Evaluation of a fully automated glycoprotein G-2 based assay for the detection of HSV-2 specific IgG antibodies in serum and plasma.

Background: Ranking after infections with Chlamydia trachomatis and human papillomavirus, genital herpesvirus is the third most common sexually transmitted disease. The majority of recurrent genital herpes infections are caused by herpes simplex virus type-2 (HSV-2). Seroepidemiological studies on the prevalence of HSV-2 specific IgG antibodies are especially important to study the impact of this infection among risk groups.

Antiviral treatment for human immunodeficiency virus patients co-infected with hepatitis B virus: combined effect for both infections, an obtainable goal?

A large percentage of human immunodeficiency virus (HIV) patients have serological evidence of a past or present hepatitis B virus infection (HBV). Long-term survival is increasing for HIV patients because of highly active antiretroviral therapy. Therefore, the chronic hepatitis B infection may become an important determinant of disease outcome in these co-infected patients.

The TNF-alpha system in heart failure and after heart transplantation: plasma protein levels, mRNA expression, soluble receptors and plasma buffer capacity.

Background: The two soluble tumour necrosis factor (TNF) receptors (sTNF-R1, sTNF-R2) can bind TNF-alpha, which is a cytokine with cardiodepressant properties. In heart failure and after heart transplantation, the TNF-alpha system is unbalanced, due to elevated levels of sTNF receptors.

Aim: To assess the activity of the TNF-alpha system in patients with heart failure and after heart transplantation.

Anti-CD25 therapy reveals the redundancy of the intragraft cytokine network after clinical heart transplantation.

Background: Despite blockade of the interleukin-2/interleukin 2 receptor (IL-2/IL-2R) pathway by the murine anti-CD25 (i.e., IL-2R alpha chain) monoclonal antibody BT563, cardiac rejection can still occur.

Characteristics of the early phase of chronicity in acute hepatitis B infection.

The mechanism of development of chronicity after acute hepatitis B infection has not been elucidated fully. Following a single source outbreak of hepatitis B among 79 adult women, three patients (4%) became chronic carriers of hepatitis B virus (HBV). We compared features of the virus and antibody response of the latter three patients with those of 12 HBeAg-positive cases with resolving infection.

Early prediction of response in interferon monotherapy and in interferon-ribavirin combination therapy for chronic hepatitis C: HCV RNA at 4 weeks versus ALT.

Background/aims: There is consensus that interferon for hepatitis C should be stopped if alanine aminotransferase (ALT) remains elevated after 12 weeks; however, this may lead to unjust treatment withdrawal in around 20% of potential sustained responders. No consensus exists for interferon-ribavirin combination therapy. The aim of this study was to assess the predictive value of an HCV RNA test at 4 weeks in comparison with ALT, both in interferon monotherapy and in interferon-ribavirin combination therapy.

The sequential occurrence of viral mutations in a liver transplant recipient re-infected with hepatitis B: hepatitis B immune globulin escape, famciclovir non-response, followed by lamivudine resistance resulting in graft loss.

Background/aims: The purpose of this study was to characterize the clinical, histological and virological events in an orthotopic liver transplant (OLT) recipient with recurrent hepatitis B infection who was initially managed with hepatitis B immune globulin (HBIg) and when viral recurrence occurred, with nucleoside analogue salvage therapy. The aims were to document the mutations occurring in the hepatitis B virus (HBV) polymerase gene as a consequence of HBIg escape, famciclovir non-response and subsequent lamivudine resistance.

Methods: Throughout the follow-up of 796 days, the patient was seen at least at 4-week intervals.

Quantitative hepatitis B virus DNA assessment by the limiting-dilution polymerase chain reaction in chronic hepatitis B patients: evidence of continuing viral suppression with longer duration and higher dose of lamivudine therapy.

