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51.
Dorota Piotrowska-Kownacka Lukasz Kownacki Marek Kuch Ewa Walczak Agnieszka Kosieradzka Anna Fidzianska Leszek Krolicki 《Journal of cardiovascular magnetic resonance》2009,11(1):12
Danon disease is a rare X-linked dominant lysosomal glycogen storage disease that can lead to severe ventricular hypertrophy and heart failure. We report a case of Danon disease with cardiac involvement evaluated with cardiovascular magnetic resonance, including late gadolinium enhancement and perfusion studies. 相似文献
52.
53.
Müerköster S Weigand MA Choi C Walczak H Schirrmacher V Umansky V 《British journal of cancer》2002,86(5):828-836
The endogenous viral superantigen 7 in DBA/2 mice serves as a target antigen on syngeneic ESb-MP lymphoma cells for allogeneic graft-vs-leukaemia reactive cells. Allogeneic viral superantigen 7 reactive Vbeta6+ T cells are able to transfer graft-vs-leukaemia reactivity and to kill specifically viral superantigen 7+ ESb-MP tumour cells in vitro. Here we elucidate the mechanism of this superantigen specific cell lysis. Already 10 min after co-incubation with in vitro stimulated Vbeta6+ T cells, viral superantigen 7+ ESb-MP tumour cells show an apoptotic phenotype (Annexin V-positivity, DNA-fragmentation). This extremely rapid type of cell death is not mediated by the death inducing ligands CD95L, TRAIL and TNF but by perforin and granzyme B. Surprisingly, neither mitochondria nor any of the known caspases appear to be involved in this type of tumour cell killing. In contrast, nitric oxide, released by activated macrophages and endothelial cells, induces in the same tumour cells another type of apoptosis which is much slower and involves mitochondria and caspase activation. A synergistic effect between the two different effector mechanisms of superantigen reactive donor cytotoxic T lymphocytes and nitric oxide releasing host macrophages and endothelial cells might explain the effective immune rejection of even advanced metastasised cancer in this graft-vs-leukaemia animal model. 相似文献
54.
Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity. 相似文献
55.
Benzo[a]pyrene at an environmentally relevant dose is slowly absorbed by, and extensively metabolized in, tracheal epithelium 总被引:2,自引:0,他引:2
Gerde P; Muggenburg BA; Thornton-Manning JR; Lewis JL; Pyon KH; Dahl AR 《Carcinogenesis》1997,18(9):1825-1832
While tobacco smoke has been conclusively identified as a lung carcinogen,
there is much debate over which smoke constituent(s) are primarily
responsible for its carcinogenicity. Previous studies in our laboratory
suggested that highly lipophilic carcinogens are slowly absorbed in the
thicker epithelium of the conducting airways, potentially allowing for
substantial local metabolism. The bioactivation of polycyclic aromatic
hydrocarbons in airway epithelium may, hence, be important in tobacco
smoke-induced carcinogenesis. In the present study, the hypothesis of slow
absorption and substantial local metabolic activation of highly lipophilic
carcinogen in airway epithelium was tested in dogs. A single dose of
tritiated benzo[a]pyrene (BaP) dissolved in a saline/phospholipid
suspension was instilled in the trachea, just anterior to the carina. At
intervals of a few minutes up to 30 min over a 3-h period, blood samples
were drawn from the azygous vein, which drains the area around the point of
instillation, and from the systemic circulation. Tissue samples were taken
at the end of the experiment. The concentration of BaP with depth into the
tracheal mucosa was determined with autoradiography. BaP was slowly
absorbed into the trachea with a half-time of approximately 73 min, which
is consistent with diffusion-limited passage through the epithelium and
lead to local doses in the tracheal epithelium that were more than a
1000-fold those of other tissues. The long retention of BaP in the
epithelium provided the local metabolizing enzymes with high substrate
levels over a long period, resulting in extensive metabolism. At 3 h after
the exposure, 23% of the BaP-equivalent activity remained in the tracheal
mucosa. Of this fraction, 13% was parent compound, 28% was organic
extractable, 31% was water-soluble, and 28-7% of the instilled dose was
bound to tracheal tissues. These results explain the tendency of highly
lipophilic carcinogens, such as BaP, to induce tumors at the site of entry
and, furthermore, indicate that the highly lipophilic components of tobacco
smoke and polluted air may be the most important contributors to lung
tumors of the conducting airways.
相似文献
56.
