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31.
A gene for autosomal recessive limb-girdle muscular dystrophy maps to chromosome 2p 总被引:10,自引:3,他引:10
Bashlr Rumaisa; Strachan Tom; Keers Sharon; Stephenson Anthea; Mahjneh Ibrahim; Marconi Giamplero; Nashef Lina; Bushby Kate M. D. 《Human molecular genetics》1994,3(3):455-457
The limb-girdle muscular dystrophies are a clinically and geneticallyheterogeneous group of disorders. We have ostudied two largeinbred families of different ethnic origin and excluded linkageto LGMD2 on chromosome 15q and SCARMD on chromosome 13. Proceedingto a genomic linkage search, we have now identified linkageto markers D2S134 and D2S136 on chromosome 2p (maximum lod score3.57 at zero recombination). The phenotype in the two familieswas similar, with onset in the pelvic girdle musculature inthe late teens and usually relatively slow progression. Thiswork Identifies a second locus for autosomal recessive limb-girdlemuscular dystrophy. 相似文献
32.
There is increasing evidence that endogenous glycogen depletion may affect excitation–contraction (E–C) coupling events in vertebrate skeletal muscle. One approach employed in physiological investigations of E–C coupling involves the use of mechanically skinned, single fibre preparations obtained from tissues stored under paraffin oil, at room temperature (RT: 20–24°C) and 4°C for several hours. In the present study, we examined the effect of these storage conditions on the glycogen content in three muscles frequently used in research on E–C coupling: rat extensor digitorum longus (EDL) and soleus (SOL) and toad iliofibularis (IF). Glycogen content was determined fluorometrically in homogenates prepared from whole muscles, stored under paraffin oil for up to 6 h at RT or 4°C. Control muscles and muscles stored for 0.5 and 6 h were also analysed for total phosphorylase (Phostotal) and phosphorylase a (Phos a) activities. No significant change was observed in the glycogen content of EDL and SOL muscles stored at RT for 0.5 h. In rat muscles stored at RT for longer than 0.5 h, the glycogen content decreased to 67.6% (EDL) and 78.7% (SOL) of controls after 3 h and 25.3% (EDL) and 37.4% (SOL) after 6 h. Rat muscles stored at 4°C retained 79.0% (EDL) and 92.5% (SOL) of glycogen after 3 h and 75.2% (EDL) and 61.1% (SOL) after 6 h. The glycogen content of IF muscles stored at RT or 4°C for 6 h was not significantly different from controls. Phostotal was unchanged in all muscles over the 6 h period, at both temperatures. Phos a was also unchanged in the toad IF muscles, but in rat muscles it decreased rapidly, particularly in EDL (4.1-fold after 0.5 h at RT). Taken together these results indicate that storage under paraffin oil for up to 6 h at RT or 4°C is accompanied by minimal glycogen loss in toad IF muscles and by a time- and temperature-dependent glycogen loss in EDL and SOL muscles of the rat. 相似文献
33.
Mechanically skinned skeletal muscle fibres from rat and toad were exposed to the permeabilizing agents β-escin and saponin.
The effects of these agents on the sealed transverse tubular system (t-system) and sarcoplasmic reticulum (SR) were examined
by looking at changes in the magnitude of the force responses to t-system depolarization, the time course of the fluorescence
of fura-2 trapped in the sealed t-system, and changes in the magnitude of caffeine-induced contractures following SR loading
with Ca2+ under defined conditions. In the presence of 2 μg ml–1β-escin and saponin, the response to t-system depolarization was not completely abolished, decreasing to a plateau, and a
large proportion of fura-2 remained in the sealed t-system. At 10 μg ml–1, both agents abolished the ability of both rat and toad preparations to respond to t-system depolarization after 3 min of
exposure, but a significant amount of fura-2 remained in sealed t-tubules even after exposure to 100 μg ml–1β-escin and saponin for 10 min. β-Escin took longer than saponin to reduce the t-system depolarizations and fura-2 content
of the sealed t-system to a similar level. The ability of the SR to load Ca2+ was reduced to a lower level after treatment with β-escin than saponin. This direct effect on the SR occurred at much lower
concentrations for rat (2 μg ml–1β-escin and 10 μg ml–1 saponin) than toad (10 μg ml–1β-escin and 150 μg ml–1 saponin). The reverse order in sensitivities to β-escin and saponin of t-system and SR membranes indicates that the mechanisms
of action of β-escin and saponin are different in the two types of membrane. In conclusion, this study shows that: (1) β-escin
has a milder action on the surface membrane than saponin; (2) β-escin is a more potent modifier of SR function; (3) simple
permeabilization of membranes is not sufficient to explain the effects of β-escin and saponin on muscle membranes; and (4)
the t-system network within muscle fibres is not a homogeneous compartment.
Received: 18 November 1998 / Received after revision: 6 January 1999 / Accepted: 7 January 1999 相似文献
34.
Genetic Vaccination of Mice with Plasmids Encoding the NS1 Non-structural Protein from Tick-borne Encephalitis Virus and Dengue 2 Virus 总被引:2,自引:0,他引:2
Although there is a safe, inexpensive and efficacious vaccine against yellow fever, vaccination against other flavivirus diseases is less successful. There is no licensed vaccine against dengue fever and current vaccines against tick-borne encephalitis (TBE) and Japanese encephalitis are expensive and require several injections. Furthermore novel vaccines containing only virus envelope proteins may raise fears over antibody mediated enhancement (ADE) of disease. Here we report the successful use of genetic vaccination against TBE in an experimental animal model using a plasmid containing the coding sequence of a non-structural protein (NS1). Such vaccines would provide inexpensive protection against disease, without raising concerns over inducing ADE on subsequent exposure to heterotypic infectious virus. Attempts to generate chaemeric plasmids to protect against both TBE and dengue fever were less successful. Although these chaemeric plasmids directed the synthesis and secretion of the virus NS1 protein normally, no protection was observed against either TBE or dengue fever. 相似文献
35.
