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61.
Louise R Rodino-Klapac Paul ML Janssen Chrystal L Montgomery Brian D Coley Louis G Chicoine K Reed Clark Jerry R Mendell 《Journal of translational medicine》2007,5(1):45-11
Background
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder with monogenic mutations setting the stage for successful gene therapy treatment. We have completed a study that directly deals with the following key issues that can be directly adapted to a gene therapy clinical trial using rAAV considering the following criteria: 1) A regional vascular delivery approach that will protect the patient from widespread dissemination of virus; 2) an approach to potentially facilitate safe passage of the virus for efficient skeletal muscle transduction; 3) the use of viral doses to accommodate current limitations imposed by vector production methods; 4) and at the same time, achieve a clinically meaningful outcome by transducing multiple muscles in the lower limb to prolong ambulation. 相似文献62.
Modulating bone cells response onto starch-based biomaterials by surface plasma treatment and protein adsorption 总被引:2,自引:0,他引:2
Alves CM Yang Y Carnes DL Ong JL Sylvia VL Dean DD Agrawal CM Reis RL 《Biomaterials》2007,28(2):307-315
The effect of oxygen-based radio frequency glow discharge (rfGD) on the surface of different starch-based biomaterials (SBB) and the influence of proteins adsorption on modulating bone-cells behavior was studied. Bovine serum albumin, fibronectin and vitronectin were used in single and complex protein systems. RfGD-treated surfaces showed to increase in hydrophilicity and surface energy when compared to non-modified SBB. Biodegradable polymeric blends of cornstarch with cellulose acetate (SCA; 50/50wt%), ethylene vinyl alcohol (SEVA-C; 50/50wt%) and polycaprolactone (SPCL; 30/70wt%) were studied. SCA and SCA reinforced with 10% hydroxyapatite (HA) showed the highest degree of modification as result of the rfGD treatment. Protein and control solutions were used to incubate with the characterized SBB and, following this, MG63 osteoblast-like osteosarcoma cells were seeded over the surfaces. Cell adhesion and proliferation onto SCA was found to be enhanced for non-treated surfaces and on SCA+10%HA no alteration was brought up by the plasma modification. Onto SCA surfaces, BSA, FN and VN single solutions improved cell adhesion, and this same effect was found upscaled for ternary systems. In addition, plasma treated SEVA-C directed an increase in both adhesion and proliferation comparing to non-treated surfaces. Even though adhesion onto treated and untreated SPCL was quite similar, plasma modification clearly promoted MG63 cells proliferation. Regarding MG63 cells morphology it was shown that onto SEVA-C surfaces the variation of cell shape was primarily defined by the protein system, while onto SPCL it was mainly affected by the plasma treatment. 相似文献
63.
PS Spencer K Vandemaele M Richer VS Palmer S Chungong M Anker Y Ayana ML Opoka BN Klaucke A Quarello JK Tumwine 《African health sciences》2013,13(2):183-204
Background
Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.Objective
To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.Methods
Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.Results
Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.Conclusion
Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food. 相似文献64.
Ashok Ramasubramanian Quynh B. Chu‐Lagraff Takashi Buma Kevin T. Chico Meagan E. Carnes Kyra R. Burnett Sarah A. Bradner Shaun S. Gordon 《Developmental dynamics》2013,242(7):801-816
Background: Looping is a crucial phase during heart development when the initially straight heart tube is transformed into a shape that more closely resembles the mature heart. Although the genetic and biochemical pathways of cardiac looping have been well studied, the biophysical mechanisms that actually effect the looping process remain poorly understood. Using a combined experimental (chick embryo) and computational (finite element modeling) approach, we study the forces driving early s‐looping when the primitive ventricle moves to its definitive position inferior to the common atrium. Results: New results from our study indicate that the primitive heart has no intrinsic ability to form an s‐loop and that extrinsic forces are necessary to effect early s‐looping. They support previous studies that established an important role for cervical flexure in causing early cardiac s‐looping. Our results also show that forces applied by the splanchnopleure cannot be ignored during early s‐looping and shed light on the role of cardiac jelly. Using available experimental data and computer modeling, we successfully developed and tested a hypothesis for the force mechanisms driving s‐loop formation. Conclusions: Forces external to the primitive heart tube are necessary in the later stages of cardiac looping. Experimental and model results support our proposed hypothesis for forces driving early s‐looping. Developmental Dynamics 242:801–816, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
65.
66.
