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F Bosch

Publications and source records attributed to F Bosch.

At least 19 recordsLinked to original sources

First measurement of the linear polarization of radiative electron capture transitions.

For radiative electron capture into the K shell of bare uranium ions, a study of the polarization properties has been performed. For this purpose a position sensitive germanium detector has been used as an efficient Compton polarimeter. This enabled us to measure the degree of linear polarization by analyzing Compton scattering inside the detector and to determine the orientation of the polarization plane. Depending on the observation angle and the beam energy used, the radiation is found to be linearly polarized by up to 80%. In all cases studied, the plane of polarization coincides with the collision plane. The results will be discussed in the context of rigorous relativistic calculations, showing that relativistic effects tend to lead to a depolarization of the radiation emitted.

Journal Article↗

The Follicular Lymphoma International Prognostic Index (FLIPI) and the histological subtype are the most important factors to predict histological transformation in follicular lymphoma.

BACKGROUND: Histological transformation (HT) is a well-known event in patients with follicular lymphoma (FL) conferring an unfavorable prognosis. The aim of the study was to analyze incidence and risk factors for HT in a large series of FL patients. PATIENTS AND METHODS: 276 patients (median age: 54 years; M139/F137) diagnosed with FL (42% grade 1, 51% 2, 7% 3) in a single institution were studied. Initial treatment consisted of combined chemotherapy in most cases. Median survival was 11.3 years. Main clinic and biological variables were assessed for HT and survival. RESULTS: 30 of 276 patients (11%) presented HT after a median follow-up of 6.5 years, with a risk of 15% and 22% at 10 and at 15 years, respectively. All HT corresponded to diffuse large B-cell lymphoma (DLBCL). Grade 3 histology, nodal areas >4, increased LDH and beta(2)-microglobulin, and high-risk IPI and FLIPI were associated with HT. In multivariate analysis, grade 3 histology and FLIPI retained prognostic significance. Only FLIPI predicted HT in grade 1-2 patients. 28 patients received salvage treatment for HT, with a CR rate of 52%. Median survival from transformation was 1.2 years, with 6/13 CR patients being alive >5 years after HT. CONCLUSION: FLIPI and histology were the most important variables predicting HT. Upon HT, only patients achieving CR reached prolonged survival, thus emphasizing the need for effective therapies once this event occurs.

Adult↗

Simultaneous measurement of beta- decay to bound and continuum electron states.

We report the first measurement of a ratio lambda(beta(b))/lambda(beta(c)) of bound-state ((lambda(beta(b))) and continuum-state (lambda(beta(c))) beta(-)-decay rates for the case of bare 207Tl81+ ions. These ions were produced at the GSI fragment separator FRS by projectile fragmentation of a 208Pb beam. After in-flight separation with the Brho-deltaE-Brho method, they were injected into the experimental storage-ring ESR at an energy of 400.5A MeV, stored, and electron cooled. The number of both the 207Tl81+ ions and their bound-state beta(-)-decay daughters, hydrogen-like 207Pb81+ ions, were measured as a function of storage time by recording their Schottky-noise intensities. The experimental result, lambda(beta(b))/lambda(beta(c)) = 0.188(18), is in very good agreement with the value of 0.171(1) obtained from theory employing spectra of allowed transitions.

Journal Article↗

Isospin dependence in the odd-even staggering of nuclear binding energies.

The FRS-ESR facility at GSI provides unique conditions for precision measurements of large areas on the nuclear mass surface in a single experiment. Values for masses of 604 neutron-deficient nuclides (30 < or = Z < or = 92) were obtained with a typical uncertainty of 30 microu. The masses of 114 nuclides were determined for the first time. The odd-even staggering (OES) of nuclear masses was systematically investigated for isotopic chains between the proton shell closures at Z = 50 and Z = 82. The results were compared with predictions of modern nuclear models. The comparison revealed that the measured trend of OES is not reproduced by the theories fitted to masses only. The spectral pairing gaps extracted from models adjusted to both masses, and density related observables of nuclei agree better with the experimental data.

Journal Article↗

Quantum electrodynamics in strong electric fields: the ground-state Lamb shift in hydrogenlike uranium.

