weighed more than 75 kg. The rods offer a promising treatment for diaphyseal fractures in osteoporotic bone.

Acetals

Intracellular expression and processing of foot-and-mouth disease virus capsid precursors using vaccinia virus vectors: influence of the L protease.

cDNA cassettes of FMDV have been constructed which encode the capsid precursor (P1-2A) alone or with the proteases L and 3C which are required for processing of this precursor to the products 1AB, 1C, and 1D. These cassettes have been analyzed using in vitro transcription and translation reactions and within cells using recombinant vaccinia viruses. Processing of the precursors occurred more efficiently in cells than in cell-free systems but similar properties were observed. It was not possible to isolate recombinant vaccinia viruses containing FMDV cassettes which included the intact coding sequence for the L protein. Deletion of part of the L sequence, which abolished its proteolytic activity, also abolished this incompatibility with vaccinia virus. The vaccinia recombinant, vTF7-3, which expresses the bacteriophage T7 RNA polymerase was used in transient expression studies using plasmids containing a T7 promoter upstream of the FMDV cassettes. Under these conditions it was possible to coexpress L, P1-2A, and 3C in the vaccinia-infected cells; each of the proteolytic activities was observed and correctly processed 1AB, 1C, and 1D were produced.

Aphthovirus

The complete nucleotide sequence of enterovirus type 70: relationships with other members of the picornaviridae.

Enterovirus type 70 (EV70) is the causative agent of acute haemorrhagic conjunctivitis and may also give rise to a rare neurological complication closely resembling poliomyelitis. The complete nucleotide sequence of the genome of EV70 has been determined from cDNA cloned in Escherichia coli. The genome consists of a 5' non-coding region of 726 nucleotides (nt), a long open reading frame of 6582 nt and a 3' non-coding region of 82 nt prior to the poly(A) tract. Comparison of the nucleotide sequence and the predicted amino acid sequence of the polyprotein with those published for other enteroviruses reveals sufficiently high similarity to predict antigenic regions and polyprotein cleavage sites. The P1 region of EV70 is as similar to those of the entero- as to those of the rhinoviruses, whereas the P2 and P3 regions are more closely related to the coxsackie B and swine vesicular disease viruses than other entero- or rhinoviruses.

Amino Acid Sequence

Synthesis of foot-and-mouth disease virus capsid proteins in insect cells using baculovirus expression vectors.

Foot-and-mouth disease virus (FMDV) cDNA cassettes containing sequences encoding the capsid precursor P1-2A with and without those encoding the proteases L and 3C were introduced into Autographa californica nuclear polyhedrosis virus (AcMNPV) expression vectors. Procapsid proteins 1AB, 1C and 1D were produced in cells infected with recombinant baculoviruses, when L and 3C were present in the constructs, indicating that these FMDV proteases were active in insect cells. Unlike P1 processing in poliovirus, which has been shown to be catalysed mainly by the 3CD gene product, the 3C protease of FMDV was able to process P1 independently of 3D. Cytotoxicity of the L protease for insect cells prevented the use of the optimized transfer vector, pAcRP23, for inserting L-containing cassettes into AcMNPV. By contrast, viable AcMNPV-FMDV recombinants could be made without restriction on choice of the transfer vector when the L gene was either not expressed or inactivated by an inframe deletion. In the latter case, normal cleavage at the L-P1 junction no longer occurred in cis, and a new processing event, probably catalysed by 3C, was observed within the C-terminal region of the residual L protein. Analysis of baculovirus-expressed products in sucrose gradients showed that a fraction of the capsid proteins is present in an aggregated form, migrating at 70S and possibly resembling FMDV empty capsid particles.

Animals

Electrochemistry of cyclic alpha-imino carboxylates and their metal complexes: correlation with physiological activity.

Cyclic voltammetry data were obtained for delta 1-pyrroline-2-carboxylate, delta 3-thiazoline-4-carboxylate, delta 2-thiazoline-2-carboxylate and their complexes with Cu(II), Fe(III), and Fe(II). The free ligands were reduced at about -0.35 V and were oxidized in the range of 0.42-0.52 V. Complexing the imine carboxylates with metal ions produces reduction and oxidation in the ranges of 0.05-0.37 V and 0.52-0.74 V, respectively. Prior reports show that these ligands take part in various biological functions. We propose that electron transfer may be involved in some aspects of the physiological activity. The captodative effect can be applied.

Copper

Specificity of enzyme-substrate interactions in foot-and-mouth disease virus polyprotein processing.

A series of transcripts derived from FMDV cDNA plasmids containing defined regions of the genome were translated in a rabbit reticulocyte lysate system. The products were analysed directly or following incubation with an FMDV-infected cell processing extract. Processing by the L proteinase at the L/1A cleavage site occurred when most of the P1-2A protein was absent. Substitution of sequences upstream of the 2C/3A cleavage site showed that the 3C proteinase was also able to cleave at an entirely novel cleavage site, apparently at K-I amino acid pairs. Cleavage at the 2A/2B site was not only independent of L and 3C proteinases, but was shown to occur when 2A and as few as four 2B N-terminal amino acids were present. Thus, the disparate proteolytic activities responsible for all three primary processing events that give rise to the products L, P1-2A, 2BC, and P3 were highly resistant either to major deletion or substitution of protein sequences adjacent to, or at, the site of cleavage. By contrast, secondary processing in trans was sensitive to changes at remote sites. For example, removal of the C-terminal regions of P1-2A and 2BC precursors impaired their ability to act as substrates for 3C proteinase activity. Processing of P1-2A, particularly of the 1D/2A cleavage site, was enhanced by inclusion of sequences from the 3D region of the genome.

Aphthovirus

Reduction potentials of anthelmintic drugs: possible relationship to activity.

Electrochemical data were acquired for several categories of anthelmintic agents, namely, iminium-type ions, metal derivatives and chelators, quinones and iminoquinones, and nitroheterocycles. Reductions usually were in the favorable range of +0.2 to -0.7 V versus normal hydrogen electrode. The drug effect is believed to result in part from either the catalytic production of oxidative stress or disruption of helminth electron transport systems. Relevant literature results are discussed.

Animals

Minimum essential structural requirements for lactam antibiotic action.

A mechanism of action encompassing mono- and bicyclic beta-lactams has been proposed previously, which stresses the importance of formation of an electron transfer (ET) entity (conjugated iminium) as a requirement for antibiotic activity, in association with enzyme inactivation. Additional evidence in support of this contention is now provided. Reduction potentials for several cephalosporins and pyrazolidinones, all of which contain an oximino functionality in the side chain, were observed in the range of -0.6 to -0.7 V. Comparison is made with related compounds lacking imine. Agents containing side chain hydrazone, oxamazins (mono beta-lactams), and lactivicin are discussed based on the ET approach.

Anti-Bacterial Agents