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Biomedical subjects

M M Pienkowski

Publications and source records attributed to M M Pienkowski.

12 recordsLinked to original sources

Prostaglandin D2 and histamine during the immediate and the late-phase components of allergic cutaneous responses.

With a skin blister technique in which the mediators generated by the trauma of forming the blister are allowed to subside, we have collected human interstitial skin fluid during the course of allergic reactions to ragweed, and measured levels of histamine and prostaglandin D2 (PGD2). Of 18 ragweed-allergic individuals tested, 11 developed both an immediate and a late-phase reaction (LPR) with fivefold-elevated levels of histamine (40 ng/ml) at 30 minutes and a peak level of PGD2 (6.5 ng/ml) later at 2 1/2 hours after ragweed challenge. The other seven allergic individuals had immediate reactions without an LPR lesion and demonstrated somewhat smaller elevations of histamine (25 ng/ml) but much lower levels of PGD2 (1.6 ng/ml; p less than 0.05). The time course of appearance of these mediators was identical in both groups of patients. The fluids from unchallenged blisters of allergic and nonallergic patients and the fluids of nonallergic patients challenged with ragweed had similar levels of histamine, at the lower limit of detection, and undetectable PGD2 levels. The peak levels of PGD2 in allergic individuals correlated with the size of the LPR lesion (p less than 0.05). These data suggest that the LPR involves the secondary elaboration of mediators different from mediators responsible for the immediate manifestations of the allergic skin reaction.

Adolescent↗

Basophil histamine release remains unaffected by clinical desensitization to penicillin.

A penicillin-allergic patient who required therapy with beta-lactam antibiotics was desensitized with increasing parenteral doses of benzylpenicillin. After desensitization, the patient tolerated, without signs of allergic reaction, intravenous piperacillin. Immunologic studies were undertaken to investigate humoral and cellular changes accompanying desensitization. Serum penicilloyl IgG and IgE antibodies did not change significantly during induction of clinical tolerance to the drug. The patient's previously positive immediate skin reaction to penicilloyl polylysine (PPL) converted to negative. Nonspecific releasability of skin mast cells as tested with polymyxin B skin test was unchanged. In contrast, in vitro blood basophil activation, both by specific antigen (penicilloyl-human albumin) and a nonspecific IgE-dependent stimulus (anti-IgE) remained strong after the desensitization procedure and during weeks of high-dose piperacillin therapy. A monovalent penicilloyl hapten inhibited penicilloyl-albumin-induced basophil histamine release, whereas the patient's own serum taken while the patient was receiving treatment did not. Moreover, the patient's treatment serum, while the patient was receiving piperacillin, was able to trigger histamine release from passively sensitized basophils of a donor not allergic to penicillin, suggesting the presence of a sufficient amount of complete multivalent antigen to initiate release and/or desensitization. The presence of high concentrations of penicilloated serum proteins in the patient's treatment serum was confirmed by immunoassay. Basophil histamine release could, nevertheless, be elicited from the patient's whole blood sample taken while the patient was receiving piperacillin treatment by adding penicilloyl-human albumin in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Identification of histamine releasing factor(s) in the late phase of cutaneous IgE-mediated reactions.

We have shown that fluids collected from antigen-challenged skin blisters during the late phase reaction cause the release of substantial amounts of histamine (means = 42%, n = 14) from human basophils in vitro. Control fluids collected either during the immediate phase or from an unchallenged blister released less than or equal to 10% histamine from both basophils and lung mast cells. Late phase blister fluids induced low levels of histamine release from human lung cells (means = 11%, n = 4) that were slightly but not significantly greater than levels induced by control blister fluids. The characteristics of basophil release were similar to IgE-mediated stimuli in dose dependence, calcium and temperature requirements, and kinetics. The IgE dependence of the late phase blister fluid was demonstrated by desensitization of the basophils to anti-IgE, which obviated the response to anti-IgE and blister fluid but did not affect a non-IgE-mediated stimulus. Removal of the cell surface IgE with lactic acid also abolished the response to both anti-IgE and late phase blister fluid. Incubation of the "stripped" cells with serum containing IgE myeloma restored the response to anti-IgE but failed to affect response to late phase blister fluid. The characteristics of release obtained with this factor closely resemble those of an IgE-dependent histamine releasing factor from cultured macrophages previously described by our group.

Allergens↗

Suppression of late-phase skin reactions by immunotherapy with ragweed extract.

