PubMed Health⌕ Search

Biomedical subjects

S Schmitt

Publications and source records attributed to S Schmitt.

At least 19 recordsLinked to original sources
PubMed1992

Hypothalamic failure as a sequela of heterozygous protein C deficiency?

Protein C deficiency can lead to cerebrovascular occlusive disease. We describe a patient in whom heterozygous protein C deficiency (type 1) is suspected on the grounds of reduced protein C activity and who suffered from multiple thrombo-embolic events involving the brain and peripheral organs. The patient developed hypothalamic failure with hypernatraemia, hypodipsia, hypersomnolence and hyperkapnia, obesity, hyperprolactinaemia, hypogonadotropic hypogonadism and growth hormone deficiency. We hypothesize that protein C deficiency caused cerebrovascular occlusions which eventually led to hypothalamic insufficiency in this patient. Disorders of the anticoagulant system should be looked for in patients with unexplained hypothalamic disease.

Adolescent↗
PubMed1992

Angiotensin-converting enzyme inhibitors in patients with bronchial responsiveness and asthma.

Twenty-one subjects with known bronchial hyperreactivity were prospectively randomized in double-blind fashion to receive one of two angiotensin-converting enzyme inhibitors (ACE-I), enalapril or spirapril, for three weeks. Spirometry and methacholine provocation were performed prior to, during, and following ACE-I usage. Three of 21 subjects developed a nonproductive cough. However, only one subject wheezed slightly. Spirometry and bronchial reactivity (PD20) were unchanged throughout the study.

Adolescent↗
PubMed1992

[Long-term study "Neurodermatitis therapy using urea-containing Externa"].

A long-term study on the therapy of atopic dermatitis with topical urea agents was conducted by over 400 practising dermatologists and pediatricians in Western Germany from March 1989 to March 1991. 1905 patients of all ages who had a baseline diagnosis of acute exacerbation of their neurodermatic skin condition were entered into this open, uncontrolled, multicenter study. Acute attacks were treated with a combination of hydrocortisone and urea. Once the acute symptoms had subsided, therapy was continued with a 10% urea ointment. Over the 12-month observational period, a total of 84% of the patients were exclusively treated with the two trial preparations and only 16% additionally required other corticosteroids.

Administration, Topical↗
PubMed1990

Differentiation of the nucleotide-binding sites on nucleotide-depleted mitochondrial F1-ATPase by means of a fluorescent ADP analogue.

The interaction of the fluorescent ADP analogue lin-benzo-ADP (containing a linearly extended version of adenine, in which a benzene ring is inserted between pyrimidine and imidazole ring) with nucleotide-depleted mitochondrial F1 was investigated. It was found that lin-benzo-ADP is able to occupy all six nucleotide-binding sites present on the enzyme. Two sites exhibit a very high affinity for the analogue (dissociation constant, Kd, less than 10 nM) and bind it rapidly (association rate constant, k+1, about 1.10(6) M-1 S-1). A third site shows a lower affinity for the analogue (Kd = 1-2 microM) and is occupied relatively fast (k+1 approximately 10(4) M-1 S-1). Binding of lin-benzo-ADP to these three sites is prevented not only in the presence of excess ADP and ATP, but also by IDP and ITP, thus indicating that these sites are the catalytic ones. As it will be discussed, this conclusion is further corroborated by the finding that release of the analogue from the two high affinity sites can be promoted by binding of nucleoside di- and triphosphates to the third site. The remaining three sites were found to bind lin-benzo-ADP with identical affinity (Kd = 1-2 microM) and with a rather low association rate (k+1 = 300-600 M-1 S-1). Binding of the analogue to them is only prevented by ADP and ATP, but not by IDP and ITP, which confirms that these sites are the noncatalytic ones. The analogue could be displaced by excess ADP also from these sites; however, in contrast to the catalytic sites, no promotive effect was observed here. The obvious changes in the nucleotide binding behavior of the non-catalytic sites after depletion of endogenous nucleotides will be discussed.

Adenosine Diphosphate↗
PubMed1990

One-step purification of trypsin and alpha-chymotrypsin by affinity chromatography on Eupergit-aprotinin, a novel carrier for purification of serine proteases.

Aprotinin isolated from bovine lungs was covalently immobilized on Eupergit C. The highly selective affinity adsorbent was used to purify trypsin and alpha-chymotrypsin from pancreatic extract in a single step. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis indicated that both enzymes were highly purified. The maximum binding capacity of Eupergit-aprotinin for bovine trypsin was calculated to be ca. 7.5 mg per gram of gel (wet resin).

