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Biomedical subjects

R Penny

Publications and source records attributed to R Penny.

At least 109 records · Page 6Linked to original sources
PubMed1989

Congenital adrenal hyperplasia due to combined 21- and 11 beta-hydroxylase deficiency.

A 26-day-old male was evaluated because on routine follow-up visit his weight was noted to be 3292 g which was not a significant weight gain over his birth weight of 3178 g. His serum electrolytes (NA 107 meq/1, K 8.0 meq/1, Cl 82 meq/1, and HCO2 12 meq/1) were abnormal, urine Na concentration (68 meq/1) was high, and his serum concentrations of 21-deoxycortisol 10, 113 ng/dl (normal 1.2-13), 11-deoxycortisol 15,000 ng/dl (normal 50-250), and 11-deoxycorticosterone 148 ng/dl (normal 2-13) were markedly elevated. Patients having increased levels of the three indicated steroids are diagnosed as having combined 21- and 11 beta-hydroxylase deficiency. On glucocorticoid and mineralocorticoid replacement therapy his electrolytes returned to normal and his weight increased 428 g by the 10th day post initiation of therapy. We hypothesize that the elevated steroid pattern designated as combined 21- and 11 beta-hydroxylase deficiency could result from extraadrenal conversion of 17-hydroprogesterone to 11-deoxycortisol and progesterone to 11-deoxycorticosterone in subjects with adrenal 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Response of microvascular endothelial cells to biological response modifiers.

This study investigated in vitro biological response modifiers (BRM) possibly involved in initiation and regulation of human capillary endothelial cell (HCEC) growth. An indicator assay was developed using tritiated thymidine to measure increased DNA turnover. Purified or recombinant BRMs tested singly and in combination included: interferon (IFN; alpha and gamma), tumour necrosis factor (TNF; alpha and beta), transforming growth factor (TGF; alpha and beta), rIL-1, rIL-2, pIL-2, platelet derived growth factor (PDGF) and retinoic acid. Under limiting serum conditions only rIL-2 (greater than or equal to 10 U/mL) caused proliferation of the cells. gamma IFN together with TNF alpha(500 U/mL of each) was cytotoxic. Under maximal stimulus conditions, a cytostatic effect resulted from exposing HCEC to: alpha or gamma IFN (greater than or equal to 1000 U/mL), TGF beta (greater than or equal to 5 ng/mL), rIL-1 (greater than or equal to 0.5 U/mL) and rIL-1 plus gamma IFN. gamma IFN (500 U/mL) plus TNF alpha exhibited synergism in the inhibition of proliferation and produced a cytotoxic effect at TNF alpha concentrations greater than or equal to 500 U/mL. By contrast, rIL-2 enhanced proliferation at greater than 5 U/mL. When rIL-2 was combined with gamma IFN, an inhibitory effect on proliferation was observed, although to a lesser extent than gamma IFN alone. Pretreating the cells with 100 U/mL gamma IFN prior to rIL-1 or IL-2 exposure produced no change in the trends observed above.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗
PubMed1989

The neurological features of early and 'latent' human immunodeficiency virus infection.

Neurological manifestations of unknown cause occurring in patients who become or are HIV antibody positive with presumed normal immune function have been described recently. This report adds a further six cases, all of whom had normal CD4+ cell counts either throughout the period of observation or after the episode of seroconversion. Three had an acute presentation, two in the context of documented seroconversion consisting of one of the following: an encephalitis, an ataxia, and confusion with neuralgic amyotrophy. Three had a subacute disorder occurring at a later phase of HIV infection but before opportunistic infections or neoplasms, and marked by a static mild cognitive deficit. This report extends the range of abnormalities that may be seen at seroconversion and documents the presence of a non-progressive cognitive deficit occurring in the latent phase of HIV infection.

AIDS Dementia Complex↗
PubMed1988

Radiation-induced lung injury: a hypersensitivity pneumonitis?

