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Biomedical subjects

M Schulz

Publications and source records attributed to M Schulz.

At least 181 records · Page 10Linked to original sources

[Treatment of chronic hepatitis B with interferon alpha-2b].

In a prospective randomized trial 58 patients (46 men, 12 women; mean age 41 [18-65] years) with histologically proven chronic hepatitis B and demonstration of HBs antigen and hepatitis B virus DNA in serum were randomly divided into two groups: 30 patients were treated with recombinant alpha 2b interferon. The interferon was administered subcutaneously, 3 x 10(6) IU, three times weekly for four months. 28 patients served as untreated controls. There was a six-month post-treatment follow-up. Two patients in the treatment group and one in the control group had to be excluded later. In the treatment group one patient responded completely (HBs antigen, HBe antigen and HBV-DNA negative) and eight partially (HBe antigen and HBV-DNA negative). In three patients of the control group, HBe antigen and HBV DNA were no longer demonstrated (P less than 0.05). The loss of HBV features was associated with normalization of serum transaminases activity. Reactivation of liver inflammation after seroconversion was not observed.

Adolescent↗

Treatment of chronic hepatitis B with interferon alfa-2b.

A total of 58 patients with histologically confirmed chronic viral hepatitis B and presence of hepatitis B surface antigen and hepatitis B virus DNA (HBV DNA) in the serum were randomized in a prospectively controlled trial. Thirty patients were treated with 3 megaunits of recombinant interferon alfa-2b (INTRON A, R Schering-Plough, Essex Corporation) subcutaneously thrice weekly for 4 months. Twenty-eight controls received no treatment. The post-treatment follow-up period consisted of 6 months. Twenty-eight treated patients and 27 controls completed the protocol. One female patient of the treatment group showed a complete response, and eight other treated patients (32%) showed a partial response to therapy. Three patients in the control group (11%) lost hepatitis B e antigen and HBV DNA spontaneously. This finding is statistically significant (p less than 0.05). The elimination of hepatitis B virus markers from the serum was associated with a normalization of aminotransferase activities in the serum. Reactivation of hepatitis was not observed after seroconversion.

Adult↗

Lidocaine metabolite formation as a measure of liver function in patients with cirrhosis.

A method for rapid assessment of hepatic function in cirrhotics based on the formation of the lidocaine metabolite, monoethylglycinexylidide (MEGX), was evaluated. The formation kinetics and urinary excretion patterns of MEGX clearly distinguished cirrhotics (n = 12) from healthy volunteers (n = 16). In a prospective study, we compared the prognostic value of the MEGX test with that of traditional parameters in transplant candidates. Patients who underwent transplantation during follow-up were excluded. The study included 58 adult patients with biopsy-proven posthepatitic or biliary cirrhosis. During the follow-up period of 120 days, 10 of 58 patients died of their liver disease. At the time of inclusion, we recorded MEGX formation, indocyanine green (ICG) half-life, caffeine clearance, and the Child-Pugh score. These variables were subjected as covariates to a survival analysis (Cox proportional hazards regression model). The results of the MEGX and the ICG test were significantly related to the 120-day survival. In the stepwise analysis, none of the parameters evaluated contributed to a further significant improvement of our predictive ability when added to the values of ICG (improvement: p less than 0.0005) and MEGX (improvement: p less than 0.0005). These findings suggest that the ICG and MEGX tests were the best short-term prognostic indicators. The easy handling favors the MEGX test over the ICG test as a tool for assessment of hepatic function and short-term prognosis in transplant candidates with cirrhosis.

Adult↗

Monoclonal antibody to the prostate specific antigen.

Somatic cell hybrids were made from mouse myeloma cells and spleen cells derived from BALB/c mice immunized with homogenized epithelial fractions of BPH. The screening by immunoperoxidase staining on human prostate and non-prostate tissue resulted in one monoclonal antibody identifying a prostate specific antigen. Upon SDS-PAGE and Western blot this antigen exhibited a single band at the position of 34 kDa molecular weight. The immunoreactivity of the prostate antigen was found to be localized exclusively in the epithelial lining of ducts and secretions of normal prostate, BPH and prostate cancer. Anti-p34 antibody reacted with an antigenic determinant on the PSA molecule cancer. Anti-p34 antibody reacted with an antigenic determinant on the PSA molecule and inhibited the binding of Anti-PSA antibody to PSA by about 80 to 90% in the RIA.

