Elliot Alpert

The pathogenesis of arthritis associated with viral hepatitis. Complement-component studies.

Abstract Eighteen patients with acute viral hepatitis had initial symptoms of arthralgia, arthritis or urticaria. Total serum hemolytic complement (CH50) and C4 tended to be severely depressed in the nine patients studied in the acute phase of their joint symptoms. The C3 levels were moderately depressed, and the C1q levels were widely variable. C1 inhibitor and C9 serum concentrations were normal. Patients with viral hepatitis in convalescence or remission from arthritis, or without a history of these symptoms, had a normal or elevated serum CH50 and C3 level, a widely variable C1q level and low normal C4 levels. Low serum levels of complement in viral hepatitis were associated with high titers of hepatitis-associated antigen. Five patients with acute nonviral hepatitis had normal or elevated serum complement levels. The correlation of joint and skin symptoms with hepatitis-associated antigen and depressed levels of complement activity in the acute state suggests that this serum-sickness-like syndrome ma...

The pathogenesis of arthritis associated with acute hepatitis-B surface antigen-positive hepatitis. Complement activation and characterization of circulating immune complexes.

Circulating immune complexes were identified in cryoproteins isolated from serial samples of serum from six patients with acute viral hepatitis with and without arthritic symptoms. Cryoprecipitates were analyzed for the presence of hepatitis-B surface antigen (HBsAg) and hepatitis-B surface antibody (anti-HBs) by hemagglutination inhibition and hemagglutination. Complement components were detected by counter electrophoresis, and immunoglobulins were detected by gel diffusion. HBsAg, IgG, and IgM were identified in cryoprecipitates from all hepatitis patients, but were higher in concentration in patients with arthritis. Only cryoprecipitates from hepatitis patients with arthritis contained IgA and complement components C3, C4, and C5 as well as IgG and IgM, which disappear with resolution of the arthritis. The subtypes of IgG in these cryoprecipitates were predominantly the complement-fixing IgG1 and IgG3, HBsAg and anti-HBs were concentrated several-fold in the cryoprecipitates when compared to the serum concentration. Sequential studies in two patients demonstrated that the initial appearance of anti-HBs in the cryoprotein complex was associated with the detection in the complex of IgM suggesting a primary immune response to HBsAg. The C3 activator fragment (C3A) of the properdin complex was found in fresh serum obtained from three hepatitis patients with arthritis and not in uncomplicated hepatitis. The cryoprecipitable immune complexes from patients with arthritis converted C3PA in fresh normal sera to C3A in vitro whereas cryoprotein isolated from patients with uncomplicated hepatitis had no such effect. Thus, the transient appearance of circulating complement-fixing immune complexes in patients with the arthritis of acute hepatitis is associated with activation of both classical and alternate complement pathways and suggests that they play an important role in the pathogenesis of these serum sickness-like extrahepatic symptoms.

Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein

This study reports the use of radiolabeled antibodies to alpha‐fetoprotein for the detection and localization of hepatocellular and germ cell carcinomas. Twelve patients with histories of histologicallyconfirmed neoplasia received a total dose between 1.0 and 4.4 mCi of 131I‐labeled goat IgG prepared against human alpha‐fetoprotein. Total‐body photoscans were taken with a gamma scintillation camera at various intervals after injection of the radioactive antibody. Computer subtraction of radioactive technetium background images from the antibody 131I scans permitted the visualization of all tumor sites known to be present in 4 patients with either primary hepatocellular cancer or metastatic germ cell carcinoma of the testis. In contrast to the results with the specific antibody, radioactive normal goat IgG given to one of these patients with metastatic embryonal carcinoma of the testis failed to show equivalent localization. Among 8 patients with diverse neoplasms not believed to contain alpha‐fetoprotein, 5 of 19 tumor sites showed radioactive antibody accretion, although significantly less than in the patients with liver or testicular cancer. Circulating antigen levels of up to 15,000 ng per milliliter did not prevent successful tumor imaging after intravenous injection of the radioantibody. This investigation indicates that alpha‐fetoprotein‐containing tumors can be detected and localized in vivo by the method of radioimmunodetection.

Prenatal diagnosis of neural tube defects: VIII. The importance of serum alpha-fetoprotein screening in diabetic pregnant women☆

Maternal serum alpha-fetoprotein (AFP) screening of routine pregnancy is a valuable tool for the prenatal detection of neural tube defects (NTDs). Against our background experience with greater than 24,000 screened pregnancies, we have studied 411 pregnant insulin-dependent diabetic women. More than a tenfold increase (19.5/1,000) in the frequency of NTDs was observed in the offspring of these diabetic patients (p less than 0.000001). Serum AFP values were lower in diabetic than in nondiabetic women. Our data indicate that the normal standard of care for diabetic pregnancy should include serum AFP screening.

Cell-mediated immunity in acute and chronic hepatitis.

