Mechanisms involved in the immunotoxicity induced by dermal application of JP-8 jet fuel.

Dermal application of JP-8 jet fuel induces immune suppression. Classic delayed-type hypersensitivity as well as the induction of contact hypersensitivity to allergens applied to the shaved skin of JP-8-treated mice is suppressed. In addition, the ability of T cells isolated from JP-8-treated mice to proliferate in vitro is suppressed. Here we focused on further characterizing the immunotoxicity induced by JP-8 exposure and determining the mechanism involved. Suppression of T-cell proliferation was first noted 3 to 4 days after a single JP-8 treatment and lasted for approximately 3 weeks, at which time T-cell proliferation returned to normal. Cellular immune reactions appear to be more susceptible to the immunosuppressive effects of JP-8, as antibody production in JP-8-treated mice was identical to that found in normal controls. The mechanism through which dermal application of JP-8 suppresses cell-mediated immune reactions appears to be via the release of immune biological-response modifiers. Blocking the production of prostaglandin E(2) with a selective cyclooxygenase-2 inhibitor abrogated JP-8-induced immune suppression. Neutralizing the activity of interleukin-10 with a highly specific monoclonal antibody also blocked JP-8-induced immune suppression. Furthermore, injecting JP-8-treated mice with recombinant interleukin-12, a cytokine that drives cell-mediated immune reactions in vivo, overcame the immunotoxic effects of JP-8 and restored immune function. These data indicate that immune suppressive cytokines, presumably produced by JP-8-treated epidermal cells, are responsible for immune suppression in JP-8-treated mice and that blocking and/or neutralizing their production in vivo overcomes the immunotoxic effects of JP-8.

Potassium-induced secretion of melanocyte-stimulating hormone from the melanotrophs of the neurointermediate lobe of the lizard Anolis carolinensis.

Secretion of melanocyte-stimulating hormone (MSH) from the melanotrophs of the neurointermediate lobe (NIL) of the lizard Anolis carolinensis was studied to investigate the role of membrane potential and extracellular calcium ions in the control of secretion in this species. MSH secretion was monitored from perifused NILs which had been in organ culture for 7-14 days prior to experiment to allow the nerve terminals present in the tissue to degenerate. Elevation of the K(+) concentration in the perifusate induced a marked increase in MSH secretion. Perifusion of the cultured NILs with a nominally Ca-free solution did not reduce basal MSH secretion but blocked K-induced secretion. Moreover, nimodipine, an antagonist of voltage-gated Ca(2+) channels, inhibited K-induced secretion, whereas BAY K 8644, a Ca(2+) channel agonist, potentiated it; but neither drug affected basal secretion. High ¿K(+) perifusate also stimulated MSH secretion from freshly excised (acute) NILs. Furthermore, in these preparations nominally Ca-free solution reduced basal secretion by 40% in addition to blocking K-induced secretion. As in the cultured NILs, nimodipine blocked and BAY K 8644 potentiated K-induced secretion in the acute NILs while not affecting basal secretion. The results from the cultured NILs are consistent with the hypothesis that stimulated MSH secretion from the melanotrophs of the anole is dependent upon Ca(2+) influx through voltage-gated calcium channels. The qualitatively similar results obtained from the acute NILs in response to high ¿K(+), nimodipine, and BAY K 8644 suggest that, for the most part, what is being observed are the direct effects of these substances on the melanotrophs. Basal secretion of MSH in cultured NILs is significantly less than that in the acute preparations. The calcium-sensitive fraction of basal secretion present in acute NILs may require the presence of nerve terminals.

Histopathologic features of the liver in pediatric acquired immune deficiency syndrome.

Autopsy and liver biopsy specimens from 30 pediatric patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex (ARC) were retrospectively reviewed. Of 28 cases with histologic abnormalities, the following findings were noted singly or in combination: giant-cell transformation, cytomegalovirus inclusions, Kaposi's sarcoma, diffuse lymphoplasmocytic infiltrate, granulomatous hepatitis, mild portal inflammation, necrosis around central veins, steatosis, and cholestasis. For the most part, abnormalities in the liver were not predictive of those in other organs, but the two children with the diffuse parenchymal lymphoplasmocytic infiltrate also had lymphoid interstitial pneumonitis (LIP). Liver histopathology in pediatric patients with AIDS shares some features with that in adults, but appreciable differences are noted. In particular, these differences include the higher frequency of giant-cell transformation and the lower frequency of granulomas in children and the observation of diffuse lymphoplasmocytic infiltrate associated with LIP.

Seminal vesicle and coagulating gland growth induced by intraperitoneal inoculation of fungi in mice.