Adult↗

A retinal ganglion cell neurotrophic factor purified from the superior colliculus.

Dissociated neonatal rat retinal ganglion cells can be maintained by the addition of an extract from the neonatal superior colliculus. This extract can support 95% of ganglion cells over 24 h in culture; in addition it promotes the expression of neurites from these cells. This report describes the purification of a neurotrophic factor from the superior colliculus which supports the survival of 80% of retinal ganglion cells over 24 h in vitro. The purification procedure involves a combination of dye-ligand, anion-exchange, and molecular sieve chromatography. The purified neurotrophic factor has a Stokes radius of approximately 200 A using molecular sieve chromatography in the presence of a chaotropic agent. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified factor indicates that it is a glycoprotein that migrates with a molecular mass greater than 400 kDa. Further characterization of this high-molecular-mass glycoprotein by enzymatic digestion demonstrated that it is a chondroitin sulfate proteoglycan. This factor is clearly distinguishable from other neurotrophic factors that have an effect on retinal ganglion cells such as brain-derived neurotrophic factor and fibroblast growth factor. The chondroitin sulfate proteoglycan from the neonatal superior colliculus is the first proteoglycan to be identified as a neurotrophic factor.

Animals↗

Regulation and cellular localization of the membrane-bound thyrotropin-releasing hormone-degrading enzyme in primary cultures of neuronal, glial and adenohypophyseal cells.

Using monolayer cultures from murine brain and reaggregate cell cultures of rat anterior pituitary we observed that TRH (pyroGlu-His-Pro-NH2) added to the culture medium was not taken up by these cells but hydrolyzed at the pyroGlu-His bond by an enzyme obviously located at the cell surface. This enzyme exhibited a high degree of substrate specificity and other characteristics of the membrane-bound TRH-degrading enzyme. Relatively high enzymatic activity was associated with cultured neuronal cells from embryonic rat brain while glial cells were almost devoid of this peptidase activity. Rather low, but significant activity was found on anterior pituitary cell aggregates. In agreement with previous in vivo studies we observed that the TRH-degrading ectoenzyme on adenohypophyseal cells was regulated by estradiol and stringently controlled by T3, but that the activity of the brain enzyme was not. When pituitary cells were separated according to their size and density and established in reaggregate cell culture, a close correlation was always observed between enzyme activity and the distribution of lactotrophic cells regardless of the animal models (eu- and hypothyroid adult male rats) used and the cell fractionation techniques (velocity sedimentation and sequential velocity/buoyant density sedimentation) employed. Such a close correlation was not observed with other cell types, such as the somatotrophic cells, the folliculo-stellate cells, the ACTH-producing AtT20 pituitary cells, or thyrotrophic cells. In conclusion, the high degree of substrate specificity, the tissue-specific regulation, and the very heterogeneous distribution of the TRH-degrading ectoenzyme on brain and pituitary cells strongly support the hypothesis that this enzyme serves very specialized functions in the transmission of TRH signals at specific target sites.

Aminopeptidases↗

Anti-viral protection and prevention of lymphocytic choriomeningitis or of the local footpad swelling reaction in mice by immunization with vaccinia-recombinant virus expressing LCMV-WE nucleoprotein or glycoprotein.

The viral antigen specificity of primary cytotoxic T cell responses (CTL) of H-2b, H-2k, H-2q, H-2s, H-2f and some H-2-recombinant mice against lymphocytic choriomeningitis virus (LCMV-WE isolate) as well as the specificity of some CTL clones and T cell lines was defined on target cells infected with vaccinia-recombinant virus expressing nucleoprotein (Np) or glycoprotein (Gp). Np was recognized together with H-2q (Dq), H-2d (DLd), H-2s and H-2b (Db). Gp specificity was restricted to H-2f and H-2b (Kb and Db); H-2k-restricted CTL anti-LCMV responses were neither Gp nor Np specific. The anti-viral protective immunity induced by vaccinia-Gp or vaccinia-Np recombinants was evaluated in mice. In vivo protection was T cell mediated by class I restricted Ly-2+ T cells; it correlated well with the CTL specificity defined in vitro. Some of the CTL-nonresponder H-2 allele plus Np or H-2 plus Gp combinations were, however, protected to variable and low degrees by vaccinia-recombinant viruses, indicating that anti-viral protection is a more sensitive readout for CTL activity than the in vitro assay. For example, B10.D2 H-2d mice generated measurable CTL responses only to Np; after immunization with a vaccinia-Np recombinant, LCMV titers were 10(4) times lower in spleens than in vaccinia-primed controls. Although vaccinia-Gp-immunized BALB/c mice revealed no CTL activity in vitro, they nevertheless had 10(2) times lower LCMV titers in spleens than controls. Anti-viral protection, particularly in low-responder combinations, was usually short-lived and diminished after 3 weeks. In a high-responder situation, protection was of a longer duration (greater than 8 weeks). Vaccination with vaccinia-Np or Gp recombinants protected mice against lethal T cell-mediated lymphocytic choriomeningitis induced by LCMV or prevented the local footpad swelling reaction; these in vivo effects were H-2 dependent and followed the identical roles established for CTL recognition in vitro.

