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Biomedical subjects

M E Ward

Publications and source records attributed to M E Ward.

At least 109 records · Page 6Linked to original sources
PubMed1991

Expression of MHC class II antigens by conjunctival epithelial cells in trachoma: implications concerning the pathogenesis of blinding disease.

In an attempt to understand the pathogenesis of corneal changes and conjunctival scarring in trachoma, which are responsible for blindness in some 7 million people worldwide, the surface expression of major histocompatibility complex class II antigens on conjunctival epithelial cells was sought in patients with different clinical features of the disease. Class II expression was significantly associated with active (inflammatory) trachoma, but an independent association with corneal pannus or conjunctival scarring could not be shown. Longitudinal data suggest that class II expression may antedate clinically active disease and persist after it has resolved.

Adolescent↗
PubMed1990

Sulfur-rich proteins of Chlamydia trachomatis: developmentally regulated transcription of polycistronic mRNA from tandem promoters.

RNA was extracted at various times from cells infected with Chlamydia trachomatis serovar L1. Northern-blot analysis showed that transcription of the CrP gene encoding the 60-kDa cysteine-rich outer membrane protein (CrP) produces a temporally controlled polycistronic mRNA. Primer extension analysis indicated the presence of tandem promoters separated by 66 nt with transcriptional start points (tsp) located 577 and 643 nt upstream from the start codon of the mature 60-kDa CrP. Nucleotide (nt) sequencing of this region revealed a small open reading frame (SORF) with coding potential for an 88-amino acid protein containing 13 cysteine residues. This SORF is transcribed as both a polycistronic 2300-nt mRNA together with the CrP gene, and as a separate 480-nt mRNA. Analysis of the upstream sequences, around the tsp for these mRNAs, revealed the presence of three inverted repeat structures that might act as binding domain(s) for a regulatory protein.

Amino Acid Sequence↗
PubMed1990

Two cases of barotrauma associated with transtracheal jet ventilation.

Two patients suffered barotrauma whilst undergoing transtracheal jet ventilation (TTJV). In the first, TTJV was provided by a Sanders injector and in the second it was given by a high frequency jet ventilator. Barotrauma was a consequence of the expiratory pathway becoming blocked. The mechanism of barotrauma and a method of airway pressure monitoring during TTJV are discussed. It is recommended that meticulous care is taken to ensure an adequate path for expiration when jet ventilation is used.

Barotrauma↗
PubMed1990

Isolation of recombinant fragments of the major outer-membrane protein of Chlamydia trachomatis: their potential as subunit vaccines.

Recombinant fragments of the major outer-membrane protein (MOMP) of Chlamydia trachomatis, expressed at high levels in Escherichia coli, were isolated and purified. Antisera to the recombinant proteins reacted preferentially with overlapping synthetic peptides covering the immunoaccessible variable segments of MOMP. These sera also reacted in a species-specific manner with the surface of intact infectious elementary bodies, and in a Chlamydia genus-specific manner in assays using denatured or bound chlamydial antigens. The ability of recombinant MOMP preparations to elicit antibody to the surface of chlamydial elementary bodies raises the possibility that these proteins may be useful for chlamydial vaccine development.

Animals↗
PubMed1990

The major outer-membrane proteins of Chlamydia trachomatis serovars A and B: intra-serovar amino acid changes do not alter specificities of serovar- and C subspecies-reactive antibody-binding domains.

