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Biomedical subjects

B Schulze

Publications and source records attributed to B Schulze.

At least 37 records · Page 2Linked to original sources

Biosynthesis of vitamin B12 in anaerobic bacteria--experiments with Eubacterium limosum on the transformation of 5-hydroxy-6-methyl-benzimidazole, its nucleoside, its cobamide, and of 5-hydroxybenzimidazolylcobamide in vitamin B12.

In anaerobic bacteria 5-hydroxybenzimidazole and 5-hydroxy-6-methylbenzimidazole are precursors of the 5,6-dimethylbenzimidazole moiety of vitamin B12. In order to elucidate the pathway from these bases to vitamin B12, experiments on the transformation of 5-hydroxy-6-methylbenzimidazole, of 5-hydroxy-6-methylbenzimidazole-alpha-D-ribofuranoside, of 5-hydroxybenzimidazolylcobamide and of 5-hydroxy-6-methylbenzimidazolylcobamide into vitamin B12 were carried out. The vitamin B12 synthesized by the anaerobe Eubacterium limosum in the presence of 5-hydroxy-6-methylbenzimidazole and L-[methyl-13C]methionine was subjected to NMR spectroscopy. It revealed that the methyl group at C5 of the 5,6-dimethylbenzimidazole moiety was 13C labeled, whereas the methyl group at C6 was unlabeled. This shows that the transformation of 5-hydroxy-6-methylbenzimidazole into the base moiety of vitamin B12 occurs regiospecifically. 5-Hydroxy-6-methylbenzimidazole-alpha-D-ribofuranoside as well as 5-hydroxybenzimidazolylcobamide and 5-hydroxy-6-methylbenzimidazolylcobamide were also transformed into vitamin B12 by E. limosum. When 5-hydroxy-6-methylbenzimidazolylcobamide 13C labeled at C2 of the base part and 14C labeled in the ribose was used for this experiment, the vitamin B12 obtained from this cobamide was 13C and 14C labeled in the same positions. This demonstrates that the alpha-glycosidic bond of the precursor cobamide is not split during the formation of vitamin B12. It can be deduced from these results that the precursor bases are transformed regiospecifically into their alpha-nucleotides, and partially into their cobamides. The alpha-nucleotides are then transformed into alpha-ribazole-5'-phosphate and, subsequently, into vitamin B12. Most likely the cobamides are degraded to the alpha-nucleotides before being used for the biosynthesis of vitamin B12. A pathway for the latter process is suggested.

Benzimidazoles↗

The psychiatric epidemiology of violent behaviour.

This paper reviews the current state of the debate on the relationship between mental disorder and violent behaviour. Starting from the discussion of methodological approaches to assessing a possible association, the most important studies carried out on the issue in recent years are discussed. Their results concur in supporting the assumption that there is a moderate but reliable association between mental disorder and violence. However, this does not imply that people with mental illness are generally more likely to commit violent acts than members of the general population. An elevated risk of violent behaviour is only evident for specific psychiatric diagnoses and symptom constellations. For schizophrenia and other psychotic disorders, a significant increase in the likelihood to commit violent acts is reported. Substance use disorders and antisocial personality disorder, however, represent a markedly higher risk for violent behaviour. The article further discusses possible determinants of violent behaviour such as psychotic symptoms and comorbidity with substance abuse and considers who is at particular risk of becoming a target of violent acts.

Comorbidity↗

'Eye-witness'.

Explore the source record for details and available documents.

Adult↗

The effect of the peroxisome proliferator ciprofibrate on the gastric mucosa and particularly the gastrin cell.

The peroxisome proliferator ciprofibrate induces hypergastrinemia without inhibiting acid secretion. The present study was carried out to assess the effect of ciprofibrate on serum gastrin and gastrin (G) cells in different strains of rats and to compare the effect of ciprofibrate with other lipid-reducing agents (lovastatin and simvastatin) which have a different mechanism of action. Serum gastrin was determined by a radioimmunoassay method, G cell density by histomorphometry after immunostaining for G cells, and gastrin, somatostatin and histidine decarboxylase (HDC) mRNA abundance by Northern blot analysis. Ciprofibrate (100 mg/kg/day for three weeks) induced a marked hypergastrinemia (P < 0.01) in male and female Fischer rats as well as in female Wistar rats. Simvastatin and lovastatin did not affect serum gastrin. Antral G cell density increased significantly in female Wistar rats (P < 0.05) and non-significantly in the other rats after ciprofibrate. Both gastrin and somatostatin mRNA abundance in antral mucosa increased markedly and significantly (P < 0.01) after ciprofibrate treatment. The present study shows that the peroxisome proliferator ciprofibrate induces hypergastrinemia secondary to an increased storage and synthesis of antral gastrin. Since somatostatin mRNA abundance also increased, the present study suggests that ciprofibrate and possibly other peroxisome proliferators in sufficient concentrations have a stimulatory effect on endocrine cells.

