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Biomedical subjects

R Thomssen

Publications and source records attributed to R Thomssen.

At least 73 records · Page 4Linked to original sources
PubMed1989

[Lyme borreliosis--the most frequent cause of acute peripheral facial paralysis in childhood].

A prospective hospital-based multicentre study in Lower Saxony allowed to investigate the frequency of acute peripheral facial palsy due to Lyme borreliosis and its clinical and laboratory characteristics. Diagnosis of Lyme Borreliosis was based on detection of IgM antibodies against Borrelia burgdorferi in serum and CSF as well, using an IgM capture ELISA. Between June 1986 and October 1987 27 consecutive cases with acute peripheral facial palsy were studied. Lyme borreliosis is the main cause of peripheral facial palsy in childhood. It was verified serologically in two thirds of the cases. All cases with a positive history for a tick bite and/or an erythema migrans in the head-neck region showed ipsilateral neurological affection suggesting a direct invasion via the affected nerve by Borrelia burgdorferi. Peripheral facial palsy due to Lyme borreliosis represents a monosymptomatic meningoradiculitis. All children with Lyme borreliosis revealed a lymphocytic CSF pleocytosis, whereas in cases of unknown etiology CSF findings usually were normal. Therefore, in any case of facial palsy with an inflammatory CSF syndrome Lyme borreliosis has to be suspected unless proven otherwise.

Adolescent↗
PubMed1988

[Approaches to developing an optimal vaccine against hepatitis B viruses].

Using recombinant DNA methods, many different approaches may be followed to optimize immunoprophylaxis against hepatitis B viruses. Most obviously a future vaccine should contain besides the known major surface protein two further envelope proteins which have recently been identified. All three envelope proteins should be present on the same particle in natural proportion and conformation. Such a vaccine may induce a more reliable and more durable immune protection even in difficult cases. The protective potential of the viral core protein, in particular of HBeAg, ought to be studied further experimentally. Possibly, the core proteins may be helpful in an immune therapy of already infected persons.

Antigen-Presenting Cells↗
PubMed1987

Active immunization against hepatitis B: immunogenicity of a recombinant DNA vaccine in females, heterosexual and homosexual males.

Three groups of subjects (58 females, 54 heterosexual males, and 50 homosexual males) received three doses of a recombinant DNA yeast-derived hepatitis B vaccine according to a 0, 1, and 6 month vaccination schedule. Local and general side effects were mild. Seroconversion rates after three injections were not significantly different between the groups. Females showed a significantly higher anti-HBs response than both groups of males, and heterosexual males had higher antibody titres than homosexual males. Among the four homosexual non-responders, three were carriers of the human immunodeficiency virus.

Adolescent↗
PubMed1986

Assay of hepatitis B virus genome titers in sera of infected subjects.

A method for quantitative standardization of the DNA hybridization assay for hepatitis B virus (HBV) DNA protein complex in serum is described. This method was used to determine the titer of HBV DNA in various groups of subjects with HB surface antigen (HBsAg) in order to ascertain its accuracy as an index of infectivity. The method's detection limit was 10(5) genome equivalents or 0.3 pg DNA per ml. Titers of 5 X 10(7) to 5 X 10(8) genome equivalents per ml were found to be typical for persistent massive viremia, which occurred more frequently in symptomatic (30 of 48) than in asymptomatic (24 of 72) carriers positive for HBe antigen (HBeAg). Moderate viremia (10(5)-5 X 10(7)) was usually found in patients eliminating the virus from the blood. Patients with resolving acute hepatitis B were frequently positive at the onset (18 of 26) with moderate titers, but became negative within several weeks. In 11 patients who developed chronic hepatitis B, titers increased until typical massive viremia was evident. Whereas healthy HBsAg carriers with anti-HBe always had negative genome titers (144 of 144), symptomatic carriers with anti-HBe often had moderate genome titers (9 of 30). It is recommended that genome titers be monitored in HBeAg-positive and in symptomatic anti-HBe positive virus carriers in order to distinguish between virus carriers with high (greater than 5 X 10(7)), moderate (10(5) -5 X 10(7)) and low (less than 10(5)) infectivity.

Acute Disease↗
PubMed1986

Cytostatic effect of gangliosides present in the membrane of macrophages.

Stimulated macrophages are known to inhibit the growth of certain tumor cells. Using mouse peritoneal exudates as a source of macrophages and the mastocytoma cell line P815 as the target, the inhibition was found to depend on direct contact between the macrophages and the growing cells. Cytostatic activities were detected in extracts of macrophages as well as in membranes of macrophages bound to substances of low molecular weight. Physical and biochemical characteristics of the cytostatic activity hint toward N-acetylneuraminic acid containing glycosphingolipids (gangliosides). The different macrophage gangliosides were separated by thin-layer chromatography. All types showed cytostatic activity, but the most effective gangliosides were identified as monosialoganglioside GM1 and disialoganglioside GD3.

