Biomedical subjects

T Denny

Publications and source records attributed to T Denny.

32 records · Page 2Linked to original sources

PubMed1992

An unusual case of false-positive serology for the human immunodeficiency virus: report from the heterosexual HIV transmission study.

A man was found to have a repeatedly positive enzyme immunoassay (EIA) that was confirmed by a western blot with six positive bands. He was told that he was seropositive for the human immunodeficiency virus (HIV), but subsequent EIAs were negative and western blots were either negative or indeterminant. All other HIV-related studies were unrevealing, and no explanation for the false-positive result was found. We have not absolutely eliminated the possibility of mislabeled specimens, but we believe this to be unlikely. The possibility, albeit infrequent, of concomitant false-positive EIAs and western blots should be kept in mind when formulating public policy with regard to HIV testing.

AIDS Serodiagnosis↗

PubMed1991

Clinical and laboratory correlates of Pneumocystis carinii pneumonia in children infected with HIV.

The case histories of 27 children with Pneumocystis carinii pneumonia (PCP) who were followed up in the AIDS Program at the Children's Hospital of New Jersey, Newark, are reviewed. The mean and median age at PCP diagnosis were 10.8 and 7.7 months, respectively. All of the children had other clinical evidence of infection with the human immunodeficiency virus that was documented prior to the diagnosis of PCP or found at the time of PCP diagnosis. Most patients who presented to the hospital were acutely ill, and complications of treatment occurred in 70%. Overall, 89% of the patients died and 70% survived for less than 6 months after diagnosis of PCP. Median survival after the diagnosis of PCP was only 2.0 months and the median life span of children with PCP was only 14.4 months. Only 40% of children with PCP had CD4 lymphocyte counts at or below the threshold for institution of PCP prophylaxis in adults of 200 x 10(6) cells/L (200 cells/mm3).

CD4-Positive T-Lymphocytes↗

PubMed1990

Decreased suppressor-inducer T lymphocytes in multiple sclerosis and other neurological diseases.

Decreased numbers of CD4+CD45R+ suppressor-inducer T cells have been reported in patients with a variety of autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis but not in patients with other neurological diseases. We now report our findings using murine monoclonal antibodies and two-color flow cytometric analysis on CD4+CD45R+ T cells in 22 patients with chronic progressive multiple sclerosis, 23 patients with other neurological diseases and 42 normal, healthy controls. Suppressor-inducer T cells were significantly reduced (p less than 0.001) in both patients with multiple sclerosis and other neurological diseases as compared to controls. Both patient populations had elevated helper T cell subset ratios. Thus, our data suggests that decreases in suppressor-inducer T cells may represent a common immunological defect among autoimmune and presumably non-autoimmune neurological disorders.

Adult↗

PubMed1989

Positively selected Leu-11a (CD16+) cells require the presence of accessory cells or factors for the lysis of herpes simplex virus-infected fibroblasts but not herpes simplex virus-infected Raji.

Previous studies from our laboratory indicated that human NK activity against HSV-infected fibroblasts (HSV-Fs) but not K562 targets was sensitive to treatment with anti-HLA-DR plus C. In the current study, we have selected Leu-11a+ (CD-16) cells by fluorescence activated cell sorting and found that although Leu-11a enriched populations lysed K562 targets in 14-h 51Cr-release assays, they were unable to kill HSV-Fs targets unless a Leu-11a-depleted population was added back to the effectors or unless known activators of NK cells (IFN-alpha or IL-2) were added to the assays. In contrast, Leu-11a-enriched populations were able to mediate ADCC against HSV-Fs in the presence of sera from HSV-seropositive individuals without the requirement for accessory cells. We have begun preliminary characterization of the accessory cells which allow lysis of HSV-Fs by NK cells: they are HLA-DR+ cells which enrich in the light density fractions of Metrizamide density gradients. They need be present in very small numbers for lysis to take place and are not MHC restricted in that heterologous add-backs between anti-HLA-DR plus C and anti-Leu-11b plus C-treated populations are capable of target cell lysis at levels similar to those achieved with the autologous add-backs. Further, the levels of lysis in heterologous add-back experiments reflected the lytic potential of the effector rather than the accessory cell donor. Finally, although the requirement for accessory cells for NK lysis has been demonstrated for fibroblasts infected with HSV-1, CMV, and VZV, lysis of HSV-infected Raji lymphoblastoid cells is relatively accessory-cell independent, indicating that the requirement for accessory cells for lysis by NK cells is not a property of all herpesvirus-infected targets.

