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Biomedical subjects

J Sutherland

Publications and source records attributed to J Sutherland.

At least 73 records · Page 4Linked to original sources
PubMed1988

Quantitative immunological differences between newly diagnosed Graves' disease patients and relapsed patients.

Class 2-positive T cells, T-cell and mononuclear cell subsets, thyrotropin receptor antibodies (TRAb) and immune complexes were evaluated in 34 newly diagnosed Graves' patients and in 13 relapsed patients before a cycle of specific medical treatment. Class II-positive T lymphocytes were detected by monoclonal antibodies against different epitopes of class II antigens, whereas 4F2-positive cells were detected by 4F2 monoclonal antibody. 4F2-positive cells were statistically increased in newly diagnosed Graves' patients compared to relapsed patients (p less than 0.05). An increased percentage of class II activated T cells, detected by monoclonal antibodies L243, was found in newly diagnosed patients in comparison with relapsed subjects (p less than 0.025). Newly diagnosed Graves' patients showed a significant decrease in the ratio suppressor/cytotoxic T cells in comparison with normal control subjects but not with relapsed patients. Ninety-one % of newly diagnosed Graves' patients showed a high TRAb value, whereas only 69% of relapsed patients showed increased values (p less than 0.025). No difference was observed in the immune complex positivity between newly diagnosed Graves' patients and relapsed subjects. In conclusion, both humoral and cellular immune differences were found in relapsed patients vs newly diagnosed Graves' patients. The immunological abnormalities are quantitatively more pronounced in the latter group.

Adolescent↗
PubMed1988

Selective modulation of hepatic and ileal Na+-K+-ATPase by bile salts in the rat.

Sodium-potassium adenosinetriphosphatase (Na+-K+-ATPase) is modulated by functional demands. We determine whether Na+-K+-ATPase specific activity was changed by oral administration of different bile salts and whether upregulation in the liver is due to increased numbers of catalytic units. In rats after bile duct drainage for 18 h, Na+-K+-ATPase activity was reduced to 50% of control in liver and ileum but unchanged in jejunum and kidney. Increased Na+-K+-ATPase activity after short-term feeding of bile salts was noted only following trihydroxy bile salts, i.e., taurocholate (100 mg/100 g body wt) increased hepatic Na+-K+-ATPase 143% and ileum 138% above control, whereas jejunum and kidney were unchanged. Chronic feeding of trihydroxy bile salts for 4 days increased hepatic Na+-K+-ATPase (214-260%) and alkaline phosphatase (189-274%), whereas 5'-nucleotidase and Mg2+-ATPase activities were unchanged from control. Plasma membrane Na+-K+-ATPase activity significantly increased as early as 4 h after taurocholate administration, whereas homogenate activity did not rise until 16 h; both reached a new steady state between 24 and 48 h. Sixteen hours after bile salt feeding, increased Na+-K+-ATPase activity was blocked by cycloheximide, and in the liver increased enzyme activity (179%) was associated with a comparable change in sodium-dependent [gamma-32P]ATP binding (162%) to liver plasma membrane fractions. These studies show Na+-K+-ATPase activity adapts selectively in liver and ileum following administration of trihydroxy bile salts, and the process involves increased density of Na+-K+ pump sites on the liver plasma membrane.

Animals↗
PubMed1987

Immunology in diabetic pregnancy: activated T cells in diabetic mothers and neonates.

Lymphocytes bearing surface antigens indicating early and full activation have been evaluated, in addition to T cell subsets, in blood samples from diabetic pregnant patients, neonates from diabetic mothers and control groups. The type of diabetes and the trimester of pregnancy were taken into account. Monoclonal antibodies were used to enumerate total T cells, helper/inducer, cytotoxic/suppressor Tlymphocytes and activated mononuclear cells using antibodies binding lymphocyte surface antigens as markers of early lymphocyte activation, and MHC Class II surface antigens as markers of late activation. A decrease in T-helper cells during the third trimester of pregnancy in Type 1 (insulin-dependent) and gestational diabetic patients (p less than 0.02) and a decrease in T-suppressor cells in Type 2 (non-insulin-dependent) diabetic pregnant patients during the third trimester (p less than 0.01) were observed in relation to normal values. As in normal pregnancy, 4F2-positive cells were increased in 48% of diabetic pregnant patients during the second and third trimesters of gestation. Class II-positive cells were increased in almost 60% of Type 1 and gestational diabetic patients during the last trimester of pregnancy in comparison with normal pregnant women and control subjects. A decrease in T-helper cells (p less than 0.02) and a clear increase in 4F2-positive cells (p less than 0.001) and Class II-positive lymphocytes (p less than 0.005) were observed in the infants of diabetic mothers in comparison with control subjects. The maternal cellular immune system, actively altered in pregnancy, is fully activated in a number of Type 1 and gestational diabetic pregnant patients. Activated lymphocytes are even found in the neonates of diabetic mothers, but these do not trigger the events leading to the onset of diabetes in the short term.

