The anticonvulsant activity of a series of phenanthridine basic ethers.
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Biomedical subjects
Publications and source records attributed to G R Brown.
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The testis is a complex organ in which local control is achieved by signalling between its constituent cells. Herein we describe the responses of cultured rat testicular cells and a mouse Sertoli cell-line to stimulation by endothelin and ATP, and elsewhere we have shown that rat peritubular myoid cells possess phosphoinositidase C-coupled V1a-vasopressin receptors identical to those of liver (Howl, J. et al, 1995, Endocrinology 136: 2206-2213). 1. Peritubular myoid cells from pre-pubertal rats responded through ETA receptors with PtdIns(4,5)P2 hydrolysis [EC50 for endothelin-1 (ET-1) approximately 0.4 nM], elevation of intracellular [Ca2+], and tyrosine phosphorylation of a variety of cellular proteins. They also showed enhanced adenylate cyclase activity, with an EC50 for ET-1 of approximately 3 nM, also through ETA receptors. Pharmacological elevation of [cAMP] did not immediately change the ET-1-stimulated formation of inositol phosphates, but attenuated the response after several hours. 2. Pre-pubertal rat Sertoli cells showed no detectable responses to ET-1, but responded to FSH with elevated [cAMP] and to ATP with PtdIns(4,5)P2 hydrolysis. PtdIns(4,5)P2 hydrolysis was equally responsive to ATP and UTP, and so appears to be activated by P2U-purinergic receptors. This response was enhanced by protein kinase C inhibition and attenuated by PKC activation. 3. Despite its lack of effect on rat Sertoli cells in primary culture, ET-1 provoked PtdIns(4,5)P2 hydrolysis in the TM4 murine Sertoli cell line (EC50 approximately 0.6 nM), and this response was negatively regulated by protein kinase C activation. 5. No receptor-stimulated activation of phosphoinositase C was detected in 'germ cell' populations, but the non-specific G protein activator A1F4-provoked inositol phosphate accumulation in these cells, so demonstrating their potential to respond through yet to be identified G protein-coupled receptors with phosphoinositidase C activation. 6. Immunoblotting studies showed the presence in rat testis of phosphoinositidase C-beta 1 and the alpha-subunits(s) of the G-protein(s) Gq and/or G11. These studies show that testicular myoid and Sertoli cells use at least three G protein-coupled receptors (V1a-vasopressins, ETA-endothelin and P2U-purinergic) to signal through phosphoinositidase C activation, that ET-1 can activate multiple signalling pathways in myoid cells, and that the ET-1-stimulated phosphoinositidase C responses of myoid and Sertoli cells have different regulatory characteristics.
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The authors report on the use of the Rey-Osterrieth Complex Figure Copy (ROC) and Memory (ROM) test as a bedside screening measure of cognitive impairment in 67 HIV-seropositive persons (43 men, 24 women). HIV-seropositive individuals scored significantly worse than 49 HIV-seronegative matched individuals (33 men, 16 women) in the control group on the ROC (P = 0.045, effect size = 0.39), but not on the ROM test. The scores did not correlate with stage of HIV infection, CD4a cell counts, cerebrospinal fluid parameters, or measures of affective state. No gender effects on performance were noted. It is concluded that while cognitive deficits may occur early in asymptomatic HIV disease, the ROC/ROM test as the authors used it is not a useful screening tool for clinicians. The study also suggests that the growing number of HIV-positive women should be included in neuropsychological studies of early HIV disease.
As part of a military universal HIV screening program, 442 men were assessed for the presence of DSM-III-R defined psychiatric disorders and symptoms of anxiety and depression after notification of HIV seroconversion. Of them, 84.4% were in the earliest, asymptomatic stages of disease at the time of interview (96% did not have AIDS). The Structured Clinical Interview for DSM-III-R and Structured Interview Guide for the Hamilton Anxiety and Depression Scales were used. Relevant comparisons were made to Epidemiologic Catchment Area prevalence data. HIV seropositive men were more likely than age-matched men in the community to have current diagnoses of major depression (ages 18-44) and anxiety disorders (ages 25-44). Higher lifetime rates of major depression and alcohol use disorder, and high current prevalence of sexual dysfunction (21.7%) were noted. We conclude that men who become HIV seropositive have high rates of mood and substance use disorders prior to knowledge of seroconversion, and that early in the course of HIV infection men are at risk for developing major depression, anxiety disorders, and disorders of sexual desire.
What are the relative roles of mothers and infants in maintaining proximity with one another? How do the relative roles of the mother and infant change over time? What do proximity measures tell us about the mother-infant relationship? Questions such as these have been addressed using proximity indices devised by Hinde and coworkers in the 1960s. In this paper, I review how these indices are derived and discuss what they do, and do not, infer about the nature of the mother-infant relationship. An additional index is proposed which indicates whether the mother or the infant is responsible for the majority of changes in proximity.
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The adsorption of bilirubin from aqueous phosphate buffer solutions (pH = 7.8) containing bovine serum albumin (BSA) by polyacrylamide resins, with pendants consisting of the oligopeptides (Arg)5(Ala)3-, (Arg)2(Ala)3-, (Lys)5(Ala)3-, His(Arg)2(Ala)3-, has been studied at 0 degrees C under N2. The ability of the oligopeptide-resins to retain adsorbed bilirubin in the presence of BSA follows the order (Arg)5(Ala)3- greater than (Arg)2(Ala)3- greater than (Lys)5(Ala)3- = His(Arg)2(Ala)3-resin. The (Arg)5(Ala)3-resin is able to abstract the second bilirubin on the albumin assuming that BSA binds two bilirubin molecules strongly.
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