X-ray spectra following radiative recombination of free electrons with bare uranium ions (U92+) were measured at the electron cooler of the ESR storage ring. The most intense lines observed in the spectra can be attributed to the characteristic Lyman ground-state transitions and to the recombination of free electrons into the K shell of the ions. Our experiment was carried out by utilizing the deceleration technique which leads to a considerable reduction of the uncertainties associated with Doppler corrections. This, in combination with the 0 degree observation geometry, allowed us to determine the ground-state Lamb shift in hydrogenlike uranium (U91+) from the observed x-ray lines with an accuracy of 1%. The present result is about 3 times more precise than the most accurate value available up to now and provides the most stringent test of bound-state quantum electrodynamics for one-electron systems in the strong-field regime.

Journal Article↗

Electron-electron interaction in strong electromagnetic fields: the two-electron contribution to the ground-state energy in He-like uranium.

Radiative recombination transitions into the ground state of cooled bare and hydrogenlike uranium ions were measured at the storage ring ESR. By comparing the corresponding x-ray centroid energies, this technique allows for a direct measurement of the electron-electron contribution to the ionization potential in the heaviest He-like ions. For the two-electron contribution to the ionization potential of He-like uranium we obtain a value of 2248+/-9 eV. This represents the most accurate determination of two-electron effects in the domain of high-Z He-like ions, and the accuracy reaches already the size of the specific two-electron radiative QED corrections.

Journal Article↗

Predictive value of Follicular Lymphoma International Prognostic Index (FLIPI) in patients with follicular lymphoma at first progression.

BACKGROUND: Different prognostic scores have been proposed to predict the outcome of follicular lymphoma (FL) patients at diagnosis. A new prognostic index specifically addressing FL patients, the Follicular Lymphoma International Prognostic Index (FLIPI), has recently been developed, which might also be useful in patients with progression. PATIENTS AND METHODS: One hundred and three patients (55 male, 48 female; median age 59 years) with FL in first relapse/progression after an initial response to therapy (50 complete responders/ 53 partial responders) were included in the study. RESULTS: Five-year survival from progression (SFP) was 55% (95% confidence interval 44%-66%). The distribution according to the FLIPI at relapse was 39% good prognosis, 24% intermediate prognosis and 37% poor prognosis. Five-year SFP for these groups were 85%, 79% and 28%, respectively (P < 0.0001). Other variables at relapse with prognostic significance for SFP were age, presence of B symptoms, performance status, bulky disease, number of involved nodal sites, lactate dehydrogenase level, hemoglobin level, histological transformation, the Italian Lymphoma Intergroup prognostic index for FL and the International Prognostic Index for aggressive lymphomas. In the multivariate analysis bulky disease (P=0.01), presence of B symptoms (P=0.03) and FLIPI at relapse (P=0.0003) were the most important variables for predicting SFP. CONCLUSIONS: In patients with FL at first relapse/progression, the FLIPI, along with the presence of bulky disease and B symptoms, are features that predict SFP and thus could be useful to select candidates for experimental treatments.

Age Factors↗

Long-term overexpression of glucokinase in the liver of transgenic mice leads to insulin resistance.

AIMS/HYPOTHESIS: Glucokinase overexpression in the liver increases glucose uptake and utilization, and improves glucose tolerance in young transgenic mice. Here, we examined the long-term effects of hepatic overexpression of glucokinase on glucose homeostasis. Moreover, we determined whether glucokinase overexpression counteracted high-fat diet-induced insulin resistance. METHODS: Transgenic mice overexpressing glucokinase in liver under the control of the phosphoenolpyruvate carboxykinase promoter, fed either a standard diet or a high-fat diet, were studied. We used non-transgenic littermates as controls. RESULTS: Transgenic mice over 6 months old developed impaired glucose tolerance. In addition, at 12 months of age, transgenic mice showed mild hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia. In spite of increased glucokinase activity, the liver of these mice accumulated less glycogen and increased triglyceride deposition. When 2-month-old glucose-tolerant mice were fed a high-fat diet, transgenic mice gained more body weight and became hyperglycaemic and hyperinsulinaemic. This was concomitant to glucose intolerance, liver steatosis and whole-body insulin resistance. CONCLUSION/INTERPRETATION: Long-term overexpression of glucokinase increases hepatic lipogenesis and circulating lipids, which lead to insulin resistance. Our results also suggest that the liver plays a key role in the onset of diabetes.

