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D R Milich

Publications and source records attributed to D R Milich.

103 records · Page 6Linked to original sources
PubMed1981

Interactions between polymerized human albumin, hepatitis B surface antigen, and complement: II. Involvement of Clq in or near the hepatitis B surface antigen receptor for polyalbumin.

A species-specific receptor for polymerized human albumin (PHALB) has been reported on hepatitis B surface antigen (HBsAg)-carrying particles. Our previous observations that human Clq also binds PHALB in a species-restricted manner led us to investigate the possibility that HBsAg-associated Clq is involved in the PHALB receptor on HBsAg particles. The temperature, ionic strength, and pH requirements necessary for binding of PHALB to both Clq and HBsAg were compared and found to be similar. Normal human serum and purified Clq inhibited the PHALB-HBsAg interaction; the inhibition was markedly reduced in heat-inactivated and Clq-depleted serum. Heat-denatured or reduced and alkylated Clq failed to inhibit the PHALB-HBsAg binding. Moreover, human Clq was found to be present in purified preparations of HBsAg and the quantity detected paralleled the degree of PHALB-HBsAg binding. While anti-Clq inhibited the PHALB-HBsAg interaction, anti-Clr, - Cls, -C3, and -Ig were not inhibitory. Collagenase treatment of purified HBsAg reduced both PHALB-binding activity and the degree of HBsAg-associated Clq. These observations provide evidence that HBsAg-associated Clq is involved in or near the HBsAg-binding site for PHALB.

Blood↗
PubMed1981

Hepatitis B viral markers in patients with primary hepatocellular carcinoma in Taiwan.

The presence of hepatitis B viral markers in patients with primary hepatocellular carcinoma (PHC) was studied retrospectively at the Taiwan Veterans General Hospital in Taipei, Taiwan. Serum samples from 102 PHC patients and from 100 control individuals were tested for hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs), antibody to hepatitis B core antigen (anti-HBc), hepatitis Be antigen (HBeAg), and antibody to HBeAg (anti-HBe). Of the 102 PHC patients, 72 (71%) were positive for HBsAg. Nine (9%) additional patients were positive for anti-HBc alone in high titer, 19 (19%) had both anti-HBc and anti-HBs, and 9 (9%) had HBsAg, anti-HBc, and anti-HBs. In the 100 controls, 12 (12%) were HBsAg-positive, whereas 22 (22%) had anti-HBc alone and 50 (50%) had both anti-HBc and anti-HBs. Only 4 (4%) controls and no PHC patients had anti-HBs alone. Of the HBsAg-positive patients with PHC, 17 (29%) had HBeAg and 36 (61%) had anti-HBe. The alpha-fetoprotein (AFP) levels above 400 ng/ml were found in 44% of the PHC patients. Values of AFP above 1 x 10(5) ng/ml were more frequently detected in PHC patients who were HBsAg-positive. Categorization of the geographic origins of the families whose members had PHC revealed that most families had originated from southern China. This study confirms that hepatitis B viral markers are frequently present in Chinese patients with PHC.

Adult↗
PubMed1981

Characterization of the interaction between polymerized human albumin and hepatitis B surface antigen.

The interaction of polymerized human albumin with hepatitis B surface antigen was characterized utilizing a solid-phase radioimmunoassay. The interaction was specific as shown by quantitative inhibition of binding by soluble polymerized human albumin. The interaction was species restricted in that hepatitis B surface antigen did not bind nonhuman polymerized albumins. The albumin polymer size was critical to the binding reaction as was the concentration of hepatitis B surface antigen; the interaction was also temperature, ionic strength, and pH dependent. Hepatitis B e antigen positive sera possessed greater polyalbumin binding reactivity than hepatitis B e antigen negative sera. This interaction was shown to be inhibited by normal human serum which suggested that the polyalbumin receptor on hepatitis B surface antigen may be a host rather than viral component. In view of our previous observation that polymerized human albumin binds human C1q, the interactions between polymerized human albumin, hepatitis B surface antigen, and human C1q may be relevant to hepatitis B virus-host receptor mechanisms.

Animals↗
PubMed1980

The pathogenesis of autoimmunity in New Zealand mice.

