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Biomedical subjects

J Schulze

Publications and source records attributed to J Schulze.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effect of therapeutic dietary biotin on the healing of uncomplicated sole ulcers in dairy cattle--a double blinded controlled study.

The objective of this study was to investigate the influence of orally administered biotin on the healing of uncomplicated sole ulcers in dairy cattle. In a double-blind controlled study, 24 dairy cows with a mild, uncomplicated sole ulcer on a lateral hind claw were given either 40 mg biotin per day or a placebo feed over a period of 50 days. An orthopaedic shoe was fitted to the medial claw of the affected foot. The healing process was assessed clinically and by histological examination of horn samples. In the biotin-treated animals, the newly formed epidermis covering the sole ulcers was found to be of significantly better histological quality after 50 days than at the start of the study. The significant improvement in histological horn quality found in the biotin-treated animals suggests that biotin exerts a positive influence on the healing of sole ulcers, however the study period of 50 days appears to have been too short to permit macroscopic detection of the improvement in horn quality.

Administration, Oral↗
PubMed2002

Mutations and intronic variants in the HNF-1 beta gene in a group of German and Czech Caucasians with type 2 diabetes mellitus and progressive diabetic nephropathy.

Mutations in the hepatocyte nuclear factor - 1 beta (HNF-1 beta) gene cause maturity onset diabetes of the young type 5 (MODY 5). A clinical feature of the resulting phenotype besides impaired glucose tolerance is a variety of renal abnormalities, ranging from renal cysts to end-stage renal failure. Using a candidate gene approach we investigated the prevalence of mutations in the HNF-1 beta gene in a group of 63 patients from two different European populations (33 Germans, 30 Czechs) with type 2 diabetes mellitus and diabetic nephropathy diagnosed by increased albuminuria (39 patients) or end-stage renal failure (24 patients). No mutations were found in any of the 9 exons or in a minimal promoter region. Three intronic variants (single nucleotide polymorphisms - SNPs) were detected. The frequencies of these variants showed no difference between the two studied populations and were comparable to data reported from healthy subjects. No association between SNPs or formed haplotypes and any clinical parameters (like age of disease onset, BMI and severity of renal failure) was found. The results confirm that the genetic variations in the HNF-1 beta gene would be a very uncommon cause of progressive nephropathy in patients with type 2 diabetes mellitus.

Age of Onset↗
PubMed2001

[Neuropathy after cyclophosphamide high dose chemotherapy in a Morbus Werlhof patient]

Neuropathy after cyclophosphamide high dose chemotherapy in a Morbus Werlhof patient. PERSONAL HISTORY: A 24 year old patient with longstanding autoimmune idiopathic thrombocytopenic purpura (M. Werlhof) was treated with glucocorticoids, immunoglobulins, splenectomy, immunosuppression and vincristin without lasting success. After a second treatment cycle with cyclosphosphamide and autologous peripheral stem cell transplantation she acutely develpod symptoms of a peripheral sensoric and motoric polyneuro-pathy. MEDICAL EXAMINATION: At admission she was in good general health, but had steroid-induced Cushing's symptoms, generalized petechial bleeding and thrombocytopenia (1000/ micro l). THERAPY AND COURSE: After 2.5 g/m 2 cyclophosphamide and stem cell transplantation distally pronounced polyneuropathy developed within a week with bladder insufficiency. Major bleeding or brain damage were excluded, and symptoms only partially reversed when treated with steroids, carbamazepine and amitriptyline. Thrombocytopenia persisted, and the patient died 4 month later from acute brain hemorrhage. CONCLUSIONS: Direct neurotoxicity has to be assumed as the likely causative agent in this case, illustrating the possibility of peripheral neuropathic lesions by high dose cyclophosphamide treatment.

Journal Article↗
PubMed2001

[Healing process of uncomplicated sole ulcers in dairy cows kept in tie stalls: clinical description and blood chemical investigations].