Animals↗
PubMed1986

Precore sequence of hepatitis B virus inducing e antigen and membrane association of the viral core protein.

Hepatitis B virus (HBV) DNA contains a precore (pre-c) sequence of 29 codons with unknown function upstream of its gene for the major core protein. Its significance was studied by expression of core proteins with and without pre-c in Escherichia coli. Core protein without pre-c, P22c, assembled spontaneously to core particles and formed core antigen. It had the same size and antigenicity as core particles from infected liver. Core protein with pre-c, P25e, instead formed membrane-associated e antigen (HBeAg). The data suggest that pre-c functions as a signal peptide for the attachment of core protein P25e to cellular membranes. This hypothesis can explain the not yet understood relation between viremia and HbeAg and the protective role of anti-HBe antibody.

Amino Acid Sequence↗
PubMed1986

Cutoff levels of immunoglobulin M antibody against viral core antigen for differentiation of acute, chronic, and past hepatitis B virus infections.

The titer of antibody against core antigen of hepatitis B virus in the immunoglobulin M class (IgM anti-HBc) was determined by an IgM capture assay of reduced sensitivity (30 arbitrary units). The distribution of titers among 235 acute hepatitis patients who were hepatitis B surface antigen (HBsAg) positive suggested that 600 U forms a lower cutoff value for acute hepatitis B. Clinically apparent cases of acute hepatitis with high IgM anti-HBc and without HBsAg were rare (2.6%). Acute, non-B hepatitis in HBsAg carriers was more frequent (9.4%). In chronic hepatitis B, 39% of 174 biopsy-proven cases had moderate titers of 30 to 600 U, whereas healthy HBsAg carriers were rarely (4/84) positive. In mild or inapparent infections without HBsAg, titers were between 50 and 400 U. Thus, sufficiently accurate and sensitive quantitation of IgM anti-HBc allows for differentiation of acute and nonacute hepatitis B virus infection in acute hepatitis, partial differentiation between clinically symptomatic and asymptomatic chronic infections, and identification of recent subclinical infections.

Acute Disease↗
PubMed1985

Active immunization against hepatitis B: immunogenicity study in homosexual men.

In a group of 238 homosexual men a hepatitis B vaccine developed at the National Reference Center for Viral Hepatitis (Göttingen/Germany) was evaluated. The vaccine was well tolerated. Three intramuscular injections of inactivated HBsAg (subtype ad; 11300 Natl. Units/dose) induced antibody production in 89.7% of the subjects. Four participants exhibited signs of hepatitis B infection. Vaccine recipients younger than 30 years produced higher antibody levels than older vaccinees. More than one half of the subjects who had only anti-HBs (anti-HBc negative) prior to immunization did not show an anamnestic booster response but formed IgM-anti-HBs. Antibody levels were significantly lower in anti-HBs negative/anti-HBc positive recipients than in subjects who had only anti-HBs or no hepatitis B markers. Immunological studies of T and B cell function did not provide conclusive evidence for the underlying cause of the different immune responses.

Adult↗
PubMed1983

Increase in immunoglobulin M antibodies against gut bacteria during acute hepatitis A.

The marked increase in the total serum immunoglobulin M (IgM) is a characteristic feature of acute hepatitis A. To study the nature of this IgM, we assayed serial titers of IgM antibodies against various antigens during and after acute hepatitis A. The antibodies against blood group antigen remained unchanged throughout the observation period. Thus, the production or metabolism of IgM was not nonspecifically altered. The IgM antibody against hepatitis A antigen decreased and finally disappeared during convalescence as expected. However, its time course did not correlate quantitatively with the concentration of the total serum IgM. In contrast, IgM antibodies against gut bacteria Bacteroides fragilis and Streptococcus faecalis were considerably elevated in all patients at the onset of the disease, and they normalized similarly to the total IgM during convalescence. IgM antibodies against Escherichia coli were elevated only in some of the patients. The data suggest that the amount of IgM antibodies against gut bacteria contributes significantly to the increase in the total serum IgM in acute hepatitis A.

Antibodies, Bacterial↗
PubMed1983

Kinetics, subtype specificity and immunoglobulin class of anti-HBs induced by hepatitis B vaccine.

The protective effect of anti-HBs against hepatitis B virus is proven only for the common antibody anti-HBs/a but not for subtype specific antibody. Using subtype specific radioimmunoassays, anti-HBs/a and anti-HBs/d were quantitated in recipients of an HBsAg/ad vaccine. All persons developed anti-HBs/a. The relative proportion of anti-HBs/d was variable and very high at the beginning of the immune response. At this time the anti-HBs was predominantly in the IgM class. IgM-anti-HBs disappeared rapidly after its peak value and was more slowly replaced by IgG-anti-HBs. Persons who had only anti-HBs or anti-HBc as the only antibody did usually not react with an anamnestic booster response and developed IgM- anti-HBs after vaccination. An injection schedule of 0, 1, 4 months produced ten times higher titers than a 0, 1.5, 3 months schedule 4 weeks after the third injection. However, 6 months later titers were essentially identical. Nine of ten "non-responders" became positive after a fourth injection.