Aprotinin↗
PubMed1989

[Biotransformation of benzamidine and benzamidoxime by microsomal enzymes of the rabbit].

At pH 7.4 neither benzamidine (1) is ring-hydroxylated nor benzamidoxime (2) is N-hydroxylated, reduced or ring-hydroxylated by aerobic incubations with microsomal fractions (12000 g supernatant, microsomes) of rabbit liver homogenates and NADPH. Products of hydrolytic processes are also not detected. A very long incubation period and a pH 6.3 are necessary for the detection of a slight reduction of benzamidoxime (2) to benzamidine (1). Results are obtained by use of synthetic reference material and by newly developed HPLC methods. Thus, kinetic studies of the microsomal N-hydroxylation of benzamidine (1) to benzamidoxime (2) in the presence of N-methylbenzamidine (3) performed at pH 7.4 are not influenced by other transformations and provide evidence for the involvement of the same isoenzyme of cytochrome P-450 for both the N-hydroxylation of 1 and the N-dealkylation of 3.

Amidines↗
PubMed1989

The mutagenic potential of high flash aromatic naphtha.

Catalytic reforming is a refining process that converts naphthenes to aromatics by dehydrogenation to make higher octane gasoline blending components. A portion of this wide boiling range hydrocarbon stream can be separated by distillation and used for other purposes. One such application is a mixture of predominantly 9-carbon aromatic molecules (C9 aromatics, primarily isomers of ethyltoluene and trimethylbenzene), which is removed and used as a solvent--high-flash aromatic naphtha. A program was initiated to assess the toxicological properties of high-flash aromatic naphtha since there may be human exposure through inhalation or external body contact. The current study was conducted partly to assess the potential for mutagenic activity and also to assist in an assessment of carcinogenic potential. The specific tests utilized included the Salmonella/mammalian microsome mutagenicity assay, the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) forward mutation assay in CHO cells, in vitro chromosome aberration and sister chromatid exchange (SCE) assays in CHO cells, and an in vivo chromosome aberration assay in rat bone marrow.

Administration, Inhalation↗
PubMed1989

Continuous monitoring of mixed venous oxygen saturation in infants after cardiac surgery.

Continuous mixed venous oxygen saturation (SvO2c) was measured in 16 infants immediately after cardiac surgery. A polyurethane 4F, dual channel catheter (Opticath, Modell U440, Oximetrix) with fiberoptic filaments was introduced into the pulmonary artery during cardiothoracic surgery. The catheters were left in place for an average of 67.5 h (range 27 h -125 h) and there were no catheter-related complications. Correlation between continuous in vivo SvO2 values and in vitro values was satisfactory (r = 0.85), whereas a correlation between SvO2c and arterial oxygen saturation (SaO2) was not found (r = 0.07). The sampled arterial lactate values were inversely correlated to the simultaneously measured SvO2c, but the correlation coefficient was only r = -0.4. There was an inverse correlation between SvO2c and arteriovenous oxygen content difference (Ca-vDO2) (r = -0.82), and a marked inverse correlation to the calculated oxygen utilization ratio (r = -0.97). Therefore SvO2c continuously reflects the overall balance between oxygen consumption and delivery, but the use of SvO2 as a predictor of blood lactate levels is unreliable. A further purpose of the present study was to demonstrate the clinical applications and to show the usefulness of SvO2c-monitoring; particularly as a surveillance and early warning system, as a guide for assessing therapy and its relevance in interpreting other monitored parameters. In our opinion continuous SvO2 measurement is a reliable and valuable indicator of cardiopulmonary function in the immediate post-operative period, even in infants with complicated repair of cardiac malformations.

Blood Gas Analysis↗
PubMed1989

Interaction of non-piliated Neisseria gonorrhoeae strain 7122 and protein IA with an epithelial cell monolayer.

Studies with [14C] uracil-labelled bacteria revealed that the interaction of Neisseria gonorrhoeae with epithelial cells occurred in a time-dependent reaction which is slightly pH-dependent and optimal at pH 6.5. Immunofluorescence tests and immunoelectron microscopy of ultrathin sections confirmed the attachment of these bacteria to the epithelial cell membrane. The interaction of purified protein I with epithelial cells was time-dependent and reached equilibrium after four hours as shown by tracer experiments with 125I-labeled protein I. Cleavage experiments with trypsin followed by SDS-PAGE and autoradiography indicated that protein I (labeled with 125I) was associated with the membrane of the epithelial cells and only partly accessible by trypsin after its interaction with these mammalian cells. Immunofluorescence tests as well as immunoelectron microscopy with the monoclonal antibody G7A2C and gold-labeled protein A confirmed a dense association pattern of protein I with the cell monolayer.

