Second-generation hepatitis C antibody testing.
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Hepacivirus↗
Biomedical subjects
M G Peters
Publications and source records attributed to M G Peters.
Day-5 protocol liver allograft biopsies document early rejection episodes and are predictive of recurrent rejection.
METHODS: The day-5 posttransplant protocol biopsy specimens and clinical courses of 27 consecutive orthotopic liver transplant recipients followed up at least 6 months were reviewed. RESULTS: Twelve (44%) of 27 patients had histologic evidence of rejection on the day-5 biopsy; 8 (67%) of these 12 patients required OKT3 for reversal of the rejection. No significant differences in biochemical liver test results, bile output, or cyclosporine levels were observed between this group and the 15 patients (56%) without histologic evidence of rejection on day 5. Eight (67%) of the 12 patients with rejection had recurrent rejection episodes, with one recurrence each in six patients, two recurrences in one patient, and three recurrences in one patient. Of the 15 patients without rejection on day 5, nine (60%) subsequently had rejection at 10 days, 14 days, and 1 1/2, 3 1/2, 4, 5, and 11 months after transplantation. Only one (11%) of these nine patients had a recurrent rejection episode. There were no differences in the incidence of posttransplant cytomegalovirus infections between the two groups. Two cases of posttransplant lymphoma were seen; they developed in two patients without rejection on the day-5 biopsy. No patients or allografts were lost to acute or chronic rejection. No complications occurred as a result of the day-5 protocol biopsy. CONCLUSION: The day-5 protocol biopsy is useful in detecting rejection episodes that may not otherwise be clinically apparent.
Adult↗
FK506: inhibition of humoral mechanisms of hepatic allograft rejection.
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Adult↗
Abnormal response to a human B cell growth factor in patients with common variable immunodeficiency (CVI).
Patients with common variable immunodeficiency (CVI) generally fail to produce antigen-specific IgG. We have identified a lymphokine called high molecular weight B cell growth factor (HMW BCGF) that expands an IgG-producing subpopulation of B cells. The B cells from 15 of 16 patients with CVI evaluated in this study failed to proliferate to HMW BCGF, although they proliferated normally to another BCGF, low molecular weight BCGF (LMW BCGF). Nevertheless, 11 patients had more than normal numbers of B cells expressing HMW BCGF receptors. The HMW BCGF receptors on the B cells of three patients with CVI studied were the same molecular weight as the normal HMW BCGF receptor. Examination of B cells from four patients with CVI for intracellular signals produced in normal B cells after stimulation with HMW BCGF revealed that B cells from patients with CVI failed to developed significant increases in cyclic adenosine monophosphate or phosphoinositides after HMW BCGF stimulation. However, cytoplasmic phosphoinositides in the B cells from all four patients with CVI were already increased above what is observed in normal B cells before stimulation with HMW BCGF (either freshly isolated or Staphylococcus aureus Cowan I-activated B cell). Thus, the failure of B cells from patients with CVI to respond to HMW BCGF may be related to their abnormal activation in vivo. Since HMW BCGF expands a subpopulation of memory B cells, the inability of CVI B cells to respond to HMW BCGF may contribute to their abnormal secondary responses to antigens.
Adolescent↗
FK 506: reversal of humorally mediated rejection following ABO-incompatible liver transplantation.
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ABO Blood-Group System↗
Fulminant hepatic failure after repeated exposure to isoflurane anesthesia: a case report.
A previously healthy but obese 26-yr-old woman was diagnosed as having hepatic dysfunction 17 days after the third of three consecutive exposures to isoflurane anesthesia for paranasal sinus surgery. Serum laboratory findings included elevated aminotransferases and bilirubin. Radiographical evaluations showed no evidence of extrahepatic disease. Serological studies were negative for acute viral infections, and serum copper was normal. The patient's condition deteriorated over the ensuing 17 days, with hyperreflexia, hypoglycemia and a rapid fall in serum aminotransferases with a concomitant rise in bilirubin level and prothrombin time despite maximal medical support. The liver volume as shown by computed tomography fell from 1,290 cm3 to 680 cm3 over 6 days. The patient underwent successful orthotopic liver transplantation 25 days after onset of symptoms. Histopathological examination of the resected liver showed submassive and massive necrosis, with a few foci of microvesicular steatosis and ultrastructural evidence of mitochondrial abnormalities. Although we found insufficient evidence to prove that this case was caused by isoflurane anesthesia, the clinical course and histopathological findings are similar to those in hepatic injury caused by halothane anesthesia. Therefore we report this as a possible case of fulminant hepatic failure resulting from isoflurane anesthesia.