The major outer-membrane protein (MOMP) of Chlamydia trachomatis is a promising candidate antigen for chlamydial vaccine development. We have sequenced the MOMP genes for a serovar A and a serovar B isolate and have compared these new sequences with those already reported. Intra-serovar changes in the inferred amino acid sequences of the surface-exposed variable segments known to be responsible for binding of neutralizing antibody were observed. Nevertheless, epitope mapping with solid-phase peptides showed that these intra-serovar changes did not affect the binding of serovar- and subspecies-specific, potentially protective antibodies. Variable segment 1 of C. trachomatis serovar A contained two adjacent antibody-binding sites, one of which was C-subspecies specific while the other was serovar A specific. Therefore the subspecies binding site for C-complex organisms is in variable segment 1, whilst that for B-complex organisms is in variable segment 4. This work shows that MOMP sequences are relatively stable within the serovar categorization for isolates taken decades apart from different continents. Within a given serovar, however, limited interchange of functionally related amino acids may occur without impairing the binding of serovar-specific antibody.

Amino Acid Sequence↗
PubMed1990

Respiratory muscle incoordination in stuttering speech.

We investigated the role of respiratory muscle incoordination during stuttering by measuring esophageal, gastric, and transdiaphragmatic pressures to obtain subglottic pressure (Psg) and indices of diaphragmatic, rib cage, and abdominal muscle contraction during speech in normal volunteers and in severe stutterers. We found in contrast to the relatively constant subglottic pressure during normal conversational speech that speech in stutterers was characterized by failure to control Psg because of contraction of the diaphragm, rib cage, and abdominal muscles singly or in various combinations. As a result, Psg varied substantially and sometimes chaotically from too high to too low, rendering normal speech impossible. During periods of fluency, Psg was much better controlled. We conclude that incoordination of the respiratory muscles is a major problem in stuttering, resulting in failure to control the pressure difference across the vocal cords. It is unclear if this is a primary abnormality or is a secondary response to a primary abnormality elsewhere.

Adolescent↗
PubMed1990

Correlation of infertility with altered tubal morphology and function in mice with salpingitis induced by a human genital-tract isolate of Chlamydia trachomatis.

Progesterone-treated C3H mice were inoculated into the uterus or ovarian bursa with a human genital tract isolate of C. trachomatis (serovar E), or with control medium alone. The mice were then observed at various times up to 260 days after inoculation. Before being killed the mice were given pituitary gonadotrophins to induce ovulation. Eggs were sought in the oviducts and ciliary activity in the fimbrial and ampullary sections of the oviducts was determined by light microscopy, before detailed examination by scanning electron microscopy. Eggs were visible in all control oviducts and both mucosal ultrastructure and ciliary activity appeared normal. By contrast, eggs were not recovered from the inoculated oviducts of mice infected intrabursally, nor was ciliary activity observed up to 28 days after inoculation. After this, ciliary activity reappeared but eggs were still not transported to the oviduct. Ultrastructural studies suggested that severe mucus congestion accompanied by tubal oedema and loss of ciliated epithelia play a major role in the aetiology of chlamydial-induced tubal damage. Infertility following chlamydial salpingitis could be associated with failure of egg transportation to the oviduct. Egg transport was still impaired even when luminal ciliary activity, ultrastructural integrity and patency had recovered. Our results suggest that chlamydial salpingitis in this mouse model closely resembles the human disease in its pathology and consequences for fertility, making the model particularly relevant for research on chlamydial vaccine development.

Animals↗
PubMed1990

Capital management balances charitable, financial goals.

Effective capital management allows not-for-profit healthcare organizations to make investment decisions that fulfill their missions and meet financial goals. The process involves identifying components of the hospital's value and creating policies aimed at maximizing it; determining the hospital's ability to produce financial capital; and developing a process for allocating this financial capability among the components of value. Once this is completed, hospitals should determine criteria that balance charitable and financial goals, enabling them to pursue sound investments.

Capital Expenditures↗
PubMed1989

Chlamydia trachomatis 60 kDa cysteine rich outer membrane protein: sequence homology between trachoma and LGV biovars.

