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Biomedical subjects

D Shouval

Publications and source records attributed to D Shouval.

At least 163 records · Page 9Linked to original sources
PubMed1981

Immunological evaluation of asymptomatic carriers of hepatitis B virus.

The immune system of 69 asymptomatic HBsAg carriers with normal liver function tests was evaluated. B cell function, as documented by serum immunoglobulin levels, number of mouse rosette-forming lymphocytes and lymphocyte reactivity to staphylococcal protein A, was intact. On the other hand, T cell function was markedly impaired. This was manifested by a significant decrease in E rosette-forming lymphocytes, an increase in stable rosette-forming cells and decreased reactivity to phytohaemagglutinin and concanavalin A. These data rule out the possibility that the immunological aberrations associated with hepatitis B infection are secondary to liver injury. The abnormal immune state either precedes the viral infection, thus predisposing to the acquisition of a carrier state or, alternatively, is a direct result of the infection.

Adult↗
PubMed1981

Study of 90 hepatitis B surface antigen carriers in Israel.

A study of 90 asymptomatic hepatitis B surface antigen (HBsAg) carriers in Jerusalem showed a predominance of males over females (4:1) and of North African Jews over Jews of European or American Origin. The predominance of males remained apparent, but was not significant, when origin was controlled. Possible sources of infection were contact with jaundiced patients (29%), dental treatment (58%) and drug addiction (8%). Fifty-one percent had hepatitis B core antibody (anti-HBc) of the IgM class, 2% had hepatitis B e-antigen (HBeAg), 94% hepatitis B e-antibody (anti-HBe) and 93% had hepatitis A antibody (anti-HAV). Fourty-two percent had donated blood at least once prior to the detection of the carrier state. Fifty-five percent of 128 asymptomatic family contacts had evidence of hepatitis B virus infection. Minor abnormalities in liver function tests were found in 22% of the carriers and splenomegaly in 11%. Of ten liver biopsies performed in these cases, one had chronic active hepatitis, five had minimal histological changes, and four were normal.

Adolescent↗
PubMed1980

Chronic hepatitis in chimpanzee carriers of hepatitis B virus: morphologic, immunologic, and viral DNA studies.

Years after infection with hepatitis B virus, chimpanzees may have manifestations of the carrier state as described in man. In addition to serologic evidence for persistent viral infection, percutaneous liver biopsy specimens showed hepatitis B virus surface antigen in the cytoplasm and hepatitis B virus core antigen in the nucleus. Four carrier animals had portal inflammatory reaction as seen in human chronic persistent hepatitis. Viral DNA was demonstrated in nucleic acid extracts of liver biopsy specimens by molecular hybridization to cloned plasmic pA01 containing hepatitis B virus DNA sequences. Although a viral molecule of length greater than the putative virus was identified, it did not appear to represent integration of viral DNA into the host genome. The chimpanzee model may serve as a means to study the mechanism of hepatitis B viral persistence and progression to chronic liver disease.

Animals↗
PubMed1979

Premature appearance of hepatic phosphoenolpyruvate carboxykinase in fetal rats, not mediated by adenosine 3':5'-monophosphate.

Injection of streptozotocin in utero to fetuses elicited a premature appearance of cytosolic hepatic activity of phosphoenol pyruvate carboxykinase. This was due to a precocious initiation of the synthesis of the enzyme. The streptozotocin-induced appearance of enzyme activity was not mediated by adenosine 3':5'-monophosphate since the concentration of the cyclic nucleotide in the liver was unaffected by the antibiotic, the administration of dibutyryladenosine 3':5'-monophosphate to streptozotocin-treated fetuses elicited an additive increase in enzyme activity, and insulin administration in utero repressed the streptozotocin effect while the effect due to dibutyryladenosine 3':5'-monophosphate was not inhibited by simultaneous insulin injection. Streptozotocin treatment also caused a small but consistent retardation of fetal growth and a marked reduction of liver wet weight. Histological analysis of the liver demonstrated a premature loss of some hematopoietic elements, while hepatocytes appeared normal. Hepatic protein synthesis was unaffected by the streptozotocin treatment. Streptozotocin treatment had no effect on fetal renal phosphoenol pyruvate carboxykinase activity or kidney wet weight.

Animals↗
PubMed1979

Chronic active hepatitis with cholestatic features. I. A clinical and immunological study.