Adult↗
The Ba fragment of complement factor B inhibits human B lymphocyte proliferation.
Normal human B lymphocyte function is finely regulated by both positive and negative signals at each stage of activation, proliferation, and differentiation. Activation signals include antigen and surface Ig cross-linking agents such as anti-mu or anti-delta. Signals inducing proliferation include IL-2, high m.w.-B cell growth factor (BCGF), and low m.w.-BCGF. IL-2 as well as IL-6 and other partially characterized B cell differentiation factors can induce terminal differentiation of proliferating B cells into Ig-secreting plasma cells. Various C components have been described to regulate B cell function including Bb that enhances proliferation, C5a that enhances Ig production, and C3a that inhibits Ig production. In our study, we examined the ability of the factor B cleavage fragment Ba to influence human B cell function. Ba did not affect the activation of resting B cells but inhibited the proliferation of activated B cells stimulated with either high m.w.-BCGF or low m.w.-BCGF. The inhibition occurred with doses of Ba as low as 1 microgram/ml (29 nM). Ba was found to bind to activated human B lymphocytes in a saturable manner with an apparent K of approximately 25 nM and an apparent Bmax of 56,000 sites/cell. A peptide made of the carboxy terminal 10 amino acids of Ba (GHGPGEQQKR), was also found to inhibit growth factor induced proliferation of activated B cells but at an ID50 of approximately 5 microM. Finally, Ba was found to inhibit the terminal differentiation of Staphylococcus aweus Cowan-activated B cells stimulated with B cell differentiation factors but not Ig secretion by the partially differentiated EBV-transformed cell line SKW.6. Thus, concentrations of Ba achievable in vivo at sites of active inflammation were found to act on human B lymphocytes by inhibiting their proliferation. This may act to limit the immune response to a specific antigenic challenge.
Amino Acid Sequence↗
Fulminant hepatic failure caused by acute fatty liver of pregnancy treated by orthotopic liver transplantation.
A previously healthy 35-year-old woman was seen at 37 weeks' gestation with a 10-day history of fever, vomiting, diarrhea and malaise. Serum laboratory findings included elevation of serum bilirubin and AST, prolongation of serum prothrombin time and a positive monospot. A tentative diagnosis of acute fatty liver of pregnancy was made, and a healthy male infant was delivered by emergency cesarean section because of fetal distress. Over the subsequent 3 days, acute progressive oliguric renal failure, disseminated intravascular coagulation, hypoglycemia requiring intravenous dextrose infusion and pancreatitis developed; her mental status progressed to stage III encephalopathy. Quantitative computed tomography estimated the liver volume to be 770 cm3. The decision to proceed with orthotopic liver transplantation was made on the basis of progressive clinical deterioration despite aggressive support and because of her small liver size. After transplant, the patient's multisystem failure rapidly reversed. Histopathological examination of the native liver demonstrated predominantly zone 3 microvesicular steatosis with characteristic ultrastructural changes consistent with acute fatty liver of pregnancy. Southern blot analysis for Epstein-Barr virus DNA was negative. We conclude that orthotopic liver transplantation should be considered for the small group of patients with fulminant hepatic failure associated with acute fatty liver of pregnancy who manifest signs of irreversible liver failure despite delivery of the fetus and aggresive supportive care.
Acute Disease↗
Base-pair substitutions alter the site-specific mutagenicity of UV and MNNG in the SUP4-o gene of yeast.
