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Biomedical subjects

L McLean

Publications and source records attributed to L McLean.

17 recordsLinked to original sources
PubMed1992

Clinical and radiographic results of the Muller straight stem used as a press-fit.

Prior to the introduction of porous coating, 21 patients had 24 ME Muller straight-stem femoral prostheses inserted as a press fit for the treatment of osteoarthrosis. Five hips have been revised for aseptic loosening; the remaining 19 prostheses are still in situ after a mean of 7.3 years (range, 6.2-8.3 years). A prospective clinical assessment has been undertaken using a modified Harris hip score, with scores increasing on average from a preoperative 43 to a postoperative 79. Eighteen of the 19 remaining hips are functioning well. Variable distances of subsidence are evident in 10 hips. Despite the use of a prosthesis that was not designed for cementless proximal wedge fitting, the results indicate an exceptionally low incidence of bone resorption and lysis. Unlike cemented and some porous-coated prostheses, stress shielding and osteopenia were not a feature in this series.

Aged↗
PubMed1992

Small intestinal bacterial overgrowth and enhanced intestinal permeability in healthy beagles.

The small intestine of healthy adult Beagles was examined to determine whether subclinical abnormalities might exist that would be relevant to the use of Beagles in pharmacologic studies. Duodenal juice was obtained for qualitative and quantitative bacteriologic examinations; jejunal mucosa was taken for morphologic and biochemical investigation, and intestinal permeability was assessed by quantification of 24-hour urinary excretion of 51Cr-labeled EDTA after its oral administration. Comparisons were made with findings in healthy adult dogs of other breeds that served as controls. Small intestinal bacterial overgrowth was found in 14 of the 21 Beagles examined, and represented a mixed flora that included obligate anaerobic bacteria in 8 dogs and exclusively aerobic bacteria in 6 dogs. Intestinal permeability (percentage urinary recovery of 51Cr-labeled EDTA; mean +/- SEM) was considerably higher (P < 0.01) in Beagles with anaerobic overgrowth (37.6 +/- 3.2%) or aerobic overgrowth (30.5 +/- 4.8%), compared with Beagles with no overgrowth (17.3 +/- 1.6%) and with controls (11.1 +/- 1.0%). In Beagles, significant (r = 0.54, P = 0.03) correlation was observed between 24-hour urinary recovery of 51Cr-labeled EDTA and bacterial numbers in duodenal juice. Morphologic changes in jejunal mucosa were minimal, and specific activities of brush border enzymes were not significantly decreased, apart from aminopeptidase N, but activities of lysosomal and endoplasmic reticular marker enzymes were higher in the 3 groups of Beagles with anaerobic, aerobic, or no overgrowth, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Reaction of antibody to mycobacterial 65 kDa heat-shock protein with human chondrocytes.

We report on the reactivities of four monoclonal antibodies generated against mycobacterial proteins to human chondrocytes, cells in cartilage which may be subject to immune attack in rheumatoid arthritis. Only one of the monoclonal antibodies, ML30, which had been shown previously to react with a human homologue to heat-shock protein (hsp), reacted strongly to chondrocytes. By immunocytochemical methods using fixed chondrocytes, ML30 reacted to cytoplasmic constituents in a granular pattern. There were no marked qualitative differences in the staining intensities and patterns of chondrocytes kept at ambient temperatures and those subjected to 42 degrees C heat treatment. No significant staining was observed with normal peripheral blood mononuclear cells. By indirect immunofluorescence, the distribution of ML30 reactive constituents was very low on the cell surface. Reactivities of each of the monoclonal antibodies were tested on frozen sections of cartilage. Significant reactivity was found only with ML30, and the staining was only associated with chondrocytes, not with the cartilage matrix surrounding the cells. These findings may have significance in view of the possibility that an hsp homologue may be a target for inciting or perpetuating the autoimmune process in rheumatoid arthritis.

Antibodies, Monoclonal↗
PubMed1991

Effect of MK-458 (HPMC) in Parkinson's disease previously untreated with dopaminergic drugs. A double-blind, placebo-controlled multicenter study.

