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Biomedical subjects

S Oswald

Publications and source records attributed to S Oswald.

At least 19 recordsLinked to original sources
PubMed2000

Escherichia coli O157:H7 strains that express Shiga toxin (Stx) 2 alone are more neurotropic for gnotobiotic piglets than are isotypes producing only Stx1 or both Stx1 and Stx2.

Infection with Escherichia coli O157:H7 can lead to hemolytic uremic syndrome (HUS) in some children. Epidemiologic data suggest that Shiga toxin (Stx) 2-producing strains are more frequently associated with HUS than are Stx1-producing strains. Less clear is whether strains that express Stx2 alone are more frequently associated with HUS than strains that express Stx1 and Stx2. Isogenic mutants 933stx1- and 933stx2- were produced from strain 933 (Stx1 and Stx2 producer), and 86-24stx2- was produced from strain 86-24 (Stx2 producer). Neurologic lesions or symptoms developed in 18 (90%) of 20 gnotobiotic piglets orally infected with strain 86-24, in 15 (85%) of 18 infected with mutant 933stx1-, in 9 (31%) of 29 infected with strain 933, in 0 of 5 infected with mutant 86-24stx2-, and in 0 of 6 infected with mutant 933stx2-. It was concluded that strains expressing Stx2 alone are more neurotropic for piglets when fed orally than are those strains expressing Stx1 and 2, whereas Stx1-producing strains induce only diarrhea. It is also conceivable that strains that produce Stx2 may constitute a significant predictive risk factor for HUS in humans.

Animals↗
PubMed1999

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility.

A major function of the cell-to-cell adhesion molecule E-cadherin is the maintenance of cell adhesion and tissue integrity. E-cadherin deficiency in tumours leads to changes in cell morphology and motility, so that E-cadherin is considered to be a suppressor of invasion. In this study we investigated the functional consequences of three tumour-associated gene mutations that affect the extracellular portion of E-cadherin: in-frame deletions of exons 8 or 9 and a point mutation in exon 8, as they were found in human gastric carcinomas. Human MDA-MB-435S breast carcinoma cells and mouse L fibroblasts were stably transfected with the wild-type and mutant cDNAs, and the resulting changes in localization of E-cadherin, cell morphology, strength of calcium-dependent aggregation as well as cell motility and actin cytoskeleton organization were studied. We found that cells transfected with wild-type E-cadherin showed an epitheloid morphology, while all cell lines expressing mutant E-cadherin exhibited more irregular cell shapes. Cells expressing E-cadherin mutated in exon 8 showed the most scattered appearance, whereas cells with deletion of exon 9 had an intermediate state. Mutant E-cadherins were localized to the lateral regions of cell-to-cell contact sites. Additionally, both exon 8-mutated E-cadherins showed apical and perinuclear localization, and actin filaments were drastically reduced. MDA-MB-435S cells with initial calcium-dependent cell aggregation exhibited decreased aggregation and, remarkably, increased cell motility, when mutant E-cadherin was expressed. Therefore, we conclude that these E-cadherin mutations may not simply affect cell adhesion but may act in a trans-dominant-active manner, i.e. lead to increased cell motility. Our study suggests that E-cadherin mutations affecting exons 8 or 9 are the cause of multiple morphological and functional disorders and could induce the scattered morphology and the invasive behaviour of diffuse type-gastric carcinomas.

Actins↗
PubMed1999

Loss of immunohistochemical E-cadherin expression in colon cancer is not due to structural gene alterations.

E-cadherin, a transmembrane cell adhesion molecule, has been observed to have an altered pattern of immunoreactivity in several types of carcinomas. In lobular breast cancer, loss of immunoreactivity has been shown to be due either to out-of-frame deletions or to nonsense mutations of the E-cadherin gene. We analysed 29 cases of completely resected colon carcinoma with immunohistochemistry using the HEC-D1 antibody. Normal protein expression similar to that in the adjacent nonmalignant mucosa was seen in 6 cases, whereas 23 tumours had reduced or absent E-cadherin expression. In the 8 cases with no expression of E-cadherin revealed by immunohistochemistry, the entire E-cadherin cDNA sequence was analysed. In these cases, sequence analysis failed to reveal any cDNA mutations despite the negative immunohistochemistry. Possible explanations for this discrepancy include regulatory defects in the E-cadherin promoter, abnormalities at the translation or protein processing levels and mutations in other parts of the gene that were not investigated by the cDNA analysis (e.g. intronic sequences), which could play a role in causing abnormal processing of the E-cadherin protein.

Adult↗
PubMed1998

Nociceptin (orphanin FQ): high-affinity and high-capacity binding site coupled to low-potency stimulation of guanylyl-5'-O-(gamma-thio)-triphosphate binding in rat brain membranes.

