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Biomedical subjects

S Middleton

Publications and source records attributed to S Middleton.

At least 19 recordsLinked to original sources
PubMed1996

Rat plasma triglycerides and hepatic fatty acid synthetase mRNA, but not apolipoprotein B and A-IV mRNA, respond to dietary fat content.

The objective was to determine whether apolipoprotein B and A-IV mRNA abundance or plasma lipid concentrations would be altered by chronic or acute consumption of diets that differed in fat content. Forty Wistar male rats were fed either a low fat (5 g/ 100 g) or high fat (20 g/100 g) diet for 4 wk. Animals were killed unfed or 3 h after consumption of a test meal of the diet to which they had been adapted (n = 8). In addition, a low fat diet-adapted group was fed a high fat test meal and killed 3 h after the meal. Adaptation to the high or low fat diets did not result in differences in triglyceride or cholesterol concentrations in the plasma of unfed rats. In fed animals, plasma, VLDL, and LDL triglyceride concentrations were significantly higher in those fed the high fat test meal than in those fed the low fat test meal. Feeding did not alter plasma cholesterol concentrations; however, LDL cholesterol concentrations in the groups fed the high fat meals were significantly higher than in the group fed the low fat meal. There were no differences in plasma apolipoproteins B, A-IV, E, and A-I nor in the liver or intestinal apolipoprotein B and A-IV mRNA contents. Fatty acid synthetase (FAS) activity was significantly higher in rats adapted to the low fat diet, and no increase in activity due to feeding was observed. Hepatic FAS mRNA was higher in fed than unfed rats, and the low fat test meal resulted in a higher level than the high fat test meal. Plasma lipid concentrations were affected by the fat content of test meals rather than by the adaptation diet fat content. Apolipoprotein B and A-IV mRNA do not seem to respond to dietary fat or meal feeding.

Animals↗
PubMed1995

A CQI approach to the investigation of noise levels within the intensive care unit environment.

In February 1991, the Intensive Care Unit (ICU) at Liverpool Hospital was extended and relocated to a larger area. It soon became apparent that noise levels within the newly renovated unit were particularly worrying to patients, staff and relatives. A Continuous Quality Improvement (CQI) group was formed to investigate, and develop measures to reduce these noise levels. Through the implementation of various CQI tools a study plan was developed to investigate the noise problem. The study plan included: a patient, relative and staff questionnaire; a literature search; identification of levels of noise using a sound level meter; contracting a noise consultant to visit and review the ICU environment. The results of the CQI investigations revealed that there was an inappropriately high level of noise in the ICU. Several key contributing factors were also identified. These findings provided the basis for several positive measures to be undertaken including: the installation of sound absorbing ceilings; removal of rubbish bin lids; revision of the telephone ringing system; revision of the mobile x-ray machine; prioritisation of audible machine alarms; education of staff in noise level awareness; The application of the Continuous Quality Improvement (CQI) process to the noise problem facilitated the exploration of the source of noise, the effects on staff and patients, and ways to reduce noise levels in the intensive care environment.

Health Facility Environment↗
PubMed1995

Nutrient infusion into the ileum of rats does not lower plasma lipids or alter apolipoprotein mRNA abundance.

Viscous polysaccharides enhance the delivery of nutrients to the ileum. Our objective was to determine if the presence of nutrients in the ileum, in the absence of fiber, alters plasma and hepatic lipids. Twenty-four Wistar male rats weighing 150-160 g were fed a fiber-free purified diet (30% of energy as fat) for 7 d. The small intestine was cannulated 30 cm proximal to the ileo-cecal junction. The animals consumed the purified diet ad libitum and the intestine was infused (3 mL/h) with saline, or an enteral solution contributing 10, 20 or 30% total energy for half of a 12-h feeding period. Infusion was performed for 14 d, after which the animals were killed. The animals adjusted their food intake so that each group had an equivalent energy intake and weight gain over the experimental period. The relative ileal mucosa weight was increased with nutrient infusion indicating hypertrophy. Plasma cholesterol in the nutrient-infused animals tended to be higher than in the saline-infused animals (P < 0.06). Apolipoprotein B and A-IV mRNA were not affected by ileal infusion. Thus, enhanced delivery of nutrients to the ileum, without fiber present in the diet, does not lower plasma cholesterol.

Animals↗
PubMed1995

The incidence of testicular cancer in Royal Air Force personnel.

OBJECTIVES: To review the incidence of testicular cancer within the Royal Air Force (RAF) compared with the national incidence. METHODS: The medical statistics for RAF personnel (supplied by the Central Statistics Office, categorized by occupation) were reviewed for the incidence of testicular cancer and compared to the national rate. RESULTS: A significantly elevated incidence of testicular neoplasm was detected in RAF personnel, which was well above the national rate. The increased incidence appeared most marked in those personnel working directly with aircraft. CONCLUSION: The only cause of the significantly higher incidence of testicular cancer in RAF personnel is probably related to working with aircraft. This concurs with a finding that aircraft technicians in the US Navy had an increased incidence of testicular cancer, and the exposure to hydrocarbon carcinogens in the workplace was implicated.

