Testosterone regulation of sex differences in fetal lung development.

Fetal lung development, in particular surfactant synthesis, exhibits a sexual dimorphism. Dihydrotestosterone (DHT) has been shown to delay fetal pulmonary surfactant production, but the potential role for testosterone is unknown. Both testosterone and DHT are potent masculinizing hormones, yet in some instances, an end organ specificity for DHT is present. We hypothesized that the delay in fetal lung surfactant production is dependent upon DHT such that inhibition of the synthesis of DHT from the precursor hormone testosterone would eliminate the sex difference by allowing the male fetus to produce surfactant at the female level. We tested this hypothesis using 17 beta-N,N-diethylcarbamoyl-4-aza-4-methyl-5-alpha-androstane-3-one (4-MA), a potent inhibitor of the enzyme 5 alpha-reductase, which converts testosterone into DHT. First, studies were performed in vivo. 4-MA (20 mg/kg/day) or an equivalent volume of vehicle was injected into pregnant rabbits from Day 12 through Day 26 of gestation. On Day 26, the fetuses were delivered, the lungs were lavaged, and fetal sex was noted. Treatment with 4-MA resulted in a lack of any male-female difference in the anogenital distance and no DHT was detected in the serum of any treated fetus. Phosphatidylcholine (PC), saturated phosphatidylcholine (SPC), and sphingomyelin (S) were measured in the lung lavage, and were expressed as the ratios of PC to sphingomyelin (PC:S) and SPC to sphingomyelin (SPC:S). Sex differences in the PC to sphingomyelin ratio of 4-MA-treated fetuses (female PC:S ratio, 1.43 +/- 0.14; male PC:S ratio, 1.00 +/- 0.13 [mean +/- SE]; P = 0.04) and in the SPC:S ratio of the 4-MA-treated group (female SPC:S ratio, 0.68 +/- 0.10; male SPC:S ratio, 0.35 +/- 0.10; P = 0.03) were present after treatment with 4-MA. The effect of testosterone and of 4-MA on fibroblast pneumonocyte factor (FPF) production was studied in vitro. Fetal rat lung fibroblasts were cultured to confluence with either no added androgen, DHT, testosterone, or testosterone plus 4-MA, and conditioned media for FPF were prepared. Conditioned media were added to fetal Type II cell cultures and FPF activity was measured as the degree of stimulation of the incorporation of [3H] choline into SPC. The conversion of radiolabeled testosterone to DHT by the fibroblasts was inhibited by 4-MA (10(-5) M). Conditioned media from untreated female fibroblasts stimulated with cortisol exhibited significant FPF activity ([3H]choline incorporation into SPC, 140 +/- 17% of control).(ABSTRACT TRUNCATED AT 400 WORDS)     

Synopsis of Adenanthera (Leguminosae-Mimosoideae)

The generic relationship, the palynology and the infrageneric classification of the tropical Asian-Australian-Melanesian genus Adenanthera is discussed. Twelve species are recognized. Adenanthera microsperma and A. tamarindifolia are reinstated. A. kostermansii and A. marina are described as new, and A. malayana is divided in two subspecies, ssp. malayana from Malaya and Sumatra and ssp. andersonii from Borneo. All species are illustrated.     

Structured modeling of a microbial system: I. A theoretical study of lactic acid fermentation

Most fermentation models presented in the literature are unstructured, i.e., the biomass composition is assumed constant during all operating conditions. These models are unable to simulate experiments carried out at widely different operating conditions. It is therefore interesting to examine simple structured models where knowledge of the cell physiology is taken into account in the modeling phase. In this article, a simple structured model is presented. The model is based on experimental work with the lactic acid bacteria Streptococcus cremoris, but due to the similarities in basic metabolism for many microorganisms it is applicable also for other fermentation system. The basic assumption in the model is that the biomass can be divided into two parts (compartments)-an active part and a mainly inactive structural part. The size of the active part has a pivotal role in the model.     

Sequence comparison of the rDNA introns from six different species of Tetrahymena.

