Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer--II. A differential effect of megestrol acetate and medroxyprogesterone acetate on serum estrone sulfate and sex hormone binding globulin

Serum estradiol, estrone, estrone sulfate and sex hormone binding globulin were measured in 10 postmenopausal patients with advanced breast cancer receiving sequential treatment with medroxyprogesterone acetate and megestrol acetate. Treatment with megestrol acetate caused a non-significant reduction in serum estradiol (mean reduction of 19%, 0.05 less than P less than 0.1) but significant reductions in serum estrone (mean reduction of 20%, P less than 0.02) and serum estrone sulfate (mean reduction of 54%, P less than 0.005) compared to treatment with medroxyprogesterone acetate. In contrast, treatment with medroxyprogesterone acetate reduced serum sex hormone binding globulin more compared to treatment with megestrol acetate (mean reduction of 69%, P less than 0.01). These findings suggest that the two progestins have differential effects on serum hormone levels. The finding that treatment with megestrol acetate causes a significant reduction in serum estrone sulfate level warrants further investigations of this potentially important mechanism of action of this drug in advanced breast cancer.     

Differential enhancement of sister-chromatid exchange frequencies by alpha-naphthoflavone in cultured lymphocytes from smokers and non-smokers

The sister-chromatid exchange (SCE) frequency was assessed in peripheral lymphocytes from 4 smokers and 8 non-smokers in the absence or presence of alpha-naphthoflavone (ANF) in the culture media. ANF produced a concentration-dependent increase in the frequency of SCEs in smoking individuals. At an ANF concentration of 11 micrograms/ml, average SCE levels were 54% and 13% above the baseline levels in smokers and non-smokers, respectively. The ANF-enhanced increase in the SCE frequency ranged from 3.12 to 5.72 among smokers, and from 0 to 1.96 among the non-smokers. No significant difference in the mean SCE baseline levels between smokers and non-smokers was detected. The mechanism responsible for the enhanced frequency of SCEs in smokers following in vitro exposure to ANF is not clear, but may reflect changes in metabolic activation/deactivation or increased sensitivity to genetic effects of ANF.     

Sulfide oxidation by spheroplasts of Thiobacillus ferrooxidans.

Thiobacillus ferrooxidans is an acidophilic organism important to metal leaching of low-grade ores. The aforementioned importance is related to the ability of the bacterium to oxidize reduced iron and sulfur, principally found in nature as pyrite (FeS2). The present study dealt with sulfide oxidation at low pH values and the involvement of the cell envelope in the process of the inorganic oxidations. Sulfide oxidation was noted in spheroplasts of T. ferrooxidans prepared by enzymatic and chemical treatments and partially purified by differential centrifugation. No enzyme activities were noted in membrane fractions containing enrichments of lipopolysaccharide symbolic of outer membrane material or in membrane vesicles containing (or associated with) higher levels of proteins. Results to date indicate that in an acid milieu the envelope structure containing both the outer membrane and the intact inner cytoplasmic membrane is required for sulfide oxidation.     

Prostacyclin does not change during an oxygen induced increase in pulmonary blood flow in the fetal lamb

The role of prostacyclin in mediating the increase in pulmonary blood flow caused by an increase in oxygen tension in the fetal lamb was investigated. Plasma concentrations of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin, were measured during an increase in pulmonary blood flow caused by a rise in oxygen tension in eight intrauterine fetal lambs. Fetal oxygen tension was increased by placing the pregnant ewes in a hyperbaric chamber and having them breathe 100% oxygen at three atmospheres absolute pressure. This increased fetal PaO2 from 27 +/- 3 to 60 +/- 6 torr (mean +/- S.E., p less than or equal to 0.0001) and increased the proportion of right ventricular output distributed to the fetal lungs from 6 +/- 2 to 45 +/- 7% (mean +/- S.E., p less than or equal to 0.001). However, the fetal plasma concentration of 6-keto-PGF1 alpha did not change, 186 +/- 26 to 208 +/- 40 pg/ml (mean +/- S.E.). Indomethacin decreased plasma concentrations of 6-keto-PGF1 alpha in each of three fetuses but did not decrease the proportion of right ventricular output distributed to their lungs. The increase in pulmonary blood flow caused by an increase in oxygen tension in the fetal lamb is not associated with an increase in plasma concentrations of 6-keto-PGF1 alpha. Prostacyclin does not appear to be involved in the increase in pulmonary blood flow caused by the increase in oxygen tension at birth.     

