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11.
A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy 总被引:3,自引:4,他引:3
Milasin J; Muntoni F; Severini GM; Bartoloni L; Vatta M; Krajinovic M; Mateddu A; Angelini C; Camerini F; Falaschi A; Mestroni L; Giacca M 《Human molecular genetics》1996,5(1):73-79
X-linked dilated cardiomyopathy (XLDC) is a familial heart disease
presenting in young males as a rapidly progressive congestive heart
failure, without clinical signs of skeletal myopathy. This condition has
recently been linked to the dystrophin gene in some families and deletions
encompassing the genomic region coding for the first muscle exon have been
detected. In order to identify the defect responsible for this disease at
the molecular level and to understand the reasons for the selective heart
involvement, a family with a severe form of XLDC was studied. In the
affected members, no deletions of the dystrophin gene were observed.
Analysis of the muscle promoter, first exon and intron regions revealed the
presence of a single point mutation at the first exon-intron boundary,
inactivating the universally conserved 5' splice site consensus sequence of
the first intron. This mutation introduced a new restriction site for MseI,
which cosegregates with the disease in the analyzed family. Expression of
the major dystrophin mRNA isoforms (from the muscle-, brain- and Purkinje
cell-promoters) was completely abolished in the myocardium, while the
brain- and Purkinje cell- (but not the muscle-) isoforms were detectable in
the skeletal muscle. Immunocytochemical studies with anti- dystrophin
antibodies showed that the protein was reduced in quantity but normally
distributed in the skeletal muscle, while it was undetectable in the
cardiac muscle. These findings indicate that expression of the muscle
dystrophin isoform is critical for myocardial function and suggest that
selective heart involvement in dystrophin- linked dilated cardiomyopathy is
related to the absence, in the heart, of a compensatory expression of
dystrophin from alternative promoters.
相似文献
12.
These studies test the hypothesis that vascular endothelia in sponge allografts may develop a function and phenotype resembling the high endothelial venules (HEV) in lymph nodes, thus facilitating the lymphocytic infiltration that is characteristic of allograft rejection. Using limiting dilution analysis to quantitate helper-T-cell accumulation at graft sites, immunohistologic analysis of graft reactivity with the HEV-specific monoclonal antibody MECA 325, and ex vivo lymphocyte-endothelial adhesion assays with graft tissues, we obtained evidence to suggest that HEV-like endothelia may develop at a graft site but that the process whereby lymphocytes accumulate at a graft site is more complex than was initially expected. 相似文献
13.
Steffanie Sabbaj Michael F. Para Robert J. Fass Patrick W. Adams Charles G. Orosz Caroline C. Whitacre 《Journal of clinical immunology》1992,12(3):216-224
The lymphocyte proliferative response to recall antigens is lost following HIV infection. We sought to devise a means by which the functional immune status of persons in the early stages of HIV infection could be monitored quantitatively. The response to tetanus toxoid was examined in 45 HIV-infected individuals and 11 controls using conventional lymphocyte proliferative assays concurrently with limiting dilution analysis utilizing the secretion of interleukin-2 as the measure of a response. Our data show that the limiting dilution analysis detects tetanus toxoid-reactive T cells in 80% of those tested, as compared to only 44% by proliferation. However, the frequency of tetanus-reactive T cells in HIV-infected individuals (median frequency = 1/59,156) is decrease five-fold as compared to seronegative controls (median frequency = 1/11,599). Longitudinal studies demonstrated a time-dependent decrease in the frequency of tetanus-specific T cell responses in the HIV-infected individuals. Thus, the limiting dilution analysis is a quantitative approach for detecting antigen-specific T cells in HIV-infected individuals, and may be used to monitor changes in T cell function in HIV infection. 相似文献
14.
Eva M. Hoefnagels Lucas Weerheijm Angelique GM Witteveen Jan-Willem K Louwerens Noel Keijsers 《Foot and Ankle Surgery》2021,27(5):543-549
BackgroundThe aetiology of chronic therapy resistant plantar fasciitis (CTRPF) is multifactorial with more focus in recent times on the gastroc-soleus complex. This study evaluates the effect of lengthening the gastrocnemius muscle in CTRPF.MethodsAll patients with CRTPF complaints for at least one year underwent the same standard conservative treatment prior to surgery. 32 patients failed this treatment and underwent gastrocnemius recession. Silfverskiöld test, questionnaires and plantar pressure measurements were obtained at 5 visits.ResultsOne year follow up showed a significantly increase in dorsiflexion of the ankle (16 degrees), a decrease in VAS; 78 (SD: 19) to 20 (SD: 24) and significant improved functional scores. Plantar pressure measurements showed an increase of pressure under the medial proximal part of the midfoot and the 1 st metatarsal and a decrease under the hallux.ConclusionsA gastrocnemius recession results in a significant gain in dorsiflexion, altered loading of the foot and good clinical outcome in patients with CTRPF.Level of EvidenceLevel 2 相似文献
15.
