Biomedical subjects

P Schott

Publications and source records attributed to P Schott.

10 recordsLinked to original sources

PubMed2001

Hepatitis C virus-associated mixed cryoglobulinemia. Clinical manifestations, histopathological changes, mechanisms of cryoprecipitation and options of treatment.

Chronic hepatitis C virus (HCV) infection is frequently associated with a variety of autoimmune phenomenons. Mixed cryoglobulinemia (MC) appears in up to 50% of chronic HCV-infected patients. Cryoglobulins consist of immunoglobulin complexes precipitating in vitro when cooled below body temperature. In most cases IgM with rheumatoid factor activity is found in cryoprecipitates which could lead to vasculitis induced by the deposition of immnuocomplexes in small vessels. This vasculitis is thought to cause clinical symptoms called Meltzer's triad. This triad is represented by purpura, arthralgia and weakness. One third of patients suffering from HCV-associated mixed cryoglobulinemia are developing typical symptoms during their course of disease. The striking association between HCV infection and MC has conduced to the hypothesis that HCV is of major importance in the production of MC with followed vasculitis. Both hepatrophism and lymphotrophism have been reported for the hepatitis C virus. Infection of B-cells by HCV could probably lead to a bcl-2 translocation and immunoglobulin gene rearrangement which results in clonal lymphoproliferation and in synthesis of monoclonal IgM with rheumatoid factor activity. These IgM form immunocomplexes with IgG in the cold, which are finally responsible for the described vasculitis. Histopathological changes of the liver are dominated by chronic HCV infection. The majority of times mild activity of hepatitis or mild fibrosis could be found. Nevertheless, cirrhosis is more often found in HCV-infected patients suffering from MC compared to patients without MC. Conventional treatment of MC is aimed to reduce circulating immune complexes by immunosupression and plasmapheresis. With the emerging concept of a viral pathogenesis the therapeutic approach has changed during the last decade. Interferon treatment of MC, particularly of HCV-associated MC is well established nowadays.

Cryoglobulinemia↗

PubMed1999

Clearance of HCV RNA in a chronic hepatitis C virus-infected patient during acute hepatitis B virus superinfection.

The routes of hepatitis B virus and hepatitis C virus transmission are quite similar and coexistence of both viruses in one patient is not a rare phenomenon. Until now, the natural course of liver diseases induced by coinfections has not been well documented and the mechanisms of interaction between the two viruses and the human host have not been fully clarified. We report the case of a patient suffering from chronic hepatitis due to hepatitis C virus who developed an acute hepatitis B virus superinfection. Serum hepatitis C virus ribonucleic acid became undetectable by reverse transcriptase/polymerase chain reaction at diagnosis of acute hepatitis B virus infection. At the same time, there was a striking increase in the serum concentrations of the antibodies against C22 and C33c hepatitis C virus antigens. Four months after clinical resolution of the acute hepatitis, hepatitis B surface antigen was undetectable in serum and three months later antibodies against hepatitis B surface antigen appeared. Two years after acute hepatitis B virus infection, the patient has had no relapse of markers for viral replication of hepatitis B virus. Transaminases are within the reference range and hepatitis C virus ribonucleic acid is undetectable in both serum and liver tissue. We hypothesize that acute hepatitis B virus infection stimulated a specific humoral response against hepatitis C virus as well as triggering non-specific defense mechanisms which finally eliminated both viruses.

Acute Disease↗

PubMed1998

Hepatitis C virus infection-associated non-cryoglobulinaemic monoclonal IgMkappa gammopathy responsive to interferon-alpha treatment.

