The role of maternal thyroid hormones on the development of the brushtail possum, Trichosurus vulpecula

Thyroxine (T4) is a vital hormone for the development of mammals. To determine the role of maternal thyroid hormones on organ development, methimazole, an inhibitor of T4, was first administered via a minipump to 13 mothers with pouch young between days 10 and 80 post partum for 28 days. Three young survived and 10 of the young died at 104.0 +/- 10.8 days post partum (mean, SEM). Methimazole was then administered for 28 days to 6 lactating adult possums with pouch young at day 20 post partum. The effects of this treatment on the maternal plasma concentrations of T4 were monitored and the development of the lung, kidney and brain of the young were examined at day 90 post partum. There was no difference in the morphology of the lung, kidney and brain of pouch young at day 90 post partum whose mothers were treated with methimazole or saline. Thus methimazole administered to lactating possums for a short period early in lactation can cause the demise of the young about day 100 post partum although the cause of death is unknown. It is possible that the development of the central nervous system or some other vital organ has been inhibited, this altered state not being apparent morphologically. Nevertheless the marsupial appears to be similar to the eutherian in its requirement for thyroxine for normal development. However whereas this requirement is apparent during fetal development and around the time of birth in eutherians thyroxine is of importance during pouch development in marsupials.     

Reported changes in sexual behavior in response to AIDS in the United States

BACKGROUND: The AIDS epidemic has profoundly affected public health policy and everyday choices of individuals. Understanding the self-protective strategies adopted by the general population is crucial to designing appropriate and more effective primary AIDS prevention strategies. METHODS: A probability sample of the U.S. adult population in 1992, the National Health and Social Life Survey (n = 3,159), addressed detailed aspects of sexual behavior. How respondents changed their sexual behavior due to AIDS was recorded verbatim and categorized for analysis. RESULTS: Twenty-nine percent of U.S. adults reported some sexual behavior change, primarily, reducing numbers of partners (12%), using condoms more frequently (9%), selecting partners more carefully (7%), changing attitude toward sex (4%), and abstinence (3%). Individuals most at risk show the greatest propensity to change although the actual risk-reduction strategies and the meanings assigned to those strategies vary considerably. Strategies are not all compatible with each other nor equally likely to be adopted by individuals with different lifestyles. CONCLUSIONS: Self-protective strategies to avoid AIDS are widespread, but primary prevention efforts should be targeted to particular circumstances and the self-protective propensities of each individual.     

The changing mole. Additional warning signs of malignant melanoma

The causal involvement of bovine viral diarrhoea virus (BVDV) and border disease virus (BDV) infection in bovine and ovine abortion and perinatal mortality remain unclear. From 1992 until 1994, 213 bovine and 31 ovine foetuses as well as 36 calves and 25 lambs which had died perinatally were investigated. Tissue samples were tested for the presence of pestiviruses and serum or fluid from the body cavities were analysed for the presence of pestivirus antibodies. Detection of pestiviruses was performed by (i) cell culture isolation, (ii) antigen ELISA and (iii) immunohistochemical staining for viral antigen. For antibody-testing an indirect ELISA was used. In nine bovine foetuses and in two calves BVDV was isolated. Pestiviruses, most likely BDV were detected in one ovine foetus and three lambs. In 6% of the bovine and 11% of the ovine foetuses anti-pestivirus antibodies were detected. However, clinical features and history of bovine cases did not show a correlation with the diagnostic results, In contrast, the presence of central nervous system signs in neonatal lambs and the detection of BDV was correlated.     

