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21.
Arbour NC; Zlotogora J; Knowlton RG; Merin S; Rosenmann A; Kanis AB; Rokhlina T; Stone EM; Sheffield VC 《Human molecular genetics》1997,6(5):689-694
Achromatopsia is an autosomal recessive disease of the retina,
characterized clinically by an inability to distinguish colors, impaired
visual acuity, nystagmus and photophobia. A genome-wide search for linkage
was performed using an inbred Jewish kindred from Iran. To facilitate the
genome-wide search, we utilized a DNA pooling strategy which takes
advantage of the likelihood that the disease in this inbred kindred is
inherited by all affected individuals from a common founder. Equal molar
amounts of DNA from all affected individuals were pooled and used as the
PCR template for short tandem repeat polymorphic markers (STRPs). Pooled
DNA from unaffected members of the kindred was used as a control. A
reduction in the number of alleles in the affected versus control pool was
observed at several loci. Upon genotyping of individual family members,
significant linkage was established between the disease phenotype and
markers localized on chromosome 2. The highest LOD score observed was 5.4
(theta = 0). When four additional small unrelated families were genotyped,
the combined peak LOD score was 8.2. Analysis of recombinant chromosomes
revealed that the disease gene lies within a 30 cM interval which spans the
centromere. Additional fine-mapping studies identified a region of
homozygosity in all affected individuals, narrowing the region to 14 cM. A
candidate gene for achromatopsia was excluded from this disease interval by
radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an
essential first step in the identification of the disease-causing gene.
相似文献
22.
23.
Krug A Towarowski A Britsch S Rothenfusser S Hornung V Bals R Giese T Engelmann H Endres S Krieg AM Hartmann G 《European journal of immunology》2001,31(10):3026-3037
Human plasmacytoid dendritic cells (DC) (PDC, CD123+) and myeloid DC (MDC, CD11c+) may be able to discriminate between distinct classes of microbial molecules based on a different pattern of Toll-like receptor (TLR) expression. TLR1-TLR9 were examined in purified PDC and MDC. TLR9, which is critically involved in the recognition of CpG motifs in mice, was present in PDC but not in MDC. TLR4, which is required for the response to LPS, was selectively expressed on MDC. Consistent with TLR expression, PDC were susceptible to stimulation by CpG oligodeoxynucleotide (ODN) but not by LPS, while MDC responded to LPS but not to CpG ODN. In PDC, CpG ODN supported survival, activation (CD80, CD86, CD40, MHC class II), chemokine production (IL-8, IP-10) and maturation (CD83). CD40 ligand (CD40L) and CpG ODN synergized to activate PDC and to stimulate the production of IFN-alpha and IL-12 including bioactive IL-12 p70. Previous incubation of PDC with IL-3 decreased the amount of CpG-induced IFN-alpha and shifted the cytokine response in favor of IL-12. CpG ODN-activated PDC showed an increased ability to stimulate proliferation of naive allogeneic CD4 T cells, butTh1 polarization of developing T cells required simultaneous activation of PDC by CD40 ligation and CpG ODN. CpG ODN-stimulated PDC expressed CCR7, which mediates homing to lymph nodes. In conclusion, our studies reveal that IL-12 p70 production by PDC is under strict control of two signals, an adequate exogenous microbial stimulus such as CpG ODN, and CD40L provided endogenously by activated T cells. Thus, CpG ODN acts as an enhancer of T cell help, while T cell-controlled restriction to foreign antigens is maintained. 相似文献
24.
To understand the mechanisms of glaucoma in retinopathy of prematurity (ROP), anterior segment evaluation is essential. The authors prospectively examined the anterior segment of 27 eyes of 17 premature infants with stages IV and V ROP. Twenty-six eyes received no previous surgery or treatment. Schi?tz and applanation tonometry were performed. Structural evaluation of each anterior segment was conducted by biomicroscopy and Koeppe gonioscopy. In the 26 eyes, angle closure of greater than 180 degrees was noted in 3 (12%). The authors noted prominent Schwalbe's line in 4 eyes (15%), high iris convexity in 15 (58%), hypopigmentation of the iris root in 19 (73%), translucent matrix in the angles ("Barkan's-type" membrane) in 18 (69%), posterior synechiae in 16 (62%), visible iris or angle vessels in 12 (46%), and pigment clumping in the angle recess in 12 (46%). This study identified structural abnormalities in the anterior segment of ROP infants, including pathologic changes and anatomic features that could have a developmental origin. 相似文献
25.
