| 301. |
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| 302. |
- Bjerlin, J., et al.
(författare)
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Dipolar particles in a double-trap confinement : Response to tilting the dipolar orientation
- 2018
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Ingår i: Physical Review A. - 2469-9926. ; 97:2
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Tidskriftsartikel (refereegranskat)abstract
- We analyze the microscopic few-body properties of dipolar particles confined in two parallel quasi-one-dimensional harmonic traps. In particular, we show that an adiabatic rotation of the dipole orientation about the trap axes can drive an initially nonlocalized few-fermion state into a localized state with strong intertrap pairing. With an instant, nonadiabatic rotation, however, localization is inhibited and a highly excited state is reached. This state may be interpreted as the few-body analog of a super-Tonks-Girardeau state, known from one-dimensional systems with contact interactions.
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| 303. |
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| 304. |
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| 305. |
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| 306. |
- Blystad, A K, et al.
(författare)
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High-dose therapy with autologous stem cell transplantation in patients with peripheral T cell lymphomas.
- 2001
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 27:7, s. 711-6
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Tidskriftsartikel (refereegranskat)abstract
- Peripheral T cell lymphomas (PTCL) have a poorer prognosis after conventional treatment than do high-grade B cell lymphomas. The place for high-dose therapy (HDT) with autologous stem cell support in these patients is still not clear. Forty patients, 10 women and 30 men, median age 41.5 years (range 16-61) with PTCL were treated with HDT and autologous stem cell support at The Norwegian Radium Hospital, Oslo, Norway and The University Hospital, Uppsala, Sweden, between February 1990 and September 1999. The histologic subtypes were: PTCL unspecified, 20 patients; intestinal, two patients; angioimmunoblastic (AILD), two patients; angiocentric, two patients and anaplastic large cell lymphoma (ALCL), 14 patients. All patients had chemosensitive disease and had received anthracycline-containing regimens prior to transplantation. At the time of HDT, 17 patients were in first PR or CR and 23 were in second or third PR or CR. Conditioning regimens were BEAM in 15 patients, BEAC in 14 patients, cyclophosphamide and total body irradiation (TBI) in eight patients, BEAC, without etoposide and TBI in one patient and mitoxantrone and melphalan in two patients. There were three (7.5%) treatment-related deaths. The estimated overall survival (OS) at 3 years was 58%, the event-free survival (EFS) 48% and the relapse-free survival (RFS) 56%, with a median follow-up of 36 months (range 7-100) for surviving patients. The patients with ALCL tended to have a better prognosis compared to those with other PTCL subtypes, OS 79% vs 44%, respectively. In conclusion, patients with chemosensitive PTCL who are failing to achieve CR with first-line chemotherapy or are in relapse can successfully be treated with HDT and autologous stem cell support.
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| 307. |
- Boguszewski, C L, et al.
(författare)
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22-kD growth hormone exclusion assay: a new approach to measurement of non-22-kD growth hormone isoforms in human blood.
- 1996
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Ingår i: European journal of endocrinology. - 0804-4643. ; 135:5, s. 573-82
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Tidskriftsartikel (refereegranskat)abstract
- Human growth hormone (GH) exists in a variety of isoforms. In the pituitary, the most abundant isoform is 22-kD GH (22 K GH), while other isoforms (non-22 K GH) are present in variable amounts. In human plasma, the GH heterogeneity contributes to the wide variability in GH levels measured by different immunoassays. The physiological role of the non-22 K GH isoforms is poorly understood, but they may represent a spectrum of agonists or antagonists of the GH receptor. It is possible that increased amounts of non-22 K GH isoforms in the circulation contribute to the growth failure observed in some short children and may be involved in the pathophysiology of acromegaly and other unrelated diseases. Currently, there is no method available to evaluate the ratio of non-22 K GH isoforms to total GH in large sets of serum samples. In this report, a novel assay procedure is described in which monomeric and dimeric isoforms of 22 K GH are removed from serum and non-22 K GH isoforms are quantitated. The 22 K GH exclusion assay (22 K GHEA) was established as a screening method to identify conditions in which the ratio of non-22 K GH isoforms to total GH in human blood is altered. A 22 K GH-specific monoclonal antibody (MCB) is used for binding to 22 K GH in serum. Magnetic beads coated with rat anti-mouse immunoglobulin G and a magnetic device are used to remove the 22K GH-MCB complexes from serum. The non-22 K GH isoforms are measured by a polyclonal antibody-based immunoradiometric assay (GH-IRMA). The assay procedure was optimized systematically by statistical experimental designs. In serum spiked with monomeric or dimeric 22 K GH, the 22 K GH extraction was efficient at GH levels up to 100 microg/l (range 96.3-100%). The intra- and interassay precision for non-22K GH levels of 3.9 microg/l were 2.6% and 8.7%, respectively, while for levels of 0.6 microg/l, which were very close to the detection limits of the assay, the coefficients were 17.0% and 21.6%, respectively. The percentage of non-22 K GH isoforms determined in serum samples from three different groups of subjects showed clearly distinctive values. The 22 K GHEA is a new method for evaluation of non-22 K GH isoforms in human blood under different physiological and pathophysiological conditions.