Ninety-four patients with early Parkinson's disease were investigated in a double-blind, placebo-controlled evaluation of MK-458 [hydroxypropyl methylcellulose/lactose matrix (HPMC)], a sustained release formulation of a novel naphthoxazine compound with selective D-2 dopamine receptor agonism. Patients were previously untreated with dopaminergic drugs. Efficacy was assessed by clinical rating scales and by patient self-evaluation. MK-458 (HPMC) caused a significant decrease in most parkinsonian symptoms. Though disability rating scores were lowered by the drug, the scores did not differ significantly from placebo. However, statistically significant improvement occurred with MK-458 (HPMC) on both the physician and the patient global assessments. Adverse reactions such as nausea and vomiting, sedation, confusion, and hallucinations occurred more with MK-458 (HPMC) than with placebo. MK-458 (HPMC) possesses antiparkinsonian efficacy in early Parkinson's disease; however, side-effects are frequently associated with its use. Selective D-2 receptor agonists, such as MK-458 (HPMC), may not be the ideal treatment as monotherapy for Parkinson's disease.

Aged↗
PubMed1990

Increased antibody responses to human papillomavirus type 16 L1 protein expressed by recombinant vaccinia virus lacking serine protease inhibitor genes.

The L1 gene of human papillomavirus type 16 (HPV-16) driven by the vaccinia virus major late 4b gene promoter has been inserted into three different sites of the vaccinia virus genome. Insertion into the thymidine kinase (TK) gene was achieved by selection of TK- mutants in BUdR on TK- cells. Insertion into two vaccinia virus serine protease inhibitor (serpin) genes was achieved by co-insertion of the Escherichia coli xanthine guanine phosphoribosyltransferase gene linked to the vaccinia virus 7.5K promoter and selection of mycophenolic acid-resistant recombinant viruses. Each recombinant virus expressed a 57K L1 protein at similar levels and with similar kinetics. However, immunization of mice with these recombinant viruses induced different levels of antibody to the L1 protein. Viruses lacking serpin genes B13R and B24R induced significantly higher antibody levels than did viruses lacking the TK gene. The presence of functional B13R and B24R gene products is therefore somehow immunosuppressive at least for antibody responses to the L1 protein of HPV-16.

Animals↗
PubMed1990

Role of immunity to mycobacterial stress proteins in rheumatoid arthritis.

'Stress Proteins in Inflammation' provided a forum for the discussion of topical issues in this rapidly moving field. The mycobacterial 65 kDa stress proteins play a key role in certain animal models of inflammatory arthritis. However, the impression emerging is that the mechanism probably involves more than a simple cross-reaction between mycobacterial SP65 and either the host SP65 or a cartilage antigen, and that evidence for a primary role in human rheumatoid arthritis is lacking. A realistic role for immune responses against stress proteins might be the amplification or perpetuation of inflammation. If so, this is unlikely to be limited to arthritis.

Animals↗
PubMed1989

Circulating concentrations of trypsin-like immunoreactivity and activities of lipase and amylase after pancreatic duct ligation in dogs.

The possibility that assay of circulating trypsin-like immunoreactivity (TLI) could assist in the diagnosis of acute pancreatitis in dogs has been examined by assaying plasma TLI concentrations after pancreatic duct ligation and comparing the results with plasma activities of lipase and amylase. Venous blood samples were obtained from 8 dogs before surgery, then daily for 5 days and at 14 days after ligation of pancreatic ducts. Plasma concentrations of TLI increased within 24 hours and tended to peak before and to decrease more rapidly than activities of lipase and amylase, remaining greater than the control range for 5 days in all but 2 dogs. Plasma lipase and amylase activities increased together and remained greater than the control range in all dogs for 5 days after surgery. Regression analysis of all postoperative data indicated significant correlations between concentration of TLI and lipase activity (r = 0.67, P less than 0.001), concentration of TLI and amylase activity (r = 0.53, P less than 0.001), and between lipase and amylase activities (r = 0.74, P less than 0.001). These findings suggested that assay of TLI may provide an early indication of acute pancreatitis in dogs. Because TLI is specifically pancreatic in origin, high plasma TLI concentration may prove a more reliable indicator of clinical pancreatitis than high activities of amylase or lipase, which may be derived from extrapancreatic tissues.

Amylases↗
PubMed1989

Status of an unpaired thiol group on the HLA-B27 epitope.

Sequence analysis and site-directed mutagenesis of HLA-B27 indicate an unpaired cysteine at position 67 of the hypervariable region corresponding to its serologically defined, disease-associated epitope. We investigated whether chemical modification of this thiol group affected the serological reactions of B27. B27-positive cells were treated with thiol-blocking agents and then tested for recognizable B27 expression. Anti-HLA-B27 alloantisera and monoclonal antibodies were used in cytotoxicity, absorption, and cellular ELISA (cELISA). The semi-quantitative cytotoxicity-based assays showed some decrease in both B27 and controls. However, cELISA indicated that the inhibition of B27 was significantly greater than control antigens, and dependent on thiol-blocker concentration. This suggests that a proportion of HLA-B27 molecules have a free, reactive thiol at the antibody-defined epitope. Incomplete inhibition by thiol-blocking agents indicates that the remainder are inaccessible.

