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Biomedical subjects

B Henderson

Publications and source records attributed to B Henderson.

At least 181 records · Page 10Linked to original sources
PubMed1986

Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint.

Interleukin 1 (IL-1) is a polypeptide released by activated macrophages and is thought to be a key mediator of host responses to infection and inflammation. The availability of highly purified and recombinant material has now permitted the evaluation of IL-1 as a mediator of chronic inflammatory processes in vivo. We have demonstrated that intraarticular injection of IL-1 into rabbit knee joints induces the accumulation of polymorphonuclear and mononuclear leukocytes in the joint space and the loss of proteoglycan from the articular cartilage. The effects on cartilage could not be explained solely by the presence of leukocytes, since injections of endotoxin also stimulated leukocyte accumulation in the joint but had no effect on proteoglycan loss. Responses to IL-1 were not associated with increased production of the icosanoids prostaglandin E2 or leukotriene B4 and were not reduced by an inhibitor of their synthesis. The pattern of leukocyte infiltration and cartilage breakdown 24 hr after IL-1 injection was similar to that seen in animals with antigen-induced arthritis of 1 week's duration. These observations support the hypothesis that IL-1 acts directly to mediate the erosive processes of chronic arthritis.

Animals↗
PubMed1986

Tomography of regional ventilation and perfusion using krypton 81m in normal subjects and asthmatic patients.

Single photon emission computed tomography, a rotating gamma camera, and continuous inhalation or infusion of krypton 81m (half life 13 seconds) were used to measure regional ventilation (V), perfusion (Q), and ventilation-perfusion (V/Q) ratios in five normal subjects in supine, prone, and lateral decubitus postures and in three asthmatic patients (supine posture only) before and after inhalation of 2.5 mg nebulised salbutamol. Vertical and horizontal gradients of V, Q, and V/Q were examined at three levels in each lung in regions of 1.9 cm3 size. In normal subjects V and Q increased along the axis of gravity in all postures and at all levels in the lung except for V in the prone position. Smaller horizontal gradients were found with an increase in V and Q from caudal to cranial--again except in the prone posture, where the gradient was slightly reversed. Constraint to outward motion of the ventral chest and abdominal wall is the most likely explanation for the different behaviour in the prone posture. In chronic asthma the vertical gradients of V and V/Q were the reverse of normal, but the Q gradient was normal. Bronchodilator treatment did not affect the vertical or horizontal gradients significantly, but analysis of individual regions showed that, relatively, V/Q worsened in 42% of them; this was associated in two thirds with an increase in fractional Q. After inhalation of beta agonist local vasodilatation may influence V/Q ratios in some units more than bronchodilatation.

Adult↗
PubMed1986

Serum testosterone levels in healthy young black and white men.

Blacks in the United States have the highest prostate cancer rate in the world and nearly twice that of whites in the United States. The 2:1 black-to-white ratio in prostate cancer rates is already apparent at age 45 years, the age at which the earliest prostate cancer cases occur. This finding suggests that the factor(s) responsible for the difference in rates occurs, or first occurs, early in life. Testosterone has been hypothesized to play a role in the etiology of prostate cancer, because testosterone and its metabolite, dihydrotestosterone, are the principal trophic hormones that regulate growth and function of epithelial prostate tissue. This report gives the results of assays of circulating steroid hormone levels in white and black college students in Los Angeles, CA. Mean testosterone levels in blacks were 19% higher than in whites, and free testosterone levels were 21% higher. Both these differences were statistically significant. Adjustment by analysis of covariance for time of sampling, age, weight, alcohol use, cigarette smoking, and use of prescription drugs somewhat reduced the differences. After these adjustments were made, blacks had a 15% higher testosterone level and a 13% higher free testosterone level. A 15% difference in circulating testosterone levels could readily explain a twofold difference in prostate cancer risk.

