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Biomedical subjects

C Lock

Publications and source records attributed to C Lock.

14 recordsLinked to original sources
PubMed2001

The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease.

Multiple sclerosis is a demyelinating disease, characterized by inflammation in the brain and spinal cord, possibly due to autoimmunity. Large-scale sequencing of cDNA libraries, derived from plaques dissected from brains of patients with multiple sclerosis (MS), indicated an abundance of transcripts for osteopontin (OPN). Microarray analysis of spinal cords from rats paralyzed by experimental autoimmune encephalomyelitis (EAE), a model of MS, also revealed increased OPN transcripts. Osteopontin-deficient mice were resistant to progressive EAE and had frequent remissions, and myelin-reactive T cells in OPN-/- mice produced more interleukin 10 and less interferon-gamma than in OPN+/+ mice. Osteopontin thus appears to regulate T helper cell-1 (TH1)-mediated demyelinating disease, and it may offer a potential target in blocking development of progressive MS.

Animals↗
PubMed1999

Prevalence of back, neck and shoulder problems in the inner city: implications for the provision of physiotherapy services in primary healthcare.

BACKGROUND AND PURPOSE: More general practitioners are offering physiotherapy services within primary healthcare; however, this provision may result in increased demand. Resource allocation, based on previous patterns of consultation for musculoskeletal conditions, may be inadequate since the need for treatment in the community may not have been met in the past. Therefore the aim of this study was to determine the prevalence of back, neck and shoulder problems that had restricted normal activity for more than one week during the last year and which health professionals (if any) patients had consulted about their symptoms. METHOD: A postal survey of 2400 adult patients selected at random from four general practices in Newcastle upon Tyne (600 from each practice). RESULTS: A total of 1546 questionnaires were returned, a 64% response rate. Overall, 40% of respondants reported having at least one back, neck and/or shoulder problem. Back problems were most common (30%), followed by those with neck (21%) and shoulder (20%) problems. Approximately one-third of those with problems consulted no one, a further third consulted a general practitioner and only one in six consulted a physiotherapist. CONCLUSIONS: There is a high prevalence of substantial back, neck and shoulder problems in the community and thus a wider provision of physiotherapy services within primary healthcare may be required to manage the considerable levels of potentially unmet need.

Adolescent↗
PubMed1998

Microfabricated device coupled with an electrospray ionization quadrupole time-of-flight mass spectrometer: protein identifications based on enhanced-resolution mass spectrometry and tandem mass spectrometry data.

We describe the coupling of a microfabricated fluidic device to an electrospray ionization (ESI) quadrupole time-of-flight mass spectrometer (QqTOFMS) for the identification of protein samples. The microfabricated devices consisted of three reservoirs connected via channels to a main capillary, which in turn was linked via a microspray interface to the QqTOFMS. Here we present preliminary results obtained using this system. Standardized solutions of myoglobin tryptic digest were analyzed indicating a limit of detection at the low to sub fmol/microL. The combination of the microfabricated device for rapid sample delivery and the rapid acquisition capability, enhanced resolution and mass accuracy of the QqTOF offers unique possibilities for the rapid identification of proteins by database searching. This platform can generate MS data suitable for protein database searching by the peptide-mass fingerprinting approach and MS/MS data suitable for protein database searching. Here the results of the two database-searching approaches are compared and the possibilities of combining the two approaches for rapid identification of protein are discussed. Also, we present a comparison of the results obtained using the three-position microfabricated device coupled to the ESI-QqTOFMS and to an ESI-ion trap MS. Finally the combination of C-terminal 18O labeling of peptides and the microfabricated system for automated combined peptide-mass fingerprinting and sequence-tag database searching is discussed.

Databases, Factual↗
PubMed1996

What value do computers provide to NHS hospitals?

As the NHS spends around pond 220 million a year on information technology for use by acute hospitals that are hard pressed for resources, it is reasonable to ask what value is provided. A review of rigorous scientific evidence for the value of information technology to NHS hospitals found that published evidence is scarce and far from conclusive. Information technology in NHS hospitals needs further assessment so that future decisions on such necessary and important investments are based on clear, well documented experience and research.

Computer Systems↗
PubMed1996

Amino acid profiles and muscle protein composition in rats with a reduced renal mass in the fed state.

