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Biomedical subjects

C Fischer

Publications and source records attributed to C Fischer.

At least 163 records · Page 9Linked to original sources

Cloning and characterization of the Bacillus subtilis prkA gene encoding a novel serine protein kinase.

We have cloned and sequenced a 3574-bp Bacillus subtilis (Bs) DNA fragment located between the nrdA and citB genes at about 169 degrees on the chromosome. An Escherichia coli strain, LBG1605, carrying a mutated ptsH gene (encoding HPr (His-containing protein) of the bacterial phosphotransferase system (PTS)) and complemented for PTS activity with the ptsH of Staphylococcus carnosus, exhibited reduced mannitol fermentation activity when transformed with a plasmid bearing this 3574-bp Bs fragment. This fragment contained an incomplete and two complete open reading frames (ORFs). The product of the first complete ORF, a protein composed of 235 amino acids (aa) (25038 Da), was found to be responsible for the observed reduced mannitol fermentation. The 3' part of this 705-bp second ORF and the 428-bp incomplete first ORF encode aa sequences exhibiting almost 40% sequence identify. However, the function of these two proteins remains unknown. The third ORF, the 1893-bp prkA gene, encodes a protein (PrkA) of 72889 Da. PrkA possesses the A-motif of nucleotide-binding proteins and exhibits distant homology to eukaryotic protein kinases. Several of the essential aa in the loops known to form the active site of cyclic adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase appeared to be conserved in PrkA. After expression of prkA and purification of PrkA, we could demonstrate that PrkA can indeed phosphorylate a Bs 60-kDa protein at a Ser residue.

Amino Acid Sequence↗

Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB.

The basic/leucine zipper (bZip) transcription factor, CREB, binds to the CRE element (TGANNTCA). The transcriptional activity of CREB requires phosphorylation of the protein on a serine residue at position 119 (ref. 6). CREs are present in a number of T-cell genes but the precise role of CREB in T-cell differentiation and function was unknown. Here we show that resting thymocytes contain predominantly unphosphorylated (inactive) CREB, which is rapidly activated by phosphorylation on Ser 119 following thymocyte activation. T-cell development is normal in transgenic mice that express a dominant-negative form of CREB (CREBA119, with alanine at position 119) under the control of the T-cell-specific CD2 promoter/enhancer. In contrast, thymocytes and T cells from these animals display a profound proliferative defect characterized by markedly decreased interleukin-2 production, G1 cell-cycle arrest and subsequent apoptotic death in response to a number of different activation signals. This proliferative defect is associated with the markedly reduced induction of c-jun, c-fos, Fra-2 and FosB following activation of the CREBA119 transgenic thymocytes. We propose that T-cell activation leads to the phosphorylation and activation of CREB, which in turn is required for normal induction of the transcription factor AP1 and subsequent interleukin-2 production and cell-cycle progression.

Activating Transcription Factors↗

Programs, databases, and expert systems for human geneticists--a survey.

We present an overview of the variety of databases and programs that offer substantial aid to medical and molecular geneticists. Databases and expert systems for genetic diseases and birth defects, programs for segregation and linkage analysis, certain DNA and protein sequence databases, and information resources in general for molecular biology are addressed. These systems cannot be used effectively without the newly developed techniques of information exchange based on international computer networks. A short introduction is given to the Internet and to European institutions and organizations that offer help with the acquisition and use of bioinformatic resources.

Computer Communication Networks↗

Metabolic rate and energy balance in very low birth weight infants during kangaroo holding by their mothers and fathers.

The aim of the study was to compare effects of maternal and paternal kangaroo care on oxygen consumption, carbon dioxide production, energy expenditure, skin and rectal temperatures, heart and respiratory rates, arterial saturation, and behavioral states. Eleven preterm infants with gestational age of 28 to 31 weeks, birth weight of 560 to 1390 gm, and postnatal age of 8 to 48 days were studied before, during, and after maternal and paternal kangaroo care. Skin temperature (lower leg) increased significantly during both maternal (36.2 +/- 0.9 degrees vs 36.9 +/- 1.2 degrees C) and paternal (36.3 +/- 0.9 degrees vs 36.8 +/- 0.9 degrees C) kangaroo care. The other parameter changed neither during maternal nor during paternal kangaroo care. We conclude that both maternal and paternal kangaroo care have no adverse effects on energy expenditure.

