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Biomedical subjects

E Werner

Publications and source records attributed to E Werner.

305 records · Page 17Linked to original sources
PubMedDate not supplied

Retrovirus genomes methylated by mammalian but not bacterial methylase are non-infectious.

The biological importance of DNA methylation for gene expression in eukaryotes is becoming increasingly evident, and a direct role of methylation in gene expression has been suggested by an analysis of the infectivity of integrated retroviral genomes in a transfection assay. These studies, however, did not address whether specific methylatable residues are involved in gene regulation. Methylation by sequence-specific bacterial DNA methylases has been shown to suppress the expression of some genes, but not others. To investigate the effect of methylation on gene expression without having to rely on sequence-specific methylases, a rat liver enzyme was used to methylate in vitro all C-G dinucleotides of a proviral genomic clone. This treatment reduced the biological activity of Moloney murine leukaemia virus (M-MuLV) proviral DNA by more than three orders of magnitude, whereas complete methylation of 35 HpaII sites in the same DNA had only a marginal effect. The rat methylase-induced inactivation was reversible, as treatment of recipient cells with 5-azacytidine rendered the non-infectious viral genomes biologically active. This suggests that methylation in other C-G dinucleotides than those detectable with restriction enzymes can be crucial for gene expression.

Animals↗
PubMedDate not supplied

[Congenital Hyposplenia with multiple additional anomalies: a variant of the Ivemark Syndrome].

We report an 18-months-old boy with congenital spleen hypoplasia and cardiovascular defects. Besides, several minor clinical manifestations such as facial anomalies, hypospadia glans penis, agenesis of the corpus callosum and iris anomalies were observed. A partial or complete lateralisation defect could be excluded. The patient's phenotype comprises a previously undescribed combination of major and minor clinical features of the Ivemark syndrome. The case indicates that a common genetic defect might be the cause of this syndrome, which shows a variable expression.

Abnormalities, Multiple↗
PubMedDate not supplied

Factors influencing transperitoneal calcium balance during CAPD.

A dialysate containing a calcium concentration of 1.75 mmol/L has been the standard in CAPD for a long time. This concentration was chosen to achieve a positive calcium balance to suppress hyperparathyroidism. In the measurement of peritoneal calcium mass transfer, conflicting results have been published, with positive and negative calcium balances reported. These differences have been explained by differences in the filtration rate, and a negative correlation between the filtration rate and the peritoneal calcium mass transfer can be found. Whereas nearly all patients in this study had a negative calcium balance using a glucose solution of 3.86%, a wide variation was found for the 1.36% glucose solution. There were several patients who had a positive calcium balance despite a positive filtration rate. The explanation for this finding lay in differences in serum concentrations of calcium, and especially differences in the size of the total exchangeable calcium pool that contains the plasma calcium compartment. A negative correlation between peritoneal calcium balance and the size of the total exchangeable calcium pool could be demonstrated. This finding may explain the differences in the peritoneal calcium flux reported in the literature. As an enlargement of the exchangeable calcium pool correlates with the progression of vascular calcification, therapeutic efforts should be directed toward prevention of an enlargement of this pool.

Adult↗
PubMedDate not supplied

Susceptibility testing of Candida species for fluconazole: the role of buffering in the agar dilution assay.

The role of buffering in the determination of the minimal inhibitory concentration (MIC) of fluconazole was studied with Candida species. Agar dilution tests were performed on media (pH 7.25) buffered with either phosphate or morpholinopropane-sulfonic acid (MOPS) or endomethylene-tetrahydrophthalic acid (EMTA), 0.1 mol l-1 each, or on the unbuffered medium. It consisted of casitone and glucose supplemented with FeCl3 and MgSO4. The MICs recorded after 24 h at 37 degrees C extended from 0.1 mg l-1 to > or = 100 mg l-1 on the phosphate and EMTA medium, being concordant on both media. On the MOPS medium and the unbuffered medium the readings were also concordant; the MICs, however, were mostly 25 mg l-1 or higher. This increase of the values--up to six dilution steps--could not be correlated with the amount of acid secreted by the single strains. EMTA proved to be an alternative to phosphate in this system, and because it allows a faster growth of the yeasts it might be superior to phosphate. The concordance of the MIC values in the presence of such different buffer compounds tends to suggest that they indeed indicate the strongest inhibition attainable in vitro by fluconazole. MOPS was confirmed to be of no use in this system.

Candida↗
PubMedDate not supplied

Testing susceptibility of Candida species to fluconazole and itraconazole using the microdilution assay.

