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Biomedical subjects

L Ernst

Publications and source records attributed to L Ernst.

At least 19 recordsLinked to original sources
PubMed2004

Acquired and partially de novo synthesized pyrrolizidine alkaloids in two polyphagous arctiids and the alkaloid profiles of their larval food-plants.

The profiles of pyrrolizidine alkaloids (PAs) in the two highly polyphagous arctiids Estigmene acrea and Grammia geneura and their potential PA sources in southeastern Arizona were compiled. One of four species of Boraginaceae, Plagiobothrys arizonicus, contained PAs; this is the first PA record for this plant species. The principle PA sources are Senecio longilobus (Asteraceae) and Crotalaria pumila (Fabaceae). The known PA pattern of S. longilobus was extended; the species was found to contain six closely related PAs of the senecionine type. Three novel PAs of the monocrotaline type, named pumilines A-C, were isolated and characterized from C. pumila, a species not studied before. The pumilines are the major PAs in the seeds, while in the vegetative organs they are accompanied by the simple necine derivatives supinidine and as the dominant compound subulacine (1beta,2beta-epoxytrachelanthamidine). In both plant species, the PAs are stored as N-oxides, except C. pumila seeds, which accumulate the free bases. Great variation in PA composition was observed between local populations of C. pumila. The PA profiles were established for larvae and adults of E. acrea that as larvae had fed on an artificial diet supplemented with crotalaria-powder and of G. geneura fed with S. longilobus. In both experiments, the larvae had a free choice between the respective PA source and diet or food plants free of PAs. The profiles compiled for the two species reflect the alkaloid profiles of their PA sources with one exception, subulacine could never be detected in E. acrea. Besides acquired PAs, insect PAs synthesized from acquired necine bases and necic acids of insect origin were detected in the two arctiid species. These insect PAs that do not occur in the larval food sources accounted for some 40-70% (E. acrea) and 17-37% (G. geneura) of total PAs extracted from the insects. A number of novel insect PAs were identified. Plant-acquired and insect PAs were found to accumulate as N-oxides. The results are discussed in relation to specific biochemical, electrophysiological, and behavioral mechanisms involved in PA sequestration by arctiids.

Animals↗
PubMed2000

Deuterium isotope effects on (13)C NMR chemical shifts reflect the smaller steric size of CD(3) compared to CH(3) groups

A CD(3) group close in space to (but many bonds distant from) a carbon atom A causes a substituent effect on the chemical shift of C(A) that is algebraically smaller than the effect of a CH(3) group, in agreement with the notion of shorter C-D relative to C-H bonds. Hence, the deuterium isotope effect of CD(3) upon delta(C(A)) is shielding when the substituent effect is deshielding, and vice versa.

Journal Article↗
PubMed1996

Retinopathy screening in type 2 diabetes: reliability of wide angle fundus photography.

The purpose of the study was to assess the reliability of mydriatic 60 degrees fundus photography in a retinopathy screening programme for Type 2 diabetic patients in a primary health care setting. In 323 eligible consecutive Type 2 diabetic patients above 40 years of age, attending a regional shared care diabetes project, mydriatic wide angle fundus photography was compared with standardized fundoscopy in dilated pupils as the recommended test for the detection of diabetic retinopathy. Fundus photography included two black and white transparencies per eye visualizing the central and nasal retinal field. Fundoscopy findings and pictures were scored according to modified Wisconsin criteria. Fundoscopy revealed in 95/646 eyes (14.7%) some degree of diabetic retinopathy. Sensitivity and specificity of fundus photography (omitting ungradable transparencies) were 97% for the diagnosis of any diabetic retinopathy (DRP). All patients with moderate and severe DRP (Wisconsin grade 3 and worse) according to fundoscopy were detected by fundus photography. In conclusion, mydriatic wide angle 60 degrees fundus photography, making two pictures per eye, can be applied effectively and reliably in the detection of diabetic retinopathy in patients with Type 2 diabetes.

Adult↗
PubMed1996

Placental basal plate myometrial fibers: clinical correlations of abnormally deep trophoblast invasion.

