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Biomedical subjects

G Schulz

Publications and source records attributed to G Schulz.

At least 55 records · Page 3Linked to original sources

Altered relationships between rCBF in different brain regions of never-treated schizophrenics.

AIM: of this study was to investigate the relations between regional cerebral blood flow (rCBF) of different brain regions in acute schizophrenia and following neuroleptic treatment. METHODS: Twenty-two never-treated, acute schizophrenic patients were examined with HMPAO brain SPECT and assessed psychopathologically, and reexamined following neuroleptic treatment (over 96.8 days) and psychopathological remission, rCBF was determined by region/cerebellar count quotients obtained from 98 irregular regions of interest (ROIs), summed up to 11 ROIs on each hemisphere. In acute schizophrenics, interregional rCBF correlations of each ROI to every other ROI were compared to the interregional correlations following neuroleptic treatment and to those of controls. RESULTS: All significant correlations of rCBF ratios of different brain regions were exclusively positive in controls and patients. In controls, all ROIs of one hemisphere except the mesial temporal ROI correlated significantly to its contralateral ROI. Each hemisphere showed significant frontal-temporal correlations, as well as cortical-subcortical and some cortico-limbic. In contrast, in acute schizophrenics nearly every ROI correlated significantly with every other ROI, without a grouping or relation of the rCBF of certain ROIs as in controls. After neuroleptic treatment and clinical improvement, this diffuse pattern of correlations remained. CONCLUSIONS: These results indicate differences in the neuronal interplay between regions in schizophrenic and healthy subjects. In never-treated schizophrenics, diffuse interregional rCBF correlations can be seen as a sign of change and dysfunction of the systems regulating specificity and diversity of the neuronal functions. Neuroleptic therapy and psychopathologic remission showed no normalizing effect on interregional correlations.

Adult↗

Relationship between rhythmic discharge patterns of neurons in the central nucleus of the amygdala, blood pressure fluctuations and cortical activity.

In the discharge sequences recorded from single neurons in the central nucleus of the amygdala of chronically instrumented awake cats, rhythmical patterns with period durations of 5-12 s were observed. At the same time blood pressure and the degree of synchronisation of the EEG showed similar period fluctuations with positive correlation to neuronal activity. It is proposed that the central amygdaloid nucleus uses rhythmic patterns to coordinate somatomotor and vegetative systems.

Amygdala↗

Endoglucanase II (EGII) of Penicillium janthinellum: cDNA sequence, heterologous expression and promotor analysis.

The cDNA coding for the endoglucanase EGII of P. janthinellum was cloned and sequenced. The open reading frame comprises 1230 nucleotides and the deduced amino-acid sequence shows an overall homology of 63% with the T. reesei egl2. The cellulose-binding domain of EGII represents a typical member of the A family of cellulases. The egl2 gene is only induced by cellulose or cellobiose and not by sophorose. A promotor fragment including 1 kb was cloned and sequenced. Three major transcription startpoints were identified. Five motifs matching the binding site of the carbon-catabolite repressor CREA of A. nidulans were detected. Their potential implication in repression was analyzed by bandshift assays.

Base Sequence↗

Umbilical cord blood: an alternative to the transplantation of bone marrow stem cells.

Recent in vitro analyses of human UCB have demonstrated the potential of UCB as a source for haematopoietic stem and progenitor cell harvest. Clinical data have further indicated that UCB can be given in vivo to fully and partially HLA-matched siblings or non-familial recipients for marrow reconstitution in genetic disorders as well as malignancies. In comparison to adult peripheral blood, UCB displayed decreased immune responses to alloantigens and was enriched in the numbers of CD34+ progenitor cells with high proliferative and long-term marrow reconstituting potential. Cord blood banks now store large transplantable resources of UCB that are analysed with respect to immunological parameters. Cryopreserved UCB cells may fill the gap in finding a stem-cell transplant for patients who lack a matched related or unrelated donor when a bone marrow transplant is needed.

Blood Preservation↗

Imaging of beta-oxidation by static PET with 14(R,S)-[18F]-fluoro-6-thiaheptadecanoic acid (FTHA) in patients with advanced coronary heart disease: a comparison with 18FDG-PET and 99Tcm-MIBI SPET.

