PubMed Health⌕ Search

Biomedical subjects

B Fischer

Publications and source records attributed to B Fischer.

At least 19 recordsLinked to original sources
PubMed2007

Differential expression of oxygen-regulated genes in bovine blastocysts.

Low oxygen conditions (2%) during post-compaction culture of bovine blastocysts improve embryo quality, which is associated with a small yet significant increase in the expression of glucose transporter 1 (GLUT-1), suggesting a role of oxygen in embryo development mediated through oxygen-sensitive gene expression. However, bovine embryos to at least the blastocyst stage lack a key regulator of oxygen-sensitive gene expression, hypoxia-inducible factor 1alpha (HIF1alpha). A second, less well-characterized protein (HIF2alpha) is, however, detectable from the 8-cell stage of development. Here we use differential display to determine additional gene targets in bovine embryos in response to low oxygen conditions. While development to the blastocyst stage was unaffected by the oxygen concentration used during post-compaction culture, differential display identified oxygen-regulation of myotrophin and anaphase promoting complex 1 expression, with significantly lower levels observed following culture under 20% oxygen than 2% oxygen. These results further support the hypothesis that the level of gene expression of specific transcripts by bovine embryos alters in response to changes in the oxygen environment post-compaction. Specifically, we have identified two oxygen-sensitive genes that are potentially regulated by HIF2 in the bovine blastocyst.

Animals↗
PubMed2007

[Emergency ward management of traumatic head injury in children].

BACKGROUND: The controversial situation relating to assessment and management of the traumatic head injury (THI) in children inspired us to study our own patient pool. The aims were to find a significant correlation between skull fracture or clinical symptom and intracranial lesion as well as to determine the importance of each radiological diagnostic method in the initial management of the pediatric THI. PATIENTS AND METHODS: In 1 year 1,637 children had been treated in the emergency room of pediatric surgery with the diagnosis of THI. Age, sex, injury pattern, symptoms, radiological diagnostic methods, diagnosis, and clinical follow-up had been registered. RESULTS: A significant correlation between skull fracture or clinical symptom and the intracranial injury in children could not be found, but risk factors exist. Cranial computed tomography is the imaging method of choice. X-ray, ultrasound, and MRI of the head are reserved for a few indications. CONCLUSION: A management plan for pediatric head and brain injury in the emergency room based on our own and published international results is introduced.

Adolescent↗
PubMed2006

A fast online hit verification method for the single ion hit system at GSI.

For a single ion hit facility built to irradiate specific targets inside biological cells, it is necessary to prove that the ions hit the selected targets reliably because the ion hits usually cannot be seen. That ability is traditionally tested either indirectly by aiming at pre-etched tracks in a nuclear track detector or directly by making the ion tracks inside cells visible using a stain coupled to special proteins produced in response to ion hits. However, both methods are time consuming and hits can be verified only after the experiment. This means that targeting errors in the experiment cannot be corrected during the experiment. Therefore, we have developed a fast online hit verification method that measures the targeting accuracy electronically with a spatial resolution of +/-1 microm before cell irradiation takes place.

Cell Culture Techniques↗
PubMed2006

Opposite diastereoselective activation of P2Y1 and P2Y11 nucleotide receptors by adenosine 5'-O-(alpha-boranotriphosphate) analogues.

BACKGROUND AND PURPOSE: We explored the stereoselective activation of the P2Y11 receptor, stably expressed and tagged with GFP, in 1321N1 cells, in comparison to its closest homologue, the P2Y1 receptor. EXPERIMENTAL APPROACH: The potency of several chiral ATP analogues was determined by measuring increases in intracellular calcium concentration ([Ca2+]i). In a series of ATP-alpha-B and ATP-alpha-S analogues, a non-bridging oxygen atom of Palpha was substituted by BH3 or sulphur, respectively, introducing a chiral center at Palpha. The pairs of diastereoisomers (A and B isomers) were each applied as purified compounds. KEY RESULTS: The (B) isomers (ATP-alpha-B Sp isomers and ATP-alpha-S Rp isomers) of all derivatives tested were more potent at the P2Y11 receptor than the corresponding (A) isomers (ATP-alpha-B Rp isomers and ATP-alpha-S Sp isomers) and the parent compounds. This characteristic of the P2Y11 receptor is opposite to the behaviour of the same diastereoisomers at the P2Y1 receptor, at which the (A) isomers are more active. CONCLUSIONS AND IMPLICATIONS: The distinctly opposite diastereoselective activity of ATP derivatives at the P2Y11 and the P2Y1 receptor will allow the deciphering of structural differences of the ligand recognition sites between these receptor subtypes and may aid in the development of subtype-selective agonists. Moreover, ATP-alpha-B diastereoisomers are not active at the P2Y2 receptor. Thus, they are compounds suitable for distinguishing the functional contribution of the two ATP-activated P2Y receptors, the P2Y2 and P2Y11 receptor, in physiological or pathophysiological responses of cells.