Antibodies, Monoclonal↗
PubMed1988

Activation of MHC-restricted rat T cells by cloned syngeneic thyrocytes.

We have previously demonstrated that rat thyrocytes express MHC class II Ag (RT1.B&D) in response to IFN-gamma. To determine whether MHC class II-positive thyrocytes can be recognized by MHC-restricted T cells, we used our clone of rat thyroid cells (1B-6) derived from the Fisher rat thyroid cell line (FRTL-5) and known to express MHC class II Ag in response to recombinant rat IFN-gamma. CD4+ and CD8+ normal syngeneic Fisher rat spleen T cells were selected by flow cytometry and averaged greater than 96% purity. We demonstrated that irradiated MHC class II-positive but not class II-negative 1B-6 thyrocytes stimulated CD4+ T cells in a primary sensitization reaction over 4 days. In contrast, CD8+ T cells had no response in similar experiments. This stimulation of CD4+ T cells was dose dependent for 1B-6 thyrocytes and was abrogated by anti-rat MHC class II mAb (MRC OX-6). Autoreactive (Fisher) and alloreactive (Buffalo) T cell lines and isolated CD4+ T cells derived from these lines, which were developed against Fisher rat spleen cells, similarly recognized MHC class II Ag expressed on 1B-6 cells but had no detectable response to 1B-6 MHC class II-negative thyrocytes or MHC class II-positive human thyroid cells. The CD4+ T cell recognition of 1B-6 cells via MHC class II Ag supports our previous data with autologous human thyroid T cell co-cultures and is indicative of an autospecific role for thyrocytes in the development of autoimmune thyroiditis.

Animals↗
PubMed1988

Genotoxic activities of benzamidine and its N-hydroxylated metabolite benzamidoxime in Salmonella typhimurium and mammalian cells.

The genotoxic potentials of benzamidine and benzamidoxime were determined to study the toxicological relevance of the metabolic N-oxygenation (N-hydroxylation) of benzamidines to benzamidoximes. Benzamidoxime induced DNA single-strand breaks (in rat hepatocytes) and DNA amplification in SV40-transformed hamster cells. In the experiments performed, benzamidine itself was only marginally positive in the hepatocyte/DNA single-strand break assay. Since these cells possess an intact metabolization apparatus, the biological activities may be attributed to toxic and genotoxic metabolites formed by biotransformation. In the Salmonella typhimurium mutagenicity test (TA 98 and TA 100) benzamidoxime alone exhibited a low mutagenicity in the TA 98 strain in the presence of rabbit liver S-9 fractions. These results permit recognition of the metabolic N-hydroxylation of benzamidines to benzamidoximes as a process to toxication. Indirect evidence for the formation of a glucuronide of benzamidoxime has been obtained from in vitro experiments, but it could not be established that this process was a decisive factor in the genotoxicity of benzamidoxime.

Amidines↗
PubMed1988

Thymocyte maturity in male and female hypogonadal mice and the effect of preoptic area brain grafts.

Hypogonadal mice with a genetic deficiency of gonadotropin-releasing hormone (GnRH) have low levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and gonadal steroids. In this study we found differences from normal mice in many aspects of thymic development. Thymus weights and cellularity were higher in hypogonadal than in normal male mice but lower in hypogonadal than in normal females. Although all normal mice had higher proportions of mature, single staining thymocytes (CD8+ or CD4+) than seen in hypogonadal mice, there was a sex difference in the basis for this shift. Significantly more double-staining (CD8+, CD4+) thymocytes were seen in hypogonadal males than in normal males while both groups had similar single-staining populations. However, in females, both single-staining CD8+ and CD4+ thymocytes were more numerous in normal than in hypogonadal females while numbers of double-staining cells were similar in the two groups. These studies indicate that a mature thymocyte profile may be arrived at through differential effects of reproductive hormones in males and females. When brain grafts containing GnRH cells were used to correct reproductive deficits in hypogonadal mice, there were higher splenocyte counts in males with grafts, a similar trend in females, and a lower ratio of single staining CD4+ to CD8+ thymocytes in all females with grafts vs. all females without, regardless of whether or not the grafts corrected the reproductive hormone status of the recipients, indicating an effect of the graft surgery on the immune system.

Animals↗
PubMed1988

Surface immunolabeling of Neisseria gonorrhoeae employing monoclonal antibodies to proteins IA and IB.

