Farouk M. Ali

Tyrosine transaminase activity in normal and cirrhotic liver

Most cirrhotics have tyrosinemia and subnormal tyrosine tolerance; in some the ability to metabolizep-hydroxyphenylpyruvic and homogentisic acids is impaired. In previous studies, the initial transamination appeared to be the rate-limiting step. In this study, hepatic tyrosine transaminase activity was compared in liver biopsies from eight noncirrhotic and ten cirrhotic subjects to determine whether the subnormal tyrosine tolerance was related to decreased maximal activity of this enzyme. Fasting plasma tyrosine in the cirrhotics (133±43 μmol/liter) was significantly higher (P<0.005) than in the noncirrhotic subjects (64±25 μmol/liter). Tyrosine transaminase activity in the cirrhotic livers (42±11 μmol PHPA/g liver/hr, or 0.47±0.1 μmol PHPA/mg protein/hr) was not significantly different from the enzyme activity in the noncirrhotic liver (43±7 μmol PHPA/g liver/hr, or 0.39±.12 μmol PHPA/mg protein/hr.) Thus elevated tyrosine levels in cirrhotics cannot be explained by decreased tyrosine transaminase activity in the liver, and other explanations must be sought.

Impaired monoamine oxidase activity in dogs with portacaval shunt

Abstract In dogs with portacaval shunt, hypertyraminemia could result from either impaired degradation by monoamine oxidase (MAO) and/or from failure of tyramine to reach this enzyme. MAO activity was evaluated in liver obtained from dogs before and after the construction of an end-to-side portacaval shunt. Diversion of portal blood from the liver by a portacaval shunt resulted in a significant (P −1 · hr −1 ] as compared to controls [28.7 ± 6.3 nmoles PHA formed · (mg protein) −1 · hr −1 ]. Activity was maximally reduced in shunted dogs with stages II and III hepatic encephalopathy. In addition, more than a 50 per cent reduction in both the V max and the K m of hepatic MAO for tyramine was noted in shunted dogs as compared to controls. Similar kinetic abnormalities [post-shunt, K m 52.63 ± 14.3, V max 3.8 ± 1.2 vs sham group, K m 120.1 ± 22.3 μM tyramine, V max 14.3 ± 4.5 nmoles PHA · (mg protein) −1 · hr −1 ], as well as decreased MAO activity [post-shunt, 1.85 ± 0.83 vs sham group, 6.7 ± 2.1 nmoles PHA formed · (mg protein) −1 · hr −1 ], were found in cerebral cortex from encephalopathic dogs with portacaval shunt. In summary, defective MAO activity may contribute to many of the pathophysiologic events observed in dogs with portacaval anastomosis. Such abnormalities could explain the hypertyraminemia and encephalopathy that have been reported in patients and experimental animals with liver disease.

Platelet-monoamine oxidase activity in Reye's syndrome.

Summary Platelet and liver monoamine oxidase (MAO) activity (mean ± SD) was evaluated in patients with liver-biopsy-proven Reyes syndrome. MAO was measured by a radioenzymatic technique with [3H]tyramine as a substrate. A marked decrease in MAO activity [3.3 ± 2.4 nmol of [3H]4-hydroxyphenylacetic acid formed X (mg protein)-1 x h-1] was observed in platelets on admission in all patients (n = 13) with Reyes syndrome when compared with hospitalized patients without liver disease (n = 8) [9.8 ± 2.5 nmol of [3H]4-hydroxyphenylacetic acid formed x (mg protein)-1 x h-1] and with liver disease (n = 10) [9.1 ± 2.0 nmol of [3H]4-hydroxyphenylacetic acid formed x (mg protein)-1 x h-1]. Following recovery from the disease, platelet MAO approached levels that were not significantly different from those of controls. Contrastingly, reduction of hepatic MAO in Reyes syndrome was similar to that seen in patients with liver disease of different etiologies. These studies suggest that reduced platelet MAO activity is a specific abnormality in Reyes syndrome, and it may be representative of generalized impairment of mitochondrial function in these patients. Furthermore, the pattern of liver and platelet MAO activity in Reyes syndrome may allow for the differentiation of this disease from other hepatopathologic conditions.

Evaluation of transsphenoidal hypophysectomy in the management of patients with advanced malignant melanoma

Transsphenoidal hypophysectomy was performed in 13 patients with advanced malignant melanoma. Although three minor responses were observed, there were no complete or partial responses. All three patients with bone pain had a decrease in discomfort lasting 1–2 months. All five patients with minor responses or stable disease had postoperative decreases in the excretion of the dihydroxyphenylalanine (DOPA) metabolite 3‐O‐methyldopamine; all but one patient with clinical progression had postoperative increases in excretion. Average survival of those whose postoperative excretion fell (143+ days; range, 60–217+) was significantly longer (P < 0.004) than that of those whose postsurgical values rose (30 days; range, 15–58).