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Biomedical subjects

J Schilling

Publications and source records attributed to J Schilling.

At least 55 records · Page 3Linked to original sources
PubMed1993

A new approach in the treatment of hypotension in human septic shock by NG-monomethyl-L-arginine, an inhibitor of the nitric oxide synthetase.

NG-monomethyl-L-arginine (L-NMMA) is an inhibitor of the enzyme nitric-oxide-synthetase. Nitric oxide (NO), produced by endothelial and vascular cells regulates physiological vascular tone, blood pressure and tissue perfusion via guanylate-cyclase and cGMP. In an advanced stage of therapy resistant septic shock in response to inflammatory mediators, NO is overproduced. This leads to vasodilatation, a fall in systemic blood pressure and an attenuated vasoconstriction-response to sympathetic-stimuli. Two episodes of severe and prolonged hypotension in a patient with sepsis were successfully treated twice by bolus therapy of L-NMMA within 4 weeks. On both occasions blood pressure was reversed to normal and the continuous use of high doses of catecholamines were stopped. In contrast to the immediate response of blood pressure, heart rate and central venous pressure remained stable. Cardiac output dropped to 68% and PaO2 increased. These findings indicate that NO-synthetase-inhibitors may be of value in the therapy of human septic shock.

Adult↗
PubMed1993

Randomized comparative trial of imipenem/cilastatin versus aminoglycoside plus amoxycillin plus clindamycin in the treatment of severe intra- and post-operative infections.

In a prospective, randomized, controlled study, clinical and bacteriological efficacy of imipenem/cilastatin (I/C) was compared with a standard combination of aminoglycoside + amoxycillin + clindamycin (C) in patients (pts) with severe intra- and postoperative infections. A total of 84 pts were randomly separated into two groups of 42 pts. Diagnoses were pneumonia n = 21 (14 in I/C group and 7 in C), peritonitis n = 45 (16 in I/C group and 29 in C), septicaemia n = 12 (9 in I/C group and 3 in C), and 7 other infections (3 in I/C group and 4 in C). Doses used were imipenem/cilastatin 1 g q 8 h and amoxycillin 2 g q 8 h plus clindamycin 0.6 g q 6 h, plus netilmicin according to serum concentrations. Success rates were 85.4% (n = 35: 34 cured and one improved) in the I/C group and 83.3% (n = 35: 30 cured and five improved) in the C group. Six pts in group I/C and 7 in group C failed to respond to treatment. One patient in the I/C group was not assessable. 62% of the bacterial isolates were eradicated in the I/C group and 55% in group C. 7% were suppressed in I/C and 5% in C. It is concluded that imipenem/cilastatin is an effective and well-tolerated alternative to antibiotic combinations in severe intra- and post-operative infections. It offers the advantages of fewer drug doses and less renunciation of serum drug concentration monitoring.

Aminoglycosides↗
PubMed1993

Antibiotic prophylaxis in cardiovascular surgery: a prospective randomized comparative trial of one day cefazolin versus single dose cefuroxime.

With the intention of reducing prophylactic antibiotic dosage, previous studies in the Zurich University Hospital have shown that a one/day prophylactic antimicrobial regimen with cefazolin was as effective as a single dose of ceftriaxone. In this prospective randomized study one day cefazolin prophylaxis (1 g q 8 h i.v.) was compared with a single dose of cefuroxime prophylaxis (1.5 g). In cases of cardiopulmonary bypass 0.75 g was added in the priming solution. In case of re-operation prophylaxis was repeated. 496 patients were enrolled in the study protocol; 78 patients were subsequently excluded. Of the remaining patients 224 (158 male, 66 female, mean age 61) were in the cefazolin group and 194 (142 male and 52 female, mean age 60) in the cefuroxime group. Mean duration of the intensive care unit (ICU) stay was three days in both groups and mean hospital stay was 16 days in the cefazolin group and 15 days in the cefuroxime group. The overall postoperative infection rate was 15.3%; 18.8% in the cefazolin group and 11.3% in the cefuroxime group. The statistical differences were found as in trend (p = 0.095). The lower incidence of infectious complications in the single cefuroxime dose group may indicate an improvement in effectiveness of antimicrobial prophylaxis: it offers patients a reliable antimicrobial protection. In addition, the single dose prophylaxis has the advantage of easier handling, reduced dosage frequency and lower cost.

Bacterial Infections↗
PubMed1993

[Lung abscess: evolution of a complication over 45 years].