BACKGROUND/AIMS: An association of HCV infection with lymphoproliferative disorders, particularly B-cell non-Hodgkin's lymphoma has been described. In the majority of reported patients, mixed cryoglobulinaemia was present as well. Rarely, HCV-associated lymphoproliferative disorders have been observed in the absence of cryoglobulinaemia. In these latter patients, the response to interferon-alpha is largely unknown. CASE REPORT: We report a case of an asymptomatic 31-year-old male with chronic HCV infection and non-cryoglobulinaemic monoclonal IgMkappa gammopathy responsive to interferon-alpha therapy. Prior to therapy, elevated plasma transaminase activities known for longer than a year, serum anti-HCV antibodies and HCV RNA detected by reverse transcriptase-polymerase chain reaction were present. Serum IgM concentration was markedly elevated, immunofixation demonstrated monoclonal serum IgM, and urine kappa-light chains were detected. Cryoglobulins were undetectable in several consecutive serum samples. Bone marrow aspirate and biopsy specimens were unremarkable. Further evaluation, e.g. by ultrasonography and radiography, did not reveal evidence for lymphoma. Treatment with interferon-alpha2a for 12 months resulted in a long-term sustained response to HCV infection and in a normalisation of serum IgM concentration. CONCLUSION: Therefore, the corresponding effects of interferon-alpha on HCV infection and on a monoclonal B-cell population observed in the present case might suggest a pathogenetic connection, similarly, to what has been described for HCV and mixed cryoglobulinaemia. The molecular events, however, leading to HCV-induced monoclonal B-cell expansion remain unknown.

Adult↗

PubMed1998

In vitro reactivity of cryoglobulin IgM and IgG in hepatitis C virus-associated mixed cryoglobulinemia.

BACKGROUND/AIMS: Mixed cryoglobulinemia is frequently associated with chronic hepatitis C virus infection. We aimed to clarify the mechanism, kinetics and participating proteins in cryoprecipitate formation, which are still being debated. METHODS: Eighteen patients with cryoglobulinemia were studied. Isolated serum cryoprecipitates and purified cryoglobulin IgM and IgG fractions were analyzed in vitro by turbidimetry for temperature-dependent complex formation. Immunoglobulin reactivity, i.e. in cryoprecipitates and in cryoglobulin-free sera, was studied using immunoblot and enzyme immunoassays. HCV RNA was detected by reverse transcriptase/polymerase chain reaction. RESULTS: By turbidimetry, purified cryo-IgM precipitated (in the absence of HCV RNA) with cryo-IgG as well as with non-cryoglobulin IgG and with IgG Fc or F(ab')2 fragments. In contrast, purified cryo-IgG did not precipitate with non-cryoglobulin IgM. Anti-HCV IgG reactivity was found in cryoglobulin-free sera, in cryoprecipitates and in purified cryoglobulin IgG fractions. The respective titers were similar. Purified cryo-IgM did not react to HCV-encoded proteins. Binding of cryo-IgM to heterologous IgG was inhibited by intact IgG (up to a mean of about 52%) as well as by IgG Fc (33%) and F(ab')2 fragments (17%). Binding of cryo-IgM to IgG was enhanced at low temperature (4 degrees C vs. 37 degrees C), particularly for type III cryoglobulin IgM. CONCLUSIONS: In hepatitis C virus-associated cryoglobulinemia the in vitro precipitate formation depended on cryo-IgM, while IgG appeared to act as an unspecific antigenic partner. Hepatitis C viral particles were probably not required. Cryo-IgM binding occurred primarily to intact IgG. Anti-HCV reactivity of either cryo-IgM or cryo-IgG was not necessary for precipitate formation. Regarding the pathogenesis, a direct hepatitis C virus protein-dependent stimulation of B-cells producing cryo-IgM seems to be unlikely.

Cryoglobulinemia↗

PubMed1998

Attentional modulation of central odor processing.

Two studies were conducted to investigate the influence of attention on the components of the chemosensory event-related potential (CSERP). In the first study the odors linalool and eugenol were delivered to six male subjects, in the second study three male and two female subjects were presented with their own body odor (axillary hair) and the body odor of a same sex donor. In both studies the odors were presented in an oddball paradigm under ignore and attend conditions via a constant-flow olfactometer. In the ignore condition attention was diverted from the odors with a distractor task, while in the attend condition the subjects were asked to respond to the infrequently occurring odor. In both studies the allocation of attention led to a decrease in the latency of the early components (N1, P2, N2) and to an increase in the amplitude of the late positivities. The modulation of the early components suggests that attentional gating in olfaction might already be effective at an early processing level.

Acyclic Monoterpenes↗

PubMed1997

Interferon-alpha treatment of hepatitis C virus-associated mixed cryoglobulinemia.

