Biomedical subjects

D L Mann

Publications and source records attributed to D L Mann.

At least 163 records · Page 9Linked to original sources

PubMed1988

HTLV-I infection and chronic lymphocytic leukemia.

We have captured the immunoglobulin genes of CLL cells by fusing the peripheral blood lymphocytes from CLL cells with the B lymphoblastoid line. The hybridoma cell line established from the fusion of CLL cell from two patients who were HTLV-I seropositive produced antibody directed against HTLV-I proteins. The antibody activity of the immunoglobulin produced by the fused cells is different in the two patients in one case being directed against a gag protein and in the other against the viral large envelope protein. In an attempt to explore possible mechanisms whereby HTLV-I may contribute indirectly to the pathogenesis of B cell CLL, we have determined that B cell lines infected with HTLV-I produce growth factor(s) which stimulate and expand populations of normal B cells as well as CLL cells. These results suggest that HTLV-I infection may contribute in several ways to the development of a malignancy in cell where the virus is not present in the cellular genome.

HTLV-I Infections↗

PubMed1988

Dosimeters of human exposure to carcinogens: polycyclic aromatic hydrocarbon-macromolecular adducts.

The metabolic activation of polycyclic aromatic hydrocarbons (PAH), for example benzo[a]pyrene, leads to the formation of carcinogen-macromolecular adducts. Methods that make it possible to detect low levels of these adducts in human peripheral blood samples should be useful in the dosimetry of human exposure to carcinogens. We demonstrated previously the usefulness of enzyme immunoassays and of synchronous fluorescence spectroscopy (SFS) for detecting and characterizing low levels of PAH-macromolecular adducts present in synthetic adduct mixtures. These methods have now been refined and applied to the analysis of samples of peripheral blood collected from occupationally exposed individuals (coke-oven workers) and from people attending smoking cessation clinics. The results of both immunoassays and SFS show the presence of benzo[a]pyrene diol epoxide (BPDE)-DNA, BPDE-haemoglobin and other putative PAH-macromolecular adducts in peripheral blood samples from certain individuals.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1988

HLA antigen frequencies in HIV-1 seropositive disease-free individuals and patients with AIDS.

HLA-A, -B, -C, -DR, and -DQ antigen phenotypes were determined in 266 Caucasian homosexual men, 90 of whom were HIV-1 seronegative, 94 HIV-1 seropositive AIDS-free, and 82 with a diagnosis of AIDS [36 with Kaposi's sarcoma (KS), 34 with opportunistic infection (OI), and 12 with KS and OI]. No significant differences in HLA-A or -B antigen frequencies were found in any comparisons of these groups. However, in comparisons of seropositive AIDS-free men with the AIDS groups, HLA-Cw7 was increased in frequency in OI and HLA-DR1, -DRw14, and -DQw1 in KS. HLA-DR3 and -DQw3 frequencies were decreased in KS, and DRw53 was decreased in OI. In a cohort of 102 HIV seropositive individuals that were followed for a mean of 43 months, AIDS developed in HLA-DR1 positive men more frequently than in individuals with other HLA-DR phenotypes (p = 0.02). These results demonstrate probable genetic differences between individuals developing KS and OI and indicate that the HLA-DR1 phenotype is a risk factor in disease progression in human immunodeficiency virus (HIV)-infected individuals.

Acquired Immunodeficiency Syndrome↗

PubMed1987

HTLV-I--associated B-cell CLL: indirect role for retrovirus in leukemogenesis.

Serum containing antibodies to the human T-lymphotropic virus type I (HTLV-I) has been observed at a higher than expected frequency in patients with B-cell chronic lymphocytic leukemia (CLL) in an area endemic for HTLV-I. An attempt was made to determine whether the cells from patients with this leukemia were HTLV-I antigen-committed B cells that had undergone malignant transformation. Cells from two HTLV-I seropositive Jamaican patients with CLL were fused with a human B-lymphoblastoid cell line. The hybridoma cells that resulted from the fusion of CLL cells from patient I.C. produced an immunoglobulin (IgM) that reacted with the p24 gag protein from HTLV-I, HTLV-II, and HTLV-III (now referred to as HIV), but showed preferential reactivity with HTLV-I. The specific immunoglobulin gene rearrangement (IgM, kappa) in the CLL cell was demonstrated in the hybridoma cell line, indicating that the captured immunoglobulin was from the CLL cells. The IgM secreted by the fusion of CLL cells from patient L.L. reacted only with HTLV-I-infected cells and with the HTLV-I large envelope protein (gp61) on Western blots. The CLL cells from these patients appear to be a malignant transformation of an antigen-committed B cell responding to HTLV-I infection, suggesting an indirect role for this retrovirus in leukemogenesis.