Adenosine Triphosphate↗
PubMed2006

An overview of illegal opioid use and health services utilization in Canada.

OBJECTIVES: Systematic research on health and treatment services availability for and utilization by illegal opioid users in Canada are very limited. Comparative data across provinces and territories is almost entirely absent. This study was designed to provide an overview of illegal opioid use and health services utilization among illegal opioid users across Canada. METHODS: A combination of statistical data and key informant data was used. Surveys were sent to key informants in all provinces and territories of Canada. Survey questions covered the number of illegal opioid users in each province, the number of opioid users receiving methadone maintenance treatment (MMT), the number of physicians authorized to prescribe methadone, and the number of opioid users receiving other outpatient and inpatient treatment. In addition, relevant data were collected from several statistical sources, both provincial and federal. The number of substance-use-related overdose deaths was obtained from the provincial coroners' offices. RESULTS: It is estimated that there were more than 80,000 regular illegal opioid users in Canada in 2003. The most prevalent treatment utilized was MMT; about one-quarter (26%) of the estimated opioid users received this type of treatment in 2003. Other forms of outpatient and inpatient treatment were of only minor importance compared with MMT. The number of illegal drug-related overdose deaths in Canada was 958 in 2002. Rates of drug use, health services utilization and overdose deaths showed considerable variation by province. CONCLUSIONS: Although the opioid use treatment system in Canada has expanded in recent years, especially with respect to the availability of MMT, the treatment utilization rates are still lower than in most countries in Western Europe. Rates of current treatment utilization as well as the relatively high number of overdose deaths suggest that there is still room for improvement in the Canadian health and social care system with respect to opioid use.

Adolescent↗
PubMed2006

Towards characterization of palmoplantar keratoderma caused by gain-of-function mutation in loricrin: analysis of a family and review of the literature.

Loricrin keratoderma is an autosomal dominant palmoplantar keratoderma heterogeneous in clinical appearance. We report a family with diffuse ichthyosis and honeycomb palmoplantar keratoderma but no occurrence of pseudoainhums or autoamputations. All patients were born as collodion babies and displayed prominent knuckle pads. We identified the previously reported mutation 730insG in LOR, which elongates loricrin by 22 amino acids because of delayed termination. As pseudoainhums are missing in all patients of the family reported, we propose two compulsory features of loricrin keratoderma: (i) honeycomb palmoplantar keratoderma and (ii) diffuse ichthyosiform dermatosis. Therefore we suggest that the condition should be described clinically as 'honeycomb palmoplantar keratoderma with ichthyosis'. Furthermore, we have assessed the amounts of transcript of LOR using pyrosequencing. This revealed an equal expression of mutant and wild-type alleles of LOR in an affected individual. These findings further underline the gain-of-function theory for mutant LOR in loricrin keratoderma.

DNA Mutational Analysis↗
PubMed2006

Antimicrobial silk clothing in the treatment of atopic dermatitis proves comparable to topical corticosteroid treatment.

BACKGROUND: Atopic dermatitis (AD) is aggravated by mechanical irritation and bacterial colonization. OBJECTIVE: This study compared the efficacy of an antimicrobial silk fabric (DermaSilk) with that of a topical corticosteroid in the treatment of AD. METHODS: Fifteen children were enrolled and wore a dress, where the left side was made of DermaSilk and the right side was made of cotton. The right arm and leg were treated daily with the corticosteroid mometasone for 7 days. The treatment efficacy was measured with a modified EASI (Eczema Area and Severity Index) and with an assessment by the patients/parents and by a physician. All patients were evaluated at baseline, as well as 7 and 21 days after the initial examination. RESULTS: All parameters showed that, irrespective of the treatment, there was a significant decrease of eczema after 7 days. No significant difference between DermaSilk-treated and corticosteroid-treated skin could be observed. CONCLUSION: DermaSilk showed potential to become an effective treatment of AD.

