Search PubMed⌕ Search

Biomedical subjects

M Scott

Publications and source records attributed to M Scott.

At least 217 records · Page 12Linked to original sources
PubMed1993

PGAIPG, a repeated hexapeptide of bovine and human tropoelastin, is chemotactic for neutrophils and Lewis lung carcinoma cells.

Fetal bovine ligamentum nuchae fibroblasts express a 67-kDa, lactose-sensitive receptor that binds to VGVAPG, a repeated hexapeptide, of bovine and human tropoelastin. Recently, studies utilizing recombinant tropoelastin deletion proteins in conjunction with synthetic peptides identified a second fibroblast receptor binding site, PGAIPG. To evaluate whether PGAIPG is a ligand for elastin receptors of other cells, the chemotactic response of neutrophils and Lewis lung carcinoma tumor cells (M27) was studied. PGAIPG was chemotactic for both of these cells. The maximal response was seen at 10(-9) M. VGVAPG desensitized neutrophils to migration induced by PGAIPG confirming that PGAIPG was binding to the 67-kDa receptor. GAIPG, a chemokinetic peptide for fibroblasts, did not induce neutrophil migration. This corroborates the conclusion that GAIPG's mechanism of action in fibroblasts was independent of the 67-kDa receptor. Unlike fibroblasts and neutrophils, GAIPG was chemotactic for M27 tumor cells.

Animals↗
PubMed1993

PGAIPG, a repeated hexapeptide of bovine tropoelastin, is a ligand for the 67-kDa bovine elastin receptor.

Tropoelastin is composed of alternating hydrophobic and hydrophilic domains. A hydrophobic peptide, VGVAPG, has been shown to be a ligand for a 67-kDa elastin cell surface receptor expressed on fetal bovine auricular chondrocytes and ligamentum nuchae fibroblasts. To explore the possibility that tropoelastin contains additional peptide ligands for this elastin receptor, we have constructed two deletion proteins that are expressed in E. coli and lack the repeated VGVAPG sequence. These proteins supported bovine fibroblast attachment implying the presence of a receptor binding site. Experiments using synthetic peptides contained within these proteins identify a chemotactic peptide, PGAIPG, and a chemokinetic peptide, GAIPG, PGAIPG was identified as a ligand for the bovine elastin receptor.

Amino Acid Sequence↗
PubMed1993

Transdifferentiation of adult human pigment epithelium into retinal cells by transfection with an activated H-ras proto-oncogene.

The identification of homologs to viral oncogenes in normal cells coupled with development of techniques for DNA transfer into cells offers a powerful approach to dissect the processes associated with differentiation-specific oncogenes. We have derived cell lines by transfection of viral DNAs and proto-oncogenes into primary retinal pigment epithelial (RPE) cells. Establishment of cell lines was successfully achieved with the SV40 large T-antigen gene activated form of Harvey (H)-ras proto-oncogene, c-myc, and adenovirus E1A. The cell lines derived using the H-ras oncogene appeared to contain cells with a neuronal phenotype. This feature was not observed in cell lines established with the other oncogenes. Characteristically, H-ras-transfected cells all exhibited features associated with neurons around 10-14 passages. The transdifferentiated cells were biochemically characterized and found to express neuronal markers, such as neurofilament protein and neuron-specific enolases. The specific neuronal changes were restricted to only two primary cultures of RPE derived from carcinoma donors. Although transdifferentiation of pigmented cells of iris, or the retina, into the lens has been demonstrated, our studies presented in this report provide evidence that RPE cells from adults can transdifferentiate into neurons under the influence of a specific oncogene. To the best of our knowledge, this is the first report on transdifferentiation of adult human pigment epithelium into a neuronal cell type.

Cell Differentiation↗
PubMed1993

An evaluation of the efficacy and safety of tetrahydroaminoacridine (THA) without lecithin in the treatment of Alzheimer's disease.