A microdilution system was established for testing the susceptibility of Candida species to fluconazole and itraconazole. The assay used a sodium phosphate-buffered (0.1 mol l-1) Casitone/glucose medium (pH 7.2) supplemented with potassium, iron, magnesium, trace elements and vitamins. Tests were read photometrically after 24 h, and the minimum inhibitory concentration (MIC) was defined as the IC90. In nearly all strains sharp end points were observed. The MICs against Candida species without any known pre-exposure to azoles were found to range from 0.2 to 1.56 micrograms ml-1 for fluconazole and from 2.3 to 12 ng ml-1 for intraconazole. For strains from candidosis patients refractory to treatment with fluconazole the MICs of fluconazole ranged from 6.25 to 100 micrograms ml-1, while those for itraconazole varied between 12 and > 450 ng ml-1. The strains did not respond congruent to both azoles. A similar disparity of the MICs was observed with Candida tropicalis and Candida krusei. The unusually low MICs of itraconazole were attained because (1) the dilution series was prepared from a preformed (concentrated) dilution series in 75% dimethylsulphoxide and not directly by serial dilution in the broth and (2) the incubation was performed in microtitre plates made of quartz glass rather than in the generally used polystyrene microtitre plates.

Antifungal Agents↗
PubMedDate not supplied

Ferrokinetic studies with stable isotopes as tracers.

A methodology for ferrokinetic studies based on the administration of iron stable isotopes was developed. Fractional plasma clearance and intestinal iron absorption in rabbits were determined using the double tracer technique. Three rabbits were given 58Fe solution intravenously and about 40 min later 57Fe solution orally. Blood samples were drawn at different times following administration. The analysis of the single iron isotopes content in plasma samples was made by proton nuclear activation. The results were compared with those obtained from the administration, to the same rabbits, of the radioactive isotopes 55Fe and 59Fe. The agreement was found to be satisfactory.

Animals↗
PubMedDate not supplied

An iron metabolism study in humans by means of stable tracers.

An investigation of iron metabolism in a female patient volunteer by administration of stable iron isotopes as tracers was performed. The applied methodology had already been tested in rabbits in comparison with radioactive tracer technique. The subject under study was given 58Fe solution intravenously and about 45 min later 57Fe solution orally. Ten blood samples were drawn at different times within 522 min from injection. Single iron isotopes content in plasma samples was determined by proton nuclear activation. A Compton suppressor system was utilized to improve the detector limits. The characteristic parameters of iron plasma clearance and of iron intestinal absorption were determined.

Activation Analysis↗
PubMedDate not supplied

Molybdenum metabolism studied by means of stable tracers.

An investigation on molybdenum metabolism by administration of molybdenum stable isotopes was performed. Fractional intestinal absorption was determined in animals by the double tracer technique. The investigated subjects were given an enriched solution of Mo-96 orally and, a few minutes later, an enriched solution of Mo-95 intravenously. Blood samples were drawn at different times following the tracer administration. The Mo-95 and Mo-96 contents in plasma samples were determined by proton nuclear activation. The described methodology offers a means for the study of molybdenum metabolism in humans without radiation risk.

Administration, Oral↗
PubMedDate not supplied

Partial parenteral nutrition in preterm and newborn infants during the first three days of life.

Eight preterm infants, five with postnatal asphyxia, as well as two hypotrophic neonates and one term infant with severe postnatal asphyxia (mean birth weight 2300 g) were fed, in addition to oral nutrition, partially parenterally with glucose solution and mother's-milk-adapted amino acid solution during their first three days of life. By increasing protein supplies with a parenteral share of more than 50% during the three days, the nitrogen balances were positive on all days, although the calories supplied were far below the postulated optimum. On days 2 and 3, nitrogen retention was about 60% of the supply. Every 4 hrs after discontinuation of the 16 hr amino acid infusion, the amino acid levels in the plasma were examined by column chromatography. The resulting mean values did not show any imbalances of amino acid homeostasis. The maximum mean loss in weight of the present groups was 4% of the birth weight during the first 10 days of life and thus equalled the loss in weight of normal healthy preterms. Clinical and chemical parameters did not reveal any disadvantageous side effects of partial parenteral nutrition.

Amino Acids↗
PubMedDate not supplied

Maffucci's syndrome as cause of chronic liquorrhea.