A total of 74 dairy cows with 105 separate lesions were treated and the healing process was observed for half a year and the results compared with the biochemical data. The mean time for the formation of a closed layer of horn was 25 days for lesions with slight corium alterations, 33 days for moderate and 42 days for severe alterations. Thirty days after the initial treatment 68% of all lesions were completely covered by a solid layer of new horn. The further evaluation of the healing process was based on quality and rate of the new horn formation, recovery from lameness and sensitivity to hooftesters. Using these parameters the healing potential of exposed corium was judged one month after treatment with a scoring system. The 30-day-healing process was considered to be good in 61% and moderate to bad in 39% of the cows. The concentration of glucose, cholesterin, LDH and blood urea was increased in one third of the animals. Phosphorus and magnesium concentrations were lower than the reference values in 30%, and 26% of the animals, respectively. Cows with prolonged healing had higher levels of bilirubin, creatinkinase, LDH, ALT and AST than cows with a good healing process. Concentration of iron, vitamin A and biotin were significantly lower in cows with moderate to bad healing parameters than cows with a good healing potential. From these results it is suggested that biochemical blood parameters and the vitamin status might influence the healing of uncomplicated sole ulcers, respectively.

Animals↗
PubMed2000

Residue 285 in cytochrome P450 2B4 lacking the NH(2)-terminal hydrophobic sequence has a role in the functional association of NADPH-cytochrome P450 reductase.

Cytochrome P450 2B4 (CYP2B4) lacking the NH(2)-terminal signal anchor sequence (2-27) was used to study the impact of replacement of histidine with alanine at position 285 on electron transfer from NADPH-cytochrome P450 reductase (P450R). Absorption and circular dichroism spectra of the recombinant hemoproteins indicated that amino acid substitution neither grossly perturbed the geometry of the immediate heme vicinity nor the global polypeptide backbone folding. Fitting of the initial-velocity patterns of P450R-directed reduction of the ferric CYP2B4 (2-27) forms to the Michaelis-Menten kinetics revealed an approximately 3.5-fold increase in the apparent K(m) value for the electron donor of the H285A mutant, while its reductive capacity (V(max)) remained unchanged; this caused a strong drop in reductive efficiency of the engineered enzyme. Circumstantial analysis suggested that impaired association of the redox partners accounted for this phenomenon. Thus, deletion of the positive charge at position 285 of CYP2B4 (2-27) might have disrupted contacts with oppositely charged entities on the P450R surface. Measurements of the stoichiometry of aerobic NADPH consumption and H(2)O(2) production disclosed the oxyferrous H285A species to autoxidize more readily compared with the shortened wild type. This was assumed to arise from less efficient coupling of the system due to defective donation of the second electron by P450R. These results are consistent with the view that His-285 in the truncated CYP2B4 is of importance in the functional interaction with the flavoprotein reductase.

Amino Acid Substitution↗
PubMed2000

Low level radioactivity measurement in support of the CTBTO. Comprehensive Nuclear-Test-Ban Treaty Organization

Radioactivity measurements, together with three other technologies: seismic, hydroacoustic and infrasound, are able to detect, identify and locate nuclear explosions down to 1 kt. Eighty stations worldwide, with a sensitivity of 10-30 microBq/m3 for 140Ba and 1 mBq/m m3 for 133Xe, have been or will be established in order to provide an estimated 90% detection probability within 10 days after a nuclear explosion. The equipment for manual stations--the high volume samplers, high sensitivity HPGe detectors and auxiliary measurement systems, as well as the automatic stations are described. The problems and results of atmospheric transport, site location as well as equipment and station operation are discussed.

Journal Article↗
PubMed2000

[Comparative results after endoscopic synovectomy and open bursectomy in chronic bursitis olecrani].