Adolescent↗
PubMed1985

A key role for fibronectin in the sequential binding of native dsDNA and monoclonal anti-DNA antibodies to components of the extracellular matrix: its possible significance in glomerulonephritis.

The interactions of DNA, monoclonal anti-DNA autoantibodies and isolated purified components of the extracellular matrix (ECM) were studied in a solid phase model system. Binding of DNA to each of the components was assessed using monoclonal antibody and enzyme conjugated antiglobulin in direct binding and inhibition assays. Each of the genetically distinct collagens (Types I-IV), proteoglycan monomer and laminin, bound ssDNA, but dsDNA bound significantly only to fibronectin. When used in an inhibition system, fibronectin linked DNA and anti-DNA antibodies to the collagens; it had a differential effect on the binding of ssDNA and dsDNA to a Type IV collagen matrix, the most striking feature being a 100 fold increase in dsDNA binding to Type IV collagen in the presence of fibronectin. It is likely that fibronectin binds dsDNA to collagen by separate binding domains for these molecules, and that this may be involved in the deposition of DNA in kidneys in some forms of glomerulonephritis.

Animals↗
PubMed1985

Suppression of collagen type II-induced arthritis by transfer of lymphoid cells from rats immunized with collagen.

Rats were immunized with type II collagen to induce polyarthritis. Spleen and lymph node cells were taken at various times and transferred to normal syngeneic animals. Disease was not observed in recipients of cells taken from donors either during the pre-clinical phase or the acute clinical phase of the disease. However, arthritis could not be induced in the recipient animals that had received cells taken from donors during the preclinical phase. Animals receiving cells from donors with clinical disease appeared to have a normal susceptibility to disease induced subsequently. In contrast with the differences in their susceptibility to induced disease, all recipient animals made unmodified antibody responses to a challenging injection of type II collagen. The results showed that before the appearance of clinical disease in CII immunized rats, there were cells in the spleen and lymph nodes that inhibit the development of disease but not antibody responses.

Animals↗
PubMed1984

A quantitative study of peroxidase activity in unfixed tissue sections of the guinea-pig thyroid gland.

A technique for the cytochemical demonstration of peroxidase activity in unfixed guinea-pig thyroid tissue is described in this paper. The substrate 3,3'-diaminobenzidine tetrahydrochloride (DAB) is oxidized by the peroxidase to form an insoluble reaction product. Optimal results were obtained after 20 min incubation at 37 degrees C in reaction medium containing 1.4 mM DAB (in 0.1 M Tris-HCl) and 0.15 mM hydrogen peroxide at pH 8.0. Peroxidase activity was seen in the thyroid follicle cells as a diffuse brown reaction product (which was more dense and granular in erythrocytes). The enzyme activity was quantified using a scanning-integrating microdensitometer, and the effects of two specific peroxidase inhibitors were evaluated. Both 3-amino-1,2,4-triazole and methimazole inhibited peroxidase activity in the follicle cells (enzyme activity was still seen in the erythrocytes), maximal inhibition occurring at 10 mM. Stimulation of peroxidase in the thyroid was observed in vivo (1 I.U. TSH administered every 8 h for two days), with the maximal stimulation occurring after 1 day.

3,3'-Diaminobenzidine↗
PubMed1984

Increase in the activity of lysosomal acid hydrolases in the chondrocytes of arthritic joints of rabbits with experimental allergic arthritis.

Undecalcified cryostat sections of the cartilage-covered ends of the femurs have been prepared from the control and inflamed knees of rabbits with experimental allergic arthritis. The activities of two lysosomal hydrolases, naphthylamidase and beta-glucuronidase, were assayed in the chondrocytes of the articular cartilage in such sections by scanning and integrating microdensitometry. The activities of both enzymes were found to increase significantly in the chondrocytes of the inflamed joints.

Aminopeptidases↗
PubMed1984

The anti-arthritic and immunosuppressive effects of cyclosporine on arthritis induced in the rat by type II collagen.

