Serologic detection of a rare case of Q fever in New York City having hepatic and unusual renal complications.

We describe the case of a 46-year-old resident of New York City with a one-year history of frequent urination and 3 weeks of undulating fevers. He also had liver and bone marrow abnormalities where a non-culturable Gram-negative rod was identified. Q fever was suspected and confirmed based on highly elevated phase I and II serum IgM/IgG antibodies against Coxiella burnetii.

Placental 11 beta-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies.

Apparent mineralocorticoid excess and licorice induced hypertension, both hypertensive disorders, have been attributed to a defect in the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which interconverts cortisol to cortisone. Therefore, we undertook this study to determine the role of human placental 11 beta-HSD activity in preeclampsia, which is a hypertensive disorder in pregnancy. 11 beta-HSD activities were determined in placentas of 17 normotensive and 11 preeclamptic patients matched for gestational age at 34-42 weeks. Cortisol levels in umbilical venous and arterial sera were also determined for both groups. Statistical analysis was performed using Student's t-test, significance at p < 0.05. 11 beta-dehydrogenase (oxidation activity of 11 beta-HSD) activity was significantly lower in placentas of preeclamptic compared to normotensive patients (0.19 +/- 0.09 vs. 0.26 +/- 0.08 mmoles/min/placenta, p = 0.02). Cortisol level in umbilical cord blood was significantly higher in the preeclamptic group (14.99 +/- 14.08 vs. 6.71 +/- 3.69 g/dL, p = 0.02). The decreased 11 beta-HSD activity is accompanied by an expected increase in umbilical cord blood cortisol level and decrease in fetal weight. This enzyme may play an important role in influencing fetal growth.

Cytofluorometric analysis of the neutrophil-specific BH2-Ag on cells from neonates to adults.

Monoclonal antibody (MAB) BH2C6 recognizes a plasma membrane antigen, the BH2-Ag, specifically expressed by human neutrophils. While studies with peripheral blood and bone marrow from healthy adults clearly demonstrate the absence of BH2-Ag from other cellular components except neutrophils, they also indicate that the BH2-Ag is expressed more strongly by mature than immature neutrophils. The purpose of this study was to determine the expression of the BH2-Ag by peripheral blood neutrophils from premature newborns to adults. Seventy-two donors were studied in six age groups: newborns <36 weeks of gestational age; newborns >36 weeks of gestational age; 0.5-2 years; 4-8 years; 12-17 years; >30 years. Expression of the BH2-Ag by peripheral blood neutrophils was examined by cytofluorography using MAB BH2-C6 directly labeled with fluorescein isothiocyanate (FITC). Neutrophils were reacted in parallel with FITC-MAB directed against CD11b, the alpha-chain of the CD11b/CD18 antigen (CR3). BH2-Ag is expressed by 98.3-99.6% of the neutrophils in all groups, and is absent on other blood cells, including those of very premature newborns. Statistical comparisons with respect to the mean fluorescence intensity of the FITC-MAB BH2C6 bound did not support a significant difference in the expression of BH2-Ag in any age group. CD11b expression was also detected in every individual studied and its mean fluorescence intensity correlated significantly with that of BH2Ag (p <0.001). The uniform presence of BH2Ag in every individual including a very premature infant suggests that BH2-Ag is likely to be an essential component of neutrophil development in humans. A highly significant correlation between the mean fluorescence intensity obtained with MAB BH2C6 and MAB CD11b suggests a possible interactive role of the two antigens in neutrophil development and/or function.

Inhibition of mammalian xanthine oxidase by folate compounds and amethopterin.

We have examined the effects of folate compounds and the folate analog amethopterin (methotrexate) as inhibitors of mammalian xanthine oxidase and have found that they offer potent inhibition of the enzyme. We have compared the inhibitory potency of folic acid and its coenzyme derivative tetrahydrofolic acid to that of allopurinol, a known inhibitor of xanthine oxidase, and have demonstrated that folic acid and tetrahydrofolic acid are severalfold more potent than allopurinol as inhibitors of xanthine oxidase. Comparative inhibition constants calculated were 5.0 X 10(-7) M for folic acid. 1.25 X 10(-6) M for tetrahydrofolic acid, and 4.88 X 10(-6) M for allopurinol. Incubation of xanthine oxidase with folic acid at a concentration of 10(-6) M abolished 94% of the enzymic activity within 1 min of incubation with the enzyme. At the same concentration, allopurinol was almost ineffective as an inhibitor of xanthine oxidase. The substrate xanthine protected the enzyme against total inhibition by folic acid. Reversibility of the enzymic inhibition by folic acid was demonstrated. Folic acid-inactivated enzyme was totally regenerated either by filtration through Sephadex G-200 or by precipitation with ammonium sulfate. 2-Amino-4-hydroxypteridine was a poor substrate for the enzyme but a potent inhibitor for the oxidation of xanthine by the enzyme. The inhibition constant calculated was 1.50 X 10(-6) M. In the presence of an excess of xanthine oxidase, neither folic acid nor tetrahydrofolic acid and allopurinol exhibited any change in intensity of their absorbance or in the wavelength of their maximal absorbance that might have been suggestive of substrate utility. The folate analog amethopterin was also determined a potent inhibitor of mammalian xanthine oxidase. The inhibition constant calculated was 3.0 X 10(-5) M.

Variations in human placental 11 beta-dehydrogenase and 11-oxoreductase activities of 11 beta-hydroxysteroid dehydrogenase enzyme during pregnancy.

Human placental 11 beta-hydroxysteroid dehydrogenase enzyme has an important role in controlling glucocorticoids reaching the fetus. Excess glucocorticoids impair fetal growth. Recent investigations show that the placenta is rich in NAD- and NADP-dependent 11 beta-hydroxysteroid dehydrogenase activity. Elucidation of the activities of both these isoforms is necessary to understand placental glucocorticoid metabolism. Hence we determined both NAD- and NADP-dependent 11 beta-hydroxysteroid dehydrogenase activities throughout pregnancy. 11 beta-dehydrogenase (oxidative) and 11-oxoreductase (reductive) activities of 11 beta-hydroxysteroid dehydrogenase were determined in 16 first-trimester (9-12 weeks) and 14 second-trimester (13-22 weeks) and 17 term (38-42 weeks) placentae. Both NAD- and NADP-dependent activities increased with pregnancy. The second-trimester NAD-dependent activity was higher than the first-trimester activity (p = 0.02). At term this activity was higher than during the second (p = 0.05) and first (p = 0.0002) trimesters. A similar increase was obtained with NADP isoform except that the difference between first and second trimesters was not significantly different at p = 0.05. The NADH-dependent 11-oxoreductase activity was also detected throughout the pregnancy. However, the activity at term was significantly higher than during the second (p = 0.005) and first (p = 0.001) trimesters. This increase may result in a concomitant increase of cortisol reaching fetus, thus helping fetal lung maturation.