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Pregnancy is a major risk factor for coccidioidal dissemination. Because rates of Coccidioides immitis growth and endospore release are stimulated in vitro by levels of unbound progesterone and 17 beta-estradiol that are achievable, in vivo, in the sera of pregnant women (i.e., 10(-9) to 10(-8) M), a specific-hormone-binding system in C. immitis was sought. Fungal cytosols were incubated with tritiated steroids plus or minus radioinert steroids to identify specific binding systems. All five strains of C. immitis tested exhibited specific saturable binding for progestin, estrogen, androgen, and (to a lesser extent) corticosterone and glucocorticoid hormone classes. Only low or inconsistent estrogen or androgen binding was found in Blastomyces dermatitidis and Torulopsis glabrata. Cryptococcus neoformans, Paracoccidioides brasiliensis, and non-albicans Candida species showed no binding. Scatchard analysis of progestin and estrogen binding in C. immitis revealed a high-capacity, low-affinity binding system that was unaffected by RNase and DNase, but 40 to 60% degraded by trypsin or heating. Ammonium sulfate precipitation resolved a high-affinity, low-capacity binding system (Kd = 1.24 X 10(-9) to 3.60 X 10(-8) M; number of binding sites = 0.014 to 0.20 pmol/mg of protein). The Kd of this system is sufficient to compete for unbound hormone in the sera of pregnant women. The high-capacity, low-affinity system may serve as a repository for hormone before its attachment to the specific binder. These studies suggest that the effects of nanomolar concentrations of sex hormones on C. immitis may be mediated by a specific cytosol protein-binding system and that stimulatory events observed in vitro may have relevance for the mechanism of coccidioidal dissemination in pregnancy.

The presence or absence of venous thrombosis was determined by the technique of autologous 111indium-labelled platelets in 64 patients following reduction and fixation of fractures of the neck of femur. Venous thrombosis was found in 41 (64%) of these patients. Compared to the thrombosis-negative group, the thrombosis-positive group had a significantly lower mean serum antithrombin, and higher mean antithrombin consumption during clotting in the immediate preoperative period. No significant differences were seen between the two groups in plasma ATIII activities, fibrinogen, alpha-2-macroglobulin, serum lipoproteins or age. Significant correlations were seen between ATIII activities and lipoprotein fractions; these are discussed.

A swedish isolate of bovine papillomavirus type 1 (BPV1) was cloned and a 4807 base pairs long sequence was determined, covering the entire late region of the BPV1 genome and strategic parts of the early region. The sequence reveals two large uninterrupted reading frames, designated L1 and L2, which encode tentative polypeptides with molecular weights of 55.5 and 50.0 K. The promoter region for early transcription and the common 3'-end of early transcripts were identified in the sequence by performing S1 nuclease analysis of RNA isolated from a BPV1 transformed cell line. A detailed comparison between the established sequence and sequences from human papillomavirus type 1a (HPV1a) (1) and another BPV1 isolate (2) was also carried out. Only five differences were found when the sequences of the two BPV1 isolates were compared, two of which are located in reading frame L2. The results revealed furthermore that the genomes of BPV1 and HPV1a appear to be organized in a very similar fashion and the homology between reading frames L1 in BPV1 and HPV1 were particularly striking. A comparison of the established BPV1 sequence with sequences from SV40 and polyomavirus revealed no significant homology.

We have evaluated the endocrine changes in 10 male subjects with hemochromatosis. Two subjects initially had aplastic anemia, and the remainder had idiopathic hemochromatosis. Four of the ten patients had diabetes mellitus. Sexual dysfunction (impotence and/or decreased libido) was observed in 8 subjects. Six patients had subnormal testosterone levels; FSH levels were almost uniformly low, but LH concentrations were more variable. Only three patients had normal testosterone responses to hCG. Hypothyroidism, free T4 less than 0.9 ng/dl, was present in 4 subjects, and the etiology was heterogeneous. Basal prolactin levels were elevated in 2 patients and failed to respond adequately to TRH in 2 other patients. Growth hormone reserve was normal in all but 1 patient, and pituitary-adrenal reserve was normal in all but 1 patient. We conclude that disturbances in both pituitary and end-organ function are observed in hemochromatosis. These central and end-organ defects may exist alone or simultaneously. Hypogonadism is almost universal, and is a consequence of defective function of the hypothalamic-pituitary axis and/or primary Leydig cell disturbance. Other evidence of pituitary disturbance are observed but are rather uncommon.

Five infants enrolled in a day care center (DCC) developed invasive disease due to Haemophilus influenzae type b during a 25-week period. The isolates from four patients had identical outer membrane proteins and were biotype 1. Although rifampin prophylaxis was recommended on two different occasions, retrospective surveys demonstrated that 39 and 60%, respectively, of infants failed to receive the agent for various reasons. Pharyngeal cultures were obtained from infants, their families and DCC staff after prophylaxis was given the second time. Forty-seven % of DCC infants had positive cultures, and 59% of their households had at least one carrier of the invasive strain. Rifampin prophylaxis administered a third time to infants and members of their households was unsuccessful in eradicating the invasive Haemophilus influenzae type b strain from DCC infants. The possible reasons for failure of rifampin in this DCC outbreak included incomplete understanding by physicians and health department officials of the factors affecting a DCC outbreak of Haemophilus influenzae type b disease and failure properly to implement rifampin prophylaxis to all contacts and the index cases.

Protamine sulfate (salmine), a basic protein with a molecular weight of 4,626 +/- 109, is a known antiheparin agent which in the absence of heparin demonstrates an anticoagulant activity. To date, much work has been done to elucidate the interaction of heparin with thrombin and its physiologic inhibitor, Antithrombin III (ATIII). Little is known, however, about the mechanism of anticoagulant action of protamine sulfate and its mode of thrombin inactivation. We provide information about the interaction of protamine sulfate with purified, labeled thrombin and ATIII through binding experiments in which protamine is shown to inhibit the inactivation of thrombin by ATIII. Furthermore, we show in clotting assays that protamine sulfate has an inhibitory effect on thrombin in the conversion of fibrinogen to fibrin, and that this inhibition is concentration dependent, partial, and reversible.

Two hundred and eighty-eight primary breast tumours were examined for the presence or absence of oestrogen (REc) and progesterone (RPc) receptors. Analysis has shown a relative interdependence between the steroid receptor status of primary breast cancer and other prognostic variables such as histological grade, lymphocytic infiltration and tumour elastosis. There were significant associations between epithelial cellularity, stromal fibrosis and the value of REc in those tumours in which the receptor was present. Cellularity and fibrosis were unrelated to the presence or absence of oestrogen receptor. By contrast, neither the presence or absence nor the value of RPc could be related to cellularity or fibrosis. The value of REc and RPc analysis as an indicator of prognosis was examined in a sub-group of 175 patients receiving no additional treatment following mastectomy. Overall relapse-free survival (RFS) was no different for those patients with receptors compared to those without them (REc P = 0.11, RPc P = 0.7). There was no difference in RFS of receptor positive and negative tumours when the axillary node status was taken into account.