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Biomedical subjects

H Scott

Publications and source records attributed to H Scott.

At least 19 recordsLinked to original sources
PubMed1992

Pitfalls in determining IgG and IgG subclass antibodies to food antigens.

Several variables were found to influence enzyme-linked immunosorbent assay (ELISA) measurements of IgG and IgG subclass antibodies to food antigens. Two polyclonal rabbit antibody reagents to human IgG, and two sets of murine monoclonal antibodies to human IgG subclasses, were compared as secondary reagents. The choice of both polyclonal and monoclonal reagents affected significantly the results. High levels of IgA to an antigen depressed the measurements of comparable total IgG antibodies but did not influence the percentages of the four IgG subclass activities. Different ways of expressing the IgG subclass results were compared and the validity of the reference measurements used to obtain them was examined. Information from previous studies, together with the present data, suggests that absolute values cannot be reliably determined. We have therefore chosen to express the results for IgG subclass activities on a relative basis with reference to units of total IgG activity against the same antigen in each subject. This approach is practical and appears scientifically acceptable but limits the use of such determinations to comparisons between groups of subjects studied in the same laboratory.

Adolescent↗
PubMed1992

Association of subepithelial deposition of activated complement and immunoglobulin G and M response to gluten in celiac disease.

Patients with celiac disease produce not only immunoglobulin A (IgA) but also immunoglobulin G (IgG) and M (IgM) antibodies to gluten. Intake of dietary gluten may hence induce local complement activation and mucosal damage. Jejunal tissue sections from adult patients with celiac disease were examined by immunofluorescence with monoclonal antibodies to activation neoepitopes in C3b and the terminal complement complex (TCC). Subepithelial deposition of TCC was observed in 93% of 28 untreated and in 57% of 23 partly treated study subjects. The immunofluorescence staining intensity was well correlated with the serum level of gluten-specific IgG and IgM (but not IgA), the number of mucosal IgG-producing cells, and the degree of villous atrophy. Similar immune deposits were not observed in 5 successfully treated patients with celiac disease, 5 patients with dermatitis herpetiformis without jejunal villous atrophy, and 90% of 21 control patients with histologically normal jejunal mucosa. Gluten challenge increased the amount of subepithelial TCC and produced additional C3b deposition, suggesting recent complement activation. Ingested gluten might thus, via Ig-mediated subepithelial complement activation, damage the surface epithelium in celiac disease and induce compensatory crypt hyperplasia.

Adolescent↗
PubMed1992

Epithelial expression of HLA, secretory component (poly-Ig receptor), and adhesion molecules in the human alimentary tract.

Epithelial HLA class II is differentially expressed (DR >> DP) only after birth in salivary glands and small intestinal mucosa, in contrast to class I determinants and secretory component (SC) which appear early in gestation. However, there is a brisk postnatal increase in SC expression along with the class II induction, suggesting stimulation by cytokines from activated immune cells. T lymphocytes remain quite scanty in postnatal salivary glands, and the striking SC and class II expression might reflect a synergistic effect of IFN-gamma and TFN-alpha on immature epithelial cells. Enhanced epithelial expression of both SC and class II in salivary glands from sudden infant death victims could be the effect of immunostimulation caused by an infectious agent. Strikingly upregulated SC and epithelial class II expression (DR > DP > DQ) is seen in various inflammatory lesions such as obstructive sialadenitis, Sjögren's syndrome, chronic gastritis, and celiac disease. IFN-gamma and TNF-alpha are most likely involved as the expression patterns can be reproduced with these cytokines in vitro on colonic epithelial cell lines. However, these molecules of the Ig supergene family do not show a selective response in epithelia of inflammatory lesions because increased expression is also seen for lysozyme, lactoferrin and some other proteins. ICAM-1 can be upregulated on epithelial cells by various cytokines in vitro although the situation remains uncertain in mucosal inflammation. The expression pattern in IBD is complicated by dysplastic epithelial changes leading to reduced SC levels which may thus, in turn, jeopardize the poly-Ig transport mechanism. Epithelial class II molecules appear to have antigen-presenting properties, but the immunopathologic role of their increased expression in inflammatory disease in terms of induction of autoimmunity and/or abrogation of oral tolerance is a matter of continuing dispute.

Animals↗
PubMed1992

Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease.

Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha-lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy.

Adolescent↗
PubMed1992

Expression of receptors for tumor necrosis factor in human placenta at term.

