Anticomplement receptor activity in the serum of patients with primary biliary cirrhosis.

Patients with primary biliary cirrhosis have a defect in the receptor mediated clearance of complement coated erythrocytes by fixed macrophages of the reticuloendothelial system. To investigate the probable mechanism of this defect peripheral blood monocytes were isolated from nine patients with primary biliary cirrhosis and seven control subjects and the ability of these cells to form rosettes with complement coated, IgM-sensitised sheep erythrocytes was assessed. Primary biliary cirrhosis peripheral blood monocytes formed rosettes to the same extent as control peripheral blood monocytes (71.0 +/- 7.1% [SEM] versus 73.3 +/- 4.3%) suggesting normal complement receptor function of primary biliary cirrhosis peripheral blood monocytes. When primary biliary cirrhosis or control peripheral blood monocytes were preincubated with primary biliary cirrhosis serum, however, the per cent of peripheral blood monocytes that formed rosettes was decreased: 2.4 +/- 0.8 and 3.1 +/- 1.3 fold respectively. To study this phenomenon further, fractions containing IgG or IgM synthesised by cultures of control or primary biliary cirrhosis lymphocytes were prepared. Rosette formation was not affected by exposure to fractions containing control or primary biliary cirrhosis IgG or control IgM, but was markedly inhibited (6.0 +/- 4.8 fold) by exposure to fractions containing primary biliary cirrhosis IgM. Similar results were obtained when freshly isolated peripheral blood monocytes or peripheral blood monocytes that had been cultured for 7-10 days--that is, macrophages, were used. Assuming that one can draw inferences concerning the status of fixed macrophages from data obtained using peripheral blood monocytes, the results of this study suggest that the complement specific defect in reticuloendothelial system clearance function in primary biliary cirrhosis is not caused by abnormality in the functional status of complement receptors on fixed macrophages but rather by a factor present in the serum of patients with primary biliary cirrhosis that has the capacity to inhibit the adherence of complement coated erythrocytes to complement receptors present on the surface of fixed macrophages. This serum factor does not appear to be a complement component but rather a product of peripheral blood mononuclear cells, other than IgG.     

Interleukin-6 production by peripheral blood monocytes in patients with chronic liver disease and acute viral hepatitis.

The in vitro production of the acute-phase mediator interleukin-6 by peripheral blood monocytes derived from patients with various liver diseases was studied. Compared with healthy controls (n = 45; 860 +/- 92 U/ml, mean +/- SEM), monocytes from patients with chronic hepatitis B produced significantly lower amounts of interleukin-6 (n = 14; 424 +/- 126 U/ml) after stimulation with lipopolysaccharide (p = 0.02), whereas monocytes from patients with chronic hepatitis non-A, non-B secreted normal amounts of interleukin-6 (n = 13; 672 +/- 151 U/ml; n.s.). In contrast, monocytes of patients suffering from alcoholic liver cirrhosis (n = 22; 1310 +/- 153 U/ml) or primary biliary cirrhosis (n = 6; 1450 +/- 186 U/ml) produced higher amounts of interleukin-6 than healthy control individuals (p = 0.03, respectively). Lipopolysaccharide-stimulated monocytes derived from patients with acute hepatitis A, B and non-A, non-B showed an interleukin-6 production not different from that seen in healthy control individuals and did not experience a discernible change during the course of the acute disease. These results suggest that the production of the acute-phase mediator interleukin-6 varies in chronic liver disease in accordance with various etiologies with a reduced lipopolysaccharide-inducible interleukin-6 response in chronic hepatitis B and an enhanced response in alcoholic liver cirrhosis and primary biliary cirrhosis.     

Assessment of the (14C) aminopyrine breath test in liver disease.

Different methods of performing the (14C) aminopyrine breath test have been assessed. A tracer dose of 2 muCi without a loading dose and with a single breath collection at two hours was the method selected, since it gave the best discrimination between patients with hepatocellular diseases and normal subjects (5.2 +/- 0.2%, mean +/- SEM). Reduced values occurred in patients with chronic active hepatitis (with and without cirrhosis) (1.5 +/- 0.2%), alcoholic cirrhosis (1.7 +/- 0.4%) and hepatitis (2.5 +/- 0.3%), and late primary biliary cirrhosis suggesting defective microsomal function with respect to demethylation. Normal results were common in early primary biliary cirrhosis. Two weeks of prednisolone therapy caused some improvement in the breath test in nine of 10 patients with chronic active hepatitis. It is concluded that the (14C) aminopyrine breath test is a simple test for detecting hepatocellular dysfunction, but has no obvious diagnostic advantage over the determination of serum aspartate transaminase and two hour post-prandial bile-acids.     

