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排序方式: 共有1014条查询结果,搜索用时 15 毫秒
91.
Brunner R Aissaoui H Boss C Bozdech Z Brun R Corminboeuf O Delahaye S Fischli C Heidmann B Kaiser M Kamber J Meyer S Papastogiannidis P Siegrist R Voss T Welford R Wittlin S Binkert C 《The Journal of infectious diseases》2012,206(5):735-743
The increasing spread of drug-resistant malaria strains underscores the need for new antimalarial agents with novel modes of action (MOAs). Here, we describe a compound representative of a new class of antimalarials. This molecule, ACT-213615, potently inhibits in vitro erythrocytic growth of all tested Plasmodium falciparum strains, irrespective of their drug resistance properties, with half-maximal inhibitory concentration (IC(50)) values in the low single-digit nanomolar range. Like the clinically used artemisinins, the compound equally and very rapidly affects all 3 asexual erythrocytic parasite stages. In contrast, microarray studies suggest that the MOA of ACT-213615 is different from that of the artemisinins and other known antimalarials. ACT-213615 is orally bioavailable in mice, exhibits activity in the murine Plasmodium berghei model and efficacy comparable to that of the reference drug chloroquine in the recently established P. falciparum SCID mouse model. ACT-213615 represents a new class of potent antimalarials that merits further investigation for its clinical potential. 相似文献
92.
Mouse bone marrow (BM) was separated into low-density, lineage- negative, wheat germ agglutinin-positive (WGA+), Rhodamine-123 bright (Rhbright) or dim (Rhdim) cells to obtain populations that were highly enriched for committed progenitors (Rhbright cells) or for more primitive stem cells (Rhdim). When 2,500 Rhbright or Rhdim cells were seeded onto 6-week-old irradiated (20 Gy) long-term BM cultures (LTBMC), the nonadherent cell production from Rhbright cells was transient and ended after 5 weeks. Production from Rhdim cells did not begin until week 3, peaked at week 5, and ended at week 8, when the irradiated stroma seemed to fail. Termination of cell production from Rhdim cells did not occur in nonirradiated LTBMC from W41/Wv mice. During peak nonadherent cell production, 25% to 30% of the cells in the nonirradiated LTBMC from W41/Wv mice had donor cell markers. Two approaches were tested to try to enhance the proportion or number of donor cells. Addition of Origen-HGF at the time of seeding Rhdim cells caused a nonspecific increase in both host and donor cell production, but a specific increase in production of donor cells was obtained by seeding the cultures at 2 weeks rather than 6 weeks. Limiting dilution of Rhdim cells gave the same frequency of wells producing cells on both irradiated +/+ and nonirradiated W41/Wv or W/Wv cultures. 相似文献
93.
Martin Gotthardt Decio L. Eizirik Henk-Jan Aanstoot Olle Korsgren Dick Mul Frank Martin Marti Boss Tom J. P. Jansen Sanne A. M. van Lith Mijke Buitinga Olof Eriksson Miriam Cnop Maarten Brom 《Diabetologia》2018,61(12):2516-2519
In this issue of Diabetologia, Alavi and Werner ( https://doi.org/10.1007/s00125-018-4676-1) criticise the attempts to use positron emission tomography (PET) for in vivo imaging of pancreatic beta cells, which they consider as ‘futile’. In support of this strong statement, they point out the limitations of PET imaging, which they believe render beta cell mass impossible to estimate using this method. In our view, the Alavi and Werner presentation of the technical limitations of PET imaging does not reflect the current state of the art, which leads them to questionable conclusions towards the feasibility of beta cell imaging using this approach. Here, we put forward arguments in favour of continuing the development of innovative technologies enabling in vivo imaging of pancreatic beta cells and concisely present the current state of the art regarding putative technical limitations of PET imaging. Indeed, far from being a ‘futile’ effort, we demonstrate that beta cell imaging is now closer than ever to becoming a long-awaited clinical reality. 相似文献
94.
95.
Dr. Johanan E. Naschitz M.D. Daniel Yeshurun M.D. Isaac L. Horovitz M.D. Albert Dahaan M.D. Nissim B. Lazaro M.D. Yochanan E. Boss M.D. 《Diseases of the colon and rectum》1986,29(8):521-523
Immunoblastic lymphoma of the colon, complicated by colosplenic fistulization, is reported. It is suggested that ulceration and extensive coagulative necrosis of a bulky large cell lymphoma in the absence of a desmoplastic reaction are the prerequisites for fistula formation. 相似文献
96.