Rapid decrease in tuberculin skin test reactivity at preschool age after newborn vaccination 总被引:2,自引:0,他引:2
L Kröger ML Katila M Korppi E Brander M Pietikäinen 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(9):678-681
A study of tuberculin sensitivity was performed in 353 children aged 4-6 years, all vaccinated at birth with British BCG vaccine. Significant waning of tuberculin reactions with increasing age was found (p < 0.05). In the age group < 4.5 years, the mean tuberculin reaction was 6.6 mm, in the age group 4.5-5.5 years 5.2 mm and in the age group of > 5.5 years 3.5 mm. The number of children with positive reactions (> or = 5 mm) was 165 (40%) and those with strong reactions (> or = 10 mm) 49 (14%). None of the latter children had active tuberculosis during a follow-up period of 12 months. Eighty-three (24%) of the children had no reaction. The children who had been revaccinated with the MPR vaccine against measles, rubella and parotitis (n = 31) had significantly larger tuberculin reactions than the non-revaccinated children. Atopic dermatitis or infections during the preceding six months did not have any significant influence on reaction sizes. Our results demonstrate that the variation in size of tuberculin reactions after BCG vaccination at birth is large. We conclude that tuberculin sensitivity wanes rapidly by the age of 4.0-6.3 years. 相似文献
67.
CF Lanata RE Black H Creed-Kanashiro F Lazo ML Gallardo H Verastegui KH Brown 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(S383):98-103
Dietary intake during diarrhea in children less than three years of age was estimated from information recorded on illustrated dietary forms used by children's caretakers during the first week of illness in a prospective community-based study of diarrheal diseases in Lima, Peru. The frequency of consumption and the amount consumed of food groups and selected commonly consumed foods were analyzed by the final duration of the diarrheal episode. Cereals were less frequently consumed during the acute phase of diarrheal episodes that ultimately became persistent (>14 days'duration), apparently shortening the duration of the episode by one day (median duration of four days in children not consuming vs three days in children consuming cereals during diarrhea, p <0.02 Kaplan-Meier logrank test). Only roots and tubers (mainly potatoes) were consumed in greater quantity during episodes that became persistent. There was no evidence that consumption of breast milk or non-maternal milk was associated with an alteration in diarrheal duration. This study provides further evidence of the beneficial effects of continuing feeding during diarrhea using foods available at the home level, especially cereals, which are commonly used in the diet of young children. 相似文献
68.
M Korppi ML Katila J Jääskeläinen M Leinonen 《Acta paediatrica (Oslo, Norway : 1992)》1992,81(12):993-996
During a 12-month surveillance period in 1981-1982, Moraxella catarrhalis was detected in cultures from nasopharyngeal aspirates from 76 (17%) of 449 children hospitalized with middle or lower respiratory tract infection. Seroconversion to M. catarrhalis was positive in 4(5%) of the 76 patients with M. catarrhalis present in nasopharyngeal aspirates and in 4(1%) of 373 patients with a negative finding. Although children with respiratory tract infections were often colonized by the organism, this was rarely the infective agent of the middle or lower airways. Four of 8 patients with seroconversion to M. catarrhalis exhibited a concomitant RSV infection. The carriage of this species was more closely associated with parainfluenza virus infections. Serological responses to M. catarrhalis were not associated with acute otitis media, and were also rare in children with pneumonia. It is concluded that bronchopulmonary infections caused by M. catarrhalis are rare in children, and that M. catarrhalis aetiology need not be considered in the selection of antibiotics in cases of community-acquired pneumonia or other infections of the middle or lower respiratory tract affecting primarily healthy children. 相似文献
69.
JN HANNA WL SEXTON JL FAOAGALI PJ BUDA ML KENNETT KA BRUSSEN 《Journal of paediatrics and child health》1995,31(4):345-349
Objective: To determine the immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children in north Queensland.
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children. 相似文献
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children. 相似文献
70.
There are well-described sexually dimorphic differences both in the electrocardiogram and in the propensity to develop drug-induced arrhythmias. The QT interval and the risk of ventricular proarrhythmia are reduced in males compared with females. Inward rectifier potassium current (IK(1)) is a primary determinant of the ventricular resting membrane potential, and an important contributor to myocardial excitability.Methods and results: Using the whole-cell patch-clamp technique, we evaluated the effects of dihydrotestosterone (DHT) on IK(1) in ventricular myocytes from castrated rabbits that were treated with either replacement DHT or vehicle-control for 3 weeks. Compared with the DHT-treated group, myocytes from the control animals had a significant reduction in inward IK(1) conductance (p < 0.005) and rectification ratio (RR) (p < 0.04) with no significant change in peak outward current. Acute DHT superfusion of the myocytes increased inward IK(1) conductance from baseline (p < 0.05) and increased the RR (p < 0.05). Testosterone has been reported to increase intracellular ornithine decarboxylase activity in ventricular tissue, which would increase intracellular polyamines, known modulators of IK(1) rectification. We found that inclusion of the intracellular polyamines spermidine and putrescine in the pipette solution caused a decrease in inward IK(1), accompanied by an increase in peak outward current and a reduction in the RR. Conclusion: In summary, DHT modulates IK(1) in a chronic, as well as, an acute fashion. These effects are not because of altered intracellular polyamines. DHT may modulate myocardial excitability through effects on IK(1). 相似文献