The biological effects of tumor necrosis factor (TNF) are mediated through its interaction with high affinity receptors on target cells. Secretion of soluble cytokine receptors has been suggested as a mechanism of regulating cytokine activity in vivo. In a previous study we detected soluble TNF receptors (TNFRs) in amniotic fluid and urine samples from pregnant women, suggesting that secretion of soluble TNFRs may provide a mechanism for protection of the fetus against TNF action during pregnancy. In the present study, TNFR containing cells in cryostat sections from normal placentas at term were evaluated by monoclonal antibodies against the 55 kD--and the 75 kD TNFR in an indirect immunofluorescence technique. The 55 kD TNFR was expressed by the villous syncytiotrophoblasts, by vascular endothelial cells, by some decidual cells and by occasional cells in the placental stroma. Staining for the 75 kD TNFR was confined to the vascular endothelial cells, a relatively small number of stromal cells and decidual cells, whereas the villous syncytiotrophoblasts were negative. The abundant expression of TNFRs in placental tissue suggests: 1. That a considerable number of the placental cells are receptive to the regulatory activities of TNF; 2. That placental cells may be the cellular origin of soluble TNFRs secreted during pregnancy.

Antibodies, Monoclonal↗
PubMed1992

Primary malignant lymphoma of the brain. A report of 24 cases from the Norwegian Radium Hospital.

Between 1975 and 1987, 24 patients with primary central nervous system lymphoma were seen and treated at the Norwegian Radium Hospital. The overall median survival was 24 months. Patients with poor performance status (WHO 3-4) had a median survival of 3 months whereas patients with good performance status (WHO 0-2) had a median survival of 40 months (p < 0.0001). Patients who were not steroid-dependent after operation had a better survival than those patients who were steroid-dependent (p = 0.02). Nine patients were still living without evidence of disease at last follow-up, 18-130 months after the initial treatment.

Adolescent↗
PubMed1991

Identification and characterization of a hepatic microsomal glucose transport protein. T3 of the glucose-6-phosphatase system?

A 52 kDa polypeptide in rat liver microsomes was identified as a glucose-binding protein by its ability to weakly bind cytochalasin B and by its cross-reactivity to an antibody raised against the human erythrocyte glucose transport protein. The microsomal glucose binding polypeptide was purified by affinity chromatography and an antibody was raised against it. The inhibitory effect of this antibody on rat microsomal glucose-6-phosphatase activity and on glucose transport out of microsomal vesicles indicates that this protein is a microsomal glucose transport protein.

Animals↗
PubMed1991

Impedance measurement of absolute blood flow using an angioplasty catheter: a validation study.

An angioplasty catheter was developed to allow measurement of absolute coronary blood flow during interventional procedures. This method uses electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and indicator-dilution principles. The indicator is injected through a port located just proximal to the dilating balloon and the resulting changes in blood impedance are measured by electrodes at the catheter tip. Excellent linear correlations were found between known flow in 2 to 4 mm to diameter plastic tubes and catheter measurements (r = 0.99) and between timed collection canine femoral artery flow and catheter measurements (r = 0.97). Final validation was performed in canine coronary arteries using electromagnetic flowmeter data as the standard (r = 0.94). Thus accurate clinical determination of absolute coronary blood flow can be accomplished using this relatively inexpensive and simple catheter technique.

Angioplasty, Balloon, Coronary↗
PubMed1991

Torsion of the gall-bladder: rare, unrecognized or under-reported?

Four cases of torsion of the gall-bladder are reported. The clinical features closely mimic those of acute cholecystitis. Although conservative management was initially instituted, close monitoring of our patients led to appropriate surgical intervention. Review of the literature suggests that torsion is uncommon. Four surgical registrars at busy district general hospitals seeing four cases in one year suggests that it is under-reported. Acute torsion can develop after a period of recurrent abdominal pain--retrospectively diagnosed as 'chronic torsion'. A prospective study using currently available imaging procedures to assess gall-bladder mobility, itself associated with torsion, could reveal whether this leads to chronic pain.

Acute Disease↗
PubMed1990

Human CD8+ intraepithelial T lymphocytes are mainly CD45RA-RB+ and show increased co-expression of CD45R0 in celiac disease.

Expression of various CD45 isoforms (RA, RB and R0) on CD3+, CD4+ and CD8+ intraepithelial and lamina propria T cells was examined in situ by a three-color immunofluorescence technique in jejunal biopsy specimens from 32 patients with celiac disease and 18 controls. The median percentage of CD3+ intraepithelial lymphocytes (IEL) that expressed CD45R0 increased from 52% in controls to 69% in untreated celiac disease (p less than 0.01). Furthermore, the percentages of CD4+ and CD8+ IEL strongly positive for CD45R0 rose respectively from 94% and 24% in controls to 100% and 55% in untreated celiac disease. Conversely, CD45R0 was strongly expressed on most CD3+ lamina propria lymphocytes (LPL) both in control (81%) and diseased (77%-81%) mucosa. A variable fraction of the intraepithelial and lamina propria CD3+ T cells expressed mainly CD45RB (controls, 46% and 20%, respectively; celiac disease, 29% and 15%). Only 2% IEL and 4% LPL were positive for CD45RA. Expression of different CD45R isoforms thus identified three distinct CD8+ T cell subsets in human intestinal mucosa. In addition, our results suggested that antigen-primed CD8+CD45R0+ memory cells accumulate in the jejunal epithelium of patients with untreated celiac disease.

