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Biomedical subjects

R Penny

Publications and source records attributed to R Penny.

At least 235 records · Page 13Linked to original sources

Lymphokine-like activity in the serum of patients with haemopoietic malignancies.

Serum from patients with haemopoietic malignancies was tested for the presence of migration inhibition factor (MIF) and leucocyte inhibition factor (LIF) activity by standard assays. There was no correlation between the specific disease state and positivity of the sera for MIF or LIF activity. MIF activity in the serum of one patient with myeloma was present in the isolated IgG cryoglobulin fraction.

Animals↗

Monitoring immune function during immunosuppressive therapy.

Twenty-nine patients with a variety of connective tissue disorders were studied for the effects of immunosuppressive therapy on non-specific parameters of immune function. Baseline studies prior to therapy showed a frequent incidence of anergy (13%) lymphopenia (31%) and abnormal PHA response (43%). Despite these abnormalities in untreated patients it was possible to show an even higher incidence of anergy (31%), lymphopenia (66%) and abnormal PHA response (77%) following immunosuppressive treatment. The changes in lymphocyte count and PHA response were found to be statistically significant. It was found, paradoxically, that delayed hypersensitivity responses improved following institution of therapy in three patients. Clinical efficacy of immunosuppression correlated with lymphopenia and depressed PHA responses; in particular in the five patients with uncontrolled disease, these parameters were normal. Lymphocyte counts and PHA responses are the most simple and informative procedures to monitor immunosuppression in patients.

Collagen Diseases↗

The role of immune complexes in the pathogenesis of disease.

Circulating antigen-antibody complexes are incriminated in the pathogenesis of auto-immune and inflammatory disease, and more recently malignancy. Extensive knowledge of the immunopathological reactions has evolved from from the study of experimental serum sickness in animals and of the potential aetiological agents (e.g. viruses) from spontaneous immune complex diseases in animals. Numerous techniques, both direct and indirect, have now been described to identify immune complexes in serum, though no single technique will identify regularly immune complexes in all clinical situations, nor will it demonstrate the pathogenicity of the immune complex in a given patient. Human disorders with a definite immune complex basis (glomerulonephritis, systemic lupus erythematosus, rheumatoid arthritis) and others with a possible immune complex basis (e.g. cutaneous vasculitis, are presented. Management of immune complex disorders is based on removal of the initiating agent if known (e.g. infection, drug, malignancy) or the use of non-specific anti-inflammatory therapy. Specific immunotherapy, in practice and theory, is discussed.

Animals↗

Defective immune and phagocytic functions in uraemia and renal transplantation.

The humoral, cellular and neutrophil responses of uraemic patients maintained by haemodialysis were compared with those of renal transplant recipients. Humoral immunity was reduced only in the transplant group. Cell-mediated immunity was abnormal in both groups but more decreased in the transplant group studied particularly within 3 months of transplantation. The neutrophil bactericidal capacities were defective cellular immunity, but fatal infections occurred only in transplant patterns over 40 years of age with combined cellular and neutrophil defects. No single test was predictive of graft survival in uraemic patients. The depressed cellular immune responses in uraemia, of the degree seen in the immunosuppressed transplant recipient, may explain the better prognosis of renal transplants compared with other organ transplants.

Antibody Formation↗

Paraproteinemia: blood hyperviscosity and clinical manifestations.

Many of the clinical features of paraproteinemia result from impairment of blood flow through the vascular tree because of blood hyperviscosity. Studies were carried out in 65 patients with serum paraproteins (31 with IgG, 25 with IgM, and 9 with IgA) to examine the relationship between the blood viscosity and the frequency of selected clinical features. The blood and plasma viscosities were measured at low rates of shear. Blood hyperviscosity was present in 91% of the patients and plasma hyperviscosity in 75% of the patients. In each of the three immunoglobulin classes both the blood and plasma viscosities increased logarithmically with the paraprotein concentration being greatest in the case of IgM. In addition, the relationship between the hematocrit and the logarithm of blood viscosity tended to be linear at any given protein concentration. In patients with very high levels of paraprotein the blood viscosity was modified by low hematocrits; the latter was below 30 in 70% of patients in whom the concentration of paraprotein was above 4 g/100 ml. The prevalence of clinical complications involving the retinal circulation, the peripheral vascular system, and the central nervous system increased markedly with increasing blood viscosity, measured at 0.18 S-1. One or more of these regions was affected in greater than 80% of patients with blood viscosity above 60 centipoise and in less than 23% of patients with blood viscosity below 40 centipoise. These observations illustrate the complex relationship between blood viscosity, concentration of paraprotein, immunoglobulin class and hematocrit, and emphasize the importance of measuring the whole blood viscosity at low rates of shear in determining the risk of vascular complications.