Animals↗

Precise determination of the 2s(1/2)-2p(1/2) splitting in very heavy lithiumlike ions utilizing dielectronic recombination.

The 2s(1/2)-2p(1/2) energy splittings DeltaE(L) of the lithiumlike ions 19779Au76+, 20882Pb79+, and 23892U89+ have been measured at the Experimental Storage Ring, utilizing low energy dielectronic recombination. The resonance energies in total 41 different 1s(2) 2p(1/2)nl(j(')) (n > or =20) autoionizing Rydberg states populated in the dielectronic capture process have been determined. The 2s(1/2)-->2p(1/2) excitation energies have been obtained by extrapolation of these resonance energies to the associated series limits n--> infinity. The combined analysis of the experimental data for all three ions yields DeltaE(L)=216.134(96) eV for Au76+, 230.650(81) eV for Pb79+, and 280.516(99) eV for U89+.

Journal Article↗

Malignant transformation in IgM monoclonal gammopathy of undetermined significance.

Monoclonal gammopathy of undetermined significance (MGUS) is a frequent disorder characterized by the presence of a small serum M-protein in individuals with no evidence of multiple myeloma (MM), Waldenstrom's macroglobulinemia (WM), or primary amyloidosis (AL). Although one fourth of these individuals will develop a malignant disease, there are no well-established predictors of outcome, particularly in the IgM type MGUS. Among 434 patients diagnosed with MGUS from 1970 to 2001 with a minimum follow-up of 1 year, 52 (27 men and 25 women; median age, 67 years) of IgM type were identified. After a median follow-up of 5 years, five patients (9.6%) have developed WM. The risk of transformation was 13.3% (95% confidence interval [CI], 0 to 27) and 27.7% (95% CI, 0.3 to 55.1) at 10 and 20 years, respectively. The variables significantly associated with transformation were the proportion of bone marrow plasma cells (BMPC) and the percentage of bone marrow lymphocytes (BML). No significant differences in the risk of transformation were found between IgM MGUS and the remaining MGUS types. Thus, in IgM MGUS the rate of transformation was similar to the risk observed in other MGUS types, the percentage of BMPC and BML being the features significantly associated with evolution into WM.

Aged↗

High Rydberg resonances in dielectronic recombination of pb(79+).

Dielectronic recombination resonances of Pb (79+) associated with 2s(1/2)-->2p(1/2) excitations were measured at the heavy-ion storage ring ESR at GSI. The fine structure of the energetically lowest resonance manifold Pb (78+)(1s(2)2p(1/2)20l(j)) at around 18 eV could partially be resolved, and rate coefficients on an absolute scale were obtained. A comparison of the experimental data with results of a fully relativistic theoretical approach shows that high-angular-momentum components up to j=31/2 significantly contribute to the total resonance strength demonstrating the necessity to revise the widespread notion of negligible high-angular-momentum contributions at least for very highly charged ions.

Journal Article↗

Multiple cell cycle regulator alterations in Richter's transformation of chronic lymphocytic leukemia.

To investigate the role of the cell cycle regulators p21(Waf1), p27(Kip1), retinoblastoma (Rb), and cyclin D1 in Richter's transformation of chronic lymphocytic leukemia (CLL), we analyzed 19 CLL and eight Richter's syndrome (RS) tumors, previously characterized for p53 and ARF/INK4a abnormalities. p21(Waf1)immunohistochemical expression was negative in 12 of 15 CLL (80%), whereas it was moderate or strong in three of seven RS (43%). p21(Waf1) gene was in germline configuration in all the tumors analyzed. Four immunohistochemical patterns of p53 and p21(Waf1) expression were observed: (1) p53-/p21- in 10 of 15 CLL (67%), but only in two of six RS (33%); (2) p53+/p21+ in three CLL (20%) and two RS (33%); (3) p53-/p21+ in one RS; and (4) p53++/p21- in two CLL and one RS. Two p53+/p21+ CLL evolved into RS. p53 mutations clustered around the p53++/p21- (two CLL and one RS) and p53-/p21- (one CLL and one RS) tumors. While the majority of CLL displayed strong p27 immunoreactivity, RS tumors were constantly p27-negative. p27(Kip1) gene was in germline configuration in all the tumors analyzed. Most CLL cases were negative for Rb expression. In contrast, all RS exhibited strong Rb expression. Cyclin D1 overexpression was only detected in one CLL evolving into RS and one RS. In conclusion, a p53+/p21- immunohistochemical pattern is shown exclusively by p53-mutated CLL/RS. Additionally, our results suggest a possible implication of moderate/strong p21(Waf1) expression, loss of p27 expression, and cyclin D1 overexpression in the Richter's transformation of CLL.

