Endogenous opioids and TSH secretion in azotemic male rats

The role of endogenous opioids in the control of thyroid-stimulating hormone (TSH) secretion in uremic male rats was investigated using the narcotic antagonist naloxone. In order to eliminate the effect of weight loss due to uremia-induced anorexia as a cause of altered TSH secretion in uremia, we also studied a group of normal control animals who were pair-fed with the uremic animals, so that their weights were comparable to that of the uremic animals. Naloxone administration produced a significant increase in the basal concentration of TSH response to TRH (5 micrograms i.v.) was significantly blunted in the uremic animals compared to the normal controls and the starved animals. Naloxone administration did not alter the peak thyrotropin-releasing hormone (TRH) stimulated TSH response in any of the experimental groups of rats. Because of the possibility that the effects of naloxone on TSH secretion in the uremic rats were related to impaired clearance of the naloxone in those animals, an additional group of normal rats was given twice the dose of naloxone administered to the uremic animals. The higher dose of naloxone was similarly without effect on the basal or TRH-stimulated TSH secretion in this group. The data suggest that experimental renal failure is associated with diminished sensitivity of the thyrotroph to TRH stimulation and that this blunted sensitivity cannot be abolished by blockade of endogenous opioids by naloxone. Opioid blockade does, however, increase basal TSH secretion in uremic animals, suggesting an increase in endogenous opioidergic tone in uremia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Random phage mimotopes recognized by monoclonal antibodies against the pyruvate dehydrogenase complex-E2 (PDC-E2).

Dihydrolipoamide acetyltransferase, the E2 component of the pyruvate dehydrogenase complex (PDC-E2), is the autoantigen most commonly recognized by autoantibodies in primary biliary cirrhosis (PBC). We identified a peptide mimotope(s) of PDC-E2 by screening a phage-epitope library expressing random dodecapeptides in the pIII coat protein of fd phage using C355.1, a murine monoclonal antibody (mAb) that recognizes a conformation-dependent epitope in the inner lipoyl domain of PDC-E2 and uniquely stains the apical region of bile duct epithelium (BDE) only in patients with PBC. Eight different sequences were identified in 36 phage clones. WMSYPDRTLRTS was present in 29 clones; WESYPFRVGTSL, APKTYVSVSGMV, LTYVSLQGRQGH, LDYVPLKHRHRH, AALWGVKVRHVS, KVLNRIMAGVRH and GNVALVSSRVNA were singly represented. Three common amino acid motifs (W-SYP, TYVS, and VRH) were shared among all peptide sequences. Competitive inhibition of the immunohistochemical staining of PBC BDE was performed by incubating the peptides WMSYPDRTLRTS, WESYPDRTLRTS, APKTYVSVSGMV, and AALWGVKVRHVS with either C355.1 or a second PDC-E2-specific mAb, C150.1. Both mAbs were originally generated to PDC-E2 but map to distinct regions of PDC-E2. Two of the peptides, although selected by reaction with C355.1, strongly inhibited the staining of BDE by C150.1, whereas the peptide APKTYVSVSGMV consistently inhibited the staining of C355.1 on biliary duct epithelium more strongly than the typical mitochondrial staining of hepatocytes. Rabbit sera raised against the peptide WMSYPDRTLRTS stained BDE of livers and isolated bile duct epithelial cells of PBC patients more intensively than controls. The rabbit sera stained all size ducts in normals, but only small/medium-sized ductules in PBC livers. These studies provide evidence that the antigen present in BDE is a molecular mimic of PDC-E2, and not PDC-E2 itself.     

Prognostic value of the intravenous 14C-aminopyrine breath test compared to the Child-Pugh score and serum bile acids in 84 cirrhotic patients.

The prognostic value of the intravenous 14C-aminopyrine breath test (ABT) in liver cirrhosis was compared to that of the well-established multiparametric Child-Pugh classification and that of serum bile acids, an endogenous parameter of liver function for which a prognostic value in patients with liver cirrhosis has been demonstrated previously. 84 patients with liver cirrhosis were studied. 32 of the patients died during the observation period. Survival was analyzed for periods of 3, 6 and 12 months after examination. For all chosen observation periods, the Child-Pugh score was of prognostic value. ABT gave prognostic information for periods of 6 and 12 months of survival, but was by far inferior to the Child-Pugh score. Serum bile acids in our population did not yield prognostic information at any time interval studied. We conclude that in our group of cirrhotic patients, the prognostic value of the Child-Pugh classification was by far superior to quantitative liver function tests in predicting survival.     

Angiomyolipoma of the kidney with lymph node involvement.

A case of renal angiomyolipoma with regional lymph node involvement is added to 20 cases previously reported. This represents the 11th case reported in a non-tuberous sclerosis patient. The electron microscopic features of the tumor are discussed and correlated with the light microscopic findings.     

Toxicokinetics of monochloroacetic acid: a whole-body autoradiography study

Monochloroacetic acid (MCA) is a toxic chemical used as a herbicide and in the synthesis of various organic compounds. MCA has also been shown to be present in chlorinated drinking waters. In order to understand the mechanism of MCA toxicity, we studied the tissue distribution of [1-14C]MCA in rats, by whole-body autoradiographic technique. Male Sprague-Dawley rats were given a tracer dose of [1-14C]MCA [6.8 micrograms/100 g (40 mu Ci) body weight] by tail vein and euthanized at different time intervals (5 min, 1, 4, 12, 24 and 48 h). The animals were embedded in carboxymethyl cellulose and frozen immediately. Frozen animals were sectioned and processed using whole-body autoradiographic techniques. Analysis of developed sections showed that at 5 min, there was a rapid accumulation of 14C-activity in the kidney cortex and stomach walls. The radioactivity was rapidly removed from the circulation. There was high accumulation of 14C-activity in the myocardial tissues. The liver was also loaded with MCA and/or its metabolites. After 1 h following administration of [14C]MCA, radioactivity was extensively excreted into the small intestinal lumen. the accumulation of 14C-activity in the brain, thymus, salivary glands and tongue was prominent at 1 h. After 4 h the liver and other tissues started to eliminate most of the radioactivity. Contrary to other tissues, however, the central nervous system, thymus and pancreas started to accumulate the radioactivity at later time periods. These observations suggest the accumulation of MCA and/or its metabolites into hydrophilic tissues at earlier time periods and into lipophilic tissues at later times.