334 results match your criteria: "University of Manchester Medical School.[Affiliation]"

Rat CD4+ T cells are divided phenotypically by the anti-CD45RC monoclonal antibody OX22 into subsets with contrasting functions. Stimulation of T cells in vitro is known to induce a change in isoform from CD45RC+ to CD45RC-. We have investigated the in vitro conditions which promote a switch in isoform in the opposite direction.

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Using epitope scanning of 272 short, synthetic peptides representing the amino acid sequence of the CB-11 peptide of type II collagen, we have shown that five strains of rat, immunized with type II collagen, produce antibodies to a region 37-45 amino acids from the amino end of CB-11 peptide. Antibodies to this region always gave the highest binding values suggesting that it is an immunodominant region. Wistar rats immunized with a synthetic peptide representing this region, coupled to keyhole limpet haemocyanin, produced antibodies to this peptide which could still be detected at 1:4000 to 1:8000 dilution but none developed clinical arthritis.

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Collagen fibrils generated in vitro at 37 degrees C by enzymic removal of C-terminal propeptides from type I pC-collagen (an intermediate in the normal processing of type I procollagen to collagen containing the C-terminal propeptides but not the N-terminal propeptides) display shape polarity, with one tip fine tapered and the other coarse tapered. Mass measurements by scanning transmission electron microscopy show that the mass per unit length along both kinds of tip increases roughly linearly over distances of approximately 100 D periods from the fibril end [D (axial periodicity) = 67 nm]. The fine tips of fibrils of widely differing lengths exhibit near-identical mass distributions, the mass in all cases increasing at the rate of approximately 17 molecules per D period, irrespective of fibril length.

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Aim: To determine the presence and nature of amyloid in prostatic corpora amylacea using immunohistological studies.

Methods: Prostatic tissue from 18 transurethral and two open resection specimens was studied. Paraffin wax embedded tissue sections were stained with haematoxylin and eosin and the alkaline Congo red method with and without previous treatment with potassium permanganate.

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Milestones in cystic fibrosis.

Br Med Bull

October 1992

Paediatric Genetics Unit, Royal Manchester Children's Hospital, University of Manchester Medical School, UK.

The study of cystic fibrosis (CF) provides a fascinating insight into developments in medicine in the 20th century. Milestones include the first clear clinical descriptions in the 1930s, discovery of a sweat electrolyte abnormality, establishing the autosomal recessive mode of inheritance and improvements in treatment. Microdissection experiments on sweat glands allowed the main defect to be delineated as one of chloride transport.

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Thirty isolates of Torulopsis glabrata were examined by pulsed-field gel electrophoresis, which resolved 13 DNA pieces, allowing the identification of 12 types. Bands at 1,400, 1,200, 1,070, 1,025, 681, and 500 kbp were conserved. When applied to 18 isolates from an outbreak, 10 distinct types were identified by this technique.

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1. The effects of endothelium removal and of a number of pharmacological agents known to modify endothelial cell function on the contractile response of rabbit isolated basilar arteries to 5-hydroxytryptamine (5-HT) and other vasoconstrictors were studied. 2.

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The binding sites for MoAbs to the 65-kD heat-shock protein (hsp65) of mycobacteria have been investigated by epitope scanning. Five hundred and twenty-six 8-mer peptides representing the complete sequence of Mycobacterium tuberculosis hsp65 were synthesised in duplicate using the Epitope Scanning Kit (CRB Ltd.).

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The potent anabolic effects of the beta 2-adrenoceptor agonist clenbuterol on skeletal muscle have been reported to be independent of actions on beta-adrenoceptors. In the present study clenbuterol, presented to rats in the diet (4 mg/kg), caused significant increases in gastrocnemius muscle mass, protein, and RNA content and a decrease in epididymal fat pad mass. These effects were not mimicked by oral administration of the beta 2-adrenoceptor agonist salbutamol even at high dose (52 mg/kg diet), and the effects of clenbuterol were not inhibited by addition of DL-propranolol (200 mg/kg diet).

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Various parameters for assessing endothelial cell (EC) metabolism, including immunohistochemistry and adenosine uptake, have been compared in the clinically uninvolved skin of patients with diffuse systemic sclerosis (DSS), CREST, incomplete CREST syndrome (ICREST), primary Raynaud's disease (1 degree RD) and normal controls. Evidence of platelet adhesion to EC, decreased EC storage of factor VII-related antigen, changes in EC morphology and decreased adenosine uptake by EC, were found in the dermal microvasculature of normal skin of patients with DSS, CREST and ICREST, but not in 1 degree RD. These data indicate that a generalized microvascular endothelial dysfunction is present in the skin of patients with the systemic forms of scleroderma.