Serum dolichols in chronic cholestatic liver diseases

BACKGROUND/AIMS: Dolichols are long-chain polyisoprenoid alcohols. It has been suggested that they modify membrane fluidity, stability and permeability. Some lysosomal diseases are associated with elevated serum dolichol levels. Liver has been suggested to play an important role in the regulation of serum dolichol levels and biliary excretion of dolichols has been proposed to be the main elimination route for dolichols from the body. The possible effect of liver diseases on serum dolichol, however, is not known. METHODS: We therefore studied the effect of early or intermediate primary biliary cirrhosis, primary sclerosing cholangitis and alcoholic liver cirrhosis on serum dolichol concentration. Furthermore, serum dolichol content was measured in patients with end-stage primary biliary cirrhosis, primary sclerosing cholangitis and chronic active hepatitis, waiting to be transplanted. RESULTS: As compared to age-adjusted controls, serum dolichol was significantly increased in early and intermediate primary biliary cirrhosis (451+/-56 ng/ml vs. 225+/-13 ng/ml, p<0.0001) and primary sclerosing cholangitis (315+/-16 ng/ml vs. 224+/-7 ng/ml, p<0.0001). However, in alcoholic liver cirrhosis serum dolichol was unaffected. Serum dolichol content was also significantly elevated in patients with end-stage primary biliary cirrhosis (844+/-210 ng/ml vs. 225+/-13, p<0.001) and chronic active hepatitis (594+/-198 vs. 224+/-7 ng/ml, p<0.02). Furthermore, in patients with liver diseases serum dolichol concentration correlated positively with serum high density lipoprotein (HDL)-cholesterol (r = +0.50, p<0.0001). CONCLUSIONS: Serum dolichol levels are elevated in all stages of chronic cholestatic liver diseases but not in alcoholic liver cirrhosis. Impaired biliary excretion of dolichols appears to be the primary explanation for this finding.     

Value of serum immunoglobulins in the diagnosis of liver disease

Serum immunoglobulins were determined in 145 consecutive patients with biopsy-proven steatosis, alcoholic hepatitis, alcoholic hepatitis with fibrosis, alcoholic hepatitis with cirrhosis, inactive cirrhosis, chronic active alcoholic hepatitis, chronic active hepatitis, primary biliary cirrhosis and nonspecific hepatitis. IgM was both a sensitive (90.5%) and specific (86.2%) marker for primary biliary cirrhosis, and mean IgM levels were higher in primary biliary cirrhosis than in other diagnostic categories (p less than 0.05). IgA levels were most commonly elevated in alcoholic liver disease (p less than 0.005). IgA detected 95% of alcoholic disease, but was poorly specific (41.1%). A trend of rising IgA with increasing severity of alcoholic injury was observed, but the differences were not significant. IgG was most commonly elevated in chronic active hepatitis and alcoholic hepatitis with cirrhosis, but the IgG values did not differ significantly from those found in other diagnostic categories. Our results substantiate assertions of a diagnostic sensitivity for elevated IgA in alcoholic liver disease and IgM in primary biliary cirrhosis. With the exception of IgM in primary biliary cirrhosis, however, serum immunoglobulins are not specific markers of liver histology.     

Evidence of an increased nitric oxide production in primary biliary cirrhosis

OBJECTIVE: Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS: Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS: Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55+/-1.75 arbitrary units vs 1.95+/-0.57 and 0.84+/-0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7+/-192.0 microg/L vs 51.1+/-34.3 and 38.0+/-11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS: Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.     

