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H Schulz

Publications and source records attributed to H Schulz.

At least 91 records · Page 5Linked to original sources
PubMed2000

Long-chain acyl-CoA dehydrogenase is a key enzyme in the mitochondrial beta-oxidation of unsaturated fatty acids.

The first reaction of mitochondrial beta-oxidation, which is catalyzed by acyl-CoA dehydrogenases, was studied with unsaturated fatty acids that have a double bond either at the 4,5 or 5,6 position. The CoA thioesters of docosahexaenoic acid, arachidonic acid, 4,7,10-cis-hexadecatrienoic acid, 5-cis-tetradecenoic acid, and 4-cis-decenoic acid were effectively dehydrogenated by both rat and human long-chain acyl-CoA dehydrogenases (LCAD), whereas they were poor substrates of very long-chain acyl-CoA dehydrogenases (VLCAD). VLCAD, however, was active with CoA derivatives of long-chain saturated fatty acids or unsaturated fatty acids that have double bonds further removed from the thioester function. Although bovine LCAD effectively dehydrogenated 5-cis-tetradecenoyl-CoA (14:1) and 4,7,10-cis-hexadecatrienoyl-CoA, it was nearly inactive toward the other unsaturated substrates. The catalytic efficiency of rat VLCAD with 14:1 as substrate was only 4% of the efficiency determined with tetradecanoyl-CoA, whereas LCAD acted equally well on both substrates. The conclusion of this study is that LCAD serves an important, if not essential function in the beta-oxidation of unsaturated fatty acids.

Acyl Coenzyme A↗
PubMed2000

Function of human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism.

Human brain short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) has been demonstrated to be a unique 3alpha-hydroxysteroid dehydrogenase (HSD) that can convert 5alpha-androstane-3alpha, 17beta-diol (3alpha-adiol) to dihydrotestosterone (DHT), whose affinity to the androgen receptor is 10(5)-fold higher than that of 3alpha-adiol. The catalytic efficiency of human SCHAD for this oxidative 3alpha-HSD reaction was estimated to be 164 min(-1) mM(-1), about 10-fold higher than that measured for the backward reaction. Thus, human brain SCHAD may function in androgen metabolism as a new kind of 3alpha-HSD by counteracting all other known 3alpha-HSDs, which would unidirectionally catalyze the reduction of DHT to the almost inactive 3alpha-adiol. Human SCHAD is identical to an amyloid-beta binding protein (ERAB) involved in Alzheimer's disease, which was previously reported to be associated with the endoplasmic reticulum. This protein is, in fact, localized in mitochondria, not endoplasmic reticulum, as evidenced by immunocytochemical studies and its noncleavable mitochondrial targeting sequence and lack of endoplasmic reticulum targeting signals or transmembrane segments. These results prompt the suggestion that the mitochondrion plays not only an essential role in the initial step of steroidogenesis, but also important roles in the intracellular homeostasis of sex steroid hormones. Northern blot analysis revealed that the human SCHAD gene is expressed in both gonadal and peripheral tissues including the prostate whose growth notably requires DHT, the most potent androgen. This study represents the first report of a 3alpha-HSD that could act to generate DHT from 3alpha-adiol and thereby maintain intracellular DHT levels. We propose that inhibitors of the 3alpha-HSD activity of human brain SCHAD could be useful for the treatment of benign prostatic hyperplasia and other disorders involving DHT metabolism, in combination with known inhibitors of steroid 5alpha-reductases.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase.

The alcohol dehydrogenase (ADH) activity of human short-chain l-3-hydroxyacyl-CoA dehydrogenase (SCHAD) has been characterized kinetically. The k(cat) of the purified enzyme was estimated to be 2. 2 min(-1), with apparent K(m) values of 280 mM and 22microM for 2-propanol and NAD(+), respectively. The k(cat) of the ADH activity was three orders of magnitude less than the l-3-hydroxyacyl-CoA dehydrogenase activity but was comparable with that of the enzyme's hydroxysteroid dehydrogenase (HSD) activity for oxidizing 17beta-oestradiol [He, Merz, Mehta, Schulz and Yang (1999) J. Biol. Chem. 274, 15014-15019]. However, the k(cat) values of intrinsic ADH and HSD activities of human SCHAD were found to be two orders of magnitude less than those reported for endoplasmic-reticulum-associated amyloid beta-peptide-binding protein (ERAB) [Yan, Shi, Zhu, Fu, Zhu, Zhu, Gibson, Stern, Collison, Al-Mohanna et al. (1999) J. Biol. Chem. 274, 2145-2156]. Since human SCHAD and ERAB apparently possess identical amino acid sequences, their catalytic properties should be identical. The recombinant SCHAD has been confirmed to be the right gene product and not a mutant variant. Steady-state kinetic measurements and quantitative analyses reveal that assay conditions such as pH and concentrations of coenzyme and substrate do not account for the kinetic differences reported for ERAB and SCHAD. Rather problematic experimental procedures appear to be responsible for the unrealistically high catalytic rate constants of ERAB. Eliminating the confusion surrounding the catalytic properties of this important multifunctional enzyme paves the way for exploring its role(s) in the pathogenesis of Alzheimer's disease.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2000