BACKGROUND/AIMS: Chronic hepatitis C virus infection is frequently associated with mixed cryoglobulinemia. The efficacy of interferon-alpha treatment in the presence of cryoglobulinemia, particularly the rate of sustained responders, has not yet been well defined. METHODS: Fifty-nine consecutive patients with chronic HCV infection were studied prospectively with regard to the presence of cryoglobulinemia and their biochemical and virological response to interferon-alpha2a therapy. RESULTS: Cryoglobulins were detected in sera of 23 patients. For this latter group of patients, significant differences were found compared to the 36 patients without cryoglobulinemia, i.e. the prevalence of female sex was higher, the duration of liver disease was longer and distinctive laboratory abnormalities, e.g. higher rheumatoid factor activity, were noted as well as a higher prevalence of cirrhosis. The distribution of HCV genotypes and serum HCV RNA titers was similar in the two groups. Interferon-alpha treatment regimens were not different regarding mean cumulative dose and mean duration of therapy. The response to therapy was almost identical, i.e. 35% of patients with cryoglobulinemia showed a sustained response compared to 22% of patients without cryoglobulinemia. The percentages of patients showing a relapse or breakthrough were similar in both groups. Pre-treatment viremia levels were higher in non-responders compared to sustained responders. Non-responders appeared to be more frequent among patients infected with genotypes 1a and 1b, especially among male patients without cryoglobulinemia. CONCLUSIONS: The presence of cryoglobulinemia per se in chronic HCV-infected patients does not adversely affect the outcome of interferon-alpha therapy, including the rate of sustained response.

Adult↗

PubMed1997

CD95/CD95L-mediated apoptosis of the hepatic stellate cell. A mechanism terminating uncontrolled hepatic stellate cell proliferation during hepatic tissue repair.

During liver tissue repair, hepatic stellate cells (HSC), a pericyte-like mesenchymal liver cell population, transform from a "quiescent" status ("resting" HSC) into myofibroblast-like cells ("activated" HSC) with the latter representing the principle matrix synthesizing cell of the liver. Presently, the mechanisms that terminate HSC cell proliferation when tissue repair is concluded are poorly understood. Controlled cell death known as apoptosis could be a mechanism underlying this phenomenon. Therefore, apoptosis and its regulation were studied in HSC using an in vitro and in vivo approach. Spontaneous apoptosis became detectable in parallel with HSC activation because resting cells (2 days after isolation) displayed no sign of apoptosis, whereas apoptosis was present in 8% (+/- 5%) of "transitional" cells (day 4) and in 18% (+/- 8%) of fully activated cells (day 7). Both CD95 (APO-1/Fas) and CD95L (APO-1-/Fas-ligand) became increasingly expressed during the course of activation. Apoptosis could be fully blocked by CD95-blocking antibodies in normal cells and HSC already entering the apoptotic cycle. Using CD95-activating antibodies, transition of more than 95% cells into apoptosis was evident at each activation step. The apoptosis-regulating proteins Bcl-2 and p53 could not be detected in resting cells but were found in increasing amounts at days 4 and 7 of cultivation. Whereas p53 expression was induced by the CD95-activating antibody, no change was inducible in Bcl-2 expression. The Bcl-2-related protein bax could be found at days 2 and 4 in similar expression, was considerably up-regulated at day 7, but was not regulated by CD95-agonistic antibodies. In vivo, acute tissue damage was first accompanied by activation and proliferation of HSC displaying no sign of apoptosis. In the recovery phase, apoptotic HSC were detectable in parallel to a reduction in the total number of HSC present in the liver tissue. The data demonstrate that apoptosis becomes detectable in parallel with HSC activation, which suggests that apoptosis might represent an important mechanism terminating proliferation of activated HSC.

Animals↗

PubMed1997

Clinical, biochemical, and histological changes in hepatitis C virus infection-associated cryoglobulinemia.