143 patients with lung abscesses were hospitalised at the Department of Surgery at University Hospital Zurich from 1946 to 1990. Analysing our patients in a retrospective study we concluded as follows: 1. Lung abscesses have nearly disappeared in our patients. 2. Lung abscesses can be cured without lethality. 3. Cancers of the lung causing abscesses were not seen any more since 1960. 4. A compromised immunological system appeared as a new pathogenetical factor since the beginning of the 1980ies.

Cause of Death↗
PubMed1992

Penetration of fleroxacin into human lung, muscle, and fat tissue.

Fleroxacin is a new fluoroquinolone with established potent antimicrobial and pharmacokinetic properties, and the aim of this study was to determine its rate of penetration into human lung, muscle, and fat tissues. In a total of eight patients undergoing lung surgery, plasma and tissue concentrations of unmetabolized fleroxacin were determined. This was done in subgroups of two patients each, receiving either 6, 8, 12 or 24 hours prior to surgery one single oral dose of 400 mg fleroxacin. It was found that fleroxacin penetrates well into muscle and lung tissues, but not into fat tissue. The levels in muscle and lung were 1.1 to 4.7 times higher than the according plasma concentrations.

Adipose Tissue↗
PubMed1992

[The course of pregnancy with placenta praevia diagnosed in the 2nd and 3rd trimester].

Selected clinical features of the course of pregnancy in 118 gravidas with placenta praevia diagnosed ultrasonographically on the first breeding were compared. The clinical features significantly connected with bleeding and the prognostic features for the way of delivery were stated. The longest bleeding was observed in patients with partial or marginal placenta praevia. The most common anterior location of low placenta praevia was connected with the lowest risk as regards the cesarean section due to hemorrhage. The earlier occurrence of the bleeding was associated with its longer duration. The time of the occurrence of the first bleeding and its duration were associated with a duration of the pregnancy and a body mass of the newborn. The recurrence of bleeding was of no prognostic importance. The appearance of the first bleeding after the 28th week of pregnancy was significantly connected with the necessity of performing a cesarean section due to hemorrhage in case of central, partial or marginal placenta praevia. In case of low-lying placenta the way on delivery was significantly related to the time of appearance of the first bleeding and the distance between the placenta and the internal os. Fisher's linear discriminative function of the two features allowed for the determination of a mathematical formula for the prognosis of the way of delivery in case of a low-lying placenta.

Adolescent↗
PubMed1991

Synthesis and characterization of the Kunitz protease-inhibitor domain of the beta-amyloid precursor protein.

To understand the pathological process by which amyloid is deposited in Alzheimer's disease, it is important to characterize the proteolytic processing events of the beta-amyloid precursor protein (beta-APP) from which the amyloid-forming fragment is excised. A potentially important component in beta-APP processing is the 57-amino acid (aa) Kunitz serine protease inhibitor (KPI) located within the extracellular domain of both the 751- and 770-aa isoforms of beta-APP. We have synthesized DNA encoding the 57-aa KPI domain as a necessary step in identifying the role of the protease inhibitor in beta-APP processing and amyloid formation. A bacterial secretion system directed by the alkaline phosphatase signal peptide of Escherichia coli linked to a synthetic gene encoding KPI was used to produce soluble, extracellular recombinant KPI (reKPI) protein. The reKPI protein was purified to homogeneity from bacterial supernatants and was biochemically and biologically characterized. Complete aa sequence analysis confirmed the fidelity of the reKPI, and fast-atom bombardment mass-spectral analysis was used to document that reKPI was of the predicted Mr. The reKPI is as active on a molar basis as the inhibitor-containing beta-APP when assayed for inhibition of trypsin activity. Together these data suggest that reKPI protein is properly folded and lacking in modified aa. Hence, this reKPI will be an important reagent in gaining a better understanding of the role of the KPI domain in beta-APP function and metabolism, as well as in the proteolytic events involved in beta-amyloid formation.

Alzheimer Disease↗
PubMed1991

A synaptic vesicle specific GTP-binding protein from ray electric organ.

A cDNA encoding a synaptic vesicle associated GTP-binding protein was identified by screening a lambda gt11 expression library derived from the electric lobe of Discopyge ommata with polyclonal antibodies recognizing vesicle-specific proteins of Mr 25,000. Nucleotide sequence analysis defines an open reading frame of 218 amino acids. The protein belongs to the ras superfamily and shares about 75% amino acid identity with smg-25A, B and C identified in bovine brain and rab3A characterized in rat brain. Northern blot analysis revealed a 4.5 kb transcript present only in neural tissues, the highest level of expression being observed in electric lobe. Western blot analysis of total tissue homogenates derived from D. ommata detected the protein in electric organ, forebrain and to a lesser extent in electric lobe and spinal cord. No immunoreactivity was detected in non-neuronal tissues. Blotting of subcellular fractions derived from electric ray electric organ revealed that the GTP-binding protein co-purifies with synaptic vesicles. The neural specific expression and the localization to synaptic vesicles suggest a role of this protein in synaptic vesicle trafficking and targeting.