Adjuvants, Immunologic↗

PubMed1989

Elevated serum levels of tumor necrosis factor are associated with progressive encephalopathy in children with acquired immunodeficiency syndrome.

The cytokine tumor necrosis factor (TNF) was assayed in the sera (n = 31) and cerebrospinal fluid (n = 26) of children with acquired immunodeficiency syndrome, using a competitive radioimmunoassay. Elevated serum levels of TNF were found in 15 (79%) of 19 patients with progressive encephalopathy (PE), compared with 1 (8%) of 12 patients without neurologic involvement. There was a significant association of PE with elevated serum TNF levels. Conversely, of 16 patients with elevated serum TNF levels, 15 (94%) were found to have PE, and of 8 patients with serum TNF levels greater than 100 pg/ml, all 8 (100%) had PE. No association was found between cerebrospinal fluid levels of TNF and PE. Neither serum nor cerebrospinal fluid TNF levels correlated with the degree of cachexia. These data suggest that circulating TNF may be responsible for the myelin damage that occurs in human immunodeficiency virus type 1-associated PE.

Acquired Immunodeficiency Syndrome↗

PubMed1988

T cell subsets and disease progression after total lymphoid irradiation in chronic progressive multiple sclerosis.

T lymphocyte subset percentages were determined in 16 total lymphoid irradiation (TLI) treated and 18 sham treated control patients with chronic progressive multiple sclerosis. During the first year after treatment, the ratio of T helper/inducer to T suppressor/cytotoxic cells (Th/Ts ratio) was significantly higher in sham treated multiple sclerosis patients who worsened clinically compared with TLI treated and sham treated multiple sclerosis patients who remained clinically stable. TLI caused a fall in the percentage of T helper cells in treated patients, while the percentage of T suppressor cells remained stable during the first year after treatment. In contrast, the percentage of T suppressor cells fell in sham treated multiple sclerosis patients who worsened clinically.

Follow-Up Studies↗

PubMed1987

Effects of human growth hormone on immune functions: in vitro studies on cells of normal and growth hormone-deficient children.

We have studied the in vitro effects of human growth hormone on cell surface markers and mitogenic responses of peripheral blood lymphocytes (PBL) of normal and growth hormone-deficient children before, during and after treatment with growth hormone. Growth hormone resulted in a decrease in B cell expression but it did not affect expression of T cell subsets. Growth hormone depressed the proliferation of PBL of normal and untreated growth hormone-deficient children. The proliferative responses to phytohemagglutinin (PHA) versus PHA with growth hormone were not statistically different, though the responses of most normal and on treatment children were diminished by the addition of growth hormone. PBL derived from growth hormone-deficient children during treatment with human growth hormone exhibited significantly greater spontaneous proliferation then the PBL of normal children. Growth hormone further significantly enhanced their proliferation. PHA and PHA with growth hormone resulted in significantly greater proliferation of these patients' PBL when compared to those of normal children. We demonstrated that human growth hormone had substantial in vitro effects on immune functions. These effects, some of which depend on the treatment status of the children, may need to be considered in the clinical use of human growth hormone.

Child↗

PubMed1987

Polyclonal polymorphic B-cell lymphoproliferative disorder with prominent pulmonary involvement in children with acquired immune deficiency syndrome.