Adult↗
PubMed1993

Human cartilage aggrecan CS1 region contains cryptic T-cell recognition sites.

Cartilage proteoglycan aggregates (PG) are candidate T-cell autoantigens in the pathogenesis of rheumatoid arthritis (RA). We have investigated the possibility that responses to class II-restricted T-cell recognition sites in human cartilage aggrecan (core protein) may depend upon whether these sites are available as free peptide antigens or as part of intact monomers. Analysis of mouse T-cell responses to intact or deglycosylated monomers, purified from human articular cartilage, and to synthetic peptides of the chondroitin sulphate (CS) attachment region homologous repeat sequence showed that recognition of T-cell epitopes in the CS1 region was strongly dependent upon the form of antigen used. The results show that the CS1 region contains cryptic T-cell recognition sites and raise the possibility that fragments of PG, released through the action of extracellular proteases in inflamed joints, may be capable of activating T cells with specificities for epitopes which are not made available following processing of intact PG. T cells with specificities for cryptic epitopes in PG may play a role in the pathogenesis of RA.

Aggrecans↗
PubMed1991

Comparative analysis of murine T lymphocyte responses to cartilage proteoglycans.

Cartilage proteoglycans are large molecules consisting of several sub-regions each of which comprises homologous repeating subunits. Comparisons of murine primed popliteal lymph node responses to human cartilage proteoglycans in BALB and B10 congenic mice showed that the major histocompatibility complex (MHC) influences T cell responsiveness to this antigen. H-2k and H-2d were higher responders than H-2b. Responses were MHC class II-restricted, and human cartilage proteoglycans were cross-reactive with mouse cartilage proteoglycans for a BALB/c T cell line. The proportion of proteoglycan-specific T lymphocytes in BALB/c primed popliteal lymph nodes was about 45% lower in females than males. These results show that in mice both MHC haplotype and sex can determine T lymphocyte responsiveness to cartilage proteoglycans. If the same mechanisms apply in humans they could be important in determining the HLA-DR haplotype associations and the predilection of rheumatoid arthritis for females.

Analysis of Variance↗
PubMed1991

[Francisco Hoffmann, pioneer of physiological research in Chile].

Francisco Hoffmann MD became a Professor of Physiology at the University of Chile School of Medicine in 1934. After postgraduate studies in Germany he came back to Chile in 1931 when he began proposing the creation of an Institute of Physiology. This became a reality in 1936. He was a proponent of full time job and of greater participation of students in the learning process. The main research interest of the Institute was centered on thyroid function and its relation to the nervous and circulatory systems. Professor Hoffmann was made a corresponding member of the Royal and the Spanish Academies of Medicine. In 1960 he retired from the Institute to help develop an Anthropology Center leaving many of his disciples to continue his work in physiology.

Chile↗
PubMed1990

Cytokines, thyroid autoantibody synthesis and thyroid cell survival in culture.

In autoimmune thyroid disease lymphoid cells infiltrating the thyroid gland occur in conspicuous aggregates or as a diffusely distributed population invading the thyroid follicles. Consequently cytokines secreted by activated T cells or macrophages could influence neighbouring thyroid cells as well as other lymphocytes. We have investigated this possibility using recombinant cytokines. Thyroid cell survival was assessed in terms of mitochondrial dehydrogenase activity in monolayers exposed to tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1 (IL-1 alpha and beta) and interleukin-2 (IL-2) in the presence or absence of thyroid-stimulating hormone (TSH). Neither TNF-alpha nor IL-2 affected thyroid cell survival, IFN-gamma was usually inhibitory and IL-1 alpha slightly enhanced cell survival in some experiments. However, the effects were small and variable and were not enhanced by potentially synergistic combinations of cytokines, longer periods of exposure, or different culture conditions. In contrast, IFN-gamma, IL-2 and TNF-alpha inhibited the ability of thyroid lymphocytes from patients with Graves' disease and Hashimoto's thyroiditis to synthesize autoantibodies to thyroid peroxidase (TPO) and thyroglobulin (Tg). Comparison of lymphoid populations isolated by digestion and/or mechanical disaggregation indicated that a population of activated B cells, plasma cells and T cells, intimately associated with thyroid cells since they could only be extracted by digestion, was influenced by cytokines. Our studies suggest that in addition to its well-recognized ability to induce MHC class II antigens on thyroid cells, IFN-gamma may inhibit thyroid cell proliferation and TNF-alpha, IFN-gamma and IL-2 may down-regulate thyroid autoantibody synthesis.

Autoantibodies↗
PubMed1990

Bone pain as the presenting manifestation of secondary syphilis.

A 31 year old fireman presented with acute pain and tenderness in both shins and forearms. Radiographs were normal but bone scintigraphy showed widespread increased isotope uptake. Serology was consistent with a diagnosis of secondary syphilis, and the patient's symptoms resolved completely six weeks after a course of penicillin.

