Biomedical subjects

H Keller

Publications and source records attributed to H Keller.

At least 37 records · Page 2Linked to original sources

PubMed2003

EPR study of some rare-earth ions (Dy3+, Tb3+, and Nd3+) in YBa2Cu3O6-compound.

We investigate the low temperature X-band electron paramagnetic resonance (EPR) of YBa(2)Cu(3)O(x) compounds with x congruent with 6.0 doped with Dy(3+), Tb(3+), and Nd(3). The EPR spectra of Dy(3+) and Tb(3+) have been identified. The EPR of Tb(3+) is used also to study the effect of suppression of high T(c) superconductivity by doping with Tb(3+). The EPR of Nd(3+) is probably masked by the intense resonance of Cu(2+). All experimental EPR results compare well with theoretical estimations.

Journal Article↗

PubMed2003

Bone morphogenetic protein 2 induces placental growth factor in mesenchymal stem cells.

Bone-forming osteoblasts differentiate from pluripotent mesenchymal stem cells (MSCs) in a multistage process that can be modeled in vitro using MSCs isolated from adult human trabecular bone or bone marrow. To identify new genes involved in osteoblast differentiation, we have performed large-scale gene expression profiling using high-density cDNA microarrays in primary human MSCs treated with the known osteogenic agent bone morphogenetic protein 2 (BMP-2). The vascular endothelial growth factor (VEGF) family member placental growth factor (PlGF) was found as an early regulated gene whose induction was already detected after 2 h treatment with BMP-2. Tissue distribution analysis of PlGF mRNA expression using microarrays revealed a very restricted expression of PlGF only in BMP-2-treated MSCs and in placenta as expected. Ribonuclease protection assay (RPA) confirmed the induction of PlGF and showed preferential expression of the PlGF-1 isoform over PLGF-2 in MSCs and MG63 cells. BMP-2 stimulated PlGF expression in MG63 cells with an EC50 of about 50 ng/ml and mRNA levels peaked between 24 and 32 h after stimulation. Furthermore, induction of PlGF by BMP-2 appeared specific, as other osteogenic agents including vitamin D3, transforming growth factor beta, and basic fibroblast growth factor were inactive. BMP-2 stimulated PlGF secretion from MG63 and MSC cells, but PlGF had no effect on MSC proliferation and osteoblastic differentiation. Based on the known function of PlGF in the recruitment of endothelial and hematopoietic stem cells, these results suggest a paracrine role for MSC-derived PlGF in the angiogenesis and hematopoiesis that accompany BMP-2-induced bone formation.

Amino Acid Sequence↗

PubMed2002

Temperature and field dependence of the anisotropy of MgB2.

The anisotropy gamma of the superconducting state of high quality single crystals of MgB2 was determined, using torque magnetometry with two different methods. The anisotropy of the upper critical field was found to be temperature dependent, decreasing from gamma approximately 6 at 15 K to 2.8 at 35 K. Reversible torque data near T(c) reveal a field dependent anisotropy, increasing nearly linearly from gamma approximately equal to 2 in zero field to 3.7 in 10 kOe. The unusual temperature dependence is a true bulk property and can be explained by nonlocal effects of anisotropic pairing and/or the k--> dependence of the effective mass tensor.

Journal Article↗

PubMed2002

Stem cell characteristics of human trabecular bone-derived cells.

Human trabecular bone-derived cells (HTBs) have been used for many years as osteoblast progenitors. In this study we tested whether HTBs have stem cell characteristics; that is, whether they are pluripotent and able to self-renew. We show that HTBs readily differentiate into osteoblasts, chondrocytes, and adipocytes if subjected to the appropriate differentiating conditions. Importantly, differentiation into these three lineages is maintained in single cell clones derived by limiting dilution, following expansion over more than 20 cumulative population doublings. We conclude that cultures of HTBs are equivalent to cultures of "mesenchymal stem cells" (MSCs) isolated from bone marrow.

Adipocytes↗

PubMed2002

Percutaneous minimal osteosynthesis of fractures of the proximal humerus in elderly patients.

