Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN -amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (ΔMYCN) that was recently identified in fetal tissues. Both MYCNOS and ΔMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level. 相似文献
The acrosome reaction is an important marker for human sperm function.
Since different laboratory techniques may be used for the detection of this
exocytotic process, the purpose of the present study was to compare three
common markers [Pisum sativum agglutinin (PSA), concanavalin A (ConA),
double staining] and transmission electron microscopy for identification of
acrosomal changes. Preliminary findings had demonstrated that similar
results were achieved with Trypan Blue and Hoechst 33258 staining.
Therefore, supravital stainings were omitted. In various experiments, human
spermatozoa were treated with two concentrations (10 and 3.3 microM) of
calcium ionophore A23187 for 15, 30 and 60 min after capacitation for 3 and
6 h at 37 degrees C. The percentages of spermatozoa with acrosomal loss
detected by fluorescein isothiocyanate (FITC)-ConA were consistently lower
than those obtained by double staining or FITC-PSA, which showed comparable
results. Following 6 h of capacitation and incubation with 10 microM
ionophore for 1 h at 37 degrees C, 25.9 +/- 15.7% of all spermatozoa showed
almost complete loss of the acrosomal content. Binding of FITC- ConA to the
acrosomal region was observed in 27.0 +/- 13.2% of spermatozoa obtained
from the same sample. FITC-ConA and double staining or FITC-PSA detect
different stages of the acrosome reaction and may be helpful for a
differentiated evaluation of this sperm function.
相似文献
Charcot‐Marie‐Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory peripheral neuropathies. On the basis of electrophysiologic properties and histopathology, CMT has been divided into demyelinating (type 1) and axonal (type 2) neuropathies. The form of Charcot‐Marie‐Tooth neuropathy that maps to Xq13 may present mild electrophysiological changes (NCV > 40 M/s), mixed neuropathy (NCV: Intermediate (30–40 M/s), or demyelinating neuropathy (NCV: Slow (<37 M/s). On molecular grounds, CMTX is caused by mutations in GJB1 gene, coding for Connexin 32 protein. A 42‐year‐old man, with no other affected family members, was clinically evaluated for CMT. Three years ago he noticed thumb abductor atrophy and then leg muscle atrophy. He presented with hand and leg muscle atrophy, bilateral pes cavus, areflexia, and apallesthesia. The median and ulnar motor NVC were 35–38 m/s, and the median sensory NVC was 35 m/s. Both motor and sensory nerve action potentials were markedly reduced. After exclusion of CMT1A and 1B, analysis for CMTX was performed. The mutation screening of GJB1 gene showed a 9bp insertion upstream the 194ATG codon (Met194) with preservation of the downstream sequence. The three new amino acids (Thr‐Val‐Phe) inserted are localized between the end of the second extracellular domain and the beginning of the fourth transmembrane domain. This is the first 9bp insertion found in GJB1 gene; a genotype‐phenotype correlation may be deduced. 相似文献
Cutaneous leiomyosarcoma typically presents as solitary, well‐circumscribed, firm plaques or nodules. We describe a case of cutaneous leiomyosarcoma clinically presenting as a skin tag on the thigh of a 50‐year‐old male. Histological examination of the lesion revealed a dome‐shaped tumor with interlacing fascicles of smooth muscle with pleomorphism, cellular atypia and multiple mitoses. Malignant tumors may rarely present as a skin tag, and these are most frequently basal cell carcinomas. We are unaware of previously reported leiomyosarcoma clinically presenting as a skin tag. This case suggests that solitary, wide‐based, papilloma‐like lesions or skin tags should be submitted for histologic examination to rule out malignancy. 相似文献
Cisplatin and carboplatin are effective antineoplastic agents. They are also considered to be potentially highly ototoxic. To date, no long-term follow-up data from well-documented cohorts with substantial numbers of childhood cancer survivors (CCS) with platinum-related hearing loss are available. Therefore, in this study, we studied the reversibility of ototoxicity from discontinuation of treatment onwards in a national cohort of platinum-treated survivors with hearing loss at the end of cancer treatment. Of the 168 CCS with follow-up audiograms, we longitudinally evaluated the course of hearing function in 61 CCS who showed hearing impairment at discontinuation of treatment according to the Münster criteria (>20 dB at ≥4–8 kHz). Survivors were treated with platinum (median total cumulative dose cisplatin: 480 mg/m2 and median total cumulative dose carboplatin: 2520 mg/m2). Median follow-up time was 5.5 years (range: 1.0–28.8 years). The results showed that none of these survivors revealed improvement of hearing function even till 28.8 years after discontinuation of treatment (grade <2b during long-term follow-up). An increase in hearing loss with two or three Münster degrees was observed in five of 61 survivors after 1.6–19.6 years. Overall, this indicates that ototoxicity after platinum treatment may be irreversible and that longitudinal clinical audiological monitoring and care is required in long-term survivors of childhood cancer on a large scale. 相似文献
Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH+) and microglia markers (Iba-1+; CD68+) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68+/ Iba-1+ cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.