Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep

We compared the development of antigen-induced airway hyperresponsiveness (AHR) 24 h after challenge with Ascaris suum antigen in allergic sheep with acute (n = 7) and with dual (n = 7) airway responses and then attempted to modify this AHR. Cholinergic airway responsiveness was determined by measuring the carbachol dose required to increase specific lung resistance (sRL) 150% (i.e., PC150). Subsequently the sheep were challenged with antigen and sRL was measured at predetermined times to document the presence or absence of a late response. PC150 was redetermined 24 h later followed by bronchoalveolar lavage (BAL) to assess inflammation. Only dual responders developed AHR (PC150 decreased, P less than 0.05). There were no significant differences in BAL between the two groups. Six dual responders were then, on separate occasions (greater than or equal to 3 wk), pretreated with placebo, indomethacin (2 mg/kg iv), or a leukotriene antagonist, FPL-57231 (30 mg inhaled). Neither agent significantly affected the acute response to antigen. Only FPL pretreatment blocked the late response, but both agents blocked the antigen-induced AHR 24 h later. BAL at 24 h showed no significant differences. These results indicate that only dual responders develop AHR 24 h after antigen challenge. This AHR appears independent of the late increase in sRL or the severity of pulmonary inflammation. AHR appears to be sensitive to agents that interfere with the early release or actions of cyclooxygenase and lipoxygenase metabolites in dual responders.     

Enzymo-Serological Comparison of Proteolytic Enzymes Produced by Salmonella Species and Other Enterobacteria

The proteolytic enzymes produced by 11 Salmonella species of the Sub-genera I, II and IV, have been compared by a so-called enzymo-serological procedure. In sub-genus I, the enzymes of S. schleissheim and S. abortus-bovis showed an identical, or closely related, serological picture, whereas S. texas was serologically distinct. All the 7 examined strains of sub-genus II produced proteolytic enzymes which were serologically very similar, or identical. No enzymo-serological cross-reactions were observed between these organisms and the members of sub-genus I. The only examined species of sub-genus IV, S. argentina, was enzymo-serologically distinct from all other species. Intergeneric cross-reactions occurred between the enzymes from Salmonella species, Enterobacter (Aerobacter) cloacae and Serratia marcescens. The significance of these cross-reactions is discussed.     

Factors Neutralizing the Bacteriocidal Effect of Lysolecithin

The investigations indicate that a variety of non-dialyzable proteins and peptides, including hemoglobins, blood serum proteins, casein, soy protein and hydrolyzed proteins (peptones) are able to neutralize the bacteriocidal effect of lysolecithin. A number of lysolecithin-resistant bacteria are shown to produce lysolecithin-inhibiting metabolites that also promote growth of sensitive organisms in lysolecithin-containing media. On lysolecithin-con- taining agar this can result in a characteristic satellite growth of sensitive organisms around resistant “mother colonies”. Stable resistant mutants were easily selected from a wild type of Staphylococcus aureus after heavy inoculation on lysolecithin-containing nutrient agar. The bacterial lysolecithin-neutralizing factors examined are not considered to be of enzymatic nature. The factors in culture filtrate of Escherichia coli were separated into two active fractions by gel filtration. Due to extremely small amounts of the substances responsible for the neutralizing activity, chemical analyses of these fractions proved problematic, and only a few amino acids could be demonstrated. The neutralizing activity of the bacterial factors, and some of the proteins and peptides, resisted 100° C, or more, for several min. Some aspects of the lysolecithin-inhibitor-interaction are discussed.     

Circadian and Circannual Variations of Cell Cycle Distribution in the Mouse Bone Marrow

The cell cycle distribution of bone marrow cells from the femurs of female C3H mice has been investigated by flow cytometry according to the time of the day and month of the year. Both circadian and seasonal variations were found for the different cell cycle phases as well as the total cell numbers per femur. Both the mesor, the acrophase and the amplitude of the S, G₂ and (G₁ + G₀) phases varied significantly in some months, while in other months only insignificant rhythms were found. The relative cell cycle distribution only partly reflected variations in the total numbers of proliferating cells, since the total cell number per femur was also variable.

The total numbers of cells in DNA synthesis seem to be higher in the first part of the year, indicating increased cell proliferation during winter and spring. In this period the acrophases of DNA synthesis and G₂ were in the morning, while the second half of the year showed the peak later in the day.

In general, hemopoietic cell proliferation seems to constitute a labile equilibrium with rapidly changing activities.     

Light sensitivity of the ciliate Tetrahymena vorax induced by the fluorescent dye acridine orange

The ciliate Tetrahymena vorax is normally insensitive to light. However, after uptake of acridine orange, blue light evokes instant backward swimming. The dye accumulates mainly in posterior vacuoles, with half-maximal uptake after 1 min. Illumination for 10 s induced a depolarisation of approximately 15 mV lasting less than 2 s, followed by a sustained hyperpolarisation of approximately 20 mV. Deciliated cells displayed a similar response. The hyperpolarisation was linked to reduced membrane resistance, showed a reversal potential of approximately −55 mV and was blocked by 1 mmol l⁻¹ TEA. The rate of rise of electrically evoked Ca²⁺-spikes was reduced during the hyperpolarisation, which is compatible with elevated cytosolic Ca²⁺ concentration. This suggests that the hyperpolarisation may be caused by activation of Ca²⁺-sensitive K⁺ channels. The depolarisation was abolished in Ca²⁺-free medium, whereas the hyperpolarisation was unaffected. Illumination for 2 s, or prolonged stimulation restricted to the anterior part of the cell, induced depolarisation only. Illumination of the posterior part caused delayed hyperpolarisation with no preceding depolarisation. We conclude that the induced backward swimming is associated with Ca²⁺ influx through anterior channels, while Ca²⁺ released from intracellular stores activates K⁺ channels responsible for the delayed hyperpolarisation.     

Controlled gelation of xanthan by trivalent chronic ions

Addition of trivalent chromic ions to xanthan solutions gives rise to gel formation. The dynamic shear storage and loss moduli (0.01 – 10 rad/s) of xanthan solutions with polymer concentrations ranging from 1 to 7 mg/ml and Cr³⁺ concentrations ranging from 0 to 50 m have been studied. It is found that the rate of gel formation is strongly dependent on the Cr³⁺ concentration, but to a much smaller extent on the xanthan concentration. The gelation time is less than 1 h for 50 m Cr³⁺ and about 40 h for 2 m Cr³⁺. It is found that the minimum Cr³⁺ concentration needed to give gelation of 1–7 mg/ml xanthan is 1–2 m .