Biomedical subjects

A Richter

Publications and source records attributed to A Richter.

At least 37 records · Page 2Linked to original sources

PubMed2005

RAS gene hot-spot mutations in canine neoplasias.

Point mutations in the cellular homologues HRAS, KRAS2, and NRAS of the viral Harvey and Kirsten rat sarcoma virus oncogenes are commonly involved in the onset of malignancies in humans and other species such as dog, mouse, and rat. Most often, three particular hot-spot codons are affected, with one amino acid exchange being sufficient for the induction of tumor growth. While RAS genes have been shown to play an important role in canine tumors such as non-small lung cell carcinomas, data about RAS mutations in canine fibrosarcomas as well as KRAS2 mutations in canine melanomas is sparse. To increase the number of tumors examined, we recently screened 13 canine fibrosarcomas and 11 canine melanomas for point mutations, particularly within the mutational hot spots. The results were compared to the already existing data from other studies about these tumors in dogs.

Animals↗

PubMed2005

"Best friends" sharing the HMGA1 gene: comparison of the human and canine HMGA1 to orthologous other species.

HMGA1 nonhistone proteins are reported to participate in various cellular processes including regulation of inducible gene transcription, integration of retroviruses into chromosomes, and the induction of neoplastic transformation and promotion of metastatic progression of cancer cells. Overexpression of HMGA1 was shown to be characteristic for various malignant tumors, suggesting a relation between the neoplastic phenotype and a high titer of the protein. Also chromosomal aberrations affecting the human HMGA1 gene at 6p21 were described in several tumors, e.g., uterine leiomyomas, pulmonary chondroid hamartomas, and follicular thyroid adenomas. We characterize the molecular structure of the canine HMGA1 cDNA, its splice variants, and predicted proteins HMGA1a and HMGA1b. Furthermore, we compared the CDS of both splice variants for 12 different breeds, screened them for SNPs, characterised a basic expression pattern, and mapped the gene via FISH. Additionally, we compared the known human, canine, murine, rat, hamster, bovine, pig, Xenopus, and chicken HMGA1 transcripts.

Animals↗

PubMed2005

"Safe" Coulomb excitation of 30Mg.

We report on the first radioactive beam experiment performed at the recently commissioned REX-ISOLDE facility at CERN in conjunction with the highly efficient gamma spectrometer MINIBALL. Using 30Mg ions accelerated to an energy of 2.25 MeV/u together with a thin (nat)Ni target, Coulomb excitation of the first excited 2+ states of the projectile and target nuclei well below the Coulomb barrier was observed. From the measured relative deexcitation gamma-ray yields the B(E2;0(+)gs-->2(+)1) value of 30Mg was determined to be 241(31)e2 fm4. Our result is lower than values obtained at projectile fragmentation facilities using the intermediate-energy Coulomb excitation method, and confirms the theoretical conjecture that the neutron-rich magnesium isotope 30Mg resides outside the "island of inversion."

Journal Article↗

PubMed2005

Experimental investigations of chaos-assisted tunneling in a microwave annular billiard.

We present detailed investigations of the experimental signatures of chaos-assisted tunneling in the two-dimensional annular billiard, as already summarized in Phys. Rev. Lett. 84, 867 (2000). We have performed analog experiments with two-dimensional, electromagnetic resonators allowing for a direct simulation of the corresponding quantum system. Spectra from a superconducting cavity with a high-frequency resolution are combined with electromagnetic intensity distributions of high spatial resolution experimentally determined using a normal conducting twin cavity. Thereby all eigenmodes were obtained with properly identified quantum numbers. Besides distributions of quasi-doublet splittings, which serve as fundamental observables for the tunneling between whispering gallery types of modes, we also focus on the distributions of resonance widths of the doublets. These directly reflect the role of lifetime of certain modes in the tunneling process. Here, as theoretically expected, the class of so-called beach modes is found to play a particular role in mediating between regular and chaotic states to enhance the tunneling strength. This behavior is found in the spectrum and also in the structure of the wave functions.

Journal Article↗

PubMed2005

Distribution of resonance strengths in microwave billiards of mixed and chaotic dynamics.

A new measure for statistical properties of the wave function components of quantum systems, the distribution of the product of two partial widths, is introduced. It is tested with data obtained in analog experiments with microwave billiards, where the product of two partial widths equals the resonance strengths in the microwave spectra. The billiards are from the family of the Limaçons, one with chaotic and two with mixed classical dynamics. For completely chaotic systems the partial widths generically obey a Porter-Thomas distribution. We show that in this case the distribution of their product equals a K0 distribution. While we find deviations of the experimental strength distribution from the K0 distribution for the billiards with mixed dynamics, the distributions agree perfectly for the chaotic billiard, when taking into account the experimental threshold of detection in the theoretical description. Hence, the strength distribution provides another stringent test for the connection between statistical properties of systems with classical chaotic dynamics and random matrix theory.