In the past few years there has been an explosion of information in the area of NZ mouse research. This has reflected a general increase in knowledge and technology in cellular immunology and lymphocyte biology. Continuing research in many specific areas promises to expand this increasing data base. The numerous abnormalities of CMI in NZ mice chronicled in the past are currently being analyzed in terms of cell synergism rather than as simple effector mechanisms. Such analysis is indicating more selective rather than general impairment of CMI in aging NZ mice. Similarly, the allogeneic H-2 identical cytotoxic activity expressed by NZ mice and its relevance to autoimmune disease are being explored. In the area of suppressor functions in NZ mice, continued refinement and standardization of suppressor assays must be achieved before adequate interpretation of the present information can be made. Suppressor activity in aging NZ mice has been described as depressed, normal, and elevated. This is an area of acute interest. While the primary etiologic significance of T cell regulatory defects is currently being minimized, their possible secondary role in pathogenesis of autoimmune disease in NZ mice is being investigated. The recent discovery of a significant B cell abnormality present from birth in all SLE-prone murine strains has increased the probability that intrinsic B cell hyperactivity is a primary etiologic factor in murine autoimmunity. The hypersecretion of IgM and the increased incidence of B cell colony-forming units observed in NZ mice is being subjected to further genetic analysis in many laboratories. Similarly, the continued evaluation of the (CBA/N x NZB) hybrid promises to be enlightening, particularly the development of congeneic mice with the CBZ/N X chromosome on the NZB background. In addition, the development of H-2 congeneic NZB strains and immunoglobulin allotype congeneic NZB strains are proceeding. These strains will provide information on the possible roles of MHC and VH regions in autoimmune pathogenesis. The NZB.ch congeneic strain has already proven to be of great value. The continued development and further characterization of congenitally immunologic mutant NZ mice has been and will continue to be useful in elucidating the mechanism of autoimmune development in these animals. While NZ mice express a variety of host-viral interactions, recent genetic analysis suggests that viral infection is not a primary etiologic agent in the autoimmune disease of NZ mice. A well-defined clinical entity and a range of abnormalities have been delineated in NZ mice. The present goal is to define the cellular basis of autoimmunity through continued immunologic and genetic analysis of this important animal model of human autoimmune disease.

Animals↗
PubMedDate not supplied

Production of two distinct and independent hepatic immunoregulatory molecules by the perfused rat liver.

By manipulating dietary sugar intake and perfusate glucose concentration, we have identified two independent hepatic immunoregulatory molecules produced by the perfused rat liver. The first is released by injured hepatocytes, appears in perfusates together with hepatocellular glutamic pyruvic transaminase, is quantitatively inhibited by exogenous L-arginine and coelutes with arginase on high-pressure liquid chromatography. Based on these findings, we conclude that this activity is due to the release of cytoplasmic arginase from injured hepatocytes. Since supplementation studies reveal that lymphocyte proliferation is exquisitely arginine-dependent, it is conceivable that arginase released by injured hepatocytes might influence lymphocyte function in vivo by local arginine depletion. The second immunoregulatory molecule is released by noninjured hepatocytes following induction by sugar, particularly glucose, both in vivo or in vitro. This inducible activity is arginase-independent, triglyceride-rich and floats at a density less than 1.006 gm per ml upon ultracentrifugation. Based on these characteristics, we tentatively ascribe this activity to hepatic very low density lipoprotein, the serum counterpart of which is known to express many immunoregulatory properties. These results directly illustrate for the first time the pathophysiological conditions required for the secretion and release of these distinct and independent hepatic immunoregulatory molecules, and they suggest possible routes by which they may influence immunological homeostasis and immunologically mediated liver disease.

Alanine Transaminase↗
PubMedDate not supplied

Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site.

The nucleocapsid (HBcAg) of the hepatitis B virus (HBV) can induce antibody responses via both a T-cell dependent and a T-cell independent pathway and is highly immunogenic during infection. We have examined the T-cell determinants of the antigen and find that HBcAg-specific helper T cells (TH) can help B cells produce antibody against envelope (HBsAg) antigens as well as HBcAg, even though these antigens are found on separate molecules. We have also been able to prime helper T cells with synthetic T-cell epitopes of HBcAg; helper cells primed with a single synthetic epitope can induce B cells to produce antibody that reacts with multiple HBsAg epitopes. One problem with the development of an HBV vaccine is that some vaccinees and patients do not respond to HBsAg directly; our results indicate that this problem can be circumvented using the response to HBcAg.

Animals↗
PubMedDate not supplied

Probing T cell antigen recognition: use of synthetic peptides.

The availability and use of synthetic peptides have significantly enhanced our understanding of T cell recognition of antigen. This review is an attempt to chronicle applications of synthetic peptide technology to examine various aspects of T cell recognition. Specifically, a historical prospective of T cell antigen recognition precedes a description of the use of synthetic peptides to probe T cell recognition in the context of a trimolecular complex, in terms of regulatory and cytotoxic T cells, with respect to T cell tolerance and the concept of immunodominance, and its relevance to autoimmunity.

Animals↗