14(R,S)-[18F]-fluoro-6-thiaheptadecanoic acid (FTHA) has been proposed as a PET tracer of the beta-oxidation pathway. The aim of this study was to investigate the diagnostic value of FTHA using static PET imaging in patients with ischaemically reduced left ventricular function. Twenty-one patients with angiographically proven advanced coronary heart disease were examined. All patients underwent SPET with 400 MBq [99Tcm]-2-methoxy-isobutyl-isonitrile (MIBI) for perfusion assessment and PET with 250 MBq FTHA under fasting conditions and with 150 MBq 2-[18F]-fluoro-2-deoxyglucose (FDG) following an oral glucose load. The uptake of FTHA and FDG was analysed quantitatively in 33 regions. Regional uptake was normalized to the region with highest MIBI uptake and expressed as a percentage. FTHA uptake paralleled MIBI uptake (r = 0.80) but not FDG uptake (r = 0.57). Mean FTHA uptake (38.1 +/- 16.3%) in 190 regions with severely reduced perfusion (MIBI uptake < 50%, mean uptake 36.8 +/- 9.4%) was significantly lower compared to FDG uptake (54.6 +/- 25.0%). FTHA uptake was preserved (> or = 70%) in 8 of 52 (13%) regions only with severely reduced perfusion but preserved glucose metabolism (FDG uptake > or = 70%). The similarity between FTHA and MIBI uptake suggests that static PET imaging with FTHA is of limited value when distinguishing between ischaemic or hibernating myocardium and scar. The underestimation of viability may be caused both by the dependence of uptake on flow and the suppression of beta-oxidation in regional chronic ischaemia under fasting conditions.

Aged↗

[Assessment of myocardial viability using 201TL SPECT at rest to predict the reversibility of left ventricular wall motion abnormalities].

AIM: The aim of the present study was to predict preoperatively the reversibility of left ventricular wall motion abnormalities using TI-201 SPECT at rest. METHODS: 19 patients with advanced coronary artery disease and regional wall motion abnormalities were examined at rest with TI 201 SPECT (acquisition 15 minutes and 3 hours post injection). Successfully revascularized, proven by a second coronary angiography three month after revascularisation. Wall motion was again evaluated by cineventriculography. RESULTS: The preoperative a- or dyskinetic segments were best separated by the minimal relative TI-201 uptake in the defect 3 hrs p.i. in (i) postinterventionally improved wall motion (TI-201 uptake 67 +/- 14%, viable) and in (ii) without recovery (TI-201 uptake 46 +/- 12%, p < 0.001, non viable). A threshold at a TI-201 uptake of more than 50% yielded a positive predictive value of 0.73 and a negative predictive value of 0.86. If the segments with wall motion abnormalities (hypokinetic included) were evaluated as one group, no such threshold was obtained all segments which occurred a TI-201 uptake of more than 80% showed a functional recovery, wall motion did not improve in any segment with a TI-201 uptake of less than 40%. In the present study a considerable influence of the defect localisation with regard to the posterior wall was not observed. The values of TI-201 redistribution under resting condition were not useful to predict functional recovery. CONCLUSION: TI-201 SPECT in rest predicts preoperatively the reversibility in regions with severe wall motion abnormalities only and indicates myocardial viability in these cases. Thus, the method is basically useful to determine myocardial viability. In hypokinetic segments, however, a wide range of TL-201 uptake values exists without definite evidence to functional recovery.

Aged↗

[Effect of myocardial viability and coronary revascularization on clinical outcome and prognosis: a follow-up study of 161 patients with coronary heart disease].

