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Biomedical subjects

P Haas

Publications and source records attributed to P Haas.

At least 19 recordsLinked to original sources
PubMed2006

Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders.

Combinations of HLA and killer immunoglobulin-like receptors (KIR) may affect outcome in T-cell depleted haematopoietic stem cell transplantation (HSCT). The KIR gene family includes inhibitory (KIR2DL and 3DL) and activating receptors (KIR2DS). Ligands are HLA-C (KIR2D) and HLA-Bw4 (KIR3DL1) for inhibitory KIR and are still unknown for activating KIR. The impact of activating KIR genotypes from donor and recipient is poorly documented in HSCT outcome. Here, HLA and KIR genotypes were determined in 131 pairs from non-T-cell depleted HLA-identical sibling HSCT. No effect of 'missing KIR ligand' was detected on acute graft-versus-host disease (GVHD), relapse, survival or infections even in myeloid malignancies. However, additional activating KIR genes in the donor compared to the recipient's genotype or an identity between donor and recipient activating KIR genotypes was associated with a lower transplant-related mortality (TRM) (P=0.005) and in a multivariate analysis with a better survival (P=0.02, HR=0.28; P=0.013, HR=0.29) and a lower incidence of cytomegalovirus (CMV) reactivation (P=0.009, HR=0.36). These data highlight the impact of donor-activating KIR genes on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT.

Adolescent↗
PubMed2005

[Ten critical theses for patient applied telematic applications in health care].

Telematics applications in health care improve patient care in many ways. Especially the improvements through electronic communication, documentation and cooperation between the different providers have high potential for a qualitative and effective health care. Immaterialization of patient records enables their availability as health records across all health care institutions that are involved in the treatment of a patient. However, the realization of a telematic platform in health care raises new questions concerning ethical and technical issues. These questions must be answered in consideration of the interests of citizens, patients, health care providers and insurance companies. Against this background ten critical theses regarding patient-oriented applications in health telematics are presented and discussed. Special attention is paid to the changes in the relationship between patients and physicians and the necessity to establish a new cooperative medical documentation culture, based on controlled vocabularies and where patients and physicians together decide, which information should be added to the central health record, as well as the creation of the necessary trustworthiness and the balance of effective benefit of health telematics and the informational self determination of the patient.

Computer Communication Networks↗
PubMed2005

Leishmaniosis due to Leishmania infantum in a FIV and FelV positive cat with a squamous cell carcinoma diagnosed with histological, serological and isoenzymatic methods.

Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox) constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative), visceral (spleen and lymph nodes) and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot). The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis.

Animals↗
PubMed2003

Suppression of the charge-density-wave state in Sr14Cu24O41 by calcium doping.

The charge response in the spin chain and/or ladder compound Sr14-xCaxCu24O41 is characterized by dc resistivity, low-frequency dielectric spectroscopy and optical spectroscopy. We identify a phase transition below which a charge-density wave (CDW) develops in the ladder arrays. Calcium doping suppresses this phase with the transition temperature decreasing from 210 K for x=0 to 10 K for x=9, and the CDW gap from 130 meV down to 3 meV, respectively. This suppression is due to the worsened nesting originating from the increase of the interladder tight-binding hopping integrals, as well as from disorder introduced at the Sr sites. These results altogether speak in favor of two-dimensional superconductivity under pressure.

Journal Article↗
PubMed2002

Extremely small energy gap in the quasi-one-dimensional conducting chain compound SrNbO3.41.

Resistivity, optical, and angle-resolved photoemission experiments reveal unusual one-dimensional electronic properties of highly anisotropic SrNbO3.41. Along the conducting chain direction, we find an extremely small energy gap of only a few meV at the Fermi level. A discussion in terms of typical 1D instabilities (Peierls, Mott-Hubbard) shows that neither seems to provide a satisfactory explanation for the unique properties of SrNbO3.41.

Journal Article↗
PubMed2002

Rapid automated simultaneous screening of (G1691A) Factor V, (G20210A) prothrombin, and (C677T) methylenetetrahydrofolate reductase variants by multiplex PCR using fluorescence scanning technology.

The Factor V Leiden mutation (G1691A), and mutations in the prothrombin (G20210A) and 5,10-methylenetetrahydrofolate reductase (C677T) genes are common hereditary risk factors associated with venous thrombosis. The aim of this study was to develop an automated, PCR-based genotyping assay for rapid simultaneous screening of these three mutations. We adapted multiplex PCR, using primer modifications to introduce cleavage sites for restriction endonucleases into the fragments bearing each of the mutations. The three mutations were analyzed in a single tube by fluorescence scanning. An internal digestion control was introduced to prevent false-negative results due to incomplete digestion or a total lack of digestion. DNA fragment analysis was carried out using an automated capillary electrophoresis instrument (ABI310). This reliable, efficient, easy-to-use assay can be applied to specimens from large clinical trials and epidemiological surveys.