Adult↗

Simultaneous diagnosis of hairy cell leukemia and chronic lymphocytic leukemia/small lymphocytic lymphoma: a frequent association?

The association of hairy cell leukemia (HCL) with other neoplasms, mainly non-Hodgkin's lymphomas, is well known. However, the simultaneous diagnosis of HCL and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is rare, with only few cases of such an association having been reported. We describe three patients with a well-characterized HCL in whom a CLL/SLL population was detected. Of note, these cases represent a significant proportion (11.5%; 95% CI: 0% to 24%) of the total number of HCL cases diagnosed in our institution during the same period of time. All three patients were treated with deoxycoformycin. They achieved a complete response of the HCL, whereas the CLL/SLL population persisted in all cases. The immunoglobulin gene rearrangement analysis, in two informative cases, suggested that the HCL and CLL/SLL populations arose from different B cell clones. This study indicates that the association of HCL and CLL/SLL might be much more frequent than previously recognized. Therefore, a large panel of monoclonal antibodies, including those necessary to detect CLL/SLL, should be employed when studying patients with HCL.

Antimetabolites, Antineoplastic↗

Survival after progression in patients with follicular lymphoma: analysis of prognostic factors.

BACKGROUND: The purpose of this study was to identify prognostic parameters for patients with follicular lymphoma (FL) in first progression/relapse. These would be useful for selection of high-risk patients for inclusion in trials aimed at determining the effect of new treatment approaches in such patients. PATIENTS AND METHODS: Ninety patients (48 male, 42 female, median age 56 years) diagnosed with FL, in a single institution during a 20 year period and relapsing/progressing after an initial response to therapy, were recruited. The main end-point of the study was survival from progression (SFP). Univariate and multivariate analyses were performed, including among the predictive variables the response duration (RD) after the initial treatment and the main features of the patients at the first progression or relapse. RESULTS: Five-year SFP was 47% (95% confidence interval 35% to 58%). Patients with RD following initial therapy >2 years had a longer SFP (5-year SFP 63 versus 33%, P = 0.012). Other variables with prognostic interest for SFP were stage at diagnosis and the following variables at relapse: age, bulky disease, performance status, serum lactate dehydrogenase level, serum beta2-microglobulin level, bone marrow involvement, stage and International Prognostic Index rating. In the multivariate analysis, poor performance status at progression and a RD <2 years were the most important unfavorable variables to predict SFP. CONCLUSION: In patients with FL, RD along with performance status at progression are features that predict SFP. These variables could thus be useful to select candidates for experimental treatments.

Age Factors↗

Activity of oral fludarabine phosphate in previously treated chronic lymphocytic leukemia.

PURPOSE: A prospective, multicenter, open-label phase II clinical trial was conducted to assess the efficacy and safety of oral fludarabine phosphate. Reference to an historical group of patients treated with the intravenous (IV) formulation allowed the investigators to compare the two formulations. PATIENTS AND METHODS: Efficacy was assessed using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) and National Cancer Institute (NCI) criteria for complete remission (CR), partial remission (PR), stable disease, or disease progression. Safety monitoring included World Health Organization (WHO) toxicity grading for all adverse events. RESULTS: Seventy-eight (96.3%) of 81 recruited patients with previously treated B-cell chronic lymphocytic leukemia (CLL) received 10-mg tablets of fludarabine phosphate to a dose of 40 mg/m(2)/d for 5 days, repeated every 4 weeks, for a total of six to eight cycles. According to IWCLL criteria, the overall remission rate was 46.2% (CR, 20.5%; PR, 25.6%). The comparative figures using NCI criteria were 51.3% (CR, 17.9%; PR, 33.3%). Overall, 30 incidents of severe adverse events were reported for 22 patients. WHO grade 3 or grade 4 hematologic toxicities included granulocytopenia (53.8%), leukocytopenia (28.2%), thrombocytopenia (25.6%), and anemia (24.4%). Gastrointestinal adverse events were more common with the oral formulation than previously reported with IV fludarabine phosphate. However, these events were generally mild to moderate. CONCLUSION: This study demonstrates that oral fludarabine phosphate has similar clinical efficacy to the IV formulation and a safety profile that is both predictable and essentially similar to that of the IV formulation.