Total deposition of therapeutic particles during spontaneous and controlled inhalations.

Treatment of systemic diseases by means of the inhalation route is hampered by uncertainties of the drug dose applied by inhalation. In this study, the hypothesis was tested that by standardization of the breathing maneuver used for inhalation, the interindividual variability of the dose deposited intrathoracically can be reduced. Therefore, breathing pattern during routine inhalations with jet nebulizers was measured in 18 patients with lung disease. Using monodisperse 3 microm particles, total deposition was then assessed for the measured spontaneous and for three controlled, slow breathing patterns. Particle deposition for the three controlled breathing patterns was additionally measured in 14 healthy subjects. The study has shown that within the study population the inhaled air volume and flow rate were quite different. Consequently, total particle deposition varied between 20 and 95%, depending on breathing pattern. For controlled, slow breathing patterns, deposition was on average higher, intersubject variability of deposition was smaller, and differences in deposition between healthy subjects and patients were negligible. Therefore, to perform efficient systemic treatment with aerosolized drugs, controlled, slow breathing patterns should be used.

Administration, Inhalation↗
PubMed2000

Application of laser ablation inductively coupled mass spectrometry (LA-ICP-MS) for the determination of major, minor, and trace elements in bark samples.

The large surface area of barks from many tree species enables the effective accumulation of pollutants. Therefore, the analysis of bark material will provide useful information about the degree of pollution of a certain region. The determination of main, minor, and trace elements (Al, Ca, Cd, Ce, Cr, Cu, Fe, Mn, P, Pb, S, Ti and Zn) in bark was performed with an Nd:YAG laser coupled to an ICP-MS system. Bark standards for the calibration by laser ablation ICP-MS were prepared from different bark layers which differ for some relevant elements in concentrations. Four digestion procedures for the decomposition of the standard pellets, the numbers of laser shots per sample and of samples per region necessary have been investigated. Representative results were obtained for 5 or more samples taken from different individuals of one species of a sampling area and the averaged element concentrations of 10 separately placed laser shots for each sample. Laser ablation ICP-MS was applied for the characterization of real bark samples from different regions with high and low pollution burden. It was shown that the method is well suited to characterize different degrees of environmental impact. Anthropogenic sources were responsible for the higher concentrations of most of the elements under investigation.

Environmental Pollutants↗
PubMed2000

Long-term administration of galactoside-specific mistletoe lectin in an animal model: no protection against N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder carcinogenesis in rats and no induction of a relevant local cellular immune response.