Peripheral lymphocytes from patients with hepatitis-B surface antigen (HBsAg)-positive and -negative acute hepatitis (AH), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and normal controls were tested for in vitro cytotoxicity and blast transformation. Cytotoxicity was measured by chrominum (21Cr) release into the medium from 51Cr-labeled Chang liver cells after incubation for 6 h with peripheral lymphocytes at a lymphocyte target cell ratio of 200:1. Concomitant 72-h incubation studies were performed to assess thymus cell-dependent (T) lymphocyte function as measured by conccanavalin A (Con A)- stimulated incorporation of tritiated thymidine (blast transformation) and by cytotoxicity. It was found that (a) lymphocytes from patients with AH are cytotoxic to Chang liver cells compared to controls (P less than 0.001); (b) lymphocytes from patients with acute and chronic hepatitis are less cytotoxic when incubated with autologous and homologous HB2Ag-positive and -negative AH, CAH, and CPH are as cytotoxic as normal controls when stimulated with a nonspecific mitogen such as Con A; and (d) lymphocytes from patients with CAH while on prednisone therapy showed marked depression of cytotoxicity when stimulated with Con A. Thus these studies show that patients with AH have circulating T lymphocytes which are capable of causing the destruction of Chang liver cells. There is no defect in T-cell function as measured by Con A-stimulated cytotoxicity. There is a serum factor (s) in patients with acute and chronic hepatitis which inhibits spontaneous and induced lymphocyte cytotoxicity and blast transformation. Finally, prednisone treatment appears to inhibit lymphocyte cytotoxicity in patients with CAH.

Human Isoferritins: Organ Specific Iron and Apoferritin Distribution

Summary. Ferritins from human liver, spleen, heart, pancreas and kidney were compared by electrophoresis and isoelectric focusing in polyacrylamide gels, by immunodiffusion against antisera to homologous and heterologous ferritin, and in some cases by their cyanogen bromide peptides. All ferritins appeared to consist of a single species on gel electrophoresis with the exception of heart ferritin which separated into two major components. Small differences in electrophoretic mobility were found in all tissue ferritins. By contrast, all tissue ferritins were found to consist of multiple forms when analysed by gel electrofocusing. At least five isoferritins were found in most tissues, several of which were common to most tissues. At least two were common to all tissues. Those ferritins which were most easily distinguishable electrophoretically, e.g. spleen and heart ferritin, showed the greatest differences on gel electrofocusing. The ferritin profile was characteristic of each organ and was reproducible both within individuals and between individual tissues. There were striking differences in the iron content of the various isoferritins within a tissue. Further, the iron content of isoferritins common to more than one tissue varied with the tissue of origin. Some isoferritins in several organs and all of the isoferritins in pancreas appeared to contain little, if any, iron. All five tissue ferritins contained antigenic determinants in common with liver ferritin. However, an additional antigenic determinant was found in liver ferritin which was not detectable in the ferritins from the other organs.

Alpha-Fetoprotein in a Patient with Gastric Carcinoma Metastatic to the Liver

ALPHA-fetoprotein (AFP) is detectable in the serums of most patients with hepatoma and not in those of normal adults or adult patients with a variety of liver and neoplastic diseases. The presence ...

Prenatal diagnosis of neural tube defects

Abstract Total cholinesterase activity in amniotic fluid obtained from 150 fetuses was measured. Elevated values were found in 94% of samples from fetuses known to have neural tube defects (spina bifida, anencephaly) when compared to nonbloody samples from normal fetuses. Contamination of amniotic fluid with blood was observed to elevate total cholinesterase activity in some, but not all, such specimens. Total cholinesterase activity did not vary gestational age between 15 two 24 weeks. These data were compared to our large alpha-fetoprotein (AFP) assay experience used for the prenatal detection of neural tube defects. We concluded that the assay of total cholinesterase activity in amniotic fluid could be useful adjunct to the AFP assay, especially in those samples contaminated with blood.

Galactosyltransferase Isoenzyme II in the Detection of Pancreatic Cancer: Comparison with Radiologic, Endoscopic, and Serologic Tests

We assessed the value of several serologic markers in detecting pancreatic carcinoma in a prospective study of 270 patients. The sensitivity and specificity of galactosyltransferase isoenzyme II (GT-II), carcinoembryonic antigen (CEA), alpha-fetoprotein, ferritin, C1q binding, and ribonuclease were determined. GT-II was the most sensitive (67.2 per cent) and specific (98.2 per cent) for discriminating between benign and malignant disease and was more sensitive and specific than CEA, the next most useful marker. Sensitivity was 64 per cent for ultrasound, 79.4 per cent for computerized body tomography (CBT), and 92.8 per cent for endoscopic retrograde cholangiopancreatography (ERCP). As a single test, only ERCP was more sensitive than GT-II, but more sensitive diagnoses resulted when GT-II was combined with ultrasound (92 per cent), CBT (88 per cent), or ERCP (100 per cent). Serum GT-II may be useful both by itself and in combination with imaging techniques in distinguishing benign from malignant pancreatic disease; however, this test does not discriminate between pancreatic carcinoma and other gastrointestinal neoplasms.

Lysyl Oxidase and Collagenase in Experimental Acute and Chronic Liver Injury

Lysyl oxidase and collagenase activities were measured in experimental acute and chronic liver injury in mice and rats, and correlated with collagen synthesis and accumulation. Acute liver injury was induced in mice and rats by a single dose of carbon tetrachloride given by gavage, and also in mice by a single injection of murine hepatitis virus. Chronic liver injury was induced in rats by repeated injections of carbon tetrachloride. Elevated plasma glutamic oxaloacetic transaminase levels, increased hepatic prolyl hydroxylase activity, and increased synthesis of collagen-bound hepatic hydroxyproline occurred in animals with acute as well as with chronic liver injury. However, only chronic liver injury appeared to be associated with fibrosis, increased collagen-bound hydroxyproline content, increased hepatic lysyl oxidase and collagenase activities, as well as with increased serum lysyl oxidase activity. These data suggest that lysyl oxidase and collagenase may play an important role in the collagen accumulation associated with hepatic fibrosis.