Four cases of pediatric Acquired Immune Deficiency Syndrome (AIDS) with lymphoproliferative disorder are described and other lymphoid lesions in previously reported cases of pediatric AIDS are reviewed. The lymphoproliferative disorder was characterized by polyclonal, polymorphic B-cell content without evidence of cellular atypia, necrosis or prominent mitotic activity but with predominantly extranodal systemic and prominent pulmonary involvement. Since the lesion has overlapping features it is considered to be intermediate between benign and malignant lymphoproliferations and designated as polyclonal, polymorphic B-cell lymphoproliferative disorder (PBLD) of pediatric AIDS. The PBLD is part of a spectrum of lymphoid lesions in pediatric AIDS consisting of follicular lymphoid hyperplasia of nodal and extranodal sites, pulmonary lymphoid hyperplasia/lymphoid interstitial pneumonitis complex (PLH/LIP complex) in cases previously reported by the authors, and also malignant lymphoma reported by others. It is possible that Epstein-Barr virus (EBV) by itself or in synergism with human T-lymphotropic virus-type III (HTLV-III) is related to pathogenesis of PBLD in children with AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Suppression of immune function in growth hormone-deficient children during treatment with human growth hormone.

Inasmuch as growth hormone is known to interact with the immune system, we studied immune functions including immunoglobulins, cell surface markers, mitogen responses, and polymorphonuclear cell function in eight children with growth hormone deficiency, ages 1 to 17 years, before and during treatment with human growth hormone for 12 to 16 months. Before treatment immune functions were normal in all children. Treatment with human growth hormone did not significantly affect serum immunoglobulins, polymorphonuclear cell function, or percent T cells. However, percent B cells decreased to subnormal levels in seven of seven patients. T helper/suppressor ratios decreased in all patients, to subnormal values in seven of eight patients; and mitogen responses decreased to below normal in all. The decline of percent B cells was transient in all patients, of T helper/suppressor ratios in seven of eight, and mitogen responses in five of eight patients. In vitro incubation of lymphocytes with growth hormone resulted in no changes in cell surface markers or mitogen responses. Although the depression of immune functions resulted in no increased rate of infections during the observation period, we do not know the possible effects of prolonged treatment and therefore caution against the indiscriminate use of human growth hormone. The effects of biosynthetically obtained growth hormone on immune function remain to be determined.

Adolescent↗

PubMed1984

Analysis of T-cell subsets in B-cell chronic lymphocytic leukemia: a correlation with the stage of disease.

T-cell subsets were determined by the Leu monoclonal antibodies in the peripheral blood and/or bone marrow of 52 patients with B-cell chronic lymphocytic leukemia (B-CLL) not on therapy at the time of study. The diagnosis of B-CLL required that the leukemic cells expressed surface receptors for "la-like" antigen, Fc fragment of IgG, mouse red blood cells (MRBC), C3-coated red cells (EAC), and low density of monoclonal surface immunoglobulin. The Leu-3a+/2a+ ratio was applied to define the balance between the helper/suppressor subsets in the residual T-lymphocytes. Most patients showed a decrease in the Leu-3a+/2a+ ratios at all stages of disease. The decrease in ratio was mainly related to a decrease in the Leu-3a+ T-cell subset. The more advanced stages of B-CLL were associated with lower Leu-3a+/2a+ ratio, higher total white cell and percent lymphocyte counts. There was no correlation between the proportion of EAC or MRBC rosetting cells and stages of B-CLL. This analysis further suggests that B-CLL is an immunosuppressed state that becomes more pronounced in the advanced stages and is characterized by a progressive decrease in the Leu-3a+ (helper) T-cell subset.

Antibodies, Monoclonal↗

PubMed1982

Characterization of B-cell type chronic lymphocytic leukemia cells by surface markers and a monoclonal antibody.

