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Biomedical subjects

R Penny

Publications and source records attributed to R Penny.

At least 181 records · Page 10Linked to original sources
PubMed1983

The effect of alpha 1 antitrypsin on the proliferative response of human peripheral blood lymphocytes.

In evaluating immune aberrations in patients with alpha 1 antitrypsin (alpha 1 AT) deficiency, we have previously shown that they exhibit enhanced lymphocyte responsiveness to PHA that is serum mediated. In this study, we demonstrate suppression of the PHA response by using purified alpha 1 AT, and also similar but less marked suppression of the Con A response. alpha 1 AT, however, has no effect whatsoever on PWM-induced proliferation. This effect is demonstrable provided alpha 1 AT is added within 4 hr of mitogen activation and is mediated by its action on adherent cells rather than on proliferating lymphocytes. Adherent cells still exhibit this effect if pulsed with alpha 1 AT, then thoroughly washed before their activation. This suggests that it may be inhibiting a membrane serine esterase already activated before the addition of PHA. Thus alpha 1 AT may modulate the activation of T cells through its effect on monocytes, leading to abnormalities in immunoregulation, and hence a predisposition to the development of a variety of immunologic disorders in alpha 1 AT-deficient subjects.

Adult↗
PubMed1983

Familial occurrence of alpha 1-antitrypsin deficiency and Weber-Christian disease.

Severe panniculitis of the Weber-Christian type occurred in two brothers, both with marked alpha 1-antitrypsin (alpha 1-AT) deficiency and phenotype PiZZ. Studies of inflammatory and immunologic function were undertaken in these two patients as well as in a third brother with severe alpha 1-AT deficiency but without Weber-Christian disease. The findings of these investigations were suggestive of exaggerated immunologic and inflammatory function with enhanced lymphocyte responsiveness to phytohemagglutinin, enhanced activation of neutrophils and monocytes, and accelerated delayed hypersensitivity responses in all three subjects. This hyperreactivity may explain the apparent association of alpha 1-AT deficiency with Weber-Christian disease.

Adult↗
PubMed1983

Cell-mediated immune response to chlamydia in anterior uveitis: role of HLA B27.

The relationship between HLA B27 anterior uveitis (AU) and evidence of chlamydia trachomatis infection was investigated in 35 consecutive patients attending a uveitis research clinic, using a complement fixation test and lymphocyte transformation test to chlamydia (ornithosis-psittacosis) group antigen. A significant stimulation index (SI greater than 2) was found in 73% (11/15) of the HLA B27 positive patients compared with the HLA B27 negative AU patients and controls (P less than 0.03). There was no difference between AU patients with and without associated rheumatic disease or in terms of antibody response. The results of the present study indicate a significant relationship between the cell-mediated immune response to chlamydia group antigen and the HLA B27 positive subgroup of patients with AU.

Adult↗
PubMed1983

The effect of alpha 1 antitrypsin on phagocyte function.

alpha 1 antitrypsin (alpha 1AT) deficiency is a common genetic variant associated with many immunological and inflammatory disorders. Previous studies in alpha 1 AT deficient subjects have indicated possible monocyte (MN) and neutrophil (PMN) abnormalities with enhanced chemiluminescence (CL) and accelerated delayed hypersensitivity reactions. We have therefore extended these observations by investigating the effect of purified alpha 1 AT on MN and PMN motility and CL. These studies indicated that alpha 1 AT in physiological amounts inhibits PMN and MN chemokinesis by about 35% but chemotaxis by only 10%. It however has no direct effect on the zymosan induced CL of these cells. This study suggests that the increased incidence and severity of some inflammatory diseases in alpha 1 AT deficient subjects may in part be explained by increased motility and activation of MN and PMN, the former due to the absence of an inhibitor of PMN and MN locomotion and the latter due to secondary changes in serum resulting in enhanced chemiluminescence.

Chemotaxis↗
PubMed1982

Genetic study of a family with two members with Weber Christian disease (panniculitis) and alpha 1 antitrypsin deficiency.

Alpha 1 antitrypsin phenotypes and serum levels are presented for a family in which two brothers have Weber Christian disease and alpha 1 antitrypsin (PI) Z phenotypes. Clinical histories are described for these two men. A younger brother has the PI Z phenotype but does not have the disease, indicating that additional genetic and/or environmental factors contribute to the pathogenesis of Weber Christian disease. However, the two cases described provide additional evidence for a relationship between alpha 1 antitrypsin deficiency and the development of symptoms.

Adult↗
PubMed1982

Immunogenetic factors in inflammatory eye disease. Influence of HLA-B27 and alpha 1-antitrypsin phenotypes on disease expression.