Factor V↗
PubMed2001

Tissue microarrays for rapid linking of molecular changes to clinical endpoints.

Advances in genomics and proteomics are dramatically increasing the need to evaluate large numbers of molecular targets for their diagnostic, predictive or prognostic value in clinical oncology. Conventional molecular pathology techniques are often tedious, time-consuming, and require a lot of tissue, thereby limiting both the number of tissues and the number of targets that can be evaluated. Here, we demonstrate the power of our recently described tissue microarray (TMA) technology in analyzing prognostic markers in a series of 553 breast carcinomas. Four independent TMAs were constructed by acquiring 0.6 mm biopsies from one central and from three peripheral regions of each of the formalin-fixed paraffin embedded tumors. Immunostaining of TMA sections and conventional "large" sections were performed for two well- established prognostic markers, estrogen receptor (ER) and progesterone receptor (PR), as well as for p53, another frequently examined protein for which the data on prognostic utility in breast cancer are less unequivocal. Compared with conventional large section analysis, a single sample from each tumor identified about 95% of the information for ER, 75 to 81% for PR, and 70 to 74% for p53. However, all 12 TMA analyses (three antibodies on four different arrays) yielded as significant or more significant associations with tumor-specific survival than large section analyses (p < 0.0015 for each of the 12 comparisons). A single sample from each tumor was sufficient to identify associations between molecular alterations and clinical outcome. It is concluded that, contrary to expectations, tissue heterogeneity did not negatively influence the predictive power of the TMA results. TMA technology will be of substantial value in rapidly translating genomic and proteomics information to clinical applications.

Adult↗
PubMed2000

Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis.

BACKGROUND: Studies by comparative genomic hybridization (CGH) have shown that chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We used microarray analyses to measure the expression levels of genes in this region and to explore their prognostic importance. METHODS: A microarray that contained 4209 complementary DNA (cDNA) clones was used to identify genes that are overexpressed in the MCF-7 breast cancer cell line as compared with normal mammary tissue. Fluorescence in situ hybridization was used to analyze the copy number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to localize it to the 17q23 region. Northern and western blot analyses were used to measure S6K gene and protein expression, and an enzymatic assay was used to measure S6K activity. Tumor tissue microarray analysis was used to study amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the relationship between amplification and prognosis was analyzed. The Kaplan-Meier method was used for data analysis, and the log-rank test was used for statistical analysis. All P values are two-sided. RESULTS: S6K was amplified and highly overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of 668 primary breast tumors, and a statistically significant association between amplification and poor prognosis (P =.0021) was observed. Amplification of both S6K and HER-2 implied particularly poor survival (P =.0001). CONCLUSIONS: The combination of CGH information with cDNA and tissue microarray analyses can be used to identify amplified and overexpressed genes and to evaluate the clinical implications of such genes and genomic rearrangements. S6K is likely to be one of the genes at 17q23 that is amplified during oncogenesis and may adversely affect the prognosis of patients with this amplification.

Blotting, Northern↗
PubMed2000

[Therapy of venous thromboembolism with low-molecular-weight heparins].

Low-molecular-weight heparins, nowadays already widely used for the prevention of thromboembolism, have now also become available for the treatment of deep-vein thrombosis. This article should serve to explain the rationale for this development and to demonstrate the clinically relevant advantages of the use of low-molecular-weight heparins. After briefly describing the characteristic properties of heparins the most relevant studies comparing the use of low-molecular-weight heparin versus unfractionated heparin for the treatment of thromboembolism are discussed. In conclusion, clinical trials suggest that low-molecular-weight heparins given subcutaneously can replace the hitherto standard intravenous application of unfractionated heparin in the initial treatment of deep-vein thrombosis, granting equal or even better efficacy and potentially lower rates of adverse side effects. Furthermore, the simplicity of this therapeutic regime allows for treatment of patients at home, thus offering patients mobility and also reducing the cost of treatment.

Anticoagulants↗
PubMed1999

The role of age in cost-benefit analysis of thromboprophylaxis.

Socioeconomic studies about deep-vein thrombosis prophylaxis with low-molecular-weight heparins have shown that general prophylaxis in patients at risk is economically justified. However, the question arises whether the guidelines for thromboprophylaxis developed hitherto provide a fair balance between the medical as well as the socio-economic standpoint and the need of the individual patient. Thromboprophylaxis has to be performed according to acknowledged professional standards under the restraints of cost-effectiveness, whereas the patient is only interested in receiving the best treatment available. Guidelines for thromboprophylaxis are based on the allocation of risk factors, one of those, a higher age of the patient. Most guidelines mention a threshold of 40 years, only in cases where additional risks prevail, thromboprophylaxis in younger patients is recommended. Because some trials suggest that the thromboembolic risk in young patients has been underestimated so far, a computer model was developed to determine the age-dependent cost-benefit ratio for thromboprophylaxis. The results with different sets of input data show that providing thromboprophylaxis to younger patients is also cost-effective, suggesting to reconsider the existing medical guidelines.

