Thyroid goiter is a common condition that is often associated with iodine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic search on a single large Canadian family with 18 cases of nontoxic multinodular goiter in which 2 individuals also had papillary lesions highly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TSHR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid cancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric methods indicates that only a very small proportion of familial NMTC (point estimate 0.001, support intervals 0-.6 under a dominant model) is attributable to MNG1.

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The pathophysiological mechanisms responsible for cerebral edema and hepatic encephalopathy (HE), two major central nervous system complications of acute liver failure, have not been fully elucidated. The current consensus of opinion is that neurotransmitter-related mechanisms, 1-3 rather than a primary deficit of cerebral energy metabolism, 4,5 are responsible. Alterations of both glutamatergic 2 and serotoninergic 1 systems have been described in HE resulting from experimental acute liver failure, and there is a growing body of evidence that central noradrenergic systems may also be implicated in the pathogenesis of HE in this setting. Hepatectomy, 3,6,7 liver devascularization, 8 and thioacetamide-induced acute liver failure 1 in the rat consistently result in decreases in brain concentrations of noradrenaline (NA), and hepatectomy results in increased NA release into ventriculocisternal perfusates, 9 suggesting that increased noradrenergic activity could contribute to the pathogenesis of HE in acute liver failure. However, little (if any) information is available on extracellular brain concentrations of monoamines in experimental liver failure, nor of the status of the recently characterized multiple monoamine receptor subtypes in this condition. As part of a series of studies to address these issues, the present study had two objectives, namely to evaluate the effects of acute liver failure resulting from hepatic devascularization on: 1) extracellular brain concentrations of NA in relation to the severity of HE and to the appearance of brain edema; and 2) central NA receptor subtypes, at coma stages of encephalopathy, in these animals. MATERIALS AND METHODS MaterialsRinger' s solution constituents, sodium phosphate (monobasic), ethylenediaminetetraacetic acid, sodium octanesulfonate, Tris-HCl, ascorbic acid, WB4101, phentolamine, serotonin, epinephrine, NA, and isoproterenol were purchased from Sigma Chemical Co. Surgical TechniquesMale Sprague-Dawley rats (Charles River, St. Constant, Quebec, Canada) (range, 175-200 g at the time of surgery), were anesthetized with halothane, and an end-to-side portacaval anastomosis was performed as previously described. 2 The inferior vena cava was partially clamped, and an elliptical piece of vein was removed. The portal vein was ligated, cut, and an end-to-side anastomosis (shunt [SH]) was performed under a dissecting microscope, according to the guidelines of Lee and Fisher. 10 Total surgery time was Ϸ15 min. Sham-operated animals (matched for weight) were similarly anesthetized, and, following laparotomy, the inferior vena cava and portal vein were clamped for 15 minutes (sham [SM]). After surgery, the animals had free access to standard laboratory food and water. All rats were housed under constant conditions of temperature, humidity, and light cycles.Twenty-four hours after portacaval shunt or laparotomy, an