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Biomedical subjects

J H Dean

Publications and source records attributed to J H Dean.

At least 73 records · Page 4Linked to original sources
PubMed1982

Procedures available to examine the immunotoxicity of chemicals and drugs.

The discipline of immunology should provide toxicology with sensitive models to assess toxicity as well as provide better safety assessment. More information on correlations between immune function and host resistance changes and a more standardized panel of methods for immunotoxicity screening will add further credence to the already impressive immunotoxicology data base. Research efforts are needed to evaluate newer in vitro methods with microsome activation systems to screen chemicals for immunotoxicity, to evaluate chemicals for induction of hypersensitization or allergy, and to better determine whether there are chemical structure activity relationships for chemically induced immunotoxicity. The studies described here represent preliminary examples of these approaches.

Animals↗
PubMed1982

Cell-mediated immunity to mouse mammary tumor virus antigens by patients with hyperplastic benign breast disease.

Peripheral blood leukocytes of patients with preoperative breast cancer, benign breast disease, and benign gynecologic disorders and normal healthy females were tested, as blind coded specimens, with murine mammary tumor virus (MuMTV) antigens in the direct and indirect leukocyte migration inhibition (LMI) assays. The incidence of reactivity by patients with breast cancer was low. (From 5 to 35% breast cancer patients reacted, depending on which group of control individuals they were compared to and what antigen was used.) Nonparametric analyses showed no differences between control groups (normal donors and patients with gynecologic disorders) and breast cancer patients with either assay. However, there was a significant difference between benign breast disease patients with hyperplasia and 1) benign breast disease patients without hyperplasia (P less than 0.03) and 2) patients with gynecologic disorders (P less than 0.04) in the direct assay when it was performed blindly with the gp52 antigen. Patients with hyperplasia (benign breast disease as well as breast cancer) had a higher incidence of enhanced migration in the indirect test than breast disease patients without hyperplasia. The enhanced migration to the MuMTV was correlated to enhanced migration to a 3-M KCI extract of the breast cancer cell line MCF-7 in simultaneous tests. Thus the LMI assays with MuMTV antigens do not appear valuable in breast cancer diagnosis, but they may help to identify a small group of benign breast disease patients whose breast pathology is thought to be associated with a high risk for developing breast cancer.

Antigens, Viral↗
PubMed1982

Immune functions in methyl and ethyl carbamate treated mice.

Female B6C3F1 hybrid mice (5-7 weeks of age) were given methyl or ethyl carbamate over a 2 week period and subsequently examined for alterations in various immunological parameters. Exposure to methyl carbamate, a non-carcinogen, did not cause any alterations in the parameters examined. In contrast, exposure to the multipotential carcinogen, ethyl carbamate (urethan) at tumourigenic dosages caused severe myelotoxicity at all dosage levels. Related to the myelotoxicity was a marked depression of natural killer cell activity. Other parameters including susceptibility to tumour cell challenge, humoral immunity, cellular immunity and macrophage function were less affected. These studies indicate that non-toxic, but carcinogenic dosages of urethan, have profound but selective effects on the immune system which can be related to alterations in bone marrow functions.

Animals↗
PubMed1982

Effect of indomethacin on the bone marrow and immune system of the mouse.

Bone marrow cellularity, hematopoietic progenitor cells and immune alterations were evaluated in mice following short term adult exposures to non-ulcerogenic levels of indomethacin. Body and organ weights showed no significant changes with the exception of the spleen where a dose dependent weight increase was noted. Bone marrow cellularity and pleuripotent hemopoietic stem cells (CFU-S) were unaltered while granulocyte-macrophage progenitors (CFU-GM) and splenic erythropoiesis were increased. Indomethacin exposure caused increased macrophage function as evidenced by enhanced phagocytosis. Lymphoproliferative response of splenocytes to T-cell mitogens was depressed while B-cell mitogenic response was not affected. These results indicate that indomethacin affects selective components of the immune and hemopoietic cells at dose levels that cause no other significant pathological alterations.

Animals↗
PubMed1981

Lymphoproliferative responses to autologous tumor extracts as prognostic indicators in patients with resected breast cancer.

Patients with operable breast cancer were tested postoperatively to assess lymphoproliferative responses. Patients with lymphocytes capable of recognizing and proliferating in response to autologous tumor extracts had a significantly longer disease-free interval than those with a low response to their autologous extract. In this group of patients, immunological responses to autologous tumors predicted subsequent clinical course better than pathological evaluation based on tumor presence in axillary lymph nodes. Low or negative reactivity to autologous tumor often was not accompanied by a general, impaired ability to respond in LP assays. In fact, patients with low autologous tumor response and normal MLC were at particularly high risk for recurrence.