Radiation pneumonitis occurs 6 to 12 weeks after thoracic irradiation, and is thought to be due to direct radiation-induced lung injury. Four patients who developed pneumonitis after unilateral thoracic irradiation for carcinoma of the breast were studied with bronchoalveolar lavage, gallium scan of the lung, and respiratory function tests. On the irradiated side of the chest, all four patients showed an increase in total cells recovered from the lavage fluid and a marked increase in the percentage of lymphocytes. When results for the unirradiated lung were compared with results for the irradiated lung, there was a comparable increase in total cells and percentage of lymphocytes. Gallium scans showed increases for both irradiated and unirradiated lungs. Prompt improvement was seen after corticosteroid therapy in all patients. The fact that abnormal findings occur equally in irradiated and unirradiated lung is inconsistent with simple direct radiation-induced injury and suggests an immunologically mediated mechanism such as a hypersensitivity pneumonitis.

Aged↗
PubMed1988

Effects of interferon on natural killer (NK) cells assessed by fluorescent probes and flow cytometry.

The effects of interferon-alpha and -gamma (IFN) on natural killer (NK) cells was investigated by labelling cells with fluorescent membrane and intracellular probes and analysing these by flow cytometry. Peripheral blood mononuclear cells (PBMCs), sorted NK cells and non-NK cells were labelled with one of the fluorescent probes, 3,3'-dihexyloxacarbocyanine (DiOC6(3], N-phenyl-1-naphthylamine (NPN) or Quin 2, subsequent to incubation with IFN-alpha or IFN-gamma and the change in their fluorescence was monitored by flow cytometry. NK activity after treatment with IFN-alpha or -gamma was also monitored in parallel using a standard 51Cr-release assay. IFN-alpha treatment of PBMCs caused an apparent depolarisation and subsequent hyperpolarization of the cell membranes. Such changes reflect movement of ions across the cell membrane and also the binding of IFN-alpha to the cell surface receptor. Molecular conformational changes in the cell membrane due to IFN-alpha and IFN-gamma were monitored by labelling cell populations with NPN. Changes in NPN-labelled cell fluorescence intensity, indicating changes in membrane conformation, were greatest in NK cell populations activated by IFN-gamma. IFN-alpha had a more profound effect on non-NK cell populations. The concentration of free intracellular Ca2+ ions is also affected by IFN-alpha and IFN-gamma activation, as monitored by the fluorescent probe, Quin 2. There is an apparent decrease in intracellular Ca2+ ion concentration in the NK cell population when treated with IFNs, with the greatest effect being shown by IFN-gamma. These data indicate that the effects of IFNs on NK cells can be monitored at a cellular level using fluorescent probes and flow cytometry. As analysed by these probes, IFN-alpha and IFN-gamma appear to affect NK cells via different mechanisms.

1-Naphthylamine↗
PubMed1988

The effects of scleroderma serum on human microvascular endothelial cells. Induction of antibody-dependent cellular cytotoxicity.

To investigate the vascular immunopathology of systemic sclerosis, we developed a model consisting of human microvascular endothelial cells, leukocytes, and serum. Sera from 19% of the patients studied mediated antibody-dependent cellular cytotoxicity against endothelial cells. Some sera also mediated cytotoxicity against aortic endothelium and fibroblasts. K lymphocytes, the cells that mediate antibody-dependent cellular cytotoxicity, were identified in the skin of some patients. The sera alone were not cytotoxic or growth inhibitory, and did not affect endothelial prostacyclin production.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1988

Characterization of T lymphocyte responses during primary infection with human immunodeficiency virus.

