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Biomedical subjects

K Harris

Publications and source records attributed to K Harris.

7 recordsLinked to original sources

The effect of histamine-1 and histamine-2 antagonists on airway responses to histamine in the rhesus monkey.

This study used rhesus monkeys with consistent respiratory responses to aerosolized histamine. Two systems of histamine challenge were evolved to study the effects of histamine antagonists on the histamine-induced respiratory response. One system consisted of administering increasing subreactive concentrations of histamine until an airway response (H) occurred. This threshold histamine dose was repeated (H'). The pulmonary function changes occurring with the H' challenge were less intense than those with H. M, a histamine-2 receptor antagonist, when given before the H' dose was associated with a potentiated H' response compared with the threshold H response. This provides evidence for histamine-2 receptor sites in rhesus monkey airways. A second system used duplicate histamine challenges with a known reactive dose of histamine. In this system, the pulmonary function changes occurring with the repeated challenge (H') were greater than with the first reactive challenge dose (H). This H' response was inhibited partially with diphenhydramine, a histamine-1 receptor antagonist. These two systems of histamine challenge provide an experimental model for evaluating pharmacologic alteration of histamine-induced respiratory responses. There is evidence for the existence of histamine-1 and histamine-2 receptor sites in the airways of the rhesus monkey.

Animals

The evaluation of selected parameters of immune function in asthmatics after long-term corticosteroid therapy.

The availability of inhaled beclomethasone diproprionate permitted the discontinuation of continuous, long-term systemic corticosteroid therapy (SCT) in a group of asthmatics who had previously required SCT to control their asthma. Twelve patients had been on SCT for a period of 2-22 years with an average duration of 7 years. To determine whether this previous long-term SCT and the current use of inhaled beclomethasone diproprionate had an effect on leucocyte functions, a variety of studies reflecting T lymphocyte, B lymphocyte and granulocyte function was done. The results were compared with those of twelve asthmatic patients of similar age ranges who had never received steroids. Results showed that the two patient populations could not be differentiated on the basis of phytohaemagglutinin stimulation of lymphocytes, sheep erythrocyte rosette formation, IgG, IgA, IgM and IgE concentrations or granulocyte bactericidal activity. Delayed skin reactivity was present in both groups, with more positive reactions in the non-SCT group. Polymorphonuclear adherence values were slightly lower in the SCT female population using beclomethasone diproprionate. The latter two minor differences may be due to the previous SCT, the use of beclomethasone diproprionate or the limited population of patients studied. We conclude from these studies that the long-term use of SCT at the low doses required for control of asthma resulted in little permanent effect on the variety of lymphocyte and granulocyte functions tested.

Adrenal Cortex Hormones

In vitro activities of some synthetic substance P analogs.

Substance P (SP) and several analogs and fragments have been synthesized and evaluated on non-stimulated and stimulated guinea-pig ileum. In the former test system the potency order was as follows: SP(4--11) greater than SP = [Tyr7]-SP = [Eth11]-SP = [Nle11]-SP greater than [Dala9]-SP greater than SP(7--1) = [Tyr7]-SP(7--11) greater than [Eth11]-SP(7--11) greater than [DAla9]-SP(7--11) greater than [Nle11]-SP(7--11) greater than SP(1--7). The spasmogenic activity of SP and analogs was preserved in the same potency order on stimulated guinea-pig ileum; none of these modifications resulted in an analog with narcotic-like activity. These data are discussed in terms of a hypothetical SP receptor in extravascular smooth muscle.

Animals

Characterization of a unique cell line (LAZ 221) from human acute lymphocytic ("null" cell) leukemia.

A unique human cell line designated LAZ 221 has been established from the peripheral blood of a patient with acute lymphocytic leukemia of the "null" cell type. The cell line does not possess the Epstein-Barr virus nuclear antigen and has a karyotype of 45,XX,-9,-12,+(9q12q). Both the established cell line and the patient's uncultured blast cells share the same phenotypic markers. They both lack T-cell markers. They fail to form sheep erythrocyte rosettes and do not react with T-cell-specific antisera (TH1-, HTL-), nor do they possess B-cell markers. They do not form rosettes with erythrocytes sensitized with complement, and they are surface immunoglobulin negative. However, they do possess an HLA-D-related glycoprotein complex of 23,000 to 30,000 daltons, an la-like antigen. Thus, LAZ 221 shares the phenotype of the patient's uncultured blasts and is a cell line representative of about 75% of all human acute lymphocytic leukemias. In this respect it differs from previously described human hematopoietic cell lines.

Adult

Dynamic parameters of membrane lipids in normal and leukemic human lymphocytes isolated from peripheral blood and bone marrow.

The degree of microviscosity (eta), and lipid fluidity (LFU) of cellular membranes of normal and leukemic lymphocytes obtained from peripheral blood and bone marrow of normal donors and acute lymphatic leukemic (ALL) patients was quantitatively monitored by fluorescence polarization analysis with the aid of the fluorescent lipophilic probe 1,6-diphenyl-1,3,5-hexatriene when embedded in cellular membranes of intact cells. The results have shown a marked decrease in eta and a significant increase in LFU in lymphocytes obtained from both peripheral blood and bone marrow of ALL patients at admission when compared to both T- and B-lymphocytes obtained from peripheral blood of normal donors. Moreover, both dynamic parameters, eta and LFU, show normal characteristic values in lymphocytes obtained from bone marrow of ALL patients in complete hematological remission. Since in few cases a decrease in eta and an increase in LFU were observed in bone marrow lymphocytes isolated from ALL patients in remission, the possibility that these dynamic parameters may serve as a diagnostic tool for an early detection of a new relapse is discussed.

B-Lymphocytes