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Biomedical subjects

F V Chisari

Publications and source records attributed to F V Chisari.

At least 181 records · Page 10Linked to original sources
PubMed1982

Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). I. H-2 restriction of the murine humoral immune response to the a and d determinants of HBsAg.

In hepatitis B virus (HBV) infection correlation of disease activity with major histocompatibility complex (MHC) antigens has been suggested. However, no data are available regarding the nature and regulation of the immune response to the surface viral protein (HBsAg). This consideration and the current emphasis on production of an HBV vaccine led us to investigate the humoral immune response to HBsAg in inbred strains of mice to assess genetic factors that may regulate the humoral anti-HBs response. Studies with H-2 congenic and noncongenic inbred strains revealed the T-dependent humoral immune responses to the group-specific a and subtype-specific d determinants of HBsAg are regulated by gene(s) mapping to the murine MHC. The H-2q haplotype conferred high responsiveness, the H-2s,f haplotypes conferred low to nonresponsiveness, and the H-2a,b,d,k haplotypes were intermediate. Studies of H-2 recombinant strains allowed tentative mapping of regulation of the anti-a response and possibly the anti-d response to the K/I-A, I-B region of the MHC. The H-2-restricted regulation of the humoral immune response to HBsAg was circumvented by immunization with 10-fold higher HBsAg doses. These findings demonstrate a clear linkage between the murine MHC and the regulation of the immune response to specific determinants on HBsAg.

Animals↗
PubMed1981

Ocular reticulum cell sarcoma. Presentation as retinal detachment with demonstration of monoclonal immunoglobulin light chains on the vitreous cells.

A 61-year-old man with a history of cerebral reticulum cell sarcoma-microglioma (histiocytic lymphoma) in remission was initially seen with uveitis and exudative retinal detachment. Pars plana vitreous biopsy established the diagnosis by cytologic findings and allowed the immunofluorescent demonstration of a monoclonal immunoglobulin within the vitreous cells. Direct immunofluorescent microscopy of the vitreous infiltrate may prove to be of benefit in the workup of patients with uveitis in whom malignant lymphoma must be excluded.

Brain Neoplasms↗
PubMed1981

Physiologic concentrations of normal human plasma lipoproteins inhibit the immortalization of peripheral B lymphocytes by the Epstein-Barr virus.

Epstein-Barr virus (EBV)-induced immortalization of adult human B lymphocytes is suppressed by physiologic concentrations of human plasma lipoproteins. Several inhibitory mechanisms appear to be operative. First, low density lipoproteins (LDL) directly reduce the ability of EBV to transform human B cells. Second, LDL as well as intermediate and very low density lipoproteins modulate early inductive events rendering the B cell refractory to transforming signals from EBV. Third, LDL also selectively inhibit an EBV-inducible step that occurs within 24 h after transformation. Finally, very low density lipoproteins can abrogate the ongoing, cellular proliferation of EBV-transformed, established B cell lines. The plasma lipoproteins may therefore prevent the emergence of EBV-transformed malignant B cell clones in vivo. Conceivably, on this basis, environmental and genetic influences on plasma lipoprotein concentrations may affect the global distribution of Burkitt's lymphoma, a lymphoid malignancy putatively caused by EBV.

Animals↗
PubMed1981

Functional properties of lymphocyte subpopulations in hepatitis B virus infection. I. Suppressor cell control of T lymphocyte responsiveness.

Hepatocellular injury in hepatitis B virus infection may be produced by an autoaggressive hepatocytotoxic immune response. To test the hypothesis that acquired suppressor cell defects may participate in such a response, we assessed the functional integrity of 2 suppressor cell populations in patients with type B viral hepatitis. Spontaneous suppression of the 1-way mixed lymphocyte response by radiation-resistant, adherent peripheral blood mononuclear cells decreases during the acute phase of disease, returns towards normal with clinical recovery, but remains depressed in patients with chronic hepatitis. The degree of spontaneous suppressor cell dysfunction correlates inversely with at least 1 biochemical parameter of hepatocellular injury (SGPT). The functional integrity of this suppressor cell fluctuates during chronic hepatitis and may reflect currently undefined biologic variables in this disease. Mitogen-induced suppression on lymphocyte activation by radiation resistant, nonadherent suppressor cells is also depressed in acute and chronic hepatitis, but it does not correlate with biochemical evidence of hepatocellular injury on an individual-patient basis. Documentation of these generalized defects of nonspecific suppressor cell function establishes a basis for the possible existence of specific anomalies of immuno-regulation that may permit the expression of normally suppressed auoaggressive hepatocytotoxic immune mechanisms in viral hepatitis.