Body Temperature↗

Reduction in thyroid volume after radioiodine therapy of Graves' hyperthyroidism: results of a prospective, randomized, multicentre study.

The reduction in thyroid size in 92 patients treated with radioiodine for Graves' thyrotoxicosis was monitored by ultrasound volumetry. The patients were randomly treated with either a standard 131I activity of 555 MBq or an activity calculated to deliver a thyroid dose of 100 Gy. Within 1 year after radioiodine treatment, a remarkable volume reduction of about 71% (median) (quantile 25% (Q 25) = 49%, Q 75 = 82%, n = 67) was observed. The bulk of this reduction (median 57%, Q 25 = 21%, Q 75 = 74%, n = 92) was found within the first 6 months. Statistical analysis reveals that the effect was clearly related to the thyroid dose actually achieved during therapy. The median reduction obtained 6 months after radioiodine application was 45% for < 100 Gy, 56% for 100-200 Gy and 67% for > 200 Gy (n = 28, 39, 25 respectively). Twelve months after radioiodine application, the effect became less evident: 53%, 68% and 75% respectively (n = 17, 29, 21). The higher median thyroid dose actually achieved by standard than by calculated activity (215 Gy vs. 116 Gy) explains the more pronounced volume reduction in the standard group than in the calculated group; 60% vs. 47% 6 months (n = 47, 45) after radioiodine treatments and 74% vs. 66% 12 months (n = 31,36) after radioiodine application. The relative reduction in thyroid size was just as marked in patients with large thyroids as in those with small glands. The goitre prevalence (thyroid volume > 20 mL in women and > 25 mL in men) was reduced from 73% to only 16% 1 year after radioiodine treatment. In patients with a thyroid volume of more than 60 mL, the median pretherapeutic thyroid volume of 102 mL was reduced to 29 mL. In conclusion, radioiodine treatment in Graves' hyperthyroidism sufficiently reduces thyroid volume in a dose-dependent manner. The findings of this study demonstrate that radioiodine is also an attractive mode of therapy for Graves' patients with substantial thyroid enlargement.

Adult↗

Autonomic nervous system and neuroendocrine changes in patients with idiopathic trigeminal neuralgia.

To investigate sympathetic nervous system and neuroendocrine changes in idiopathic trigeminal neuralgia, we determined the plasma level of the catecholamines norepinephrine and epinephrine, as well as cortisol and ACTH in 16 patients (55.3 +/- 8.3 years) with trigeminal neuralgia at four different times during the day (7.00, 13.00, 17.00 and 23.00). Morning and evening values of plasma norepinephrine as well as the daily mean value (dmv) were significantly higher (p < 0.01) in patients with trigeminal neuralgia than in an age- and gender-matched control group. Moreover, morning, afternoon and dmv epinephrine values were also significantly elevated. The dmv norepinephrine levels correlated with the intensity of the attacks (r = 0.68, p < 0.01), the frequency of the attacks (r = 0.75, p < 0.01) and the duration of the disease (r = 0.78, p < 0.01). In addition to elevated catecholamines, trigeminal neuralgia patients also demonstrated significantly increased morning, evening and daily mean values of plasma cortisol. Thus, patients with trigeminal pain have an increased sympathetic nervous system activity for an extended period of time without a direct link to pain attacks, which suggests that the sympathetic nervous system itself is at least co-activated in trigeminal neuralgia and perhaps plays a role in the induction and maintenance of trigeminal pain. The neuroendocrine changes are similar to cluster headache and point to a central dysregulation of the hypothalamic-pituitary-adrenal axis, possibly due to the cyclic phenomena in idiopathic trigeminal neuralgia.

