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Biomedical subjects

M Schulz

Publications and source records attributed to M Schulz.

At least 19 recordsLinked to original sources
PubMed1992

Vaccination with a synthetic peptide modulates lymphocytic choriomeningitis virus-mediated immunopathology.

Vaccination with a nucleopeptide (NP 118; amino acids 118 to 132) representing a cytotoxic T-cell epitope of lymphocytic choriomeningitis virus (LCMV) can modulate immunopathology. Immunization with NP 118 protected H-2d mice against intracerebral infection with the LCMV-ARMSTRONG isolate. However, when NP 118-primed H-2d mice were challenged intracerebrally with an intermediate dose (5 x 10(4) PFU) of the LCMV-DOCILE strain, all mice primed with NP 118 emulsified in incomplete Freund's adjuvant died, whereas unprimed mice survived. Correspondingly, peptide vaccination enhanced specifically the cytotoxic T-cell response, influencing the critical balance between T-cell response and virus spread.

Animals↗
PubMed1992

Inactivation of the thyrotropin releasing hormone.

Thyrotropin Releasing Hormone (TRH; pyroGlu-His-Pro-NH2) is rapidly hydrolyzed at the pyroGlu-His bond by a heterogeneously distributed ectoenzyme and a TRH-degrading serum enzyme. For these enzymes, the high degree of substrate specificity, the tissue specific hormonal regulation, the unusual tissue and the heterogenous cellular distribution strongly suggests that they serve very specialized functions for the transmission of TRH signals at specific target sites.

Animals↗
PubMed1991

Peptide-induced antiviral protection by cytotoxic T cells.

A specific antiviral cytotoxic immune response in vivo could be induced by the subcutaneous injection of the T-cell epitope of the lymphocytic choriomeningitis virus (LCMV) nucleoprotein as an unmodified free synthetic peptide (Arg-Pro-Gln-Ala-Ser-Gly-Val-Tyr-Met-Gly-Asn-Leu-Thr-Ala-Gln) emulsified in incomplete Freund's adjuvant. This immunization rendered mice into a LCMV-specific protective state as shown by the inhibition of LCMV replication in spleens of such mice. The protection level of these mice correlated with the ability to respond to the peptide challenge by CD8+ virus-specific cytotoxic T cells. This is a direct demonstration that peptide vaccines can be antivirally protective in vivo, thus encouraging further search for appropriate mixtures of stable peptides that may be used as T-cell vaccines.

Amino Acid Sequence↗
PubMed1991

Major histocompatibility complex binding and T cell recognition of a viral nonapeptide containing a minimal tetrapeptide.

The primary immune response of cytotoxic T lymphocytes in H-2d and H-2q mice to infection with lymphocytic choriomeningitis virus is directed mostly towards the common major T cell epitope of amino acids 112-132 on the viral nucleoprotein (NP). The molecules responsible for presentation of the T cell epitope NP112-132 are in both haplotypes the MHC class I L antigens (Ld, Lq). Truncations of the amino and carboxy termini of the NP 112-132 sequence revealed the nonapeptide RPQASGVYM (NP118-126) as a most effective peptide antigen, but even the tetrapeptide GVYM was recognized by CTL of both haplotypes in a class I antigen-restricted specificity. When tyrosine (Y) or methionine (M) were substituted with alanine, CTL recognition of the altered nonamer required 10(6) to 10(8) times higher peptide concentrations and in one case (Y----A on Ld) the peptide was not recognized at all. Up-modulation of the expression of Ld and Lq class I antigens as measured by flow cytometry correlated with the ability to present the peptide antigens. The only exception was peptide NP118-126 (M----A), which was recognized by T cells on L-Ld and L-Lq target cells but failed to up-regulate Ld and Lq antigens.

Amino Acid Sequence↗
PubMed1991

[Therapeutic and toxic plasma concentrations and elimination half-lives of commonly used drugs].

For 253 frequently used drugs therapeutic and, if data were available, toxic, and fatal plasma concentrations as well as elimination half-lives were compiled in a table. To assess the significance of drug levels for the therapeutic monitoring of patients, it is essential that a collection of data is readily available. In addition, this list can assist the diagnostic assessment in case of intoxications.

Drug Therapy↗
PubMed1991

Assessment of pretransplant prognosis in patients with cirrhosis.

The objective of this prospective study was to assess the prognostic value of dynamic liver function tests and traditional methods of evaluating liver function in potential candidates for hepatic transplantation. Patients who underwent orthotopic liver transplantation within the follow-up period of 120 days were excluded. The study included 107 adult and 57 pediatric patients with cirrhosis. Postnecrotic cirrhosis was present in 107 and biliary cirrhosis in 57 of 164 patients. During the follow-up period, 26 of 164 patients died of their liver disease. At the time of inclusion, we recorded monoethylglycinexylidide (MEGX) formation from lidocaine, indocyanine green (ICG) half-life, bilirubin and albumin serum concentration, activity of cholinesterase and alkaline phosphatase, prothrombin time, the clinical complication of ascites, and--in adults--the Pugh score also. These variables were subjected as covariates to a survival analysis (Cox proportional hazards regression model) using separately the data from adults, pediatric patients, all patients with postnecrotic cirrhosis, and all patients with biliary cirrhosis. In all of these four subgroups there was a significant relationship between MEGX and ICG test results and the 120-day survival. In the stepwise analysis, none of the remaining parameters contributed to a further relevant improvement of our predictive ability when added to the values of ICG and MEGX. Our results suggest that the ICG and the MEGX test are superior to conventional liver function tests and the Pugh score in assessing short-term prognosis in cirrhotics independently from the etiology of the underlying liver disease. These findings may have important implications for determining the optimum timing of transplantation.

Adolescent↗
PubMed1991

[Evaluation and objective assessment of the treatment course of burn injured children].

Between 1984 and 1989 70 out of 76 children, who underwent a primary inpatient treatment for thermal injury, had predominant second degree burns affecting 3 to 25% of body surface. Data of them, concerning epidemiology, first aid, run of inpatient and following outpatient therapy, were documented and summarised. All patients were physical examined and we judged functional and cosmetic results at least half a year after the injury. A uniform score allowed us a comparison of two different concepts of local therapy: closed treatment with impregnated gauze dressings vs. application of ointment (Flammacerium). Kind of documentation and score are proved to be of advantage in estimating run and results of treatment.

Adolescent↗
PubMed1990

Antiviral cytotoxic T cell response induced by in vivo priming with a free synthetic peptide.

Induction in vivo of antiviral cytotoxic T cell response was achieved in a MHC class I-dependent fashion by immunizing mice three times with a free unmodified 15-mer peptide derived from the nucleoprotein of lymphocytic choriomeningitis virus in IFA. The effector T cells are CD8+, restricted to the class I Ld allele of the analyzed mouse strain, and are specific both at the level of secondary restimulation in vitro and at the effector T cell level. These results suggest that cocktails of viral peptides may be used as antiviral T cell vaccines.

Amino Acid Sequence↗
PubMed1990

[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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