Serum complement in chronic liver disease

Total serum haemolytic complement activity (CH(50)) and the serum concentrations of both the third and fourth components of the complement system (C3 and C4) have been measured in 29 control subjects, 92 patients with chronic hepatocellular disease, and eight patients with large duct biliary tract obstruction. The mean C4 concentration was reduced in all types of chronic liver disease studied. However, the mean CH(50) and C3 values were increased in compensated primary biliary cirrhosis, were relatively normal in non-cirrhotic chronic active hepatitis, and were decreased in cryptogenic cirrhosis, particularly when ascites was present. There was a significant correlation between CH(50) and C3 in patients with chronic liver disease but no correlation between CH(50) and C4 or between C3 and C4. Raised values for CH(50) and C3 in primary biliary cirrhosis may be due at least in part to concomitant cholestasis since these values tend to be raised in patients with large duct biliary tract obstruction. Although primary biliary cirrhosis, chronic active hepatitis, and cryptogenic cirrhosis are considered to be part of a spectrum of chronic liver disease associated with disturbed immunity, the results of this study emphasize that there are clearly definable differences between these diseases in terms of the pattern of changes in serum complement.     

Neutrophil adherence in chronic liver disease and fulminant hepatic failure.

Abnormal adherence of neutrophils to nylon fibre in vitro was found in blood from 17 of 51 (33.3%) patients with chronic or acute liver disease of different aetiologies. Patients with chronic liver disease had a much wider range of values than the controls and the sub-group with alcoholic cirrhosis had significantly higher adherence (72.4 +/- SD 6.2%) than that of controls (65.8 +/- SD 5.2%). The patients with chronic active hepatitis (68.2 +/- 12.7%) or primary biliary cirrhosis (69.2 +/- 6.6%) were not different from controls. Significantly reduced neutrophil adherence (56.2 +/- 8.7%) was found in blood from patients with fulminant hepatic failure. These abnormalities in neutrophil adherence may be due to the effects of the split components of serum complement and dependent on the degree and duration of exposure of the neutrophils. Defects in neutrophil adherence may in part contribute to the increased susceptibility to infection in patients with acute and chronic liver disease.     

Defects in serum attractant activity in different types of chronic liver disease.

Serum attractant activity, measured in 57 patients with chronic liver disease, was significantly reduced in 66% of the 27 patients with alcoholic liver disease and in 29% of the 17 patients with chronic active hepatitis, but was normal in 13 patients with primary biliary cirrhosis despite the presence of established cirrhosis in nearly half of them. In patients with alcoholic liver disease, but not in those with chronic active hepatitis, there was a correlation between the serum defect and severity of liver disease. The defect could not be related to the deficiency of key complement components, raised concentrations of IgA or G or the concurrent presence of bacterial infection. These findings suggest that the aetiology of liver disease may be an important factor in the development of serum attractant abnormalities.     

Detection of male DNA in the liver of female patients with primary biliary cirrhosis

BACKGROUND/AIMS: Primary biliary cirrhosis is a chronic cholestatic liver disease characterized by progressive inflammatory destruction of bile ducts, with eventual hepatic fibrosis and cirrhosis. Since primary biliary cirrhosis affects predominantly middle-aged women and has pathological similarities to hepatic graft-versus-host-disease, we investigated whether fetal cell microchimerism might be involved in the development of this disease. METHODS: The presence of Y-chromosome-specific sequences was analyzed by polymerase chain reaction using peripheral blood mononuclear cells from women with primary biliary cirrhosis (n=18) and healthy (control) women (n=18), and by in situ hybridization of liver biopsy sections from women with primary biliary cirrhosis (n=19) and women with chronic hepatitis C or alcoholic liver disease (n=20). RESULTS: Male cells were detected in liver biopsy specimens of 8 of 19 patients (42%) with primary biliary cirrhosis. Y-chromosome-containing cells were not seen in any of the liver biopsy specimens from women with chronic hepatitis C or alcoholic liver disease. Male cells were detected in peripheral blood mononuclear cells from one healthy control at a level of 1 male cell per 10(6) female cells, but were not detected in peripheral blood mononuclear cells of women with primary biliary cirrhosis. CONCLUSIONS: The presence of male cells in the liver of women with primary biliary cirrhosis raises the possibility that fetal cell microchimerism may be involved in the pathogenesis of this chronic liver disease.     