Adult↗
PubMed1981

Functional properties of lymphocyte subpopulations in hepatitis B virus infection. II. Cytotoxic effector cell killing of targets that naturally express hepatitis B surface antigen and liver-specific lipoprotein.

Cytotoxic effector cell responsiveness to host and/or virus-determined hepatocyte surface membrane antigens has been postulated as an important pathogenetic determinant of hepatocellular injury in hepatitis B virus infection. Assuming that such effector cell populations would be detectable in peripheral blood, the present study was designed to examine 2 questions: first, whether target cells that normally express liver-specific protein (LSP) and hepatitis B surface antigen (HBsAg) are selectively destroyed by peripheral blood effector cells from patients with viral hepatitis; second, whether cytotoxic effector cell function emerges coincident with the development of defective suppressor cell activity in the same patients. No evidence of increased HBsAg or LSP specific cytotoxic effector cell activity was found in the peripheral blood natural killer (NK) or T killer cell populations of patients with acute or chronic viral hepatitis.

Antigens, Surface↗
PubMed1980

Subretinal neovascular membrane and disciform scar in Behçet's disease.

A 33-year-old woman with a three-year history of aphthous ulceration of the mouth, vaginal ulceration, and erythema nodosum, also had a subretinal neovascular membrane in the left eye. She showed antibodies to guinea pig lip epithelium by indirect immunofluorescence. Thus, Behçet's disease must also be considered in the differential diagnosis of subretinal neovascular membrane in young patients, especially when antibodies to oral mucosa can be shown.

Adult↗
PubMed1979

Immunoregulatory properties of human esophageal tumor extract.

Noncytotoxic aqueous extracts of esophageal tumors (TEx) inhibit the spontaneous uptake of 3H-thymidine by human peripheral blood mononuclear cells (PBM). TEx also inhibits mitogen- and antigen-induced PBM blastogenesis, mitogenesis, 3H-thymidine uptake, and 3H-leucine incorporation. Inhibition is reversible and is mediated by a heat-labile protein with a m.w. of approximately 70 to 80,000 daltons. Inhibitory activity is not due to trivial binding of mitogen or neucleotide by the inhibitor, nor is it entirely tumor specific since similar but quantitatively less activity is extractable from adjacent normal esophageal mucosa. Assorted cell surface membrane phenomena such as contact inhibition of in vitro endothelial cell proliferation, lymphocyte E rosette formation, and cap formation are unaffected by TEx. In contrast, immunoglobulin synthesis by pokeweed mitogen-stimulated PBM is enhanced by TEx. The potential importance of the local production of immunoregulatory agents like TEx in the immunologic control of tumor cell growth is discussed.

Cell Membrane↗
PubMed1978

Regulation of human lymphocyte function by a soluble extract from normal human liver.

The blastogenic and DNA synthetic response of human peripheral blood lymphocytes (PBL) to phytohemagglutinin (PHA) and allogeneic cells can be inhibited by a nontoxic aqueous extract (LEx) of normal human liver. LEx reversibly inhibits the activation of PBL by PHA, arrests ongoing DNA synthesis, and limits the duration of the DNA synthetic response to PHA at concentrations as low as 0.7 to 1.5 microgram LEx protein/culture. In contrast, human T lymphocyte E rosette formation is unaffected by LEx concentrations in excess of 900 microgram/culture. LEx has been partially purified by ultracentrifugation, ammonium sulfate precipitation, and molecular exclusion chromatography and appears to be a heat labile protein with a m.w. of approximately 65,000 and an isoelectric point of approximately 4.08. LEx is distinct from other previously described human immunoregulatory molecules and is potentially releasable in vivo from injured or necrotic liver cells. Because of its potency and anatomic distribution LEx may potentially modulate immunopathogenetic events responsible for assorted inflammatory and neoplastic liver diseases.