Administration, Cutaneous↗
PubMed2005

[Willing to undergo hepatitis C treatment in a sample of injection drug users in Toronto, Canada].

BACKGROUND: The majority of prevalent and incident hepatitis C (HCV) infections in Canada are related to injection drug use (IDU), thus positioning injection drug users (IDUs) as a critical population to be targeted for HCV treatment. Little research has been undertaken in order to discover the willingness of IDUs to receive HCV treatment, however. METHODS: The study sample was part of the Opican (illicit OPIoid use in CANada) cohort study of illicit opioid and other drug users in five Canadian cities. RESULTS: Data were collected from a sub-sample of 50 HCV-positive IDUs in Toronto. Four fifths of participants indicated general willingness to participate in HCV treatment. Two conditional treatment questions led to significant decreases in treatment willingness (potential treatment side effects and requirement of addiction treatment). CONCLUSION: The majority of IDUs in this sample indicated willingness to participate in HCV treatment, yet the particular needs and situations of this marginalized population have to be considered and addressed for responsive HCV treatment delivery.

Adult↗
PubMed2005

The Pro12Ala and C-681G variants of the PPARG locus are associated with opposing growth phenotypes in young schoolchildren.

AIMS/HYPOTHESIS: Peroxisome proliferator-activated receptor gamma is an important regulator of adiposity in mouse and man, and common variation in the PPARG gene has been associated with birthweight, adult obesity, insulin sensitivity and type 2 diabetes. We hypothesised that these variants may be associated with childhood obesity. METHODS: Height and weight were recorded for 2454 prepubertal children aged between 4 and 10 years, who were then genotyped for three common variants of the PPARG locus: C-681G, Pro12Ala and C1431T. RESULTS: No single variant of PPARG was significantly associated with height, weight or BMI. However, when modelling the variants together we detected an opposing interaction between the -681G and the Ala12 variants in height and weight, but not BMI (p=0.018, 0.013 and 0.119 respectively). The data were consistent with the Ala12 carriers being deficient in energy storage/utilisation, leading to reduced growth. In contrast, the -681G variant, which has been associated with increased adult height, was associated with accelerated growth. The two variants were in strong linkage disequilibrium. However, rare individuals bearing the isolated variants demonstrated the greatest variation from the mean, the most contrasting genotypes being associated with a variation of 7 kg in weight and 6 cm in height, standardised to 7.4-year-olds (p=0.006 and p=0.02 respectively). CONCLUSIONS/INTERPRETATION: This study demonstrates that quantitative trait analysis of energy balance/growth and the PPARG locus is complex and requires the use of multiple genetic markers.

Alleles↗
PubMed2005

A phase I clinical and pharmacokinetic study of fenretinide combined with paclitaxel and cisplatin for refractory solid tumors.

BACKGROUND: Fenretinide is a semi-synthetic retinoid that has pro-apoptotic effects as a single agent and synergistically with chemotherapy in vitro. We performed this study to determine the toxicity of cisplatin, paclitaxel and fenretinide in patients with advanced cancer, the recommended phase II dose of these agents together, and the pharmacokinetics (PK) of fenretinide when administered with chemotherapy. PATIENTS AND METHODS: Fourteen patients (mean age 57.3) were assessable for pharmacokinetics, toxicity and response. Fenretinide was given orally in 2 divided daily doses for 7 days, starting 24 hours prior to cisplatin and paclitaxel. Cisplatin and paclitaxel were given in standard fashion. Cycles were repeated every 3 weeks. Cycle one fenretinide PK was obtained on days 2 and 8. RESULTS: Dose limiting toxicity (Gr 3 diarrhea and Gr 4 neutropenia) was encountered in two patients during cycle one at 80/175/1,800 mg/m(2) of cisplatin/paclitaxel/fenretinide (dose level 2), respectively. Seven patients received 2-8 cycles at the recommended level of 60/135/1,800 (dose level 1). Severe cumulative toxicities included fatigue, nausea/vomiting, neuropathy, and dehydration. Two patients had a partial response and 4 patients had stable disease for up to 8 cycles. PK analysis demonstrated a reduction in fenretinide Cmax on day 8 compared to day 2, accompanying a decrease in AUC. CONCLUSIONS: Cisplatin/paclitaxel/fenretinide can be administered safely at 60/135/1,800 mg/m(2) respectively on an every three-week schedule. This combination may have activity in a variety of tumors, however, the number of pills required complicates oral dosing of fenretinide, and limits the applicability of this regimen.