Soluble interleukin 2 receptor in acute viral hepatitis and chronic liver disease

Serum levels of soluble interleukin 2 receptor were determined in patients with acute viral hepatitis and patients with various chronic liver diseases. In addition, the ability of peripheral blood mononuclear cells of patients with alcoholic cirrhosis to generate soluble interleukin 2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin 2 receptor concentrations in all patients with acute viral hepatitis were found to be significantly elevated (1,319 +/- 527 units per ml) during the first week after onset of disease, as compared to healthy control individuals (375 +/- 102 units per ml; p less than 0.0005) and declined toward normal levels during the course of the illness. Similarly, patients suffering from chronic liver disease such as alcoholic liver cirrhosis (1,172 +/- 507 units per ml), primary biliary cirrhosis (619 +/- 190 units per ml) or chronic active HBsAg+ hepatitis (941 +/- 357 units per ml) showed increased serum soluble interleukin 2 receptor concentrations (p less than 0.0005 vs. controls, respectively). In vitro mitogen stimulation of peripheral mononuclear cells derived from patients with alcoholic cirrhosis resulted in a soluble interleukin 2 receptor production not different from that seen in healthy individuals, suggesting that elevated soluble interleukin 2 receptor serum levels seen in this disease are not the result of an increased synthesis by circulating lymphocytes. Due to the ability of soluble interleukin 2 receptor to bind free interleukin 2--thus making it a potential immunoregulatory molecule--its high serum levels could explain some of the immunologic abnormalities observed in acute and chronic liver disease.     

Serum lysyl oxidase activity in patients with various liver diseases

Serum lysyl oxidase activity was examined in patients with various liver diseases. The activity of the enzyme was detected mainly in the serum fraction of the supernatant 80% saturated with (NH4)2SO4, and its molecular weight was estimated to be about 30,000 by Sephadex G-150 column filtration. Mean serum lysyl oxidase activity in 18 healthy controls was 129 +/- 50 (+/- SEM) cpm/ml and was significantly increased in patients with acute hepatitis, chronic active hepatitis, alcoholic liver disease and primary biliary cirrhosis, but not in those with chronic inactive hepatitis or liver cirrhosis. Serum lysyl oxidase activity was not correlated with the histological grade of hepatic fibrosis, but appeared to reflect active hepatic fibrogenesis in patients with liver diseases.     

Depression of peripheral blood monocyte aryl hydrocarbon hydroxylase activity in patients with liver disease: possible involvement of macrophage factors

Aryl hydrocarbon hydroxylase activity was detectable in cultured macrophage monolayers of peripheral blood monocyte origin. Peripheral blood monocytes were isolated from patients with biopsy-confirmed liver disease and healthy volunteers. Macrophage monolayers were prepared and incubated at 37 degrees C. After 24 hr, the aryl hydrocarbon hydroxylase activity and cellular protein concentration were assayed on cell homogenates. The monocyte aryl hydrocarbon hydroxylase activity in cultured macrophages from normal volunteers was 1.23 +/- 0.16 (n = 19). The aryl hydrocarbon hydroxylase activity in macrophage cultures from patients with biopsy-confirmed liver disease was 0.48 +/- 0.05 (n = 20). This represents a significant (61%) decrease in monocyte aryl hydrocarbon hydroxylase compared to controls. The 20 patients have established cirrhosis or early stage liver disease. The established cirrhosis group includes alpha 1-antitrypsin deficiency-associated cirrhosis; primary biliary cirrhosis; alcoholic (Laennec's) cirrhosis; cryptogenic cirrhosis, and hemochromatosis. Early stage liver disease is attributed to methotrexate (Stage III), early stage primary biliary cirrhosis and alpha 1-antitrypsin deficiency. Our results indicate that the depression in monocyte aryl hydrocarbon hydroxylase activity is greater in patients with established cirrhosis than early stage liver disease. Our results further suggest that cultured monocytes from patients with liver disease spontaneously release soluble factors into the culture medium. Incubation of this medium, containing macrophage factors, with isolated hepatocytes significantly depress hepatocyte aryl hydrocarbon hydroxylase activity compared to medium obtained from cultures of monocytes from normal volunteers.(ABSTRACT TRUNCATED AT 250 WORDS)     

Protease Inhibitors in Liver Disease

Measurements of the principal protease inhibitors were carried out in patients with two types of chronic liver disease: alcoholic cirrhosis and primary biliary cirrhosis. Measurement of the two major protease inhibitors operative in the haemostatic mechanism—that is, antithrombin III and α₂-antiplasmin—showed significantly reduced levels in the alcoholic cirrhosis group, who satisfied clinical and biochemical criteria of impaired hepatocellular function, but not in the primary biliary cirrhosis group, who had relatively good preservation of hepatocellular function. Significant correlation of levels of both these major protease inhibitors with the serum albumin concentration was also found. No evidence of disseminated intravascular coagulation was detected, and therefore failure of synthesis by the liver is the likely explanation of the low levels noted.     

