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Biomedical subjects

G Schulz

Publications and source records attributed to G Schulz.

At least 163 records · Page 9Linked to original sources

Synthesis of alternate linear and branched repeating units of the Escherichia coli LP 1092 capsular polysaccharide containing 3-deoxy-alpha-D-manno-2-octulosonic acid (KDO) linked to secondary positions of D-ribose.

The oligosaccharides, methyl 3-O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-beta-D-ribofuranosid e, methyl 2-O-beta-D-ribofuranosyl-3-O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-beta-D-ribofuranosid e, and methyl O-(sodium 3-deoxy-alpha-D-manno-2-octulopyranosylonate)-(2----2)-O-beta-D- ribofuranosyl-(1----2)-beta-D-ribofuranoside were prepared in high purity and good over-all yields. The constitutions of the trisaccharide derivatives correspond to the repeating units of the proposed linear and branched structures of the capsular polysaccharide(s) from Escherichia coli LP 1092. The alpha-KDO-(2----3)-beta-D-Ribf and alpha-KDO-(2----2)-beta-D-Ribf units were synthesized by a modification of the Helferich procedure using methyl (4,5,7,8-tetra-O-acetyl-3-deoxy-alpha-D-manno-2-octulopyranosyl bromide)-onate and appropriate beta-D-ribofuranosyl derivatives. The constitutional and configurational assignments were based on the 250-MHz 1H-n.m.r.-spectra of protected derivatives of the oligosaccharides.

Carbohydrate Conformation↗

Empirical 13C-n.m.r.-correlations between the Escherichia coli K 13 and LP 1092 capsular polysaccharides and model oligosaccharides containing D-ribose and 3-deoxy-D-manno-2-octulosonic acid.

The proton-decoupled, Fourier-transform, 13C-n.m.r. spectra of the two anomeric sodium (methyl 3-deoxy-7-O-beta-D-ribofuranosyl-alpha- and beta-D-manno-2-octulopyranosid)onates, of the two anomeric sodium [methyl 3-deoxy-7-O-(2-O-beta-D-ribofuranosyl-beta-D-ribofuranosyl)-alpha- or -beta-D-manno-2-octulopyranosid]onates, and of methyl 2-O-beta-D-ribofuranosyl-beta-D-ribofuranoside have been recorded. The constitutions of these compounds correspond to repeating units and partial structures of the capsular polysaccharides from Escherichia coli K 13, K 20, K 23, and LP 1092 strains. The 13C-n.m.r.-line patterns of these oligosaccharide derivatives and the corresponding polysaccharides show striking differences dependent upon the anomeric configurations of the KDO residues. These differences may be used for the identification, by visual or computer-assisted pattern analysis, of the anomeric configurations of KDO-residues in oligo- or poly-saccharides. Thus, it was confirmed that the KDO residues in the K 13, K 20, and K 23 polysaccharides have the beta anomeric configuration, whereas those in the LP 1092 polysaccharide have the alpha anomeric configuration.

Carbohydrate Conformation↗

Eradication of established human melanoma tumors in nude mice by antibody-directed effector cells.

The simultaneous injection of monoclonal antibody 9.2.27, directed against a chondroitin sulfate proteoglycan preferentially expressed on human melanoma cells, and 2 X 10(7) mononuclear splenocytes, eradicated established, progressively growing human melanoma tumors in nude mice. Neither splenocytes nor antibody alone achieved significant tumor regression. The cells responsible for tumor elimination are most likely natural killer (NK) cells: they are present in splenocytes of T cell-deficient nude mice, and cloned cells with NK activity are able to suppress tumor growth. Moreover, splenocytes treated with anti-asialo GM1 and complement or harvested from NK-deficient C57BL/6 beige mice did not cause tumor rejection. Furthermore, treatment of BALB/c nude mice just before injection with anti-asialo GM1 antiserum, which is known to eliminate NK activity in vivo, resulted in better tumor growth. In addition, evidence is presented that cells with NK activity are probably the effectors responsible for melanoma target cell lysis in vitro: Antibody-dependent and -independent cell-mediated lysis of M21 melanoma cells was suppressed when splenocytes were preincubated with complement and antibodies specific for cell surface antigens of NK cells, i.e., anti-asialo GM1, anti-Qa5, and anti-NK1.1. Moreover, splenocytes of C57BL/6 beige mice were not able to lyse M21 cells in vitro. These results strongly support the conclusion that cells with NK activity are indeed responsible for the antibody-dependent destruction of M21 melanoma cells in vivo and in vitro.