Administration, Oral↗
PubMed2005

An unusual presentation of giant cell arteritis.

A 77-year-old-man with giant cell arteritis who developed bitemporal scalp ulcerations is described. Since 1946 when Cooke et al. reported the first case of scalp necrosis there were approximately 55 cases published. Scalp ulceration is a rare complication of giant cell arteritis and occurs mainly in elderly persons, particularly women. About half of all patients were presented to dermatologists. Most of the patients (70%) had other serious complications of giant cell arteritis: blindness, gangrene of the tongue and nasal septum necrosis. Seventy percent of the cases were confirmed by a temporal artery biopsy. The necrosis were of varying extent and uni- or bilateral. Although, in most cases necrosis has been located bilaterally as in the presented case. Scalp healing was complete nearly in all patients by conservative treatment within a year. Scalp ulceration is a potentially reversible complication of giant cell arteritis which indicates extensive vessel involvement and adequate coricosteroid therapy is required and essential.

Aged↗
PubMed2005

Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction.

The dioxin/aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor responsive to both natural and man-made environmental compounds. AhR and its nuclear partner ARNT are expressed in the female reproductive tract in a variety of species and several indications suggest that the AhR might play a pivotal role in the physiology of reproduction. Furthermore, it appears to be the mediator of most, if not all, the adverse effects on reproduction of a group of highly potent environmental pollutants collectively called aryl hydrocarbons (AHs), including the highly toxic compound 2,3,7,8-tetrachlor-odibenzo-p-dioxin (TCDD). Although a large body of recent literature has implicated AhR in multiple signal transduction pathways, the mechanisms of action resulting in a wide spectrum of effects on female reproduction are largely unknown. Here we summarize the major types of molecular cross-talks that have been identified for the AhR and linked cell signaling pathways and that are relevant for the understanding of the role of this transcription factor in female reproduction.

Animals↗
PubMed2004

Subtype specific internalization of P2Y1 and P2Y2 receptors induced by novel adenosine 5'-O-(1-boranotriphosphate) derivatives.

P2Y-nucleotide receptors represent important targets for drug development. The lack of stable and receptor specific agonists, however, has prevented successful therapeutic applications. A novel series of P-boronated ATP derivatives (ATP-alpha-B) were synthesized by substitution of a nonbridging O at P(alpha) with a BH(3) group. This introduces a chiral center, thus resulting in diastereoisomers. In addition, at C2 of the adenine ring a further substitution was made (Cl- or methylthio-). The pairs of diastereoisomers were denoted here as A and B isomers. Here, we tested the receptor subtype specificity of these analogs on HEK 293 cells stably expressing rat P2Y(1) and rat P2Y(2) receptors, respectively, both attached to the fluorescent marker protein GFP (rP2Y(1)-GFP, rP2Y(2)-GFP). We investigated agonist-induced receptor endocytosis, [Ca(2+)](i) rise and arachidonic acid (AA) release. Agonist-induced endocytosis of rP2Y(1)-GFP was more pronounced for the A isomers than the corresponding B counterparts for all ATP-alpha-B analogs. Both 2-MeS-substituted diastereoisomers induced a greater degree of agonist-induced receptor endocytosis as compared to the 2-Cl-substituted derivatives. Endocytosis results are in accordance with the potency to induce Ca(2+) release by these compounds in HEK 293 cells stably transfected with rP2Y(1). In case of rP2Y(2)-GFP, the borano-nucleotides were very weak agonists in comparison to UTP and ATP in terms of Ca(2+) release, AA release and in inducing receptor endocytosis. The different ATP-alpha-B derivatives and also the diastereoisomers were equally ineffective. Thus, the new agonists may be considered as potent and highly specific agonist drug candidates for P2Y(1) receptors. The difference in activity of the ATP analogs at P2Y receptors could be used as a tool to investigate structural differences between P2Y receptor subtypes.

Adenosine Triphosphate↗
PubMed2004

Expression of the insulin-responsive glucose transporter isoform 4 in blastocysts of C57/BL6 mice.