Seventy-nine patients with probable Alzheimer's disease were enrolled into a double-blind, placebo-controlled cross-over study to assess the therapeutic effect and safety of THA (tetrahydroaminoacridine; tacrine) without concomitant lecithin administration. Forty-one patients completed the trial which consisted of two 12-week treatment phases separated by a 4-week wash-out period. Twenty-six subjects were withdrawn during the active treatment phase, mostly because of elevated transaminases or cholinergic side-effects, and ten during treatment with placebo. Statistical analyses were conducted on two groups of patients; those completing the cross-over and those with at least one evaluation in the first treatment period. This latter analysis, using the last observation carried forward was used to approximate an intention-to-treat analysis. THA was favoured over placebo in all three primary outcome measures (MMSE, ADAS Non-cognitive Scale, and the Functional Life Scale), but the results did not reach statistical significance. THA was favoured over placebo in five of the seven secondary outcome measures, but for only two of these was statistical significance attained. In terms of a three-point or greater increase in MMSE score, three to four times as many subjects improved on THA as on placebo.

Activities of Daily Living↗
PubMed1993

Immunologic and molecular biologic studies of prion proteins in bovine spongiform encephalopathy.

Bovine spongiform encephalopathy (BSE) is a transmissible neurodegenerative disease. Six brain regions from 11 cattle were examined for the presence of the abnormal isoform of the prion protein (PrPBSE). The highest concentrations of PrPBSE were found in the brain stem, where the greatest degree of spongiform change was observed. Molecular cloning of the bovine PrP gene showed that it encodes a protein of 256 or 264 amino acids with five or six Gly:Pro-rich octarepeats, respectively, in contrast to all other mammalian PrP genes, which encode only five octarepeats. The bovine PrP gene is single copy, and the entire open-reading frame lies within a single exon. Since the transmission of prions across species seems to be restricted by differences in PrP sequence, the high degree of homology between sheep and bovine PrP (98%) correlates with the proposed cause of BSE.

Amino Acid Sequence↗
PubMed1993

Cefepime as treatment for osteomyelitis and other severe bacterial infections.

Cefepime, a novel, injectable alpha-methoxyimino aminothiazolyl cephalosporin, is active in vitro against many of the Gram-positive and Gram-negative bacteria which cause severe infections, including Pseudomonas aeruginosa. It is more active than existing third-generation cephalosporins against multiply-resistant strains of Enterobacteriaceae because of its low affinity for beta-lactamases and its resistance to hydrolysis by these enzymes. Cefepime retains its high potency of activity against methicillin-susceptible Staphylococcus aureus, coagulase-negative staphylococci and streptococci other than enterococci. Seventy-four patients (46 male and 28 female) were treated with cefepime 2 g i.v. every 12 h; 61 patients were evaluable for efficacy (39 male and 22 female). The infections included pneumonia caused by Gram-negative bacilli (21 patients, six with bacteraemia), septicaemia (seven), pyelonephritis (two), osteomyelitis (23, mainly caused by S. aureus), septic arthritis (four) and soft tissue infections (four, one with bacteraemia). Responses were as follows: 52 (85.3%) patients cured; three (4.9%) improved and six (9.8%) failed. The failures included three patients with osteomyelitis, one with pyelonephritis and two with pneumonia. The pathogens and eradication rates were: S. aureus 23/24 (96%), Staphylococcus epidermidis 4/4, Streptococcus spp. 10/10 (100%), P. aeruginosa 11/14 (79%), Enterobacteriaceae 28/28 (100%), Haemophilus spp. 3/3 and others 7/7. Clinical adverse effects included diarrhoea in 11 patients (14.9%) nausea in five (6.8%) and pruritus in three (4.1%). Laboratory abnormalities included leucopenia in three patients (4.1%) and direct Coombs' conversion in 32 (43.2%). Patients were treated for an average of 31.8 days for osteomyelitis and 11.9 days for other infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Effects of cholinoceptor and 5-hydroxytryptamine3 receptor antagonism on erythromycin-induced canine intestinal motility disruption and emesis.

1. Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and emesis. This study in the dog investigates the underlying mechanisms. 2. Intestinal myoelectrical activity and the occurrence and latency of emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3. Erythromycin (7 mg kg-1) increased contractions of the proximal small intestine, and caused emesis in all fasted dogs and in 5 dogs after food. Atropine (50 mg kg-1 min-1) and hexamethonium (10 mg kg-1 h-1) partially inhibited the GI motility effects but did not significantly reduce emesis. 4. Metoclopramide at a high dose (2 mg kg-1 h-1) reduced the incidence of emesis in the presence of increased intestinal motility, but a low dose (150 micrograms kg-1 h-1) was ineffective. 5. A 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL 72222 (1 mg kg-1), reduced emesis when given alone and combined with metoclopramide (low dose). The 5-HT4 receptor agonist BRL24924 (Renzapride, 1 mg kg-1) had no effect on emesis either alone in combination with metoclopramide. 6. In conclusion, erythromycin-induced GI motility disturbances and emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated, emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the dopamine system.

Animals↗
PubMed1993

The development and implementation of a respite care program for paediatric peritoneal dialysis patients.

When a child is sent home on peritoneal dialysis, the family is faced with enormous challenges. Despite the coordination of community resources, there are few opportunities for relief from the many tasks required to keep a child home on dialysis. The intensity and duration of the home care required for children awaiting renal transplantation have often led to overwhelming parental stress, marital discord and burn-out. These events can lead to the detriment of the well-being of the child and may result in a higher incidence of peritonitis. Many families had identified the need for some form of relief. Recognizing this, the staff of the home dialysis program of the Toronto Hospital for Sick Children (HSC) joined forces with the staff at Bloorview Children's Hospital (a chronic care/rehabilitation centre) to develop a respite program for these families. The HSC staff provided staff education, medical back-up and financed the equipment and supply costs while the Bloorview Hospital provided the accommodation and the medical and nursing staff to care for the children. In addition to providing parental relief, Bloorview Hospital was able to provide extended care to children requiring peritoneal dialysis until their parents were able to care for them at home. This enabled HSC to use their beds for more acutely ill children. Initial evaluation of the program was favourable and efforts are now being made to streamline the system.

Child↗
PubMed1992

Crystallization and preliminary X-ray studies of the pectate lyase from Bacillus subtilis.

The pectate lyase (EC 4.2.2.9) from Bacillus subtilis has been crystallized. Crystals of form 1, grown by the hanging drop method using polyethylene glycol as precipitant, diffract to at least 2.4 A resolution. They belong to the spacegroup P2(1) with a = 132.9 A, b = 41.2 A, c = 156.8 A and beta = 114.9 degrees with probably four molecules in the asymmetric unit. A second crystal form grown from 2-methyl-2,4-pentandiol also belongs to the spacegroup P2(1) with a = 55.0 A, b = 88.1 A, c = 50.2 A and beta = 109.0 degrees. These crystals diffract to at least 2.0 A and have one molecule in the asymmetric unit. Both crystal forms are suitable for the determination of high-resolution structures.

Bacillus subtilis↗
PubMed1992

Molecular cloning of a candidate chicken prion protein.

Fractions enriched for acetylcholine receptor-inducing activity from chicken brain were found to contain a protein that was approximately 30% homologous with mammalian prion proteins [Harris, D. A., Falls, D. L., Johnson, F. A. & Fischbach, G. D. (1991) Proc. Natl. Acad. Sci. USA 88, 7664-7668]. To extend these observations, we recovered genomic clones encoding a putative chicken prion protein (PrP). Like mammalian PrP molecules, the candidate chicken PrP is encoded by a single-copy gene and the entire open reading frame is found within a single exon. All of the structural features of mammalian PrP were found in the chicken protein. When the N-terminal repeats of PrP were not considered, the chicken and mammalian proteins were approximately 55% homologous, allowing for conservative substitutions. Screening of a chicken genomic DNA library failed to identify a more closely related chicken PrP homologue. These findings argue that the protein which purifies with acetylcholine receptor-inducing activity is chicken PrP.

