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Biomedical subjects

E Alpert

Publications and source records attributed to E Alpert.

At least 73 records · Page 4Linked to original sources
PubMed1981

Human albumin synthesis via an albumin precursor in liver tissue slices.

A percursor of plasma albumin on man was identified in liver obtained from cadaver renal transplant donors. After 30 incubation with 14C-(U) leucine, most of the labeled immunoreactive albumin was identified as proalbumin, as was evident from its characteristic elution profile on DEAE cellulose 52. After an additional 30 min incubation with unlabeled leucine (60 min total), no precursor form could be identified and the label coeluted with serum albumin. These data strongly suggest that human albumin is initially synthesized in a precursor form and is subsequently transformed into serum albumin.

Humans↗
PubMed1981

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.

Angiography↗
PubMed1980

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 histologically-confirmed 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.

Adult↗
PubMed1980

Alcoholic liver disease. Absence of alpha-fetoprotein elevations in the recovery phase.

Serum alpha-fetoprotein (AFP) may be detected in patients with nonneoplastic liver diseases such as massive hepatic necrosis, viral hepatitis, and experimental liver injury, AFP levels have not been serially assessed in patients with alcoholic liver disease, with or without cirrhosis, during the period following cessation of alcohol. Thirty-two such patients were studied with weekly AFP determinations, an average of five such measurements being obtained per patient. The severity of alcoholic liver disease in this group varied from mild alcoholic hepatitis to advanced cirrhosis, and overall mortality was 31%. Thirty-one of the 32 patients had consistently negative AFP determinations. One patient with persistently elevated AFP levels proved to have hepatoma at autopsy. This study failed to detect AFP evelations in a group of patients with alcoholic liver disease and suggests that positive AFP determinations in such patients shoudl raise the question of underlying hepatocellular carcinoma.

Female↗
PubMed1980

Derivation and characterization of a monoclonal hybridoma antibody specific for human alpha-fetoprotein.

A monoclonal antibody specific for human alpha-fetoprotein (HAFP) was derived by the hybridoma technique. Spleen cells from mice immunized with pure HAFP were fused with a mouse myeloma cell line (P3x63-Ag-8) and an anti-HAFP secreting hybridoma cell line was cloned in soft agarose. The HAFP specific antibody was shown to be a monoclonal IgG1 subclass with extremely high avidity for HAFP.

Animals↗
PubMed1980

Inflammatory bowel disease associated circulating immune complexes.

Circulating immune complexes have been detected in patients with inflammatory bowel disease (IBD). To determine if these complexes are related specificially to IBD or more generally to loss of intestinal mucosal integrity, we compared circulating immune complex levels in the sera of 86 IBD patients, nine pseudomembranous and nine bacterial colitis patients, and 42 healthy controls. Immune complexes were measured by a Raji cell radioimmunoassay. Raji detectable circulating immune complex levels were significantly higher in the IBD group than in the healthy controls (P<0.001). Circulating immune complex levels in the pseudomembranous-bacterial colitis group and the healthy controls were essentially identical. While nearly 20% of the IBD patients (16 of 86) had abnormally high levels, none of the patients with the other forms of intestinal inflammation (0 of 18) had abnormal levels. These data suggest that the circulating immune complexes present in inflammatory bowel disease patients are related to the IBD process rather than to non-specific mucosal cell (barrier) damage. Patients with intestinal inflammation and normal peripheral immune complex levels also had normal mesenteric vein levels. These data suggest that lack of formation, rather than more efficient hepatic reticuloendothelial clearance, was primarily responsible for the absence of detectable complexes in Raji negative individuals. Circulating immune complex levels did not correlate with type, location, severity, or extraintestinal manifestations of inflammatory bowel disease. The absence of Raji detectable circulating immune complexes in the majority of patients, even in those with extraintestinal manifestations, raises serious doubts about the pathogenic significance of such complexes. Nevertheless, as the circulating immune complexes appear to be disease related, they may be used to isolate and identify disease specific antigen(s) of possible aetiological importance.

Antigen-Antibody Complex↗
PubMed1980

Inflammatory bowel disease: study of cell mediated cytotoxicity for isolated human colonic epithelial cells.