Journal Article↗

PubMed2005

Test of a numerical approach to the quantization of billiards.

A method for computing large numbers of eigenvalues of self-adjoint elliptic operators [J. Comput. Phys. 184, 321 (2003)] is tested in numerical studies of the spectral properties of quantum billiards. To this extent, we study a time-reversal invariant quantum billiard of threefold symmetry, that undergoes a transformation in its symmetry properties from C(3v) to C3 . Thereby a transition from Gaussian orthogonal to Gaussian unitary ensemble statistics is observed, verifying earlier experimental indications and theoretical predictions. At the same time our numerical ansatz is shown to be applicable to arbitrary billiard shapes.

Journal Article↗

PubMed2005

An autosomal recessive cerebellar ataxia syndrome with upward gaze palsy, neuropathy, and seizures.

The authors describe three siblings born to consanguineous parents with early onset ataxia, dysarthria, myoclonic, generalized tonic clonic seizures, upward gaze palsy, extensor plantar reflexes, sensory neuropathy, and normal cognition. Direct screening excluded mutations in FRDA, TDP1,and SACS genes and at 8344, 3243, and 8993 positions of mitochondrial DNA. Linkage analysis excluded AOA-1, EPM1, EPM2A, EPM2B, CAMOS, and recessive ataxias linked to chromosome 9q34-9qter. This clinical constellation may represent a distinct form of early onset cerebellar ataxia.

Cerebellar Ataxia↗

PubMed2005

Decreased adenosine receptor binding in dystonic brains of the dt(sz) mutant.

In patients with paroxysmal non-kinesigenic dyskinesias, episodes of dystonia can be provoked by stress and also by methylxanthines (e.g. caffeine), which inhibit adenosine A(1)/A(2A) receptors. In the dt(sz) mutant hamster, a model of this movement disorder, adenosine A(1) receptor antagonists were previously found to worsen dystonia, while adenosine A(1) and A(2A) receptor agonists exerted pronounced beneficial effects. Therefore, in the present study, adenosine receptor A(1) and A(2A) binding was determined by autoradiographic analyses in dt(sz) hamsters under basal conditions, i.e. in the absence of a dystonic attack, and in a group of mutant hamsters which exhibited severe stress-induced dystonic attacks prior to kill. In comparison with non-dystonic control hamsters, [(3)H]DPCPX (8-cyclopentyl-1,3-dipropylxanthine) binding to adenosine A(1) receptors and [(3)H]CGS 21680 (2p-(2carboxyethylphen-ethylamino-5'-N-ethlycarboxamindoadenosine) binding to adenosine A(2A) receptors were significantly lower throughout the brain of dystonic animals. Under normal resting conditions, mutant hamsters showed significant decreases in adenosine A(1) (-12 to-42%) and in A(2A) (-19 to-34%) receptor binding compared with controls. Stressful stimulation increased adenosine A(1) and A(2A) receptor binding in almost all brain regions in both control and dystonic hamsters. The stress-induced increase was more marked in mutant hamsters, leading to a disappearance of differences in most regions compared with stimulated controls, except the striatum. In view of previous findings of striking beneficial effects of adenosine A(1) and A(2A) receptor agonists and of striatal dysfunctions in the dt(sz) mutant, the reduced adenosine receptor binding may be an important factor in the pathogenesis of paroxysmal dystonia.

Animals↗

PubMed2005

Population history and its impact on medical genetics in Quebec.

Knowledge of the genetic demography of Quebec is useful for gene mapping, diagnosis, treatment, community genetics and public health. The French-Canadian population of Quebec, currently about 6 million people, descends from about 8500 French settlers who arrived in Nouvelle-France between 1608 and 1759. The migrations of those settlers and their descendants led to a series of regional founder effects, reflected in the geographical distribution of genetic diseases in Quebec. This review describes elements of population history and clinical genetics pertinent to the treatment of French Canadians and other population groups from Quebec and summarizes the cardinal features of over 30 conditions reported in French Canadians. Some were discovered in French Canadians, such as autosomal recessive ataxia of the Charlevoix-Saguenay (MIM 270550), agenesis of corpus callosum and peripheral neuropathy (MIM 218000) and French-Canadian-type Leigh syndrome (MIM 220111). Other conditions are particularly frequent or have special genetic characteristics in French Canadians, including oculopharyngeal muscular dystrophy, hepatorenal tyrosinaemia, cystic fibrosis, Leber hereditary optic neuropathy and familial hypercholesterolaemia. Three genetic diseases of Quebec First Nations children are also discussed: Cree encephalitis (MIM 608505), Cree leukoencephalopathy (MIM 603896) and North American Indian childhood cirrhosis (MIM 604901).

Ethnicity↗

PubMed2005

Hypogammaglobulinemia in pediatric liver transplant recipients.