The effect of fungi on the growth of body organs in mice was investigated. Single, intraperitoneal injections of yeasts (Cryptococcus albidus, Saccharomyces cerevisiae, Schizosaccharomyces octosporus) or molds (Aspergillus niger, Geotrichum candidum, Mucor haemalis) induced an increase in the mass of seminal vesicles and coagulating glands independent of whole body weight changes in mice.

Seminal vesicle growth induced by Ascaris suum infection.

This study was designed to determine the effect of Ascaris suum infection upon growth of mouse vesicular glands. Mice were infected with varying dosages of A. suum eggs and killed after six weeks. Results indicated a dose dependent increase in seminal vesicle weight, independent of total body weight.

Studies on the mechanism of renin release from rat kidney slices: calcium, sodium and metabolic inhibition.

1. The coincident release of renin and lactic dehydrogenase (LDH) from rat renal cortical tissue slices was studied during calcium depletion, metabolic inhibition, and with the addition of ouabain (1 mM) to the incubation medium.2. The results indicate that although LDH accumulated in the medium during incubation, the pattern was dissimilar to that of renin. Ouabain significantly inhibited renin release in calcium containing medium, but had no effect on LDH release. Renin release was potentiated in calcium ;free' media, while calcium depletion reduced the release of LDH.3. The addition of potassium cyanide (2 mM) significantly inhibited the release of renin from these tissue slices. Cyanide was ineffective, however, when administered in calcium ;free' medium.4. At reduced incubation temperatures (5 degrees C) the release of both renin and LDH were significantly reduced.5. Medium sodium depletion caused a significant inhibition of renin release. The simultaneous removal of calcium from the medium did not restore renin release to control levels.6. These results are not consistent with the hypothesis that spontaneous renin release during calcium depletion and metabolic inhibition is a result of cell enlargement and increased membrane permeability. On the other hand, the in vitro release of renin during these experiments appeared to be inversely related to the intracellular concentration of calcium.

Lack of inhibition of hog renin by heparin.

These experiments were performed to test if heparin inhibits the production of angiotensin I from rat renin substrate acted upon by either rat or hog renin. Substrate was prepared from the plasma of nephrectomized rats; commercially prepared hog renin and heparin (0-50 units/ml, final concentration) were added and angiotensin I production was measured by radioimmunoassay following incubation of the mixture at 37-38 degrees C for 30 min. Heparin had no effect on the radioimmunoassay for angiotensin I, nor on the Vmax nor the Km of the renin-renin substrate reaction. Heparin (0 and 50 units/ml, final concentration) was added to rat plasma which contained renin and renin substrate. No effect of heparin on the rate of production of angiotensin I was observed in this system. In conclusion, rat and hog renin are not inhibited by heparin within the range of concentrations used.

Effect of intrarenal arterial infusion of magnesium on renin release in dogs.

Magnesium chloride was infused into the renal artery of anesthetized dogs in order to determine its effect on renal function. Natriuresis and diuresis were observed during MgCl2 infusion, but there appeared to be no effect on glomerular filtration rate (GFR), or plasma sodium or potassium concentrations. Although mean arterial blood pressure and renal plasma flow (RPF) decreased throughout the experiment, the fall was not significant until after stopping MgCl2 infusion. A significant stimulation of renin secretion occurred during magnesium administration.

Renin secretion from rat renal cortical cell suspensions.

Renin secretion of rat renal cortical cell suspensions was studied as a functionof variations in the composition of the suspension media. Renin secretion was determined by incubating samples of the suspension media with rat renin substrate and measuringthe angiotensin I generated by radioimmunoassay. Increasing the medium sodium concentration (50-144 meq/liter) linearly decreased the rate of renin secretion. This relationship was unaffected by adding ouabain (10 minus 3 M) to the suspensions. The addition of furosemide (from 10 minus 5 to 10 minus 3 M) stimulated renin secretion. Considered with previous observations, these results suggest that renin secretionis controlled by some function of sodium on the lumenal boder of the macula densa cells.

The influence of ouabain on in vitro renin secretion and intracellular sodium.

Renin secretion has been hypothesized to be inversely related to the tubular sodium concentration or load. Using rat kidney cortex slices, in vitro renin secretion was measured as a function of sodium concentration of the medium. We found, as have many others, that renin secretion increases with increasing medium sodium concentration. However, in the presence of 10(-3) M ouabain, renin secretion decreased with increasing medium sodium concentration. We also found that intracellular sodium concentration varied directly with medium sodium both in the presence and absence of ouabain. Furosemide, a known renin stimulator in vivo, had no effect on renin secretion from tissue slices. Although obvious differences exist between in vitro and in vivo results, no simple relationship may exist between intracellular sodium concentration and renin secretion.