Emily Stephenson Simone Webb Prof. Muzlifah Haniffa 《European journal of immunology》2021,51(4):764-772
The development of the human immune system during embryonic and fetal life has historically been difficult to research due to limited access to human tissue. Experimental animal models have been widely used to study development but cellular and molecular programmes may not be conserved across species. The advent of multiomic single-cell technologies and an increase in human developmental tissue biobank resources have facilitated single-cell multiomic studies focused on human immune development. A critical question in the near future is "How do we best reconcile scientific findings across multiple omic modalities, developmental time, and organismic space?" In this review, we discuss the application of single-cell multiomic technologies to unravel the major cellular lineages in the prenatal human immune system. We also identify key areas where the combined power of multiomics technologies can be leveraged to address specific immunological gaps in our current knowledge and explore new research horizons in human development. 相似文献
36.
The findings reported in patients undergoing excretory urography for recurrent urinary tract infection
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There was little difference between the proportion of lesions found by excretion urography in patients with recurrent urinary tract infections referred by general practitioners or hospital staff, or between Horton General Hospital which is a district general hospital, and the United Oxford Hospitals, which is a teaching group. Many patients with urinary tract infections may be saved an unnecessary visit to the hospital consultant if this is first investigated by the general practitioner.
About one fifth of all patients had significant lesions shown by excretory urography which suggests that the investigation is worthwhile in patients with recurrent urinary tract infections.
相似文献37.
M B Podlisny D T Stephenson M P Frosch I Lieberburg J A Clemens D J Selkoe 《Neurobiology of aging》1992,13(5):561-567
Because progressive amyloid beta-protein (A beta P) deposition and surrounding neuritic dystrophy occur spontaneously in primates, we evaluated the in vivo effects of synthetic A beta P in monkey cortex. Experimental and control A beta P were stereotactically injected into multiple neocortical sites of adult rhesus monkeys in a vehicle of either artificial cerebrospinal fluid or acetonitrile. After 2 weeks or 3 months, injection sites were identified and characterized histologically and immunocytochemically. A beta P antibodies specifically detected the injected A beta P1-40 peptide. Serial sections stained with silver and antineurofilament protein demonstrated comparable degrees of degenerating neurons, dystrophic neurites, and axonal spheroids associated with both experimental and control peptide injections. Alz 50 staining was sparse or absent in all sites. We conclude that specific cellular changes closely resembling AD pathology were not detected in these experiments, and that control and experimental A beta P peptides produced indistinguishable effects. Methodological concerns regarding the in vivo modeling of A beta P bioactivity are discussed. 相似文献
38.
C-myc oncogene product P62c-myc in ovarian mucinous neoplasms: immunohistochemical study correlated with malignancy.
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The monoclonal antibody Myc 1-6E10 was used to determine the cellular distribution of the c-myc oncogene product p62c-myc in 60 mucinous ovarian tumours. Three patterns of immunostaining were apparent: (i) nuclear staining alone; (ii) staining of the nucleus and basal cytoplasm; and (iii) staining of the entire cell. Of the 21 cases of mucinous cystadenoma, 11 showed nuclear staining alone, and a further case showed additional weak staining of the basal cytoplasm. Nuclear staining alone was not present in any of the 17 borderline mucinous tumours examined. Strong staining of the nucleus and basal cytoplasm was seen in 16 of these borderline cases, six of which also showed focal staining of the apical cytoplasm. All 22 cases of mucinous cystadenocarcinoma showed staining of the cell nucleus and entire cell cytoplasm. Focal staining of the apical cytoplasm in six of 17 borderline mucinous tumours produced a pattern of c-myc immunostaining similar to that of cystadenocarcinoma. Retrospective analysis of the clinical data showed that no significant differences between patients with borderline tumours of these two categories could be defined. Although immunostaining with Myc 1-6E10 can be used in the categorisation of mucinous ovarian tumours, it is concluded that standard histological criteria are more accurate indicators of tumour behaviour than is an assessment of c-myc expression. 相似文献
39.
Takada D Emi M Ezura Y Nobe Y Kawamura K Iino Y Katayama Y Xin Y Wu LL Larringa-Shum S Stephenson SH Hunt SC Hopkins PN 《Journal of human genetics》2002,47(12):0656-0664
40.
Detection of a 15q deletion in a child with Angelman syndrome by cytogenetic analysis and flow cytometry 总被引:1,自引:0,他引:1
A Cooke J L Tolmie F J Glencross E Boyd M M Clarke R Day J B Stephenson J M Connor 《American journal of medical genetics》1989,32(4):545-549
A proximal 15q deletion, del(15) (q11:q13), was detected in a child with Angelman syndrome by cytogenetic analysis of peripheral lymphocytes. The chromosomes of both parents appeared normal. Flow karyotype analysis carried out on lymphoblastoid cell lines derived from the child and her parents confirmed the presence of a de novo 15 deletion. The estimated size of the deleted segment ranged from 6.1-9.5% of chromosome 15 (approximately 6-9.3 million base pairs). The parental origin of the deleted chromosome could not be resolved by flow cytometry, but cytogenetic evidence suggested that it was derived from the smaller chromosome 15 homologue in the mother. 相似文献