Adult↗
PubMed1987

Reduced protection against hepatitis B virus following vaccination in patients with type 1 (insulin-dependent) diabetes.

Twenty patients with well controlled Type 1 (insulin-dependent) diabetes of at least 10 years duration and 47 control subjects were vaccinated against the hepatitis B virus using the Hevac B vaccine. The vaccine was administered into the deltoid region on three occasions at intervals of 1 month. Thereafter a fourth dose was given to subjects still negative for antibody to hepatitis B surface antigen (HbsAb). The median rise of HbsAb titres was 230 mIU/ml in normal subjects and 50 mIU/ml in diabetic patients (p less than 0.001). Eight patients (40%) failed to reach HbsAb titres above 30 mIU/ml, the level considered to give optimal protection against the infection, whereas only one normal control subject failed to reach this level. Five patients (25%) showed no response despite a fourth dose of the vaccine. There was an increased frequency of HLA-DR7 in low responders and a decreased (less than 1.5) helper/suppressor lymphocyte ratio. Diabetic patients are thus less likely to mount a protective antibody response following vaccination against hepatitis. Since hepatitis B surface antigen is reported to be considerably more common in diabetic patients than control subjects, infection with hepatitis B virus may have a greater risk of chronicity in diabetes.

Adult↗
PubMed1987

Ultrastructure of lymphocyte subsets and of activated lymphocytes in type 1 diabetes as defined by monoclonal antibodies and the immunogold technique.

The ultrastructure of peripheral blood lymphocyte subsets and activated lymphocytes from 5 patients with recent onset insulin-dependent diabetes as identified by monoclonal antibodies (CD4, CD8 and 4F2) and labelled with gold coupled goat anti-mouse IgG are described and depicted. Electron microscopy revealed no differences in appearance between investigated lymphocyte subsets at the single cell level. Activated lymphocytes as defined by an early activation antigen (4F2) do not always have a characteristic appearance nor do they show morphological signs of activation in all cases. We would conclude that it is not possible to recognize different lymphocyte subsets based only on their ultrastructure.

Antibodies, Monoclonal↗
PubMed1986

A study of the kinetics of the reaction of ligands with the liganded states of mouse embryonic haemoglobins.

The reactivities of the liganded states of the embryonic haemoglobins of the mouse with both O2 and CO were measured and compared with the reactivities of the adult protein. Laser-photolysis experiments on the recombination of O2 with the partially oxygenated proteins indicates chain heterogeneity in the adult and embryonic EII and EIII species, with the difference in subunit reactivity being greatest in the embryonic species. Haemoglobin EI shows chain equivalence in these experiments. The homogeneous time courses observed for the O2-dissociation reactions are consistent with chain equivalence within all the proteins with regard to this reaction. The specific values obtained for the respective rate constants from each of these studies indicates that the high O2 affinity previously reported for haemoglobin EI is, in greatest part, due to its low O2 dissociation rate. Flash-photolysis studies on the binding of CO with the partially liganded forms of the proteins show the same patterns of chain heterogeneity as seen in O2-binding studies.

Animals↗
PubMed1986

An investigation of the ligand-binding properties of Pseudomonas aeruginosa nitrite reductase.

The low-temperature e.p.r. and m.c.d. (magnetic-circular-dichroism) spectra of Pseudomonas aeruginosa nitrite reductase, together with those of its partially and fully cyanide-bound derivatives, were investigated. The m.c.d. spectra in the range 600-2000 nm indicate that the native axial ligands to haem c are histidine and methionine, and furthermore that it is the methionine ligand that must be displaced before cyanide binding at this haem. The m.c.d. spectra in the range 1000-2000 nm contain no charge-transfer bands arising from low-spin ferric haem d1, a chlorin. New optical transitions in the region 700-850 nm were found for the cyanide adduct of haem d1. The g-values of haem d1 in the native enzyme are 2.51, 2.43 and 1.71, suggesting co-ordination by two histidine ligands in the oxidized state. There is clear evidence in the e.p.r. data of an interaction between the c and d1 haem groups. This is not apparent in the optical spectra. The results are interpreted in terms of haem groups that are remote from each other, their interaction being mediated through protein conformational changes. The possible implications of this in relation to reduction processes catalysed by the enzyme are considered.