UNLABELLED: The surgical treatment of choice in cases with chronic bursitis of the elbow usually consists of an open radical bursectomy. PURPOSE OF THIS STUDY: Comparison of the outcome after the endoscopic synovectomy and internal drainage with the conventional operative procedures (control). METHODS: Clinical follow-up in nine endoscopically treated patients and conventionally operated controls in the similar year that were comparable in age and number of prior surgical procedures in that region. Comparison by means of the score of Morrey et al. using Mann-Whitney-U-test and chi 2-test. DISCUSSION: All patients in both groups were highly satisfied with the results of their treatment. The analysis revealed no differences in score Morrey et al. (endoscopy: 97.11 points vs. control: 95.33 points; p = 0.564). However, the endoscopically treated patients returned significantly earlier to work (10 d vs. 18 d, p = 0.041). CONCLUSION: The endoscopical synovectomy in cases with chronic bursitis olecrani is an easy and safe method to obtain excellent results.

Adult↗
PubMed2000

Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus.

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

Adult↗
PubMed2000

Transfer of symbiotically fixed nitrogen in an alfalfa-grass mixture studied through isotope dilution in a pot experiment.

The nitrogen transfer between alfalfa and ryegrass was studied through isotope dilution at three different levels of N fertilization (20 mg N/pot, 200 mg N/pot, 400 mg N/pot) in a pot experiment using quartz sand as a substrate. An isogenic, nodulating, but non nitrogen fixing alfalfa line was used as a reference crop. Fixed N was transferred to the grass in the 20 mg N treatment and contributed markedly to the N nutrition of the grass (about 50% of the N in the plants). No transfer of fixed N could be detected in the higher fertilized treatments, although nitrogen fixation was only slightly inhibited by the presence of the fertilized mineral N. It is concluded that N transfer is strongly influenced by the N concentration in the substrate and transferred N contributes only slightly to the productivity of the legume/grass mixture under the given experimental conditions.

Fertilizers↗
PubMed2000

Identification of key residues in rabbit liver microsomal cytochrome P450 2B4: importance in interactions with NADPH-cytochrome P450 reductase.

A cytochrome P450 2B4 (CYP2B4) model was used to select key residues supposed to serve in interactions with NADPH-cytochrome P450 reductase (P450R). Eight amino acid residues located on the surface of the hemoprotein were chosen for mutagenesis experiments with CYP2B4(Delta2-27) lacking the NH(2)-terminal signal anchor sequence. The mutated proteins were expressed in Escherichia coli, purified, and characterized by EPR- and CD-spectral analysis. Replacement of histidine 226 with alanine caused a 3.8-fold fall in the affinity for P450R with undisturbed reductive capacity of the system. Similarly, the K225A, R232A, and R253A variants exhibited P450R-directed activity that was depressed to about half that of the control enzyme, suggesting that the deletion of positive charges on the surface of CYP2B4(Delta2-27) resulted in impaired electrostatic contacts with complementary amino acids on the P450R protein. While the Y235A mutant did not show appreciably perturbed reduction activity, the conservative substitution with alanine of the phenylalanine residues at positions 223 and 227 gave a 2.1- to 6. 1-fold increase in the K(m) values with unchanged V(max); this was attributed to the disruption of hydrophobic forces rather than to global structural rearrangement(s) of the engineered pigments. Measurement of the stoichiometry of aerobic NADPH consumption and H(2)O(2) formation revealed the oxyferrous forms of the F223A, H226A, and F227A mutants to autoxidize more readily owing to less efficient coupling of the systems. Noteworthy, the F244A enzyme did not exhibit significant reduction activity, suggesting a pivotal role of Phe-244 in the functional coupling of P450R. The residue was predicted to constitute part of an obligatory electron transfer conduit through pi-stacking with Phe-296 located close to the heme unit. All of the residues examined reside in the putative G helix of CYP2B4, so that this domain obviously defines part of the binding site for P450R.

Aerobiosis↗
PubMed2000

The molybdenum cofactor biosynthetic protein Cnx1 complements molybdate-repairable mutants, transfers molybdenum to the metal binding pterin, and is associated with the cytoskeleton.