Antibodies, Viral↗

PubMed1987

HTLV-III large envelope protein (gp120) suppresses PHA-induced lymphocyte blastogenesis.

The addition of inactivated preparations of purified human T cell lymphotropic virus (HTLV-III) was found to inhibit normal human lymphocyte phytohemagglutinin (PHA)-induced blastogenesis but had no effect on concanavalin A (Con A), pokeweek mitogen, or allogeneic stimulation. The inhibition was concentration-dependent and also dependent on adding the virus preparation before or at the same time as PHA. The CD4 molecule is the receptor for HTLV-III binding. Immunopurified large envelope protein (gp120) from HTLV-III was found to bind to the CD4 molecule and also inhibited PHA-induced lymphocyte blastogenesis. These results suggest that the gp120 viral protein may alter immune function by binding to the CD4 molecule, which in turn serves as an "off" signal to lymphocyte response to PHA stimulation. Alternatively, by binding to the CD4 molecule, gp120 may interfere with the interaction of this molecule with class II histocompatibility antigens on accessory cells, thus selectively suppressing PHA response.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1987

Effect of T4 count and cofactors on the incidence of AIDS in homosexual men infected with human immunodeficiency virus.

We prospectively evaluated potential markers and cofactors for the acquired immunodeficiency syndrome (AIDS) in 86 homosexual men who were seropositive for human immunodeficiency virus antibodies. During three years of follow-up, 19 men developed AIDS. Risk of AIDS was clearly predicted by the total number of circulating OKT4-positive lymphocytes (T4 count) at enrollment, while the corresponding T8 count was unrelated to subsequent AIDS development. Subjects in Manhattan had a higher risk of Kaposi's sarcoma than did subjects in Washington, DC, and the risk of AIDS tended to increase with numerous homosexual partners. Several of 40 potential cofactors defined ex post facto, including receptive fellatio, enemas, methaqualone use, and high levels of antibody to hepatitis B surface antigen, appeared to be associated with Kaposi's sarcoma but not with Pneumocystis pneumonia. Our data suggest that potent cofactors for Pneumocystis pneumonia were not prominent, pointing to the need for effective drug therapies, particularly to reduce the high AIDS risk of persons with human immunodeficiency virus infection and low T4 counts.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Left ventricular volume during supine exercise: importance of myocardial scar in patients with coronary heart disease.

Existing studies suggest that exercise-induced ischemia produces an increase in left ventricular end-diastolic volume; however, all of these studies have included patients with previous myocardial infarction. To test whether the end-diastolic volume response to exercise is related to the extent of myocardial scar, the results of gated radionuclide supine exercise tests performed on 130 subjects were reviewed. The patient group comprised 130 subjects were reviewed. The patient group comprised 130 men aged 35 to 65 years (mean +/- SD 52 +/- 5) with documented coronary heart disease. The extent of myocardial ischemia and scar formation was assessed by stress electrocardiography and thallium-201 scintigraphy. Patients were classified into three groups on the basis of left ventricular end-diastolic volume response at peak exercise: group 1 (n = 72) had an increase of end-diastolic volume greater than 10%, group 2 (n = 41) had a change in end-diastolic volume less than 10% and group 3 (n = 17) had a decrease in end-diastolic volume greater than 10% (n = 17). At rest there was no significant difference among groups in heart rate, systolic blood pressure, end-diastolic (EDVrest) or end-systolic volumes or ejection fraction (p greater than 0.05); however, at peak exercise the end-systolic volume response was significantly greater for group 1 (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Epidermal Langerhans cells--a target for HTLV-III/LAV infection.