Animals↗

[Mentally ill patients--a danger?].

This paper reviews the current state of the debate on the relationship between mental disorder and violent behaviour. Starting from the discussion of methodological approaches to assessing a possible association, the most important studies carried out on the issue in recent years are discussed. Their results concur in supporting the assumption that there is a moderate but reliable association between mental disorder and violence. However, this does not imply that people with mental illness are generally more likely to commit violent acts than members of the general population. An elevated risk of violent behaviour is only evident for specific psychiatric diagnoses and for particular symptom constellations. For schizophrenia and other psychotic disorders, a significant increase in the likelihood to commit violent acts is reported. Substance use disorder and antisocial personality disorder, however, represent a markedly higher risk for violent behaviour. The article further discusses possible determinant of violent behaviour such as psychotic symptoms and comorbidity with substance abuse, and considers who is at particular risk of becoming a target of violent acts.

Comorbidity↗

The histone H1 genes of the dipteran insect, Chironomus thummi, fall under two divergent classes and encode proteins with distinct intranuclear distribution and potentially different functions.

Four histone H1 genes of the midge, Chironomus thummi piger, and three H1 genes of the subspecies C. thummi thummi have been cloned and assigned to the four different H1 proteins from C. thummi larvae. Together with an earlier cloned H1 gene from C. thummi thummi [Hankeln, T. & Schmidt, E. R. (1991) Chromosoma 101, 25-31], these genes probably constitute the complete complement of H1 genes in both subspecies. They were found to fall under two classes that differ remarkably in their gene copy numbers, genomic organization, structure of flanking sequences, codon usage, and expression during embryonic development, and that encode H1 proteins of divergent structure. Histone H1 I-1 contains an inserted sequence, KAPKAPKAPKSPKAE in C. thummi piger, and KAPKAPKSPKAE in C. thummi thummi, that is lacking in the other H1 variants, H1 II-1, H1 II-2, and H1 III-1. In the immediate neighbourhood to the inserted sequence, a substitution in the H1 I-1 protein sequence dramatically enhances the potential to form a reversed turn. In early development, H1 I-1 is expressed at a higher rate than the other H1 genes. The transcripts have a size of about 1 kb; in addition, the H1 I-1 gene exhibited two minor transcripts of about 2.5 and > 3 kb size in middle blastoderm that are possibly polyadenylated. Together with our earlier finding that histone H1 I-1 is found in a limited number of polytene chromosome bands whereas the other H1 histones are uniformly distributed in chromatin, these results intimate functional differences between the two classes of H1 genes and their products.

Amino Acid Sequence↗

Mosaicism in trisomy 8: phenotype differences according to tissular repartition of normal and trisomic clones.

Three new observations of trisomy 8 mosaicism are presented. In two postnatal cases, both patients showed agenesis of corpus callosum associated with different clinical findings. In a third case, the prenatal diagnosis revealed trisomy 8 mosaicism exclusively in chorionic villi (CV) cells long term culture. Normal results were obtained in CV direct preparation and in cultured amniotic cells. In lymphocytes, the child showed low level trisomy 8 mosaicism. The only clinical findings were deep palmar and plantar furrows. The present cases as well as reports in the literature indicate that the variation in tissular repartition of normal and trisomic clones in trisomy 8 mosaicism is possibly responsible for the missing correlation between cytogenetic findings and clinical severity in this syndrome.

Child, Preschool↗

Structural and functional analysis of the globular domain IVa of the laminin alpha 1 chain and its impact on an adjacent RGD site.