PURPOSE: At present the mechanisms of ischemic or hypoxic tolerance are not fully understood at the cellular level. METHODS: In order to further characterize the effects of conditioning hypoxia on the synaptic transmission in the hippocampal area CA1, rats were exposed to a moderate normobaric hypoxia for 8 h. Transverse hippocampal slices were prepared 1, 7 or 14 days after this conditioning hypoxia and evoked field potentials were recorded in the CA 1 region upon stimulation of the Schaffer collaterals before, during and up to 4 h after ischemia in vitro (hypoxia and reduced glucose). RESULTS and CONCLUSIONS: The time to disappearance of the evoked potential during ischemia was significantly prolonged after seven, but not after one or 14 days in slices taken from conditioned animals. In addition the input/output (I/O) curves of evoked potentials were not altered 4 h after the ischemia. In contrast, the time to disappearance of the evoked potentials was shorter and the I/O curves were diminished in slices from control animals. Possible mechanisms of the protective effect are discussed. 相似文献
26.
Marc J. Claeys Frank E. Rademakers Chris J. Vrints Bruno Krug Johan M. Bosmans Viviane Conraads Leo L. Bossaert Jo P. Snoeck Pierre P. Blockx 《European journal of nuclear medicine and molecular imaging》1996,23(7):748-755
Rest technetium-99m sestamibi single-photon emission tomography (SPET) has been shown to under-estimate viability in some patients with chronic ischaemic myocardial dysfunction. The present study was designed to appraise the value of99mTc-sestamibi as a viability tracer in patients with a recent myocardial infarction and to determine factors that might influence its accuracy in assessing infarct size. Therefore, rest99mTc-sestamibi SPET, low-dose dobutamines stress echocardiography and quantitative coronary angiography were performed in 51 patients with a recent myocardial infarction. Perfusion activity and regional wall motion were scored semi-quantitatively using the same segmental division of the left ventricle. Assessment of99mTc-sestamibi uptake as a marker of viability was performed by comparing a binary uptake score (viable=>50% vs necrotic =50% of the maximal tracer activity) with a binary wall motion classification during low-dose dobutamine infusion (viable=normal/hypokinetic vs necrotic=akinetic/dyskinetic). Infarct size, expressed as the number of segments with evidence of necrotic tissue, was significantly greater in the scintigraphic study than in the echocardiographic study (2.8±1.5 vs 2.2±1.3,P=0.006). This overestimation of infarct size by99mTc-sestamibi was present only in patients with a severe infarct-related stenosis (% diameter stenosis 65%–100%) and particularly those with late reperfusion therapy (time delay 180 min). In patients without a severe infarct-related stenosis,99mTc-sestamibi was able to accurately distinguish viable from necrotic segments. Thus, rest99mTc-sestamibi scintigraphy early after acute myocardial infarction may underestimate residual viability within the infarct region, particularly in patients with low flow state coronary anatomy, as a result of a severe infarct-related stenosis and/or late reperfusion therapy.This paper was presented in part at the European Nuclear Medicine Congress, Brussels, Belgium, August 1995 相似文献
27.
Lee M Krug Christopher G Azzoli Mark G Kris Vincent A Miller Nushmia Z Khokhar William Tong Michelle S Ginsberg Ennapadam Venkatraman Leslie Tyson Barbara Pizzo Valerie Baez Kenneth K Ng F M Sirotnak 《Clinical cancer research》2003,9(6):2072-2078
PURPOSE: 10-propargyl-10-deazaaminopterin (PDX) has superior antitumor efficacy in mouse xenograft models, likely attributable to increased uptake by the RFC-1 folate transporter and greater intracellular polyglutamylation. In a previous Phase I trial, stomatitis was the dose-limiting (and only clinically significant) toxicity of PDX. The recommended Phase II dose was 150 mg/m(2) i.v. every 2 weeks. Responses observed in patients with non-small cell lung cancer (NSCLC) in the Phase I trial prompted this Phase II trial. EXPERIMENTAL DESIGN: Patients had stage IIIB or IV NSCLC and either no previous chemotherapy or progression after initial response or stable disease to one previous chemotherapy regimen. Initially, PDX was administered at a dose of 150 mg/m(2) every 2 weeks. However, to decrease the frequency of stomatitis, the last 10 patients were treated at a dose of 135 mg/m(2). We planned to correlate PDX effects with folate and homocysteine levels and the expression of genes associated with folate transport and polyglutamylation. RESULTS: Thirty-nine patients were enrolled, 38 of whom were evaluable for response. Four patients had confirmed, major objective responses (10% based on intent to treat, 95% confidence interval 3-25) lasting 4, 9, 12, and 15 months. Twelve patients (31%) had stable disease. The median survival was 13.5 months. The predicted 1- and 2-year survival rates were 56 and 36%, respectively. Two patients (5%) suffered grade 4 stomatitis, and 6 (15%) had grade 3. No clinically significant myelosuppression occurred. No correlation between homocysteine or serum folate levels and severity of stomatitis was observed. Area under the curve (calculated using a limited sampling model) correlated with mucositis grade. A trend was noted between folate transporter expression and treatment effect. CONCLUSIONS: The broad applicability of this new antifolate with limited toxicity and proven efficacy in NSCLC encourage further development of this compound. Several trials are now underway combining PDX with other chemotherapeutic agents and testing its efficacy in other cancers. 相似文献
28.