One hundred and sixty-one consecutive patients (144 male, 57 +/- 9 years) with stable coronary artery disease underwent nuclear imaging for assessment of myocardial viability using Tc-99m sestamibi single-photon emission computed tomography (SPECT) and F-18 fluoro-deoxy-glucose (FDG) positron emission tomography (PET). 88% had a history of chronic myocardial infarction and all had angiographically proven regional wall motion (RWM) abnormalities in the distribution territory of a stenosed or occluded coronary artery. Patients were followed for 29 +/- 6 (22-44) months with 84/161 patients (52%) receiving elective revascularization by either bypass surgery or angioplasty. 61/84 patients underwent follow-up angiography after 5 +/- 2 months for quantitative assessment of RWM changes using serial analysis with the centerline method in 45 pts with technically suitable paired angiograms. Myocardial regions were classified according to semiquantitative analysis of regional sestamibi and FDG uptake as either normal, regions with evidence for maintained viability but no mismatch ("mild match"), regions with a perfusion/metabolism "mismatch," or scar. RWM improved in "mismatch" regions from -2.2 +/- 1.0 SD to -1.0 +/- 1.4 SD (p < 0.01) compared to the mean of a normal reference population. In contrast, in regions with a "mild match" or those classified as scar, RWM analysis revealed no functional changes at follow-up. For the assessment of clinical outcome, patients were divided into three groups depending on the result of viability imaging. Those with predominantly scar tissue in the target region for viability assessment (group A, n = 90), those with a "mild match" (B, n = 26), and group C (n = 45) consisting of patients with a "mismatch" pattern. Subsequent treatment was not blinded to nuclear imaging results and revascularization was performed in 30% of group A (group A2), 81% of group B, and 80% of group C, while the other patients were treated medically only. Cardiac events during follow-up were defined as cardiac death, myocardial infarction, unstable angina with subsequent revascularization, cardiac transplantation, and survived resuscitation without evidence for myocardial infarction. Group C demonstrated a significant reduction of cardiac events from 22% to 0% following revascularization, whereas in group A coronary revascularization did not influence the frequency of events. Subjective assessment of angina pectoris and heart failure symptoms revealed more patients with improvement following revascularization as compared to those treated medically. Thus, combined nuclear imaging using sestamibi SPECT and FDG PET with quantitative tracer uptake analysis allows detection of absent or preserved myocardial viability in regions with reduced perfusion and function with prognostic implication for regional myocardial functional outcome as well as for identification of patients who benefit most from coronary revascularization.

Adult↗

Granulocyte-macrophage-colony stimulating factor for prevention of neutropenia and infections in children and adolescents with solid tumors. Results of a prospective randomized study.

BACKGROUND: Chemotherapy is an essential modality of curative strategies in pediatric oncology. Dose and dose intensity are, above all, restricted by the myelosuppressive effects of cytotoxic drugs. Neutropenia constitutes an important risk of morbidity and mortality. Granulocyte-macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor that increases the number of circulating neutrophils as demonstrated in adults. METHODS: A prospective randomized study of the effects of GM-CSF was performed with 11 patients who were treated for solid tumors and received GM-CSF for 2 weeks starting 48 hours after completion of chemotherapy. Forty-two intraindividual identical chemotherapy-courses with and 42 without GM-CSF were compared. The monitoring program included the surveillance of the hematological reconstitution and the number and duration of infectious episodes. RESULTS: The average nadir of the absolute neutrophil count (ANC) with GM-CSF was higher than without GM-CSF. The average number of days with an ANC below 500/microliters was significantly reduced by GM-CSF. Fewer infectious episodes were observed among those who received GM-CSF therapy. Erythropoiesis was not significantly influenced by GM-CSF, whereas patients with GM-CSF therapy showed a longer thrombocytopenia without requiring more platelet transfusions. Rashes developed in two patients. CONCLUSIONS: In children and adolescents undergoing intensive chemotherapy for solid tumors, GM-CSF reduces neutropenia and infectious episodes at the cost of mild thrombocytopenia.

Adolescent↗

Cardiac rhythmic patterns in neuronal activity related to the firing rate of the neurons: II. Amygdala neurons of cats.

Neurons of the central and basal part of the amygdala complex were recorded in conscious, freely moving cats. These neurons have various cardiac rhythmic discharge patterns (CRDPs) which are estimated by post-event-time histograms (PETH). When the firing level of the neurons changed, the CRDPs were modulated. These modulations became obvious, when 'partial' PETHs of the neuronal activity were constructed according to the discharge level of the neurons. With changes of the neuronal discharge level different types of CRDPs were observed, interlaced in time during recordings of the same neuron. In 'total' PETHs, taken from the continuous periods of neuronal activity, cardiac rhythm was hidden or often was not so clearly visible as in 'partial' PETHs, taken at different discharge levels. As in case of neurons of the nucleus tractus solitarii (NTS) and for brainstem reticular neurons, amygdala neurons exhibited modulations of CRDPs as their activity level changed. The results indicate that the processing of activity patterns in these neurons depends on their activity level and functional organization, which is essentially dependent on afferent signals and influences from central structures reaching these neurons.