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The genetic epidemiology of rheumatoid arthritis.

Clin Exp Rheumatol

June 1992

Arthritis and Rheumatism Council Epidemiology Research Unit, University of Manchester Medical School, U.K.

This review considers the epidemiological aspects of the genetic investigation of rheumatoid arthritis (RA). Problems both of disease definition and disease heterogeneity render studies difficult to undertake and interpret. The selection of individuals both in population and family studies can explain divergent results.

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Aims: To develop a genome based DNA fingerprinting system for Aspergillus fumigatus mould.

Methods: DNA was extracted from 21 isolates obtained from eight patients with an aspergilloma. This was with a freeze-dried mycelial extract fragmented in liquid nitrogen.

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Objective: To establish whether Bordetella pertussis is essentially clonal.

Design: Analysis of restriction fragments of XbaI digests of DNA from clinical and control isolates of B pertussis by pulse field gel electrophoresis.

Materials: 105 isolates of B pertussis: 67 clinical isolates from throughout the United Kingdom and 23 from Germany (collected during the previous 18 months); vaccine strains 2991 and 3700; and 13 control isolates from Manchester University's culture collection.

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Wistar rats (type II collagen-induced arthritis-susceptible) and PVG.RT1u rats (arthritis-resistant) were immunised with type II collagen and histological changes in the synovial tissues of the hind feet and in the popliteal lymph nodes draining these feet were examined and compared with unimmunised rats. There were no apparent differences in the joints of unimmunised rats of each strain, but the popliteal lymph nodes of the Wistar rats appeared more "activated", suggesting possible differences between strains in the continuous, low-grade release of antigens from the joints.

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Aims: To assess the accuracy of the Mast-ID 15 system compared with API 20 E for the identification of stock and fresh clinical strains of Enterobacteriaceae and Acinetobacter spp; to compare the accuracy of 19 pin and 36 pin multipoint inoculator heads.

Methods: One hundred frozen stock cultures of Enterobacteriaceae and Acinetobacter spp which had previously been identified by the API 20E were classified by the Mast-ID using 19 and 36 pin multipoint inoculator heads. Reproducibility was determined by testing 36 randomly selected organisms in duplicate.

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A number of congenic and recombinant rat strains with different RT1 haplotypes on a PVG/c background were immunised with native bovine or chick type II collagen. Only strains with the "u" haplotype were good responders to bovine type II collagen whilst all strains responded to chick type II collagen. However, the "u" haplotype was again associated with the production of the highest amounts of antibody.

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During a 20-month period, 382 arthroscopies were performed and the type of washout fluid obtained was noted. When a torn meniscus was found, the fluid was macroscopically abnormal in 97.4% of cases.

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Luminal and mucosal pH were measured endoscopically in patients with reflux esophagitis and antral gastritis and in control subjects. In all subjects, significant lumen-to-mucosa gradients were observed in the esophagus, stomach and acidified proximal duodenum. In the reflux patients luminal pH was lower in the fundus (mean +/- SEM, control vs.

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HLA haplotype sharing in rheumatoid arthritis sibships: risk estimates in siblings.

Scand J Rheumatol

May 1992

Arthritis and Rheumatism Council Epidemiology Research Unit, University of Manchester Medical School, Lancashire, UK.

The distribution of the number of parental HLA haplotypes shared by sibs with rheumatoid arthritis (RA) has been used to obtain information on the genetics of the disease. Thirty-four RA sibships (25 sib-pairs, 9 sib-trios) were ascertained, all of which were HLA typed and which satisfied the 1958 American Rheumatism Association criteria for "definite" RA. These were combined with other published but nonoverlapping data from the literature; thus, 143 sib-pairs, 36 sib-trios and 4 sibquads were identified.

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A cardinal feature of generalised nodal osteoarthritis is the loss of articular cartilage. To determine if autoimmunity to these cartilage collagens occurred, serum antibodies to native and denatured type II collagen were measured by enzyme linked immunosorbent assay (ELISA) in 96 patients (90 women, six men, aged 47-91 years) with generalised nodal osteoarthritis. Generalised nodal osteoarthritis was diagnosed by typical clinical and radiological features.

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It is generally agreed that a multiplicity of mechanisms are involved in the rejection of various grafts across different histocompatibility barriers. Recent publications have concentrated less on the characterization of the cells involved in the rejection process and more on their initial activation and their infiltration into the graft.

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