Administration, Oral↗

Prognostic features and outcome in patients with diffuse large B-cell lymphoma who do not achieve a complete response to first-line regimens.

BACKGROUND: The current study was conducted to analyze the outcome and prognostic factors of patients with diffuse large B-cell lymphoma (DLCL) who did not achieve a complete response (CR) to first-line treatment. METHODS: The current study was comprised of 83 patients (43 males and 40 females with a median age of 62 years) who did not achieve a CR (58 of whom had primary refractory disease and 25 of whom achieved a partial response) with initial treatment (doxorubicin-containing regimens in 87% of cases) from a series of 239 patients consecutively diagnosed with DLCL at a single institution. Initial variables, response to therapy, and salvage treatment were analyzed to predict survival. RESULTS: Compared with patients who achieved a CR, nonresponders or partial responders more frequently were of advanced age and had a poor performance status (PS), B-symptoms, advanced stage of disease, bone marrow infiltration, increased serum lactate dehydrogenase, and a high-risk International Prognostic Index. Among the 58 patients with primary refractory disease, 18 died during initial treatment due to toxicity (14 patients) or disease progression (4 patients). The main variables predicting early death were a poor PS, age > 60 years, and an immunoblastic DLCL subtype. Twenty-five of these 58 patients were able to receive salvage regimens, with only 1 of them achieving a CR. The median survival for this group of patients was 10 months. With regard to those patients achieving a partial response, 18 of the 25 patients received further therapy with 28% of them achieving a CR. The median survival was 23 months. The degree of the response was found to be the only significant variable with which to predict survival, with 2-year survival rates of 4% and 40%, respectively, for patients with primary refractory disease and patients who achieved a partial response. CONCLUSIONS: The prognosis of patients with primarily refractory DLCL is extremely unfavorable, whereas that of patients who achieve a partial response is slightly better. The inclusion of these patients in experimental trials is limited due to their tendency to be of an older age and to have a poor general status.

Adolescent↗

Nucleotide sequence, transcription map, and mutation analysis of the 13q14 chromosomal region deleted in B-cell chronic lymphocytic leukemia.

Deletions of the 13q14 chromosome region are associated with B-cell chronic lymphocytic leukemia (B-CLL) and several other types of cancer, suggesting the presence of a tumor suppressor gene. In previous studies the minimal region of deletion (MDR) was mapped to a less than 300-kilobase (kb) interval bordered by the markers 173a12-82 and 138G4/1.3R. For the identification of the putative tumor suppressor gene, the entire MDR (approximately 347 kb) has been sequenced, and transcribed regions have been identified by exon trapping, EST-based full-length complementary DNA cloning, database homology searches, and computer-assisted gene prediction analyses. The MDR contains 2 pseudogenes and 3 transcribed genes: CAR, encoding a putative RING-finger containing protein; 1B4/Leu2, generating noncoding transcripts; and EST70/Leu1, probably representing another noncoding gene (longest open reading frame of 78 codons). These genes have been sequenced in 20 B-CLL cases with 13q14 hemizygous deletion, and no mutations were found. Moreover, no somatic variants were found in the entire MDR analyzed for nucleotide substitutions by a combination of direct sequencing and fluorescence-assisted mismatch analysis in 5 B-CLL cases displaying 13q14-monoallelic deletion. The nondeleted allele of the CAR and EST70/Leu1 genes was expressed in B-CLL specimens, including those with monoallelic loss, whereas no expression of 1B4/Leu2 was detectable in B-CLL, regardless of the 13q14 status. These results indicate that allelic loss and mutation of a gene within the MDR is an unlikely pathogenetic mechanism for B-CLL. However, haplo-insufficiency of one of the identified genes may contribute to tumorigenesis. (Blood. 2001;97:2098-2104)

Animals↗