Uptake and degradation of soluble aggregates of IgG by monocytes of patients with rheumatoid arthritis: relation to disease activity.

Monocytes from patients with rheumatoid arthritis (RA) and rheumatoid vasculitis have a diminished ability to degrade soluble complexes of aggregated IgG in the absence (mediated by Fc receptors) as well as in the presence of complement (C) (mediated by (Fc + C) receptors). To investigate whether a relation exists between the receptor mediated degradation of aggregated IgG by adherent monocytes and disease activity a longitudinal study was performed in 79 patients with RA and rheumatoid vasculitis over a period of 16 months. Adherent monocytes were incubated in vitro with 125I labelled IgG aggregates of restricted size in the absence or presence of fresh serum and the percentage of catabolised IgG aggregates was measured. Cross sectionally the degradation of aggregated IgG by monocytes, mediated by Fc and (Fc + C) receptors, correlated significantly with disease activity as scored by the Ritchie articular index, the presence of extra-articular features, and circulating immune complexes. A high number of Fc receptors on monocytes correlated with diminished degradation, whereas high numbers of complement receptors 1 and 3 correlated with enhanced degradation of aggregated IgG mediated by both Fc and (Fc + C) receptors. The degradation of aggregated IgG by monocytes did not correlate with disease activity in individual patients followed up longitudinally. When patient groups were formed according to the results of longitudinal studies, however, degradation of aggregated IgG mediated by Fc and (Fc + C) receptors was significantly decreased in patients with rheumatoid vasculitis and in patients with active RA in comparison with patients with inactive RA and healthy controls. Patients with active RA and rheumatoid vasculitis also expressed significantly more Fc receptors and less complement receptors on the monocytes than patients with inactive RA. Drug treatment did not correlate with receptor expression or the degradation of aggregated IgG by monocytes either in cross sectional or longitudinal studies. It is concluded that in RA disease activity is related to receptor expression and the degradation of soluble immune aggregates by monocytes.     

Human alveolar macrophage antibacterial activity in the alcoholic lung.

Alcoholic individuals are predisposed to respiratory infections. However, mechanisms of perturbations leading to increased susceptibility to lung infections of individuals with alcoholic liver cirrhosis (ALC) are not fully understood. We studied the antibacterial activity and oxidant generation (before and after stimulation by phorbol myristate acetate or opsonized zymosan) of alveolar macrophages from 16 patients with ALC. Our results were compared with those obtained from 12 healthy control subjects, from 8 patients with primary biliary cirrhosis (PBC), and from 8 alcoholic individuals without cirrhosis. All were nonsmokers, had normal chest X-rays, and did not present evidence of lung infection 3 months before. The total number of cells recovered by bronchoalveolar lavage did not significantly differ between control subjects and patients. The cellular viability of alveolar macrophages (trypan blue exclusion) was greater than 90% in all cases. The antibacterial activity of alveolar macrophages versus Staphylococcus aureus was severely impaired in ALC (-21 +/- 8.2%) whereas it was normal in PBC (52 +/- 4.2%), in alcoholic subjects (44.6 +/- 5.4%), and in control subjects (60 +/- 5.5%). The same pattern of results was observed versus Escherichia coli (-47.7 +/- 10,28 +/- 8,28 +/- 12, and 29 +/- 8.5%, respectively). Previous incubation of normal alveolar macrophages with serum or BAL fluid from ALC patients or with normal serum or normal BAL fluid did not result in a significant decrease in antibacterial activity of normal alveolar macrophages. To distinguish ingested bacteria from adherent extracellular bacteria, cells that had been incubated with bacteria for 90 min were then incubated with lysostaphin (1 microgram/ml).(ABSTRACT TRUNCATED AT 250 WORDS)     

Profiles of serum complement in patients with hepatobiliary diseases.