The technique of immunomarking intact bacteria with monoclonal antibodies (MAb) and gold-labeled anti-IgG provides a rapid and reliable method for localization of surface-exposed antigens. Cell suspensions of Neisseria gonorrhoeae were incubated with monoclonal antibodies directed against different epitopes of protein I as shown by ELISA inhibition test (unpublished data). The bound IgG molecules were detected with gold labeled anti-mouse IgG or protein A. MAbs against various epitopes of protein I showed differences in their reaction pattern with intact bacteria. We compared the results achieved by the gold immunomarking technique with coagglutination (CoA) and immunofluorescence (IF) tests. The results of the three methods correlated for some antibodies and were ambiguous for other MAbs. The advantage of the immunogold method over immunofluorescence and coagglutination is that distribution and localization of antigen on the surface of gonococci can be exactly determined using electron microscopy.

Agglutination Tests↗
PubMed1986

Surface-exposed antigenic cleavage fragments of Neisseria gonorrhoeae proteins 1A and IB.

Whole bacteria, isolated outer membranes, and purified protein I (PI) from one transparent (O-) and two different opaque (O+) phenotype gonococcal strains (serogroups I, II, and III; PI serotypes 1, 5, and 9b) were each treated with tolylsulfonyl phenylalanyl chloromethyl ketone-trypsin, alpha-chymotrypsin, and proteinase K. Protein IA (PIA) of strain 7122 (O-, serotype 1, serogroup I) was resistant to proteolysis by tolysulfonyl phenylalanyl chloromethyl ketone-trypsin and alpha-chymotrypsin and only slightly affected by proteinase K, as long as it was associated with intact bacteria or isolated outer membranes. Purified PIA however was cleaved by these enzymes, resulting in two to five fragments. In contrast, all preparations of strains 5766 opaque phenotype (O+, serotype 7, serogroup II) and 1955 (O+, serotype 9b, serogroup III) were accessible to proteolysis, resulting in cleavage fragments of PIB compatible to those described previously by O. Barrera and J. Swanson (Infect. Immun. 44:565-568, 1984), M. S. Blake et al. (Infect. Immun. 33:212-222, 1981), and Blake (in G. K. Schoolnik, ed., The Pathogenic Neisseriae, 1985). Our data indicated that the purified PIB fraction was more accessible to proteases than the PIBs of whole bacteria or outer membranes. The fragmentation pattern of PIA cleavage products were quite different from PIB fragments, consistent with the different structure of these two groups of PI molecules. Time-dependent cleavage experiments with proteases, i.e., alpha-chymotrypsin, indicated that PIA was subsequently cleaved into smaller fragments. Highly reactive monoclonal antibodies, each specific for a surface-exposed epitope of PIA of strain 7122 or PIB of strains 5766 and 1955, as assessed by coagglutination, Western blot, and immunofluorescence, were reacted with PIA and PIB cleavage fragments in Western blot experiments. All cleavage fragments of the purified PIA and PIB preparations with molecular weights of greater than or equal to 14,200 showed immune reaction in Western blotting, whereas whole cell and outer membrane PIB fragments were less reactive with the specific monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1985

Rapid diagnosis of acute mumps infection by a direct immunoglobulin M antibody capture enzyme immunoassay with labeled antigen.

A new immunoglobulin M (IgM) antibody capture enzyme immunoassay with peroxidase-labeled mumps antigen (dMACEIA) is described, and its suitability for practical diagnosis of acute mumps infection is evaluated. All 54 patients with proven mumps infection that were tested showed mumps-specific IgM antibodies. On the other hand, no specific IgM antibodies were present in 16 cases of suspected mumps that could not be confirmed by classical complement fixation serology, and IgM mumps virus antibodies could be detected neither in the sera of 100 healthy individuals nor in those of 16 patients positive for rheumatoid factor. In all, 22 children with acute respiratory illness caused by parainfluenza virus and 44 patients with infections due to other viruses showed no IgM response in mumps dMACEIA. The particular characteristic in which complement fixation antibodies against mumps nucleocapsids appear before and disappear earlier than antibodies to the enveloped mumps virus could not be demonstrated in the dMACEIA. In an extensive epidemic of mumps virus infection, the dMACEIA gave a clear diagnosis of mumps infection in 200 out of 371 suspected cases. By day 2 of the illness, 71% of the patients had detectable IgM, and by day 3, all of them had detectable IgM. In 99% of the cases, dMACEIA gave a positive result in the first available serum specimens, most of which were negative for complement fixation antibodies. A positive but only moderate correlation was thus observed between the two serological procedures. IgM antibodies persisted for at least 6 weeks. The dMACEIA, performed in 3 h, offers a reliable, simple, and rapid alternative to routine methods for detection of acute mumps infection.

Adult↗