A better understanding of the mechanism(s) of cell mediated toxicity for colon cells in vitro may help clarify the pathogenesis of inflammatory bowel disease (IBD). We have examined both the cytotoxicity of IBD peripheral blood mononuclear cells and the kinetics of induction of such toxicity by soluble plasma factors. Peripheral blood mononuclear cells from IBD patients were found to be cytotoxic for the colon cells. With the use of Chang cells, this cytotoxicity was shown not to be due to an increase in spontaneous cell mediated cytotoxicity. Colon cell toxicity in vitro did not correlate with site of disease or severity, but decreased toxicity appeared to be associated with in vivo steroid administration. Plasma from some IBD patients was capable of inducing normal peripheral blood mononuclear cells to be toxic to colon cells. This ability was not affected by steroid therapy. The induction capacity of IBD plasma was not associated with the presence of circulating immune complexes, as measured by Raji RIA, suggesting that large complement fixing complexes are not the inducing and directing factors. Unlike findings in other systems, induction could be demonstrated after a one hour preincubation of mononuclear cells with IBD plasma. The kinetics of induction are consistent with the hypothesis that either cytophilic antibody or small circulating immune complexes arm K cells for specific colon cell lysis.

Antigen-Antibody Complex↗
PubMed1980

Prenatal diagnosis of neural tube defects. IV. Maternal serum alpha-fetoprotein screening.

The maternal serum alpha-fetoprotein (AFP) in 6161 women in routine pregnancy [2771 in a hospital obstetric clinic (group 1) and 3390 in private practices (group 2)] was studied. Group 1 studies enabled the delineation of the normal range of serum AFP, whereas group 2 represented a true screening experience. In group 2, 39 (2.5%) of 1566 women at 16 to 18 weeks' gestation had raised (2.5 times the median or more) serum AFP. Of these 39 women, 3 (7.8%) had neural tube defects (NTDs), 6 (15.4%) had multiple pregnancies, 1 (2.6%) had congenital nephrosis, 7 (17.9%) had spontaneous abortions, 7 (17.9%) had miscellaneous associated factors, and 15 (38.5%) had raised serum AFP for no obvious reason. Only 16 (1%) women had "unnecessary" amniocenteses. None of these aborted subsequently. Analysis of the combined data showed that NTDs were detectable in 87.5% of patients-all 6 with anencephaly and 1 of 2 with spina bifida (1 spina bifida lesion closed); multiple pregnancy was determined in 45% (18/40 cases), and spontaneous abortion ensued in 14.5%. In group 1 a raised serum AFP was associated with a host of complications in 77.3% of the women. Low AFP values had associated complications in 72.2% of cases. Maternal serum AFP screening represents another potentially important tool for early detection of high-risk pregnancy.

Amniocentesis↗
PubMed1980

Radioimmunodetection of cancer with radiolabeled antibodies to alpha-fetoprotein.

Sixteen patients with histologically proven malignant neoplasia were investigated by radioimmunodetection, using goat anti-alpha-fetoprotein (AFP) antibody radiolabeled with 131I. Images of the chest and abdomen were made with a scintillation camera, usually at 24 and 48 hr following injection of 1 to 2.5 mCi of radioiodinated antibody. Computer-assisted processing for the subtraction of 99mTc background radioactivity was used to enhance the detection and localization of tumors visualized by immune scintigraphy. All 12 sites involved by five AFP-producing tumors could be demonstrated by radioimmunodetection, while normal goat immunoglobulin G labeled with 131I failed to show similar results in one of the patients in whom the radioactive AFP antibody achieved tumor radiolocalization. Five patients in whom the tumors were not expected to produce AFP also had their large tumors demonstrated by immune scintigraphy in 6 of 16 tumor sites. The average tumor to non-tumor 131I image count density ratios were 3.20 and 1.96 for the AFP-containing and putatively AFP-deficient tumors, respectively. The image contrast was significantly greater for the AFP-containing tumors, and the subtraction technique enhanced the image contrast more than 2-fold. Based upon these initial results, the sensitivity of the method (true-positive rate) was 100%, its specificity (true-negative rate) was 80%, and the accuracy of the technique was 85%. This study thus indicates that radioimmunodetection of cancer with radioactive AFP antibodies can be useful in the evaluation of patients with AFP-containing neoplasms.

Adult↗
PubMed1980

Immune regulation in inflammatory bowel disease: absence of a serum inhibitor of suppressor cell function.