Adolescent↗
PubMed1990

Secretory immunity in celiac disease: cellular expression of immunoglobulin A subclass and joining chain.

Two-color immunofluorescence staining in situ demonstrated increased proportions of immunoglobulin A2 subclass-producing cells in jejunal mucosa from adult patients with untreated (47%, P less than 0.01) or treated (37%, P less than 0.05) celiac disease compared with controls (28%). Costaining was also performed for joining chain, which is a key factor in the epithelial transport of secretory antibodies; its expression by immunoglobulin A2 cells was only marginally reduced in untreated patients (96%) compared with treated patients and controls (98%). Also, immunoglobulin A1 cells showed similar joining chain positivity (89%) in all three groups. Considering the expanded total jejunal immunoglobulin A-cell population and the subclass-associated joining chain expression, it could be calculated that the potential of immunoglobulin A2 cells for contribution to secretory immunity was increased 3.9 times in untreated (P less than 0.01) and 1.8 times in treated (P less than 0.05) patients and that of immunoglobulin A1 cells was increased 1.7 times in untreated (P less than 0.05) but remained unaltered in treated patients. The estimated relative contributions of locally produced immunoglobulin A2 to secretory immunoglobulin A would thus be 51% and 37% in the two patient categories, respectively, compared with 31% in the controls. These data suggested enhanced secretory immunity in celiac disease and might reflect a protective, possibly antimicrobial, immune response. It could not be excluded, however, that increased generation of secretory immunoglobulin A at the same time contributes to the gluten-induced pathogenesis of celiac disease.

Adult↗
PubMed1990

Ioversol in ascending phlebography--a clinical trial.

In this controlled randomised double-blind parallel group study of the use of ioversol-240 and ioversol-320 in venography all studies were considered diagnostic with comparable quality in the two groups. Patient tolerance was high with mild heat observed in 7 patients in the ioversol-320 group and 1 patient in the ioversol-240 group. Assessment of pain was also comparable (2 patients in the ioversol-240 group and 1 in the ioversol-320 group). Both strengths of the contrast agent produced no clinically significant, drug related, changes in vital signs or laboratory parameters and there were no significant clinical adverse reactions.

Contrast Media↗
PubMed1990

Intraepithelial TcR alpha/beta+ lymphocytes express CD45RO more often than the TcR gamma/delta+ counterparts in coeliac disease.

Expression of CD45RO on intraepithelial lymphocytes (IEL) bearing the T-cell receptor (TcR) alpha/beta or gamma/delta was studied in situ by three-colour immunofluorescence on jejunal tissue sections from 21 patients with coeliac disease and eight controls. CD45RA-TcR alpha/beta+ IEL expressed CD45RO significantly more often (75%) than the preferentially expanded TcR gamma/delta+ counterpart (59%). Triple staining for CD3, CD4/8 and CD45RA or CD45RB revealed that all CD3 + 4 - 8 - IEL (taken to be TcR gamma/delta+) expressed CD45RB and none were CD45RA. CD45RO positivity was of the same magnitude (66%) on the predominating monoclonal antibody delta TCS1-reactive fraction of TcR gamma/delta+ cells as on the remainder of the TcR gamma/delta+ subset. These results suggest that gluten exposition in patients with coeliac disease leads to accumulation of CD45RA-, putative antigen-primed memory cells of both TcR phenotypes. The less marked CD45RO expression within the preferentially expanded TcR gamma/delta+ subset of IEL may be of particular biological interest.

Adolescent↗
PubMed1990

Measurements of serum IgA and IgG activities to dietary antigens. A prospective study of the diagnostic usefulness in adult coeliac disease.

Serum samples from 458 consecutive adult patients with intestinal symptoms and/or suspected food intolerance were examined for IgG and IgA antibody activities to gluten, egg, and cow's milk antigens by an enzyme-linked immunosorbent assay (ELISA). Increased IgA and/or IgG activities to gluten were seen in 61 patients: 35 had coeliac disease (CD) as suggested by jejunal villous atrophy and subsequent histologic and/or clinical improvement on a gluten-free diet; 4 were previously diagnosed CD patients with clinically suspected dietary failure; 2 had dermatitis herpetiformis with a CD-like intestinal morphology; and 3 had possible gluten intolerance without villous atrophy. The rest had other disorders that might have affected the permeability of the gastrointestinal mucosa or the hepatic IgA catabolism. When the IgA activity to gluten was increased, neither the IgA/IgG activities to nongluten antigens nor the ratio of nongluten to gluten antibodies could discriminate between CD patients and those without CD. However, the median IgA activity to gluten was significantly higher in the CD group. The probability for CD thus increased from 33% in patients with IgA activity to gluten between 0.4 and 0.8 OD units to 90% in those with such activity above 2.4 OD units. Nevertheless, seven untreated CD patients had IgG and IgA activities to gluten within the normal range. ELISA determinations of serum antibodies to gluten antigens are a valuable adjunct in the diagnosis of adult CD, but a negative test does not exclude this disorder.

Adolescent↗