The relationship between the nature and severity of inflammatory eye disease was analyzed with respect to HLA antigens and alpha 1-antitrypsin phenotypes. Using standard ophthalmologic criteria, we divided patients with anterior uveitis into acute, chronic (greater than 3-month duration), bilateral, or recurrent disease. There was a significantly increased incidence of alpha 1-antitrypsin-deficient phenotypes in anterior uveitis, especially in those patients with severe (chronic, bilateral, or recurrent) disease. HLA-B27 acts as an independent predisposing factor: it was present in 22% of patients with their first attack of acute uveitis compared with 51% of patients with recurrent disease. Together, these genetic factors are present in 63% of patients with severe anterior uveitis and represent the most significant predisposing and prognostic factors so far detected.

HLA Antigens↗
PubMed1982

Melatonin excretion in normal males and females: increase during puberty.

Melatonin in chloroform extracts of timed overnight urine collections was measured by radioimmunoassay. Melatonin excretion was determined in 88 boys and 82 girls 9-16 yr of age, in 16 adult males, and throughout the menstrual cycle of one adult female. By succeeding age groups (9-10.9, 11-12.9, 13-14.9, and 15-16.9 yr) boys showed a progressive increase in mean +/- SD melatonin excretion from 3.0 +/- 1.3 ng/hr for the 9-10.9 yr age group to 9.8 +/- 2.8 ng/hr for the 15-16.9 yr age group. The girls' excretion increased for the 11-12.9 yr age group (9-10.9 versus 11-12.9 = 4.0 +/- 2.3 versus 6.1 +/- 2.7 ng/hr, p less than 0.005), plateaued for the 13-14.9 yr age group (5.8 +/- 3.3 ng/hr, p greater than 0.3), and decreased for the 15-16.9 yr age group (2.0 +/- 1.4 ng/hr, p less than 0.005). Subjects with initial signs of puberty as compared to prepubertal subjects had increased melatonin excretion (boys, 4.7 +/- 1.4 versus 2.4 +/- 0.9 ng/hr; girls 5.7 +/- 1.9 versus 2.4 +/- 0.9 ng/hr, p less than 0.005). Excretion of the adult males (1.6 +/- 1.1 ng/hr) was less (p less than 0.005) than that of boys of all age groups. At the time of menstrual bleeding melatonin excretion was elevated; peak excretion (15.5 ng/hr) occurred 3 days prior to the midcycle gonadotropin surge. Follicular phase (10.7 +/- 2.9 ng/hr) excretion was (p less than 0.005) greater than luteal phase (4.2 +/- 1.1 ng/hr) excretion. These data show that melatonin excretion increases when the initial signs of puberty are present. This finding is inconsistent with an inhibitory influence of melatonin on pubertal development. Gonadal function may influence melatonin secretion during puberty and melatonin may play a role in adrenarche.

Adolescent↗
PubMed1982

Immunology of ocular toxoplasmosis.

Toxoplasma gondii, due to its ability to escape and modify the normal immune response, is able to survive within the retina indefinitely with the production of an occasional acute inflammatory response. The cellular immune system is mainly responsible for limiting infection. Diagnosis is based on clinical features coupled with measurements of antibody response (systemic and ocular) and cell mediated immunity. The treatment of toxoplasma chorioretinitis when indicated should be specific and immunosuppressive agents should only be used in conjunction with antibiotics to avoid dissemination of the organism.

Humans↗
PubMed1982

Biosynthesis of immunoglobulin in human immunoproliferative diseases. II. Comparison of tumour cell mass in multiple myeloma measured by synthetic rate studies with that calculated from clinical staging systems.

Tumour cell mass (TCM) in patients with multiple myeloma has been measured by synthetic rate studies of bone-marrow tumor cells in culture. From the measurements of Salmon and co-workers, a simple clinical staging system in which TCM is calculated by a programmable pocket calculator has been developed. We have compared the measurement and calculation of TCM in patients with IgG and IgA multiple myeloma by these methods in our own laboratory. There was correlation between synthetic rate and serum IgG paraprotein concentration but not the serum IgA paraprotein concentration. In patients with IgG myeloma there was correlation between measured and calculated TCM as well as measured TCM and serum IgG paraprotein concentration, urine Bence-Jones protein excretion, and serum albumin concentration. Measured TCM also inversely correlated with haemoglobin concentration. In patients with IgA myeloma, however, there was no correlation between measured TCM and calculated TCM or any other individual clinical laboratory parameter. A number of problems have contributed to the overall failure of this method to measure and calculate TCM including methodological differences, definition of myeloma cells, proteolysis of newly synthesized paraprotein in culture, changes in synthetic rates with time and assessment of the degree of bone lesions by skeletal roentgenograms. We cannot recommend these methods as they stand to measure and calculate TCM in patients with multiple myeloma.