Molybdenum (Mo) plays an essential role in the active site of all eukaryotic Mo-containing enzymes. In plants, Mo enzymes are important for nitrate assimilation, phytohormone synthesis, and purine catabolism. Mo is bound to a unique metal binding pterin (molybdopterin [MPT]), thereby forming the active Mo cofactor (Moco), which is highly conserved in eukaryotes, eubacteria, and archaebacteria. Here, we describe the function of the two-domain protein Cnx1 from Arabidopsis in the final step of Moco biosynthesis. Cnx1 is constitutively expressed in all organs and in plants grown on different nitrogen sources. Mo-repairable cnxA mutants from Nicotiana plumbaginifolia accumulate MPT and show altered Cnx1 expression. Transformation of cnxA mutants and the corresponding Arabidopsis chl-6 mutant with cnx1 cDNA resulted in functional reconstitution of their Moco deficiency. We also identified a point mutation in the Cnx1 E domain of Arabidopsis chl-6 that causes the molybdate-repairable phenotype. Recombinant Cnx1 protein is capable of synthesizing Moco. The G domain binds and activates MPT, whereas the E domain is essential for activating Mo. In addition, Cnx1 binds to the cytoskeleton in the same way that its mammalian homolog gephyrin does in neuronal cells, which suggests a hypothetical model for anchoring the Moco-synthetic machinery by Cnx1 in plant cells.

Amino Acid Sequence↗
PubMed2000

Specific type IV phosphodiesterase inhibitor rolipram mitigates experimental colitis in mice.

The specific type IV phosphodiesterase inhibitor rolipram is a potent suppressor of tumor necrosis factor-alpha (TNF) synthesis. We examined the efficacy of rolipram for the prevention and treatment of experimental colitis. To induce colitis, BALB/c mice received 5% dextran sulfate sodium in their drinking water continuously for up to 11 days. Colitis was quantified by a clinical activity score assessing weight loss, stool consistency, and rectal bleeding (range from 0 to 4); by colon length; by a semiquantitative histologic score (range from 0 to 6); and by detecting TNF concentration in colonic tissue by enzyme-linked immunosorbent assay. In a first protocol, rolipram (10 mg/kg b.wt./day i.p.) was started on the same day as dextran sulfate sodium. Rolipram reduced the clinical activity of colitis (score 1.1 +/- 0.3) compared with mice that did not receive rolipram (2.4 +/- 0.4; P =.041). Rolipram also partially reversed the reduction of colon length (without rolipram, 12.4 +/- 0. 3 cm; with rolipram, 15.4 +/- 0.7 cm; P =.004) and improved the histologic score (1.5 +/- 0.6 in rolipram-treated mice versus 4.6 +/- 0.5; P =.020). Rolipram suppressed colonic tissue TNF concentrations. The beneficial effect of rolipram was confirmed in a second protocol in which dextran sulfate sodium exposure was discontinued on day 7 and rolipram was administered from day 8 through day 15. These three series of experiments on a total of 153 mice documented the efficacy of rolipram in both the prevention and treatment of experimental colitis.

Animals↗
PubMed1999

Clindamycin and nicotinic neuromuscular transmission.

Upon clindamycin treatment a patient with Parkinson's disease showed marked tremor improvement which may be explained by clindamycin's ability to inhibit in-vitro nicotinergic, but not muscarinic signal transmission.

Animals↗
PubMed1999

The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells.

The molybdenum cofactor (Moco), a highly conserved pterin compound complexing molybdenum, is required for the enzymatic activities of all molybdenum enzymes except nitrogenase. Moco is synthesized by a unique and evolutionarily old pathway that requires the activities of at least six gene products. Some of the proteins involved in bacterial, plant, and invertebrate Moco biosynthesis show striking homologies to the primary structure of gephyrin, a polypeptide required for the clustering of inhibitory glycine receptors in postsynaptic membranes in the rat central nervous system. Here, we show that gephyrin binds with high affinity to molybdopterin, the metabolic precursor of Moco. Furthermore, gephyrin expression can reconstitute Moco biosynthesis in Moco-deficient bacteria, a molybdenum-dependent mouse cell line, and a Moco-deficient plant mutant. Conversely, inhibition of gephyrin expression by antisense RNA expression in cultured murine cells reduces their Moco content significantly. These data indicate that in addition to clustering glycine receptors, gephyrin also is involved in Moco biosynthesis and illustrate the remarkable conservation of its function in Moco biosynthesis throughout phylogeny.