INTRODUCTION: The aim of this study was to evaluate the subjective and objective outcome of the percutaneous minimal osteosynthesis in elderly patients. Untreated, unstable and dislocated proximal humeral fractures show poor functional and subjective results. Reduction and fixation of the fragments is essential to achieve a good clinical outcome. Especially noted in elderly patients, the osteosynthesis is concurrent with the implantation of a prosthesis. PATIENTS AND METHODS: We examined 31 patients with a mean age of 72 years (51-87) after an average follow-up period of 15.8 months (9-31). To assess the functional and subjective results, we used the Constant Score as well as an adapted version of the Oxford Shoulder Score. Radiographs in two planes displayed the anatomical situation, the healing of the fracture, and the evidence or absence of avascular necrosis. RESULTS: There were no local complications such as hematomas or wound infections. The results of the Constant Score showed an average of 63.5 Pts. (18-82 Points) and adapted to age and gender by 90.2% (28.1-118.8%). Compared with the uninjured arm with an average of 77.1 Points (20-89 Points) and 109.5% (29-129%) respectively, we achieved an average functionality of 82.6%, operated versus non-operated side. All but one fracture, that showed signs of avascular necrosis with disintegration of the humeral head, were fully consolidated. The subjective results were very good in 18 patients, good in 7, satisfying in 3 and poor in 3 patients. CONCLUSION: Our data indicate that the percutaneous minimal osteosynthesis is a valuable method for the fixation of proximal fractures of the humerus in elderly patients. The technique has a very low rate of complications and the time of convalescence is short. If closed reduction fails or a stable percutaneous fixation of the fracture by K-wires is not possible, the change to open reduction and internal fixation or the implantation of a prosthesis is required.

Aged↗

PubMed2002

Monte Carlo study of a highly efficient gas ionization detector for megavoltage imaging and image-guided radiotherapy.

The imaging characteristics of an arc-shaped xenon gas ionization chamber for the purpose of megavoltage CT imaging were investigated. The detector consists of several hundred 320 microm thick gas cavities separated by thin tungsten plates of the same thickness. Dose response, efficiency and resolution parameters were calculated using Monte Carlo simulations. The calculations were compared to measurements taken in a 4 MV photon beam, assuming that the measured signal in the chambers corresponds to the therein absorbed dose. The measured response profiles for narrow and broad incident photon beams could be well reproduced with the Monte Carlo calculations. They show, that the quantum efficiency is 29.2% and the detective quantum efficiency at zero frequency DQE(0) is 20.4% for the detector arc placed in focus with the photon source. For a detector placed out of focus, these numbers even increase. The efficiency of this kind of radiation detector for megavoltage radiation therefore surpasses the reported efficiency of existing detector technologies. The resolution of the detector is quantified with calculated and measured line spread functions. The corresponding modulation transfer functions were determined for different thicknesses of the tungsten plates. They show that the resolution is only slightly dependent on the plate thickness but is predominantly determined by the cell size of the detector. The optimal plate thickness is determined by a tradeoff between quantum efficiency, total signal generation and resolution. Thicker plates are more efficient but the total signal and the resolution decrease with plate thickness. In conclusion, a gas ionization chamber of the described type is a highly efficient megavoltage radiation detector, allowing to obtain CT images with very little dose for a sufficient image quality for anatomy verification. This kind of detector might serve as a model for a future generation of highly efficient radiation detectors.

Animals↗

PubMed2001

Isotope effects in underdoped cuprate superconductors: a quantum critical phenomenon.

We show that the unusual doping dependence of the isotope effects on transition temperature and zero temperature in-plane penetration depth naturally follows from the doping driven 3D-2D crossover and the 2D quantum superconductor to insulator transition in the underdoped limit. Since lattice distortions are the primary consequence of isotope substitution, our analysis clearly reveals the strong involvement of lattice degrees of freedom in mediating superconductivity.

Journal Article↗

PubMed2001

Rhogocytes (pore cells) as the site of hemocyanin biosynthesis in the marine gastropod Haliotis tuberculata.

Rhogocytes (pore cells) are specific molluscan cell types that are scattered throughout the connective tissues of diverse body parts. We have identified rhogocytes in large numbers in tissue taken from mantle, foot and midgut gland of the abalone Haliotis tuberculata (Vetigastropoda). Within cisternae of the endoplasmic reticulum, particles are visible that resemble, in shape and size, hemocyanin molecules, the respiratory protein of many molluscs. Immunohistochemical experiments using hemocyanin-specific antibodies demonstrated that these cells contain hemocyanin. In situ hybridization with a cDNA probe specific for Haliotis hemocyanin showed that hemocyanin-specific mRNA is present in rhogocytes, which confirmed that they are the site of hemocyanin biosynthesis in this gastropod. A possible path of hemocyanin release into the hemolymph is discussed. Also in the vetigastropod Megathura crenulata, many rhogocytes could be detected. However, they lacked hemocyanin molecules which, together with published data, indicates a seasonal expression of hemocyanin in this animal.

