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61.
Moyle GJ DeJesus E Cahn P Castillo SA Zhao H Gordon DN Craig C Scott TR;Ziagen Once-Daily in Antiretroviral Combination Therapy 《Journal of acquired immune deficiency syndromes (1999)》2005,38(4):417-425
The long intracellular half-life of abacavir (ABC) supports its once-daily use, and this would be expected to simplify treatment if ABC could be given as part of a complete once-daily regimen. A randomized double-blind clinical trial compared the efficacy and safety of 600 mg of ABC administered once daily (n = 384) versus 300 mg of ABC administered twice daily (n = 386) in combination with 300 mg of lamivudine (3TC) and 600 mg of efavirenz (EFV) administered once daily in antiretroviral-naive patients over 48 weeks. The baseline median plasma HIV-1 RNA level was 4.89 log10 copies/mL (44% with viral load >100,000 copies/mL), and the median CD4 cell count was 262 cells/mm. ABC administered once daily was non-inferior to the twice-daily regimen, with 66% and 68% of patients in these respective treatment arms achieving a confirmed plasma HIV-1 RNA level <50 copies/mL (95% confidence interval: -8.4%, 4.9%). The ABC once-daily and twice-daily regimens were similar with respect to infrequency of virologic failure (10% vs. 8%), emergence of resistance mutations, CD4 cell increases from baseline (median, 188 vs. 200 cells/mm), safety profile, and incidence of ABC-related hypersensitivity reactions (9% vs. 7%). ABC administered once daily in combination with 3TC and EFV administered once daily was non-inferior to the ABC twice-daily dosing schedule when combined with 3TC and EFV over 48 weeks. 相似文献
62.
骨髓源间充质干细胞在异基因小鼠免疫器官内的分布及其免疫功能调节作用 总被引:20,自引:2,他引:20
目的:探讨骨髓源间充质干细胞(Bone marrow mesenchymal stem cells,BMSC)在异基因小鼠免疫器官内的分布及其免疫调节作用。方法:以CM-Dil荧光染料示踪BMSC的体内分布情况,并辅以PCR检测Y染色体的方法进一步鉴定;体外实验采用MTT法、ELISA和FACS等方法检测BMSC的免疫调节作用。结果:BMSC可进入并较长期(30天)存在于异基因小鼠免疫器官内;在体外,BALB/C小鼠的BMSC对由ConA诱导的BALB/C和C57BL/6(B6)和BXSB小鼠的T细胞增殖均有抑制作用;而对前两种小鼠由12S诱导的B细胞增殖和分泌k方面表现为促进作用,对BXSB小鼠由IPS诱导的B细胞增殖和k分泌有抑制作用。BALB/C小鼠的BMSC对BALB/C和B6小鼠由ConA诱导的IL-4生成细胞的数量无明显影响,却可降低由ConA诱导的两种品系小鼠的IFN-γ生成细胞的数量;但对于BXSB小鼠却不同,BALB/C的BMSC可降低由ConA诱导的BXSB小鼠的IL-4生成细胞的数量,而提高由ConA诱导的IFN-γ生成细胞的数量。结论:异基因BMSC不但可进入受体的免疫器官,且可较长期(30天)存在;另外,BMSC对同基因正常、异基因正常和异基因自身免疫病的个体均有一定程度的免疫调节作用。 相似文献
63.
Heinrich Büssow und On the Histo-and Cytogenesis of the Tapetum lucidum cellulosum of the Cat A Light Electron Microscope Study 《Anatomy and embryology》1974,146(2):141-156
Zusammenfassung Die postnatale Entwicklung des Tapetum lucidum cellulosum der Katze wird mit licht- und elektronenmikroskopischen Methoden untersucht. Bereits am ersten postnatalen Tag sind im Bereich des prospektiven Tapetum zwei Zellarten voneinander zu unterscheiden: 1. mesenchymale Bindegewebszellen und 2. prospektive Tapetumzellen, die durch elektronendichte Tapetumstäbchen gekennzeichnet sind. Die Mesenchymzellen unterteilen als parallel zur Retinaoberfläche ausgebreitete Zellplatten in der Choriodea am hinteren Augenpol den weiten extracellulären Raum in 20–25 etwa 5 m hohe Schichten. Die Tapetumzellen liegen zwischen den Mesenchymzellplatten und wachsen im Verlaufe der ersten vier postnatalen Wochen innerhalb der Schichten in die Breite, bis sie den extracellulären Raum vollständig ausfüllen und als polygonale Zellen direkt aneinander grenzen. Im weiteren Verlauf der Entwicklung werden die Mesenchymzellplatten rückgebildet, so daß bei der adulten Katze die Tapetumzellschichten direkt übereinander liegen und nur von Netzen elastischer und kollagener Fasern getrennt sind.Die von einer Elementarmembran umgebenen Tapetumstäbchen enthalten einen elektronendichten, in den ersten postnatalen Wochen mit einer Periode von 100 Å quergestreiften Kern. Zunächst nehmen sie an Zahl und Länge zu und füllen am Ende der vierten postnatalen Woche, zu Bündeln von parallel verlaufenden Stäbchen geordnet, das Cytoplasma der Tapetumzellen. Dann nehmen die Tapetumstäbchen an Dicke zu, und ihre Querstreifung wird von einem elektronendichten Material überlagert. Die Entwicklung der Tapetumstäbchen hat eine starke Ähnlichkeit mit der in der Literatur beschriebenen Entwicklung von Melanosomen in Melanocyten. Das Tapetum lucidum cellulosum wird als ein dichter Verband hochdifferenzierter extrakutaner Melanocyten angesehen.