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.

Agammaglobulinemia↗

PubMed2005

Hepatoblastoma in a child with progressive familial intrahepatic cholestasis.

End-stage liver cirrhosis because of metabolic or infectious diseases predisposes to hepatic malignancies like hepatocellular carcinoma. We report the first case of hepatoblastoma incidentally detected in the explanted liver of a 2-yr-old child undergoing liver transplantation for cirrhosis because of progressive familial intrahepatic cholestasis (PFIC). The diagnosis was difficult to obtain. The hepatoblastoma was not seen on ultrasound examination of the cirrhotic liver. As we could confirm retrospectively, alpha fetoprotein (AFP) was found elevated prior to transplantation. Two years after successful transplantation, there are no signs of malignancy detectable by clinical and radiological methods. We conclude from this case that PFIC may induce hepatoblastoma and that children with liver cirrhosis should undergo routine screening of serum AFP concentration.

Child, Preschool↗

PubMed2005

Patient characteristics and costs associated with dyslipidaemia and related conditions in HIV-infected patients: a retrospective cohort study.

BACKGROUND: Metabolic abnormalities are common in HIV-infected individuals and, although multifactorial in origin, have been strongly associated with antiretroviral therapy. METHODS: Using automated claims and clinical databases, combined with medical record data, we evaluated the burden of dyslipidaemia (DYS) and associated metabolic abnormalities among a cohort of 900 HIV-infected patients aged 18 years and older who received their care from a large multispecialty medical group between 1 January 1996 and 30 June 2002. A Cox proportional hazards model for DYS was developed. Resource use was compiled and subsequently costed with stratification to account for variable length of follow-up. RESULTS: Mean follow-up time was 3.3 years. DYS was present in 54% of the cohort and 3.4% experienced a cardiovascular (CV) event. Both unadjusted and adjusted results found patients with dyslipidaemia and cardiovascular events significantly more likely to have received protease inhibitor (PI) treatment for longer periods of time. In the Cox proportional hazards model the following factors were significantly associated with an increased risk for DYS: older age, white race, PI use and male sex. Diagnoses of hypertension, hepatitis C virus infection, depression or opportunistic infections were all negatively associated with a DYS diagnosis. When controlled for length of follow up, patients with DYS (and no CV-related events) incurred greater median and mean total average costs than patients without DYS or CV-related events. For patients with more than 2 years of follow up, these total cost differences were statistically significant (P<0.05). CONCLUSIONS: These findings indicate that DYS is common among patients with HIV infection and is associated with increased use of medical resources.

Adult↗

PubMed2005

Infection, health problems, and health care utilisation, and the risk of sudden infant death syndrome.

AIM: To examine whether symptoms suggestive of infection, health problems, and health care utilisation are risk factors for SIDS. METHODS: Matched case-control study with 333 SIDS infants and 998 control infants matched for region, age, gender, and reference sleep. Information was obtained by parental interview, paediatrician completed questionnaire, and hospital admission data. RESULTS: No symptoms were associated with SIDS after adjustment for potential confounders. Illness in the last four weeks as reported by the paediatrician did not differ between cases and controls. Developmental problems and special investigations at any stage of life significantly increased the risk of SIDS (adjusted OR = 2.14 and 2.07). Admission to hospital after the first week of life was associated with an increased risk of SIDS (adjusted OR = 1.88). CONCLUSION: Symptoms of infection and illness are no longer risk factors for SIDS in communities such as Germany where few infants sleep prone. The increased risk of SIDS with developmental problems may indicate that infants which subsequently die of SIDS are abnormal or in some way vulnerable.

Analysis of Variance↗

PubMed2005

Functional determination of plasmin in arginine-stabilized plasma.

Reliable data on plasmin activities in blood of patients during fibrinolytic treatment are lacking. This is due to continuing plasminogen activation by plasminogen activators after blood withdrawal. The purpose of this study was to establish a new method for stabilization of blood and to detect plasmin activity in stabilized plasma. For optimization of plasma stabilization by arginine, 50 microL pooled normal citrated plasma was incubated with 50 microL of 0 to 1500 mM arginine, pH 8.7, and 25 microL 100 IU/mL u-PA, 1250 IU/mL t-PA, 10000 U/mL reteplase, 400 U/mL plasminogen-streptokinase-activator complex, 10 microg/mL tenecteplase in 6% BSA-PBS or 25 microL 25 microg/mL plasmin in 20% glycerol. Twenty-five microliters 3 mM HD-Val-Leu-Lys-pNA were added immediately (1 step) or after 90 minutes (room temperature [RT]). The same experiment was performed with pooled normal citrated plasma supplemented with 3.2 mg/mL EDTA, preoxidized with 0 mM or 20 mM chloramine-T for 10 minutes (37 degrees C). For optimization of plasmin activity, the oxidation time of the arginine-stabilized plasma sample containing 0.5 U/mL active plasmin and the chloramine-T amount was varied. Citrated plasma is stabilized against the in vitro action of all six plasminogen activators tested if the final arginine concentration is greater than 500 mM. Neither the addition of EDTA nor the addition of chloramine-T changes this plasma-stabilizing power of arginine. The optimized functional plasmin assay consists of incubation of 10 microL arginine-stabilized plasma with 10 microL 1.5 M arginine, pH 8.7, and 10 microL 100 mM CT in PBS. After 30 minutes (37 degrees C), 75 microL 1.2 M KCl, 1.6 M Arg, 0.75 mM Val-Leu-Lys-pNA (Stop-CS Reagent), and 175 microL 6% BSA-PBS are added and the absorbance increase (DeltaA) at 405 nm is determined. With the present arginine stabilization procedure of plasma and the determination of plasmin activity in arginine-stabilized plasma as described, it is feasible to determine the activity of plasmin in blood of patients receiving fibrinolytic treatment without artefactual in vitro changes in the samples.

