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51.
The cytoskeleton in Chediak-Higashi syndrome fibroblasts 总被引:2,自引:0,他引:2
The Chediak-Higashi syndrome (CHS) trait is expressed in cultured human skin fibroblasts as an abnormal perinuclear concentration of moderately enlarged lysosomes. The cytoskeleton of CHS fibroblasts appears intact. Microtubules are normal in number and morphology, as assessed by colchicine binding studies, antitubulin immunofluorescence, and electron microscopy. Deformability by shear force is unaltered and microfilaments are abundant. However, CHS lysosomes appear to interact abnormally with the cytoskeleton, since the perinculear aggregation partially disperses after depolymerization of cell microtubules with colchicine. These results suggest that CHS is associated with a defect of either the lysosomal membrane itself or of lysosomal membrane- microtubule interaction. 相似文献
52.
Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia 总被引:4,自引:0,他引:4
Foon KA; Schroff RW; Bunn PA; Mayer D; Abrams PG; Fer M; Ochs J; Bottino GC; Sherwin SA; Carlo DJ 《Blood》1984,64(5):1085-1093
A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody. 相似文献
53.
Epitaxial Ni-Mn-Ga thin films have been extensively investigated, due to their potential applications in magnetic micro-electro-mechanical systems. It has been proposed that the martensitic phase in the <1 1 0>A-oriented film is much more stable than that in the <1 0 0>A-oriented film. Nevertheless, the magnetic properties, microstructural features, and crystal structures of martensite in such films have not been fully revealed. In this work, the <1 1 0>A-oriented Ni51.0Mn27.5Ga21.5 films with different thicknesses were prepared by epitaxially growing on Al2O3(1 1 0) substrate by magnetron sputtering. The characterization by X-ray diffraction technique and transmission electron microscopy revealed that all the Ni51.0Mn27.5Ga21.5 films are of 7M martensite at the ambient temperature, with their Type-I and Type-II twinning interfaces nearly parallel to the substrate surface. 相似文献
54.
Demewoz Haile Kenneth H. Brown Christine M. McDonald Hanqi Luo Michael Jarvis Ismael Teta Alex Ndjebayi Guintang Assiene Jules Martial Stephen A. Vosti Reina Engle-Stone 《Nutrients》2022,14(4)
Nutrient reference values (NRVs) for zinc set by several expert groups differ widely and may affect the predicted prevalence of inadequate zinc intake. We examined this possibility using NRVs published by four different authorities and nationally representative dietary intake data collected among children aged 12–59 months and women in Cameroon. Usual zinc intake was estimated from 24 h recall data using the National Cancer Institute method. Prevalences of total zinc intake below the dietary requirement and of “absorbable zinc intake” below the physiological requirement were estimated using NRVs published by the World Health Organization (WHO), US Institute of Medicine (IOM), International Zinc Nutrition Consultative Group (IZiNCG), and European Food Safety Authority (EFSA). The prevalence of inadequate zinc intake ranged from 10% (IZiNCG—physiological requirement, 95% CI 7–13%) to 81% (EFSA—physiological requirement, 95% CI 78–84%) among children and 9% (WHO—physiological requirement, 95% CI 8–11.0%) to 94% (IOM—physiological requirement, 95% CI 92–95%) among women These differences in the prevalence of inadequate intake translated into sizeable differences in the predicted benefit and cost-effectiveness of zinc fortification programs. Depending on the NRVs applied, assessments differ regarding the need for and design of zinc fortification programs. Efforts are needed to harmonize NRVs for zinc. 相似文献
55.