Summary The postnatal development of the tapetum lucidum cellulosum of the cat was studied by light and electron microscopy. Already by the first postnatal day two cell types can be distinguished in the prospective tapeta area: 1. mesenchymal cells and 2. prospective tapetal cells, characterized by electron dense, membrane bound, rod-like inclusions. The flattened mesenchymal elements form 20–25 separate layers of cells, which are arranged parallel to the surface of the retina, subdividing the extracellular space of the chorioidea at the posterior pole of the eye into 5 m high compartments. These compartments contain the tapetal cells which enlarge (in their longitudinal axis) during the first four weeks post partum until they occupy the extracellular space almost completely. At this stage, the tapetal cells are polygonal in shape and closely attached to each other. During the subsequent period of development there is a gradual involution of the mesenchymal cell plates. Thus, in adult cats the individual layers of tapetal cells are only separated from each other by networks of collagen and elastic fibers.The tapetal rods are bound by unit membranes and contain an electron dense core which, during the early postnatal weeks, exhibits a periodic cross-striation (100 Å). The tapetal rods increase in number and length during the first four weeks post partum; by the end of the fourth week, they occupy the whole cytoplasm of the tapetal cells. Parallelly arranged rods are grouped into individual bundles coursing inside the cytoplasm in different directions. Thereafter, the tapetal rods increase in thickness and their cross-striation becomes obscured by an electron dense material. This development of the tapetal rods closely resembles that of melanosomes.Thus the tapetum lucidum cellulosum can be regarded as a compact tissue made up of modified extracutaneous melanocytes.
Auszugsweise vorgetragen auf der 69. Versammlung der Anatomischen Gesellschaft in Kiel, Juni 1974. 相似文献
64.
Kristiansen OP Karlsen AE Larsen ZM Johannesen J Pociot F Mandrup-Poulsen T;Danish IDDM Epidemiology Genetics Group Danish Study Group of IDDM in Childhood 《Scandinavian journal of immunology》2004,59(6):582-591
CD4 is a candidate gene in autoimmune diseases, including Type 1 diabetes mellitus (T1DM), because the CD4 receptor is crucial for appropriate antigen responses of CD4(+) T cells. We previously found linkage between a CD4-1188(TTTTC)(5-14) promoter polymorphism and T1DM. In the present study, we screened the human CD4 promoter for mutations and identified three frequent single nucleotide polymorphisms (SNPs): CD4-181C/G, CD4-521C/G and CD4-1050T/C. The SNPs are in strong linkage disequilibrium (LD) and association with the CD4-1188(TTTTC)(5-14) alleles, and we observed nine CD4 promoter haplotypes, of which four are frequent. We genotyped the SNPs in 253 Danish T1DM families (1129 individuals) and found evidence for linkage and association of a CD4 (A4(-1188)T(-1050)G(-521)C(-181)) haplotype to T1DM. In reporter studies, we show that (1) the T1DM-associated CD4 haplotype encodes high constitutive promoter activity and (2) the CD4-181G variant encodes higher stimulated promoter activity than the CD4-181C variant. This difference is in part neutralized in the frequently occurring CD4 promoter haplotypes by the more upstream genetic variants. Thus, we report functional impact of a novel CD4-181C/G SNP on stimulated CD4 promoter activity and the identification of a novel CD4 haplotype with high constitutive promoter activity that is linked and associated with T1DM. 相似文献
65.