Two functionally different Na/K pumps in cardiac ventricular myocytes

The whole-cell patch-clamp technique was used to voltage clamp acutely isolated myocytes at -60 mV and study effects of ionic environment on Na/K pump activity. In quiescent guinea pig myocytes, normal intracellular Na+ is approximately 6 mM, which gives a total pump current of 0.25 +/- 0.09 pA/pF, and an inward background sodium current of 0.75 +/- 0.26 pA/pF. The average capacitance of a cell is 189 +/- 61 pF. Our main conclusion is the total Na/K pump current comprises currents from two different types of pumps, whose functional responses to the extracellular environment are different. Pump current was reversibly blocked with two affinities by extracellular dihydro-ouabain (DHO). We determined dissociation constants of 72 microM for low affinity (type-1) pumps and 0.75 microM for high affinity (type-h) pumps. These dissociation constants did not detectably change with two intracellular Na+ concentrations, one saturating and one near half-saturating, and with two extracellular K+ concentrations of 4.6 and 1.0 mM. Ion effects on type-h pumps were therefore measured using 5 microM DHO and on total pump current using 1 mM DHO. Extracellular K+ half-maximally activated the type-h pumps at 0.4 mM and the type-1 at 3.7 mM. Extracellular H+ blocked the type-1 pumps with half-maximal blockade at a pH of 7.71 whereas the type-h pumps were insensitive to extracellular pH. Both types of pumps responded similarly to changes in intracellular-Na+, with 9.6 mM causing half-maximal activation. Neither changes in intracellular pH between 6.0 and 7.2, nor concentrations of intracellular K+ of 140 mM or below, had any effect on either type of pump. The lack of any effect of intracellular K+ suggests the dissociation constants are in the molar range so this step in the pump cycle is not rate limiting under normal physiological conditions. Changes in intracellular-Na+ did not affect the half-maximal activation by extracellular K+, and vice versa. We found DHO-blockade of Na/K pump current in canine ventricular myocytes also occurred with two affinities, which are very similar to those from guinea pig myocytes or rat ventricular myocytes. In contrast, isolated canine Purkinje myocytes have predominantly the type-h pumps, insofar as DHO-blockade and extracellular K+ activation are much closer to our type-h results than type-1. These observations suggest for mammalian ventricular myocytes: (a) the presence of two types of Na/K pumps may be a general property. (b) Normal physiological variations in extracellular pH and K+ are important determinants of Na/K pump current. (c) Normal physiological variations in the intracellular environment affect Na/K pump current primarily via the Na+ concentration. Lastly, Na/K pump current appears to be specifically tailored for a tissue by expression of a mix of functionally different types of pumps.     

Parkinson''s disease: from pallidotomy to L-dopa and back to pallidotomy

CR3 (iC3b receptor), composed of CD11b/CD18, is a beta 2 integrin. A protein that shares antigenic and structural homology with the alpha-chain of CD11b/CD18 has been isolated from the surface of Candida albicans. This molecule is thought to be essential in the pathogenesis of disseminated candidiasis. To evaluate the effects of anti-iC3b receptor antibodies on adhesion between human dermal microvascular endothelial cells (HDMEC) and C. albicans, and in treatment of candidal infection, a binding assay of C. albicans to cultured HDMEC was performed in vitro. An anti-iC3b receptor-specific monoclonal antibody was administered to mice infected with C. albicans. The mice were monitored for mortality and renal involvement by culture and histopathological findings. Flow cytometric analysis demonstrated surface expression of iC3b receptor on C. albicans. The adherence of C. albicans to HDMEC was significantly decreased by treatment with anti-iC3b receptor antibodies. Anti-iC3b receptor antibodies significantly increased the survival time and rate while lowering the renal fungal burden. The iC3b receptors are involved in the adherence of C. albicans to vascular endothelial cells and are likely to be involved in the pathogenesis of disseminated candidiasis. The increased survival in mice infected with C. albicans after treatment with anti-iC3b receptor antibodies indicates that this modality may be beneficial for future development of a new therapy for candidiasis.     

Accumulation and metabolism of low density lipoprotein-derived cholesteryl linoleate hydroperoxide and hydroxide by macrophages

Cholesteryl linoleate hydroperoxide (CLOOH) and hydroxide (CLOH) are present in human atheroma. The intracellular metabolism of low density lipoprotein (LDL)-derived CLOOH and CLOH remain undefined because extensive free radical-mediated LDL oxidation, which modifies LDL apolipoprotein B sufficiently to allow endocytosis by the scavenger receptor (ScR), also degrades CLOOH and CLOH. This problem was approached by first acetylating LDL lysine residues (AcLDL) to achieve protein modification, then exposing AcLDL to the aqueous radical donor 2,2'-azobis(2-amidinopropane) HCl (AAPH), to generate mildly oxidized AcLDL (OxAcLDL). Murine peritoneal macrophages incubated with OxAcLDL accumulated large quantities of CE and small, non-toxic quantities of CLOOH and CLOH in a time- and concentration-dependent manner, and accumulation was inhibited by fucoidin. Inhibition of acyl CoA: cholesterol acyltransferase during loading did not inhibit the accumulation of either CLOOH or CLOH, whereas NH4Cl decreased intracellular clearance of accumulated CLOOH from 68.3 +/- 1.7% to 35.3 +/- 1.0% over 12 h, suggesting lysosomal or pre-lysosomal accumulation. Intracellular clearance of unoxidized lipoprotein-derived CE decreased from 84.0 +/- 5.9% to 43.1 +/- 2.3% over 12 h when cells were loaded with AcLDL or OxAcLDL, respectively. Aggregation of mildly oxidized LDL, even without acetylation, also promoted cellular accumulation of CLOOH and CLOH. We conclude that intracellular accumulation of cholesteryl linoleate hydroperoxide and cholesteryl linoleate hydroxide can follow charge modification or aggregation of mildly oxidized LDL, and that LDL-derived oxidation products may inhibit hydrolysis of LDL-derived CE in foam cell macrophages.