Animals↗

PubMed2001

Do bacteriostatic urethral lubricants affect the clinical efficacy of intravesical bacillus Calmette-Guérin therapy?

OBJECTIVES: To investigate the effect of a bacteriostatic urethral lubricant on the clinical efficacy of intravesical bacillus Calmette-Guérin (BCG) therapy. METHODS: Between July 1987 and August 1999, 389 patients with superficial urothelial carcinoma of the bladder (pTa [multilocular, size greater than 2 cm, recurrent tumor], pT1, pTis) were treated adjuvantly with BCG in a 6-week intravesical cycle after complete transurethral tumor resection of the bladder. Within the framework of a prospective study on recurrence and progression of superficial urothelial carcinoma of the bladder after transurethral resection and BCG therapy, we retrospectively studied the clinical value of the observation that the use of bacteriostatic urethral lubricants reduces the viability and thus the efficacy of BCG. If a lubricant induces a clinically relevant reduction in the viability of BCG, instillation without lubricant should lead to a lower rate of recurrence and possibly a lower rate of progression. Lubricant (11 mL) was used during catheterization in every male patient in our population (group 1, n = 317, 81.5%); no lubricant was used in the women serving as the control group (group 2, n = 72, 18.5%). The two groups were similar with respect to age, distribution of tumor stage and grade, multifocality, and frequency of previous bladder carcinoma (Levene test, P = 0.008). The median follow-up was 54 months (range 4 to 143). RESULTS: Of the 389 patients, 90 (23.1%) developed recurrence during the follow-up period: 73 (23%) in group 1 and 17 (23.6%) in group 2 (P value not significant). Progression occurred in 14 patients in group 1 (4.4%) and in 8 patients in group 2 (11%) (P = 0.043). In groups 1 and 2, 19.2% and 47.1%, respectively, of the recurrences were progressive (P = 0.026). CONCLUSIONS: The use of bacteriostatic lubricants in the usual dose before BCG instillation had no detectable adverse effect on the clinical efficacy of intravesical BCG immunotherapy. To avoid traumatic catheterization with possible systemic BCG administration, we therefore recommend, especially in men, the additional use of a sufficient quantity of urethral lubricant.

Adjuvants, Immunologic↗

PubMed2001

A local accumulation of the Ralstonia solanacearum PopA protein in transgenic tobacco renders a compatible plant-pathogen interaction incompatible.

Plants activate disease resistance responses when they recognize pathogen-derived molecules (elicitors). Frequently, recognition results in a hypersensitive response (HR), which is characterized by local host cell death at the infection site. Here we describe a genetic engineering approach to generate an HR in plants, whether or not an invading micro-organism produces a recognized elicitor. To that aim we created transgenic tobacco plants in which the pathogen-inducible promoter of the hsr203J gene from tobacco controls the expression of the popA elicitor gene from Ralstonia solanacearum. Because PopA itself also induces the hsr203J promoter, transgenic plants rapidly accumulate the bacterial elicitor in the pathogen infection sites. The elicitor becomes converted in plant tissues into its fully active derivatives PopA1-PopA3, showing that the previously observed processing events are not dependent on the bacterial type III secretion system. The outcome of induced PopA accumulation is a localized HR and a high degree of resistance of the transgenic plants to an oomycete pathogen. The system is functional in hybrids between different tobacco varieties, and we show that the engineered resistance, but not the associated cell death, is dependent on the salicylic acid signalling cascade. Although the approach is powerful in generating oomycete resistance, the induced HR might affect plant health. Its application thus requires a careful selection of individual transgenic lines and trials with various pathogens.

Bacterial Proteins↗

PubMed2001

Treatment of Peyronie's disease with local interferon-alpha 2b.