We have studied the sequence variation of the rDNA intron among six species of Tetrahymena. From these data, the intron appears to be relatively well conserved in evolution. We have evaluated the sequence variations among the most distant of these species in relation to the secondary structure model for the intron RNA of Cech et al. (Proc. Natl. Acad. Sci. U.S.A. 80, 3903 (83)). Most of the sequence variation in the four new sequences reported here is found in single stranded loops in the model. However, in four cases we found nucleotide substitutions in duplex stem regions, two of them involving compensating base pair changes. Interestingly, one of these is found in a region that is known to be dispensable in the in vitro splicing reaction suggesting differences between the in vivo and in vitro reactions. One of the single nucleotide deletions is found in the so-called "internal guide sequence" which has been implicated in the alignment process during splicing. In conclusion, none of the observed natural sequence variations are in disfavor of the proposed secondary structure model.     

Monocyte chemotaxis in patients with nonseminomatous testicular carcinoma

Summary The chemotactic responsiveness of blood monocytes was tested in 16 patients with nonseminomatous testicular carcinoma before, during, and after chemotherapy. All the patients initially had monocyte chemotaxis within the normal range. No correlation with the histology of the tumor, the clinical stage, or the presence in serum of -fetoprotein and human chorionic gonadotropin was observed. Plasma from the patients did not inhibit the chemotaxis of normal monocytes, and serum from the patients contained no chemotactic factor inhibitor. During intensive chemotherapy with cis-platinum, bleomycin, and vinblastine a reversible defect in chemotaxis occurred without correlation to the development of fever. Two months after the completion of chemotherapy the chemotactic responsiveness was unchanged compared with pretreatment values. In conclusion, this study shows normal monocyte chemotaxis in patients with testicular carcinoma, which is in contrast to reports on a variety of other solid tumors.     

Recurrent mutation pressure does not explain the prevalence of the marker (X) syndrome

Summary In order to test the hypothesis that the high prevalence of the mar(X) syndrome is caused by a high mutation rate in male germ cells only, the fraction of new mutants among mothers of probands in 112 informative families has been examined by segregation analysis among their brothers and sisters. The estimated fraction of new mutants among these mothers is much lower than expected if a stable equilibrium existed between an unusually high mutation rate and a selective disadvantage of mentally retarded, male and female mar(X) carriers. Hence, the above-mentioned hypothesis could not be confirmed.     

Variation in human T lymphotropic virus III (HTLV-III) antibodies in homosexual men: decline before onset of illness related to acquired immune deficiency syndrome (AIDS).

Western blot analysis was used to document the development and changes in human T lymphotropic virus III (HTLV-III) antibody among Danish homosexual men followed longitudinally over three years. Reactivity against p15, p24, and p55 appeared earliest. After seroconversion the antibody concentration fluctuated, but in one instance a steady decline in banding intensity was seen during the 18 months before onset of the acquired immune deficiency syndrome (AIDS) and throughout the remaining eight months of his life.     

Human keratinocytes that have not terminally differentiated synthesize laminin and fibronectin but deposit only fibronectin in the pericellular matrix

Fibronectin and laminin production by human keratinocytes cultured in serum-free, low-calcium medium without a fibroblast feeder layer were examined by several techniques. By indirect immunofluorescence, fibronectin but not laminin appeared as short radial fibrils between the cells and the substratum, and in the pericellular matrix. Synthesis of fibronectin and laminin by 7-day keratinocyte cultures was determined by 18 hr 35S-methionine metabolic labeling followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. Fibronectin accounted for 2.9% of total synthesized protein, 26.5% of fluid phase protein secretion, and 4.3% of deposited ECM protein. In contrast, only 0.1% of the total synthesized protein was laminin, little (6.3%) of this product was secreted, and none of this product was deposited in the ECM. Our results indicate that human keratinocytes under culture conditions that prevent terminal differentiation in vitro can synthesize, secrete, and deposit fibronectin in the extracellular matrix. Although these cells synthesize laminin, they secrete very little and deposit no detectable laminin in the matrix under these culture conditions. From these data we believe that fibronectin may play an important role in the interaction of epidermal cells with connective tissue matrix during wound healing or morphogenesis in in vivo situations in which the epidermis is not terminally differentiated.