Aqueous extracts from leaves of the European mistletoe (Viscum album L.) are postulated to exert an anticancer efficacy by cytotoxic and/or immunological mechanisms of action. Although popular as an unconventional therapy modality, no controlled randomized clinical trials are available, reliably documenting a clinically beneficial antineoplastic potential of the various commercial mistletoe preparations. Since previous investigations have focused on the purified galactoside-specific lectin (Viscum album L. agglutinin, VAA) as major biological response modifier in the low-dose range, the objective of the present experimental study was to examine its effect on N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced carcinogenesis in the urinary bladder of rats, a suitable animal model for human disease. The carcinogen was fed by gavage in three fractionated low doses (150 mg/kg body weight each) to obtain low-grade and low-stage transitional cell carcinomas. From the onset of the experiment VAA was injected subcutaneously twice a week (1 ng/kg body weight) continuously for either 6 or 15 months. Following an experimental period of 6 months the incidence of bladder carcinomas was 10.2% in rats given exclusively BBN and 6.7% in those additionally treated with VAA. After an experimental time of 15 months 25.8% of the rats fed BBN only and 19.7% of the animals additionally receiving VAA had developed urothelial carcinomas. The differences of the tumor incidences did not reach the level of statistical significance, neither after an experimental duration of 6 (P = 0.88) nor of 15 months (P = 0.71). A difference was found in the size of the transitional cell carcinomas. They proved to be significantly larger (P = 0.02) in the rats additionally treated with VAA for 15 months (mean maximum diameter: 3.31 mm) than in those without lectin treatment (mean maximum diameter: 1.88 mm). Quantitative immunocytochemistry analyzing a panel of immune cells yielded no evidence for the ability of the lectin to provoke a substantial, biologically relevant local cellular immune response in the wall of tumor-free and tumor-bearing bladders. From the current experiment it is obvious that galactoside-specific mistletoe lectin failed to protect against, inhibit, delay or reduce development of chemically induced urothelial carcinomas of the urinary bladder even after long-term administration in the clinically recommended schedule. It seems highly unlikely that adjuvant treatment with mistletoe extracts or VAA might favorably influence bladder cancer in patients by immunological effector mechanisms.

Animals↗
PubMed2000

A real-time PCR assay for the quantification of residual malignant cells in B cell chronic lymphatic leukemia.

Several new therapeutic approaches for the treatment of monoclonal B cell lymphomas are currently being investigated. In parallel with new therapeutic modalities, more sensitive diagnostic methods are needed. These methods should be highly sensitive in detecting very low amounts of malignant cells and should be specific for the malignant clone. In addition, these methods should allow the quantification of residual tumor cells. In this study a new real-time polymerase chain reaction (LightCycler) was evaluated to quantify residual tumor cells in monoclonal B cell malignancies. This technology combines the advantages of rapid cycling PCR with the online detection of PCR products using fluorescent dyes. Our assay is based on immunoglobulin heavy chain (IgVH)-specific PCR with allele-specific primers complementary to hypervariable CDRII and CDRIII regions. A set of framework region III (FRIII)-specific hybridization probes was used for detection of the specific amplification product, and IgVH copy number was quantified with the cloned IgVH sequence as an external standard. The approach was evaluated with the Hodgkin lymphoma cell line L428 in order to quantify L428 dilutions. L428 cells mixed with peripheral blood mononuclear cells (PBMNCs) were detected and quantified with a sensitivity of one cell within 1 x 10(5) PBMNCs. Sample DNA from the peripheral blood and from the bone marrow of two patients with B-CLL was analyzed in the new set up at different time points before and after therapy. Statistically significant changes in IgVH copy numbers were documented in both patients. We conclude that this technology offers an additional opportunity to detect and quantify residual tumor cells in B-CLL over several log steps with a high sensitivity. The kinetics of residual tumor cell counts in B-CLL can be analyzed by this method.

Antibodies, Monoclonal↗
PubMed2000

New insights into the role of CcmC, CcmD and CcmE in the haem delivery pathway during cytochrome c maturation by a complete mutational analysis of the conserved tryptophan-rich motif of CcmC.

Maturation of c-type cytochromes in Escherichia coli is a complex process requiring eight membrane proteins encoded by the ccmABCDEFGH operon. CcmE is a mediator of haem delivery. It binds haem transiently at a conserved histidine residue and releases it for directed transfer to apocytochrome c. CcmC, an integral membrane protein with six transmembrane helices, is necessary and sufficient to incorporate haem covalently into CcmE. CcmC contains a highly conserved tryptophan-rich motif, WGXXWXWD, in its second periplasmic loop. Here, we present the results of a systematic mutational analysis of this motif. Changes of the non-conserved T121 and W122 to A resulted in wild-type CcmC activity. Changes of the single amino acids W119A, G120A, W123A, W125I and D126A or of the spacing within the motif by deleting V124 (DeltaV124) inhibited the covalent haem incorporation into CcmE. Enhanced expression of ccmD suppressed this mutant phenotype by increasing the amounts of CcmC and CcmE polypeptides in the membrane. The DeltaV124 mutant showed the strongest defect of all single mutants. Mutants in which six residues of the tryptophan-rich motif were changed showed no residual CcmC activity. This phenotype was independent of the level of ccmD expression. Our results demonstrate the functional importance of the tryptophan-rich motif for haem transfer to CcmE. We propose that the three membrane proteins CcmC, CcmD and CcmE interact directly with each other, establishing a cytoplasm to periplasm haem delivery pathway for cytochrome c maturation.