CH50 and the concentrations of C3, C4, C1 INH and factor B have been measured in sera from 34 control subjects and 178 patients with various hepatobiliary diseases, including primary biliary cirrhosis (PBC), chronic active hepatitis (CAH), cryptogenic cirrhosis (CC), alcoholic liver disease (ALD), Wilson's disease (WD), large duct biliary obstruction (LDBO) and viral hepatitis (VH). CH50 was decreased in CAH and CC. C3 was increased in PBC, LDBO and VH and decreased in CAH and CC. C4 was decreased in PBC, CAH, ALD and WD. C1 INH was increased in PBC, CAH, ALD, LDBO and VH. Factor B was increased in LDBO and VH and decreased in CC. In none of the patient groups was the mean C4 level increased or the mean C1 INH level decreased. All 5 indices of serum complement were lower in ascitic than nonascitic patients. Data on serum complement were similar in HBsAg positive and negative VH. Discriminant analysis facilitated separation of all the patient groups on the basis of complement data, except PBC and VA. Analysis of data using a within-group correlation matrix revealed a significant negative correlation between C4, the most discriminating variable of serum complement in CAH, and gamma-globulin concentration in CAH. The possible contribution of factors such as activation of complement, impaired hepatic synthesis of complement components, an acute phase response and cholestasis to altered serum complement profiles in different hepatobiliary diseases is discussed.     

Intestinal absorption of cholecalciferol in alcoholic liver disease and primary biliary cirrhosis.

The intestinal absorption of (3H)cholecalciferol was studied in five patients with alcoholic liver disease, six patients with primary biliary cirrhosis, and 15 healthy subjects. The rate of appearance in plasma of (3H)cholecalciferol after oral ingestion and the subsequent appearance of (3H) polar metabolites in the alcoholic subjects were similar to those in the healthy subjects. In subjects with primary biliary cirrhosis the rate of appearance in plasma of (3H)cholecalciferol was significantly reduced. The rate of appearance of labelled polar metabolites of cholecalciferol was also lower in this group, suggesting that increased removal of labelled vitamin by conversion into more polar metabolites could not account for the reduced plasma (3H)cholecalciferol response. It is suggested that intestinal absorption of cholecalciferol is usually normal in alcoholic liver disease but impaired in primary biliary cirrhosis. Hepatic 25-hydroxylation is normal in alcoholic liver disease but may be defective in primary biliary cirrhosis.     

Vitamin E deficiency in primary biliary cirrhosis: gastrointestinal malabsorption, frequency and relationship to other lipid-soluble vitamins

In contrast to deficiencies of vitamins A, D and K, little is known of the prevalence, clinical manifestations and mechanisms of vitamin E deficiency in adult patients with cholestasis. We measured serum vitamin E levels in 45 patients with primary biliary cirrhosis, 20 with primary sclerosing cholangitis, 9 with cryptogenic cirrhosis and 12 with alcoholic cirrhosis. To correct for the hyperlipidemia often found in patients with primary biliary cirrhosis and primary sclerosing cholangitis, total serum lipids were measured and vitamin E levels were expressed as the vitamin E/total serum lipid ratio. Serum vitamin A and D levels and prothrombin time were also determined. Six of 45 patients with primary biliary cirrhosis (13%) but none of the patients with sclerosing cholangitis, cryptogenic cirrhosis or alcoholic cirrhosis and subnormal vitamin E/total serum lipids ratios. Vitamin E deficiency was found in two of eight patients with asymptomatic primary biliary cirrhosis. There was no correlation between standard liver biochemical tests, fasting serum cholylglycine and vitamin E levels. Patients with primary biliary cirrhosis and primary sclerosing cholangitis had significantly lower vitamin E/total serum lipids ratios than patients with either cryptogenic or alcoholic cirrhosis. Twenty-three percent of patients with primary biliary cirrhosis were vitamin D deficient and 14% had low vitamin A levels. Two of the six patients with vitamin E deficiency were also deficient in vitamin D, only one was vitamin A deficient and none had prolonged prothrombin time. We also investigated the gastrointestinal absorption of vitamin E in nine patients with primary biliary cirrhosis and normal vitamin E levels as well as in six normal controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neutrophil surface markers in patients with acute leukemia

The presence of complement and Fc receptors on neutrophils from patients with acute leukemia was investigated at different stages of the leukemic process. Both Fc receptors (Fc-H and Fc-R) and one complement receptor (C3d) were normal when patients were studied at diagnosis, in relapse, and in remission. In contrast, the C3b receptor was significantly reduced on te neutrophils at the time of diagnosis, but returned to normal levels when patients entered remission. Variable amounts of C3b activity were observed in patients relapse, with approximately one-half of the patients showing decreased C3b activity. To determine whether the reduction inC3b receptors was specific for patients at diagnosis, three patients were studied at different times during their diseases. Normal receptor levels were detected in these patients during remission, but the C3b receptor was markedly reduced at diagnosis and at relapse.