Animals↗
PubMed1999

The optical biosensor studies on the role of hydrophobic tails of NADPH-cytochrome P450 reductase and cytochromes P450 2B4 and b5 upon productive complex formation within a monomeric reconstituted system.

The optical biosensor study of interaction between microsomal proteins-NADPH-cytochrome P450 reductase, cytochrome P450 2B4, and cytochrome b5-was carried out in the monomeric reconstituted system in the absence of phospholipids. The formation of individual complexes was kinetically characterized and their association and dissociation rate constants were determined. The association rate constants for the complexes formed were found to be close to the diffusiion limit-(0.5-4) x 10(6) M-1 s-1-while their dissociation rate constants did not exceed 0.5 s-1. It was shown that the interprotein electron transfer can occur both through complex formation and due to random collision. The dominant role of hydrophobic membraneous protein fragments in formation of productive electron transfer complexes was demonstrated.

Animals↗
PubMed1999

Some properties of mitochondrial adrenodoxin associated with its nonconventional electron donor function toward rabbit liver microsomal cytochrome P450 2B4.

Mitochondrial adrenodoxin (Adx) was found to cross-react with microsomal cytochrome P450 2B4 (CYP2B4) as the terminal electron acceptor. When compared with NADPH-cytochrome P450 reductase (P450R), the natural redox partner of CYP2B4, Adx was less efficient both in transferring the first electron and in coupling the system. The ferredoxin yielded an unusual reverse type I spectral change with low-spin CYP2B4, which underwent transformation to a typical type I optical perturbation upon deletion of the signal anchor sequence (Delta2-27) of the hemoprotein. Truncation of CYP2B4 slightly fostered electron transfer from Adx, but was deleterious to reduction of the engineered isozyme by P450R. Addition of manganese-substituted cytochrome b5, which failed to serve as an electron donor to CYP2B4, augmented the amount of hemoprotein existing in form of a low-spin complex with Adx and affected the ferredoxin-dependent reduction kinetics through causing a proportional rise in both Km and Vmax. Conservative replacement of Asp-76 with glutamate in the Adx molecule was associated with a drastic drop in reductive efficiency toward CYP2B4, while spectral binding of the mutant to the hemoprotein was marginally changed. The results support the concept of an evolutionary relationship between the various cytochrome P450 forms as regards the conservation of surface regions participating in contacts with heterologous donor proteins.

Adrenodoxin↗
PubMed1999

Lyme arthritis in a 12-year-old patient after a latency period of 5 years.

Lyme arthritis (LA) may be confused with other rheumatic diseases, particularly in the absence of a history of erythema migrans (EM). We report the case of a 12-year-old patient who developed a large effusion of the right knee joint. The titer for antinuclear antibodies was 1:80 and the test for rheumatoid factor was negative. Investigations for antibody response to Borrelia burgdorferi demonstrated remarkable elevation of IgG antibody and no specific IgM response. These results were confirmed by immunoblotting reactivity with the bands p83/100, p58, p43, p41, p39, OspA, p30, OspC, p21, and p17. We subsequently learned that the child had suffered a tick bite followed by an EM 5 years earlier and had been treated with trimethoprim/sulfamethoxazole at that time. The patient now was given intravenous ceftriaxone, 2 g daily for 14 days. In the absence of clinical improvement 3 weeks later a knee joint aspiration was performed which resulted in a positive polymerase chain reaction (PCR) test for B. burgdorferi DNA (OspA) in the synovial fluid. The patient fully recovered 2 months later without further treatment. The case indicates that the latency period between EM and onset of LA may last up to 5 years. In addition to serologic test methods, analysis of synovial fluid using PCR may be decisive for making the final diagnosis of LA.

Antibodies, Bacterial↗