The present study was undertaken to determine T cell response to primary human immunodeficiency virus (HIV) infection. No significant difference in T cell subsets was found between subjects who later seroconverted and a group of controls. Six subjects had multiple enumerations of T cell subsets done at the time of seroconversion. Initially, total lymphocyte and T cell subset counts were reduced. An inversion of the CD4+:CD8+ ratio due to a rise in the level of CD8+ cells was found later, followed by an appreciable increase in the number of CD8+ cells and further inversion of the CD4+:CD8+ ratio. Finally, the CD8+ cell count returned toward normal but remained higher than the CD4+ cell count; the inverted ratio was maintained. Lymphocyte hyporesponsiveness to mitogens and antigens was found during the seroconversion illness in one subject. In three of five subjects for whom data were available, an increase in the absolute number of CD8+ cells followed a decrease in the serum HIV antigen level.

Acquired Immunodeficiency Syndrome↗
PubMed1988

The Sydney AIDS Project: development of acquired immunodeficiency syndrome in a group of HIV seropositive homosexual men.

The Sydney AIDS Project is a prospective immunoepidemiological study of 996 homosexual/bisexual men enrolled between February 1984 and January 1985. By January 1987, 32 of 386 homosexual men who were seropositive at enrollment in the study had developed AIDS, yielding a crude progression rate of between 2.8% and 4.2% per annum. Of these subjects, 23 (72%) developed AIDS within 12 months of enrollment. In univariate analysis, the only lifestyle differences between seropositive subjects who progressed to AIDS and those that did not progress were less frequent oral sex activity and more use of marijuana in the three months prior to enrollment. In multivariate analysis, seropositive subjects who progressed to AIDS were more likely to have a lower percentage of CD4+ cells, a higher percentage of CD8+ cells and to have used marijuana in the three months prior to enrollment than the seropositive subjects who did not progress. No HIV seropositive subject who was asymptomatic and had normal T-cell subsets at enrollment had developed AIDS by January 1987. Persistent generalised lymphadenopathy was not associated with progression to AIDS. Although there are a number of lifestyle factors that may be associated with HIV infection, this study did not implicate most of these in the progression of HIV seropositive subjects to end-stage AIDS. We conclude that antecedent changes in T-cell subsets are associated with progression to AIDS and we emphasise the prognostic value of enumeration of T-cell subsets in HIV seropositive persons.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Effect of interferon on the in vitro synthesis of paraprotein by plasma cells in myeloma.

The aim of this study was to determine the effects of interferon on in vitro immunoglobulin synthesis by the plasma cells of patients with multiple myeloma. Bone marrow cultures were set up in the presence of media alone or alpha-interferon. Supernatants were harvested over a 24-hour period and assayed for paraprotein immunoglobulin synthesis using radio-immunoassays developed in this department. The 24-hour paraprotein synthesis ranged from 9 to 493 micrograms/10(6) plasma cells in patients with IgG myeloma (n = 11), and from 0.3 to 8.3 micrograms/10(6) plasma cells in those with IgA (n = 4). Alpha-Interferon had variable effects on paraprotein synthesis in IgG myelomas, causing an inhibition of synthesis (up to 61%) in 3 patients and an enhancement of synthesis (up to 95%) in 5 cases. In IgA myelomas, on the other hand, alpha-interferon caused inhibition of synthesis in 1 case. In the 2 patients studied during alpha-interferon administration, IgG synthesis was significantly reduced. More cases are currently being investigated. Clearly, immunoglobulin synthesis by plasma cells shows variable modulation by alpha-interferon in vitro.

Adult↗
PubMed1988

Primary human immunodeficiency virus infection. Clinical and serologic aspects.

The identification of characteristic clinical, serologic, and immunologic responses to primary HIV infection has contributed greatly to our understanding of the natural history of HIV infection. Subjects usually present with a mononucleosis-like illness and during the period of primary infection there is a characteristic four-phase T cell response. Early serologic findings of infection include IgM antibody and free HIV p24 antigen. Tests for mononucleosis yield negative results, but atypical lymphocytosis may be present. We believe there are three primary goals for future research into primary HIV infection: to further define the features of this phase of infection, to develop early intervention strategies effective against HIV, and to further develop and foster education strategies that will prevent primary HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Characterization of the acute clinical illness associated with human immunodeficiency virus infection.

