Effect of prostaglandin D2 and I2 on the airways of rhesus monkeys

Prostaglandin (PG) D2 and PGI2 were evaluated to determine their effect on pulmonary function parameters when aerosolized in anesthetized rhesus monkeys. PGD2 resulted in an increase in frequency (f) and pulmonary resistance (rl) and a decrease in peak expiratory flow rate (PEFR), tidal volume (VT), and dynamic compliance (Cdyn), with the major effect on RL. PGI2 primarily effected an increase in f and a decrease in PEFR and VT. PGI2 had a variable effect, generally a decrease, on RL. The metabolite of PGI2, 6-keto-PGF 1 alpha, had no effect on the rhesus airway. PGF 2 alpha responses were similar to PGD2 except that the PGF 2 alpha produced a less strikingly consistent increase in RL. When PGI2 and PGD2 were aerosolized simultaneously, they simulated previously described antigen responses. Further, PGI2 plus PGD2 produced an airway response at 1/10 the concentration of either agent alone.     

Lymphocyte proliferation induced by autologous cells. XV. Relationships between the human autologous mixed lymphocyte reaction stimulated by non-T and activated T cells

The human {T:T act} AMLR was characterized in its relationship to the {T:Non-T} AMLR and its validity as a nonxenogeneic antigen induced response was extended. Human T cell lines, established from responding T cells in an autologous mixed lymphocyte reaction (MLR), were maintained in medium containing human serum and interleukin-2 (IL-2). These cells stimulated ³H-thymidine incorporation by autologous T cells and by autologous unfractionated blood mononuclear cells. Freshly activated T cells isolated from an autologous MLR stimulated autologous T cells to a lesser extent could be enhanced by adding IL-2. Twenty-five to 50% of T cells stimulated by activated T cells express the T8 determinant. In contrast, we have previously shown that less than 10% of T cells activated after 6 days in culture with non-T cells express the T8 determinant. The number of T8 bearing cells were increased significantly after 10 days in culture with non-T cells. This suggested that two types of reactions, the {T:Non-T} and {T:T act} AMLR, might occur in sequence when T cells and autologous non-T cells are cocultured: first, the activation of T4 cells by non-T cells, then by the activation of T8 cells by activated T4 cells. Finally, activated T cells can stimulate unfractionated autologous mononuclear cells without prior exposure to sheep erythrocytes or fetal calf serum.     

The synthesis and actions of mouse and human interferons in mouse-human hybrid cells.

Lines of mouse-human hybrid cells segregating either mouse or human chromosomes were used for the analysis of various aspects of the production and actions of mouse and human interferons. In one of the hybrid cell lines capable of producing both mouse and human interferons, the proportion of the two interferon activities produced varied greatly under different inducing conditions, suggesting that there are differences in the triggering mechanisms of the two interferons. Generally both mouse and human interferon production could be enhanced (“superinduced”) by sequential treatment with cycloheximide and actinomycin D; however, in one of the lines producing both mouse and human interferon, only the latter could be superinduced. There was no correlation between the capacity of the lines to produce mouse or human interferons and the sensitivity to their action. However, there was good correlation between the sensitivity to the antiviral action and the priming action (i.e., enhancement of subsequent interferon production) by the two interferons. Thus, line 55-91F2 produced both mouse and human interferons, but was sensitive to the antiviral and priming actions of human interferon only. Line GM52 × BalbVC15 produced only mouse interferon but was sensitive to the antiviral and priming actions of both interferons.     

Histologic studies of human skin test responses to ragweed and compound 48/80: III. Effects of alternate-day steroid therapy

Our previous studies have shown depressed eosinophil responses in skin test reactions to pollen antigens and compound 48/80 in those just completing a 1-wk course of daily steroids. Wheal reactions were unaffected. In this study, 6 ragweed-sensitive atopic subjects were studied before and on the seventh day (“day on”) and day 8 (“day off”) of a course of alternate-day steroids. Blood neutrophil levels rose on day 7 and were similar to baseline on day 8, whereas blood eosinophil levels were significantly reduced on both days 7 and 8. Neutrophil responses in skin test reactions were depressed on day 7 and normal on day 8. In contrast, the tissue eosinophil responses were depressed significantly, and to similar degree, on both days 7 and 8. These findings are of potential significance in evaluating the clinical effects of steroids in allergic diseases.     

Biological activities of glycoproteins of HVJ (Sendai virus) studied by reconstitution of hybrid envelope and by concanavalin A-mediated binding: a new function of HANA protein and structural requirement of F protein in hemolysis.

When HANA protein of HVJ (Sendai virus) was denatured by dithiothreitol treatment, concanavalin A added to the system or influenza virus hemagglutinin reconstituted with treated HVJ-envelope to form hybrid by SM-2 dialysis method could not replace a role of HANA for hemolysis. Binding of the treated samples to erythrocytes was restored by them, however. Thus, a hypothesis is proposed that intactness of not only F but also HANA protein of HVJ is required for envelope-cell fusion, in other words, HANA protein of HVJ may play some positive role other than binding in the process of the virus-induced hemolysis.     