In severe chronic renal failure (CRF) with associated metabolic acidosis, abnormalities in protein metabolism and amino acid (AA) profiles in the fed state are well described. To evaluate the effect of early uraemia and the influence of acid-base status on protein metabolism and AA profiles, three groups of pair-fed rats were studied: group I - rats with 1+ 1/2 nephrectomy; group II - rats with 1+ 1/2 nephrectomy receiving NaHCO3 supplementation, and group III - sham-operated rats with NaHCO3 supplementation. After 4 weeks, serum creatinine values were similar in groups I and II (111 +/- 5 and 119 +/- 4 mumol/l) and higher than in group III (51 +/- 5 mumol/l, p < 0.0001); HCO-3 was reduced only in group I (22.4 +/- 0.8 mmol/l) compared to group II (28.3 +/- 0.6 mmol/l, p < 0.001) and group III (28.2 +/- 1.3 mmol/l, p < 0.001). In the uraemic animals (groups I and II) arterial AA profiles showed increased levels of phenylalanine, glycine, glutamate, proline and alanine. The marked increase of threonine in group I was corrected by NaHCO3 supplementation in group II. The total nonessential AA were higher both in group I (1,832 +/- 53 mumol/l, p < 0.05) and group II (1,788 +/- 103 mumol/l, p < 0.05) than in group III (1,542 +/- 54 mumol/l). These results are similar to those described in the fed state of uraemic patients. Intracellular AA changes were detected, especially in group II namely increased glycine and a decrease in threonine and serine levels. No signs of malnutrition or changes in alkali-soluble protein (ASP) or ASP/DNA ratio in liver and muscle were observed. These results show that AA abnormalities in the fed state occur early in the course of CRF, and that the marked increase of threonine is corrected by NaHCO3 supplementation. These data suggest that either an impaired utilization of the ingested proteins might occur before the appearance of major alterations in endogenous protein metabolism or acid-base status might alter AA metabolic rate per se.

Acid-Base Equilibrium↗
PubMed1995

Prevention of insulin-dependent diabetes mellitus in nonobese diabetic mice by immunogenic but not by tolerated peptides.

In the nonobese diabetic (NOD) mouse, susceptibility to insulin-dependent diabetes mellitus is in part controlled by a single expressed class II major histocompatibility complex (MHC) molecule, I-Ag7. This molecule probably exerts its control through the representation of a self-peptide, derived from an unknown beta cell antigen, leading to T cell activation and eventual islet destruction. In this paper, synthetic peptides have been used to compete for binding to the I-Ag7 molecule in an attempt to suppress the autoimmune response. The administration of an I-Ag7-binding immunogenic peptide, lambda repressor (cI) 12-26, in a water and oil emulsion (incomplete Freund's adjuvant) can prevent the transfer of IDDM into irradiated recipients by spleen cells from diabetic donors. Nonbinding, nonimmunogenic peptides have no effect in this situation. However, the immune response to the "blocking" peptide in these experiments was a complicating factor in interpreting the results. To establish that the effect was at the level of competition for MHC binding, two additional approaches were tried. First, tolerance was induced to the immunogenic peptide, cI 12-26, before using it to "block" disease. Tolerance abolished the effect on diabetes transfer. Second, an effort was made to identify peptides that were nonimmunogenic but that bound to I-Ag7. Such a peptide, mouse prostatic secretory glycoprotein precursor 63-76, had no effect on the incidence of transferred disease. We conclude that the "blocking" effects seen in initial experiments in the NOD mouse were not caused by blockade of MHC presentation, but by other unknown effects related to the immunogenicity of the "blocking" peptide.

Amino Acid Sequence↗
PubMed1995

S100, alpha-smooth muscle actin and cytokeratin 19 immunohistochemistry in odontogenic and soft tissue myxomas.

AIMS: To compare the expression of S100 protein, alpha-smooth muscle actin (alpha-SMA) and keratin 19 in odontogenic myxomas and non-odontogenic myxoid lesions. METHODS: Formalin fixed, paraffin wax embedded tissue from seven odontogenic myxomas, three soft tissue myxomas, six hyperplastic myxoid dental follicles, two intramuscular myxomas, 12 cardiac myxomas, and seven normal dental follicles were examined immunocytochemically for S100 protein, alpha-SMA and cytokeratin 19 using the Streptavidin-biotin method. RESULTS: A minority of odontogenic myxomas (three of seven) were positive for S100 and the staining was of moderate intensity and in all myxofibroblasts. Soft tissue myxomas, normal dental follicles, intramuscular myxomas, and most enlarged myxoid follicles were negative. In the cardiac myxomas the cells forming cords and islands were positive in approximately half (seven of 12), but the dispersed stellate myxoblasts were positive in only two cases. A population of cells in all the odontogenic myxomas and hyperplastic dental follicles contained alpha-SMA, but such cells were sparse in cardiac myxomas and present in only four cases. Cytokeratin 19 was present in odontogenic epithelium of odontogenic myxoma and follicles. CONCLUSIONS: A minority of odontogenic myxomas, but not other oral myxoid lesions, may express S100 protein and this could cause difficulty distinguishing myxoma from myxoid nerve sheath tumours. Sparse myofibroblastic cells occurred in all types of myxoma tested. The epithelium sometimes found within jaw myxomas expresses cytokeratin 19 and this is consistent with an odontogenic origin.

