Evidence of Chemical Stimulation of Hepatic Metabolism by an Experimental Acetanilide (FOE 5043) Indirectly Mediating Reductions in Circulating Thyroid Hormone Levels in the Male Rat

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl]oxy]acetamide(FOE 5043) is a new acetanilide-type herbicide undergoing regulatorytesting. Previous work in this laboratory suggested that FOE5043-induced reductions in serum thyroxine (T₄) levels weremediated via an extrathyroidal site of action. The possibilitythat the alterations in circulating T₄ levels were due to chemicalinduction of hepatic thyroid hormone metabolism was investigated.Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixturewas found to significantly increase the clearance of [¹²⁵I]T₄from the serum, suggesting an enhanced excretion of the hormone.In the liver, the activity of hepatic uridine glucuronosyl transferase,a major pathway of thyroid hormone biotransformation in therat, increased in a statistically significant and dose-dependentmanner; conversely, hepatic 5'-monodeiodinase activity trendeddownward with dose. Bile flow as well as the hepatic uptakeand biliary excretion of [¹²⁵I]T₄ were increased following exposureto FOE 5043. Thyroidal function, as measured by the dischargeof iodide ion in response to perchlorate, and pituitary function,as measured by the capacity of the pituitary to secrete thyrotropinin response to an exogenous challenge by hypothalamic thyrotropinreleasing hormone, were both unchanged from the controlled response.These data suggest that the functional status of the thyroidand pituitary glands has not been altered by treatment withFOE 5043 and that reductions in circulating levels of T₄ arebeing mediated indirectly through an increase in the biotransformationand excretion of thyroid hormone in the liver.     

Three dimensional analysis of microaneurysms in the human diabetic retina

The retinal vasculature of postmortem normal human and diabetic eyes was studied using an immunohistochemical technique in conjunction with confocal laser scanning microscopy. The technique, which stained for von Willebrand factor, allowed both large areas of the retinal vasculature to be visualised and abnormalities to be studied in detail without disturbing the tissue architecture. Only one microaneurysm, defined as any focal capillary dilation, was observed in 10 normal eyes but numerous microaneurysms were seen in 4 out of 5 diabetic retinas; counts varied between 0 and 26 per 0.41 mm² sample area. Microaneurysms were classified into 3 categories according to morphology: saccular, fusiform and focal bulges. Most were saccular, these having no preferred orientation. The majority of microaneurysms were associated with just 2 vessels suggesting they were unlikely to develop at vascular junctions. The majority were observed to originate from the inner nuclear layer and were therefore in the deeper part of the inner retinal capillary plexus. Variation in the staining of microaneurysms may correlate with endothelial dysfunction seen clinically as dye leakage during fluorescein angiography.     

Protein gene product (PGP) 9.5 as a reliable marker in primitive neuroectodermal tumours—an immunohistochemical study of 21 childhood cases

A number of antibodies to neural proteins have been used to demonstrate neuronal differentiation in primitive neuroectodermal tumours. One of them is protein gene product (PGP) 9.5, a neuronal protein isolated from brain, whose function is unknown at present. We have studied differentiation in 21 cases of primitive neuroectodermal tumours of the CNS in children. Immunocytochemical staining was performed for such neuronal markers as: PGP 9.5, neuron specific enolase and synaptophysin, a glycosylated protein associated with synaptic vesicles. Positive staining for PGP 9.5 was present in 16 cases (strong staining in 12), for neuron-specific enolase in 16 cases (strong staining in 10) and for synaptophysin in 10 cases (strong staining in six). Both PGP 9.5 and synaptophysin showed a clear staining pattern with less non-specific background than with neuron-specific enolase. Our findings demonstrate the value of using more than one antibody marker in assessing neuronal differentiation in tumours. The high incidence of positive staining with antibody to PGP 9.5 suggests that this is an essential marker in the panel of antibodies used for the identification of primitive neuroectodermal tumours.     

New Method for Imaging Innervation of the Renal Preglomerular Vasculature. Alterations in Hypertensive Rats

Objective : To develop a new method for viewing adrenergic innervation along renal preglomerular vessels; to assess nerve densities and vascular lesions along arcuate arteries (ArcA), arcuate arterial branches (ArcB), and interlobular arteries (ILA) in spontaneously hypertensive rats (SHR) and in angiotensin II (AngII) and in N^G‐nitro‐l ‐arginine methyl ester (l ‐NAME) hypertensive rats. Methods : Preglomerular vasculatures were isolated after HCl maceration and were immunostained against synaptophysin, a membrane protein of synaptic vesicles. Lesions were stained with Sudan black. Longitudinal nerve densities and relative frequencies of ArcA, ArcB, and ILA endowed with sudanophilic lesions were assessed separately. Results : Synaptophysin immunostaining revealed the vascular neural plexus. Nerves were adrenergic, as the plexus was destroyed by treatment with 6‐hydroxy dopamine. Vascular lesions were not seen in SHR, and increased nerve density was observed along ArcA and ILA. In l ‐NAME‐ and AngII‐hypertensive rats, vascular lesions affected predominantly ArcB and ILA, and nerve density was reduced by 12% and 28% (ArcA), 37% and 31% (ArcB), and by 55% and 34% (ILA), respectively, versus normotensive controls. Endothelin‐1 receptor blockade did not affect AngII‐induced hypertension but prevented both lesion development and reduction of density of the vascular neural plexus. Conclusions : The method we have devised provides a direct en face view of the vascular adrenergic innervation of isolated preglomerular vasculature. Measurements in hypertensive rat models suggest a link between vascular lesions and reduction in nerve density in hypertension. Endothelin‐1 likely plays a key role in mediating both vascular injury and altered vascular nerve density in hypertension.     

Drinking, the construction of ethnic iDentity and social process in a Western Australian youth subculture

This paper presents an anthropological analysis of the meaning of drinking for the male members of the Skinhead youth subculture in Perth, Western Australia. Perth Skinheads are an exported and modified form of the original English Skinhead subculture. Using participant observation as the primary research method, the style of drinking is analysed as one of the ways in which the members of this subculture express their English ethnicity and constitutive of the social processes which underpin the subculture. The article also explores the reasons why Perth Skinheads do not conform to a pattern of drinking in rounds held to be characteristic of some working class drinking groups.