Amino Acid Sequence↗
PubMed1992

Prediction of netilmicin disposition in neonates.

Multiple regression analyses of data from 33 neonates who received netilmicin therapy showed that concurrent treatment with other drugs (Drg), creatinine clearance (CLcr), gestational age (GA), and an apgar score of less than 6 at 1 min (Agl') were significant determinants of netilmicin clearance. Apparent volume of distribution was significantly affected by postnatal age (PNA), gender, the presence of ascites and/or oedema (A/O), and whether or not the neonate was small for gestational age (SGA). The following formulae were obtained: [formula: see text] The regression formulae were shown to predict netilmicin plasma concentrations with good precision and a non-significant bias in a further 15 neonates studied prospectively.

Apgar Score↗
PubMed1992

Induction of protective class I MHC-restricted CTL in mice by a recombinant influenza vaccine in aluminium hydroxide adjuvant.

Induction of class I MHC-restricted cytotoxic T lymphocyte (CTL) responses by soluble proteins or peptides requires complex adjuvants or carrier systems which are not licensed for use with human vaccines. The data presented in this report show that vaccination with a highly purified recombinant influenza protein antigen in aluminium hydroxide adjuvant, the only adjuvant currently licensed for clinical use, elicited class I restricted CTL and protection from lethal challenge with H1N1 and H2N2 viruses. The antigen (D protein, SK&F 106160) is produced by expression of H1N1 influenza virus-derived cDNA (strain A/PR/8/34) in Escherichia coli, and is composed of the first 81 N-terminal amino acids (aa) of the non-structural protein 1 (NS1) fused via a nine nucleotide non-viral linker sequence to the 157 C-terminal aa of the haemagglutinin 2 subunit (HA2). Previous work by Kuwano et al demonstrated that in vitro stimulation of spleen cells from influenza virus-primed mice, with a partially purified preparation of the D protein, selected for CD8+ CTL clones which facilitated lung clearance of H1N1 and H2N2 viruses. In the current study, these results were extended by studying the responses of mice actively immunized with highly purified D protein in the presence or absence of adjuvants. Vaccination of CB6F1 (H-2dxb) mice with D protein in aluminum hydroxide or Freund's complete adjuvant generated H1N1 cross-reactive, H-2d-restricted, CD8+ CTL directed against an immunodominant HA2 epitope (aa 189-199). D protein without adjuvant did not elicit CTL, regardless of the route of injection. However, long-lived (greater than 6 months) splenic memory CTL were elicited by boosting mice intraperitoneally (i.p.) with the D protein in the absence of adjuvant. In mice injected subcutaneously with D protein in aluminium hydroxide at weeks 0 and 3, survival was increased relative to controls up to 16 weeks beyond the second vaccination, after which time additional boosting was required for protection. Studies in H-2b and H-2k mice vaccinated with the D protein showed that induction of CD4+ T-cell or antibody responses, in the absence of CD8+ CTL, did not correlate with protection. Passive transfer of immune sera from CB6F1 mice was also not protective. This prototype H1N1 recombinant subunit vaccine in aluminium adjuvant should directly address the feasibility of achieving a protective cell-mediated immune response in human influenza.

Adjuvants, Immunologic↗
PubMed1992

The peritoneal equilibration test in children.

The peritoneal equilibration test (PET) has been recommended in adults as a standardized means of estimating solute transport. Based on results of the PET, adult peritoneal permeability has been classified as high, high average, low average, and low. We performed a PET on 32 children aged 0.8 to 17.8 years (mean 9.3) using a dwell volume of 32 +/- 5 ml/kg of 2.5% dialysate. Dialysate to plasma (D/P) ratios for creatinine, urea, and sodium were calculated at two and four hours as were the ratios of dialysate glucose at two and four hours to the dialysate glucose at time 0 (D/Do). Stepwise logistic regression identified only the patients' age and D/Do glucose values at two hours as significant predictors of ultrafiltration. Net ultrafiltration after a four hour dwell could be predicted for 75% of children above 9.3 years, or whose D/Do glucose value at two hours was greater than 0.45. The mean and standard deviation values for D/Do glucose and D/P creatinine at four hours were 0.31 +/- 0.17 and 0.71 +/- 0.12, respectively. When children are characterized according to adult standards, at least 70% fall into the high or high average permeability categories.