An 820 bp AccI-PstI fragment of the 60 kDa cysteine rich outer membrane protein (CrP) gene from C. trachomatis serovar L1 was used as a probe to locate the 60 kDa CrP gene of a recent serovar B trachoma isolate (Jali 20/OT). The probe hybridized to a single 1.8 kb SpeI fragment in Southern blot analyses of different restriction endonuclease digests of C. trachomatis serovar B DNA. This fragment was ligated into Lambda Zap II arms and Bluescript SK(-) recombinants, released by infection with the helper phage R408, were used as template for DNA sequence determination. Sequence analysis demonstrated a very high level of homology between the Jali 20/OT 60 kDa CrP and the previously published serovar L1 60 kDa CrP with only 8 out of 507 amino acid substitutions between the two proteins.

Amino Acid Sequence↗
PubMed1989

Analysis of the household distribution of trachoma in a Gambian village using a Monte Carlo simulation procedure.

Studies on the household distribution of trachoma have reached conflicting conclusions. This paper describes a cross-sectional survey of endemic trachoma in a Gambian village. Cases of active trachoma were mapped, and the compound and household distribution of the disease analysed by a Monte Carlo simulation procedure which takes into account differences in the size and age distribution within individual households. Significant clustering of active trachoma cases both by village compound (p less than 0.0001) and bedroom (less than 0.05) were detected supporting the concept that intra-familial transmission of trachoma is important. There was no evidence of spatial clustering of rooms with higher than expected prevalence of trachoma. Clustering of disease in space or time provides important evidence of infectious aetiology and route of transmission. The methods discussed here are generally applicable in the study of other infectious diseases.

Adolescent↗
PubMed1989

Surface-exposed epitopes on the major outer-membrane protein of Chlamydia trachomatis defined with peptide antisera.

The surface exposure of computer-predicted, linear B-cell epitopes on the major outer-membrane protein (MOMP) of Chlamydia trachomatis serovar B was assessed using antibodies raised against synthetic peptides in conjunction with immunogold transmission electron microscopy. Several of the chosen peptides elicited antibodies which reacted with both denatured and native MOMP. The majority of the exposed epitopes were found within the variable segments of MOMP. For each of the epitopes identified, the extent of their surface accessibility varied both among individual organisms and different developmental forms. Evidence for two distinct subspecies-specific epitopes within VS4 is presented.

Amino Acid Sequence↗
PubMed1989

The major outer membrane protein of Chlamydia trachomatis: critical binding site and conformation determine the specificity of antibody binding to viable chlamydiae.

The major outer membrane protein (MOMP) is the prime candidate for the development of a chlamydial vaccine. Antibodies to the subspecies-specific epitope neutralize chlamydial infection. Monoclonal antibodies (MAbs) to this epitope were prepared either by immunization with whole chlamydiae or with a 16 amino acid synthetic peptide. The critical binding site on the subspecies epitope for these MAbs was determined to single amino acid resolution using several hundred solid-phase peptides. A frame shift of just one amino acid in critical binding site completely prevented antibody binding to viable chlamydiae. A single MAb to whole organisms was capable of spanning both the surface-exposed, conformation-dependent, subspecies epitope and a buried, conformation-independent species epitope some 10 A distant. Immunization with peptide generated an MAb with reduced binding constraints which permitted the antibody to bind with broadened species-specificity at the subspecies binding site. The results show for the first time the importance of both critical binding site and conformation at the subspecies epitope. We suggest that the conformational flexibility of short, epitopic peptide vaccines may in some cases be advantageous, giving rise to extended specificity not attained with the natural protein.

Amino Acids↗
PubMed1988

Molecular cloning and sequence analysis of a developmentally regulated cysteine-rich outer membrane protein from Chlamydia trachomatis.