Yeast strains carrying SUP4-o genes that have base-pair substitutions at hotspots for UV or MNNG mutagenesis were treated with these agents. In both cases, the induced mutation frequencies were substantially reduced. Furthermore, specific substitutions at positions in SUP4-o that had not been mutated by MNNG resulted in the recovery of MNNG-induced mutations at these sites. These results demonstrate that base-pair identity is an important factor determining the site-specific mutagenicity of UV and MNNG in yeast. For UV, our findings suggest that the type of lesion that is induced, but not flanking DNA sequences, plays a role in specifying mutability at the sites examined. In contrast, DNA sequence context seems to be an important factor for MNNG mutagenesis.
Base Composition↗
Disruption of the RAD52 gene alters the spectrum of spontaneous SUP4-o mutations in Saccharomyces cerevisiae.
Defects in the RAD52 gene of the yeast Saccharomyces cerevisiae confer a mutator phenotype. To characterize this effect in detail, a collection of 238 spontaneous SUP4-o mutations arising in a strain having a disrupted RAD52 gene was analyzed by DNA sequencing. The resulting mutational spectrum was compared to that derived from an examination of 222 spontaneous mutations selected in a nearisogenic wild-type (RAD52) strain. This comparison revealed that the mutator phenotype was associated with an increase in the frequency of base-pair substitutions. All possible types of substitution were detected but there was a reduction in the relative fraction of A.T----G.C transitions and an increase in the proportion of G.C----C.G transversions. These changes were sufficient to cause a twofold greater preference for substitutions at G.C sites in the rad52 strain despite a decrease in the fraction of G.C----T.A transversions. There were also considerable differences between the distributions of substitutions within the SUP4-o gene. Base-pair changes occurred at fewer sites in the rad52 strain but the mutated sites included several that were not detected in the RAD52 background. Only two of the four sites that were mutated most frequently in the rad52 strain were also prominent in the wild-type strain and mutation frequencies at almost all sites common to both strains were greater for the rad52 derivative. Although single base-pair deletions occurred in the two strains with similar frequencies, several classes of mutation that were recovered in the wild-type background including multiple base-pair deletions, insertions of the yeast transposable element Ty, and more complex changes, were not detected in the rad52 strain.(ABSTRACT TRUNCATED AT 250 WORDS)
Base Composition↗
Normal human intestinal B lymphocytes. Increased activation compared with peripheral blood.
The state of activation of normal human intestinal mononuclear cells obtained from transplant donors was studied. Compared with PBMC, freshly isolated intestinal mononuclear cells expressed significantly more cell surface activation antigens on both B and T lymphocytes. Intestinal mononuclear cells contained significant numbers of immunoglobulin secreting cells immediately after cell separation. This population included CD5-positive B cells that secreted predominantly IgA. Cells from the large bowel consistently revealed higher numbers of IgA secreting cells than cells from the small bowel. Thus, intestinal B cells are markedly activated in vivo compared with PBMC and this increased activation correlates with increased spontaneous antibody secretion. B cells from the large intestine are more highly activated and secrete more antibody than do cells from the small intestine. The intestinal lamina propria lymphoid compartment exhibits a heightened state of activation that may be important for its distinct role in mucosal defense.
Antigens↗
Primary biliary cirrhosis: management of an unusual case with severe xanthomata by hepatic transplantation.
We report a patient with advanced primary biliary cirrhosis associated with Sjögren's syndrome, xanthelasma, and extensive, painful xanthomata involving cutaneous lipid deposits on her face, abdomen, hands, and buttocks and extensor surfaces over many joints. Despite conventional dietary and drug therapy, these lesions progressed rapidly over 3 years. There was symptomatic improvement of the xanthomata, but no objective amelioration of the xanthomatosis with the use of plasmapheresis over an 18-month period. Liver transplantation was undertaken for decompensated chronic liver disease and poor quality of life due to complications of xanthomatosis. Twelve months after transplantation, all xanthomata and xanthelasma and symptoms attributable to xanthomata had disappeared. Liver transplantation is a drastic but successful remedy for complications of abnormal lipid metabolism associated with primary biliary cirrhosis.