Suppressor cell function of normal peripheral blood mononuclear cells was unaltered by preincubation with sera from patients with severe inflammatory bowel disease (IBD). These results suggest that, in contrast to juvenile rheumatoid arthritis and systemic lupus erythematosus, the decreased suppressor cell activity in IBD is not mediated by anti-suppressor cell antibodies.

Antibody Formation↗
PubMed1979

Alteration in tryptic peptide patterns of ferritins purified from human colon carcinoma.

Ferritin from malignant tissue differs electrophoretically from normal ferritin. The molecular basis of this difference has not yet been defined. Malignant tissue contains a mixture of ferritins from normal cells, inflammatory cells as well as cancer cells. GW-39 is a pure colon carcinoma cell system that synthesizes human carcinoembryonic antigen. Therefore, ferritin was isolated from normal colon mucosa and colon cancer tissues, as well as from the colon carcinoma cell line, to clarify the molecular relationship between normal and malignant ferritins. Colon carcinoma ferritin differs in primary structure from normal colon mucosal ferritin and contains at least six additional different tryptic peptides. These six peptides were also found in the ferritin from the colon carcinoma cell line. These data suggest that the alteration in ferritin structure occurs at the cellular level and is associated with the malignant state.

Amino Acids↗
PubMed1979

Failure to detect circulating immune complexes in allergic patients on injection therapy.

Injection therapy for allergic diseases may create an environment conducive to circulating immune complex formation. Therefore, we examined the sera of eleven patients receiving injection therapy for the presence of circulating immune complexes. A sensitive Raji cell radioimmune assay was used to examine the sera prior to and 4, 8 and 24 hours after allergenic injection. Levels measured in these sera were compared to values obtained from forty-two healthy controls. Ten of eleven allergic patients receiving injection therapy had values within the normal range prior to maintenance injection. These ten patients also had normal values for circulating immune complexes at each interval after maintenance injection. The data suggest that circulating immune complexes are not a routine consequence of injection therapy for allergic disease.

Adult↗
PubMed1978

The immunochemical complexity of CEA: a golden dream or molecular nightmare?

Carcinoembryonic antigen is only a tumor assoicated antigen and is less clinically useful than the original report suggested. However, the CEA assays in clinical use utilize reagents operationally defined by old criteria. There is now abundant evidence that "CEA" consists of a heterogenous family of related glycoproteins with shared, as well as distinctive, antigenic determinants. Antigenic differences can be demonstrated between some cancer sera "CEA" and various operationally defined tissue "CEA" preparations. Further definition of the biochemical and antigenic characteristics of serum and tumor tissue "CEA" is required in order to determine whether a more tumor specific antigenic determinant can be identified.

Carcinoembryonic Antigen↗
PubMed1978

Immunosuppressive characteristics of human AFP: effect on tests of cell mediated immunity and induction of human suppressor cells.

Murine AFP has been reported to be immunosuppressive in a variety of systems. However, the extent and degree of inhibition has varied in different species and laboratories. Therefore, we have examined the potential suppressive effect of purified human AFP on several in vitro tests of cellular immunity and the potential mechanism of its action. AFP purified from fetal and liver cancer sera significantly inhibited mitogen and antigen-induced proliferative responses but had no effect on lymphocyte E rosetting, MIF production or mitogen induced T cell cytotoxicity to Chang target cells. Purified human AFP induced human suppressor cell activity, capable of suppressing a one-way mixed lymphocyte reaction (MLC). In contrast to Con A induced suppressor cells, AFP induced suppressor cell activity was overcome by mitogen augmentation of the proliferative response in MLC. These data suggest that the inhibition of lymphocyte proliferation by human AFP may be mediated by the induction of a subpopulation of human suppressor cells. Furthermore, mitogen induced cell mediated cytotoxicity was partially inhibited by primary liver cancer serum and completely inhibited by newborn cord serum, in contrast to purified fetal or tumor AFP which had no effect. These data suggest that there are other immunosuppressive factors in fetal and tumor serum which require further characterization. These other serum factors may be responsible for some of the immunosuppressive effects attributed to AFP. Although AFP is unlikely to play a major immunosuppressive role physiologically in vivo, its selective effect on proliferative responses, apparently mediated by suppressor cells, may prove to be a useful pharmacologic probe of the mechanism of these in vitro lymphocyte responses and biological interactions.

Humans↗