STRUCTURE AND FUNCTION OF URIDINE DIPHOSPHATE GLUCURONOSYLTRANSFERASES

1. The uridine diphosphate (UDP)-glucuronosyltransferases (UGT) are a family of enzymes that catalyse the covalent addition of glucuronic acid to a wide range of lipophilic chemicals. They play a major role in the detoxification of many exogenous and endogenous compounds by generating products that are more polar and, thus, more readily excreted in bile or urine. 2. Inherited deficiencies in UGT forms are deleterious, as exemplified by the debilitating effects of hyperbilirubinaemia and neurotoxicity in subjects with mutations in the enzyme that converts bilirubin to its more pola. glucuronide. 3. The UGT protein can be conceptually divided into two domains with the amino-terminal half of the protein demonstrating greater sequence divergence between isoforms. This region apparently determines aglycone specificity. The aglycone binding site is presumed to be a ‘loose’ fit, as many structurally diverse substrates can be bound by the same UGT isoform. The carboxyl-terminal half, which is more conserved in sequence between different isoforms, is believed to contain a binding site for the cosubstrate UDP glucuronic acid (UDPGA). 4. Uridine diphosphat. glucuronosyltransfera.se is localized to the endoplasmic reticulum (ER) and spans the membrane with a type I topology. The putative transmembrane domain is located near the carboxyl terminus of the protein such that only a small portion of the protein resides in the cytosol. This cytosolic tail is believed to contain an ER-targeting signal. The major portion of the protein is located in the ER lumen, including the proposed substrate-binding domains and the catalytic site. 5. The microsomal membrane impedes the access of UDPGA to the active site, resulting in latency of UGT activity in intact ER-derived microsomes. Active transport of UDPGA is believed to occur in hepatocytes, but the transport system has not been fully characterized. Uridine diphosphate glucuronosyltransfer-ase activity is also highly lipid dependent and the enzyme may contain regions of membrane association in addition to the transmembrane domain.     

Clinical and demographic characteristics of 15 patients with repetitively assaultive behavior

The 15 patients with the highest numbers of assaultive incidents over a one year period in a state mental hospital were identified and information collected regarding a variety of clinical and demographic characteristics. The results showed a group of patients who are relatively young, manifest severe symptomatology that is generally unresponsive to treatment, and have now been hospitalized continuously for greater than four years. The patients experienced the onset of symptoms as teenagers in most cases, showed poor psychosocial adjustment beyond childhood, and had positive family histories for mental illness or alcohol abuse. Patients with psychotic disorders predominated and tended to have positive symptoms rated as severe to very severe on the Global Rating Scale for Psychosis. Patients with nonpsychotic or personality disorders always showed a high frequency of self-injurious behavior in addition to their aggressive behavior toward others. A number of patients had a history of head trauma with EEG abnormalities. This information provides a starting point for subsequent studies examining potential distinctions between this subpopulation of patients and others, the motivation and circumstances of such incidents, and the interaction between the behaviors and their effects on those around them.     

Anger Management Using Cognitive Group Therapy

Cognitive therapy has been applied to the treatment of various psychosocial phenomena, including ange et, the literature contains no reference to applying these concepts within a group setting. Using the basic premises of cognitive and group therapies, the author discusses anger arousal and anger management using a cognitive model in a group therapy setting.     

Angiotensin II-induced proteinuria and expression of the podocyte slit pore membrane protein, nephrin.

Sir, Proteinuria is a cardinal manifestation of kidney disease directlycontributing to its progression by inducing tubulointerstitialpathology [1]. The effectiveness of blockade of the renin–angiotensinsystem (RAS) in slowing the progression may be, at least inpart, due to the powerful anti-proteinuric actions of both angiotensinconverting enzyme (ACE) inhibitors and angiotensin receptorblockers (ARBs). However, the mechanisms whereby blockade ofthe RAS reduces the transglomerular passage of protein is multi-factorialand incompletely     

Manipulation: investigation of a proposed mechanism

The purpose of this study was to investigate whether spinal manipulation alters the posteroanterior stiffness of the manipulated region. Thirty subjects with no history of thoracic pain or contraindication to manipulation participated. The manipulation studied was a posteroanterior thrust applied to the T_4–5 spinal level. The effect of the manipulation was compared to a control intervention of supine lying. The posteroanterior stiffness of all subjects was measured at the T₄ and T₅ levels initially, and remeasured after both the manipulation and control interventions. Change scores relating to the change in posteroanterior stiffness due to manipulation and due to the control intervention were computed. A t-test comparing the change scores between interventions revealed no significant difference. However, the posteroanterior stiffness at T₅ was found to be significantly greater than at T₄. It was concluded that in the case of asymptomatic subjects these results did not provide support for the hypothesis that posteroanterior stiffness is altered by manipulation.     

Thrombin stimulates release of endothelin and vasopressin, but not substance P, from isolated rabbit tracheal epithelial cells

Release of endothelin, vasopressin and substance P from isolated rabbit tracheal epithelial cells was monitored after incubation for 2 h with thrombin (10 U/ml) in the presence and absence of cycloheximide (100 μg/ml) and 2-nitro-4-carboxyphenyl-N, N-diphenylcarbamate (NCDC, 0.6 mM). Thrombin stimulated the release of endothelin and vasopressin. Inhibition of the thrombin-stimulated release of endothelin and vasopressin by cycloheximide (44and 56%, respectively) and NCDC (59 and 88%, respectively) indicates that the release of these peptides is at least partially dependent on the ability of thrombin to stimulate protein synthesis and activate the phospholipase C pathway. Substance P, which is also present in tracheal epithelial cells, was not released by thrombin.