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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.
Metabolic and Functional Characteristics of Alveolar Macrophages Recovered from Rats Exposed to Marijuana Smoke 下载免费PDF全文
David B. Drath Jeannette M. Shorey Louise Price Gary L. Huber 《Infection and immunity》1979,25(1):268-272
Pulmonary alveolar macrophages were obtained by bronchopulmonary lavage from male rats after 30 consecutive days of in vivo exposure to marijuana and tobacco smoke. No significant differences were found between either group of experimental animals and controls in the number of cells recovered, the protein content per 10(6) cells, or the percentage of cells that adhered to plastic surfaces. The ability of macrophages to phagocytize viable bacteria was not affected by exposure to either marijuana or tobacco smoke in that both treatment groups ingested Staphylococcus aureus over a 60-min period as well as did control cells. Differences were found between the groups, however, with respect to cellular metabolism. Marijuana smoke inhalation caused a small decrease in the amount of oxygen consumed by macrophages during phagocytosis, as compared with control cells. This may have been reflected in the even greater decrease in superoxide formation observed during particle engulfment by these treated cells. Tobacco smoke, on the other hand, increased oxygen consumption and was without effect on superoxide release. Neither tobacco nor marijuana smoke treatment had an effect on the direct oxidation of glucose via the hexose monophosphate shunt. Our results indicate that, despite several metabolic alterations in response to marijuana and tobacco smoke, alveolar macrophages were not compromised with respect to their ability to ingest a particulate challenge. 相似文献
63.
Richard Cooper Ivan Soltero Jeremiah Stamler Louise Mojonnier Yolanda Hall Dorothy Moss David M. Berkson Tom Tokich 《Journal of the National Medical Association》1982,74(4):349-355
Quit-rates for cigarette smokers in a lifestyle intervention program aimed at reducing coronary risk were 24 percent for all participants and 34 percent for non-dropouts. Recidivism remained very low during participation in the program. Half of the smokers who quit did so after being in the program more than two years. These data suggest that while engaging in an effort to make other changes in lifestyle, many smokers can be helped to quit. Sustained antismoking efforts in the clinical practice of medicine can be expected to share these same positive aspects. While mass public health programs to eliminate smoking and prevent young people from taking up the habit are being developed, health practitioners can make a significant contribution by including vigorous efforts at smoking cessation as part of routine practice. 相似文献
64.
Linkage disequilibrium analysis of childhood-onset spinal muscular atrophy (SMA) in the French -- Canadian population 总被引:4,自引:0,他引:4
Simard Louise R.; Prescott Gary; Rochette Camille; Morgan Kenneth; Lemleux Bernard; Mathleu Jean; Melancon Serge B.; Vanasse Michel 《Human molecular genetics》1994,3(3):459-463
Spinal muscular atrophy (SMA) is, after Duchenne muscular dystrophy,the most common neuromuscular disorder in childhood. The generesponsible for childhood SMA has been mapped to the q11. 2 q13. 3 region of chromosome 5. We have extended ourlinkage studies of SMA In the French - Canadian population toInclude microsatellite markers at the D5S125, D5S351, D5S435,JK53CA1/ 2 and MAPI B locl. These markers span about 4 cM ofthe SMA candidate region. We observed significant evidence forlinkage between SMA and all the markers tested. The analysisof recombinant chromosomes provide evidence for the followinggenetic order: D5S125-D5S435-MAP1B-3'-JK53CA1/2 and places D5S351proximal to JK53CA1/2. Furthermore, we confirm the current localizationof the SMA gene distal to D5S435. Finally, we provide demonstrationof significant linkage disequilibrium between childhood-onsetSMA and four of the five marker loci, D5S125, D5S435, D5S351and JK53CA1/2. Analysis of SMA-region haplotypes suggests thatthere may be a predominant SMA allele that is present on about17% of SMA chromosomes in this sample of the French - Canadianpopulation. We conclude that the observed linkage disequilibriumis likely due to genetic drift among regions of Quebec, consistentwith this population's early history. 相似文献
65.
A transient decrease in excitability occurs regularly during the S1 phase of threshold electrotonus to depolarizing conditioning stimuli for sensory and, less frequently, motor axons. This has been attributed to the outwardly rectifying action of fast K+ channels, at least in patients with demyelinating diseases. This study investigates the genesis of this notch in healthy axons. Threshold electrotonus was recorded for sensory and motor axons in the median nerve at the wrist in response to test stimuli of different width. The notch occurred more frequently the briefer the test stimulus, and more frequently in sensory studies. In studies on motor axons, the notch decreased in latency and increased in amplitude as the conditioning stimulus increased or the limb was cooled. Low-threshold axons displayed profound changes in strength–duration time constant even though the threshold electrotonus curves contained no detectable notch. When a 1.0 ms current was added to subthreshold conditioning stimuli to trigger EMG, the notch varied with the timing and intensity of the brief current pulse. This study finds no evidence for an outwardly rectifying deflection due to K+ channels, other than the slow accommodation attributable to slow K+ currents. In normal motor axons, a depolarization-induced notch during the S1 phase of threshold electrotonus is the result of the conditioning stimulus exceeding threshold for some axons. The notch is more apparent in sensory axons probably because of the lower slope of the stimulus–response curve and their longer strength–duration time constant rather than a difference in K+ conductances. This may also explain the notch in demyelinating diseases. 相似文献
66.
