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Biomedical subjects

D Nunn

Publications and source records attributed to D Nunn.

At least 19 recordsLinked to original sources
PubMed1999

Bacterial type II protein export and pilus biogenesis: more than just homologies?

Protein export by Gram-negative bacteria requires devoted machineries to allow for the passage of hydrolytic enzymes and toxins through the cell envelope. The Type II export machinery has a number of distinct characteristics, which include its role as an extension of Sec-dependent secretion, its ability to recognize and export fully folded substrates efficiently and, perhaps most significantly, the relationship between a subset of its gene products with the Type IV pilus-biogenesis apparatus. An important question is whether we can extrapolate our knowledge, albeit limited, of Type IV pilus biogenesis to understand the structure and function of the Type II export apparatus. This and other questions relating to the energetics of assembly and specificity of the apparatus are addressed in this article.

Bacterial Proteins↗
PubMed1991

Interaction of Pseudomonas aeruginosa with A549 pneumocyte cells.

The interaction of Pseudomonas aeruginosa with a human lung pneumocyte cell line (A549) was studied. Wild-type strain PAK adhered efficiently to the A549 cells, while an isogenic mutant, carrying a mutation in the pilin structural gene, adhered at 10 to 20% of the wild-type levels. Another nonpiliated mutant of P. aeruginosa PAK, defective in the pleiotropic regulatory gene rpoN, did not adhere to A549 cells, suggesting the presence of a second, RpoN-controlled adhesin on the bacterial surface. Endocytosis of wild-type P. aeruginosa PAK by A549 cells was also demonstrated. A significant fraction of the internalized bacteria were recovered in a viable form after several hours of residence within the A549 cells. When examined by electron microscopy, intracellular bacteria were located in membranous vesicles, and no evidence of killing by lysosomal mechanisms was observed. These studies raise the possibility that during chronic respiratory tract infections in immunocompromised patients, P. aeruginosa may persist in intracellular compartments and therefore be protected from the defense mechanisms of the host.

Adhesins, Bacterial↗
PubMed1991

Multiple roles of the pilus biogenesis protein pilD: involvement of pilD in excretion of enzymes from Pseudomonas aeruginosa.

In Pseudomonas aeruginosa, the genes pilB, pilC, and pilD encode proteins necessary for posttranslational modification and assembly of pilin monomers into pilus organelles (D. Nunn, S. Bergman, and S. Lory, J. Bacteriol. 172:2911-2919, 1990). We show that PilD, encoding a putative pilin-specific leader peptidase, also controls export of alkaline phosphatase, phospholipase C, elastase, and exotoxin A. pilD mutants accumulate these proteins in the periplasmic space, while secretion of periplasmic and outer membrane proteins appears to be normal. The periplasmic form of exotoxin A was fully mature in size, contained all cysteines in disulfide bonds, and was toxic in a tissue culture cytotoxicity assay, suggesting that in pilD mutants, exotoxin A was folded into its native conformation. The function of the other two accessory proteins, PilB and PilC, appears to be restricted to pilus biogenesis, and strains carrying mutations in their respective genes do not show an export defect. These studies show that in addition to cleaving the leader sequence from prepilin, PilD has an additional role in secretion of proteins that are released from P. aeruginosa into the surrounding media. PilD most likely functions as a protease that is involved in processing and assembly of one or more components of the membrane machinery necessary for the later stages of protein extracellular localization.

ADP Ribose Transferases↗
PubMed1990

The effect of a metal-back without a stem upon the fixation of a tibial prosthesis.

Three methods of tibial component fixation without cement (as part of TKA) have been used at the London Hospital. All three methods have used the same polyethylene component fixed with two HDP (Day) pegs. A metal-back without a stem was added to the HDP in group 1. Group 2 consisted of an HDP-only component. In group 3 a stem was added to the metal-back used in group 1. Radiological comparison showed the fixation of the polyethylene component with metal back but no stem to be inadequate; the component tilted into varus more frequently than the other configurations. It is suggested that failure was due to the increased rigidity of the metal-backed component (as compared with the HDP only) and that the rigidity (and the resultant tendency to rock) can be offset by a stem. It is concluded that rigid (ie, metallic) tibial components should have a stem.

Aged↗
PubMed1990

ICLH double-cup arthroplasty, 1980-1987.

The results are presented of 92 double-cup arthroplasties modified in light of previously published experience. The review period lasted up to 7 years after operation. Eighty-six had a metal femoral component and six had a ceramic femoral component. Forty metal femoral cups were matched with a cemented acetabulum, while with 46 the acetabular implant was cementless. The overall revision rate for the metal femoral cups was 23.3%, and a further 31.8% demonstrated radiological signs suggestive of loosening. There was no difference between the cemented and uncemented cups in terms of revision rates or clinical results. The clinical results of those hips that have not yet loosened were excellent. A histological study showed that femoral lossening was associated with an erosive cellular response. Surface arthroplasty of the hip with current materials should be abandoned.

Adult↗
PubMed1990

Products of three accessory genes, pilB, pilC, and pilD, are required for biogenesis of Pseudomonas aeruginosa pili.