Binding Sites↗
PubMed1978

Reversibility of hepatitis B virus-induced glomerulonephritis and chronic active hepatitis after spontaneous clearance of serum hepatitis B surface antigen.

A patient presenting with nephrotic syndrome was found to have hepatitis B surface antigen-positive chronic active hepatitis and membranoproliferative glomerulonephritis. Glomeruli stained positive for hepatitis B surface antigen, IgG, and C1q. After spontaneous clearance of hepatitis B surface antigen both the glomerulonephritis and the chronic active hepatitis improved. The natural history, pathogenesis, and treatment of this disease complex are discussed.

Adult↗
PubMed1977

Extrinsic modulation of human T-lymphocyte E rosette function associated with prolonged hepatocellular injury after viral hepatitis.

Defective T-lymphocyte E rosette (ER) function associated with viral hepatitis A and B may be due to mechanisms extrinsic or intrinsic to the target lymphocyte. The extrinsic defect is induced by an immunoregulatory plasma lipoprotein (RIF) and has the capacity to regenerate ER function in vitro. The intrinsic defect is refractory to regeneration and is not associated with RIF. Although both mechanisms occur with high frequency during the acute phase of viral hepatitis they tend to segregate in accordance with progression of hepatocellular injury at later stages of the disease. The extrinsic defect was observed in 7 out of 8 patients with longstanding chronic active hepatitis and in 10 out of 10 patients with unresolved hepatitis 12 wk after the onset of jaundice. In contrast, none of nine patients with resolved hepatitis had extrinsically defective ER function 12 wk after the onset of jaundice whereas eight of them displayed an intrinsic defect of ER function at that time. Among the various viral and liver diseases studied RIF appeared to be specific for hepatitis A and B viral infections. None of 64 sera from a variety of viral infections including Epstein-Barr virus cytomegalovirus mononucleosis with associated hepatitis nor 15 sera from patients with several chronic nonviral liver diseases were positive for RIF. RIF and its associated extrinsic defect in ER function therefore appear to correlate with a particular type of hepatocellular injury initiated by the hepatitis A and B viruses that may have a propensity for persistence and(or) progression to an aggressive form of chronic hepatitis.

Acute Disease↗
PubMed1977

Recovery of soluble sheep erythrocyte receptor from the T lymphocyte surface by proteolytic cleavage.

Proteolytic digestion of the human T lymphoblastoid cell line (Molt-4) and of peripheral blood lymphocytes by trypsin, chymotrypsin, and pronase results in a progressive, time-and dose-dependent diminution of T lymphocyte-sheep red bloock cell (SRBC) rosette formation, whereas thrombin, plasmin, collagenase, DNAse, and phospholipase have not effect. Complete abrogation of SRBC binding is achieved when lymphocytes (1 x 108/ml) are incubated with either trypsin or chymotrypsin at 10 mug/ml for 30 min, and greater than 50% abrogation is observed between 3 to 10 min. Preincubation of SRBC with the 10 min and 20 min lymphocyte digest supernatants inhibited their subsequent binding by normal T lymphocytes by as much as 64%. Thirty-minute digests were less inhibitory. Equivalent digests from several human B lumphoblastoid cell lines and from a non-rosetting clone of Molt-4 cells were not inhibitory. Polyacrylamide gel electrophoresis followed by elution of serial gel slices revealed four distinct inhibitory bands (I-IV) in the 20-min digest supernatant whereas only bands I-III and band IV were present in the 10-min and 30-min digest supernatants, respectively, suggesting progressive proteolysis of a distinct receptor. These experiments indicate that the binding of SRBC by human T lymphocytes represents a receptor-ligand interaction rather than a nonspecific electrical charge phe nomenon and that the receptor is a discrete molecular species which can be isolated from the surface of T but not B lymphocytes by limited enzymatic proteolysis.

Binding Sites↗
PubMed1976

Mechanisms responsible for defective human T-lymphocyte sheep erythrocyte rosette function associated with hepatitis B virus infections.