The globular domain IVa (about 250 residues) of the laminin alpha1 chain was obtained in recombinant form from mammalian cell clones. It was prepared either with (alpha1IVa-R) or without (alpha1IVa) an adjacent cell-adhesive RGD site which seems to be masked in laminin-1. The recombinant products could be visualized as globular structures by rotary shadowing, were resistant to trypsin and shared immunological epitopes with laminin-1, indicating folding into a native structure. Sequence analysis of pepsin fragments demonstrated the insertion of the globular domain into an epidermal growth factor-like scaffold which is characteristic of the extracellular laminin domain IV (L4) module. Only little immunological cross-reaction was found, however, with other L4 modules from perlecan and different laminin isoforms. Fragment alpha1IVa-R, but not fragment alpha1IVa, bound to alphaVbeta3 integrin, although to a distinctly lower level than a laminin fragment where the RGD site is fully exposed. The fragments also had no or only little cell attachment activity. This confirmed previous predictions that the globular domain alpha 1IVa masks the RDG site in laminin-1. Domain alpha 1IVa showed, in addition, a weak binding activity for the basement-membrane protein fibulin-1.

Amino Acid Sequence↗

Structural and cell-adhesive properties of three recombinant fragments derived from perlecan domain III.

Domain III of the basement membrane proteoglycan perlecan was produced as three overlapping fragments in stably transfected mammalian cell clones. These recombinant fragments (43-48 kDa) were obtained in purified form and showed complete immunological cross-reactivity with perlecan, indicating their native structure. Rotary shadowing electron microscopy of each fragment demonstrated a small globular structure connected to a short rod. These data were interpreted to indicate that domain III has an elongated shape of 30 nm in length and consists of alternating globular domains (L4 modules) and short connecting segments attributed to tandem arrays of LE (laminin-type of EGF-like) modules which form rod-like segments in laminins. Sequence analyses of pepsin fragments were consistent with the disulfide-bonding patterns known for these modules from studies with laminin fragments, but two additional disulfide loops were also identified. Several cell lines which attached to mouse perlecan and/or human fibronectin failed to adhere to the domain III fragments, despite the fact that one of them contained an RGD (Arg-Gly-Asp) site in the L4 module. Furthermore, no significant binding was observed in solid phase binding assays with alpha 5 beta 1 and alpha v beta 3 integrins underscoring the low activity or accessibility of the RGD site.

Amino Acid Sequence↗

Structural properties of recombinant domain III-3 of perlecan containing a globular domain inserted into an epidermal-growth-factor-like motif.

A fragment comprising approximately domain III-3 of the basement membrane heparan sulfate proteoglycan perlecan was prepared in recombinant form from kidney cell clones. This fragment was predicted to contain a cysteine-free globular domain inserted within an epidermal-growth-factor(EGF)-like motif (L4 module) and three additional EGF-like motifs (LE module) without large inserts. This prediction was confirmed by electron microscopy, which demonstrated a globule joined to a very short rod-like segment. The globule was selectively destroyed by pepsin, which also demonstrated that its insertion into an EGF-like motif did not prevent the typical disulfide connections known for such motifs. Yet the globule was more stable against neutral proteinases. The fragment showed a distinct content (55-60%) of alpha helical and beta structure and a partially reversible melting of the conformation in 6 M guanidine. Antibodies raised against recombinant domain III-3 demonstrated a complete cross-reaction with tissue-derived perlecan but not with laminin and a distinct basement membrane staining of tissue sections. Most of the epitopes were lost after reduction and alkylation. Together the data demonstrated a proper folding of recombinant domain III-3 similar to its structure in the native protein and provided the first structural evidence for a novel globular protein motif L4 based on an EGF-like scaffold.

Amino Acid Sequence↗

The vertebrate linker histones H1 zero, H5, and H1M are descendants of invertebrate "orphon" histone H1 genes.

We investigated the evolutionary history of the divergent vertebrate linker histones H1 zero, H5, and H1M. We observed that the sequence of the central conserved domain of these vertebrate proteins shares characteristic features with histone H1 proteins of plants and invertebrate animals which otherwise never appear in any vertebrate histone H1 protein. A quantitative analysis of 58 linker histone sequences also reveals that these proteins are more similar to invertebrate and plant histone H1 than to histone H1 of vertebrates. A phylogenetic tree deduced from an alignment of the central domain of all known linker histones places H1 zero, H5, and H1M in close vicinity to invertebrate sperm histone H1 proteins and to invertebrate histone H1 proteins encoded by polyadenylated mRNAs. We therefore conclude that the ancestors of the vertebrate linker histones H1 zero, H5, and H1M diverged from the main group of histone H1 proteins before the vertebrate type of histone H1 was established in evolution. We discuss this observation in the general context of linker histone evolution.

