Selenium,cadmium, zinc,and copper in human kidney cortices and post mortem indices of hypertension

Kidneys from 32 autopsied Caucasian human subjects aged 16–60 were frozen then lyophilized while the flasks were kept in insulating containers. (Subjects with evidence of extensive weight loss, chronic renal failure, or carcinoma were not included). Replicate samples of cortex were removed, weighed, and wet-ashed in HNO₃?HClO₄. Zn, Cd, and Cu were estimated by atomic absorption spectrophotometry with the 2261 Å line used for Cd background correction. Se was estimated by fluorescence with DAN in a Turner fluorimeter, but a #74 Kodak Wratten filter was added to minimize the 500 nm interference noted by E. Pickett (personal communication, 1980). Means and variability for the three elements in kidney cortex were similar to those in a North Carolina study as was Cd/(Cd+Zn)×100. Cortical Cd (P<0.05), Zn (P<0.10), and Cd/(Se·Zn) (P<0.05) increased with age, whereas Se showed no significant relationship with age. Age², nonlinear effects of age, had a slight influence upon Cu (P<0.05) only if data were not adjusted for gender. There was no influence of ageper se upon Cu with or without adjustment for gender. The scatter diagrams of element concentrations plotted vs age contained several provocative “outlier” values. A positive association of kidney cortex Cd concentration, or Cd/(Se ·Zn), with postmortem indices of hypertension existed only if age, gender, and age² were omitted from the multiple regression equation. This adjustment was not included in a similar study of North Carolina cases and appears to be the source of the major difference in their respective inferences drawn about the positive relationship of kidney cortex Cd with evidence of hypertension. This difference in statistical models does not however account for the failure of the West Virginia sample to indicate a protective role of kidney cortex Se suggested for the North Carolina subjects. Larger samples, drawn from regions differing in Se abundance, will be necessary to test the latter question adequately.     

Gonadotrophs following removal of the ovaries: a fine structural study of human pituitary glands.

The fine structure of gonadotrophs has been investigated in surgically removed pituitary glands of 12 women who because of disseminated breast cancer, underwent bilateral ovariectomy at various periods before hypophysectomy. Compared with the adenohypophyses of 3 non-ovariectomized female subjects with diabetes mellitus, electron microscopy revealed that two cell types were affected by gonadectomy. These cell types corresponded to those which were regarded as FSH gonadotrophs and LH gonadotrophs in previous studies. In addition in the adenohypophyses stimulated by removal of the ovaries, intermediary cell types began to appear suggesting a transformation of LH gonadotrophs to FSH gonadotrophs. The most conspicuous change following gonadectomy was the formation of castration cells. These cells arose from FSH gonadotrophs and exhibited ultrastructural features interpreted as representing the morphologic manifestations of sustained hypersecretion of gonadotrophins. It seemed that castration cells have a limited life span and in their advanced stages of development they show ultrastructural signs indicative of irreversible involution.     

Calcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis

Variation in PPP3CC, the gene that encodes the γ isoform of the calcineurin catalytic subunit, has been reported to be associated with schizophrenia. Because of its low expression level in most tissues, there has been little research devoted to the specific function of the calcineurin Aγ (CNAγ) versus the calcineurin Aα (CNAα) and calcineurin Aβ (CNAβ) catalytic isoforms. Consequently, we have a limited understanding of the role of altered CNAγ function in psychiatric disease. In this study, we demonstrate that CNAγ is present in the rodent and human brain and dephosphorylates a presynaptic substrate of calcineurin. Through a combination of immunocytochemistry and immuno-EM, we further show that CNAγ is localized to presynaptic terminals in hippocampal neurons. Critically, we demonstrate that RNAi-mediated knockdown of CNAγ leads to a disruption of synaptic vesicle cycling in cultured rat hippocampal neurons. These data indicate that CNAγ regulates a critical aspect of synaptic vesicle cycling and suggest that variation in PPP3CC may contribute to psychiatric disease by altering presynaptic function.