Hinsch E; Ponce AA; Hagele W; Hedrich F; Muller-Schlosser F; Schill WB; Hinsch KD 《Human reproduction (Oxford, England)》1997,12(8):1673-1681
Binding of mammalian spermatozoa to the zona pellucida and the induction of
the acrosome reaction are prerequisites for successful oocyte
fertilization. It has been postulated that xenobiotics that are released in
the environment as well as exposure to pharmaceutical medications may be
associated with reproductive problems in men and wildlife. Examining
physiological and non-physiological effects of particular compounds on
sperm functions requires high quality in-vitro test systems. We established
a reliable combined in-vitro test system with bovine gametes and evaluated
if aliquots of pooled post-thaw spermatozoa are suitable for examining
essential sperm functions. Using cryopreserved semen, the PSA-FITC/Hoechst
33258 staining procedure was applicable to evaluate the acrosomal status
and cell viability. In the bovine hemizona assay, hemizona indices revealed
no differences between cryopreserved and fresh semen. Treatment of
post-thaw bovine spermatozoa with progesterone (1 microM or bovine
follicular fluid (20%) induced the acrosome reaction from 12% (untreated
spermatozoa) to 25% (P < 0.001) and to 22% [corrected] (P < 0.01),
respectively. Incubation of both compounds (1 microM progesterone and 20%
follicular fluid) raised the percentage of acrosome-reacted spermatozoa to
30% (P < 0001). Our results demonstrate that cryopreserved semen can be
integrated into an in-vitro screening model for reproductive toxicology
testing. Pooled, cryopreserved bovine spermatozoa will thus permit
reproducible experiments for clinical and basic science purposes and may
also be applicable for the human system.
相似文献
97.
A Durrer G N Wernly-Chung G Boss B Testa 《Xenobiotica; the fate of foreign compounds in biological systems》1992,22(3):273-282
1. The enzymic hydrolysis of a wide series of nicotinic acid esters was investigated using human and rat plasma, and purified hog liver carboxylesterase, and compared with previously published data from rat liver microsomes. Esterase activities were always found to obey Michaelis-Menten kinetics. 2. Rat liver microsomal and plasma enzyme velocities were six orders of magnitude smaller than those of purified hog liver carboxylesterase, and three orders smaller than human plasma activities, but the Km values were of the same magnitude. 3. The binding of nicotinate esters to human plasma esterases, and purified hog liver carboxylesterase, appears to depend mainly on hydrophobic and steric factors. 相似文献
98.
99.
Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification 总被引:2,自引:0,他引:2
OBJECTIVE: To estimate the associated risk of folate and vitamin B12 (B12) insufficiency, as well as vitamin repletion, following folic acid food fortification. DESIGN: Retrospective cross-sectional study over a 5-year period. SETTING: Two large laboratory databases in the provinces of Ontario and British Columbia, Canada. PARTICIPANTS: Canadian women aged 65 years and over who underwent concomitant clinical testing of serum folate and B12 during the pre-fortification period of January 1996 to December 1997 in Ontario (n = 733) and British Columbia (n = 3839), and in the near-complete post-fortification period of January 1998 to December 2000 in Ontario (n = 4415) and British Columbia (n = 6677). MEASUREMENTS: Geometric mean concentrations of serum folate and B12 before and after folate fortification. Prevalence ratios (PR) were used to separately compare the post- and pre-fortification period rates of folate deficiency (below 6.0 nmol/L); B12 insufficiency (below 150 pmol/L); and B12 insufficiency in combination with supraphysiological concentrations of serum folate (above 45 nmol/L). RESULTS: The mean baseline folate and B12 concentrations were similar between provinces. Using the combined provincial data, the mean serum folate concentration increased by 64% after fortification, from 14.8 to 24.2 nmol/L (p < 0.001). The average B12 concentration increased from 280 to 300 pmol/L, which was more pronounced in BC (p < 0.001) than in Ontario (p = 0.16). The prevalence of folate deficiency declined from 6.3% to 0.88% after fortification (PR 0.14, 95% confidence interval [CI] 0.11-0.18), while the decline in B12 deficiency was less pronounced (PR 0.78, 95% CI 0.71-0.86). CONCLUSIONS: The prevalence of combined B12 insufficiency with supraphysiological concentrations of serum folate increased from 0.09% pre-fortification to 0.61% post (PR 7.0, 95% CI 2.6-19.2).The introduction of folic acid food fortification was associated with a substantial improvement in the folate status of Canadian women aged 65 years and older, paralleled by a large decline in the rate of folate deficiency. Improvement in the B12 status of these women was far less pronounced. Because the prevalence of combined B12 insufficiency and supraphysiological concentrations of serum folate may have increased with folic acid food fortification, consideration should be given to confirming this finding, and possibly, to the addition of B12 to folate fortified foods. 相似文献
100.
Johanan E. Naschitz M.D. Daniel Yeshurun M.D. Elimelech Zuckerman M.D. Emil Arad M.D. Jochanan H. Boss M.D. 《The American journal of gastroenterology》1987,82(11):1186-1189
Hepatomegaly, chronic diarrhea, and weight loss in a middle-aged woman were found to be due to massive hepatic steatosis and adult celiac disease. After she was on a gluten-free diet for 1 yr, improvement in clinical, laboratory, and pathological parameters was witnessed. Massive hepatic steatosis complicating adult celiac disease is an uncommon occurrence, differing from other, more frequently encountered hepatopathies in this disease, insofar as pathogenetic and prognostic aspects are concerned. 相似文献