The expression of selected lymphocyte surface-membrane markers was evaluated in 37 patients with acute viral hepatitis B, 10 of whom were studied serially through the resolving and convalescent phases of disease. Bone marrow-derived (B) lymphocytes were identified by reference to surface immunoglobulin, whereas normal thymus-derived (T) lymphocytes were assayed by their capacity to form spontaneous nonimmune rosettes with sheep erythrocytes (E rosettes, ER). During the acute and resolving phases of viral hepatitis B, the relative and absolute number of ER-positive lymphocytes was significantly reduced, whereas the number of surface immunoglobulin-positive lymphocytes and the absolute lymphocyte count remained normal. This resulted in the appearance of a third population of cells, deficient in respect to both surface immunoglobulin and ER markers. Such cells accounted for nearly 25% of peripheral blood lymphocytes, approximately 5 x 105ml blood. Depression of the number of ER-positive lymphocytes occurred at least once during the course of disease in every patient studied serially, and was observed in 55 of 67 individual assays of the 37 cases of acute viral hepatitis B. Lymphocytes from some patients reacquired ER function when cultured in fetal calf serum but not in the presence of autologous serum. Such autologous serum was capable of suppressing ER function of lymphocytes from normal donors. The extrinsic suppression of er function by a serum factor (designated as the Rosette Inhibitory Factor), was found to be time dependent, characterized by a 4-h latent period and requiring approximately 18 h for maximum attenuation of ER function. The Serum Rosette Inhibitory Factor was: (a) heat and freeze-thaw stable, (b) nondialyzable, (c) physically separable from hepatitis B surface antigen, (d) not a lymphocytotoxic antibody, and (e) had the buoyant density of a lipoprotein. This extrinsic mechanism was observed in 41.8% of patients with reduced numbers of ER-positive lymphocytes. The Rosette Inhibitory Factor was not detectable in the serum of the remaining 58.2% of the cases of acute and resolving viral hepatitis B despite the presence of reduced numbers of ER-positive lymphocytes. The lymphocytes from these cases did not reacquire ER function when cultured in the absence of autologous serum. The mechanisms responsible for the suppression of normal ER function in these cases appears to be intrinsic to the lymphocytes and not the result of a humoral factor. The T lymphocyte lineage of cells deficient in respect to ER function, whether of intrinsic or extrinsic type, was demonstrated by their capacity to form spontaneous rosettes with neuraminidase-treated sheep erythrocytes. Both intrinsic and extrinsic suppression of T lymphocyte ER function commonly occurred during the first 4 wk of acute viral hepatitis B.9 of the 10 patients followed serially continued to manifest defective ER function at 12 wk...

Adult↗
PubMed1975

Lymphocyte E rosette inhibitory factor: a regulatory serum lipoprotein.

Rosette inhibitory factor, RIF, previously described in serum from patients with hepatitis B virus infection, has been isolated and identified as a minor species of beta-lipoprotein of the low-density (LDL) class. It is unrelated to hepatitis B virus proteins or particles. Although discrete by reference to charge and density (1.050 +/- 0.004 g/cm3), RIF appears to be a complex macromolecular structure containing apolipoproteins A, B, and C. Greater than 400% recovery is achieved upon 300,000-fold purification from RIF+ sera suggesting activation of a precursor form that is not present in normal serum. RIF inhibits E rosette function of T lymphocytes in vitro with a lag period of approximately 4 h and maximal effect at 24 h consistent with a metabolically-induced event. RIF is functionally active at concentrations of 1 X 10(-12) M or greater, rapidly binds to lymphocytes, and has a functionally effective half-life of approximately 1.5 h. Approximately 2,900 receptors for RIF appear to be present per cell and a high mutual affinity is apparent (k approximately to 9 X 10(10) liters/mol). RIF has no detectable effect on mitogen (PHA) responsiveness of lymphocytes, but inhibits the capacity of lymphocytes to respond to histoincompatible cells in vitro at concentrations greater than 10(-8) M. Equivalent RIF- lipoprotein fractions from normal serum are equally inhibitory in the mixed lymphocyte reaction suggesting that this effect is not directly attributable to RIF activity. These data indicate that RIF is a unique and functionally specific species of LDL that represents either an association complex of lipoproteins or a hybrid molecule of unusual composition. The association of this factor with viral-induced hepatocellular injury underscores the need to elucidate its structure and function in greater detail.

Adult↗