Amygdala↗

Glycan structure of the S-layer glycoprotein of Bacillus sp. L420-91.

Preliminary taxonomic characterization of isolate L420-91 has revealed that this organism is closely related to the species Bacillus aneurinolyticus. The bacterium is covered by a squarely arranged crystalline surface layer composed of identical glycoprotein subunits with an apparent molecular mass in the range of 109 kDa. A total carbohydrate content of approximately 3.5% (wt/wt) was determined in the purified surface layer glycoprotein. Glycopeptides were obtained after exhaustive Pronase digestion and purification including gel filtration, ion exchange chromatography and HPLC. From the combined evidence of composition analysis. Smith degradation and nuclear magnetic resonance spectroscopy experiments we propose the following structure for the glycan chain of the surface layer glycoprotein: [formula: see text]

Acetamides↗

Similarity of "core" structures in two different glycans of tyrosine-linked eubacterial S-layer glycoproteins.

Previously, the repeating-unit structure of the S-layer glycoprotein from the eubacterium Bacillus alvei CCM 2051 has been determined to be [-->3)-beta-D-Galp-(1-->4)-[alpha-D-Glcp-(1-->6)-]-beta-D-ManpNAc- (1-->]n (E. Altman, J.-R. Brisson, P. Messner, and U. B. Sleytr, Biochem. Cell Biol. 69:72-78, 1991). Nuclear magnetic resonance spectroscopic reexamination of this glycan reveals that the O-antigen-like domain of the polysaccharide is [see text] connected with the S-layer polypeptide through the "core" structure -->3)-alpha-L-Rhap-(1-->3)-alpha-L-Rhap-(1-->3)-alpha-L-R hap-(1-->3)-beta-D-Galp-(1-->O)-Tyr. Except for the substitution in position 4 of the nonreducing rhamnose with the modified glyceric acid phosphate residue GroA-2-->OPO2-->4-beta-D-ManpNAc-(1-->, this core is identical to the core of the tyrosine-linked glycan from the S-layer glycoprotein of Thermoanaerobacter thermohydrosulfuricus L111-69 (K. Bock, J. Schuster-Kolbe, E. Altman, G. Allmaier, B. Stahl, R. Christian, U. B. Sleytr, and P. Messner, J. Biol. Chem. 269:7137-7144, 1994).

Bacillus↗

[Comparison of relative 18FDG uptake with metabolic rate (MRGlucose) in the myocardium in CAD, classified by 99m-Tc-MIBI].

AIM: Are i) typical patterns of perfusion/metabolism (match, mismatch), gained from relative 99mTc-MIBI vs relative 18FDG uptake (normalized to the perfusion maximum) obtainable also vs absolute MRGlu and is ii) rMRGlu in the segment of maximum perfusion (MIBI = 100%) within the normal range for all degrees of coronary artery disease (CAD)? METHODS: In 55 non-diabetic patients with CAD, relative myocardial perfusion (99mTc MIBI SPECT at rest) and relative 18FDG uptake (PET after glucose load) were used to separate for various flow/metabolism constellations. In addition, regional glucose metabolic rate (rMRGlu in mumol/100 g/min; dynamic-graphic analysis from Gambhir/Patlak) was determined in 13 segments of the left ventricle each (i.e., in a total of 715 segments). RESULTS: rMRGlu revealed wide standard deviations (up to 51%). It decreased from normal (52.7 +/- 27.3 mumol/100 g/min), mismatch (45.3 +/- 17.3) and intermediate (35.2 +/- 12.4) to match ("non viable"; 26.7 +/- 13.3) significantly (p < 0.01). In 26% of the perfusion maxima, MRGlu was < 40 mumol/100 g/min. Out of these, only in five patients (of 28) with 3-vessel disease, it was even smaller (< 30 mumol). In three out of the latter, glucose blood levels were below euglycemia. CONCLUSION: rMRGlu in CAD revealed an identical perfusion/metabolism pattern as relative 18FDG uptake. Thus, the higher efforts employed to compute rMRGlu do not yield diagnostic advantage. The segmental perfusion maximum, used for normalization of relative 18FDG uptake (100% MIBI uptake = 100% FDG uptake) was reliable in euglycemic patients even with 3-vessel disease.

