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Biomedical subjects

S Ernst

Publications and source records attributed to S Ernst.

At least 91 records · Page 5Linked to original sources
PubMed1994

A pharmacodynamically responsive model of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) transfer between liver and fat at low and high doses.

We have constructed a pharmacokinetic model for TCDD in the rat, emphasizing its transfer between plasma, lipid, and cytoplasmic compartments of the liver, white adipose tissue (WAT), and brown adipose tissue (BAT). Volumes of the lipid pools are controlled by a submodel of triglyceride (TG) metabolism and transport that responds via a receptor for TCDD in WAT cytoplasm with a Kd of about 2 nM. This submodel, and one for cytochrome P450IA2 induction, allowed us to simulate binding of TCDD to the induced P450IA2 binding sites at low doses (1 ng/kg to 10 micrograms/kg) independently of the decreased feed intake and hyperlipidemia associated with higher doses (20 to 120 micrograms/kg). In low-dose simulations, the induction of cytochrome P450IA2 binding sites for TCDD dominated the redistribution of TCDD between WAT and liver. When simulations were performed using a partitioning model with constant gastrointestinal flows, increased WAT lipolysis driven by reduced feed intake (from 10 to 120 micrograms/kg) is predicted to result in a decreased WAT volume and a sharp drop in the mass of WAT-associated TCDD, while initially increasing the levels of TCDD in liver. However, the observed concentration of TCDD in WAT increased in rats treated with a high dose (72 micrograms/kg) of TCDD. The rise in tissue concentrations could not be explained without incorporating decreased intestinal flows into the gastrointestinal absorption process, which increased the resorption of TCDD. TCDD concentrations in tissue increased only when the relative tissue volumes decreased more rapidly than the whole-body TCDD elimination rate.

Adipose Tissue↗
PubMed1994

Docetaxel in advanced renal carcinoma. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Most patients diagnosed with renal carcinoma developed metastatic disease at some time during their course, with available therapy inducing response in only a small proportion of patients. Docetaxel (Taxotere, RP56976) a semi-synthetic analogue of paclitaxel with a broad range of in vitro antitumor activity, was evaluated in a phase II study. METHODS: Eligibility criteria included histologically proven metastatic or advanced, bidimensionally measurable disease, no prior chemotherapy, immunotherapy, or hormonal therapy, adequate hematologic (neutrophils > or = 2.0 x 10(9)/L, platelets > or = 100 x 10(9)/L) and biochemical (serum creatinine and bilirubin < or = 1.5 x normal, transaminases < or = 3 x normal) parameters, WHO performance status of at least 2, and a life expectancy of > 12 weeks. Docetaxel was administered in a dose of 100 mg/m2 as a 1 hour intravenous infusion every 3 weeks. The first 2 patients entered onto the study were not premedicated for hypersensitivity reactions; subsequent patients received dexamethasone 10 mg and diphenhydramine 50 mg i.v. 30 minutes prior to docetaxel. RESULTS: Twenty patients were entered onto the study, with 2 considered inevaluable for response. Sixty cycles of therapy were administered, with only 2 cycles delivered at a dose of 55 mg/m2 or less. No objective responses were seen; 1 patient demonstrated a mixed response. Neutropenia was significant, with 42/60 cycles developing grade 3/4 granulocytopenia. Fifty-five percent of patients demonstrated hypersensitivity reactions despite the premedication regimen employed, higher than that of the phase I studies which established the dose and schedule used in this trial. CONCLUSIONS: 1) Docetaxel is an ineffective agent in advanced renal carcinoma. 2) The high rate of hypersensitivity reactions suggests the need for more intensive premedication and/or slower infusion times at this dose level.

Adult↗
PubMed1994

[Leiomyosarcoma of the stomach].

Leiomyosarcoma of the stomach is a rare occurrence, amounting to only 0.5-3% of all stomach malignancies. Because of its extragastral growth, it produce clinical symptoms, mostly with bleeding, only at a late stage. The decisive method of examination is computed tomography which demonstrates the extraluminal tumor lying apparently in the mesenterium with contrast medium up-take at the borders and central necrosis. A secure differential diagnosis to leiomyoma is not possible by angiography or by computed tomography; this distinction is even difficult by histology.

Adult↗
PubMed1993

Alpha and beta adrenergic receptor involvement in catecholamine-induced growth of gram-negative bacteria.

The effect of a number of adrenergic receptor agonists and antagonists on the growth of Escherichia coli and Yersinia enterocolitica was examined in order to delineate possible receptor mechanism(s) by which the catecholamines influence the growth of gram-negative bacteria. Neither alpha or beta adrenergic receptor agonists or antagonists affected growth in a dose-dependent manner similar to that observed for norepinephrine. The physiological less active enantiomer of norepinephrine, (+)-norepinephrine, did not affect catecholamine-induced growth to a similar degree as that observed with the active enantiomer. These results suggest that a non-alpha, non-beta adrenergic receptor mediated process may play a role in catecholamine-induced growth of gram-negative bacteria.