Amino Acid Sequence↗
PubMed1991

Differential expression of the p65 gene family.

The genome of the marine ray Discopyge ommata contains at least three p65-related genes. o-p65-A is 84% identical, o-p65-B is 78% identical, and o-p65-C is only 41% identical to a previously characterized rat p65. The cytoplasmic domain, particularly the two regions that are similar to the regulatory domain of protein kinase C, are most highly conserved. The three genes are expressed in different but overlapping patterns in the central nervous system. o-p65-A immunoreactivity is found predominantly in forebrain, cerebellum, and neuroendocrine cells, while o-p65-B immunoreactivity is predominantly localized to the spinal cord, brainstem, and midbrain. Many synaptic vesicle proteins are members of small gene families that are differentially expressed, resulting in several unique combinations of these molecules in specific brain regions.

Amino Acid Sequence↗
PubMed1990

Conformation of apolipoprotein B-100 in the low density lipoproteins of tangier disease. Identification of localized conformational response to triglyceride content.

The low density lipoproteins (LDL) from patients with Tangier disease are enriched in triglycerides, 27% of LDL mass versus 7% for normal LDL. To study whether this unique LDL core lipid composition affects the surface disposition of apolipoprotein (apo) B-100, we analyzed the LDL by protease digestion and in competitive radioimmunoassays. Limited proteolytic digestion of Tangier LDL by Staphylococcus aureus V8 protease generated a prominent fragment of 120 kDa (cleavage site at residue 1076), which was not visible in similarly digested normal LDL. In competitive radioimmunoassay, Tangier LDL bound weakly to the apoB-specific monoclonal antibody MB20, compared with control LDL. We localized the MB20 epitope between residues 1031 and 1084 of apoB-100, probably very near residue 1076. DNA sequencing of exon 21 of apoB genomic clones (coding for residues 1014-1084) from a Tangier patient revealed no difference from the normal DNA sequence, thus eliminating a protein polymorphism as a basis for the altered protease sensitivity and antibody binding. When the triglyceride contents of Tangier LDL were reduced to 10% of mass by incubation with normal high density lipoproteins, production of the 120-kDa fragment by proteolysis decreased and MB20 binding increased in affinity, implying a change toward normal conformation of apoB-100. Thus, using two independent techniques, proteolytic digestion and binding of monoclonal antibodies, we have demonstrated an alternative conformation of apoB-100 in the vicinity of residue 1076, which reflects the content of triglycerides in the LDL particle.

Amino Acid Sequence↗
PubMed1990

Cloning, structure, and expression of a rat binding protein for polychlorinated biphenyls. Homology to the hormonally regulated progesterone-binding protein uteroglobin.

Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. Here, we report the isolation of a cDNA encoding the rat lung PCB-binding protein. The identity of the PCB-binding protein is supported by expression of the cDNA in Cos-1 cells where the homogenates from transfected cells show specific binding of 4,4'-bis([ 3H]methylsulfonyl)-2,2',5,5'-tetrachlorobiphenyl, a high affinity ligand for the PCB-binding protein. Also a monospecific antiserum to the PCB-binding protein recognizes a 13-kDa protein in the homogenates of transfected cells but not in the corresponding fraction of mock-transfected cells. Northern blot analysis of total RNA from different rat tissues demonstrates that the cDNA detects a approximately 600-base pair mRNA which appears to be solely expressed in lung. Interestingly, DNA sequence analysis and prediction of the amino acid sequence reveals that the PCB-binding protein shares 53% positional amino acid identity with uteroglobin, a progesterone-binding protein found in rabbit uterus and lung. Furthermore, amino acids shown by x-ray crystallography to delineate the central cavity of uteroglobin, which fits progesterone, are highly conserved in the two proteins.

Amino Acid Sequence↗
PubMed1990

Microbody phosphoglycerate kinase of Trypanosoma brucei: expression and complementation in Escherichia coli.