Adult↗
The Bb fragment of complement factor B acts as a B cell growth factor.
The process of B cell growth and differentiation into plasma cells is highly regulated and may be influenced by a large number of inflammatory mediators, including complement components. We have studied the regulatory influence of Bb, a 60-kD peptide created during the cleavage of complement Factor B by Factor D and C3b. Purified Bb alone had no effect on proliferation and differentiation of human splenic or tonsillar B cells. However, when B cells were activated by Staphylococcus aureus Cowan I (SAC), Bb enhanced proliferation in a dose-dependent manner. Bb also enhanced proliferation when cocultured with SAC and suboptimal concentrations of purified 60-kD B cell growth factor (HMW-BCGF), a previously described lymphokine that is known to possess growth-promoting activity. However, Bb had no effect on cells treated with optimal concentrations of HMW-BCGF. Like HMW-BCGF, Bb's major effect was on the larger in vivo activated B cells. Half-maximal enhancement of proliferation was reached at a Bb concentration of 1-10 nM. Of note is the fact that antibody to Factor B recognized HMW-BCGF, and an mAb to HMW-BCGF also recognized Factor B and Bb, but not Ba. Moreover, radiolabeled Bb bound saturably to activated B cells and to an EBV-transformed human B cell line. The binding of Bb was inhibited by HMW-BCGF but not by Ba or IgG. Thus, Bb is antigenically and functionally related to HMW-BCGF, and can act as a B cell growth and differentiation factor at potentially physiologic concentrations. These data suggest that Bb may be important in amplifying the immune response in areas of inflammation. Since complement activation occurs at inflammatory sites long before induction of HMW-BCGF synthesis, Bb may be an early signal for the clonal expansion of antigen-activated B cells.
B-Lymphocytes↗
Prednisone withdrawal followed by recombinant alpha interferon in the treatment of chronic type B hepatitis. A randomized, controlled trial.
STUDY OBJECTIVE: To determine the efficacy of a short course of prednisone followed by recombinant interferon treatment in patients with chronic type B hepatitis. DESIGN: Randomized, controlled trial with a 5-month treatment phase and a 9-month observation period after treatment. SETTING: Two referral-based university-affiliated medical centers. PATIENTS: Thirty-nine clinically stable patients with chronic type B hepatitis, all of whom were positive for hepatitis B antigen, hepatitis B virus-associated-DNA (HBV-DNA), and DNA polymerase for at least 6 months before entry. Patients included 20 heterosexuals and 19 male homosexuals. INTERVENTIONS: Eighteen patients were treated with a 6-week tapered regimen of prednisone, followed by 90 days treatment with recombinant interferon alpha-2b; 21 patients were untreated controls. Paired liver biopsy specimens of 27 patients (pretreatment and 9 months after treatment) were blindly evaluated. MEASUREMENTS AND MAIN RESULTS: Nine treated patients had a sustained loss of HBV-DNA. In addition, eight treated patients lost hepatitis B e antigen and four became negative for hepatitis B surface antigen (HBsAg). When compared with controls the differences were statistically significant for clearance of HBV-DNA and HBsAg (P = 0.035 and 0.037, respectively). Treated patients who had a sustained loss of HBV-DNA had higher initial alanine aminotransferase lower initial DNA and DNA polymerase levels, and were more frequently heterosexual. Patients who responded to treatment with the disappearance of hepatitis B e antigen and HBV-DNA had normal liver function tests and markedly improved liver histology during follow-up. CONCLUSIONS: The immunologic priming provided by a short course of prednisone used with alpha interferon may be an effective treatment for selected patients with chronic type B hepatitis.
Adult↗
Effects of recombinant human leukocyte interferon treatment of endogenous interferon production in patients with chronic type-B hepatitis.