Alprenolol↗
PubMed1993

Structure of recombinant ricin A chain at 2.3 A.

The plant cytotoxin ricin is a heterodimer with a cell surface binding (B) chain and an enzymatically active A chain (RTA) known to act as a specific N-glycosidase. RTA must be separated from B chain to attack rRNA. The X-ray structure of ricin has been solved recently; here we report the structure of the isolated A chain expressed from a clone in Escherichia coli. This structure of wild-type rRTA has and will continue to serve as the parent compound for difference Fouriers used to assess the structure of site-directed mutants designed to analyze the mechanism of this medically and commercially important toxin. The structure of the recombinant protein, rRTA, is virtually identical to that seen previously for A chain in the heterodimeric toxin. Some minor conformational changes due to interactions with B chain and to crystal packing differences are described. Perhaps the most significant difference is the presence in rRTA of an additional active site water. This molecule is positioned to act as the ultimate nucleophile in the depurination reaction mechanism proposed by Monzingo and Robertus (1992, J. Mol. Biol. 227, 1136-1145).

Cloning, Molecular↗
PubMed1993

Whole mount in situ hybridization shows Endo 16 to be a marker for the vegetal plate territory in sea urchin embryos.

We have used whole mount in situ hybridization to analyze the pattern of expression of the gene Endo 16 in S. purpuratus embryos. The mRNA is first detectable at 18 h post-fertilization in the cytoplasm of blastomeres derived from the Veg2 6th cleavage tier. The number of Endo 16 positive cells increases gradually through the beginning of gastrulation, and these cell numbers are in agreement with estimates of the number of cells that should be in the vegetal plate at these stages. We conclude that Endo 16 expression is indeed an early vegetal plate marker and that this gene is expressed by all Veg2 tier derivatives while they are part of the vegetal plate. The progressive regionalization of Endo 16 expression that occurs in normal embryos is also seen in lithium chloride induced exogastrulae, leading to the conclusion that genetic regulation of endoderm differentiation is programmed into the vegetal plate cells once they have been specified. Finally, we report a reproducible phenomenon seen in cultures of LiCl exogastrulae, in which the tips of the everted archenterons fuse, followed by the induction of supernumerary pigment cells.

Animals↗
PubMed1993

["Covert criticism"--a new criterion for determining the expressed emotion index in a five-minute speech sample of partners of depressed patients].

The expressed emotion (EE) index is a measure of affective attitudes held by relatives toward a mentally ill family member. In several studies it has been shown to be a predictor of relapse in the course of schizophrenia and depression. Since the Camberwell Family Interview (CFI) as the traditional method for assessing EE is time-consuming, a brief method--the Five-Minute Speech Sample (FMSS)--has been developed as an alternative for research and clinical work. The FMSS is also suitable for repeated application. Reliability and concurrent validity of the FMSS-EE have been demonstrated in cross-cultural samples of families with a schizophrenic member. However, application of the FMSS coding system to relatives of depressed patients in our sample proved to be problematic. Criticism, the most important EE-component, could not be assessed using the existing rating procedure. Therefore a modified version of the rating system has been developed. A new category named "covert criticism" has been defined which also includes indirect criticism. In an ongoing study a high degree of interrater reliability was achieved with the new system. Available data concerning concurrent validity indicate that clinically meaningful results can be derived by using the EE-ratings based on "covert criticism".

Adult↗
PubMed1993

[Radial keratotomy. Optical and functional results after a 5-year postoperative period].

The authors report a retrospective study of R.K. surgery performed on 72 eyes for simple myopia by one surgeon, five years after surgery. Fifty-four cases were observed regularly at 1 year and 5 years post-operatively, which allowed an analysis of refractive and visual parameters, for myopias between-1.5 and 6 D before surgery. Five years after: 92.9% of eyes were within +/- 1 D of emmetropia; 5.7% of eyes were undercorrected by more than 1 D; 1.4% of eyes were overcorrected by more than 1 D and 88.7% of the cases had uncorrected visual acuity of 20/40 or more. In general, our refractive and keratometric results were stable between the first and fifth year post-operatively. We report only one case of real undercorrection, and one case of progressive hyperopia with loss of best spectacle corrected visual acuity. In this study, we observed a statistically significant decrease of 1/100 in the mean uncorrected visual acuity, which is explained by remyopisations. All but one of them were less than 1 D. The review of long term results of R.K. is difficult because of the many different methodologies and protocols. However all of them show a unpredictable continuous increase in the effect of surgery in the hyperopia direction. Prolonged wound healing seems to be the most probable reason for this progressive hyperopia.

Adult↗
PubMed1992

Catecholamine induced growth of gram negative bacteria.

The addition of various catecholamines to cultures of gram negative bacteria resulted in dramatic increases in growth. The ability of norepinephrine, epinephrine, dopamine and dopa to enhance the growth of Escherichia coli, Yersinia enterocolitica and Pseudomonas aeruginosa was observed to be dependent on the bacterium employed with each strain showing marked preference for one or more of the catecholamines. Catecholamine induced increases in growth were confirmed by one or more of the following methods: uptake of tritiated thymidine into newly synthesized DNA, changes in optical density or pour plate analysis. None of the catecholamine metabolites resulting from either oxidative deamination or catechol-O-methylation were able to effect similar increases in bacterial growth as compared to either norepinephrine, epinephrine or dopamine. Norepinephrine was consistently observed to effect the greatest increase in bacterial growth for all strains tested.