Animals↗

Reticular formation of the lower brainstem. A common system for cardio-respiratory and somatomotor functions. Cross-correlation analysis of discharge patterns of neighbouring neurones.

Temporal relations of discharges of 73 pairs of neurones located in the medial parts of the reticular formation of the lower brainstem were studied by cross correlation analyses in chloralose-urethane anaesthetized dogs. The action potentials of 2 or 3 neighbouring neurones were recorded with one electrode simultaneously. Uncorrelated discharges of neurones and 4 different types of correlated discharges were observed in cross correlation histograms: they were: (1) rhythmic couplings with frequencies between 2 and 5 Hz related to the same rhythm in the EEG; (2) strong, non-rhythmic couplings with short latencies up to 5 ms; (3) a combination of strong and rhythmic couplings, and (4) high-frequency oscillation couplings. Most pairs of neurones showed different types of correlation during the recordings. The different forms of correlated discharge behaviour could be related to different types of functional organization of the neuronal network in the reticular formation.

Afferent Pathways↗

Reticular formation of the lower brainstem. A common system for cardio-respiratory and somatomotor functions. Considerations aided by computer simulations.

Parallel investigations were done using the reticular formation of the lower brainstem of dogs and computer simulated neuronal networks with properties of reticular neurones. By the aid of the simulations, understanding of the functional organisation of the common brainstem system, reticular formation and the experiments performed were optimized. The fact that discharge sequences of model neurones are very similar to those of reticular neurones was proved by interval histograms and covariance histograms. Discharges of neighbouring reticular neurones tend to be strongly coupled. In the model the discharges of the neurones could be coupled by common afferent inflows. Physiologically, neighbouring reticular neurones receive common afferents from peripheral somato-sensory systems. Neighbouring neurones with strongly coupled discharging are organized in subpopulations. The configurations of the subpopulations are determined by number and type of afferents actively influencing neurones and by the level of intrinsic activity of the network. Signal processing and transfer by neuronal subpopulations depend on the level of activity and on the degree of coupled discharging, i.e. the local organisation of the neurones.

Afferent Pathways↗

Human major histocompatibility complex class I antigens: residues 61-83 of the HLA-B7 heavy chain specify an alloreactive site.

A chemically synthesized peptide (sequence in text) homologous to residues 61-83 of the HLA-B7 heavy chain, induced antibodies that specifically recognized the HLA heavy chain-beta 2-microglobulin complex and the free heavy chain of the HLA-B7 antigen. These antibodies specifically immunoprecipitated the HLA-B7 beta 2-microglobulin complex solubilized from human lymphoblastoid cells by nonionic detergents and reacted with free HLA-B7 heavy chains in blots on nitrocellulose. These observations suggest that the antigenic conformation of this region of the HLA-B7 molecule is independent of the presence of beta 2-microglobulin and that amino acid residues 61-83 mimic an alloreactive site expressed by the HLA-B7 antigen.

Amino Acid Sequence↗

[Relevance of serum aldolase for the detection of liver metastases of bronchial cancer--comparative enzymatic and endoscopy-autopsy studies].