This study was carried out to determine the reactivity of the Leu-1 mouse monoclonal antibody with B-chronic lymphocytic leukemia and other B-cell leukemias. This antibody has been previously reported to recognize a surface antigen expressed by almost all human thymocytes and peripheral T cells. It was also detected on surface immunoglobulin-bearing cells of most patients with chronic lymphocytic leukemia but was not detectable in normal B-cells and B-cell lines. In the present series, the neoplastic lymphocytes in 33 cases of B-chronic lymphocytic leukemia expressed surface immunoglobulin, Ia antigen, and receptors for Fc, C3, and mouse erythrocytes. All but one case expressed the Leu-1 antigen as detected by indirect immunofluorescence using flow cytometry. In three other cases, the leukemic cells in the peripheral blood reacted with anti-Leu-1, whereas the bone marrow lymphocytes did not. Moreover, quantitative differences in the surface density of Leu-1 were apparent by flow cytometry. The peripheral blood and bone marrow lymphocytes in other B-cell leukemias, including 15 cases of leukemic B-cell lymphomas and three cases of hairy-cell leukemia, failed to stain positively with the anti-Leu-1 antibody. The recognition of the Leu-1 antigen adds to the phenotypic characterization of b-chronic lymphocytic leukemia and may contribute to a better understanding of the pathogenesis of the disease and its expression in different tissues.

Antibodies, Monoclonal↗

PubMed1982

Analysis of T-cell differentiation antigens in acute lymphatic leukemia using monoclonal antibodies.

Leukemic cells in 134 patients with ALL were analyzed by a panel of mouse monoclonal antibodies. Two antibodies are reactive with all peripheral blood T cells but define different surface antigens (Leu-1 and Leu-4). Two other antibodies react with antigens that are restricted to suppressor/cytotoxic T cells (Leu-2) and to helper T cells (Leu-3). We also used antibodies to the receptor for sheep red blood cells (SRBC) (Leu-5) and to a human "TL-like" antigen that is found on most thymocytes but not in peripheral T cells (Leu-6). An antibody to the human p29.34 "Ia-like" molecule was also tested. Of the 134 ALL patients, 17 had a predominance of SRBC-rosetting (Leu-5+) lymphoblasts ("T" ALL), expressing different surface phenotypes defined by this panel of monoclonal antibodies. These phenotypes were not readily classifiable according to a scheme of sequential stages of normal differentiation proposed. Moreover, the lymphoblasts in 8 of 113 patients not expressing conventional B- to T-cell markers ("null" ALL) reacted with the monoclonal anti-T-cell antibodies. This study suggests that the classification of lymphoblasts in ALL based on the reactivities observed with this panel of mouse monoclonal antibodies is not easily reconciled with current models of normal T-cell differentiation. However, it should be emphasized that the precise sequence of antigenic expression by cells undergoing thymic differentiation is still not fully known, and further phenotypic analysis of ALL cells might contribute to an improved understanding of this malignancy.

Adolescent↗

PubMed1977

Organ distribution of Corynebacterium parvum labeled with iodine-125.

Administration of iv, ip, single sc, multiple sc, and footpad injections of [125I]Corynebacterium parvum in mice revealed different patterns of radioactive vaccine distribution in various organs. High deposition and retention were found in the liver, spleen, and gastrointestinal tract and less in the lungs, kidneys, thymus, and bone marrow. Control animals given 125I showed very rapid clearance of the isotope and no retention in the organs. The pattern of distribution of [125I]C. parvum could be useful when protocols for clinical trials are designed.

Absorption↗

PubMedDate not supplied

Evidence against transmission of human T-lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV) in families of children with the acquired immunodeficiency syndrome.

Six children with the acquired immunodeficiency syndrome (AIDS) and 12 of their household contacts were investigated serologically for evidence of infection with human T-lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV), the presumed etiologic agent of AIDS. All six children had antibody against HTLV-III/LAV, as measured by enzyme-linked immunosorbent assay, in each specimen tested. Of the two mothers studied both were seropositive; one was diagnosed with and died from AIDS. Four of the remaining 10 household members were seropositive, including three adults in groups at high risk for the development of AIDS and one sibling who was younger than the child with AIDS. Among the seronegative household contacts were four foster mothers or grandmothers of the children with AIDS, three of whom had cared for the children since infancy. Household contact with children with AIDS may include persons in groups at high risk for AIDS who have been infected with HTLV-III/LAV. However, the negative findings in household contacts without risk factors for AIDS suggest that horizontal transmission of the virus within households by means other than sexual contact must be infrequent.

Acquired Immunodeficiency Syndrome↗