Actins↗
PubMed1994

Phenotypic characterisation of stellate and giant cells in giant cell fibroma by immunocytochemistry.

The origin of the stromal, stellate and multinucleate cells in oral giant cell fibroma is unclear. Sixteen giant cell fibromas were stained immunocytochemically for keratin (MNF 116), vimentin, S-100 protein, neurofilaments, glial fibrillary acidic protein, alpha-smooth muscle actin, desmin, CD31 (PECAM-1), CD68, Factor XIIIa and prolyl 4-hydroxylase (5B5). In all cases positive staining was found with vimentin and prolyl 4-hydroxylase, indicating a functional fibroblast phenotype. Reactivity for Factor XIIIa was seen in two cases and in only one was a small number of giant cells stained, suggesting that the majority of oral giant cell fibromas are unrelated to the histologically similar fibrous papule of the nose or facial angiofibroma.

Actins↗
PubMed1993

Effects of acid loading on serum amino acid profiles and muscle composition in normal fed rats.

1. Impaired body growth, loss of lean body mass and negative nitrogen balance are common findings in chronic renal failure. Enhanced endogenous protein catabolism in skeletal muscle induced by co-existent metabolic acidosis seems to be an important aetiological factor. 2. In uraemic patients abnormalities in blood amino acid profiles are present after a protein meal, suggesting impaired metabolism of ingested proteins. 3. This study demonstrates that acidosis induces changes in arterial amino acid profiles in fed non-uraemic rats. These included increased levels of threonine, histidine, proline, serine and glycine, and decreased levels of tryptophan. These changes are similar to those found in uraemic patients after a protein meal, suggesting a pathogenic role of acidosis in the impairment of exogenous protein metabolism. 4. Intracellular amino acid levels in the muscle tissue partly reflect the changes in the extracellular level. 5. Acidotic animals had a decreased body weight gain and a reduced alkali-soluble protein/DNA ratio in muscle cells compared with controls. 6. In conclusion, the results show that acidosis per se modifies the circulating amino acid profile in fed rats, resulting in a pattern similar to the post-prandial amino acid changes described in uraemic patients. These abnormalities occur together with impaired growth of skeletal muscle cells.

Acidosis↗
PubMed1991

Competitive inhibition of antigen presentation in animal models of autoimmune disease.

Competition between peptides for binding to class II major histocompatibility complex (MHC) molecules has been demonstrated both in vitro and in vivo. Peptide competition may provide a way to interfere with T cell activation in the treatment of autoimmune diseases. It may be possible to provide a substitute 'blocking' peptide to compete for presentation of an autoantigenic peptide to T cells. The approach described is a general one, which may be applicable to a number of T cell mediated MHC-linked autoimmune diseases, and to other undesirable immune responses. So far, peptide competitors have only been successfully used in the prevention of experimental autoimmune encephalomyelitis (EAE). Whether or not this approach will work in treating spontaneous disease models remains to be tested, although work in other test systems is encouraging.

Animals↗
PubMed1986

Immune factors in narcolepsy.

Most but not all subjects with the narcoleptic syndrome have the human leukocyte antigen (HLA) DR2 (and DQ1). The narcolepsy-DR2 association is the highest disease-HLA linkage known, and occurs in nonfamilial as well as familial cases of the narcoleptic syndrome. In other forms of daytime drowsiness, there is no relationship with a specific HLA, although some subjects considered to have "essential" hypersomnolence probably have the narcoleptic syndrome. The cause of the narcoleptic syndrome remains unknown, although in a few instances the condition follows infection. There is no evidence for a circulating sleep factor in the blood or in the cerebrospinal fluid of narcoleptic subjects, and no unequivocal marker of cellular immunity has yet been found. However, a few subjects with the narcoleptic syndrome have oligoclonal bands or raised immunoglobulin concentration in the cerebrospinal fluid. It is highly likely that the narcoleptic syndrome is an immune-mediated disorder, occurring in a genetically susceptible (DR2/DQ1-positive) subject.

Female↗