OBJECTIVE: To evaluate the efficacy of subcutaneous interferon-alpha 2b in the treatment of Peyronie's disease. PATIENTS AND METHODS: Twenty-three men (mean age 53 years, range 27-69) received interferon-alpha 2b in an unrandomized prospective study. The drug was injected subcutaneously adjacent to the plaque three times a week for 3 weeks at a dose of 2 x 106 IU. The effect of interferon-alpha 2b on the extent of penile deviation, plaque size and erectile pain were investigated, and the drug's side-effects were documented. The mean (range) follow-up was 22 (4-48) months RESULTS: All patients had pain relief and 13 of 19 with pain before treatment became pain-free. The penile deviation was reduced in one patient; the deviation increased despite therapy in one patient and remained stable in the others. Plaque size remained unchanged in all patients. Impaired sexual function was improved in seven (30%) of the patients. Side-effects (myalgia, fever) occurred after only four of 207 injections (2%). CONCLUSIONS: Subcutaneous interferon-alpha 2b is safe, well tolerated and relieves pain. However, with no objective reduction in penile deviation and plaque size, the outcome of interferon-alpha 2b therapy is generally unconvincing and the drug cannot be recommended for the conservative treatment of Peyronie's disease.

Adult↗

PubMed2001

On the accuracy and effectiveness of dose reconstruction for tomotherapy.

Dose reconstruction is a process that re-creates the treatment-time dose deposited in a patient provided there is knowledge of the delivered energy fluence and the patient's anatomy at the time of treatment. A method for reconstructing dose is presented. The process starts with delivery verification, in which the incident energy fluence from a treatment is computed using the exit detector signal and a transfer matrix to convert the detector signal to energy fluence. With the verified energy fluence and a CT image of the patient in the treatment position, the treatment-time dose distribution is computed using any model-based algorithm such as convolution/superposition or Monte Carlo. The accuracy of dose reconstruction and the ability of the process to reveal delivery errors are presented. Regarding accuracy, a reconstructed dose distribution was compared with a measured film distribution for a simulated breast treatment carried out on a thorax phantom. It was found that the reconstructed dose distribution agreed well with the dose distribution measured using film: the majority of the voxels were within the low and high dose-gradient tolerances of 3% and 3 mm respectively. Concerning delivery errors, it was found that errors associated with the accelerator, the multileaf collimator and patient positioning might be detected in the verified energy fluence and are readily apparent in the reconstructed dose. For the cases in which errors appear in the reconstructed dose, the possibility for adaptive radiotherapy is discussed.

Algorithms↗

PubMed2001

Elicitin genes expressed in vitro by certain tobacco isolates of Phytophthora parasitica are down regulated during compatible interactions.

Phytophthora spp. secrete proteins called elicitins in vitro that can specifically induce hypersensitive response and systemic acquired resistance in tobacco. In Phytophthora parasitica, the causal agent of black shank, most isolates virulent on tobacco are unable to produce elicitins in vitro. Recently, however, a few elicitin-producing P. parasitica strains virulent on tobacco have been isolated. We investigated the potential diversity of elicitin genes in P. parasitica isolates belonging to different genotypes and with various virulence levels toward tobacco as well as elicitin expression pattern in vitro and in planta. Although elicitins are encoded by a multigene family, parAl is the main elicitin gene expressed. This gene is highly conserved among isolates, regardless of the elicitin production and virulence levels toward tobacco. Moreover, we show that elicitin-producing P. parasitica isolates virulent on tobacco down regulate parAl expression during compatible interactions, whichever host plant is tested. Conversely, one elicitin-producing P. parasitica isolate that is pathogenic on tomato and avirulent on tobacco still expresses parAl in the compatible interaction. Therefore, some P. parasitica isolates may evade tobacco recognition by down regulating parA1 in planta. The in planta down regulation of parA1 may constitute a suitable mechanism for P. parasitica to infect tobacco without deleterious consequences for the pathogen.

Algal Proteins↗

PubMed2000

Osmotic stress response in Dictyostelium is mediated by cAMP.

DokA, a homolog of bacterial hybrid histidine kinases, is essential for hyperosmotic stress resistance in Dictyostelium: We show that a transient intracellular cAMP signal, dependent on the presence of DokA, is generated in response to an osmotic shock. This variation of cAMP levels contributes to survival under hypertonic conditions. In contrast to the low cAMP levels observed in dokA(-) strains, overexpression of the receiver domain of DokA causes an increase in cAMP levels, resulting in a rapidly developing phenotype. We present biochemical and cell biological data indicating that the DokA receiver domain is a dominant-negative regulator of a phosphorelay, which controls the intracellular cAMP phosphodiesterase RegA. The activity of the DokA receiver domain depends on a conserved aspartate, mutation of which reverses the developmental phenotype, as well as the deregulation of cAMP metabolism.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2000

Electrical transport in the ferromagnetic state of manganites: small-polaron metallic conduction at low temperatures.