Biological Transport↗

Derivatives of a novel cyclopeptolide. 1. Synthesis, antifungal activity, and structure-activity relationships.

The synthesis of a series of derivatives of the novel antifungal cyclopeptolide 1, which consists of nine S-amino acids and R-lactic acid, is described. Besides functional group variation of MeAsp4 (esters 2a-d, amides 3a-d, alcohol 4, and its derivatives) and Tyr(Me)9 (demethyl derivative 8, ethers 12a-f, 13, and oxidative degradation of the phenyl group to 14), opening of the lactone by LiOH in THF/H2O allowed manipulation of the hydroxy group of R-Hypr10 in the resulting acyclic peptide 15. Recyclization of 15 under Mitsunobu conditions followed by deprotection led to the S-Hypr10 analogue 17 of 1. Cyclic decapeptides 33 and 34 as well as cyclic undecapeptides 35 and 36 were obtained via the corresponding modified linear peptides 23, 24, 27, and 28 by cyclization. Methylation of all secondary amide groups by CH3I and KH/18crown6 gave the permethylated compound 37. Two of the derivatives (17 and 34) showed superior activities against yeasts in vitro at pH 6.5 as compared to 1, but not at a lower pH (4.5).

Administration, Oral↗

Derivatives of a novel cyclopeptolide. 2. Synthesis, activity against multidrug resistance in CHO and KB cells in vitro, and structure-activity relationships.

A series of derivatives of the novel cyclopeptolide 1 was prepared, and their ability to chemosensitize multi drug resistant CHO and KB cells in vitro was evaluated. In contrast to the parent compound, several of the derivatives were found to be highly active. In particular, conversion of the R-lactic acid residue of 1 into its S-isomer via lactone ring cleavage and recyclization with inversion resulted in a marked enhancement of activity. Some of these derivatives (e.g., 15a, SDZ 280.446) belong to the most potent resistance modulating compounds known so far.

Amino Acid Sequence↗

Cloning, sequencing, and heterologous expression of a cellulase-encoding cDNA (cbh1) from Penicillium janthinellum.

From a Penicillium janthinellum cDNA library, two clones with 1.8- and 1.9-kb inserts were isolated by hybridization to a Trichoderma reesei cellulase-encoding gene probe (egl1). Both cDNAs have identical 5' ends and coding sequences, but different polyadenylation start points in their 3' untranslated regions. In the nucleotide (nt) sequence, one open reading frame of 537 amino acids was detected which shows 56% homology with endoglucanase I of T. reesei and 70% homology with cellobiohydrolase I of T. reesei, Phanerochaete chrysosporium, and Humicola grisea. Expression of the 1.9-kb cDNA in the Escherichia coli T7 system led to the detection of a 57-kDa protein, in agreement with the theoretical value. Fusion to the promoter of the yeast phosphoglycerokinase-encoding gene led to efficient expression and partial secretion of the cDNA-encoded cellulase with cellobiohydrolase I activity in Saccharomyces cerevisiae.

Agaricales↗

Domain closure in adenylate kinase. Joints on either side of two helices close like neighboring fingers.

In large variants of adenylate kinase the AMP and ATP substrates are buried by a domain rotating by 90 degrees. Here conformational changes responsible for this domain closure are determined by an analysis of the open state of beef heart mitochondrial adenylate kinase and the closed state of Escherichia coli adenylate kinase. Although these two proteins have sequence differences, the principal structural changes responsible for the domain movements are large, and can clearly be distinguished from the effects of evolution. The mobile domain is linked to the rest of the protein by two helices packed together in an antiparallel fashion. During the closure, deformations take place in four localized regions, called joints, near the N and C termini of these helices. Three of these joints have simple motions that can be well approximated by rotations of three torsion angles, but the joint that makes contact with the ligand involves motion throughout an extended loop: i.e. two torsions on either side of a reverse turn change significantly. The main chain atoms of the joints have few packing constraints. The first pair of joints is responsible for approximately 30 degrees of the total rotation and the second pair for the remaining approximately 60 degrees. These movements carries along the regions between the joints, the two helices and the rest of the mobile domain, to a first approximation, as rigid bodies. This jointed domain closure mechanism is contrasted with the shear mechanisms found in other enzymes.

Adenylate Kinase↗