Langerhans cells (LC) are bone marrow-derived, Ia+, CD1+, CD4+, ATPase+ dendritic antigen-presenting cells within the human epidermis. Since the CD4 molecule has been implicated as a receptor structure for HTLV-III/LAV (human T-cell leukemia virus/lymphadenopathy-associated virus), we asked whether LC from HTLV-III/LAV-seropositive individuals display signs of HTLV-III/LAV infection. In skin biopsies from 7/40 HTLV-III/LAV-infected persons (1 asymptomatic carrier, 2 patients with acquired immunodeficiency syndrome (AIDS)-related complex and 4 patients with AIDS), LC were the only epidermal cells to react with a monoclonal antibody specific for the HTLV-III core protein p17. A varying percentage of p17+ LC were morphologically altered with blunt dendrites and poorly demarcated cellular contours. In one of these biopsies, the presence of LC-associated viral particles characteristic of HTLV-III/LAV as well as cytopathic changes in approximately one-third of the LC population were demonstrated by electron microscopy. These results strongly suggest that LC may harbor HTLV-III/LAV. The infection of LC with this retrovirus may have deleterious consequences for the immunologic functions of this cell system and may thus contribute to both the acquisition of immunodeficiency and the infectious and neoplastic complications of AIDS.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Biochemical and molecular epidemiology of human cancer: indicators of carcinogen exposure, DNA damage, and genetic predisposition.

The primary goal of biochemical and molecular epidemiology is to identify individuals at high cancer risk by obtaining evidence of high exposure to carcinogens, leading to pathobiological lesions in target cells, and/or increased oncogenic susceptibility due to either inherited or acquired host factors. This emerging and multidisciplinary area of cancer research combines epidemiological and laboratory approaches. Because DNA is considered to be an important target for modification by mutagens and carcinogens, damage to DNA can be used as an internal, molecular dosimeter of carcinogen exposure. The reactive species of these carcinogens may directly bind to DNA to form adducts and may indirectly cause secondary DNA lesions, e.g., via induction of free radicals and aldehydes. Highly sensitive and specific methods have been developed to measure the minute amounts of DNA lesions and DNA repair products found in biological specimens from humans exposed to carcinogens. For example, DNA adducts have been measured in cells and tissues from people occupationally exposed to carcinogenic polycyclic aromatic hydrocarbons. Antibodies recognizing carcinogen-DNA adducts have also been detected in human sera. Inherited predisposition to cancer has been revealed by recent advances in molecular genetics, including restriction-fragment-length polymorphism. For example, the hypothesis that rare alleles of the Ha-ras proto-oncogene are associated with an increased risk of lung cancer is currently being tested. These approaches afford the potential of biochemical and molecular epidemiology to predict disease risk for individual persons, instead of for populations, and before the onset of clinically evident disease.

Animals↗

PubMed1987

Voluntary intake, gain, digestibility, rate of passage and gastrointestinal tract fill in tropical and temperate breeds of sheep.

In trial 1, Coastal bermudagrass pellets were fed for 63 d to 21 growing rams of Barbados Blackbelly (B), Dorset (D) and Blackbelly X Dorset (B X D) breeding to determine the effect of breed on voluntary intake (VI) and total gain. Initially, each breed group consisted of seven rams with mean weights of 18.6, 31.0 and 26.4 kg, respectively. At the end of the intake and growth phase, digestibility, rate of passage and gastrointestinal tract (GIT) fill were determined. Chromium-mordanted fiber was used as a particle phase marker. Intakes during the digestibility-marker phase averaged 75% of the VI determined in the intake and growth phase. Breeds did not differ in VI, total gain or digestibilities of dry matter (DM) and neutral detergent fiber (NDF). Apparent crude protein (CP) digestibility was approximately 3 percentage units higher (P less than .10) for B X D than for B or D rams. Rate of passage was faster (P less than .05) for B X D rams than for the other breed groups, while D rams were intermediate. Total mean retention time (MRT) was shorter (P less than .05) for B X D rams compared with the other breed groups. Ruminal retention time (RRT) was shorter (P less than .05) and GIT fill was less (P less than .10) for D and B X D than for B rams. In trial 2, chopped orchardgrass-alfalfa hay was fed for 26 d to 19 of the same rams used in trial 1. Breed, number of rams and initial weights (kg) were: B, 5, 25.6; D, 7, 39.4; B X D, 7, 35.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effects of slaframine on circulating concentrations of growth hormone and glucose.

The ability of slaframine (SF), a parasympathomimetic, to alter blood growth hormone (GH) and glucose concentrations in broiler chicks was investigated. Eighty male broiler chicks (average weight 225 g) were divided into 10 groups and dosed with either saline (control) or 1 mg SF/kg of body weight by oral intubation. Plasma samples were obtained from separate groups of chicks at 1, 2, 4, 8, and 12 hr after SF administration and analyzed for growth hormone and glucose. One hour after SF administration, glucose increased (P less than .05) 21.4% compared with controls. Growth hormone increased (P less than .05) 449 to 948% from 8 to 12 hr after SF administration. Administration of SF at 1 mg/kg of body weight was associated with increased plasma GH.