In the primitive eukaryotic parasite, Trypanosoma brucei, most of the enzymes of glycolysis are located within microbody organelles called glycosomes. Proteins destined for the glycosome are synthesized on free ribosomes and post-translationally translocated into the organelle. The gene, gPGK, encoding the glycosomal isozyme of phosphoglycerate kinase (gPGK), was cloned adjacent to a T7 promoter and cotransformed with a plasmid encoding T7 RNA polymerase into Escherichia coli Pgk-cells. Functional complementation occurred, but only after the creation of a ribosome-binding site by mutagenesis. This represents the first example of complementation of an E. coli mutant with a gene encoding a microbody protein. Enzymatically active recombinant gPGK was purified to near homogeneity by ion exchange chromatography from highly expressing E. coli. The recombinant protein will aid in studies of glycosomal biogenesis.

Animals↗
PubMed1990

Protease-specificity of Kunitz inhibitor domain of Alzheimer's disease amyloid protein precursor.

The putative inhibitor domain of Alzheimer's disease amyloid protein precursor was purified from E. coli containing a synthetic gene encoding the Kunitz domain. The purified protein (A4 inhibitor) inhibited the activity of trypsin, forming a 1:1 molar complex with the enzyme. It also strongly inhibited plasmin (Ki = 7.5 x 10(-11) M) from human serum and tryptase (Ki = 2.2 x 10(-10) M) from rat mast cells (tryptase M). In addition, it inhibited rat pancreatic trypsin, alpha-chymotrypsin and kallikrein and human serum kallikrein, but did not inhibit rat chymase, pancreatic elastase, alpha-thrombin, urokinase, papain or cathepsin B.

Amino Acid Sequence↗
PubMed1990

Identification of an enzyme in human kidney that correctly processes prorenin.

Using pure recombinant human prorenin as a substrate, we have identified an enzyme in human kidney that accurately processes prorenin to active renin (EC 3.4.23.15). In the crude homogenate, the predominant activity of this potential renin-processing enzyme (RPE) converted the Mr 47,000 inactive prorenin to Mr 44,000 active renin and had a pH optimum of approximately 6. The activity was blocked by cysteine protease inhibitors, but not by pepstatin, EDTA, or serine protease inhibitors. This RPE activity was not detected in a similarly prepared homogenate of human chorion decidua tissue, which produces primarily prorenin, or in human plasma. The activity was purified 100-fold by ammonium sulfate precipitation, p-chloromercuribenzoate affinity chromatography, and chromatofocusing. The partially purified enzyme has a Mr of approximately 27,000 and an isoelectric point in the pH 4.8-5.6 range. The activity in the purified RPE preparation had the same pH optimum as that in crude homogenate, cleaved the prosegment at the same site used by the kidney in vivo based on amino-terminal sequencing of the processed renin, and did not degrade prorenin or renin. These data suggest that the cysteine protease we have isolated is a candidate for authentic renal RPE.

Amino Acid Sequence↗
PubMed1989

Vascular endothelial growth factor: a new member of the platelet-derived growth factor gene family.

Using applications of the polymerase chain reaction (PCR) technique, cDNA clones have been isolated encoding bovine vascular endothelial growth factor (VEGF), a mitogen with specificity for vascular endothelial cells. Analysis of the clones indicates that VEGF can exist in two forms, probably due to alternative RNA splicing. The amino acid sequences predicted from the clones also show that VEGF shares homologies of about 21% and 24% respectively with the A and B chains of human platelet-derived growth factor (PDGF), and has complete conservation of the eight cysteine residues found in both mature PDGF chains. The homology is not reflected in function, however, since the cell types responsive to VEGF are distinct from those responsive to homo- and heterodimers of the PDGF chains.

Amino Acid Sequence↗
PubMed1989

Isolation and characterization of a newly identified endothelial cell mitogen produced by AtT-20 cells.

An endothelial cell growth factor with unique specificity for vascular endothelial cells has been purified from the conditioned medium of the AtT-20 pituitary cell line. This growth factor, which has been characterized as a homodimer composed of two subunits with mol. wts of 23 kd is a potent mitogen for vascular endothelial cells in vitro with activity detectable at 50 pg/ml and saturation at 1 ng/ml. It was also angiogenic in vivo. In contrast with other endothelial mitogens of the fibroblast growth factor family, it has a unique target cell specificity. It did not stimulate the growth of other cell types of the vascular system such as vascular smooth muscle cells or that of mesoderm and neuroectoderm derived cells. Microsequencing revealed an amino-terminal sequence with no homology to any known protein. The release of this novel endothelial cell growth factor by pituitary derived cells and its unique target cell specificity suggest that it could play an important role in the angiogenic process.

Amino Acid Sequence↗