Lamivudine, a novel cytosine analogue, exhibits potent antiviral activity against hepatitis B virus (HBV) in vitro and in vivo. The standard HBV DNA hybridization assay used in phase II clinical studies has a low sensitivity, the detection limit of HBV DNA levels being approximately 10(7) genome equivalents per ml (geq ml-1). In this work we used a semiquantitative polymerase chain reaction (PCR) assay (detection limit approximately 10(3) geq ml-1) to determine HBV DNA levels during a 24-week study of lamivudine in 51 stable chronic hepatitis B patients who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg).

Monk seal mortality: virus or toxin?

During the past few months, more than half of the total population of about 300 highly endangered Mediterranean monk seals (Monachus monachus) on the western Saharan coast of Africa, died in a mysterious disease outbreak. Epizootiological and postmortem findings were reminiscent of similar outbreaks amongst pinniped and cetacean species in recent years, which were caused by an infection with newly discovered morbilliviruses (for review see osterhaus et al.).

Redundancy of the cytokine network in the development of rejection after clinical heart transplantation.

We used reverse transcriptase-polymerase chain reaction analysis to study the effects of anti-rejection prophylaxis with an anti-interleukin (IL)-2 receptor (IL-2R) monoclonal antibody (BT563) on the allogeneic process by analyzing intragraft IL-2, IL-4, and IL-15 mRNA expression. Analysis showed an association between rejection and intragraft IL-2 mRNA and IL-4 mRNA transcription, whereas IL-15 was constitutively expressed: IL-2, 62% (8/13) during rejection versus 23% (8/35) during immunological quiescence (P < 0.01); IL-4, 69% versus 23% (P < 0.

Increased intragraft IL-15 mRNA expression after liver transplantation.

To study T-cell/macrophage interactions at the molecular level in clinical allograft rejection, we measured intragraft mRNA expression of the T-cell derived cytokine IL-2 and the macrophage derived chemokine IL-15, a novel cytokine associated with T-cell activation, in post-transplant liver biopsies (n = 33) and in non-transplanted control liver tissue by reverse transcriptase-polymerase chain reaction (RT-PCR). We analyzed biopsies without evidence of rejection (n = 12), with spontaneously resolving histological rejection (n = 10), or with histological rejection accompanied with clinical rejection (n = 11) defined by rising serum bilirubin and aspartate amino transaminase levels. IL-15 mRNA expression was present in the majority of post-transplant liver biopsies (91%, 30/33) and was significantly upregulated as compared with non-transplanted liver tissue (p = 0.

Identification of more than one mutation in the hepatitis B virus polymerase gene arising during prolonged lamivudine treatment.

Lamivudine has been shown to be a potent and nontoxic inhibitor of hepatitis B virus (HBV) replication in chronically infected patients. During prolonged treatment, drug resistance may develop, related to a mutation of Met to Val or Ile in the YM552DD motif of the HBV DNA polymerase gene. Analysis of the HBV DNA polymerase gene from 8 chronic hepatitis B patients with suspected resistance to lamivudine showed that in addition to a mutation in the YM552DD motif, a second mutation located in the B domain of this gene, a Leu528-to-Met528 change, was consistently and exclusively found in 4 patients showing the YV552DD motif.

The nature of acute rejection is associated with development of graft vascular disease after clinical heart transplantation.

Background: To determine mechanisms that trigger graft vascular disease (GVD) after heart transplantation, we studied parameters that reflect both early and late intragraft allogeneic reactions.

Method: With reverse transcriptase-polymerase chain reaction analysis, mRNA expression of interleukin-2 (IL-2), interleukin-4, interleukin-6, interleukin-10, interferon-gamma, platelet-derived growth factor-alpha, and transforming growth factor-beta was measured in endomyocardial biopsy (EMB) specimens obtained from 34 recipients during the first acute rejection episode (n = 29) or at a comparable time after transplantation for patients without rejection (n = 5) and at time of assessment of GVD by coronary angiography at 1 year (n = 34).