Amino Acid Motifs↗
PubMed2000

Aerosol morphometry and aerosol bolus dispersion in patients with CT-determined combined pulmonary emphysema and lung fibrosis.

The simultaneous occurrence of pulmonary fibrosis and emphysema may present considerable problems in clinical assessment. Recent studies have shown that Aerosol Derived Airway Morphometry (ADAM) and Aerosol Bolus Dispersion (ABD) are changed in patients with pulmonary emphysema. This study was performed to assess the effect of simultaneous lung fibrosis in patients with emphysema on ADAM and ABD. ADAM and ABD measurements were performed in 20 patients with lone high resolution CT scan (HRCT) confirmed emphysema (E), and compared to those in 15 emphysematics with HRCT-confirmed superimposed pulmonary fibrosis (FE). In both groups the peripheral effective airspace dimension (EAD) (E: 0.63 +/- 0.20 mm; FE: 0.60 +/- 0.27 mm, N.S.) was increased by more than a factor of two compared to that of healthy subjects (0.28 +/- 0.05 mm) (p < 0.001). Patients with E showed a significantly higher bolus dispersion than patients with FE (724 +/- 122 cm3 vs. 546 +/- 80 cm3; p < 0.001). However, in patients with FE, bolus dispersion was still significantly higher than in previously published control groups of healthy subjects (546 +/- 80 cm3 vs. 455 +/- 68 cm3; p < 0.001). The results of this study confirm that ADAM and ABD are powerful tools for identifying emphysema even in patients with superimposed pulmonary fibrosis.

Aerosols↗
PubMed2000

Influence of different colloids on molecular markers of haemostasis and platelet function in patients undergoing major abdominal surgery.

Synthetic colloids have been reported to cause haemorrhagic complications. The effects of perioperative volume replacement with 4% gelatin (n = 20), 6% low-molecular weight (LMW) hydroxyethyl starch (HES) (Mw: 70,000 dalton; HES 70/0.5; n = 20) and 6% medium-molecular weight (MMW) HES (Mw: 200,000 dalton; HES 200/0.5; n = 20) on haemostasis were assessed in patients undergoing major abdominal surgery. Volume was administered to keep central venous pressure (CVP) between 10 and 14 mm Hg. Conventional global coagulation tests, molecular markers of coagulation, and platelet function (using a platelet function analyser (PFA-100) with ADP as inductor) were monitored prior to surgery (T0), at the end of surgery (T1), 4 h after the end of surgery (T2), and on the morning of the first postoperative day (T3). Significantly more gelatin (2900 (SD 320) ml) than HES 200 (2150 (312) ml) was given during the study period. Bleeding and the use of allogeneic blood-blood products were similar in all groups. Markers of thrombin generation (F1 + 2), of thrombin neutralization (TAT III complex), and of fibrin formation and its degradation (D-dimer) increased significantly during and after surgery without showing significant group differences. Factor VIII and von Willebrand factor (vWF) also increased in all groups beyond the normal range, showing the significantly highest increase in the gelatin-treated group (VIII: from 173 (36) to 266 (33) U dl-1; vWF: from 164(33) to 238 (31) U dl-1). Platelet function remained within the normal range and without group differences throughout the study period. We can conclude that all three solutions can be used safely in patients undergoing major abdominal surgery with regard to the haemostatic process.

Abdomen↗
PubMed2000

Interspecies complementation of Escherichia coli ccm mutants: CcmE (CycJ) from Bradyrhizobium japonicum acts as a heme chaperone during cytochrome c maturation.

Biogenesis of c-type cytochromes in alpha- and gamma-proteobacteria requires the function of a set of orthologous genes (ccm genes) that encode specific maturation factors. The Escherichia coli CcmE protein is a periplasmic heme chaperone. The membrane protein CcmC is required for loading CcmE with heme. By expressing CcmE (CycJ) from Bradyrhizobium japonicum in E. coli we demonstrated that heme is bound covalently to this protein at a strictly conserved histidine residue. The B. japonicum homologue can transfer heme to apocytochrome c in E. coli, suggesting that it functions as a heme chaperone. CcmC (CycZ) from B. japonicum expressed in E. coli was capable of inserting heme into CcmE.

Bacterial Outer Membrane Proteins↗
PubMed2000

Muir-Torre syndrome - treatment with isotretinoin and interferon alpha-2a can prevent tumour development.