Adult↗
PubMed1982

Escape of tumours from immunological destruction.

This paper reviews the mechanisms of tumour escape from immune destruction that have been delineated in the past 2 decades. Current evidence indicates that the principal escape mechanisms are (i) weak or absent immunogenicity (ii) immunosuppression by tumour antigens or antigen-antibody complexes (iii) induction of suppressor cells and (iv) production of immunosuppressive factors. A classification of tumour escape mechanisms is presented.

Aged↗
PubMed1982

Tissue distribution of IgG Fc receptors.

The mechanism causing deposition of circulating immune complexes is largely unknown. The possible role of tissue IgG Fc receptors in immune complex localization has been evaluated using IgG coated ox RBC (ox erythrocyte antisera [EA]) as indicator particles. Cryostat tissue sections of normal human synovium, skin, kidney, choroid plexus, lung and uveal tract were examined for the presence of IgG Fc receptors, with human spleen used as a positive control. Ox EA were shown to bind to splenic red pulp. This binding could be almost completely blocked by heat aggregated human IgG. In none of the other normal tissues examined were IgG Fc receptors demonstrated. To investigate the possibility that inflamed tissues express Fc receptors, biopsy specimens of rheumatoid synovium and skin demonstrating vasculitis were studied. No ox EA binding to these tissues was noted. We concluded that IgG Fc receptors are probably not present in tissues that are targets for immune complex deposition and are therefore unlikely to play a role in this process.

Animals↗
PubMed1982

Immunoregulation by alpha 1 antitrypsin.

alpha 1 antitrypsin (alpha 1 AT) deficiency is a common genetic disorder seen in about 10% of the population. It predisposes to the development of a large number of inflammatory and immunologic disorders including rheumatoid arthritis, systemic lupus erythematosus, juvenile chronic arthritis, anterior uveitis, ankylosing spondylitis, fibrosing alveolitis and emphysema. We have investigated immunologic function in subjects with severe alpha 1 AT deficiency and demonstrated serum mediated enhancement of lymphocyte response to PHA and increased zymosan activation of mononuclear cells and neutrophils as measured by their chemiluminescence. These patients also have accelerated delayed hypersensitivity responses and increased levels of factor B, C3 and C5 but normal levels of immunoglobulin and other complement components. Such abnormalities in immunoregulation demonstrate a tendency to hyperreactivity that may contribute to disease predisposition.

Complement System Proteins↗
PubMed1982

Chemiluminescence response in normal human phagocytes. I. Automated measurements using a standard liquid scintillation counter.

We present a fast, simple and highly accurate method for measuring Phagocyte Chemiluminescence by using a standard liquid scintillation counter with a simple modification. The method allows the measurement of multiple samples automatically, with standardized mixing and measurement times, at a constant temperature. This is achieved with a minimum of technician time as opposed to the single measurement facility of many of the available manual luminescence photometers. The modifications can be made to any standard liquid scintillation counter, are simple and inexpensive, can allow the handling of large numbers of samples in a short time and improve standardization.

Computers↗
PubMed1982

Chemiluminescence response in normal human phagocytes. II. Effect of paraproteins.

We have used chemiluminescence (CL) as a model for assessing the effects of paraproteins on human neutrophils and monocytes. A difference in the response of these two cell types was demonstrated. Paraprotein-containing sera (classes IgG, IgA and IgM) depressed the CL response of monocytes in almost all cases but had no effect on neutrophils. This effect was reproduced using purified paraprotein and showed a dose dependent response. It is proposed that this difference may be a function of the interaction between paraprotein and differing membrane receptors in phagocytes.

Humans↗
PubMed1981

Anti-digoxin antibody in digoxin intoxication.

This study was conducted to investigate the action of anti-digoxin antibody in digoxin intoxication. Anti-digoxin antibody was raised in sheep and administered to six dogs following intravenous infusion of digoxin (0.04 or 0.16 mg/kg body weight), either as whole serum or as partially purified gamma globulin. Plasma and urine digoxin levels, both bound and free, were determined on serial samples. Myocardial samples were analysed for digoxin content. Comparisons were made with six dogs given digoxin but no antibody. The results indicate that anti-digoxin antibody is effective through inactivation of digoxin in myocardium and removal of digoxin from myocardium into plasma. Loss of digoxin in urine is not responsible for toxicity reversal.

Animals↗