Adrenocorticotropic Hormone↗

Chromosome aberration analysis in atomic bomb survivors and Thorotrast patients using two- and three-colour chromosome painting of chromosomal subsets.

Chromosomal translocations in peripheral lymphocytes of three healthy Hiroshima atomic (A)-bomb survivors, as well as three Thorotrast patients and two non-irradiated age-matched control persons from the German Thorotrast study were studied by two- and three-colour fluorescence in situ hybridization (chromosome painting) with various combinations of whole chromosome composite probes, including chromosomes 1, 2, 3, 4, 6, 7, 8, 9 and 12. Translocation frequencies detected by chromosome painting in cells of the A-bomb survivors were compared with results obtained by G-banding. A direct comparison was made, i.e. only those cells with simple translocations or complex aberrations detected by G-banding were taken into consideration which in principle could be detected also with the respective painting combination. The statistical analysis revealed no significant differences from a 1:1 relationship between the frequencies of aberrant cells obtained by both methods. The use of genomic translocation frequencies estimated from subsets of chromosomes for biological dosimetry is discussed in the light of evidence that chromosomes occupy distinct territories and are variably arranged in human lymphocyte nuclei. This territorial organization of interphase chromosomes implies that translocations will be restricted to chromatin located at the periphery of adjacent chromosome territories.

Aged↗

Pharmacokinetics of ciprofloxacin in pediatric cystic fibrosis patients.

The pharmacokinetic characteristics of ciprofloxacin were studied in 10 children with cystic fibrosis, aged from 6 to 16 years, who had completed the standard regimen of intravenous ceftazidime and amikacin. The aim of the investigation was to derive dosing guidelines for young cystic fibrosis patients to be treated with ciprofloxacin. Each child received ciprofloxacin given as two 30-min infusions (10 mg/kg of body weight each) 12 h apart; this was followed by the administration of oral ciprofloxacin (15 mg/kg every 12 h). Blood samples were taken after both infusions and after the first oral dose. A total of 232 ciprofloxacin concentrations (203 concentrations in plasma and 29 concentrations in urine) were analyzed by use of NONMEM and a two-compartment body model with seven parameters: total body clearance (CL), volume of the central compartment (V2), volume of the peripheral compartment (V3), intercompartmental clearance, renal clearance, absorption rate constant, and bioavailability. The influences of weight (range, 18 to 42 kg) and age (range, 6 to 16 years) were investigated. CL (in liters per hour) was found to be linearly correlated with weight (typical value of CL = 8.8 + 0.396. WT, where WT is weight; (interindividual coefficient of variation, 7.8%). V2 and V3 were directly proportional to weight, with slopes of 0.7 and 1.3 liters/kg, respectively. Interindividual variabilities were calculated to be 22.6 and 14.9% for V2 and V3, respectively. No dependency of the other pharmacokinetic parameters on age or weight was seen. Because of the high correlations between age and weight, only one covariable was necessary. Weight had the strongest effect. Bioavailability (population mean) was estimated to be 61.8%, and renal clearance (population mean) was estimated to be 11.4 liters/h. The residual (intraindividual) variability was 31.9%. The protein binding was about 34%, which is similar to the results obtained for adults. In order to define the appropriate dosage regimen for children suffering from cystic fibrosis, a formula was derived so that steady-state concentrations, similar to those obtained in adults after the administration of dosages of 400 mg three times daily intravenously and 750 mg twice daily orally, could be reached. The calculated total daily dose increased with increasing body weight. Given as milligrams per kilogram of body weight, the calculated dosage regimens suggest that for younger children (weight range, 14 to 28 kg), 28 to 20 mg/kg orally twice daily should be given, and for older children (weight range, 28 to 42 kg), 20 to 15 mg/kg orally twice daily should be given. For intravenous administration, dosages of 15 to 10 mg/kg twice daily are sufficient.