Glucose is the most important energy substrate for mammalian blastocysts. In preimplantation embryos glucose uptake is mainly mediated by facilitative glucose transporter molecules (GLUT). Employing RT-PCR in 3.5-day-old mouse blastocysts of strain C57/BL6 we have investigated the expression of the GLUT isoforms 1-4 and 8. We could not only detect GLUT 1, 3 and 8 but, in contrast to earlier studies, also the insulin-responsive isoform 4. GLUT2 was not expressed. The specificity for GLUT4 amplification was verified by sequence analysis. GLUT4 protein was localized by immunohistochemistry with two GLUT4 antibodies. It was found in ICM and trophoblast cells in the cytoplasmic compartment with a strong perinuclear staining. This is the first report on the expression of the insulin-sensitive GLUT4 isoform in mouse preimplantation embryos.

Animals↗
PubMed2004

Association of the Pro12Ala and C1431T variants of PPARG and their haplotypes with susceptibility to Type 2 diabetes.

AIMS/HYPOTHESIS: The Pro12Ala polymorphism of peroxisome proliferator-activated receptor (PPAR)gamma has been consistently associated with Type 2 diabetes. The rare Ala12 variant is estimated to reduce the risk of developing Type 2 diabetes by 20 percent. This variant is in linkage disequilibrium with another common variant, T1431. Both have opposing associations with body weight. We therefore examined the association of specific haplotypes marked by these two variants with susceptibility to Type 2 diabetes. METHODS: We determined the PPARG genotype of a large Scottish cohort of Type 2 diabetic patients ( n=1997) and compared allele frequencies with a cohort of local children ( n=2444) and a middle-aged, population-based cohort from Scotland ( n=1061). RESULTS: Frequency of the Ala12 allele was slightly lower in the Type 2 diabetic cohort than in the children [odds ratio (OR)=0.91, p=0.1]. In contrast, the Ala12 variant was under-represented in the Type 2 diabetic population when compared with similarly aged non-diabetic adults (OR=0.74, p=0.0006). When the Ala12 variant was on a haplotype not bearing the 1431T variant, it conferred greater protection (OR=0.66, p=0.003). However, when it was present in haplotypes containing the 1431T variant (70% of Ala12 carriers), this protection was absent (OR=0.99, p=0.94). CONCLUSIONS/INTERPRETATION: We replicated the finding that the Ala12 variant of PPARgamma affords protection from Type 2 diabetes, and suggest that this protection is modulated by additional common variation at the PPARG locus.

Adult↗
PubMed2004

[Aripiprazole: a new atypical antipsychotic drug].

Aripiprazole is an atypical antipsychotic agent with an intrinsic dopamineagonist activity of 30 %. Aripiprazole exerts additional partial agonist action on 5-HT (1A) receptors and has antagonist properties at 5-HT (2A) receptors. Controlled studies demonstrated an effectiveness in acute relapse of schizophrenic psychosis, chronical schizophrenic and schizoaffective disorders. Aripiprazole was effective in the treatment of productive psychotic and negative symptoms. Compared to other antipsychotics aripiprazole demonstrated a favourable profile of side effects: only slight changes of body weight, mild extrapyramidal symptoms, no prolactin elevation and no significant changes in QTc interval. The efficacy in the long term treatment of schizophrenia seems to be similar to other antipsychotics (e. g. olanzapine). The first evaluations of studies with patients with bipolar disorders showed a significant efficacy in the treatment of mania.

Antipsychotic Agents↗
PubMed2004

[Paraneoplastic limbic encephalitis in small cell lung carcinoma].

We report about a 63-year-old male patient who complained of a recent onset of confusion. A mediastinal mass had been detected in his chest X-ray three days before admission to our clinic. Surprisingly, a CT scan of the brain revealed no signs of cerebral masses or oedema. MRI demonstrated bright hyperintens signals in the medial aspect of both temporal lobes. Biopsy by mediastinoscopy showed small cell lung carcinoma (SCLC). No distant metastases were found by staging procedures. Cerebrospinal fluid and serum contained antineuronal antibodies (anti-Hu). The combination of symptoms, MRI findings and paraneoplastic antibodies established the diagnosis of paraneoplastic limbic encephalitis in a patient with SCLC. Chemotherapy combined with immunosuppression by corticosteroids was started immediately. The primary tumour responded to therapy but improvement of cerebral symptoms was unsatisfactory. Severe memory loss and personality changes remained unchanged while there was a slight improvement in confusion and hallucinations.

Antineoplastic Agents↗