Axilla↗
PubMed1980

Augmentation of tumoricidal activity of human monocytes and macrophages by lymphokines.

Monocytes were separated from peripheral blood mononuclear cells of normal human donors by adherence on plastic conditioned by cell lines (microexudate-coated plastic) and harvested by exposure to ethylene diamine tetra-acetic acid. Cytolytic activity was tested by incubating effector cells for 48 h with the murine SV40-transformed TU5 kidney line or the human lung cancer-derived CaLu line prelabelled with tritiated thymidine. Lymphokine-containing supernatants were obtained from in vitrocultures of lymphoid cells with phytohemagglutinin (PHA), purified protein derivative (PPD), or with Corynebacterium parvum strains CN6134 or CNS888. The monocytes had significant levels of spontaneous cytotoxicity and exposure to lymphokine supernatants markedly enhanced their tumoricidal activity. Augmentation of monocyte-mediated cytotoxicity required a minimal exposure to lymphokine supernatants for 4 h and was maximal after 24 h of preincubation. Treatment of the effector cells with anti-human T-cell serum and complement did not affect either their spontaneous or their lymphokine-stimulated cytotoxicity, whereas silica impaired both reactivities. Supernatants of cultures with PHA, PPD and C. parvum CN6134 had significant levels of interferon (IF). Since partially purified human fibroblast or leukocyte IF was able to stimulate monocyte-mediated cytotoxicity, the IF in these supernatants could play some role in the stimulation of the monocytes. However, C. parvum CN5888 supernatants, which had little IF, enhanced monocyte cytotoxicity as effectively as the C. parvum CN6134 supernatants, strongly suggesting that lymphocyte mediators other than IF can augment the tumoricidal activity of these effector cells. Mature macrophages obtained by in vitro cultivation of monocytes for 4-7 days retained natural cytolytic activity and showed enhanced cytotoxicity in the presence of lymphokines. However, more prolonged in vitro cultivation (> 10 days) resulted in cultures of epithelioid and multinucleated cells which had little natural cytotoxicity and were not responsive to lymphokines.

Adult↗
PubMed1980

Association of depressed postoperative lymphoproliferative responses to alloantigens with poor prognosis in patients with stage I lung cancer.

Thirty-five patients with Stage I carcinoma of the lung were tested postoperatively to assess lymphoproliferative responses. Depressed lymphocyte proliferation (LP) responses to alloantaigen in the mixed leukocyte culture (MLC) as measured by thee relative proliferation index (RPI) were associated with a significantly shorter disease-free interval. In this group of patients, the immunologic responses predicted subsequent clinical course better than the TNM classification or the histological type of the tumor, and therefore this procedure appears promising for improved staging of patients with early stages of lung cancer (stage I lung cancer and T1N0M0). The depressed response to alloantaigen was a more sensitive discriminator of disease recurrence than PHA alone or even conbined with PHA.

Adenocarcinoma↗
PubMed1980

Examination of bone marrow, immunologic parameters and host susceptibility following pre- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The effects of pre/postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on various immunological, bone marrow and host susceptibility assays were examined in B6C3F1 hybrid mice. Exposure was accomplished by maternal dosing on Day 14 of gestation and again on Days 1, 7, and 14 following birth, employing dosages of 0, 1.0, 5.0 or 15.0 micrograms/kg body weight. The 15.0 micrograms/kg dosage was lethal to 70% of the offspring with the remainder of that dosage group revealing overt toxicity. Bone marrow toxicity occurred in both the 15.0 and 5.0 micrograms/kg dosage groups as evidenced by bone marrow hypocellularity and depressed colony formation of macrophage-granulocyte progenitor cells and pleuripotent stem cells. Evidence was presented that depression of lymphoproliferative responses following mitogen stimulation in TCDD-immunosuppressed mice was due to a functional defect of lymphocyte activation rather than suppressor cell activity. Administration of either Listeria monocytogenes or syngeneic PYB6 tumor cells in mice exposed to relatively low levels of TCDD during pre- and postnatal development increased their susceptibility to either bacterial or tumor challenge.

Animals↗
PubMed1980

Cardiac ischemia and cardiac hypertrophy. An autopsy study.

In 50 selected postmortem examinations, the degree of roentgenographic coronary arterial stenosis was correlated with various heart and chamber weights. An important relationship was demonstrated between increasing arterial narrowing and total heart muscle weight, particularly when patients with known hypertension or valvular disease were excluded. The relationship held true for individual chamber weights, suggesting that ischemia is associated with whole heart hypertrophy rather than simple left ventricular enlargement. No definite association could be demonstrated between left ventricular weight and any measurement of blood pressure.

Aged↗