Adult↗
PubMed1983

Safety and potency aspects in the preparation of an experimental HBsAg vaccine.

No experimental setting is available to exclude residual infectivity in HBsAg vaccines derived from human plasma. Thus, safety can be achieved only by means of their preparation. To reduce infectivity of the starting material, only plasma from healthy anti-HBe positive donors was used. In the FRG, 50% of all healthy HBsAg carriers with anti-HBe have a suitable serum level of 5 to 20 micrograms/ml. The purification procedure removed hepatitis B virus by a factor greater than 10(4). The purified product contained only the HBsAg proteins and no serum protein, as shown by SDS gel electrophoresis. The pure HBsAg was treated with formalin 1:500 at 37 degrees C for 4 days. A loss of 30 to 50% antigenicity was tolerated to achieve the highest possible destruction of known and unknown infectious agents. After inactivation, the HBsAg was bound to aluminium hydroxide gel. The gel was washed repeatedly to remove the formalin. Doses of 40 micrograms or 20 micrograms absorbed HBsAg protein were given to greater than 2500 persons without serious side effects. In greater than 97% anti-HBs was formed with a median titer of 1900 I.U./ml.

Follow-Up Studies↗
PubMed1982

[Outbreak of hepatitis B at a butcher's shop].

Within one year four butchers fell ill with acute hepatitis B in a butcher's shop with ten employees. A symptom-free hepatitis B virus carrier was detected among the non-diseased employees. Lack of IgM-anti-HBc antibodies showed that the carrier state had probably existed for more than one year. The time course of infections and the kind of cooperation made it very likely that the carrier had infected his symptomatic mates. The outbreak shows that hepatitis B can be an occupational disease also in non-medical occupations. Should hepatitis B occur in a workman exposed to trauma frequently due to his occupation, serological investigation of the workmates is required in order to identify potential sources of infection and to enable future protective measures.

Disease Outbreaks↗
PubMed1982

[Preparation and testing of a hepatitis B vaccine (author's transl)].

Starting with 41.5 l of plasma from anti-HBe positive carriers of HBs antigen, 11,400 doses of a hepatitis B vaccine with 42 micrograms HBsAg-protein and 11,300 national units HBsAg activity per dose were obtained. After purification, HBsAg is obtained in 99% purity with a yield of more than 90% protein. A possible residual infectivity was inactivated by a diluted formalin solution. The infectivity test in chimpanzees confirmed the absence of infectious hepatitis viruses (HBV and nonA-nonB). In guinea pigs the immunogenicity of the vaccine was comparable to that of the reference preparation from the U.S. National Institute of Health. The presence of Al(OH)3 in the vaccine increased the anti-HBs titre by factors of 30-50. After vaccination with two doses 41 of 45 persons became anti-HBs positive, with three doses 42 of 45 persons developed anti-HBs. Median anti-HBs titre after the third doses: schedule I (three doses in intervals of 6 weeks) 427 mWHO-U/ml; schedule II (two doses at an interval of 4 weeks, third doses 4 months after the first doses) 1535 mWHO-U/ml. The vaccine was well tolerated. There were minor local reactions only.

Animals↗
PubMed1980

Experimental non-A, non-B hepatitis: four types of cytoplasmic alteration in hepatocytes of infected chimpanzees.

On the occasion of an outbreak of non-A, non-B hepatitis in a plasmapheresis centre (81 cases, incubation period: 3--6 weeks) a pool of 12 plasma samples was obtained in the early phase of increasing transaminases. Two chimpanzees were inoculated, each receiving 12 ml of the pooled plasma. After an incubation period of 10--12 weeks a mild non-A, non-B hepatitis developed. Serum transaminases were slightly elevated. Needle biopsies, taken fortnightly, showed a slight activation of Kupffer cells (6--8 weeks), single cell necroses, and infiltration of the portal tracts (10--13 weeks). Electron microscopically four types of cytoplasmic change, were found in hepatocytes and assumed to be specific for the infection, Type I: Sponge-like inclusion (6 weeks after inoculation) composed of a dense matrix and irregularly arranged membranes. Type II: Attaching curved membranes (8 weeks), developing by close apposition of two cisternae of smooth endoplasmic reticulum. Type III: Cylindrical complexes (10 weeks), already described in literature. Type IV: Microtubular aggregates, usually neighbouring type III structures. The findings suggest 1) that the agent of the present infection is, at least in part, identical with that of the long incubation type of experimental non-A, non-B hepatitis, and 2) that ultrastructural alterations may precede manifest hepatitis.

Animals↗