Circular Dichroism↗
PubMed1986

Clinical correlation with anti-peripheral-nerve myelin antibodies in Guillain-Barré syndrome.

Anti-peripheral-nerve myelin antibodies (anti-PNM Ab) can be detected in the serum of all patients with acute-phase Guillain-Barré syndrome (GBS) thus far tested. Correlation of the titer of this antibody with the clinical course would help to establish a role for the humoral immune system in the pathophysiology of GBS. In this study, anti-PNM Ab levels were measured in serial serum samples of 7 patients with GBS with an assay that detects antibodies bound to peripheral nerve myelin antigens by fixation of the first component of complement. Although the titers of anti-PNM Ab detected in these patients varied between 0 and 256 U/ml, the antibody titer was always highest on admission (35 to 256 U/ml) and rapidly declined during a one-to-three-week period. Disappearance of antibodies or very low levels of them correlated with cessation of progression and considerable clinical improvement as documented by increased pulmonary vital capacity and muscular strength. Low but measurable antibody titers (5 to 12 U/ml) were frequently found up to four months following the acute neurological deficit. The close temporal relationship between anti-PNM Ab titer and the clinical course in GBS suggests that antibody most likely participates through complement activation in peripheral nerve demyelination.

Adolescent↗
PubMed1986

An endoscopic micromanipulator for multiplanar transesophageal imaging.

We have developed an esophageal probe with a precision micromanipulator and a transversely oriented 32 element ultrasonic array which operates at 3.5 MHz. The probe allows us to obtain multiple two-dimensional images of the heart with known angular relationships between them over a series of cardiac cycles. Our ultimate purpose is to acquire images for left ventricular volume estimation with a three-dimensional reconstruction method. Technical details of the probe design are given. In vitro tests have shown that the imaging plane can be angulated within 1.5 degree root mean square error. In vivo results with dogs have demonstrated its ability to obtain multiplanar short axis images of the heart.

Animals↗
PubMed1986

The matrix components of the epiphyseal growth plate and articular cartilages from dogs treated with ammonium tetrathiomolybdate, a copper antagonist.

As part of a project to study the effect of copper deficiency (CD) on bone development in young dogs, the composition and metabolism of proteoglycans (PGs) and extractability of collagens in the epiphyseal growth plate cartilage (EGPC) and articular cartilages (AC) were investigated. Copper deficiency was induced by feeding ammonium tetrathiomolybdate (TTM) a copper antagonist. The collagen of cartilages from TTM-treated animals was significantly more soluble in 0.5 saline than control tissues. While no distinction between TTM-treated and control cartilages was evident in terms of PG content or extractability under associative (0.5 M-GuHCl) or dissociative (4.0 M-GuHCl) conditions, the sedimentation behaviour of the PG aggregates following CsCl density gradient ultracentrifugation suggested less polydispersity of PGs in preparations from the TTM-treated animals. Moreover, analysis of the PG monomers from EGPC of TTM animals showed galactosamine/glucosamine ratios higher than control preparations, suggesting a reduced keratan sulphate content in these preparations. Organ culture of EGPC showed a significant reduction in the incorporation of 35S into PGs and of 3H-thymidine into DNA in the tissues of TTM-treated animals relative to controls. From these findings we deduce that the catabolism of PGs and the extent of collagen cross-linking in EGPC of TTM-treated animals may be reduced relative to age-matched control tissues.

Animals↗
PubMed1986

A demonstration of pharmacokinetics and physiological modelling using a microcomputer for data capture and analysis.

We describe a simple and inexpensive demonstration of mass transport and exchange using dye clearance from a hydrodynamic model. A microcomputer was used for data acquisition and storage, non-linear least squares curve fitting, compartmental analysis and parameter estimation. The system is useful for demonstrating the indicator-dilution technique for fluid volume measurement and compartmental analysis in pharmacokinetics.

Algorithms↗
PubMed1985

Induction of the expression of HLA class I antigens on K562 by interferons and sodium butyrate.

