Impairment of induction of delta-aminolevulinic acid synthase by gluconeogenic amino acids and carbohydrates in vitro.

This study was undertaken in a system of chick embryo liver cells incubated in Earle's Basal Salt Solution with hormones. Impairment of induction of delta-aminolevulinic acid synthase (ALAS) by allyl-isopropylacetamide (AIA) was observed in the presence of glucose. Fructose and various gluconeogenic substances including gluconeogenic amino acids had a similar effect.

Inhibition of experimental porphyria with colchicine.

Colchicine at the concentrations of 5 X 10(-7) - 5 X 10(-6) M decreased significantly both delta-aminolevulinic acid synthase activity and accumulation of porphyrins in monolayers of chick embryo liver cells induced by allyl-isopropylacetamide, by 3,5-diethoxycarbonyl-1,4-dihydrocollidine or by phenobarbitone. No effect was noted in non-induced cells. In rats, colchicine 0.

Effects of propranolol during pregnancy and development of rats. II. Adverse effects on development.

High doses of propranolol administered to rats during pregnancy and lactation cause inhibition of growth of the neonatal rats. Growth remains inhibited if drug treatment is continued after weaning. Cessation of drug administration after weaning leads to a nearly normal growth rate but a relatively long period elapses before normal weight is attained.

Evidence of abnormality of lymphocyte uroporphyrinogen synthase in family members of patients with lymphoproliferative diseases.

Patients with active lymphoproliferative diseases (LPD) were shown to have high activity of lymphocyte uroporphyrinogen synthase (L-UROS), the enzyme which converts porphobilinogen to uroporphyrinogen. The mean L-UROS activity of 64 first-degree relatives of patients with LPD was significantly higher than that of a control group and 45% of these relatives had pathological values of L-UROS. L-UROS activity was also determined in the spouses of 2 patients and was pathologically elevated in both.

The effects of metalloporphyrins, porphyrins and metals on the activity of delta-aminolevulinic acid synthase in monolayers of chick embryo liver cells.

The effect of various metals, porphyrins and metalloporphyrins on the activity of delta-aminolevulinate synthase (ALAS) was measured in monolayers of chick embryo liver cells in order to determine whether the metal moiety of heme or heme itself is the regulator of ALAS activity. Iron, magnesium, zinc, copper, manganese and nickel did not decrease ALAS activity in non-induced and in cells induced by allyl-isopropylacetamide (AIA). Cobalt decreased both non-induced and induced activity.

Recurrent bacteriuria and primary biliary cirrhosis: ABO blood group, P1 blood group, and secretor status.

Patients with primary biliary cirrhosis have an abnormally high incidence of urinary tract infection (35%). Susceptibility to urinary infection and other infectious diseases has been linked with certain blood group antigens and secretor status. We have therefore studied these characteristics in patients with primary biliary cirrhosis.

Effect of prolonged fasting on heme metabolism in the rat.

It is known that fasting may provoke an acute attack in patients with latent hepatic porphyrias. We examined the influence of fasting on some aspects of heme synthesis in rats. Urinary excretion of both uroporphyrin and coproporphyrin, as well as fecal elimination of protoporphyrin and coproporphyrin, were increased on fasting.

Bacteriuria and primary biliary cirrhosis.

Significant bacteriuria was found in 19% of 87 women with primary biliary cirrhosis, whereas in 89 women with other types of chronic liver disease bacteriuria was present in only 7%. In 74 women with rheumatoid arthritis 8% were bacteriuric. Midstream urine specimens obtained from 144 consecutive women with primary biliary cirrhosis attending hospital over a two year period showed that 50 (35%) developed bacteriuria during 12 months of follow up.

Erythrocyte uroporphyrinogen synthase activity as a possible diagnostic aid in the diagnosis of lymphoproliferative diseases.

Patients with active lymphoproliferative diseases were shown to have high activity of erythrocyte uroporphyrinogen synthetase (URO-S), the enzyme which converts porphobilinogen to uroporphyrinogen. In a few patients examined the lymphocyte URO-S was markedly increased. No correlation was found between the high URO-S activity and the degree of anemia, reticulocytosis, or the presence of hemolysis.

Evidence relating the inhibitory effect of cobalt on the activity of delta-aminolevulinate synthase to the intracellular concentration of porphyrins.

This study shows that the inhibition of ALAS activity caused by cobalt is directly correlated with the intracellular porphyrin concentration, thus indicating that cobalt exerts its inhibitory effect on ALAS activity as a result of the formation of cobalt-protoporphyrin.