Alkaloids↗

PubMed1986

Serological characterization of human T-cell leukemia (lymphotropic) virus, type I (HTLV-I) small envelope protein.

Murine monoclonal antibodies were developed against the protein products produced by murine C127 cells which had been transfected with a recombinant plasmid clone containing the human T-cell leukemia (lymphotropic) virus type I (HTLV-I) proviral DNA coding regions for part of env, px, and the 3' LTR. Four antibodies with different binding patterns were obtained. One of these antibodies, F1.6, reacted against HTLV-I infected cells but not against noninfected cell lines. This antibody also reacted with sucrose-gradient purified HTLV-I and -II particles with preferential binding against the HTLV-I preparation. The F1.6 antibody bound to two proteins of approximately 21 and 43 kDa in gradient purified HTLV-I preparations, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blots, and to a 43-kDa protein in cell lysates of HTLV-I infected cell lines; the F1.6 antibody did not bind significantly to any HTLV-II proteins in western blots. The three other antibodies F1.1, F1.2, and F1.5, recognized the same size proteins, 21 and 43 kDa in the gradient purified viral preparations of HTLV-I and in the case of the F1.2 antibody, the same size proteins in purified virus preparation of HTLV-II and -III. The F1.2 and F1.5 antibodies bound not only to purified HTLV particles but also to a variety of cellular proteins in HTLV-I infected and noninfected cells suggesting that they recognized epitopes which were shared between HTLV proteins and normal cells. The identity of the 21-kDa viral protein is most likely that of the small envelope glycoprotein. The identity of the larger protein is undetermined.

Antibodies, Monoclonal↗

PubMed1986

Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells.

We studied the configuration and expression of the gene encoding the beta chain of the T cell receptor (TCR beta) in cell lines and primary tumor cells infected by the human T cell leukemia/lymphoma (lymphotrophic) virus type I (HTLV-I). Most of the cell lines and all the primary tumor cells showed rearrangement of the TCR beta gene, and in each case the rearrangement was distinct. The majority of cases examined were clonal with respect to a particular TCR beta gene rearrangement. Primary tumor cells from one case (SD) were found to have a tandem duplication of a portion of chromosome 7; this appears to have resulted in the presence of three alleles of the TCR beta gene, each of which is arranged differently. This suggests that the chromosomal abnormality, and possibly infection by HTLV-I, occurred before TCR beta gene rearrangement. Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I. Cloned T cells of known antigen specificity that are infected by HTLV-I in vitro show impairment of immune function, including loss of antigen-specific responsiveness and the acquisition of alloreactivity. Comparison of the configuration of the TCR beta gene before and after infection revealed no changes detectable by Southern blot analysis. Levels of expression of the TCR beta gene at the mRNA level and surface expression of the T3 complex were also not significantly altered, suggesting that changes in immune function cannot be attributed to quantitative changes in the TCR molecule. The configuration of the TCR beta gene in primary tumor cells infected by HTLV-I was compared with that in the derived cell lines. In all pairs examined, the configuration in the primary tumor cells was different from that in the cell lines, strongly suggesting that the cells that grow in culture are not the original neoplastic cells.

Antigens, Neoplasm↗

PubMed1986

Type C retroviruses of the human T cell leukemia family are not evident in patients with systemic lupus erythematosus.

Type C retroviruses of the human T cell leukemia virus (HTLV) family have been implicated in immune aberrations observed in patients with leukemias, lymphomas, and the acquired immune deficiency syndrome. We have investigated whether retroviruses of the HTLV family are involved in the etiopathogenesis of systemic lupus erythematosus (SLE) by using 1) an immunoenzymatic assay to measure antibodies to HTLV-I and HTLV-III proteins in the sera of 30 patients with SLE, and 2) nucleic acid hybridization techniques (Southern transfer) to detect proviral sequences of HTLV-I, HTLV-II, and HTLV-III in DNA extracted from peripheral blood mononuclear cells of 10 of these patients. Sera from 20 normal individuals served as controls. None of the 30 sera from SLE patients or the 20 sera from normal controls had any detectable antibodies to HTLV-I or HTLV-III. Nucleic acid hybridization studies also failed to detect any HTLV proviral sequences. These results suggest that viruses of the HTLV family do not participate in the etiopathogenesis of SLE.