Schüpbach J Böni J Bisset LR Tomasik Z Fischer M Günthard HF Ledergerber B Opravil M;Swiss HIV Cohort Study 《Journal of acquired immune deficiency syndromes (1999)》2003,33(3):292-299
An HIV-1 p24 antigen test involving signal amplification-boosted ELISA of heat-denatured plasma was evaluated prospectively in 55 patients whose viral RNA in plasma had previously been suppressed for at least 6 months under antiretroviral combination therapy. During a median follow-up of 504 days, CD4 counts increased by a median of 62 cells per year. By univariate and multivariate linear regression analysis, the level of p24 antigen as expressed by the absorbance/cutoff ratio was a significant inverse correlate of both the CD4 count in a sample (p =.013) and its annual change in a patient (p <.0001). The p24 antigen retained significance even among 48 individuals whose HIV-1 RNA, apart from occasional blips, remained below 400 copies/mL. Batch-wise retesting of 70 samples from 5 such patients with a further improved procedure showed measurable p24 antigen in all but 1 sample and an inverse correlation with both the CD4 count (p =.0331) and percentage (p <.0001), thus confirming the prospectively generated data. Comparison of p24 antigen and HIV-1 RNA concentrations indicate that the p24 antigen detected in these samples is not associated with viral RNA-containing particles and may originate from other compartments of virus expression. 相似文献
66.
Amir?R?RazaviEmail author Hans?Gill Olle?St?l Marie?Sundquist Sten?Thorstenson Hans??hlfeldt Nosrat?Shahsavar the South-East Swedish Breast Cancer Study Group 《BMC medical informatics and decision making》2005,5(1):29
Background
A common approach in exploring register data is to find relationships between outcomes and predictors by using multiple regression analysis (MRA). If there is more than one outcome variable, the analysis must then be repeated, and the results combined in some arbitrary fashion. In contrast, Canonical Correlation Analysis (CCA) has the ability to analyze multiple outcomes at the same time. 相似文献67.
68.
Torti C Quiros-Roldan E Monno L Patroni A Saracino A Angarano G Tinelli C Lo Caputo S Tirelli V Mazzotta F Carosi G;MASTER Cohort GenPheRex Study Group;MASTER Cohort PhenGen Study Group 《Journal of medical virology》2004,74(1):29-33
This study aimed at identifying HIV-1 protease amino acid changes associated with protease inhibitor (PI) exposure and susceptibility. New amino acid substitutions were correlated with the number of experienced PIs, reaching statistical significance only for those at positions 3, 44, and 74. The correspondence multivariate model demonstrated that > or =3 experienced PIs and substitutions or mutations at positions 3, 46, 54, 73, 74, and 84 were correlated with PI cross-resistance, including resistance for lopinavir and amprenavir in this cohort of patients who were naive for these drugs. 相似文献
69.
Xiao Liu Xiaohong Meng Lizhu Yang Yanling Long Yu Fujinami‐Yokokawa Jiayun Ren Toshihide Kurihara Kazuo Tsubota Kazushige Tsunoda Kaoru Fujinami Shiying Li East Asia Inherited Retinal Disease Society Study Group 《American journal of medical genetics. Part C, Seminars in medical genetics》2020,184(3):694-707
Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4 variants. Forty‐two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full‐field electroretinography (objective function), were performed. Next‐generation sequencing (target/whole exome) and direct sequencing were conducted. Genotype grouping was performed based on the presence of deleterious variants. The median age of onset/age was 10.0 (5–52)/29.5 (12–72) years, and the median visual acuity in the right/left eye was 1.30 (0.15–2.28)/1.30 (0.15–2.28) in the logarithm of the minimum angle of resolution unit. Ten patients (10/38, 27.0%) showed confined macular dysfunction, and 27 (27/37, 73.7%) had generalized retinal dysfunction. Fifty‐eight pathogenic/likely pathogenic ABCA4 variants, including 14 novel variants, were identified. Eight patients (8/35, 22.8%) harbored multiple deleterious variants, and 17 (17/35, 48.6%) had a single deleterious variant. Significant associations were revealed between subjective functional, retinal imaging, and objective functional groups, identifying a significant genotype–phenotype association. This study illustrates a large phenotypic/genotypic spectrum in a large well‐characterized STGD1 cohort. A distinct genetic background of the Chinese population from the Caucasian population was identified; meanwhile, a genotype–phenotype association was similarly represented. 相似文献
70.
Oral Anticoagulation Monitoring Study Group 《American journal of clinical pathology》2001,115(2):288-296
We enrolled 386 subjects in a multicenter study of a point-of-care (POC) prothrombin time (PT) testing device. POC tests were performed by health care professionals using venous and finger-stick specimens and by patients using finger-stick specimens. Venous blood also was analyzed in the local hospital laboratory and a national reference laboratory. Accurate POC results were obtained by professionals using both types of specimens. Patients' results were equivalent to those of professionals. The identification of the patient's therapeutic status based on the International Normalized Ratio (INR) was equivalent for POC and local hospital laboratory PT results; 75% of local laboratory results and 77% of POC results were within 0.4 INR of reference laboratory results, while 93% of either system (POC or local laboratory) were within 0.7 INR. Patients overwhelmingly reported satisfaction with the self-test, including the finger stick and device operation. The INR from the POC device is clinically equivalent to the laboratory INR for assessment of anticoagulation status and management decisions in professional and self-testing environments. Patients can learn to perform accurate PT testing, and POC PT testing is feasible in patients' homes. 相似文献