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Biomedical subjects

J R Baker

Publications and source records attributed to J R Baker.

At least 253 records · Page 14Linked to original sources
PubMed1985

An integer linear programming model of staff retention and termination based on multiattribute utility theory.

An integer linear programming formulation was used to model several staffing alternatives available to the director of a recreation therapy department. The utility function of the decision maker was assessed using two attributes of effectiveness: performance and experience. Two utility approximations were obtained for each staff member based upon the average performance rating and number of years of experience both as a recreation therapist and at the facility. The utility obtained was viewed as a proxy for, and a comparative measure of, effectiveness, which considers the criteria of training and experience. The individuals who comprise the most effective combination of therapists, given staff reductions, were obtained by maximizing the sum of staff values. The first constraint set involved a budgetary constraint, coverage constraints, and an EEOC policy restriction. The coverage restriction and the budget were varied to reflect changes in the department resources. The model was validated with the department supervisor for the case of a one-position, 10% budget decrease.

Employment↗
PubMed1985

Antithyrotropin antibodies in the sera of Graves' disease patients.

To determine the presence and potential importance of antiidiotypic antibodies (anti-id) in the immune regulation of Graves' disease, sera from 57 patients with Graves' disease were screened before or during antithyroid therapy by enzyme-linked immunoabsorbent assay (ELISA) for presumptive anti-id, as defined by the presence of immunoglobulins (Igs) directed against TSH. The mean optical density, indicating the presence of TSH-binding antibodies, was 0.34 +/- 0.28 (+/- SD) in the sera of Graves' disease patients and 0.19 +/- 0.12 in the sera of 24 normal subjects (P less than 0.004). Control antigens (hCG and albumin) did not bind significant amounts of serum Igs. In 8 Graves' patients whose sera bound TSH, 40-80% inhibition was obtained with the addition of TSH receptor-purified IgG (approximately 1 microgram/ml) derived from a single Graves' patient's serum; no inhibition was found with normal IgG (approximately 10 micrograms/ml). Presumptive anti-id was isolated from sera of 6 Graves' patients by affinity purification with a TSH affinity column; the resultant IgG blocked immunoglobulin binding to the TSH receptor when added to the serum of the same patient from whom it had been isolated. The presence of anti-id correlated inversely with the presence of TSH receptor antibodies (r = -0.76; P less than 0.01). These studies demonstrate that 1) significant TSH binding is present in sera from Graves' disease patients, and 2) this TSH binding is specifically inhibitable by Graves' IgG, but not by normal IgG. These data support the hypothesis that TSH-binding immunoglobulins may represent anti-id that are present in Graves' disease as part of the immunological response to TSH receptor or TSH receptor antibodies. Such anti-id could modulate the expression of disease activity in Graves' disease by altering TSH receptor antibody action or production.

Antibody Affinity↗
PubMed1985

Production and characterization of monoclonal antibodies directed against connective tissue proteoglycans.

Monoclonal antibodies have been raised against determinants present in cartilage proteoglycan. Characterization of the specificity of these antibodies indicated that they recognize determinants present in the keratan sulfate glycosaminoglycan chain and on chondroitin sulfate oligosaccharide stubs attached to the proteoglycan core protein after chondroitinase digestion of the proteoglycan (i.e., delta-unsaturated 4- and 6-sulfated and unsulfated chondroitin sulfate on the proteoglycan core). The antibody recognizing keratan sulfate has been used to demonstrate the presence of a keratan sulfate-rich proteoglycan subpopulation that increases with increasing age of animal compared with chondroitin sulfate-rich proteoglycans. Monoclonal antibodies recognizing determinants on chondroitinase-treated proteoglycan have been used in immunohistochemical localization studies determining the differential distribution of 4- and 6-sulfated and unsulfated proteoglycans in tissue sections of cartilage and other noncartilaginous tissues. Digestion with chondroitinase ABC or ACII can be used to differentiate between chondroitin sulfate and dermatan sulfate proteoglycan in different connective tissues. In addition, the presence of a 6-sulfated chondroitin sulfate proteoglycan that is associated with membranes surrounding nerve and muscle fiber bundles is described. Monoclonal antibodies were also raised against the link protein(s) of cartilage proteoglycan aggregate. They have been used in peptide map analyses of link protein and in demonstrating the presence of a high-mannose oligosaccharide chain of the link proteins. The presence of high-mannose oligosaccharide structures on the link protein(s) accounts for the microheterogeneity of the link proteins (link proteins 1, 2, or 3) that is observed on sodium dodecyl sulfate-polyacrylamide gels.

Animals↗
PubMed1985

An ultrastructural analysis of the vascular damage in the lethal and sublethal Forssman reaction in the guinea-pig.