MT Bardella N Molteni L Prampolini AM Giunta AR Baldassarri D Morganti PA Bianchi 《Archives of disease in childhood》1994,70(3):211-213
The use of follow up studies was evaluated in 128 patients with coeliac disease during their first visit to a department for adults. The original diagnosis had been made in childhood in all patients. Fifty eight (45%) of the subjects were following a gluten free diet, 23 (18%) were following a gluten free diet but with occasional gluten consumption, and 47 (37%) had adopted an unrestricted, gluten containing diet for a mean of 11.2 years. There was no correlation in individual subjects between the presence of symptoms, biochemical and immunological abnormalities, severity of histological findings, and the amount of dietary gluten, despite the greater frequency of symptoms in the group following an unrestricted diet than in the other two groups. Short stature and epilepsy with cerebral calcifications only occurred in patients following an unrestricted diet. As only diagnosis based on two or three biopsy samples and regular follow up correlated positively with dietary compliance, it is suggested that a histologically confirmed diagnosis of coeliac disease and regular lifelong follow up are essential in the management of these patients. 相似文献
57.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family and has recently been shown to exert tumoricidal activity in vivo in the absence of any observable toxicity. The signaling pathways triggered by TRAIL stimulation and the mechanisms involved in resistance against TRAIL-mediated apoptosis are still poorly defined. We show here that TRAIL-induced apoptosis involves late dissipation of mitochondrial membrane potential (delta psi(m)) and cytochrome c release. These events follow activation of caspase-8 and caspase-3 and induction of DNA fragmentation. In addition, caspase-8-deficient cells are resistant against TRAIL-induced apoptosis, and inhibition of caspase-8 but not caspase-9 prevents mitochondrial permeability transition and apoptosis. In contrast, various Bcl-2- or Bcl-xL-overexpressing tumor cell lines are sensitive to TRAIL-induced apoptosis; however, they show a delay in TRAIL-induced mitochondrial permeability transition compared with control transfectants. This indicates that TRAIL-induced apoptosis depends on caspase-8 activation rather than on the disruption of mitochondrial integrity. Because most chemotherapeutic drugs used in the treatment of malignancies lead to apoptosis primarily by engagement of the mitochondrial proapoptotic machinery, we tested whether drug-resistant tumor cells retain sensitivity for TRAIL-induced apoptosis. Tumor cells overexpressing Bcl-2 or Bcl-xL become resistant to apoptosis induced by the chemotherapeutic drug etoposide. However, these cells are not protected or are only marginally protected against TRAIL-induced apoptosis. Thus, TRAIL may still kill tumors that have acquired resistance to chemotherapeutic drugs by overexpression of Bcl-2 or Bcl-xL. These data will influence future treatment strategies involving TRAIL. 相似文献
58.
STOTT DJ; MCLELLAN AR; FINLAYSON J; CHU P; ALEXANDER WD 《QJM : monthly journal of the Association of Physicians》1991,78(1):77-84
The clinical and biochemical characteristics of 15 elderly patientswith low levels of thyrotrophin (TSH) (<0.1 mU/L) but normalfree tri-iodothyronine, (T3) and free thyroxine (T4) (groupS) were compared with 10 euthyroid subjects (group E) and 10hyperthyroid patients (group T). Free T3 and free T4 were significantlyhigher (p<0.05) in group S(6.3±0.5 and 18.6±1.0pmol/l, respectively) than in group E(4.6±0.3, 12.6+0.6).In common with elderly hyperthyroid patients (group T)patientsin group S had few signs or symptoms of thyrotoxocosis, butthe Wayne score (clinical index of hyperthyroidism) was higherin group S than in euthyroid subjects (p<0.05). Thyroid microsomal,thyrogolobulin or thyrotrophin receptor antibodies were commonin group T (n=9)but not in groups S(n=2) or E(n=1). This suggestsa low prevalence of Graves' disease in group S compared to groupT. Combined thyrotrophin releasing hormone (TRH; 200 µgi.v.) and gonadotrophin releasing hormone GnRH; 100 µgi.v.) tests were performed; no cases of low TSH due to hypopituitarismwere identified in group S. During a mean of 7.9 (412)months of observation TSH reverted to the normal range (>0.2mU/L)in 7 of 15 patients in group S; thyroid hormone concentrationsrose above the normal range in four, however, only two patientsrequired treatment for hyperthyroidism. It is unlikely thatthe suppressed TSH of patients in group S was due to mild thyroidhormone excess; although this is often a transitory phenomenon,these patients are at increased risk of developing overt hyperthyroidism. 相似文献
59.
60.