Twelve of 43 patients with chronic active hepatitis (CAH) (28%) manifested clinical and laboratory features of cholestasis. The criteria for selection of these patients included at least two of the following: chronic or recurrent pruritus, serum alkaline phosphatase levels of 300 mU./ml. and cholesterol of 300 mg./dl. or more. When compared with 31 control cases these patients were found to have a preponderance of Ashkenazi Jews of Roumanian origin, a higher prevalence of joint and thyroid involvement and higher serum Ig-M Levels. Mortality was similar in both groups but patients with cholestatic features tended to die earlier in the course of the disease. Retrospectively, it was found that they had been treated more intensively, attained complete remissions less frequently and developed cirrhosis more readily. There were no significant differences in the frequency of HBsAg and anti-HBs, the mode of onset, the frequency of hepatosplenomegaly and jaundice, the hematologic findings and the prevalence of autoantibodies. Like acute cholangiolitic viral hepatitis, CAH with cholestatic features emerges as a more serious disease than the classical form of CAH.

Adolescent↗
PubMed1979

Chronic active hepatitis with cholestatic features. II. A histopathological study.

A review of 25 liver biopsies from 12 patients with chronic active hepatitis (CAH) with cholestatic features (Group 1) and of 30 biopsies from 23 patients without such features (Group 2) revealed that in Group 1 the bile duct epithelium showed significantly more hyperplasis, atypia, swelling, vacuolization and inflammation. When present in patients of Group 2, these parameters, in general seemed to be less severe. The number of bile ducts per portal space was similar in both groups. Thus, on a cumulative basis, a correlation was found between the clinical and biochemical features of cholestasis and the histological signs of bile duct damage.

Bile Ducts, Intrahepatic↗
PubMed1978

Effect of co-trimoxazole on normal creatinine clearance.

The effect of co-trimoxazole on creatinine clearance was studied in six individuals with normal kidney function. The mean decrease in creatinine clearance during treatment was 47 ml/min and the mean increase in plasma-creatinine was 0.27 mg/dl (P less than 0.01). Although creatinine clearance decreased by 29%, sodium excretion increased by 22%. Discontinuation of co-trimoxazole resulted in a prompt return of creatinine clearance to pretreatment values, and a consistent antinatriuresis.

Adult↗
PubMed1977

Fluidity of membrane lipids and lateral mobility of concanavalin A receptors in the cell surface of normal lymphocytes and lymphocytes from patients with malignant lymphomas and leukemias.

Lymphocytes isolated from the peripheral blood of patients with nonmalignant and malignant disorders were studied for fluidity of membrane lipids and lateral mobility of concanavalin A (Con A) receptors. The degree of fluidity of the surface membrane lipid core was monitored quantitatively by fluorescence polarization analysis using the probe 1,6-diphenyl-1,3,5-hexatriene embedded in lipid regions of the surface membrane of intact cells. Mobility of Con A surface receptors was determined by the cap-forming ability after binding of fluorescent Con A. The present studies were performed on lymphocytes from 28 patients with malignant lymphomas, 22 patients with leukemia, 28 individuals who either were healthy or had nonmalignant disorders, and 5 patients with carcinoma. The results showed that lymphocytes and mononuclear cells from patients with malignant lymphomas and leukemias have a more fluid lipid layer in their surface membrane than do lymphocytes obtained from healthy individuals or from patients with other malignant and nonmalignant disorders. This increase in membrane fluidity was less pronounced in lymphocytes isolated from leukemic patients in clinical remission and from leukemic patients receiving treatment with steroids. The results also show a marked difference in the cap-forming ability of lymphocytes from patients with malignant lymphomas or leukemia as compared with lymphocytes from patients with non-malignant disorders or carcinoma. Lymphocytes isolated from lymphoma and chronic lymphatic leukemia patients during remission stages of the disease exhibited a higher cap-forming ability. The cap-forming ability of cells from patients with chronic lymphocytic leukemia was unaffected by treatment with steroids. The present results, which are in line with previous observations, have shown that normal lymphocytes can be characterized by a low degree of lipid fluidity but a high degree of mobility of Con A receptors, whereas leukemic lymphocytes are characterized by a high degree of lipid fluidity but a low degree of mobility of Con A receptors. These results confirmed our general hypothesis on the dynamic interrelation between membrane lipids and membrane protein receptors, and they indicate that the widely accepted term "membrane fluidity" requires better consideration for different membrane components.

Carcinoma↗
PubMed1976

Type B and non-B viral hepatitis in Jerusalem.

In a two-year survey of adult patients hospitalized with acute viral hepatitis in Jerusalem, 27% were reactive for the hepatitis B surface antigen (HB(s)Ag) by radioimmunoassay and therefore diagnosed as having hepatitis B. The majority of patients (73%) were non-reactive for HB(s)Ag and their diagnosis was non-B hepatitis ("type unspecifiable"). Thirty-one per cent of patients with hepatitis B and only 5% of patients with non-B hepatitis had histories consistent with parenteral transmission of hepatitis by blood transfusion or drug use. An additional 19% of the patients with hepatitis B had possible parenteral exposure and 50% had no obvious parenteral exposure, indicating that non-parenteral transmission of the hepatitis B virus (HBV) may be a significant epidemiological factor (50-69%) in the Jerusalem area. The prominent role of non-parenteral transmission of HBV is further evidenced by the relatively high prevalences of HB(s)Ag (0.97%) and antibody to hepatitis B surface antigen (anti-HB(s)) (19.0%) in healthy blood donors. These findings are consistent with the view that personal contact and intra-familial spread may be important factors in the epidemiology of HBV and indicate that non-parenterally transmitted HBV contributes significantly to endemic viral hepatitis in the Jerusalem area.