Inflammatory pseudotumors have been recognized in many parts of the body. A case of a diffuse variant which involved the testis,
the epididymis and the spermatic cord is described. The patient had enlarged left testis for several months. Clinically, the
lesion mimicred cancer. Histologically, the lesion contained hyalinized fibrous tissue with spindle cells, plasma cells and
lymphocytes. Gradual involvement of vascular channels by the cellular elements of inflammatory pseudotumor was observed. Results
of immunohistochemical studies showed a myofibroblast differentiation in the majority of spindle cells: intense antibody staining
for smooth muscle actin, muscle specific actin, and vimentin. The ultrastructural findings, intracytoplasmic filaments with
dense bodies, were also consistent with the myofibroblastic nature of these cells. The histiocyte differentiation of spindle
cells is questionable in our case, because only scattered histiocyte-like cells showed positivity with the KP-1 (CD-3) antibody. 相似文献
16.
I Orosz 《Orvosi hetilap》1999,140(24):1357-1360
The author discusses the relation of female gender, diabetes mellitus and cardiovascular disease relying upon the "WHO/Europe Health For All" statistical database, data of MEDLINE and the results of Framingham Heart Study. Cardiovascular disease is multifactorial in origin, and it is in connection with increasing prevalence and incidence of diabetes mellitus and hypertension. The mortality caused by ischaemic heart disease is 3-5 times higher if the patients suffer from diabetes mellitus as well. Diabetes mellitus alters the existing difference between males and females in the epidemiological characteristics of ischaemic heart disease. Pathomechanismus (such as metabolic disorders of lipids, hemostasis, endothelial function) are in connection with the changes of estrogen/progesteron balance, have a great role in this change. Diabetes mellitus still has been of significant epidemiological importance from the point of view of cardiovascular's incidence. The prevention of micro-, and macroangiopathy caused by diabetes mellitus beside the genetic factors is one of the most important parts of the epidemiological strategy. 相似文献
17.
The number of lethal cases in hospitals keeps decreasing from year to year, whereas the rate of omitted post-mortem examinations increases. The "control" role of autopsy decreases consequently. Autopsy is omitted even in cases that have been considered as possibly "extraordinary" at the beginning of the procedure and this may mean danger also from the viewpoint of criminology. According to the observations of the authors there are still uncertainties (irregularities?) concerning the tasks connected with the autopsy of those who died in hospitals, as legal injunctions are lacking. On the basis of their experiences the authors interpret the related legal measures and describe the essentials of the procedural practice considered by them correct. 相似文献
18.
van Kranen HJ; van Iersel PW; Rijnkels JM; Beems DB; Alink GM; van Kreijl CF 《Carcinogenesis》1998,19(9):1597-1601
The variation in colorectal cancer (CRC) incidence worldwide strongly
suggests a role for dietary influences. Based on epidemiological data,
protective effects of vegetables and fruit intake on CRC are widely
claimed, while other data indicate a possible increased CRC risk from
(higher) dietary fat intake. Therefore, we have investigated single and
interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in
the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this
study, four different diets (A-D) were compared, which were either low in
fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In
addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced
by a freeze-dried VFM. The diets were balanced so that they only differed
among each other in fat/carbohydrate content and the presence of specific
plant-constituents. Because the initiation of intestinal tumors in ApcMin
mice occurs relatively early in life, exposure to the diets was started in
utero. Without the addition of VFM, mice maintained at a high-fat diet did
not develop significantly higher numbers of small or large intestinal
adenomas than mice maintained at a low-fat diet. VFM added to a low-fat
diet significantly lowered multiplicity of small intestinal polyps (from
16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male
ApcMin mice only. Strikingly, addition of VFM to female mice maintained on
a low-fat diet and to both sexes maintained on a high-fat diet
significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7
polyps/mouse). In conclusion, our results indicate that neither a lower fat
intake nor consumption of VFM included in a high-fat diet decreases the
development of polyps in mice genetically predisposed to intestinal tumor
development.
相似文献
19.
20.
Postbiopsy renal transplant arteriovenous fistulas: color Doppler US characteristics 总被引:3,自引:0,他引:3
Color Doppler ultrasound (US) with point-spectral analysis was performed on eight patients with postbiopsy renal transplant arteriovenous fistulas. Waveform analysis of the supplying artery documented decreased resistive indices in all cases and increased flow velocities in seven. The peak-systolic flow velocity in the arteries supplying the fistulas ranged from 55 to 180 cm/sec (mean, 92 cm/sec), while the range in normal arteries was 20-52 cm/sec (mean, 32 cm/sec). The resistive indices of the arteries supplying the fistulas ranged from 0.31 to 0.50 (mean, 0.45), while the resistive indices of the normal arteries ranged from 0.60 to 0.92 (mean, 0.74). Arterialization of the venous waveform from the draining vein was also documented in all cases. In six cases, the increased flow velocities resulted in increased color saturation toward white in the supplying artery (n = 2) or in both the artery and the draining vein (n = 4), which was detectable on the realtime image. In six cases, flow turbulence resulted in localized tissue vibration, which appeared as random color assignment in extravascular renal parenchyma adjacent to the fistula. Knowledge of these imaging and Doppler characteristics should aid in the identification of renal transplant arteriovenous fistulas with color Doppler US. 相似文献