Results: At the time of assessment of GVD, mRNA expression of IL-2, interleukin-4, and interleukin-6 were barely detectable, whereas messenger coding for interferon-gamma, interleukin-10, transforming growth factor-beta, and platelet-derived growth factor-alpha genes were constitutively expressed.

Transmission of hepatitis B virus among heart transplant recipients during endomyocardial biopsy procedures.

Background: The unexpected conversion to HBsAg seropositivity of three cardiac allograft recipients prompted us to conduct a multidisciplinary study to identify the source, transmission mode, and extent of the hepatitis B virus (HBV) infection among the 256 cardiac allograft recipients of our hospital.

Methods: All recipients were retrospectively screened for serum markers of HBV infection. A selected genomic region defining subtypes of the viruses involved was amplified and sequenced.

Comparison of two enzyme-linked immunosorbent assays and one rapid immunoblot assay for detection of herpes simplex virus type 2-specific antibodies in serum.

The sensitivities and specificities of three immunoassays for the detection of herpes simplex virus type 2 (HSV-2)-specific immunoglobulin G antibodies in serum, including the one-strip rapid immunoblot assay (RIBA; Chiron Corporation) and two indirect enzyme immunosorbent assays (EIA; Gull Laboratories and Centocor), were compared by testing a panel of 1,250 serum samples from individuals attending an outpatient clinic for sexually transmitted diseases. A qualitative agreement among the three assays was observed with 1,080 serum samples (86.4%); 291 of the serum samples (23.

Blockade of the interleukin (IL)-2/IL-2 receptor pathway with a monoclonal anti-IL-2 receptor antibody (BT563) does not prevent the development of acute heart allograft rejection in humans.

Background: Anti-interleukin (IL)-2 receptor (IL-2R) antibodies have been used as rejection prophylaxis after organ transplantation. Despite this induction treatment, acute rejections may occur. We wondered whether these rejections developed via the IL-2/IL-2R pathway.

Kinetics of IL-2 and IL-4 mRNA and protein production by graft-infiltrating lymphocytes responsible for rejection after clinical heart transplantation.

During cardiac rejection we studied the kinetics of IL-2 and IL-4 mRNA and subsequent protein production by in vivo primed graft-infiltrating lymphocytes (GIL), using semiquantitative RT-PCR and ELISA. Following in vitro stimulation with either donor or third-party antigens, mRNA expression of IL-2 and IL-4 were already detectable 1-2 h after stimulation, while their protein production could be measured from 4 h onwards at least until 48 h. At both the mRNA and protein level, we measured a donor-specific signal for IL-2 and for IL-4 production (p = 0.

Lamivudine resistance in immunocompetent chronic hepatitis B. Incidence and patterns.

Background: Lamivudine is a non-toxic, potent inhibitor of hepatitis B virus replication. Recently, hepatitis B virus resistance to lamivudine has been described in patients using immunosuppressive drugs after liver transplantation.

Methods: From our cohort of 81 consecutive patients treated with lamivudine, we selected all immunocompetent patients who received lamivudine monotherapy for a period over 26 weeks (n=14).

Fulminant hepatitis B virus: recurrence after liver transplantation in two patients also infected with hepatitis delta virus.

Liver transplantation for hepatitis B virus (HBV)-related liver disease is complicated by HBV recurrence and, consequently, poor patient and graft survival. Patients transplanted for hepatitis delta virus (HDV)-related cirrhosis are reported to have a diminished incidence of HBV recurrence and improved graft survival. However, only a few reported HDV-infected patients had active HBV replicative disease before liver transplantation.

Intragraft IL-4 mRNA expression is associated with down-regulation of liver graft rejection.

The mechanism underlying spontaneously resolving allograft rejection following clinical liver transplantation is unidentified. In this process, immunoregulatory T helper (Th)-2 cytokines like IL-4, often identified with down-regulation of the Th1-dependent (IL-2) cell-mediated response, might play a significant but unknown role. For this reason, we analyzed mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in 57 biopsies derived from 19 recipients.