Using sodium butyrate and alpha, beta, and gamma interferons as inducing agents it has been possible to demonstrate the triggering of HLA class I antigen synthesis in the K562 cell line. This cell line, widely used to study hemopoietic differentiation, does not naturally express HLA antigens. This effect was confirmed by the detection of HLA class I antigens on the cell membrane with specific monoclonal antibodies, by immuneprecipitation, and by isolation of specific HLA ABC messenger RNA, in the induced cells. No synthesis of HLA class II antigens was observed. Because leukemic cells can be considered as a model representing certain stages of normal hemopoietic differentiation, the expression of HLA antigens on K562 cells induced to differentiate could be interpreted as an event related to the process of differentiation itself. The lack of expression of DR antigens may result from a genetic defect as observed for beta 2-microglobin in Daudi cells.

Antibodies, Monoclonal↗
PubMed1985

Distribution and binding of glycosaminoglycan polysulfate to intervertebral disc, knee joint articular cartilage and meniscus.

The relative incorporation of 3H-Glycosaminoglycan polysulfate (3H-GP, Arteparon) into rabbit knee joint articular cartilage, patella cartilage, meniscus and intervertebral disc tissues was determined at 1, 2, 4 and 8 d after intramuscular administration (60 muCi/kg, 400 micrograms/kg). The distribution of the drug within these tissues was also examined autoradiographically. The highest uptake of 3H-GP occurred in the menisci and was observed to be largely localised about collagen fibres on the outer periphery of these tissues. Over the eight day period, the level present declined to approximately 50% of that present on day one. The level of drug attained in articular and patella cartilages was approximately 20-25% of that in the meniscus. It was uniformly dispersed and remained fairly constant over the eight day period. Of greatest interest was the finding for the disc, where the highest level of labelling, which occurred on day two, was comparable to the knee joint hyaline cartilages and was associated with the collagenous lamella structure of the outer annulus fibrosus. After day two, the level of drug in these areas declined, accompanied by an accumulation in the nucleus pulposus. Using an ion exchange assay technique, and gel permeation chromatography of 4M guanidine hydrochloride extracts of these connective tissues, binding of 3H-GP to proteoglycans, collagen and non-collagenous proteins, was demonstrated; the latter component representing the major drug binding species. It is suggested that localisation of the drug within these connective tissues may be beneficial in protecting their matrix components against enzymatic degradation in the pathological state.

Animals↗
PubMed1984

Use of somatic cell hybrids for quantitation of mutagenesis: reduction in background mutants by fluorescence-activated cell sorting (FACS).

Environmentally induced mutations, especially those involving large scale genetic damage such as deletions and chromosome loss, are of central importance in the production of human genetic disease and cancer. We have developed a methodology, the AL assay, that permits detection of such extensive genetic changes which often escape detection in other systems in which they are lethal. The AL assay employs a human-Chinese hamster ovary cell hybrid that retains a single human chromosome, number 11. A set of specific cell surface antigens result from genes located on opposite arms of this chromosome. Exposure to mutagens produces mutants which form colonies in the presence of complement and specific antiserum that kill nonmutant cells. The frequency and pattern of marker loss provides a measure of single gene mutation, large and small deletion, and loss of the entire chromosome 11. We have employed the indirect fluorescein conjugated isothiocyanate (FITC) technique and fluorescence-activated cell sorting (FACS) to remove spontaneous mutants from the initial population. The 100-fold reduction in background thus far achieved should allow accurate analysis of mutation by ionizing radiation at doses of less than 10 rad.

Animals↗
PubMed1984

A thin quartz cell suitable for vacuum ultraviolet absorption and circular dichroism measurements.

The design of a thin quartz cell suitable for absorption and circular dichroism measurements in the vacuum ultraviolet is described. Important features of the cell are (1) that it can be disassembled for cleaning and reproducibly reassembled with path lengths up to 0.3 mm, and (2) that strain in the windows from the compressed sample can be relieved by a sample overflow port. The latter feature allows the cell to be used for circular dichroism as well as absorption measurements.

Circular Dichroism↗
PubMed1984

Histoplasma capsulatum in the eye.

The ocular pathologic findings in an immunosuppressed patient who died of disseminated histoplasmosis are described. Histoplasma capsulatum was found in large numbers within the endothelial cells of the choroid, in one area each of the ciliary body and trabecular meshwork. There was a minimal inflammatory response. No granulomas were noted. Previously reported cases of ocular histoplasmosis in immunosuppressed patients are similar in that, with one exception, granulomatous inflammation was not demonstrated. Thirteen eyes in which histoplasma organisms have been found in the eye are reviewed.

Adult↗