Adult↗
PubMed1987

Production of factor VIII deficient plasma by immunodepletion using three monoclonal antibodies.

Factor VIII deficient plasma was made from pooled, HIV antibody and hepatitis B antigen screened, normal human plasma by cryoprecipitation and immuno-depletion, using three different monoclonal antibodies bound to Sepharose columns, in series. These monoclonal antibodies are specific respectively for von Willebrand factor, factor VIII heavy chain and factor VIII light chain. The immunodepleted plasma contained less than 0.002 u/ml factor VIII coagulation activity (VIII:C) less than 0.0001 u/ml von Willebrand factor antigen and 1-2 g/l fibrinogen, while the levels of other clotting factors were unchanged. This immunodepleted plasma was compared with commercial factor VIII deficient plasma obtained from a severe haemophilia A patient as substrate in the one-stage factor VIII assay. Plasmas obtained from 20 normal subjects and 28 patients with von Willebrand's disease or haemophilia A were assayed for VIII:C using the two substrates. The results were very highly correlated (r = 0.96). The columns have high capacity and can be regenerated at least 10 times. Large-scale production of a substrate for factor VIII assays free of virus contamination is now feasible.

Antibodies, Monoclonal↗
PubMed1985

The effect of carbimazole on thyroid autoantibody synthesis by thyroid lymphocytes.

Thyroid autoantibody synthesis was investigated in cultures of lymphocytes isolated from several sources, including thyroid and lymph nodes from patients with hyperthyroid Graves' disease treated preoperatively with carbimazole or propranolol. The ability of thyroid lymphocytes to secrete immunoglobulins, including thyroid microsomal or thyroglobulin autoantibodies, was markedly reduced in lymphocyte suspensions obtained from patients treated with carbimazole compared with suspensions from patients treated with propranolol. This effect (which was greater in individuals treated with carbimazole for longer periods) was attributable to a significant reduction in the number of viable lymphocytes present after the 14-day culture interval. In contrast, the type of preoperative therapy had little effect on cultures of lymphocytes obtained from lymph nodes draining the thyroid. Although it is not yet clear whether carbimazole exerts its effects in vivo by direct immunosuppression or indirectly by altering the thyroid microenvironment, our observations indicate that the fall in serum levels of thyroid autoantibodies that occurs during carbimazole therapy is related to an effect of the drug on lymphocytes within the thyroid.

Antibody Formation↗
PubMed1983

Monoclonal antibodies to human procoagulant factor VIII.

VIII:C was purified from intermediate-purity concentrate by adsorption on polyelectrolyte E5 and affinity chromatography on Sepharose/anti-VIIIR:Ag. The highly purified VIII:C preparation (sp. act. 1598 U/mg) was used to immunize Balb-C mice. Spleen cells from a mouse with a serum antibody titer of 963 U/ml were fused with P3 NSI mouse myeloma cells. Hybrid clones were screened by a coagulation inhibition assay and by a four-layer antibody adsorption procedure. Nine monoclonal antibodies specific to VIII:C were produced. Five of these antibodies have been cloned and grown in mouse ascitic fluid. Antibody titers from ascitic fluid ranged from 35 to 82,000 BU/ml. The antibodies, when radiolabeled, form a high-molecular-weight complex with antigens present in normal plasma and factor VIII concentrate, but not when incubated with CRM-negative hemophilic plasma. A two-site assay using a combination of monoclonal antibodies is able to detect VIII:CAg in normal plasma and in factor VIII concentrate. Sensitive two-site immunoradiometric assays using monoclonal antibodies as the solid phase have been set up.

Animals↗
PubMed1982

Response to infusions of polyelectrolyte fractionated human factor VIII concentrate in human haemophilia A and von Willebrand's disease.

Factor VIII was purified from cryoprecipitate by ion exchange chromatography on solid phase polyelectrolyte E-5 (PE-E5). The product was highly purified (3.5 u VIII:C/mg protein) compared to conventional concentrate (0.3 u VIII:C/mg protein) with low fibrinogen, low isoagglutinin titre, and a ratio of factor VIII coagulant activity (VIII:C) to factor VII related antigen (VIIIR:Ag) of 16:1. Trial infusions of this material (PE VIII) were given to three patients with severe haemophilia A and one patient with homozygous von Willebrand's disease. These patients also each received separate infusions of intermediate purity concentrate (IPC) for comparison. There were no adverse effects. The mean half life of VIII:C after PE VIII infusion in the haemophiliacs was 10.9 h and after IPC was 12.1 h, a statistically insignificant difference. The survival of factor VIII coagulant antigen (VIII:CAg) was similar to that of VIII:C. In contrast, the half life of VIII:C and of VIII:CAg was very short after infusion of PE VIII in the patient wih von Willebrand's disease (2.4 h). IPC when infused in this patient produced a typical secondary rise of VIII:C. Two bleeding episodes in severe haemophiliacs were satisfactorily treated with PE VIII. PE-E5 deserves further study as a means of preparing clinical concentrates of factor VIII.

Antigens↗