Sister chromatid exchange: Variation by age,sex, smoking,and breast cancer status

Variation in sister chromatid exchange (SCE) frequency in lymphocytes of 125 persons was compared using a multivariate general linear model. The study was performed to determine whether SCE frequency differs with respect to age, sex, smoking, and breast cancer status. Study subjects were divided into: members of two branches of families having an excess of cancer (primarily breast) including a brother and sister in one family who developed nonbreast malignancies within 1 yr of the study; women in both families successfully treated for breast cancer (all at least 5 yr posttreatment); and women from the general population with confirmed breast cancer.Controls consisted of spouses who married into the high-risk kindreds, hospital personnel, and others (primarily tradesmen without history of occupational exposure). Results show that: (1) Women with active breast cancer have a significantly higher mean SCE frequency than control women or women greater than 5 yr posttreatment for breast cancer; (2) Cigarette smokers show a significantly higher number of SCEs than was observed in nonsmokers; (3) The increase in SCE level in smokers is dose-related to exposure as measured by cumulative pack-years; (4) SCE values in both high-risk families are not significantly different from controls; (5) Neither the age nor sex of the individual affects SCE frequency; and (6) The observed distribution of exchanges agrees with that expected based on the proportion of the genome represented by each chromosome group.     

Sequence of centromere separation: Occurrence,possible significance,and control

This review describes the existence of a phenomenon, sequential separation of centromeres, in mitotic cells of various species including both animals and plants. Critical observations at metaanaphase show that the centromeres of chromosomes in a given genome do not separate into two sister units randomly, but that there is a genetically controlled, nonrandom, species-specific sequence which is independent of the length of the chromosome or the position of the centromere. A stricter control appears to exist for late-separating than for early-separating chromosomes. At early stages of metaanaphase several chromosomes initiate onset of separation simultaneously or in rapid succession, but late-separating chromosomes are better defined in their sequential position. The effect of Colcemid on the sequence of separation is minimal. It is proposed that aneuploidy in humans and other organisms may result from out-of-phase separation of a given chromosome. With the exception of chromosome No. 16, it appears that very early- or very late-separating centromeres are involved in human trisomies more often than those in between.Perhaps one function of centromeric heterochromatin is the control of centromere separation. The amount of such chromatin shows a positive correlation with the timing of separation of the centromeres. Superimposed upon this quantitative influence is the qualitative aspect, as discussed for various genomes. This suggestion explains a lack of extremely large quantities of heterochromatin near the centromere. Its existence in the form of homogeneously staining regions distal to the centromere, as in some cancer cells or in sex chromosomes, seemingly has no influence on the separation of centromeres.A brief discussion of centromere separation errors in human disease is provided, and suggestions for further studies are made.     

Different specificities of an HLA-DRw6 haplotype detected by alloreactive T lymphocytes

DRw6 has been difficult to define serologically. In the present experiments we have developed T cell lines in order to characterize the components of a DRw6 haplotype. This was accomplished by priming T cells with allogeneic mononuclear cells mismatched for DRw6, Dw6, and MT2. Subsequently, three sublines with distinct reactivity patterns were derived by limiting dilution. The specificities detected by these sublines included: (a) a specificity found on a subset of cells positive for DRw6 which was inhibited by monoclonal antibodies against DS(DC), the human homologue of the murine IA-encoded molecules, (b) another DRw6-associated specificity blocked by an MT2-like antibody, and (c) an MT2-like specificity blocked by monoclonal antibodies reactive with a different MT2-associated determinant. These results show that more than one IE-like, as well as the DS/DC (IA-like) molecules, carry distinctive antigenic epitopes that can be recognized by allogeneic T cells. Primed T cell lines may be useful for a better definition of certain haplotypes which are at present difficult to characterize with serological reagents alone.     

Bronchocentric granulomatosis: a complication of allergic bronchopulmonary aspergillosis.

Hypersensitivity to the fungal antigens of Aspergillus fumigatus may result in a spectrum of immune injury collectively known as allergic bronchopulmonary aspergillosis (ABPA). This report describes a 14-yr-old boy who presented clinical findings consistent with ABPA,including a history of asthma, blood eosinophilia, serum precipitins, and IgE antibodies to Aspergillus fumigatus. Sputum Aspergillus, pulmonary infiltrates, and dual types I and III skin reactions to Aspergillus fumigatus were observed also. Pathology of the resected right upper lobe revealed severe bronchial destruction with the findings of bronchocentric granulomatosis. Noninvasive septate fungal hyphae compatible with Aspergillus were identified. Cultures from sputum and surgical specimens grew Aspergillus and Mycobacterium intracellulare avium. The PPD-B (purified protein derivative-Batty) intradermal skin test produced a 6 mm induration (PPD-S was negative). The patient's condition has been well controlled with prednisone and several antituberculous drugs. In addition, inflammatory and immunologic parameters have begun to return to normal. The relationship between ABa and the atypical mycobacterial infection is not clear. The association of ABPA with the severe bronchial destruction seen in bronchocentric granulomatosis is emphasized to alert physicans to this serious sequelae of ABa seen in the asthmatic.     

A canine model for reaginic hypersensitivity and allergic bronchoconstriction

Immunization of neonatal dogs with a conjugate of 2,4-dinitrobenzene and ovalbumin (DNP₂-OA), using aluminum hydroxide as the adjuvant, elicited long-lasting (over 30 wk) anti-DNP and anti-OA IgE antibody responses of high titers as determined by homologous passive cutaneous anaphylaxis. Low antigen doses of 10 or 50 μg were more effective than the higher doses of 250 or 1,250 μg in inducing high IgE antibody levels. However, this method of immunization failed to elicit any detectable IgE antibody response in adult dogs. Bronchoprovocation with antigen of sensitized animals having IgE antibody titers in excess of 64 resulted in a marked increase in airflow resistance, which could be corrected by the administration of nebulized isoproterenol. On the other hand, sensitized animals with IgE antibody titers in the order of 64 did not manifest significant bronchoconstriction on inhalation challenge but developed anaphylaxis following intravenous injection of the antigen.