The effects of succinylacetone (4,6-dioxoheptanoic acid) on delta-aminolevulinate synthase activity and the content of heme in monolayers of chick embryo liver cells.

Succinylacetone was shown to inhibit aminolevulinate dehydratase (5-aminolevulinate hydro-lyase (adding 5-aminolevulinate and cyclizing), EC 4.2.1.

The pancreas in primary biliary cirrhosis and primary sclerosing cholangitis.

In patients with primary biliary cirrhosis, the chronic cholestasis, salivary, and lacrimal hyposecretion suggest that the disease is a "dry gland" syndrome. To determine whether or not pancreatic damage occurs in primary biliary cirrhosis and other forms of chronic cholestasis, we have studied pancreatic structure and function in primary biliary cirrhosis, and primary sclerosing cholangitis. In a retrospective study, retrograde pancreatograms were abnormal in 43% of 35 patients with primary biliary cirrhosis and 15% of 20 patients with primary sclerosing cholangitis (p less than 0.

Vitamin D, hydroxyapatite, and calcium gluconate in treatment of cortical bone thinning in postmenopausal women with primary biliary cirrhosis.

Women with primary biliary cirrhosis malabsorb calcium, phosphate and vitamin D, and develop accelerated cortical bone thinning. We have assessed the value of parenteral vitamin D, oral hydroxyapatite (HA), and calcium gluconate (CG) in the treatment of cortical bone thinning in primary biliary cirrhosis. Sixty-four postmenopausal women with primary biliary cirrhosis were assigned randomly into three groups: one group receiving no mineral supplements (control), one group receiving HA, and one group receiving CG.

Immunocytochemical identification of caeruloplasmin in hepatocytes of patients with Wilson's disease.

Decreased serum caeruloplasmin levels in patients with Wilson's disease have been attributed to decreased caeruloplasmin synthesis in the hepatocyte. An immunoperoxidase procedure was used to identify caeruloplasmin in liver biopsies. The pattern of staining in biopsies from patients with Wilson's disease did not differ from the pattern seen in normal adult or neonatal liver.

T cell subsets in autoimmune and HBV-induced chronic liver disease, HBs antigen carriers with normal histology and primary biliary cirrhosis: a review of the abnormalities and the effects of treatment.

Review of the limited data currently available on the ratios of helper (OKT4+) to suppressor (OKT8+) T cells in autoimmune liver disease (primary biliary cirrhosis and chronic active lupoid hepatitis) and virally induced liver disease indicates that this OKT4+:OKT8+ ratio is elevated in autoimmune liver disease manifesting hyperglobulinemia. This ratio was decreased in patients with chronic hepatitis B virus infection during the HBe antigen-positive phase of viral replication but reverts to normal in the majority of patients in whom HBV replication has ceased (HBe antibody-positive) and these individuals exhibit normal liver histology. Patients with HBV infection who continue to show elevated ratios after the appearance of HBe antibody also continue to exhibit signs of active hepatitis.

Radiological patterns of cortical bone modelling in women with chronic liver disease.

The pattern of cortical bone modelling in healthy and diseased populations can be derived from simple measurements taken from radiographs of tubular bones. To determine the pattern of bone modelling in women with chronic cholestatic and parenchymal liver diseases, these parameters have been measured in 83 women with primary biliary cirrhosis (PBC), 34 with steroid-treated chronic active hepatitis (CAH) and 27 with parenchymal liver disease (PLD) not treated with corticosteroids. Bone modelling profiles have been compared in these groups with expected pattern in healthy females.

The effect of porta-systemic shunting on liver, brain and kidney zinc concentrations in the rat.

Patients with alcoholic cirrhosis have subnormal liver zinc concentrations, and excessive urinary zinc excretion. It has been suggested that diversion of dietary zinc into the systemic circulation through porta-systemic shunts may be a major factor influencing the organ distribution of zinc in these patients. To test this hypothesis, we randomized Sprague-Dawley rats into a sham-operated group, and a group subjected to partial portal-vein occlusion (PPVO), which induces the formation of extensive porta-systemic collaterals.

The effect of oral copper loading and portasystemic shunting on the distribution of copper in the liver, brain, kidney, and cornea of the rat.

In Wilson's disease, redistribution of copper from the liver to extrahepatic tissue coincides with the development of liver disease and cirrhosis. We have considered the possibility that portasystemic shunting may be a factor determining the organ distribution of copper in patients with liver disease. Thirty-two Sprague-Dawley rats were randomized into a sham-operated group, and a group subjected to partial occlusion of the portal vein (PPVO).