Acute Disease↗
PubMedDate not supplied

Human hepatoma-associated cell surface antigen: identification and characterization by means of monoclonal antibodies.

A library of murine monoclonal antibodies reactive with human hepatoma cells was generated following immunization of Balb/c mice with an intact cloned human hepatoma cell line, designated PLC/PRF/5-NR. We report the characterization of one such IgG2a antibody, designated anti-PLC1. This antibody specifically stains parental PLC/PRF/5 cell membranes and membranes of SK-Hep 1 and Mahlavu human hepatoma cells grown in culture, using indirect immunofluorescence and horseradish immunoperoxidase techniques. A similar pattern of membranous staining was observed in solid tumors derived from the three hepatoma cell lines which were injected subcutaneously into athymic nude rats and mice. Spontaneous capping on the cell surface was observed in 7 to 30% of the three human hepatocellular carcinoma cell types when incubated in suspension with monoclonal anti-PLC1 at 37 degrees C. Treatment of cells with trypsin or sustained growth in culture did not affect the intensity of membranous staining. Monoclonal anti-PLC1 appeared specific, and antibodies did not stain a variety of human carcinoma cell lines and primary tumors of nonhepatic origin, or several normal human and murine tissues. Purified 125I-labeled monoclonal anti-PLC1 bound specifically to the three hepatoma cell lines in culture. Specificity of the antigen-antibody reaction was demonstrated by competitive binding inhibition in experiments using unlabeled homologous antibody. Binding of 125I-anti-PLC1 was not inhibited by unlabeled monoclonal antibodies to HBsAg or to alpha-fetoprotein. Two hepatoma cell lines secrete a protein that specifically blocks binding of 125I-anti-PLC1 antibodies to cell surface antigenic determinants. This "hepatoma-associated" protein was subsequently purified by affinity chromatography from supernates derived from the three hepatoma cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMedDate not supplied

A conjugate of 5-fluorouridine-poly(L-lysine) and an antibody reactive with human colon carcinoma.

The ribose moiety of 5-fluorouridine (FUR) was oxidized with periodate and the product was bound through a poly(L-lysine) bridge to monoclonal antibodies, denoted SF25MAb, reactive with a human colon carcinoma LS180. The antibody was linked via its polysaccharide (previously oxidized with periodate) to the poly(L-lysine)-drug conjugate. The linking of FUR-poly(L-lysine) to the antibody markedly increased the latter's binding to the tumor cells. A relatively lower increase was also observed with conjugates of nonrelated antibodies, such as anti-hepatitis B surface antigen and anti-epidermal growth factor receptor antibodies. The pharmacological activity of the specific conjugate FUR-poly(L-lysine) -SF25MAb was higher than that of the drug-substituted polymer alone. The poly(L-lysine) bridge caused toxic effects in vivo, even though substituted both by FUR and by antibody. Therefore, the additional unreacted lysyl residues were blocked by succinylation. Partial blocking of free amino groups on the conjugate rendered it nontoxic but decreased its cell-binding capacity, though to a level still higher than that of the original unmodified antibody. The pharmacological activity of the specific conjugate after blocking was also reduced and necessitated prolonged incubation periods or higher concentrations. Following periodate oxidation and reduction, FUR was as effective as the clinically preferred compound 5-fluoro-2'-deoxyuridine in vitro and in vivo, against the LS180 colon carcinoma. Experiments in nude mice, with LS180 tumor subcutaneous xenotransplants, showed that FUR-poly(L-lysine)-SF25MAb (blocked by succinylation) was not toxic and was effective in the retardation of tumor growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMedDate not supplied

Laboratory stigmata of connective tissue disorders in asymptomatic carriers of hepatitis B virus.

Sixty-nine asymptomatic HBsAg carriers have been studied for the presence of laboratory stigmata of connective tissue disorders. Anti-nuclear antibodies accompanied by a significant binding of anti-DNA were detected on one carrier only. In contrast, rheumatoid activity was detected in 10 out of 63 carriers, and lymphocytotoxins in 8 out of 33. Carriers had a significantly increased level of circulating immune complexes associated with mild hypocomplementemia. Since none of the carriers had any evidence of liver disease, it is probable that the immunologic abberations were induced by the persistent viral infection rather than liver injury. It seems that some asymptomatic carriers have an occult laboratory-wise, connective tissue disorder which, under yet unknown circumstances, gives rise to an overt immune complex disease.

Adult↗