Antiproliferative effect of interferon on a Burkitt''s lymphoma cell line

The effect of interferon (IF) on the growth of a Burkitt's lymphoma cell line was analysed. The degree of depression of cell doublings was the same if the cells were in a steady state mode of exponential growth or in a resting state (G0) when IF was added. As IF had a lag time of 24 h before decreased growth could be observed, cells in G0 did not seem to be more sensitive when growth was estimated by cell counts expressed as cell doublings. IF inhibited cells to proceed into the cell cycle and the possibility that IF may increase the escape into a G0 loop is discussed.     

Alpha-syntrophin dependent expression of tubulin alpha 8 protein in hepatocytes

The scaffold protein alpha-syntrophin (SNTA) is a component of the dystrophin glycoprotein complex and has been comprehensively studied in skeletal muscle and adipocytes. SNTA is further expressed in the liver where its biological role remains unclear. Unpublished data from our group suggested that SNTA deficiency is associated with altered tubulin alpha 8 (TUBA8) levels in fat. TUBA8 is highly expressed in different cell lines including hepatoma cells, and here we analyzed whether SNTA has a role herein. In Hepa1-6 cells, TUBA8 protein levels were increased upon SNTA knock down and were reduced upon overexpression of SNTA. This regulation was not identified when analyzing mRNA expression. In the liver of SNTA-deficient mice, TUBA8 protein was higher compared to the respective wild-type controls while RNA expression was even suppressed. Using the HaloTag platform, TUBA8 was found to form a complex with SNTA in Hepa1-6 cells. In the hepatic stellate cell line LX-2, the lack or overexpression of SNTA did, however, not change TUBA8 protein expression. SNTA and TUBA8 are described to regulate cell proliferation. Yet, knock down of SNTA did neither affect proliferation nor viability of Hepa1-6 cells. The present study shows that SNTA protein levels are inversely related to TUBA8 protein expression in the hepatocyte cell line Hepa1-6.     

Fluctuations of unbound whole blood polyamine levels during the menstrual cycle.

Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females.     

Characterization of reaerosolization from impingers in an effort to improve airborne virus sampling

Aims:  To assess the impact of reaerosolization from liquid impingement methods on airborne virus sampling.
Methods and Results:  An AGI-30 impinger containing particles [MS2 bacteriophage or 30-nm polystyrene latex (PSL)] of known concentration was operated with sterile air. Reaerosolized particles as a function of sampling flow rate and particle concentration in the impinger collection liquid were characterized using a scanning mobility particle sizer. Reaerosolization from the impinger was also compared to that from a BioSampler. Results show that reaerosolization increases as flow rate increases. While the increased particle concentration in the impinger collection liquid leads to an increase in the reaerosolization of PSL particles, it does not necessarily lead to an increase in the reaerosolization of virus particles. Reaerosolization of virus particles begins to decrease as the particle concentration in the impinger collection liquid rises above 10⁶ PFU ml⁻¹. This phenomenon results from aggregation of viral particles at high concentrations. Compared with micron-sized particles, nanosized virus particles are easier to aerosolize because of reduced inertia. Reaerosolization from the BioSampler is demonstrated to be significantly less than that from the impinger.
Conclusions:  Reaerosolization from impingement sampling methods is a mode of loss in airborne virus sampling, although it is not as significant a limitation as the primary particle size of the aerosol. Utilizing a BioSampler coupled with short sampling periods to prevent high accumulative concentrations can minimize the impact of reaerosolization.
Significance and Impact of the Study:  This study confirms reaerosolization of virus particles to be a mode of loss in impingement sampling and identifies methods to minimize the loss.