OBJECTIVE: To assess the incidence of placental basal plate myometrial fibers in preterm and term gestations and correlate this finding with clinical observations and placental histopathology. METHODS: Placentas from 457 singleton births before 32 weeks' gestation and 108 uncomplicated singleton births after 37 weeks' gestation were examined histopathologically. Pregnancies complicated by maternal chronic hypertension, diabetes mellitus, coagulopathy, placenta previa, stillbirth, multiple fetuses, and fetal congenital anomalies were excluded from both groups. In the preterm group, 158 patients had preterm labor with intact membranes, 192 had preterm premature rupture of membranes (PROM), 31 had placental abruption without hypertension, and 76 had preeclampsia. Histopathology detected the presence of placental basal plate myometrial fibers, placental vascular lesions, and villous damage related to vascular insufficiency. RESULTS: Forty-four of 457 (9.6%) of preterm placentas had basal plate myometrial fibers, compared with one of 108 (0.9%) term controls (P < .001). Uteroplacental vessels with abnormal physiologic changes were more frequent and placental weights were lower in cases with basal plate myometrial fibers (P < .003 and P < .03, respectively). No other uteroplacental vascular lesions were related to basal plate myometrial fibers. The frequency of placental basal plate myometrial fibers was nine of 76 (12%) in cases complicated by preeclampsia, 21 of 192 (11%) cases of PROM, nine of 158 (5.7%) cases of preterm labor, and four of 31 (13%) cases of placental abruption without hypertension; these frequencies were not significantly different, and there was no significant relationship to gravidity, parity, mode of delivery, or birth weight. CONCLUSION: Placental basal plate myometrial fibers occur in ten times as many preterm births as term births. This finding is associated with both abnormal uteroplacental physiologic changes and decreased placental weight, and may explain the increased incidence of abnormalities of the third stage of labor associated with preterm delivery.

Female↗
PubMed1996

Sensitive and specific quantification of sirolimus (rapamycin) and its metabolites in blood of kidney graft recipients by HPLC/electrospray-mass spectrometry.

Sirolimus (rapamycin) has a macrolide structure and is under clinical investigation as an immunosuppressant after organ transplantation. An HPLC/mass spectrometry assay to quantify sirolimus in blood was developed. 28-O-Acetyl sirolimus was used as internal standard. Blood samples were extracted with C18 columns. The extracts were injected into an HPLC system and isocratically eluted with methanol/1% formic acid (90/10 by vol) from a 150 X 4 mm C18 analytical column. The HPLC system was connected to a triple-stage quadrupole mass spectrometer with an electrospray interface and positive ions were detected. The limit of quantification in 1 mL of blood was 0.25 microgram/L and the calibration curve in blood was linear up to 250 microgram/L. The recovery from blood was 88 +/- 26% and interassay variation at 1 microgram/L was 19% and at 15 microgram/L 9.3%. Hydroxy, dihydroxy, demethyl, and didemethyl sirolimus as well as sirolimus were detected in blood of kidney graft patients.

Acetic Anhydrides↗
PubMed1995

Treatment of cyclic vomiting in childhood with erythromycin.

Cyclic vomiting syndrome (CVS) is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 24 children (10 boys, 14 girls). Many patients had mild associated abdominal pain with their vomiting. Fourteen patients had previously been given metoclopramide but none responded. Two patients were mildly developmentally delayed. Twenty-four patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in two to four divided doses for 7 days. This dose was repeated as needed when symptoms reappeared. Eighteen of 24 patients reported total resolution of symptoms when re-evaluated at 2 and 6 months. All males responded, eight of 18 responders were female, and all six with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of CVS in childhood. Because the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in CVS.

Adolescent↗
PubMed1995

Low-dose aspirin therapy and placental pathology in women with poor prior pregnancy outcomes.

PROBLEM: To determine if low dose aspirin therapy improves placental histology in women with a prior complicated pregnancy demonstrating uterine vascular pathology. METHOD: A retrospective chart review identified patients with a prior complicated pregnancy with placental changes showing uterine vascular pathology (control pregnancy, CP). In the treated pregnancy (TP), 81 mg/day of ASA was started prior to 10 weeks. Placental reports from the CP and TP were reviewed. Pregnancy outcomes and placental histology from the CP were compared to the TP for each patient. RESULTS: Thirteen patients were enrolled. The majority of patients (8/13, 61.5%) exhibited recurrent, histologic evidence of uterine vascular pathology in the TP. The TP was more likely to be uncomplicated (P < 0.05), delivered after 36 weeks (P < 0.05), and result in the delivery of a viable infant (P < 0.05) compared to the CP. CONCLUSIONS: Despite an improvement in outcomes in the aspirin treated pregnancy, histologic evidence of uterine vascular pathology persisted in the majority of women with a prior complicated pregnancy demonstrating similar placental lesions. Abnormal placental histology may be useful in identifying a group of women with poor obstetrical histories who could benefit from low-dose aspirin therapy.

Adolescent↗
PubMed1993

Treatment of cyclic vomiting in childhood with erythromycin.

Cyclic vomiting syndrome is an unusual cause of episodic emesis in children. It manifests as intermittent episodes of severe vomiting, similar in time of onset and duration, with no symptoms during the intervening period. Dehydration necessitating intravenous fluid therapy may occur. Most therapeutic maneuvers have proven unsuccessful. We report the use of erythromycin as a prokinetic agent in the treatment of cyclic vomiting in 20 children (9 boys, 11 girls). Many patients had mild associated abdominal pain with their vomiting. Thirteen patients had previously been given metoclopramide, but none responded. Two patients were mildly developmentally delayed. Twenty patients were given oral erythromycin ethylsuccinate, approximately 20 mg/kg/day, in 2-4 divided doses for 7 days. This dosage was repeated as needed when symptoms reappeared. Thirteen of 20 patients reported total resolution of symptoms when reevaluated at 2 and 6 months. All males responded, 4 of 13 responders were female, and all seven with partial or no response to therapy were female. This uncontrolled trial suggests that erythromycin may be a useful prokinetic agent in the treatment of cyclic vomiting syndrome in childhood. As the study was uncontrolled, placebo effect cannot be excluded. Case-controlled, double-blinded prospective trials should be considered to evaluate the effectiveness of erythromycin in cyclic vomiting syndrome.