Two overlapping genomic fragments have been cloned from Chlamydia trachomatis serovar L1 DNA. Sequence determination of 2530 bp has revealed two open reading frames coding for 'cysteine-rich' (Cr) proteins. One of these proteins was confirmed, by analysis of the inferred amino acid sequence, as the 60-kDa Cr outer membrane protein associated with differentiation of reticulate bodies (RBs) into elementary bodies (EBs). The other smaller 15-kDa protein contained a high percentage of methionine and cysteine and may correspond to a reported smaller and co-ordinately synthesised Cr outer-membrane protein also associated with RB to EB differentiation. Sequencing showed three potential stem-loop structures within the 5', 3' and intergenic regions of the cloned fragment. Southern-blot analysis revealed that the cloned fragment is conserved in ten serovars of C. trachomatis and that a strongly cross-hybridising fragment is also present in Chlamydia psittaci.

Amino Acid Sequence↗
PubMed1988

Analysis of the entire nucleotide sequence of the cryptic plasmid of Chlamydia trachomatis serovar L1. Evidence for involvement in DNA replication.

Chlamydia trachomatis serovar L1/440/LN possesses a 7498bp plasmid which was designated pLGV440. The plasmid was cloned at the BamH1 site of pAT153 into Escherichia coli and the recombinant plasmid was designated pCTL1. A detailed restriction endonuclease map of pCTL1 was constructed. A fragment of the chlamydial plasmid was shown to function as a promoter in E. coli when placed upstream of the lacZ gene. The entire plasmid was sequenced by the chain termination method. Open reading frames were identified from the resulting consensus sequence together with a candidate for the plasmid origin of replication consisting of four perfect tandem repeats of a 22bp sequence, an A:T rich sequence and an open reading frame which could generate a 34.8kdal product. The predicted polypeptide products of the open reading frames were compared by computer with all reported protein sequences. Homology of the predicted polypeptide product of an open reading frame to the E. coli dnaB protein and the analogous product of gene 12 of bacteriophage P22 is described.

Amino Acid Sequence↗
PubMed1988

Optimization of respiratory muscle relaxation during mechanical ventilation.

The authors calculated the active work of inspiration (Wp) and the inspiratory muscle pressure-time product (integral of Pmus.dt) in seven patients undergoing mechanical ventilation (MV). This was done by comparing the areas under the inflation pressure-volume and inflation pressure-time curves generated when the patient was contributing to the work of ventilation with those following sedation, when inspiratory muscle activity was absent (defined as absence of diaphragmatic EMG activity and of palpable accessory muscle contraction). Inspiratory muscle inactivity could be predicted by the observation of a smooth rise in inflation pressure that was highly reproducible from breath to breath. Relaxation was present without sedation during MV in the control mode with inspiratory flow rates above 65 1/min. In the assist mode (AMV), both Wp and integral of Pmus.dt were significantly (P less than 0.05) greater than in the control (CMV) mode. Reducing trigger sensitivity during AMV further increased Wp and integral of Pmus.dt (P less than 0.05). During AMV and CMV Wp and integral of Pmus.dt decreased with increasing rate of inspiratory flow delivered by the ventilator. With AMV at low trigger sensitivity and low flow rates, Wp approached 65% of the total inspiratory work. The authors conclude that inspiratory muscle activity can be substantial during MV, particularly during AMV at low trigger sensitivity and flow. Monitoring of inflation pressure is a simple means of determining the degree of inspiratory muscle rest during MV.

Humans↗
PubMed1988

Epitope mapping with solid-phase peptides: identification of type-, subspecies-, species- and genus-reactive antibody binding domains on the major outer membrane protein of Chlamydia trachomatis.

The major outer membrane protein (MOMP) of Chlamydia trachomatis carries serovar-, subspecies-, species- and genus immunodomains, antibodies to which may be protective. We have compared the inferred amino acid sequences for MOMP from different serovars of C. trachomatis and from Chlamydia psittaci to identify the likely locations of these sero-taxonomic epitopes. Overlapping peptides corresponding to each of these regions were synthesized on a solid phase and probed with monoclonal antibodies (MAbs) of appropriate specificities. We describe the primary structures of the binding sites of MAb to each of these four epitopes on C. trachomatis serovar L1 MOMP.

Amino Acid Sequence↗