Administration, Oral↗

Primary plasmacytoma of the testis. Case report and review of the literature.

A primary plasmacytoma of the testis is an extremely rare tumor. To date less than 10 cases have been published. Typically a firm mass of the testis or also of the epididymis is found. Histologically, infiltration can be seen with atypical plasma cells compressing the seminiferous tubuli. Immunohistochemical examination shows a PAS-positive reaction. Monoclonality can be confirmed by identification of the IgA lambda chain. Therapy of choice is the radical orchiectomy. The prognosis of primary plasmacytoma of the testis seems to be good. Nevertheless, a follow-up of some years is necessary to detect possible intramedullar manifestations.

Humans↗

Human papillomavirus in tissue of bladder and bladder carcinoma specimens. A preliminary study.

OBJECTIVE: To evaluate the significance of HPV type 6b, 11, 16 and 18 together with type-specific antibodies in the serum of bladder carcinoma. METHODS: The prevalence of HPV type 6b, 11, 16 and 18 in bladder tumor, normal bladder and urethra together with type-specific antibodies in serum was investigated in 23 patients with bladder cancer and 9 patients with chronic cystitis. HPV DNA analysis was done by polymerase chain reaction (PCR). Open reading frames of HPV were expressed in Escherichia coli as beta-galactosidase fusion proteins. RESULTS: HPV 6b was demonstrated in the tumor tissue of 6 patients (19%), and in the nonmalignant specimens of 6 further patients (19%). HPV 16/18 was only found in the urethral swabs of 2 patients (6%). Anti-HPV antibodies were positive in 7 patients (22%). There was no association between the demonstration of HPV 6b and the occurrence of bladder tumor in this study. CONCLUSION: Though, in this study, HPV was not associated with bladder cancer, further investigation is necessary to elucidate the role of HPV 6b in bladder tissue possibly by a semiquantitative PCR in tissue samples and of anti-HPV antibodies in serum.

Adenocarcinoma↗

Expression of CD44 isoforms in renal cell tumors. Positive correlation to tumor differentiation.

CD44 isoforms have been implicated in tumor progression and embryogenesis. Primary renal cell tumors (n = 100) of various histopathological differentiation and grading stages were analyzed for expression of CD44 isoforms in comparison with nonmalignant adult and fetal renal tissues. Evaluations were performed by immunohistochemistry using CD44 isoform-specific monoclonal antibodies and by reverse transcriptase polymerase chain reactions (RT-PCR). In the nonmalignant kidney no CD44 variant isoforms were detected. There was a significant increase in expression of CD44 standard (CD44s) and several variant isoforms (CD44v) in the course of tumor differentiation in clear cell carcinomas (n = 68) from stages G1 to G3 (P < 0.0001 for CD44s and isoforms containing CD44-6v, and P < 0.007 for those containing CD44-9v). Also, in chromophilic cell carcinomas (n = 13), CD44 isoform expression correlated with grading; ie, no CD44 expression was detected in G1 tumors, whereas in approximately 50% of the G2 tumors, CD44s, CD44-6v, and CD44-9v isoforms were present. Oncocytomas (n = 8), which are benign renal cell tumors, did not express CD44 isoforms, whereas invasive chromophobe cell carcinomas (n = 11) were positive for CD44s and CD44v isoforms. Transcript analyses by RT-PCR revealed that the upregulated isoforms in the carcinoma cells contained exons 8 to 10 and 3, 8 to 10 in combination from the variant region. In conclusion, expression of variant CD44 isoforms was strongly correlated with grading and appears to mediate a more aggressive phenotype to renal cell tumors.

Adenocarcinoma, Clear Cell↗

[Microsurgical vascular decompression in the treatment of facial hemispasm. A retrospective study of a series of 65 cases and review of the literature].