The influence of cyclosporine (CsA) on the induction and pathogenesis of type II collagen-induced arthritis has been investigated in inbred and outbred Wistar rats. The proportion of animals developing disease and the severity of disease they developed were both diminished by treatment with CsA. These effects were accompanied by a marked suppression of the antibody response to both the immunizing collagen and also to rat type II collagen. CsA treatment also resulted in a decreased accumulation of lymphocytes in arthritic joints. The results indicate that the anti-arthritic and immunosuppressive effects of CsA probably result from a modification of both systemic antibody-mediated and local cell-mediated immunity.

Animals↗
PubMed1983

The application of quantitative cytochemistry to the study of diseases of the connective tissues.

The connective tissues are a complex organisation of tissues, cells and intercellular materials spread throughout the body and are subject to a large number of diseases. Such complexity makes the study of the metabolism of the connective tissues in health and more particularly in disease states difficult if one uses conventional biochemical methodology. Fortunately the techniques of quantitative cytochemistry, as developed in recent years, have made it possible to study the metabolism of even such complex and refractory connective tissues as bone. Using properly validated assays of enzyme activity in unfixed sections from various tissues a number of the diseases of the connective tissues have been studied. For example the synovia from patients with rheumatoid arthritis and related conditions have been studied using these techniques and marked alterations in the metabolism of the synovial lining cell population of this tissue have been demonstrated. These alterations in metabolism are believed to be related to the destruction of cartilage and bone found in such diseases. Investigations of the metabolism of the chondrocytes of articular cartilage in a strain of mice which spontaneously develops osteoarthritis has revealed a lack of certain key enzymes of carbohydrate metabolism in precisely those areas where degradation of the matrix of articular cartilage begins suggesting a causal relationship between these events. These same techniques have been used to study the cellular kinetics and metabolism of the dermis and epidermis in the disfiguring disease, psoriasis. The metabolism of healing bone fractures, the diagnosis and treatment of the mucopolysaccharidoses and the metabolic effects of currently used anti-inflammatory and anti-rheumatic drugs have also been examined. Perhaps the most exciting aspect of these studies has been the development and use of the technique of the cytochemical bioassay (CBA) to study hormonally mediated diseases of the connective tissues. Such studies have recently shed new light on the molecular lesion in pseudohypoparathyroidism. Though still in their relative infancy the studies described in this review show the potential inherent in the use of quantitative cytochemistry for the study of diseases of the connective tissues.

Animals↗
PubMed1983

Synthesis of arachidonate cyclo-oxygenase products by rheumatoid and nonrheumatoid synovial lining in nonproliferative organ culture.

Specimens of human rheumatoid and nonrheumatoid synovial lining were maintained in nonproliferative organ culture for 20 hours. The culture fluids were then assayed for prostaglandin E(2) (PGE(2)), thromboxane B(2) (TXB(2)), and 6-keto-prostaglandin F(1alpha) (6-keto-PGF(1alpha)) by specific radioimmunoassay. The presence of each of these substances was confirmed by gas chromatography and mass spectrometry. Rheumatoid tissue produced significantly more of each cyclo-oxygenase product than nonrheumatoid tissue.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Asbestos exposure and lymphomas of the gastrointestinal tract and oral cavity.

An epidemiological case-control study of non-Hodgkin's lymphomas revealed an excess of male patients with large-cell lymphomas primary to the gastrointestinal tract and oral cavity who had evidence of substantial exposure to asbestos. Between 1977 and 1981, 28 men with large-cell lymphomas primary to these sites were interviewed about previous environmental exposure. Pathology slides from 26 of these cases were reviewed by haematopathologists, who confirmed each to be non-Hodgkin's lymphoma of large-cell type. Neighbourhood controls were matched to patients for age, race, and sex. 13 matched pairs were discordant for asbestos exposure, and in 12 of these the exposed individual was a lymphoma patient. 10 patients and 1 control also reported a history of malaria.

Adult↗