Adolescent↗
PubMed1992

Sensitive detection of RNAs in single cells by flow cytometry.

A rapid and sensitive fluorescent in situ hybridization method has been developed to probe RNA contents of individual cells by flow cytometry. Fixed cells in suspension were hybridized with 5' end-fluorophore-labeled oligodeoxynucleotides complementary to defined regions of the RNA of interest and analyzed by flow cytometry. With this method, we monitored combinations of histone H4 mRNA, 18S rRNA and 28S rRNA levels in synchronized HeLa S3 cells by multicolor analysis. A fluorescence signal equivalent to 1800 copies of histone H4 mRNA per cell was detected with signal-to-background ratio of 5.4. If non-specific binding of the fluorophore-labeled probe can be reduced, as few as 100 copies of mRNA of the size of H4 could be detected in individual cells by flow cytometry.

Base Sequence↗
PubMed1992

Specific and sensitive measurement of FK506 and its metabolites in blood and urine of liver-graft recipients.

A specific and sensitive assay for quantifying the immunosuppressant FK506 and its metabolites in blood and urine was developed. 32-O-Acetyl FK506 was synthesized and used as internal standard. FK506 and its metabolites were purified from the samples by solid-liquid extraction and were injected into a high-performance liquid chromatographic (HPLC) system linked to a mass spectrometer (MS) by particle-beam interface. The FK506 derivatives were separated from interfering material by use of a 100 x 4 mm C8 analytical column and water/acetonitrile or water/methanol gradient elution; they were detected by negative chemical ionization with methane as reagent gas. The limit of detection was 25 pg in a standard solution, and the limit of quantification in blood was 250 pg (extracted from 1 mL of blood). The CV was 11.3% at 5 ng, and no interferences with other drugs were found.

Chromatography, High Pressure Liquid↗
PubMed1986

A unique immune response control locus mapping with the H-2D class I region.

The immune response to the polysaccharide antigen Trinitrophenyl (TNP)-ficoll is controlled by two complementing loci in the murine major histocompatibility complex. One locus of control is present in the I-A subregion and the second is located between the S and D regions. A monoclonal antibody 48-21.7 was selected for its ability to significantly block the in vitro primary response to TNP-ficoll. This antibody bound to antigen-presenting cells does not interfere with the presentation of other antigens. Experiments are presented to demonstrate that the monoclonal antibody 48-21.7 precipitates a unique protein of approximately 40,000 daltons. Sequential immunoprecipitation with monoclonal antibodies to the class I Db antigen and to relevant Ia antigens demonstrated no cross-reactivity. Amino acid sequencing has found unique amino acids to be present at three class I N-terminal invariant positions. These observations indicate the presence of a unique class I-like molecule coded for by genes mapping between S and D and involved in the response to the polysaccharide ficoll.

Animals↗
PubMed1980

Extracellular metal-free corrinoids from Rhodopseudomonas spheroides.

Rhodopseudomonas spheroides when grown on a medium deficient of cobalt excretes significant amounts of descobaltocorrinoids into the culture broth. If grown in the presence of 4 microM CoCl2 only intracellular cobalt-containing corrinoids are detected. The extracellular corrinoids have been identified as hydrogenobyrinic acid c-amide and hydrogenobyrinic acid a,c-diamide which are accompanied by varying amounts of the corresponding 13-epicorrinoids. The latter, which could not be separated in the metal-free form, are artifacts arising from the excreted descobaltocorrinoids under the alkaline conditions of the culture broth. The red metal-free corrinoids have been converted into the corresponding cobalt-containing corrinoids and were characterized by their CD, UV, 1H NMR, and 13C NMR spectra. Insertion of cobalt into the fraction of hydrogenobyrinic acid c-amide has yielded small amounts of a cobalt-containing corrinoid, for which the structure of 18,19-didehydrocobyrinic acid c-amide is suggested. A 14C-labeled specimen of hydrogenobyrinic acid a,c-diamide was obtained by feeding [14C]acetate to growing cultures of R. spheroides. Experiments with broken cell systems of Propionibacterium shermanii and R. spheroides have indicated that metal-free corrinoids are not precursors of the cobamides. The results are discussed with respect to the final steps of the biosynthesis of vitamin B12.

Chemical Phenomena↗