The results of a series of 65 consecutive patients operated on to relieve hemifacial spasm (HFS) at Pierre Wertheimer Hospital in Lyon and at Henri Mondor Hospital in Creteil, using the same microvascular decompression (MVD) method, are reported. MDV was performed through a retromastoid keyhole approach. A neurovascular conflict (NVC) was found in 62 cases (i.e., 95.5%). The conflicting vessel was the posterior inferior cerebellar artery (PICA) in 23 cases (35.4%), the anterior inferior cerebellar artery (AICA) in 22 cases (33.8%), the vertebro-basilar artery (VBA) with PICA and/or AICA in 13 cases (20%), and VBA alone in 4 cases (3.1%). The conflicting artery was maintained apart from the REZ of VII nerve by interposing a ball made of Teflon fibers and/or a plaque of Dacron. Forty-five patients (69.2%) were totally cured, 16 patients (24.6%) had only a partial (more than 50%) improvement, and in 4 patients (6.2%) surgery failed. Follow-up ranged from 1 month to 13 years (mean: 4 years and 8 months). Important was that in 9 patients, total relief of spasm occurred only secondarily with a delay sometimes as long as one year. Post-operative complications were dominated by: 1) facial nerve deficits in 16 cases (24.6%), of which 14 were transient and 2 were permanent; 2) hearing decrease in 10 cases (15.4%), of which 5 were transient and 5 were permanent. These complications were encountered at the start of the experience and at a time when monitoring of intraoperative brainstem auditory evoked potentials (BAEP) was not routinely done. Our data proved to be consistent with those published in the literature.

Adult↗

Citrobacter emphysematous pyelonephritis in a tuberculous kidney caused by citrobacter. A case report in a diabetic patient.

Emphysematous pyelonephritis caused by gas-producing bacteria like Escherichia coli or Klebsiella pneumonia is generally observed in female diabetic patients. We report a case in which Citrobacter was the microbiologically documented pathogen. High-dose antibiotic regimen was administered, but nephrectomy was necessary to overcome the life-threatening situation.

Citrobacter freundii↗

The right skills for health systems development.

An in-service training programme has been developed for staff who operate health and family planning systems in Burkina Faso, in order to improve the services and strengthen the systems in difficult working conditions.

Burkina Faso↗

Estimation of the absolute bioavailability of flecainide using stable isotope technique.

Data on the absolute bioavailability of flecainide are controversial. We have investigated whether differences in metabolic clearances and/or the absorption profile might be responsible for the variability in its absolute bioavailability. Six subjects with a wide range of flecainide metabolic clearances (85-407 ml.min-1) simultaneously received the drug by the IV and oral routes; the oral dose was labelled with deuterium. Besides estimation of absolute bioavailability, this design permitted assessment of metabolic clearance after IV and oral administration, and absorption could be assessed from the urinary excretion of labelled and unlabelled drug and metabolites. The absolute bioavailability of flecainide ranged from 79.9 to 101.1% (mean 93.6%). The absorption was 86.1 to 101.3% (mean 93.2%). The data indicate that the variable bioavailability of flecainide is due both to metabolism and absorption. The study highlights the potential of stable isotope technique in the investigation of such issues.

Administration, Oral↗

Benign familial neonatal convulsions: confirmation of genetic heterogeneity and further evidence for a second locus on chromosome 8q.

The syndrome of benign familial neonatal convulsions (BFNC) is a rare, autosomal dominant form of epilepsy. It is characterized by spontaneous seizures beginning within the first 6 months of life. In the majority of families linkage is to chromosome 20q markers. Based on the linkage results in one large BFNC kindred, genetic heterogeneity and existence of a second locus on chromosome 8 have been suggested. Here we report on a second BFNC family in which linkage to the EBN1 locus on chromosome 20q was excluded, confirming the genetic heterogeneity of this disorder. All affected family members experienced onset of seizures before the age of 2 months. Three BFNC subjects showed subsequent epileptic seizures after 12 months of age, showing that the risk of subsequent epilepsy is not restricted to the chromosome 20q linked BFNC families. A lod score of 0.99 was obtained with the marker D8S274, suggesting linkage to chromosome 8.

Adult↗