The polar pili of Pseudomonas aeruginosa are composed of monomers of the pilin structural subunits. The biogenesis of pili involves the synthesis of pilin precursor, cleavage of a six-amino-acid leader peptide, membrane translocation, and assembly of monomers into a filamentous structure extending from the bacterial surface. This report describes three novel genes necessary for the formation of pili. DNA sequences adjacent to pilA, the pilin structural gene, were cloned and mutagenized with transposon Tn5. Each of the insertions were introduced into the chromosome of P. aeruginosa PAK by gene replacement. The effect of the Tn5 insertions in the bacterial chromosome on pilus assembly was assessed by electron microscopy and sensitivity of mutants to a pilus-specific bacteriophage. The resultant mutants were also tested for synthesis and membrane localization of the pilin antigen in order to define the genes required for maturation, export, and assembly of pilin. A 4.0-kilobase-pair region of DNA adjacent to the pilin structural gene was found to be essential for formation of pili. This region was sequenced and found to contain three open reading frames coding for 62-, 38- to 45-, and 28- to 32-kilodalton proteins (pilB, pilC, and pilD, respectively). Three proteins of similar molecular weight were expressed in Escherichia coli from the 4.0-kilobase-pair fragment flanking pilA with use of a T7 promoter-polymerase expression system. The results of the analyses of the three genes and the implications for pilin assembly and maturation are discussed.

Bacterial Outer Membrane Proteins↗
PubMed1989

Torsional stability of the femoral component of hip arthroplasty. Response to an anteriorly applied load.

Torsional instability of femoral components has not received much attention, and is difficult to detect in conventional radiographs. To test this we designed a system to apply a load in an anteroposterior direction to the head of a femoral component, implanted into a cadaveric femur. Rotation within the bone was measured, using a purpose built transducer, with and without preservation of the neck, with and without cement, and with longitudinal ridges but no cement. The results show that torsional instability may be a problem in uncemented replacement. Preservation of the femoral neck and the use of a ridged prosthesis increases resistance to rotation. Rotational movements occurring in vivo during such activities as climbing stairs and rising from the seated position may contribute to mechanical loosening.

Biomechanical Phenomena↗
PubMed1989

The measurement of migration of the acetabular component of hip prostheses.

Individual components of a total hip replacement are difficult to evaluate and quantify. We have studied the assessment of the acetabular component, and conclude that the measurement of migration allows the comparison of implants, although there is no established link between migration and significant loosening. A method of measurement based on clinical radiographs has been developed, and its limitations estimated. The accuracy of the technique was calculated to be +/- 3 mm.

Acetabulum↗
PubMed1988

Sliding hip screws and medial displacement osteotomy.

The case notes and radiographs of 108 patients who had undergone compression screw fixation of trochanteric fractures of the femur were reviewed. Forty-seven patients had unstable comminuted fractures, and 20 of these had medial displacement osteotomies performed. In 40% of this group the operation was not a success in terms of extrusion of the screw through the femoral head, compared with 20% for the whole series of 108 patients. A number of parameters were studied in the search for a cause for the failure, and there was a correlation with a superior position of the screw initially, and a low serum albumin. Although the proximal fragment abutted the plate at the time of operation, the medial cortices of the proximal and distal fragments were often not in apposition, allowing the fracture to collapse into varus with resultant extrusion. Unless a stable configuration is achieved at the time of operation, reliance on the sliding component of these implants to allow for collapse at the fracture site will not necessarily produce this stability, and failure will ensue.

Aged↗
PubMed1988

The Ring uncemented plastic-on-metal total hip replacement. Five-year results.

The Ring plastic-on-metal total hip replacement was introduced with the intention of combining the advantages of the cemented low-friction arthroplasty with those of a cementless system. Fourteen hundred and eighty-eight of these procedures have been reviewed. The results of a two to seven-year follow-up, and of a group which has completed at least five years are presented. There was an excellent clinical result in 93% of the whole series, and in 87% of the five-year group. When graded on the Charnley scale there was an average score of 5.86 for pain, 5.96 for function and 5.9 for range of movement, which compares favourably with cemented replacements. The deep infection rate was zero, and the revision rate 1.5% for the whole series. Erosive problems occurred with the smaller acetabular components and the reasons are discussed. The ease and success of exchange have been maintained.

Adult↗
PubMed1987

The Ring uncemented polyethylene cup in the abnormal acetabulum.

The results of using the Ring uncemented polyethylene-to-metal (UPM) prosthesis in patients with protrusio acetabuli or dysplasia are reported. Fifty-four cases of protrusio were analysed and a modified method of measuring the deformity is described; after operation, remodelling of the medial wall had improved, on average, by 29.6%. For the dysplastic acetabulum the main difficulty is the lack of lateral support for the cup. In order to test the hypothesis that this support improves with an uncemented prosthesis, 38 hips with an average follow-up of 31 months were studied. Lateral support, measured radiographically, showed an average increase of 21%. The remodelling effect may be attributed to the biomechanical design of the prosthesis.

Acetabulum↗
PubMedDate not supplied

Shifting the blame.

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Community Mental Health Services↗