Animals↗

Major histocompatibility complex--dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease.

In mice the immune response to infection with lymphocytic choriomeningitis virus (LCMV), a member of the arenavirus family, is mainly based on the activity of cytotoxic T cells. The immunogenic epitopes of the viral nucleoprotein recognized by cytotoxic T cells in various inbred strains of mice were defined. These epitopes were located in H-2d and H-2q mice in the amino-terminal region and in H-2b mice in the carboxy-terminal region of the nucleoprotein. A detailed analysis with synthetic peptides allowed the definition of a common epitope of 9 amino acids in H-2d and H-2q mice and of about 15 amino acids in H-2b mice. These T cell epitopes were all recognized in association with H-2 D or L transplantation antigen. The protective capacity of recombinant vaccinia viruses expressing these epitopes was documented by assaying prevention of virus replication, protection against LCM and prevention of the local footpad swelling reaction. Thus, distinct T cell epitopes on the same internal viral protein mediate protection in a major histocompatibility complex-restricted manner.

Amino Acid Sequence↗

Monoclonal antibody that defines the prostate specific antigen.

A monoclonal antibody to a protein with a single band in the 30-kD region was obtained from fusion of Balb/C mouse spleen cells immunized with epithelial fractions of BPH, with the myeloma cell line P3 x 63 Ag8 6.5.3 by standard procedures. This antigen was characterized in immunobinding studies with various cellular and target antigens and in immunoperoxidase staining.

Animals↗

[Immune neuropathies].

Immunoneuropathies constitute but a small percentage of polyneuropathies, compared to metabolic or toxic neuropathies. However, refined techniques of immunochemistry and biopsy have increasingly improved the etiological characterisation of immunoneuropathies. This review deals with the present diagnostic tools for investigation of polyneuropathies in general and with special immunological means of diagnosis. After two short case reports from our department, the main groups of peripheral nerve diseases, in which immunologic pathomechanisms are postulated, are described regarding symptomatology, special diagnostics and therapy. These groups of diseases are listed with respect to scientific evidence of their immunologic etiology, ranging from acute and chronic Guillain-Barré-Syndrome to paraneoplastic and neuropathies in HIV infections. The conclusion gives a summary of general pathogenetic considerations in immunoneuropathies.

Aged↗

Regulation by dibutyryl cyclic AMP of carnosine synthesis in astroglia-rich primary cultures kept in serum-free medium.

The synthesis of carnosine (beta-Ala-His) by astroglia-rich primary cultures was much higher if the cells were cultivated in Ham's nutrient mixture F-12 than if they were grown in Dulbecco's modified Eagle's medium. Carnosine synthesis was not affected by the presence of insulin, transferrin, phorbol myristate acetate, or dexamethasone. However, dibutyryl cyclic AMP and other agents that can, directly or indirectly, activate cyclic AMP-dependent protein kinases strongly lower the rate of carnosine synthesis. The depression of carnosine synthesis was dependent on the concentration of dibutyryl cyclic AMP. The effect was maximal (approximately 80% inhibition) in cultures preincubated with 1 mM dibutyryl cyclic AMP for 4 days. The adenylate cyclase activator forskolin, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, and 8-bromo-cyclic AMP caused the same depression as dibutyryl cyclic AMP, whereas neither butyrate nor dibutyryl cyclic GMP elicited any effect.

1-Methyl-3-isobutylxanthine↗