The cutaneous late-phase reaction (LPR) to ragweed was studied in untreated ragweed-allergic individuals and patients receiving 3 to 5 years of immunotherapy demonstrating clinical improvement. The magnitude of immediate skin reactions and the initial levels of the specific IgE and IgG antiragweed antibodies were similar in both groups. The LPR was elicited by administering a skin test with ragweed extract at 10 times the concentration required to elicit a 4 + immediate reaction and appeared as an erythematous-edematous lesion associated with pruritus. In the untreated group 94% developed an LPR (59 +/- 32 mm at 4 hours and 67 +/- 30 mm at 8 hours) at this dose. In the treated group only one third developed an LPR, one third had partial response measurable at one of these two times, and one third failed to develop any LPR (21 +/- 20 mm at 4 hours, p less than 0.002, and 20 +/- 22 mm at 8 hours, p less than 0.001). Therapy resulted in a twentyfold increase of IgG antiragweed level and in a decline of IgE antiragweed. The size of the LPR correlated inversely with the level of IgG antiragweed (p less than 0.01; r = -0.52) but not with IgE antibody. Thus, in a retrospective analysis immunotherapy was associated with the suppression of the skin LPR, and the magnitude of the LPR was correlated with the level of IgG antiragweed. We suggest that the clinical efficacy of immunotherapy is related in part to effects on the LPR.

Adult↗

Accretion of biopsy specimens of vaginal adenosis from patients exposed in utero to diethylstilbestrol, when transplanted to athymic nude mice.

Vaginal adenosis biopsy specimens from 10 patients exposed in utero to diethylstilbestrol were transplanted for 30 days into athymic (nude) mice. Almost all grafts were recovered, and they had morphologic features closely resembling those of the original biopsy specimens, i.e., cystic, complex, and simple occult glands covered mainly with an endocervical type of epithelium showing extensive squamous metaplasia. Autoradiographic analysis of these grafts after pulse administration of [3H]thymidine into the mice revealed extensive labeling of epithelial cells. These results imply that female athymic (nude) mice are compatible hosts for accretion of the human adenosis.

Adolescent↗

Thymus-dependent control of host defense mechanisms against Trypanosoma cruzi infection.

Congenitally athymic homozygous (nu/nu) mice were shown to be significantly more susceptible to Trypanosoma cruzi infection than their thymus-bearing heterozygous (nu/+) littermates, as measured by increased parasitemia, mortality rate, and shortened survival time. In addition, transplantation of neonatal thymus into athymic mice reestablished normal levels of resistance to T. cruzi, i.e., comparable to those of normal littermates. These results constitute conclusive evidence that host defense mechanisms active in experimental Chagas' disease are under thymic control.

Animals↗

A visual display board used for efficient breeding and utilization of an athymic (nude) mouse colony.

A visual display board was designed to aid in the management of a barrier sustained athymic (nude) mouse colony. The board displayed pertinent information for breeding and weaning, including phenotype and age for each animal in the colony. In addition, the board showed the availability and current status of experimental groups. This system provided an efficient means of organizing production and planning utilization of animals in the colony.

Animal Identification Systems↗

Rapid lymphocyte immunoreactivity test utilizing [3H]uridine in vitro.

A microculture assay utilizing [3H]uridine incorporation was developed to test murine spleen lymphocyte immunoreactivity in vitro. Parameters of the culture technique which included cell density, doses of LPS, Con A, PHA, [3H]uridine levels, and length of culture time were investigated. Responses were detectable at 4 h for all 3 mitogens, with labeling ranging up to 180% of the control value. By 8 h there was a 200--350% increase in mitogen-induced incorporation of radioactivity. Similar increases were observed in a serum-free system. The responses were the result of increased incorporation of label by stimulated cultures rather than decreased labeling of non-mitogen treated cultures over time. The [3H]uridine incorporation was demonstrated to be the selective response of T or B cell populations when stimulated with appropriate lectins. This assay detects early RNA synthesis, as supported by experimental observations in which accumulation of radioactivity in stimulated lymphocytes was TCA precipitable, resistant to SDS treatment, and inhibited by actinomycin D.

Animals↗

Analysis of a viral agent isolated from multiple sclerosis brain tissue: characterization as a parainfluenzavirus type 1.

A virus originally isolated from cell cultures obtained by lysolecithin-induced fusion of human multiple sclerosis brain cells with CV-1 cells has been analyzed for its antigenic, RNA, and polypeptide compositions, and for selective biological properties. Our findings establish that this isolate, designated 6/94 virus, contains a 50S RNA genome and is, as yet, indistinguishable from Sendai virus in its antigenic and total polypeptide compositions. Despite these similarities, the 6/94 and Sendai viruses differ in certain phenotypic properties. 6/94 virus is markedly less cytocidal for chick fibroblasts, especially at 37 C and, after beta-propiolactone inactivation, it possesses a greater capacity for cell fusion and a lower toxicity than does comparably treated Sendai virus. In addition, 6/94 virus shows greater hemolytic activity.

Animals↗