67.
We have known for some time that the epidemiology of human stroke is sexually dimorphic until late in life, well beyond the
years of reproductive senescence and menopause. Now, a new concept is emerging: the mechanisms and outcome of cerebral ischemic injury are influenced strongly by biological sex as well as the availability of sex steroids to the
brain. The principal mammalian estrogen (17 β estradiol or E2) is neuroprotective in many types of brain injury and has been
the major focus of investigation over the past several decades. However, it is becoming increasingly clear that although hormones
are a major contributor to sex-specific outcomes, they do not fully account for sex-specific responses to cerebral ischemia.
The purpose of this review is to highlight recent studies in cell culture and animal models that suggest that genetic sex
determines experimental stroke outcome and that divergent cell death pathways are activated after an ischemic insult. These
sex differences need to be identified if we are to develop efficacious neuroprotective agents for use in stroke patients. 相似文献
68.
Berriman M Hall N Sheader K Bringaud F Tiwari B Isobe T Bowman S Corton C Clark L Cross GA Hoek M Zanders T Berberof M Borst P Rudenko G 《Molecular and biochemical parasitology》2002,122(2):131-140
Trypanosoma brucei evades the immune system by switching between Variant Surface Glycoprotein (VSG) genes. The active VSG gene is transcribed in one of approximately 20 telomeric expression sites (ESs). It has been postulated that ES polymorphism plays a role in host adaptation. To gain more insight into ES architecture, we have determined the complete sequence of Bacterial Artificial Chromosomes (BACs) containing DNA from three ESs and their flanking regions. There was variation in the order and number of ES-associated genes (ESAGs). ESAGs 6 and 7, encoding transferrin receptor subunits, are the only ESAGs with functional copies in every ES that has been sequenced until now. A BAC clone containing the VO2 ES sequences comprised approximately half of a 330 kb 'intermediate' chromosome. The extensive similarity between this intermediate chromosome and the left telomere of T. brucei 927 chromosome I, suggests that this previously uncharacterised intermediate size class of chromosomes could have arisen from breakage of megabase chromosomes. Unexpected conservation of sequences, including pseudogenes, indicates that the multiple ESs could have arisen through a relatively recent amplification of a single ES. 相似文献
69.
Jason B. Mattingley Louise A. Corben John L. Bradshaw Judy A. Bradshaw Jim G. Phillips Malcolm K. Horne 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1998,120(2):243-256
Patients with unilateral neglect following right hemisphere damage may have difficulty in moving towards contralesional targets.
To test the hypothesis that this impairment arises from competing motor programs triggered by irrelevant ipsilesional stimuli,
we examined 16 right hemisphere patients, eight with left visual neglect and eight without, in addition to eight healthy control
subjects. In experiment 1 subjects performed sequences of movements using their right hand to targets on the contralesional
or ipsilesional side of the responding limb. The locations of successive targets in each sequence were either predictable
or unpredictable. In separate blocks of trials, targets appeared either alone or with a simultaneous distractor located at
the immediately preceding target location. Neglect patients were significantly slower to execute movements to contralesional
targets, but only for unpredictable movements and in the presence of a concurrent ipsilesional distractor. In contrast, healthy
controls and right hemisphere patients without neglect showed no directional asymmetries of movement execution. In experiment
2 subjects were required to interrupt a predictable, reciprocating sequence of leftward and rightward movements in order to
move to an occasional, unpredictable target that occurred either in the direction opposite to that expected, or in the same
direction but twice the extent. Neglect patients were significantly slower in reprogramming the direction and extent of movements
towards contralesional versus ipsilesional targets, and they also made significantly more errors when executing such movements.
Right hemisphere patients without neglect showed a similar bias in reprogramming direction (but not extent) for contralesional
targets, whereas healthy controls showed no directional asymmetry in either condition. On the basis of these findings we propose
that neglect involves a competitive bias in favour of motor programs for actions directed towards ipsilesional versus contralesional
events. We suggest that programming errors and increased latencies for contralesional movements arise because the damaged
right hemisphere can no longer effectively inhibit the release of inappropriate motor programs towards ipsilesional events.
Received: 1 October 1996 / Accepted: 21 October 1997 相似文献
70.
Zusammenfassung An 21 Patienten wurde die Harnschwelle für Zucker, die tubuläre Rückresorptionskapazität und die Zuckerausscheidung bestimmt. Hierbei ergab sich bei langdauernder Zuckerbelastung eine absolute Vergrößerung der ausgeschiedenen Zukkermengen mit Abfall der Harnzuckerschwelle. Diese Verminderung wurde durch einen absoluten Abfall der tubulären Rückresorptionskapazität und relativen Abfall im Verhältnis zur filtrierten Zuckermenge hervorgerufen. Diese Einschränkungen traten mit zunehmender Versuchsdauer in Erscheinung und werden auf eine Erschöpfung der tubulären fermentativen Vorgänge bezogen. Vielleicht finden hierin auch die anderweitig beobachteten tubulären Degenerationen bei langdauernder Zuckerbelastung ihre Erklärung. Eine länger dauernde Glykosurie scheint für die Tubulusepithelien eine echte Belastung darzustellen.Diese Arbeit ist meinem Chef, Herrn Prof.Wollheim, zu seinem 60. Geburtstag am 24. 3. 60 gewidmet. 相似文献