G protein activation by the agonist-occupied nociceptin- (orphanin FQ-) receptor in rat cerebral cortex was studied by characterizing the nociceptin-stimulated binding of the radiolabeled guanylyl triphosphate (GTP) analog 35S-guanylyl-5'-O-(gamma-thio)-triphosphate (GTPgammaS). Using 3H-Tyr14- and 125I-Tyr14-nociceptin in saturation and displacement receptor binding studies, a single high-affinity (Kd 21.6-116.7 pM) and high-capacity binding site for nociceptin (orphanin FQ) in membranes and sections of rat cerebral cortex was identified. Stable GTP analogs and NaCl lowered the affinity only moderately by 2- to 3-fold, but under these conditions nociceptin stimulated the binding of 35S-GTPgammaS to G proteins in the membranes with a potency about 100-fold lower (EC50 9.11 nM). It was estimated that this stimulation was due to a 29-fold increase in the affinity from Kd 45. 8 to 1.57 nM of only about 6.5% of the basal binding sites for GTPgammaS, and that at least 10 G protein binding sites could be stimulated by one receptor site. The link of this nociceptin-stimulated binding of GTP to the nociceptin receptor was further evidenced by the specificity of stimulation, as seen with nociceptin, nociceptin(1-13), D-Ala7-nociceptin and nociceptin(1-9), which paralleled that of their receptor affinities. Furthermore, the distribution in rat brain regions of the binding of 35S-GTPgammaS stimulated by nociceptin differed from that stimulated by the mu opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol)]-enkephalin. Especially, no stimulation by nociceptin was observed in caudate putamen, where also the absence of ORL1 receptors had been reported. The putative coupling of the high-affinity nociceptin receptor to the low-potency stimulation of GTPgammaS binding in rat cerebral cortex might be explained by the switch of a low part of occupied nociceptin binding sites to a very low-affinity state being stabilized at high peptide concentrations and catalytically stimulating the GTP binding.

Analgesics, Opioid↗
PubMed1995

Adapting a strategic management model to hospital operating strategies. A model development and justification.

Industrial organizations have employed the process of strategic management in their attempts to cope effectively with global competitive pressures, while attempting to build and maintain competitive advantage. With health-care organizations presently trying to cope with an increasingly turbulent environment created by the uncertainty as to pending legislation and anticipated reform, the need for such organizational strategic planning is apparent. Presents and discusses a methodology for adapting a business-oriented model of strategic planning to health care.

Continuity of Patient Care↗
PubMed1992

Indicators of hospital closure under PPS and Blue Cross/Blue Shield cost-based reimbursements.

Using an adaptation of discriminant analysis on a sample of 120 hospitals in the state of Alabama, this paper illuminates characteristics of hospitals closed due to financial failure under PPS and cost-based Blue Cross/Blue Shield reimbursement systems. The results show high debt levels, poor revenue and cost ratios, poor utilization management, and the inability to collect effectively on outstanding accounts in the year prior to hospital failure.

Alabama↗
PubMed1990

A structurally novel inhibitor of cGMP phosphodiesterase with vasodilator activity.

A novel, potent, competitive inhibitor of smooth muscle cGMP phosphodiesterase is described (Compound I, [4-[2-n-butyl-5-chloro-1-(2- chlorobenzyl)imidazolyl]methyl] acetate). The compound is highly selective for inhibiting cGMP phosphodiesterase compared with cAMP phosphodiesterase. Compound I inhibits the contraction of smooth muscle in response to a variety of agonists in the same concentration range to that which inhibits the enzyme. Compound I produced a dose-related reduction in the pressor responses to angiotensin II infusion while not inhibiting the responses to bolus doses of angiotensin II. Two structural analogues of Compound I which did not inhibit cGMP phosphodiesterase failed to inhibit smooth muscle contraction in vitro and did not affect angiotensin II pressor responses in vivo. We propose a mechanism to account for the effects of a cGMP phosphodiesterase inhibitor on smooth muscle contraction in vitro and in vivo.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Evaluation of different 15N-tracer substances for calculation of whole body protein parameters in infants.

The validity of using different 15N-tracer substances to measure whole body protein parameters, i.e., protein synthesis, protein breakdown, net protein gain, protein turnover, metabolic pool, and reutilization, was assessed by comparing the results obtained with: [15N]glycine, a mixture of 10 15N-labeled amino acids, and a 15N-labeled chicken egg protein in two infants, 9 and 12 weeks old, who were fed human milk. The tracer substances were fed orally as a single dose corresponding to a 15N-excess quantity of 0.2 mmol X kg-1 body weight. 15N Excretion in the urine was measured cumulatively by emission spectrometry, and the data on the protein metabolism were calculated by means of a three-pool model. All three tests yielded consistent net protein gains. The protein synthesis, protein breakdown, protein turnover, and nitrogen reutilization values produced by the [15N]glycine tracer study were higher than those produced by application of the 15N-amino acid mixture and the 15N-labeled egg protein. However, in our opinion, this discrepancy does not justify the replacement of [15N]glycine by expensive 15N-amino acid mixtures as tracer substances.

Amino Acids↗
PubMed1981

Diet and the faecal microflora of infants, children and adults in rural Nigeria and urban U.K.

The faecal microflora of breast-fed infants, weaned children and adults has been examined in rural Nigeria and urban U.K. Breast-fed infants had a similar anaerobic flora dominated by bifidobacteria but bacteroides were isolated in less than a quarter of either community. Weaned children in both communities had greater numbers of bacteroides and clostridia than breast-fed infants. Even higher numbers of bacteroides and clostridia were present in U.K. adults but not in Nigerian adults. Numbers of bacteroides and clostridia were greater in a group of Nigerian infants drinking cow's milk than those receiving breast milk alone and lower in a group of weaned children with diarrhoea compared with uninfected subjects.

Adult↗
PubMed1980

Determination of left ventricular dimensions with ultrasound.

A new ultrasonic measuring system (UM 3) is described. In addition, the construction of simple piezoelectric transducers is outlined. These can be implanted either in the epicardium or in the endocardium of the left ventricle in anesthetized or conscious dogs. The total system has a high accuracy and linearity, and zero drift is small. An automatically controlled floating window excludes most artifacts due to unwanted echoes. Together with a modified delay-time measuring circuit, better recordings of dimensions are obtained. Sources of error due to the technique of implantation or due to electrical disturbances are described. A modified technique of implantation of endocardial transducers is presented.

Animals↗