The clinical and serologic features and immune status of 39 homosexual men who had seroconversion to human immunodeficiency virus positivity were compared with 26 homosexual men who remained seronegative during a six-month period. An acute clinical illness occurred in 92.3% of seroconverted subjects and 40% of controls. The duration of illness was significantly greater in the seroconverters than the controls (10 + 4.4 days). A general practitioner was consulted by 87.2% of the seroconverters because of the illness, including 12.8% who were admitted to hospital, compared with 20% of controls. The most frequently reported symptoms in the seroconversion group were fever (76.9%); lethargy and malaise (66.7%); anorexia, sore throat, and myalgias (56.4% each); headaches and arthralgias (48.7% each); weight loss (46.2%); swollen glands (43.5%); retro-orbital pain (38.5%); and dehydration and nausea (30.8% each). Lymphadenopathy developed in 75% of seroconverters compared with 4% of controls. Changes in T-cell subsets were not found in controls, but the number of T4+ cells and the T4+/T8+ ratio decreased significantly in seroconverters.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Flow cytometry with crystal violet to detect intracytoplasmic fluorescence in viable human lymphocytes. Demonstration of antibody entering living cells.

A new method is described for the detection of intracytoplasmic fluorescence and its differentiation from surface staining of viable human lymphocytes using flow cytometry after addition of crystal violet which quenches surface but not internal fluorescence. This has then been used to study antibody penetration of viable human lymphocytes, using FITC-conjugated IgG from normal serum or serum containing anti-RNP antibody. The results showed that 54 +/- 1% normal lymphocytes were penetrated by anti-RNP antibody and 23 +/- 3% by normal IgG respectively. The lymphocyte population analysed by flow cytometry has been directly demonstrated to be viable by FDA staining. These results provide unequivocal evidence that antibody can penetrate viable human lymphocytes.

Antibodies↗
PubMed1987

The effect of radiotherapy on the natural killer (NK)-cell activity of cancer patients.

The aim of this study was to determine the effect of radiotherapy on peripheral blood natural killer (NK)-cell number and activity in 15 patients with cancer, prior to the commencement and at the completion of radiotherapy. The following observations were made. Prior to radiotherapy NK activity could not be correlated with the stage of malignancy. In all patients with advanced disease and with subnormal baseline NK activity, the outcome of radiotherapy was unfavorable. Following radiotherapy to sites including the mediastinum, patients had decreased NK activity compared with those receiving treatment to other sites. This decrease was not related to the dose of radiotherapy or stage of malignancy. The tumor response was favorable in most patients whose NK activity decreased as a result of radiotherapy. The decrease in NK activity may be associated with a decrease in the percentage of NK (N901) cells in the peripheral blood. The reduction in NK activity in those patients receiving mediastinal irradiation may be due to the large volume of blood which transits the field, so that the NK cells, or their more radiosensitive precursors, may be damaged and/or differentiation inhibited. Thus, these new observations show that radiotherapy does indeed affect the NK activity in cancer patients predominantly when the irradiation site includes the mediastinum.

Adult↗
PubMed1987

Chemotherapy influencing the course of nephrotic syndrome in colonic carcinoma.

A 50-year-old man presented with the Nephrotic Syndrome (NS). Subsequent investigations showed this to be due to a membranous glomerulonephritis. He was found to have a primary colonic carcinoma with extensive intra-abdominal spread. He was treated with 5-fluorouracil (5FU) with excellent resolution of the NS for a period of 6 months. The disease eventually progressed and the NS recurred on cessation of chemotherapy. This is the first report of such a response to 5FU of which we are aware and emphasizes the usefulness of palliative chemotherapy even in 'resistant' solid tumors when they are complicated by the NS.

Adenocarcinoma, Mucinous↗