In 100 patients with histologically confirmed bronchogenic carcinoma, the reliability of serum aldolase determination as screening test for metastases in the liver has been investigated. Demonstration respectively exclusion of liver metastases was done by laparoscopy or occasionally by autopsy. In contrast to previous results, with the presently used, more reliable technique, the results were less satisfactory. True positive aldolase values as indicators of presence of liver metastases were observed in 72,7 percent of patients carrying those. In cases of chronic liver damage of other etiology, in general no elevated aldolase values were observed. The aldolase activity correlated with the amount of tumor tissue in the liver. An improvement of the enzymatic screening might be expected from additional determination of enzymes indicating cholostasis or from determination of liver-specific aldolase isoenzyme.

Adenocarcinoma↗

Diabetes self-adjustment by a computerized program--first experiences in inpatient and outpatient treatment.

Blood glucose self-monitoring is essential to stabilize diabetes on a normoglycemic level. However, patients often do not find the correct insulin adaptation. Therefore, we developed a computer system to adapt insulin doses using a control matrix. During a first inpatient and outpatient period, we attained a very satisfactory blood glucose normalization and stabilization. During the outpatient period the HbA1c values decreased. Stopping the program in some patients blood glucose levels and HbA1c values increased again.

Blood Glucose↗

The response of some intravascular and intracellular lipid parameters of the rat after treatment with isatin.

The effect of isatin on serum lipid concentrations, the activity of lipoprotein lipase, the activity of lipogenic enzymes and the oxidation rate of fatty acids of female Wistar rats were investigated. A decrease of the triglyceride concentrations could be observed after one week of treatment of the group of sucrose-rich alimented animals, after two weeks this was also the case with the group fed with standard food. There were no changes in the cholesterol concentrations. Post-heparin lipolytic activity was not influenced. The liver enzymes malic enzyme, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase showed a remarkable increase in activity. The simultaneous rise of the oxidation rate of 14C-palmitate in the liver was measured. On the basis of the present findings the accelerated degradation rate could be responsible for the hypolipemic effect of the substance. The possible participation of the carnitine shuttle in the lipid-lowering action is discussed on the basis of changed concentrations of total carnitine, free carnitine and acylcarnitine in pooled serum samples after treatment with isatin.

Animals↗

[Effect of dietary fat on blood sugar levels and insulin consumption after intake of various carbohydrate carriers in type I diabetics on the artificial pancreas].

The role of fat on carbohydrate absorption was investigated in 14 type-I-diabetics who were connected to a glucose-monitored insulin infusion pump (Biostator, Miles). The patients received test meals in the form of potatoes, rice and apples with equal carbohydrate content, in each case with and without added fat. Comparison of carbohydrate carriers showed an increase of blood sugar and insulin consumption which was biggest after the potato meal and significantly lower after rice and apple ingestion. This is probably related to the different biologic availability of carbohydrate carriers. Addition of fat caused lowering of blood sugar and insulin consumption in the potato meal; in this case nutritional fat is likely to have slowed gastrointestinal passage. There were no major differences among rice and apple. It can be concluded that addition of fat delays absorption of rapidly split carbohydrates more than absorption of slowly split carbohydrates such as rice. The lack of influence of fat on postprandial blood sugar and insulin consumption after an apple meal is related to the slight increase of blood sugar caused by the high content of fructose.

Adolescent↗

[Diagnostic problems of pulmonary embolism].

There is no pathognomonic sign for pulmonary embolism. The diagnosis must be made from the combination of anamnestic, clinical and paraclinical parameters. An essential purpose of the paper is the demonstration of the valency of these parameters. The clinical proof of the origin of embolism facilitates the establishment of the diagnosis, is, however, often not possible. The pulmonary embolism as well as the origin of embolism are most certainly to be proved by angiographic investigation methods. On account of the vital endangering by relapses as well as the necessity of a different and extensive therapy the securing of the diagnosis is necessary.

Adult↗

Immunologic and functional characterization of anti-HLA-DR rabbit antibodies induced by synthetic peptides.