The most common extrahepatic manifestation of HCV infection is mixed cryoglobulinemia (MC). 62 unselected patients with chronic HCV infection were prospectively evaluated for the presence of cryoglobulinemia and associated clinical and biochemical parameters. Furthermore, a putative relationship between the HCV genotypes and cryoglobulinemia was tested. Histological features typical for HCV infection were comparatively analyzed in cases with and without cryoglobulinemia. Whether an intrahepatic Th2-response is responsible for the strong antibody production causing cryoglobulinemia was also examined. Cryoglobulins were detected in sera of 30 patients (approximately equal to 48%). Patients with cryoglobulinemia were on the average elder, showed an apparent longer duration of infection, and suffered more frequently from arthralgia, accompanied by a significant increase of total serum IgM concentration and rheumatoid factor activity. The HCV genotype distribution among patients with cryoglobulinemia was not different from that found in patients without cryoglobulinemia. In cases with cryoglobulinemia, an increased activity of chronic hepatitis and a higher grade of liver fibrosis was noted. The prevalence of HCV-typical histological lesions among all patients were: Portal lymphocytic aggregates (40%), bile duct damage (35%), steatosis (47%), and intracellular acidophilic bodies (29%). A significant correlation, however, could not be found between cryoglobulinemia and the presence of HCV-typical histological lesions. An intrahepatic Th2-response causing an increased antibody production could not be observed in cases with cryoglobulinemia.

Adult↗

PubMed1995

Cryoglobulinemia in chronic hepatitis C virus infection: prevalence, clinical manifestations, response to interferon treatment and analysis of cryoprecipitates.

Chronic hepatitis C virus infection can be associated with mixed cryoglobulinemia and systemic vasculitis. The pathogenesis remains poorly understood. 55 consecutive patients with chronic HCI infection (anti-HCV- and serum HCV RNA-positive) were studies prospectively. Cryoglobulinemia was detected in 28 patients (51%) with a mean cryocrit level of 2.2%. Clinical symptoms of vasculitis were encountered in six patients. Compared to those HCV-infected patients without cryoglobulinemia the following distinctive features were observed in the presence of cryoglobulinemia: increased age (p<0.02), female preponderance (p<0.002), longer-lasting HCV infection (mean of 10.7 vs. 4.7 yrs), higher prevalence of cirrhosis (42.8 vs. 0%), increased serum concentration of IgM and increased rheumatoid factor activity, decreased concentration of serum C4 (each p<0.05). The response to interferon treatment was similar in patients with and without cryoglobulinemia. When cryoprecipitates were analyzed by immunofixation, type II cryoglobulinemia was present in 1/3 and type III in 2/3 of patients. By SDS-PAGE four different proteins were demonstrable in cryoprecipitates each identified by immunoblotting as IgG and IgM heavy or light chains respectively. Cryoprecipitate IgGs were shown to react with HCV structural as well a non-structural proteins in a recombinant immunoblotting assay (RIBA). In contrast, cryoprecipitate IgMs reacted only to the HCV core protein c22-3. HCV RNA was detected in cryoprecipitates without a significant enrichment when compared to the corresponding serum or supernatant HCV RNA content. Given the monoclonality of some cryoprecipitate IgM and their reactivity to HCV core, a cross-reactivity to IgG was postulated. In fact, when performing a computer-assisted search for sequence homology, a motif within the core protein (EGLGWAGWL, conserved in HCV genotypes) was identified homologous to a sequence of IgG heavy chains. Thus, temperature-dependent affinity changes of IgM anti-HCV core (nonapeptide) and ensuing complex formation with IgG via binding to the homologous IgG sequence could be a mechanism of cryoprecipitate formation.

Adult↗

PubMed1984

[Comparative multicenter study of 2 methods of determining sensitivity to antibiotics. Gel diffusion method and semiautomatic method in fluid ABAC medium].

Susceptibility of 60 bacterial isolates to 15 antibiotics was determined by two methods in three laboratories: 48 Gram negative bacilli and 12 Staphylococci were selected because of "intermediate" susceptibility to at least one antibiotic. Results show a good correlation between the two methods: more than 90% for carbenicillin, cefazolin, cefoxitin, cefamandole, kanamycin, tobramycin, amikacin, erythromycin, pristinamycin and fusidic acid, between 80 and 90% for penicillin G, ampicillin, oxacillin, gentamicin, doxycycline, chloramphenicol, spiramycin and clindamycin, less than 80% for neomycin, tetracycline, minocycline and oleandomycin. Interpretation criteria are different in the two methods for rifampicin, colistin and cotrimoxazole. Between the three laboratories, correlation was 90,3% and 88,6% for disc diffusion method and ABAC system respectively.

Anti-Bacterial Agents↗