Arginine↗

PubMed2005

Functional determination of plasminogen activator in arginine-stabilized plasma.

Reliable data on plasminogen activator (PA) activities in blood of patients receiving fibrinolytic treatment are lacking. This is due to the continuing in vitro action of PA after blood withdrawal. We have elaborated a new simple stabilization technique for plasma involving the addition of arginine in final concentrations greater than 500 mM. In this study, new assays for PA in stabilized plasma are developed. The assay was performed with substrate plasma, that is, pooled normal plasma, preoxidized with chloramine-T; oxidant amount and oxidation time were optimized. The chloramine consumption by plasma was assayed with a KJ-assay (absorbance increase at 405 nm by addition of 200 microL 4 M KJ to 25 microL oxidized plasma). The substrate plasma concentration in the PA assay and the PA acting time was optimized. The inhibition of PA by the cations Na(+), K(+), Mg(2+), and Ca(2+) was evaluated. The optimized PA assay consists of incubation of 10 microL arginine-stabilized plasma with 10 microL 1.5 M arginine, pH 8.7 and 10 microL 100 mM CT in PBS. After 30 minutes (37 degrees C), 175 microL 15 mM CT oxidized EDTA plasma are added. After 40 minutes (37 degrees C), 75 microL Stop-CS Reagent is added and DeltaA at 405 nm was determined, giving PA + plasmin activity in plasma. A control value (basal plasmin activity) consists of the addition of Stop-CS Reagent before 175 microL oxidized EDTA plasma. To obtain plasmatic PA activity, the control value has to be subtracted from the PA main value. The assay is matrix-independent and linear up to 1250 IU/mL t-PA, 790 U/mL reteplase, or 199 IU/mL u-PA (37 nM). With arginine stabilization of plasma and the described determination of plasminogen activator activity in arginine-stabilized plasma, it is feasible to determine the activity of plasminogen activators in blood of patients receiving fibrinolytic treatment without artefactual in vitro changes of the samples.

Arginine↗

PubMed2005

[Polymer networks as actuator and sensor systems to be used for automation of biomedical devices].

Polymer networks are based on molecules which are covalently or physically connected in a three-dimensional network. In presence of an appropriate solvent these networks swell by solvent absorption to form gels. These gels, which are called hydrogels in case of water absorption, are able to change their volume by more than a hundred-fold. During the swelling or shrinking process the hydrogels perform a mechanical work. Their volume standardized working capacity can be ten-times larger than that of an electromagnet. Due to their simple design, miniaturisation properties, and their ability to realize many automatic sensor and actuator functions, smart hydrogels offer new solutions in biomedical technology.

Biomedical Engineering↗

PubMed2004

Diode pumping of a continuous-wave Pr3+-doped LiYF4 laser.

We report, for the first time to our knowledge, diode-pumped cw laser oscillation of Pr3+:LiYF4 in the red spectral range. The pump power is provided by a GaN laser diode emitting a maximum output power of 25 mW at a wavelength of approximately 442 nm. The Pr3+ laser emits 1.8 mW of output power at a 639.7-nm wavelength. Threshold pump power and slope efficiency in a nonoptimized setup are determined to be 5.5 mW and 24%, respectively.

Journal Article↗

PubMed2004

Supernova inelastic neutrino-nucleus cross sections from high-resolution electron scattering experiments and shell-model calculations.

Highly precise data on the magnetic dipole strength distributions from the Darmstadt electron linear accelerator for the nuclei 50Ti, 52Cr, and 54Fe are dominated by isovector Gamow-Teller-like contributions and can therefore be translated into inelastic total and differential neutral-current neutrino-nucleus cross sections at supernova neutrino energies. The results agree well with large-scale shell-model calculations, validating this model.

Journal Article↗