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| 308. |
- Boguszewski, C L, et al.
(författare)
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Circulating non-22-kilodalton growth hormone isoforms in acromegalic men before and after transsphenoidal surgery.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 82:5, s. 1516-21
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Tidskriftsartikel (refereegranskat)abstract
- GH represents several molecular isoforms in addition to the main 22-kDa (22K) GH. There have been reports suggesting that circulating non-22K GH isoforms are increased in acromegaly, but the possible implications of such observations in the management of the disease have not been addressed. The aim of this study was to evaluate the proportion of circulating non-22K GH isoforms in acromegaly. In addition, the relationships between the amount of non-22K GH and tumor size, biochemical measurements, and body composition also were investigated. Samples with different GH levels were selected from 24-h GH profiles from 15 acromegalic men evaluated before and 1 yr after transsphenoidal surgery and from 13 healthy men. The serum non-22K GH levels, expressed as percentage of total GH concentration, were determined by the 22K GH exclusion assay, which is based on immunomagnetic extraction of 22K GH from serum and quantitation of non-22K GH using a polyclonal GH assay. The proportion of non-22K GH isoforms was fairly constant in different samples from the same patient, regardless of the GH level. However, a wide variation of values was observed among acromegalics, both before (14-51%) and after surgery (8-62%). The proportion of non-22K GH isoforms was increased in untreated patients, compared with controls (26.6 vs. 17.4%; P < 0.01), and the values correlated significantly to tumor size, mean 24-h GH concentration, serum PRL, and extracellular water. After surgery, patients not truly cured, with mean 24-h GH concentration of 1 microg/L or more, had an increased proportion of non-22K GH, compared with those with levels less than 1 microg/L (P < 0.01). In the former group, the median values were similar than those in untreated acromegalics (34 vs. 26.6%, respectively), whereas in the latter, they were comparable with those in the controls (15.2 vs. 17.4%, respectively). We conclude that acromegalics have an increased proportion of circulating non-22K GH isoforms. The values are fairly constant in different samples from an individual, regardless of GH level, but a large spectrum can be observed among patients. This variability suggests that different pituitary adenomas secrete GH isoforms in variable amounts. Our observation that a higher proportion of non-22K GH isoforms is present in patients not truly cured after surgery suggests that the evaluation of non-22K GH isoforms can be useful in the follow-up of acromegalic patients.
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| 309. |
- Bonagas, Nadilly, et al.
(författare)
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Pharmacological targeting of MTHFD2 suppresses acute myeloid leukemia by inducing thymidine depletion and replication stress
- 2022
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Ingår i: NATURE CANCER. - : Springer Science and Business Media LLC. - 2662-1347. ; 3:2, s. 156-
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Tidskriftsartikel (refereegranskat)abstract
- The folate metabolism enzyme MTHFD2 (methylenetetrahydrofolate dehydrogenase/cyclohydrolase) is consistently overexpressed in cancer but its roles are not fully characterized, and current candidate inhibitors have limited potency for clinical development. In the present study, we demonstrate a role for MTHFD2 in DNA replication and genomic stability in cancer cells, and perform a drug screen to identify potent and selective nanomolar MTHFD2 inhibitors; protein cocrystal structures demonstrated binding to the active site of MTHFD2 and target engagement. MTHFD2 inhibitors reduced replication fork speed and induced replication stress followed by S-phase arrest and apoptosis of acute myeloid leukemia cells in vitro and in vivo, with a therapeutic window spanning four orders of magnitude compared with nontumorigenic cells. Mechanistically, MTHFD2 inhibitors prevented thymidine production leading to misincorporation of uracil into DNA and replication stress. Overall, these results demonstrate a functional link between MTHFD2-dependent cancer metabolism and replication stress that can be exploited therapeutically with this new class of inhibitors. Helleday and colleagues describe a nanomolar MTHFD2 inhibitor that causes replication stress and DNA damage accumulation in cancer cells via thymidine depletion, demonstrating a potential therapeutic strategy in AML tumors in vivo.
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| 310. |
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