We report measurements of the resistivity in the ferromagnetic state of epitaxial thin films of La(1-x)Ca(x)MnO3 and the low-temperature specific heat of a polycrystalline La0.8Ca0.2MnO3. The resistivity below 100 K can be well fitted by rho-rho(0) = Eomega(s)/sinh (2)(hs/ 2k(B)T) with h(omega)(s)/k(B) approximately 80 K and E being a constant. Such behavior is consistent with small-polaron coherent motion which involves a relaxation due to a soft optical phonon mode that is strongly coupled to the carriers. The specific-heat data also suggest the existence of such a phonon mode. The present results thus provide evidence for small-polaron metallic conduction in the ferromagnetic state of manganites.

Journal Article↗

PubMed2000

Oxygen-isotope effect on the In-plane penetration depth in underdoped La2-xSrxCuO4 single crystals

We report measurements of the oxygen-isotope effect (OIE) on the in-plane penetration depth lambda(ab)(0) in underdoped La2-xSrxCuO4 single crystals. A highly sensitive magnetic torque sensor with a resolution of Deltatau approximately 10(-12) N m was used for the magnetic measurements on microcrystals with a mass of approximately 10 &mgr;g. The OIE on lambda(-2)(ab)(0) is found to be -10(2)% for x = 0.080 and -8(1)% for x = 0.086. It arises mainly from the oxygen-mass dependence of the in-plane effective mass m(*)(ab). The present results suggest that lattice vibrations are important for the occurrence of high temperature superconductivity.

Journal Article↗

PubMed2000

Neutrophil polarity and locomotion are associated with surface redistribution of leukosialin (CD43), an antiadhesive membrane molecule.

This study analyzed the behavior of an antiadhesive membrane molecule, CD43, in neutrophil polarization and locomotion. CD43 cross-linking by antibodies induced neutrophil locomotion, with CD43 molecules clustered at the uropod of polarized neutrophils. In contrast, CD11b/CD18 cross-linking by antibodies did not affect either cell polarization or locomotion. Stimulation of suspended or adherent neutrophils with chemotactic peptide results in cell polarization and locomotion and a concomitant redistribution of CD43 to the uropod. This process is entirely reversible. The study also investigated which actin-binding protein could be involved in CD43 lateral redistribution. alpha-Actinin and moesin are preferentially adsorbed on Sepharose beads bearing a recombinant CD43 intracellular domain. Analysis by immunofluorescence confocal microscopy shows a codistribution of moesin during CD43 lateral redistribution. By contrast, alpha-actinin is located at the leading edge, an area devoid of CD43. These results shed new light on the role of CD43 membrane redistribution, which appears to be directly related to neutrophil polarity and locomotion. (Blood. 2000;95:2462-2470)

Adult↗

PubMed2000

Long-term results of intravesical bacillus Calmette-Guérin therapy for stage T1 superficial bladder cancer.

OBJECTIVES: To examine in a prospective study the incidence of recurrence and progression in patients with Stage T1 bladder carcinoma after complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). METHODS: Between July 1987 and April 1999, 126 patients presenting to our clinic with a superficial urothelial carcinoma of the bladder (Stage pT1, grade 1-3) received adjuvant intravesical immunotherapy with BCG after complete transurethral resection of the bladder tumor. In the case of recurrence of superficial tumor (pTa, pT1, or carcinoma in situ), patients received a second cycle of BCG. For muscle-invasive tumor progression (pT2, pT3, or pT4), radical cystectomy was recommended. Six of the patients (5%) presented with Stage pT1,G1 tumor, 74 (59%) with Stage pT1,G2 tumor, and 46 patients (36%) with Stage pT1,G3 tumor. Median follow-up was 53 months (range 3 to 144). RESULTS: One hundred eight patients (86%) remained tumor-free with a retained bladder during the follow-up after one or two 6-week cycles of BCG. Twenty-four patients (19%) had a recurrence of superficial tumor, 13 (10%) had muscle-invasive progression after the first BCG cycle, and an additional 4 (3%) had progression after the second BCG cycle. Six patients (5%) underwent radical cystectomy, and 9 patients (7%) died as a result of tumor progression. The tumor-free survival rate of all patients was 89% (112 of 126). CONCLUSIONS: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective primary treatment for Stage T1 carcinoma of the bladder. Even in Stage pT1,G3 tumor, immediate radical cystectomy does not appear necessary.

Adjuvants, Immunologic↗