Blood Viscosity↗

Overnight follicle stimulating hormone (FSH) and luteinizing hormone (LH) excretion in normal males.

FSH and LH in acetone precipitates of timed overnight urine collections were measured by radioimmunoassay. FSH and LH urinary excretion extrapolated to 24 h was determined in 147 boys 3-16 years and 20 normal men. FSH and LH (2nd IRP-HMG) progressively increased with age from 1.8 +/- 1.1 (FSH) and 2.1 +/- 1.2 (LH) IU/24 h for the 3-4 year age group to 8.6 +/- 3.2 (FSH) and 18.8 +/- 9.0 (LH) IU/24 h for the 15-16 year age group. FSH and LH excretion increased progressively with stage of sexual development. The integration of several hours of FSH and LH secretion and the accuracy, simplicity and convenience of collecting a single urine sample are advantages of the timed overnight urine collection which should make this technique extremely useful in the evaluation of gonadotropin function.

Adolescent↗

Immunological aspects of cancer.

Immunology occupies a central role in the area of cancer, both in research and clinical practice. This article first reviews normal immunity and describes the interaction of the cancer cell with cellular and humoral immune mechanisms. Such mechanisms play a considerable role in the emergence, proliferation, metastases, regression and recurrence of tumours. Immunological investigations are applicable to the diagnosis of some forms of cancer, especially leukaemias, lymphomas and myelomas as well as analysing the immune status of patients suffering from cancer, which give significant guidelines with respect to prognosis. Manipulation of immune response in the form of immunotherapy is emerging as an important area in cancer therapy.

Age Factors↗

Measurement of human chorionic gonadotropin (HCG) concentrations in paired maternal and cord sera using an assay specific for the beta subunit of HCG.

Human chorionic gonadotropin (HCG) concentrations were determined in paired maternal and cord sera using an essay specific for the beta subunit of HCG. The sera of 46 mothers and 46 infants, 24 female and 22 male, were studied. Results were compared to those obtained using a radioimmunoassay for luteinizing-hormone (LH) which cross-reacted with HCG. With either assay system, mean maternal HCG concentrations were lower when the sex of the fetus was male than when the sex of the fetus was female. Mean cord HCG concentrations of male (0.09 +/- 0.02 IU/ml) and female (0.09 +/- 0.04 IU/ml) infants were not different as determined by the beta HCG assay. In contrast, the mean cord serum concentration of HCG was significantly greater (P less than .005) in male infants (0.29 +/- 0.05 IU/ml) than in female infants (0.23 +/- 0.09 IU/ml) as determined by the cross-reacting assay. HCG concentrations were lower in both maternal and cord sera when assayed in the specific HCG system than when assayed in the cross-reacting system. There was a significant correlation (r=.9; P less than .005) between the results obtained with the two assays in both maternal and cord blood. Regardless of the assay system employed, the cord serum concentration of HCG was markedly less than the corresponding maternal serum concentration. There was no correlation between maternal and cord serum HCG concentrations with either assay. These data are in agreement with the results of previous studies employing less specific methodology which indicated that maternal serum HCG concentrations were less when the fetus was male than when it was female. They are also consistent with a placental barrier effect with regard to HCG transfer to the fetus. The difference in results obtained in cord blood with the two assay systems suggests that the newborn male infant secretes more LH and/or alpha LH subunits than the newborn female infant.

Adult↗

Measurement of the production rate of human luteinizing hormone using the urinary excretion technique.

Labeled and/or unlabeled human luteinizing hormone (hLH) was injected into normal and abnormal males and into hypopituitary patients. In two patients, two phases of disappearance (T 1/2) were found to be 1.2 and 2.4 hr. Labeled and unlabeled hormone were excreted in the same proportion. Of the injected hormone, normal males excreted 10.1% plus or minus 0.9%, hypopituitary patients excreted 11.4%- 17.5% and two other patients excreted 10.3% and 5.3% over 48 hr. The urinary excretion of unlabeled hLH in normal males was 22.1 plus or minus 4.9 IU/24 hr. The production rate of hLH in normal males was 224.3 plus or minus 65.3 IU/24 hr and, in the two abnormal males, was five times higher. The advantages of this methodology are discussed.