Interferon (IFN) added to cell culture systems alters the capacity of the cells to produce IFN when appropriately stimulated. To evaluate the effects of in vivo administration of IFN on the production of IFN by peripheral blood mononuclear cells (PBMCs), we studied patients with chronic type-B hepatitis who received doses of recombinant human leukocyte (alpha) IFN (IFN-alpha) ranging from 5 X 10(6) units daily to 60 X 10(6) thrice weekly. The production of endogenous IFN stimulated by specific inducers (Sendai virus for IFN-alpha; phytohemagglutinin for IFN-gamma) was studied in cell cultures containing PBMCs obtained from patients before or during courses of IFN treatment. In untreated controls, no change in the mean capacity of PBMCs to produce IFN-alpha was noted after 2 weeks. Priming of endogenous IFN-alpha production, as reflected by earlier production of IFN by PBMCs in culture, occurred in all treated patients irrespective of the dose of IFN-alpha received. Whereas mean 24-hour (total) endogenous IFN-alpha fell in all treatment groups, the response was highly variable in individual patients and half showed no change in total production. Individual variations in endogenous IFN-alpha production were unrelated to serum IFN levels achieved during treatment, changes in serum aminotransferase levels, reduction of hepatitis B virus replication during therapy, or the proportions of T and B lymphocytes in culture. In contrast to the changes in IFN-alpha production, IFN-gamma production by PBMCs was not affected by IFN-alpha treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Treatment of chronic type B hepatitis with multiple ten-day courses of adenine arabinoside monophosphate.
Ten patients with chronic type B hepatitis were treated with three courses of adenine arabinoside monosphosphate (Ara-AMP). The drug was given intramuscularly at a dosage of 10 mg/kg/day in ten-day courses during each of three sequential months. The patients were all men, aged 31-61 years, who were known to have had chronic hepatitis for one to four years. Each of the ten-day courses of Ara-AMP was accompanied by a marked inhibition in the serum levels of hepatitis B virus (HBV) DNA and DNA polymerase activity. However, HBV-DNA remained detectable in every patient during treatment and invariably rebounded to pretreatment levels soon after each course was stopped. One patient developed severe, and two patients developed mild neuromuscular side effects. During a 12-18-month follow-up period, only one of the ten patients has had a sustained clinical, serum biochemical, and serological remission. In this patient, serum HBeAg, HBV-DNA, and DNA polymerase became undetectable three months after the final course of treatment; serum aminotransferase levels subsequently fell into the normal range; and a follow-up liver biopsy showed a diminution in the chronic inflammatory cell activity and a disappearance of intrahepatic hepatitis B core antigen reactivity. Thus, multiple ten-day courses of Ara-AMP do not induce a high rate of remissions in this disease and are associated with appreciable neuromuscular toxicity. Ara-AMP is a potent inhibitor of serum levels of hepatitis B virus, but Ara-AMP therapy has not been shown to have long-term beneficial effects in chronic type B hepatitis.
Adult↗
Effects of immunosuppressive therapy with prednisolone on B and T lymphocyte function in patients with chronic type B hepatitis.
B and T lymphocyte function was studied in 10 patients with chronic type B hepatitis before, during and after a 28-day course of prednisolone therapy. Lymphocyte function was assessed by measuring the in vitro synthesis of immunoglobulin by peripheral blood mononuclear cells stimulated with pokeweed mitogen and by assaying lymphocyte proliferation in response to B and T cell mitogens. During high dose prednisolone therapy, there was a decrease in immunoglobulin synthesis by peripheral blood mononuclear cells and in lymphocyte proliferation to all mitogens. Studies using separated B and T cells showed that prednisolone treatment led to a decrease in both helper and suppressor T cell function but an enhancement of primary B cell function. When prednisolone was withdrawn, lymphocyte function rapidly returned to baseline levels. During prednisolone therapy, serum aminotransferase activities decreased by an average of 50%. In all patients, there was a subsequent rebound increase in serum aminotransferase activities 4 to 10 weeks after withdrawal of prednisolone. This was accompanied by a striking increase in suppressor T lymphocyte activity without significant changes in either helper T cell or B cell function. The close correlation between changes in helper and suppressor T lymphocyte function and serum aminotransferase activities during and after immunosuppressive therapy suggests that immunoregulatory T lymphocytes may play an important role in the pathogenesis of chronic type B hepatitis.
Adult↗