Muir-Torre syndrome is a genodermatosis in which multiple internal malignancies are associated with cutaneous sebaceous tumours and kerato-acanthomas. A 57-year-old man presented with multiple sebaceous tumours, kerato-acanthomas, verrucous carcinoma of the nose, renal cell and transitional cell carcinomas of the left kidney, adenoma of the colon and a positive family history of colon carcinoma. He was treated with interferon (IFN-alpha2a) s.c. 3 x 10(6) U three times a week along with 50 mg isotretinoin daily as well as topical isotretinoin gel. During a follow-up of 29 months, only 1 sebaceous skin tumour developed and was removed, whereas more than 30 such skin tumours had been surgically removed during the last 3 years. No evidence of internal tumour development or recurrence was found. The combination of IFN with retinoids seems to be of promise to prevent tumour development in Muir-Torre syndrome.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Ablation of Barrett's epithelium by endoscopic argon plasma coagulation in combination with high-dose omeprazole.

BACKGROUND: Barrett's esophagus is a premalignant condition induced by gastroesophageal reflux. The aim of this prospective study was to assess the efficacy of argon plasma coagulation in combination with high-dose omeprazole therapy to ablate nondysplastic Barrett's epithelium. METHODS: In 73 patients with histologically confirmed Barrett's epithelium, argon plasma coagulation was used in combination with maximal acid suppression (omeprazole 40 mg three times a day). Histologic and endoscopic changes were evaluated at 6- and 12-month intervals. RESULTS: In 69 of 70 patients (98.6%) complete squamous regeneration was achieved after a median of 2 argon plasma coagulation sessions (range 1 to 5). During a median follow-up of 12 months (range 2 to 51 months) there has been no relapse or evidence of the development of dysplasia under continuous acid suppression. Three patients (4.3%) developed a mild stricture of the distal esophagus that resolved after a single session of bougie dilation. CONCLUSIONS: In our experience, argon plasma coagulation in combination with high-dose omeprazole treatment is an effective and safe technique for complete ablation of nondysplastic Barrett's epithelium. Restoration of squamous mucosa after argon plasma coagulation appears to be long-lasting.

Adult↗
PubMed2000

Epiluminescence microscopy features of cutaneous malignant melanoma metastases.

Especially small and/or initial cutaneous malignant melanoma metastases (CMMMs) are tumours with inconspicuous clinical and sometimes histological features which may be difficult to differentiate from benign melanocytic lesions or angiomas. Thus it would be very valuable to have additional criteria for the differential diagnosis of such lesions. Thirty histologically verified CMMMs were examined using epiluminescence microscopy (ELM) in order to visualize a large number of morphological features permitting the recognition of malignancy. One hundred primary cutaneous malignant melanomas (PCMMs), 50 dysplastic naevi, 50 common naevi, 30 blue naevi and 20 haemangiomas served as the control group; these were randomly selected from a large data base and were all reviewed for histological diagnosis. Four of the 24 features studied were shown to differ significantly between CMMMs and the control group. Two features of the malignant tumour group (CMMM and PCMM) differed significantly from the benign tumour group. A polymorphic angiectatic base pattern and/or vascular aneurysms, peripheral erythema, brown-grey coloration as a negative criterion (i.e. its absence is indicative of CMMM) and a light brown halo had a specificity of 86.7-96.0% for CMMM. Areas of polymorphic and/or horizontally dilated capillaries and a saccular pattern had a specificity of 97.3-99.2% for the malignant group (CMMM and PCMM). Three features - peripheral greyish patches, lesions surrounded by grey streaks (melanoma cell infarcts of the vessels) and microscopic ovoid blood lakes (spontaneous microhaemorrhages)--were absent in the benign group. The prevalence of distinct ELM criteria in CMMM represents a useful enhancement for the diagnosis of malignancy in melanocytic skin lesions.

Adult↗
PubMed2000

Behavioural effects of subchronic lead treatment in combination with ethanol in rats.

The effect of lead acetate administration during perinatal (1. prenatal, 2. prenatal and suckling period, 3. prenatal + suckling period + 4 weeks after weaning) development in combination with ethanol was investigated in Wistar rats at the age of 12 weeks on open-field behaviour and auditory startle response. Lead intoxication has on the investigated behavioural parameters the most pronouncing effect when applied during the days 5-15 of pregnancy.

Animals↗