Amino Acid Sequence↗

Gender-specific cardiovascular adaptation due to circadian blood pressure variations in essential hypertension.

To determine the effects of circadian variation in arterial pressure on early hypertensive target organ disease, we examined systemic hemodynamics (cardiac output by indocyanine green dye dilution), renal hemodynamics (renal plasma flow by iodine-131 para-aminohippuric acid clearance), left ventricular structure and function (2D-guided M-mode echocardiogram), and 24-h ambulatory blood pressure in 20 women and 46 men with untreated essential hypertension. Both gender groups were subdivided into "dippers" and "nondippers" according to the physiologic nocturnal decrease in mean arterial pressure by 10% of daytime values. Systemic and renal hemodynamics, neurohumoral findings (norepinephrine, epinephrine, dopamine, plasma renin activity), causal blood pressure values, duration of hypertension, and body weight did not differ between the two groups. In contrast, left ventricular mass and mass index was higher in female nondippers than dippers (255 +/- 68 v 184 +/- 81 g, and 137 +/- 30 v 102 +/- 39 g/m2, P < .05, respectively), while in men no significant differences were found (234 +/- 48 v 240 +/- 54 g, and 119 +/- 27 v 121 +/- 13 g/m2, P = NS, respectively). Relative wall thickness (0.45 +/- 0.06 v 0.39 +/- 0.06, P < .05) and posterior wall thickness (1.1 +/- 0.1 v 0.89 +/- 0.2 mm, P < .05) were also found to be greater in female nondippers than in dippers, whereas no significant differences were obtained in men. Thus, the degree of left ventricular hypertrophy correlated with the circadian blood pressure variations in women only, which indicates that left ventricular structure may be more load-dependent in women than in men with essential hypertension.

Adaptation, Physiological↗

Automated imunoanalysis systems for monitoring mammalian cell cultivation processes.

Two different automated immunoanalysis systems are presented. Both are based on the principles of flow-injection analysis and were developed to provide reliable, rapid monitoring of relevant proteins in animal cell cultivation processes. One system uses a turbidimetric analysis, and the other employs a heterogeneous chemistry with immobilized immunocomponents. For both systems, the analysis time is in the range of a few minutes, and a complete analysis cycle, including triplicate analyses and various washing steps, is in the range of 20-30 minutes. Samples from cultivation processes can be analyzed directly without dilution. Quantitation of proteins such as rt-PA or monoclonal antibodies can be performed over an analyte concentration range of 1-1000 mg/L. Both systems were compared to conventional ELISA assays on microtiter plates. The turbidimetric analysis system also included a biosensor for simultaneous glucose determination.

Animals↗

Mode of transformation of [1-15N]5-hydroxybenzimidazole and [1-15N]5-hydroxy-6-methylbenzimidazole into the 5,6-dimethylbenzimidazole moiety of vitamin B12.

The transformation of [1-15N]5-hydroxybenzimidazole and [1-15N]5-hydroxy-6-methylbenzimidazole into the 5,6-dimethylbenzimidazole moiety of vitamin B12 by Eubacterium limosum-cultures was studied. The vitamin B12 obtained was exclusively 15N-labeled in N-1 of the base part, as revealed by NMR-measurements. This indicates that either the unsubstituted 5,6-dimethylbenzimidazole presumably formed is not released from the enzyme until the ribose-5'-phosphate substituent is introduced, or that the precursors are first transformed into their alpha-nucleotide-5'-phosphates which then react to form 5,6-dimethylbenzimidazole-alpha-D-ribofuranoside- 5'-phosphate (alpha-ribazole-5'-phosphate).

Benzimidazoles↗

[Dependence of noise-induced individual and group reactions on stimulus variables and moderators in the reference laboratory for community noise production of former East Germany].

The Reference Laboratory for Local Noise Protection in the former German Democratic Republic selected a random sample of 1000 citizens in the City of Erfurt, who were written to and personally interviewed, also having their exposure to noise emissions measured. This enabled a quantitative estimate to be made of the level of noise pollution to which the population was subjected, while simultaneously contributing towards determining an annovance threshold and demonstrating the important role played by subject-specific factors in any one person's perception of the annoyance caused by noise. However, it proved impossible to develop any universal, objective procedure which at the same time would be practicable and would correctly assess all types of noise in terms of the effects they generate.

Adaptation, Psychological↗