Three peptides selected from the amino acid sequence of the alpha- and beta-chains of DR2 histocompatibility antigens were chemically synthesized and coupled to carrier proteins to be used as immunogens in rabbits. This immunization resulted in the production of specific antibodies that readily recognized the antigen. However, only one of the four antibody preparations, antibody 6148, elicited by a short peptide from the beta-chain (residues 61-73), reacts with native membrane glycoproteins as well as intact human lymphoblastoid cells in enzyme-linked immunosorbant assays. This antibody was found to react also with membrane glycoproteins solubilized by nonionic detergents from cells bearing a different HLA-DR specificity: therefore it is likely that the peptide responsible for eliciting antibody 6148 represents a common framework determinant of DR alloantigens that is accessible on the surface of lymphoblastoid cells. The ability of antibody 6148 to bind to intact cells was confirmed by indirect immunofluorescence and by fluorescein-activated cell sorter analysis. This antibody is also capable of mediating antibody-dependent cellular cytotoxicity as determined by a 51Cr-release assay.

Amino Acid Sequence↗

Development of individual insulin infusion profiles for open loop infusion systems.

A computer controlled syringe-type insulin infusion pump storing up to 254 different infusion rates, eight different meal programs and two different basal rates automatically changeable during 24 h in EPROM was used for insulin infusion applying a wavy step profile. This profile approaching the physiological postprandial insulin secretion of the B-cell was calculated by an algorithm following the biphasic insulin secretion model proposed by E. Cerasi . The computer program for the open loop infusion device simulated the feed-back structure of a closed loop insulin secretion control by an algorithm based upon a theoretical postprandial blood sugar profile. Fifteen unstable juvenile onset insulin requiring diabetics could be well controlled after two to three days of an intravenous open loop insulin infusion program. The programs consisted of two constant basal rates and superimposed wavy step profile programs activated at the beginning of each meal. The preabsorptive bolus or cephalic phase was an additional tool both for improved postprandial blood sugar control and further reduction of insulin consumption. The programmable insulin infusion device proved as a valuable tool for the study of a sophisticated insulin infusion profile suitable as well for open loop as for closed loop insulin infusion systems.

Adult↗

Localization of the gangliosides GD2 and GD3 in adhesion plaques and on the surface of human melanoma cells.

The predominant gangliosides produced by two cultured human melanoma cell lines are GD3 and/or GD2. These gangliosides were found to be cell associated and present in substratum-attached material after cell removal by EDTA. Monoclonal antibodies directed to GD2 and GD3 specified the cell-surface distribution of these gangliosides and localized them in focal adhesion plaques at the interface of cells and their substratum. These attachment sites did not represent indiscriminant membrane fragments remaining after removal of cells with EDTA, because neither melanoma-associated proteoglycan nor class I histocompatibility antigens were detected by their respective antibodies. Our data suggest that the disialogangliosides GD2 and GD3 may be involved in the interaction between human melanoma cells and solid substrata.

Cell Adhesion↗

Cleavage of myelin basic protein by neutral protease activity of human white matter and myelin.

Polypeptides arising from neutral in vitro proteolysis of myelin basic protein (MBP) of human brain were evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. At pH 7 a marked breakdown of MBP resulted in the formation of 8-12 polypeptides ranging from 6 to 17 kd in molecular weight. As neutral proteolytic activity was not eliminated by either gel filtration or cation-exchange chromatography acid-soluble protease(s) involved probably have a size and electric charge similar to that of MBP. The enzymatic nature of neutral proteolysis was ascertained by heat inactivation and inhibition by alpha 2-macroglobulin. Incomplete inhibition of proteolysis and the failure of small peptides (less than 6 kd) to show up on electrophoresis seem to suggest that MBP was degraded by exopeptic proteases as well. Acid extracts of purified myelin yielded polypeptides similar to those of MBP of delipidated white matter. The results are consistent with a sequential limited proteolysis of MBP by neutral proteases probably associated with myelin and possibly related to the in situ catabolism of MBP in man.

Brain↗