The involvement of the complement system and platelets in the sublethal Forssman reaction in the guinea pig has been studied together with the ultrastructural changes observed in the endothelial cells of the pulmonary vasculature. The main ultrastructural change noted was swelling of the endothelium. This did not occur in thrombocytopenic animals or in decomplemented animals, indicating the importance of both platelets and the complement pathways in this reaction. The platelet inhibitors sulphinpyrazone or aspirin had no effect on endothelial swelling in the sublethal reaction. In the lethal reaction the degree of endothelial cell damage was more severe and included lesions in the cell membrane, lifting, necrosis and finally exposure of the basement membrane. This damage only occurred in animals with an intact complement cascade.

Anaphylaxis↗
PubMed1985

A rapid, sensitive enzyme-linked immunoassay for human thyrotropin.

In this enzyme-linked immunoassay for human thyrotropin (TSH) in unextracted serum we use 96-well immunoenzymometric assay plates, first coated with polyclonal antibody to TSH, then incubated with the serum samples and reacted with mouse monoclonal antibody to human TSH. After incubation with alkaline phosphatase-labeled antibody against mouse IgG, disodium p-nitrophenyl phosphate is added and the color change is measured spectrophotometrically. Assay sensitivity is 0.1 milli-int. unit/L. Cross reactivity with lutropin, follitropin, or choriogonadotropin was negligible. TSH concentrations ranged from 0.4 to 4.1 milli-int. units/L in 43 normal subjects (mean 2.0, SD 1.0), and were uniformly less than 0.3 milli-int. unit/L in 23 patients with hyperthyroidism. Features which make this assay advantageous to the clinical laboratory include ease of set-up, ability to assay many samples at a time, high sensitivity, rapid turnaround time (8 h), and absence of requirements for radioactive materials.

Animals↗
PubMed1985

Autoradiographic study of the distribution of [3H]- and [14C]-hydrallazine in the rat.

The distribution of [3H]-hydrallazine (HP) in the rat was investigated using autoradiography from the whole-body, to the electron microscopic level. Intravenous dosing gave rapid and persistent labelling of blood vessels, particularly arteries, whilst radiolabel from orally administered drug was detectable in the vasculature in modest amounts only at 6 h, the longest interval studied. Light microscopic autoradiographs of blood vessels showed silver grains associated with elastic laminae and the marginal region of smooth muscle cells. Analysis of electron microscopic autoradiographs of arteries from rats dosed intravenously (1 h and 6 h) and orally (6 h) revealed the greatest percentage of radiolabel in each case to be associated with the elastic laminae (34.9 to 40.3%). Significant proportions of total radiolabel (between 12.7 and 34.8%) were ascribed to the smooth muscle cells. It is concluded that radiolabel, possibly in the form of intact HP, is accessible to the vascular smooth muscle cells where the vasodilator action of HP is held to be exerted.

Animals↗
PubMed1985

Use of protein-based standards in automated colorimetric determinations of fructosamine in serum.

We have developed an automated colorimetric assay for glycated serum proteins (or fructosamines), measuring the reducing activity of serum in alkaline solution (pH 10.35) at 37 degrees C. The calibrants were prepared from a synthetic fructosamine (1-deoxy-1-morpholinofructose), although secondary standards of glycated bovine albumin were more robust in routine application. Interference was appreciable only with icteric specimens (bilirubin greater than 60 mumol/L), and between-batch imprecision (CV) was less than 2%. The range of fructosamine concentrations measured in 502 healthy (nondiabetic) blood donors was 1.87-2.87 mmol/L. There were no significant (p greater than 0.05) age- or sex-related differences in this population sample. Fructosamine accurately reflected blood glucose control as evidenced by the significant correlation with glucose concentrations in fasting plasma (r = 0.82, p less than 0.001) and with glycated hemoglobin (HbA1c) (r = 0.87, p less than 0.01) in 115 patients with type 2 (non-insulin-dependent) diabetes mellitus. The test is simple and rapid to perform (75 samples per hour) and provides an alternative to HbA1c determinations for monitoring blood glucose control and assessing the effects of changes in diabetes management.

Adolescent↗
PubMed1985

Comparison of glucose polymer and glucose for screening and tolerance tests in pregnancy.

Forty-eight of 100 pregnant women received a 100-g (nonfasting) glucose screening test at about 28 weeks' gestation, followed by a 100-g glucose tolerance test. Another 52 received a 100-g (nonfasting) glucose polymer screening test followed by a 100-g glucose polymer tolerance test. Mean plasma glucose one hour after the glucose screening test was significantly lower than after the glucose polymer screening test. A further 178 women received a glucose polymer screening test and a glucose polymer tolerance test (230 in total). These women and the infants they delivered were studied to derive diagnostic criteria for the 100-g glucose polymer tolerance test by correlating maternal carbohydrate tolerance with indexes of neonatal metabolic performance, and to determine an adequate method of screening for carbohydrate intolerance of pregnancy (gestational diabetes). Diagnostic criteria similar to those of O'Sullivan and Mahan were also developed for the glucose polymer tolerance test. These values are up to 5% lower than those recommended by the National Diabetes Data Group (1979) for the 100-g glucose tolerance test.