Giddens JB Krug SK Tsang RC Guo S Miodovnik M Prada JA 《Journal of the American Dietetic Association》2000,100(11):1334-1340
OBJECTIVE: To examine the dietary intake of pregnant adolescents during the second and third trimester of pregnancy, and to compare their nutrient intake with that of pregnant adults. DESIGN: Two 7-day food records (14 days) from subjects participating in a larger randomized clinical calcium trial: the first at 19 to 21 weeks and the second between 29 and 31 weeks gestation. Intake of energy and selected nutrients were calculated and compared with dietary standards. SUBJECTS/SETTING: Fifty-nine pregnant adolescents and 97 pregnant adults recruited from prenatal clinics at a metropolitan university hospital. STATISTICAL ANALYSES: Two sample t tests, equality of variances, and repeated measures (analysis of variance). RESULTS: There was no difference in mean nutrient intakes between the second and third trimesters. Using two 7-day food records, we found mean intakes for energy, iron, zinc, calcium, magnesium, folate, and vitamins D and E to be below recommended standards in both groups. Other nutrients examined met or exceeded reference values. Total daily intakes for energy and 11 nutrients were significantly higher in the adolescent compared to the adult diets (P < .05). These differences were not evident when nutrient values were corrected for energy, indicating that increased energy intake in the teen-aged population was contributed by nutrient-dense foods. APPLICATIONS: This study indicates the need for continued dietary monitoring of pregnant adolescents and pregnant adults, including nutrition guidance that stresses food sources of calcium, magnesium, zinc, iron, fiber, folate, and vitamins D and E, the nutrients found deficient in their diets. 相似文献
29.
Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver 总被引:2,自引:0,他引:2
Dichloroacetic acid (DCA) is a chlorination byproduct found in finished
drinking water. When administered in drinking water this chemical has been
shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over
the animal's lifetime. In this study, we investigated whether mutant
frequencies were increased in mouse liver using treatment protocols that
yielded significant tumor induction. DCA was administered continuously at
either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice
harboring the bacterial lacI gene. Groups of five or six animals were
killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of
treatment, there was no significant difference in mutant frequency between
the treated and control animals at either dose level. At 60 weeks, mice
treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency
over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60
weeks had a 2.3-fold increase in mutant frequency over the concurrent
controls (P = 0.002). The mutation spectrum recovered from mice treated
with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%)
and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T
transitions comprised 53.19% of the recovered mutants among control
animals. Although only 19.15% of mutations among the controls were at T:A
sites, 32.79% of the mutations from DCA-treated animals were at T:A sites.
This is consistent with the previous observation that the proportion of
mutations at T:A sites in codon 61 of the H-ras gene was increased in
DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates
DCA-associated mutagenicity in the mouse liver under conditions in which
DCA produces hepatic tumors.
相似文献
30.
Female sterilisation is an important component of National Family Welfare Programme. The target group is best motivated during the puerperium for such a procedure. However laparoscopic sterilisation which has got some distinct advantages, is not technically feasible at this time. The authors have used a technique where the advantages of cosmetic appearance, reduced post operative morbidity and reversibility can be conferred on the puerperal women.After trying out the method individually in some cases, a formal case control study design has been made and an evaluation study has been performed in 122 cases. The technique has been found to be cosmetically more acceptable, both at clientele and peer evaluation levels (p<0.001). Though all the four parameters of post operative morbidity have shown better results for the technique evaluated as against the conventional technique, statistical significance has been achieved in two of the parameters (p<0.05).KEY WORDS: Cosmetics, Female sterilisation, Post operative morbidity 相似文献