We present the case of a 14-year-old girl suffering from Maffucci's syndrome, a rare ailment belonging to the group of osteochondrodysplasias. At the age of 6 months, a diffuse swelling first appeared in the girl's right cheekbone region and the periauricular area. Because of recurrent meningitis with massive otoliquorrhea, several surgical revisions were performed, beginning at the age of 4 years. The histological and immunohistochemical diagnosis showed hemangioma and lymphangioma with enchondroma. As a peculiarity of our patient's diagnosis, we found multiple bone defects apparently caused by venous and lymphomatous angiomatosis. There was also enchondromatosis of the skull base and the upper cervical vertebrae, which caused the recurrent otoliquorrhea and rhinoliquorrhea. A fistula closure was undertaken through a retromastoidal, suboccipital approach and fascial graft of the posterior cranial fossa.

Adolescent↗
PubMedDate not supplied

Influence of complementary Viscum album (Iscador) administration on microcirculation and immune system of ear, nose and throat carcinoma patients treated with radiation and chemotherapy.

With the techniques of vital microscopic and reflection spectrometric imaging, representative characteristics of microcirculation and immunology of white blood cells were evaluated before, during and after radiotherapy and chemotherapy of patients suffering from ear, nose and throat carcinomas. Adverse effects of radiotherapy and chemotherapy on the microcirculation and the immune system were decreased and reconstitution processes were accelerated by complementary administration of a standardized mistletoe extract (Iscador).

Aged↗
PubMedDate not supplied

Altered pattern of calcium kinetics in hemodialysis patients after parathyroidectomy.

Six HD patients with severe secondary hyperparathyroidism (sHPT) underwent studies of calcium kinetics prior to and after parathyroidectomy (PTX) with autotransplantation. Postoperatively, patients received vitamin D and calcium supplementation. Before PTX, a markedly elevated bone turnover was found, with increased fluxes of calcium from plasma into the exchangeable calcium pool. This pool was three times larger than normal, indicating a high risk of extraosseous calcifications. Despite a marked fall in parathyroid hormone (iPTH) levels after PTX, bone cell activity was maintained, as indicated by elevated values for Ca retention. Although Ca efflux from plasma into other compartments of the exchangeable pools remained above normal, the size of the total exchangeable calcium pool markedly decreased after PTX, indicating that PTX with autotransplantation, followed by vitamin D therapy, can normalize bone turnover and shift the balance of calcium flux towards mineralized bone. Reduction in the exchangeable calcium pool may explain the clinical finding that extraosseous calcifications regress in some patients after PTX.

Adult↗
PubMedDate not supplied

Calcium kinetic studies in patients on CAPD: improvement of secondary hyperparathyroidism without concomitant improvement of calcium turnover.

OBJECTIVE: An association between the development of low turnover osteopathy and the form of dialysis treatment, that is, continuous ambulatory peritoneal dialysis (CAPD), has been described. To examine the effect of a year-long CAPD treatment on calcium (Ca) turnover, 12 patients were studied prior to and one year after initiation of CAPD treatment with a dialysate calcium of 1.75 mmol/L. DESIGN: A prospective analysis. SETTING: Academic teaching hospital dialysis unit. PATIENTS: Twelve patients with an average age of 54.8 years (range: 23-76 years) at commencement of dialysis and after 13 months of CAPD treatment. MEASUREMENTS: Calcium kinetic studies were performed using two calcium isotopes: 45Ca as an oral tracer and 47Ca as an intravenous tracer. Measurements of plasma and whole body activities were performed over a four-week period. From these measurements, kinetic parameters describing calcium turnover in different compartments were studied. These measurements were repeated after a mean time of 13.4 months. Patients were not treated with vitamin D, but received aluminum- and calcium-containing phosphate binders, in order to keep inorganic phosphate below 2.0 mmol/L and calcium within the normal range. RESULTS: After one year on CAPD, serum levels of calcium increased from 2.2 mmol/L to 2.35 mmol/L. Inorganic phosphate also increased from 1.4 mmol/L to 1.9 mmol/L, despite increased use of oral phosphate binders. Serum levels of intact parathyroid hormone (IPTH) decreased from 51.2 pmol/L to 28.3 pmol/L. Alkaline phosphatase did not change, nor did serum levels of vitamin D. Despite improvement of serum IPTH levels and better control of serum calcium, the kinetic parameters describing calcium turnover in the different calcium pools did not improve. In addition, the calcium retention of bone remained below normal range and did not rise. Perhaps more importantly, the relationship between Ca efflux and Ca retention did not change. While Ca retention remained low, plasma Ca efflux was normal. This imbalance was seen at the beginning of CAPD and did not change under CAPD. CONCLUSION: These data demonstrate that, after one year of CAPD treatment without vitamin D treatment, calcium turnover did not improve, despite a significant fall in serum IPTH levels. Studies on a larger number of patients are warranted to verify these results.

Adult↗