Adolescent↗
PubMed1999

[Therapy of thromboses with low-molecular-weight heparins].

Low-molecular-weight heparins, nowadays already widely used for the prevention of thromboembolism, have now also become available for the treatment of deep-vein thrombosis. This article should serve to explain the rationale for this development and to demonstrate the clinically relevant advantages of the use of low-molecular-weight heparins. After briefly describing the characteristic properties of heparins the most relevant studies comparing the use of low-molecular-weight heparin versus unfractionated heparin for the treatment of thromboembolism are discussed. In conclusion, clinical trials suggest that low-molecular-weight heparins given subcutaneously can replace the hitherto standard intravenous application of unfractionated heparin in the initial treatment of deep-vein thrombosis, granting equal or even better efficacy and potentially lower rates of adverse side effects. Furthermore, the simplicity of this therapeutic regime allows for treatment of patients at home, thus offering patients' mobility and also reducing the cost of treatment.

Ambulatory Care↗
PubMed1998

Disseminated feline leishmaniosis due to Leishmania infantum in Southern France.

A fortuitously discovered case of feline leishmaniosis is reported. The parasites were found in the skin and the bone marrow of a domestic female cat that spontaneously died after a few weeks of evolution. Serological tests for FeLV, FIV and PIF virus detection gave negative results. By using Western blot serology, a characteristic pattern of leishmaniosis was obtained and by performing an isoenzyme electrophoresis, a Leishmania infantum MON-1 strain was identified. The same zymodeme is implicated in most of the canine and human leishmaniosis in Southern Europe. A study on the prevalence of asymptomatic feline leismaniosis is foreseen.

Animals↗
PubMed1998

Studies on the effect of the solvents dimethylsulfoxide and ethyleneglycoldimethylether on the mutagenicity of four types of diisocyanates in the Salmonella/microsome test.

The mutagenicity of isomers and homologs of diphenylmethanediisocyanate (4,4'-diisocyanatodiphenylmethane, 2,4'-diisocyanatodiphenylmethane, a mixture of monomeric MDI isomers, and polymeric MDI), containing 55-100% of monomeric MDI, was determined in the Salmonella/microsome test using dimethylsulfoxide (DMSO) and ethyleneglycoldimethylether (EGDE) as solvents. Positive results were obtained for DMSO solutions of all four diisocyanates in the presence of S9 mix containing 30% S9 fraction. Uniformly negative results were found when the diisocyanates were dissolved in EDGE. These results correspond to those of analytical investigations. A small amount of diaminodiphenylmethane (MDA) is one of the reaction products formed when MDI is dissolved in commercial DMSO. No MDA could be detected in solutions of MDI in EGDE. It is therefore concluded that the positive results obtained with diisocyanates in DMSO solutions are due to the formation of MDA. This is artificially formed through the hydrolysis of MDI, caused by traces of water that are always present in DMSO. These findings indicate that DMSO is an inappropriate solvent and should therefore not be used in any in vitro study with diisocyanates. EGDE may be a suitable replacement. The positive test results reported so far for DMSO solutions of MDI are thus only of limited relevance for risk evaluation.

Dimethyl Sulfoxide↗
PubMed1996

Effect of transmembrane helix packing on tryptophan and tyrosine environments in detergent-solubilized bacterio-opsin.

Bacterio-opsin (bO) is folded in a nearly native conformation in mixed micelles of dimyristoyl phosphatidyl choline (DMPC) and 3-[(3-cholamidopropyl)-dimehtylamonio]-1-propane sulfonic acid (CHAPS), but bO is partially unfolded in sodium dodecyl sulfate (SDS). UV difference spectroscopy was used to study the changes in environment of bO aromatic amino acid side chains that occur upon partial unfolding. The UV difference spectra of peptides in CHAPS/DMPC minus peptides in SDS were measured for bO and the following subfragments of bO: C1 (residues 72-248), C2 (1-71), V1 (1-166), V2 (167-248), CB7 (119-145), CB9 (164-209), and CB10 (72-118). The spectra show that, in partially unfolded bO in SDS, the Tyr and Trp absorbance is blue-shifted. The difference spectra were compared to solvent perturbation difference spectra of N-acetyl-L-tyrosine ethyl ester and N-acetyl-L-tryptophanamide. The exposure change calculated from the difference spectra was found to correlate with the change in the number of van der Waals contacting atoms upon partial unfolding, and also with the number of transmembrane helical segments. This result suggests a simple experimental method of testing helix packing arrangements derived from hydropathy plots and model building.

Amino Acid Sequence↗