Antibodies, Monoclonal↗
PubMed1989

Biochemical changes in the jejunal mucosa of dogs with exocrine pancreatic insufficiency following pancreatic duct ligation.

The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora.

Alkaline Phosphatase↗
PubMed1987

Comparison of the biochemical changes in the jejunal mucosa of dogs with aerobic and anaerobic bacterial overgrowth.

Subcellular biochemical changes in the jejunal mucosa have been compared in dogs with either aerobic or anaerobic bacterial overgrowth to explore relationships between composition of the flora and mucosal damage. Affected animals comprised 17 German shepherd dogs with chronic diarrhea or weight loss, or both. Analysis of duodenal juice demonstrated aerobic overgrowth in 10 cases, most frequently comprising enterococci and Escherichia coli, and obligate anaerobic overgrowth in 7 cases, most frequently including Clostridia spp. Histologic changes were minimal; however, examination of peroral jejunal biopsy specimens by sucrose density gradient centrifugation revealed specific biochemical abnormalities. In the dogs with aerobic overgrowth, there was a selective loss of brush border alkaline phosphatase activity, and gamma-glutamyl transferase activity was increased, whereas activities of disaccharidases and aminopeptidase N were unaltered. In contrast, anaerobic overgrowth was associated with a reduction in brush border density, indicative of a considerable fall in the glycoprotein-to-lipid ratio of the brush border membrane, whereas brush border enzyme activities were unaltered. There was a loss of peroxisomal catalase activity in dogs with aerobic overgrowth, and an indication of mitochondrial disruption in dogs with anaerobic overgrowth, but little evidence for damage to other subcellular organelles. These findings demonstrate that aerobic and anaerobic overgrowth may be associated with distinct but different mucosal abnormalities particularly affecting the brush border membrane.

Alkaline Phosphatase↗
PubMed1987

Organ culture of rabbit ileum as a model for the investigation of the mechanism of intestinal damage by enteropathogenic Escherichia coli.

Organ culture of rabbit ileum has been established as a model for the investigation of the mechanism of intestinal damage by enteropathogenic Escherichia coli (EPEC). Loops of rabbit ileum were filled in vivo with saline, non-enteropathogenic P-fimbriate E coli (PFEC), or EPEC. After 45 minutes the loops were washed, then mucosal biopsies were taken and cultured for up to 48 hours. The earliest changes discernable by electron microscopy were observed at 18 hours postinfection, at which time EPEC were closely adherent to the surface of enterocytes at the base of microvilli, some of which were elongated. By 24 hours postinfection there were large areas of brush border effacement with pedestal formation around the EPEC. No such damage was seen in biopsies from the control loops (saline, PFEC), and intracellular ultrastructure was extremely well preserved in all preparations for up to 48 hours. While there were no differences at eight hours, biochemical analyses at 24 hours postinfection showed a marked increase in the release of brush border enzymes into the culture medium from EPEC-infected explants compared to explants from the control loops. These findings provide morphological and biochemical evidence for damage to the microvillus membrane by EPEC, and validate organ culture of rabbit ileum as a model for the investigation of EPEC-pathogenicity.

Alkaline Phosphatase↗
PubMed1985

Wheat-sensitive enteropathy in Irish setter dogs: possible age-related brush border abnormalities.

The pathogenesis of a wheat-sensitive enteropathy was explored in a litter bred from two Irish setters with a naturally occurring enteropathy. Jejunal biopsies from all eight progeny exhibited morphological changes comparable to those in the parents, while biochemical abnormalities appeared to be related to age. In biopsies obtained from the first group of four dogs at eight months, the activities of alkaline phosphatase and of leucyl-2-naphthylamidase were almost undetectable while disaccharidases were unaltered. In contrast, analytical subcellular fractionation of biopsies obtained from the second group of four dogs at nine months showed that specific activities now reflected a major deficiency of brush border alkaline phosphatase, and normal brush border leucyl-2-naphthylamidase accompanied by elevated soluble activity. Further studies are indicated to determine whether these findings represent an age-related abnormality affecting specific microvillus membrane proteins.

Age Factors↗