EG Burden RW Walker DJ Ferguson AMF Goubran JR Howell JB John F Khan JS McGrath JP Evans 《Annals of the Royal College of Surgeons of England》2021,103(3):173
IntroductionWith the emergence of the COVID-19 pandemic, all elective surgery was temporarily suspended in the UK, allowing for diversion of resource to manage the anticipated surge of critically unwell patients. Continuing to deliver time-critical surgical care is important to avoid excess morbidity and mortality from pathologies unrelated to COVID-19. We describe the implementation and short-term surgical outcomes from a system to deliver time-critical elective surgical care to patients during the COVID-19 pandemic.Materials and methodsA protocol for the prioritisation and safe delivery of time-critical surgery at a COVID-19 ‘clean’ site was implemented at the Nuffield Health Exeter Hospital, an independent sector hospital in the southwest of England. Outcomes to 30 days postoperatively were recorded, including unplanned admissions after daycase surgery, readmissions and complications, as well as the incidence of perioperative COVID-19 infection in patients and staff.ResultsA total of 128 surgical procedures were performed during a 31-day period by a range of specialties including breast, plastics, urology, gynaecology, vascular and cardiology. There was one unplanned admission and and two readmissions. Six complications were identified, and all were Clavien-Dindo grade 1 or 2. All 128 patients had preoperative COVID-19 swabs, one of which was positive and the patient had their surgery delayed. Ten patients were tested for COVID-19 postoperatively, with none testing positive.ConclusionThis study has demonstrated the implementation of a safe system for delivery of time-critical elective surgical care at a COVID-19 clean site. Other healthcare providers may benefit from implementation of similar methodology as hospitals plan to restart elective surgery. 相似文献
56.
Samir Gupta MD MDCS AGAF Balambal Bharti MBBS MPH PhD Dennis J. Ahnen MD Daniel D. Buchanan PhD Iona C. Cheng PhD MPH Michelle Cotterchio PhD Jane C. Figueiredo PhD Steven J. Gallinger MD MSc Robert W. Haile DrPH MPH Mark A. Jenkins PhD Noralane M. Lindor MD Finlay A. Macrae MD AGAF Loïc Le Marchand MD PhD Polly A. Newcomb PhD MPH Stephen N. Thibodeau PhD Aung Ko Win MBBS MPH PhD Maria Elena Martinez PhD 《Cancer》2020,126(13):3013-3020
57.
Scott D. Nash Tigist Astale Andrew W. Nute Danaya Bethea Ambahun Chernet Eshetu Sata Mulat Zerihun Demelash Gessese Gedefaw Ayenew Zebene Ayele Berhanu Melak Mahteme Haile Taye Zeru Zerihun Tadesse Benjamin F. Arnold Elizabeth Kelly Callahan Diana L. Martin 《The American journal of tropical medicine and hygiene》2021,104(1):207
58.
Åke Borg Robert W. Haile Kathleen E. Malone Marinela Capanu Ahn Diep Therese Törngren Sharon Teraoka Colin B. Begg Duncan C. Thomas Patrick Concannon Lene Mellemkjaer Leslie Bernstein Lina Tellhed Shanyan Xue Eric R. Olson Xiaolin Liang Jessica Dolle Anne‐Lise Børresen‐Dale Jonine L. Bernstein 《Human mutation》2010,31(3):E1200-E1240
BRCA1 and BRCA2 screening in women at high‐risk of breast cancer results in the identification of both unambiguously defined deleterious mutations and sequence variants of unknown clinical significance (VUS). We examined a population‐based sample of young women with contralateral breast cancer (CBC, n=705) or unilateral breast cancer (UBC, n=1398). We identified 470 unique sequence variants, of which 113 were deleterious mutations. The remaining 357 VUS comprised 185 unique missense changes, 60% were observed only once, while 3% occurred with a frequency of >10%. Deleterious mutations occurred three times more often in women with CBC (15.3%) than in women with UBC (5.2%), whereas combined, VUS were observed in similar frequencies in women with CBC and UBC. A protein alignment algorithm defined 16 rare VUS, occurring at highly conserved residues and/or conferring a considerable biochemical difference, the majority located in the BRCA2 DNA‐binding domain. We confirm a multiplicity of BRCA1 and BRCA2 VUS that occur at a wide range of allele frequencies. Although some VUS inflict chemical differences at conserved residues, suggesting a deleterious effect, the majority are not associated with an increased risk of CBC. © 2010 Wiley‐Liss, Inc. 相似文献
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