Adult↗
PubMed1984

Serum fructosamine concentrations in patients with type II (non-insulin-dependent) diabetes mellitus during changes in management.

The serum fructosamine concentration was examined as a new means to monitor metabolic control in non-insulin-dependent diabetes during changes in management. Weekly fructosamine estimations were compared with glycosylated haemoglobin (HbA1c), 24 hour urinary glucose, and fasting plasma glucose concentrations in a 17 week study entailing withdrawal and reinstitution of oral treatment. The serum fructosamine concentration was more sensitive than the other measurements in detecting a deterioration in diabetic control after stopping oral hypoglycaemic drugs. The response to reinstitution of treatment was not significant in the first three weeks (p = 0.266), despite a highly significant reduction in fasting plasma glucose (p = 0.001) and 24 hour urinary glucose concentrations (p = 0.012). Compared with HbA1c, concentrations of fructosamine appeared more useful in monitoring short term (three to six weeks) changes after alterations in management of diabetes. Additional advantages were lower cost and technical simplicity of measurement.

Adult↗
PubMed1984

Pharmacokinetics, distribution and elimination of a synthetic octapeptide analogue of somatostatin in the rat.

The in vivo fate of a long acting somatostatin analogue [des-AA1,2,3,4,13,14,D-Trp8,Gaba12]-somatostatin has been studied in the rat using biochemical and autoradiographic techniques. The analogue has a longer plasma half-life than somatostatin. This is due to its greater metabolic stability which renders it resistant to enzymic attack in the tissues. The primary route of elimination is by biliary excretion following clearance from the circulation by the liver. Evidence of enterohepatic circulation was found, but only to a very limited extent. When administered s.c., high plasma concentrations of intact peptide persist for a period of hours due to slow release from a stable depot at the injection site.

Animals↗
PubMed1984

Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimulating hormone (TSH) receptor antibodies by first injecting rabbits with (TSH receptor purified) IgG from Graves' patients. The resulting antiserum was then adsorbed with Sepharose-coupled TSH in an attempt to specifically bind and isolate the anti-idiotype. The antibody obtained from this process was shown to bind specifically to TSH receptor-binding antibodies from Graves' patients, and this binding could be inhibited by 56% with the addition of 10(-4) M TSH but not by HCG (10(-2) M). The anti-idiotype also bound to TSH, and this binding could be specifically inhibited by receptor-purified Graves' IgG (60% inhibition at 10 micrograms/ml IgG), but not by IgG from normal subjects (no inhibition at 50 micrograms/ml IgG). In a TSH receptor binding assay, the anti-idiotype could inhibit TSH receptor binding in Graves' sera at a 1,000-fold lower concentration than could anti-kappa/lambda antiserum; the anti-idiotypic antiserum also inhibited in vitro TSH-mediated adenylate cyclase stimulation at an IgG concentration of 5 micrograms/ml, while heterologous anti-TSH antisera and normal IgG at similar concentrations had no effect. Finally, despite being generated against a single patient's TSH receptor binding antibody, the anti-idiotype was able to block TSH receptor binding in the serum of six other Graves' patients, thus suggesting that there may be conformational conservation in the antigen that is recognized by different individuals' TSH receptor-binding immunoglobulins.

Adipose Tissue↗
PubMed1983

Studies on the properties of the inextractable proteoglycans from bovine nasal cartilage.

Bovine nasal cartilage was repeatedly extracted with the dissociative solvent, 4 M guanidinium chloride. About 25% of the total tissue proteoglycans could not be solubilized as judged by galactosamine analysis. The inextractable proteoglycan could be at least partially solubilized by treating the guanidine-extracted tissue with reagents which completely or partially degraded the proteoglycan protein core. Digestion with papain or cyanogen bromide completely solubilized the tissue and released all of the galactosamine-containing material while trypsin or hydroxylamine treatment left the cartilage macroscopically unchanged and extracted about 50% of the residual galactosamine. The degradatively solubilized material was compared to that extracted with guanidinium chloride. The papain-released glycosaminoglycan chains from the two proteoglycan preparations were similar with respect to size, degree of sulfation, position of sulfation, and hexosamine content. Furthermore, the fragments released from the cartilage residue by either cyanogen bromide, trypsin, or hydroxylamine treatment were of the same size, as judged by gel chromatography, as those derived from similarly digested guanidine-extracted proteoglycan. Trypsin digestion also released the keratan sulfate-enriched peptide as well as peptides from the hyaluronic acid-binding region. By the methods used, the inextractable proteoglycan appears to be similar to the fraction which is readily soluble under dissociative conditions and thus may be held tightly within the tissue by a nonspecific mechanism(s) such as entanglement in the collagen fibril network.

Animals↗