Antibodies, Viral↗

PubMed1986

Increased proto-oncogene expression in peripheral blood lymphocytes from patients with systemic lupus erythematosus and other autoimmune diseases.

Using RNA hybridization techniques, we examined the expression of proto-oncogenes associated with lymphocyte activation in vitro in patients with systemic lupus erythematosus and other autoimmune diseases. T and B lymphocytes from these patients were found to have significantly increased expression of c-myc, c-myb, and c-raf RNA when compared with those of normal individuals. Among the mononuclear cell subpopulations, B lymphocytes expressed higher levels of RNA for these proto-oncogenes compared with the T lymphocytes. Since prompt expression of these and other proto-oncogenes occurs in fibroblasts and lymphocytes following mitogenic stimulation, we propose that the present findings reflect the pathologically activated state of various lymphocytic subpopulations which is observed in systemic lupus erythematosus and in other autoimmune diseases. Endogenous and exogenous factors which lead to the expression of autoimmunity might share the induction of proto-oncogene expression as a common pathogenetic step.

Autoimmune Diseases↗

PubMed1986

Effects of age on ventricular performance during graded supine exercise.

To assess the effects of age on ventricular performance, graded supine exercise tests with equilibrium radionuclide ventriculography were performed in six normal subjects of mean age 37 +/- 4 years and in eight normal subjects with a mean age of 59 +/- 2 years. At a standard submaximal work load, older subjects had a similar heart rate (older: 126 +/- 10, younger: 128 +/- 5 bpm) and systolic blood pressure responses (older: 198 +/- 24, younger: 202 +/- 24 mm Hg). Cardiac output counts increased appropriately in both groups during submaximal exercise. However, when expressed as percent change from resting values, the increases in cardiac output (older: 125 +/- 14, younger: 75 +/- 10 L/min; p less than 0.05) were greater for the older subjects. The percent change in end-diastolic counts (older: 8.4 +/- 5, younger: -2.8 +/- 4), stroke counts (older: 26 +/- 6, younger: 8.6 +/- 4), and ejection fraction (older: 18 +/- 3, younger: 11 +/- 1%) in proceeding from rest to exercise Stage III (600 kg-m/min) was greater for the older subjects. Age-related differences in each of these measurements were significant at p less than 0.05. These findings suggest that cardiac output during exercise is maintained by an increased heart rate in younger subjects, and by a combination of increased heart rate and the Frank-Starling mechanism in older individuals. Since the heart rate and mean blood pressure response to exercise were similar in both groups, the use of the Frank-Starling mechanism during exercise in older subjects suggests that age-related differences in ventricular preload are important in modulating the performance of the aging left ventricle.

Adult↗

PubMed1986

Doppler and two-dimensional echocardiographic diagnosis of Björk-Shiley prosthetic valve malfunction: importance of interventricular septal motion and the timing of onset of valve flow.

In a 69 year old woman with a "sticking" Björk-Shiley mitral prosthesis, the diagnosis was suggested by both the two-dimensional and the Doppler ultrasound examinations. In particular, the findings of early diastolic paradoxic septal motion, intermittent delayed opening of the prosthetic disc and variable timing of the onset of mitral valve inflow were believed to be diagnostic of a sticking tilting disc prosthesis.

Aged↗

PubMed1985

Molecular and immunologic analysis of a chronic lymphocytic leukemia case with antibodies against human T-cell leukemia virus.

The human T-cell leukemia virus type-I (HTLV-I) is a unique, exogenous, horizontally transmitted retrovirus which is T-cell tropic, and has been associated with a specific type of aggressive leukemia/lymphoma of mature T-cell origin. In a survey of lymphoid malignancies in Jamaica, antibodies to HTLV-I were also found in 6 of 17 patients with chronic lymphocytic leukemia (CLL), raising the possibility of an etiologic relationship. Further studies were undertaken on one of these patients to clarify the nature of the disease and possible virus relationship. Cell surface marker analysis of her peripheral blood cells documented that the majority of circulating lymphocytes were B-cells. DNA-cloned probe analysis with a complete HTLV-I proviral genome of these peripheral malignant B-cells, was negative for integrated virus. A T-cell line was established in culture from her peripheral blood. The presence of HTLV-I in the cultured T-cell line was established by the detection of expressed viral specific gag protein p-19 and proviral DNA. Thus, a B-cell lymphoid malignancy can occur in the presence of HTLV-I infected T-cells, suggesting the possibility of an indirect leukemogenic mechanism.

Aged↗