Adolescent↗
PubMed1992

Replication of distinct scrapie prion isolates is region specific in brains of transgenic mice and hamsters.

Scrapie prions are composed largely, if not entirely, of PrPSc molecules. The prion isolates Sc237 and 139H exhibit markedly different incubation times in Syrian, Armenian, and Chinese hamsters, as well as in transgenic (Tg) 81 mice expressing Syrian hamster PrP (SHaPrP). Repassage of prions from transgenic mice or Chinese hamsters into Syrian hamsters revealed that the original properties of the prion isolates are retained. When Syrian hamsters were first inoculated with 139H prions and subsequently challenged with Sc237 prions, the incubation period was determined by the faster Sc237 isolate. Regional mapping studies demonstrated different kinetics and patterns of PrPSc accumulation for Sc237 and 139H prions in the brains of Syrian hamsters as well as Tg(SHaPrP)7 mice. That distinct prion isolates induce different region-specific accumulations of PrPSc in brain suggests a novel mechanism for propagation of isolates whereby they replicate in particular sets of neurons. The prion isolates could be targeted to specific CNS cells by differing conformations of PrPSc, post-translational modifications of PrPSc such as Asn-linked glycosylation, or an as yet undetected macromolecule complexed with PrPSc in the prion.

Animals↗
PubMed1992

The role of manometry, electromyography and radiology in the assessment of faecal incontinence.

The results of laboratory investigations in 156 patients presenting with faecal incontinence are reviewed to see if and how these investigations supplement a careful clinical evaluation, and in particular to see if they help in the practical management of the problem. All patients underwent anal manometry, and in addition 52 underwent anal sphincter electromyography and 27 defaecatory proctography. Anal manometry quantified sphincteric weakness, and proved superior to digital assessment in this regard. Resting and squeeze pressures were less in those with complete than those with partial incontinence but the differences were not statistically significant. The measurements of rectal sensation and compliance were not additionally helpful. Single fibre electromyography provided the best measure of denervation with re-innervation and was abnormal in about 85% of the group studied. Jitter studies were unhelpful. Most patients had some abnormality on defaecatory proctography but clinical significance could not be established. The choice of treatment was made on clinical grounds and was not influenced by these investigations.

Aged↗
PubMed1992

The role of manometry, electromyography and radiology in the assessment of intractable constipation.

An analysis is made of functional studies performed in 96 constipated patients to see how these studies influenced the choice of surgical treatment. All patients underwent anal manometry, and other investigations included colonic transit studies (56), anal sphincter electromyography (42) and defaecatory proctography (34). Additionally nine patients underwent full thickness rectal biopsy. The resting anal canal pressures of the patients studied were lower than controls, and fibre density studies on electromyography were abnormal in half the patients studied suggesting a degree of denervation of the sphincter muscles, which possibly related to chronic straining on the toilet. There was evidence of reduced rectal sensation as shown by an increase in the least perceived volume on balloon distension of the rectum, and in those with megarectum and/or megacolon an increase in maximum tolerated volume. The recto-anal inhibitory reflex was used to screen for adult Hirschsprung's disease, but in one patient the reflex was present despite absence of ganglia on full thickness rectal biopsy indicating the need for biopsy as the definitive diagnostic procedure. Delayed colonic transit using radio opaque markers was a necessary requirement before recommending colectomy, and delayed transit was demonstrated in 34% of the patients studied. Anismus on electromyography was found in 20% of the patients but there was poor correlation with failure of the anorectal angle to widen when bearing down on proctography. The investigations helped in the choice of treatment, but were difficult to interpret. They should be used in severe constipation when surgery is being contemplated.

Adolescent↗