Adult↗

Sexual maturation in subjects with sickle cell anemia: studies of serum gonadotropin concentration, height, weight, and skeletal age.

Luteinizing hormone and FSH concentrations were determined in sera obtained from 20 males and 20 females, ages 5 to 16 years, with sickle cell anemia (homozygous hemoglobin S). Height, weight, bone age, and stage of sexual development were also determined. Gonadotropin concentrations were increased for stage of sexual development, suggesting transient impairment of gonadal function during the first decade of life. Increased impairment of growth during the second decade of life (18 of 26 subjects, 69%) as compared to the first decade (4 of 14 subjects, 29%) was consistent with prior deficiency of gonadal secretion of steroids. Mean bone age (11.2 +/- 2.1 year) determined in 15 subjects was significantly less than the mean chronologic age (13.0 +/- 1.8 year). Significant additional data, particularly those which would be derived from a longitudinal study, are needed to validate the preliminary hypothesis that transient impairment in gonadal function may, in part, account for the variation in sexual maturation seen in subjects with sickle cell anemia.

Adolescent↗

Growth hormone excess and sexual precocity in polyostotic fibrous dysplasia (McCune-Albright syndrome): evidence for abnormal hypothalamic function.

A 5-5/12-year-old boy with gigantism and precocious puberty associated with the McCune-Albright syndrome is presented. Serum concentrations of growth hormone were extremely elevated (128-163 ng/ml) and were not suppressed by hyperglycemia or chlorpromazine. Serum LH (7.4 +/- 1.0 SD mIU/ml) and FSH (5.3 +/- 0.3 SD mIU/ml) concentrations were in the range observed in midpuberty. The secretion pattern of LH was episodic. The administration of estradiol suppressed the secretion of FSH and had an apparent positive feedback effect on release of LH. These findings are compatible with abnormal hypothalamic function as the mechanism for the endocrinopathies associated with the McCune-Albright syndrome.

Blood Glucose↗

T and B cell populations in blood and lymph node in lymphoproliferative disease.

Lymph node and peripheral blood lymphocytes were studied simultaneously for surface markers of T and B cells in 22 patients with lymphoproliferative diseases and 8 patients with non-neoplastic lymphadenopathy. This resulted in the classification of the malignancy from involved lymph nodes into 4 groups. Six patients had B cell lymphomata with normal or strong immunofluorescent staining for surface membrane immunoglobulin; 8 patients had B cell chronic lymphocytic leukaemia with pale staining for surface membrane immunoglobulin; 5 patients had T cell lymphomata and 3 patients were not definitely classifiable. In 6 out of 8 patients with B cell CLL, histopathology of lymph nodes showed infiltration with well differentiated lymphocytes and in all T cell lymphomata, the infiltrating cells were poorly differentiated. By the use of these markers, malignant lymphocytes were identified in the circulation in only 3 out of 6 patients with B cell lymphoma, in all patients with B cell CLL but in none of those with T cell lymphoma or unclassifiable lymphoma. Therefore a more conclusive characterization of the malignant lymphocyte in lymphoproliferative diseases must include an examination of involved lymph nodes.

B-Lymphocytes↗

Leucocyte function in paraproteinaemia.

Cellular immunity has been studied by means of lymphocyte response to PHA, delayed hypersensitivity and skin window responses in 23 patients with myeloma (14 IgG, 9 IgA) and 14 patients with macroglobulinaemia. In the myeloma patients, 14% had abnormal PHA response and 29% were anergic. In those with macroglobulinaemia, 29% showed abnormal PHA response and 57% were anergic. In myeloma, the abnormal PHA response was due to a serum inhibitor. Abnormal skin window responses were present in 75% of the patients with myeloma, but only 22% of those with macroglobulinaemia. All the myeloma patients with anergy had abnormal skin windows but this correlation did not exist in macroglobulinaemia. No correlation was found between the paraprotein concentration and anergy, PHA response or skin window. The results support the conclusion that myeloma is predominantly associated with an abnormal skin window (inflammatory) response and macroglobulinaemia with intrinsic abnormalities of cellular immunity. When anergy and abnormal PHA response are present in myeloma, it appears to be attributable to an effect of the paraprotein and not an intrinsic abnormality of lymphocytes.

Adult↗