Catecholamines↗
PubMed1992

The Intact porcine bioprosthesis: early world-wide clinical experience and analysis of a single institution's experience.

The Intact porcine bioprosthesis is a new-generation valve fixed under stress-free conditions and subjected to a mineralization-inhibiting treatment. The valve is undergoing multi-centre prospective clinical evaluation sponsored by Medtronic, Inc., with 19 centres participating world wide. Since April 1986, 1465 valves have been implanted in the aortic position (AVR, n = 965), mitral position (MVR, n = 438), or both (n = 62), and followed up to 5 years. The data recorded at our participating centre, with 115 valves implanted (AVR n = 93, MVR n = 22) closely match the overall event and death rates in the prospective study. Early mortality in the overall study is 5.6% in AVR and 6.6% in MVR; 3-year actuarial survival rates are 88.5% in AVR and 85.6% in MVR; structural valve-failure-free rates at 3 years are 99.8% in AVR and 98.5% in MVR; 3-year freedom from valve-related reoperation is 97.3% in AVR and 95.8% in MVR. The preferential use of bioprosthetic valves in patients aged 70 years and older with no other indication for anticoagulant treatment entails the not infrequent occurrence of patient/prosthesis mismatch in AVR. Hence, when implanting bioprostheses in old patients, the acceptance of some mismatch has to be weighed against the freedom from anticoagulation treatment and the expected long-term freedom from structural valve failure. Further long-term follow-up will be required to demonstrate the greater durability expected from the stress-free fixation and the anti-mineralization treatment.

Actuarial Analysis↗
PubMed1991

Crystallographic refinement of ricin to 2.5 A.

The plant cytotoxin ricin consists of two disulfide-linked chains, each of about 30,000 daltons. An initial model based on a 2.8 A MIR electron density map has been refined against 2.5 A data using rounds of hand rebuilding coupled with either a restrained least squares algorithm or molecular dynamics (XPLOR). The last model (9) has an R factor of 21.6% and RMS deviations from standard bond lengths and angles of 0.021 A and 4.67 degrees, respectively. Refinement required several peptide segments in the original model to be adjusted translationally along the electron density. A wide range of lesser changes were also made. The RMS deviation of backbone atoms between the original and model 9 was 1.89 A. Molecular dynamics proved to be a very powerful refinement tool. However, tests showed that it could not replace human intervention in making adjustments such as local translations of the peptide chain. The R factor is not a completely satisfactory indicator of refinement progress; difference Fouriers, when observed carefully, may be a better monitor.

Crystallography↗
PubMed1991

Strain-specific enhancement of splenic T cell mitogenesis and macrophage phagocytosis following peripheral axotomy.

The inbred mouse strains C57BL/6 and DBA/2 were subjected to the selective depletion of peripheral nervous system norepinephrine (NE) by the administration of the neurotoxin 6-hydroxydopamine (6-OH-DA). Measurement of mitogen-induced lymphocyte proliferation following peripheral axotomy with 6-OH-DA revealed that significant enhancement (up to 200% of control values) of T, but not B, cell proliferative responses occurred in DBA/2, while no effect was observed in C57BL/6. Enhancement (up to 196% of control values) of luminol-enhanced chemiluminescence resulting from the phagocytosis of opsonized zymosan was also observed following 6-OH-DA treatment in DBA/2, but not C57BL/6. This strain-specific enhancement of immune responses occurred even though the administration of 6-OH-DA resulted in a similar depletion of splenic NE content (greater than 97% reduction of control values) in both strains as determined by high-pressure liquid chromatography-electrochemical detection. Blockage of the neurotoxic effects of 6-OH-DA was achieved by the use of the catecholamine uptake blocker desipramine-HCl. Administration of desipramine prior to 6-OH-DA blocked the reduction of splenic NE content and abrogated the enhancement of mitogen-induced T cell proliferation. The enhancement of phagocytosis by 6-OH-DA was not, however, altered by the prior administration of desipramine.

Animals↗
PubMed1985

[Significance of ultrasound study in accident surgery].

Diagnosis via sonography has recently become firmly established also in accident surgery because of its manifold possibilities of application. The fact that the equipment is very mobile is of particular advantage in this field. It enables detection of intra-abdominal and intra-thoracic lesions, and to diagnose sequelae as well as associated diseases, especially in polytraumatised patients. If applied to the limbs, it becomes possible to discover particularly well all changes in the soft parts, such as haematomas, abscess formation, or effusions. This supplies important pointers towards deciding whether surgery should be performed, and in what way. The importance that sonography has gained in accident surgery is illustrated by the multifarious case reports covering a broad spectrum of different accidents and lesions.

Accidents↗