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1.

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Methods

In this retrospective clinical study, 3 independent CF patient cohorts (US-American: 29, Australian: 12 and Irish: 19 cases) were enrolled carrying at least one Class III CFTR CF-causing mutation (p.Gly551Asp) and being treated with CFTR potentiator ivacaftor. Plasma HE4 was measured by immunoassay before treatment (baseline) and 1–6?months after commencement of ivacaftor, and were correlated with FEV1 (% predicted), sweat chloride, C-reactive protein (CRP) and body mass index (BMI).

Results

After 1?month of therapy, HE4 levels were significantly lower than at baseline and remained decreased up to 6?months. A significant inverse correlation between absolute and delta values of HE4 and FEV1 (r?=??0.5376; P?<?.001 and r?=??0.3285; P?<?.001), was retrospectively observed in pooled groups, including an independent association of HE4 with FEV1 by multiple regression analysis (β?=??0.57, P?=?.019). Substantial area under the receiver operating characteristic curve (ROC-AUC) value was determined for HE4 when 7% mean change of FEV1 (0.722 [95% CI 0.581–0.863]; P?=?.029) were used as classifier, especially in the first 2?months of treatment (0.806 [95% CI 0.665–0.947]; P?<?.001).

Conclusions

This study shows that plasma HE4 levels inversely correlate with lung function improvement in CF patients receiving ivacaftor. Overall, this potential biomarker may be of value for routine clinical and laboratory follow-up of CFTR modulating therapy.  相似文献   
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Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a recently described familial cerebrovascular disorder shown to map to chromosome 19q12. Familial hemiplegic migraine has also been shown in some families to map close to the CADASIL locus. The fully developed CADASIL phenotype consists of recurrent strokes developing in the fourth decade, progressing to a pseudobulbar palsy, spastic quadriparesis, and subcortical dementia. In an Irish family 15 members were fully investigated by magnetic resonance scanning; 10 had typical magnetic resonance features of CADASIL. Five members of this family had familial hemiplegic migraine and 4 of these had magnetic resonance evidence of CADASIL. Two other members had migraine with and without aura as a presenting clinical symptom of CADASIL. This disorder has been shown by linkage analysis to map to the CADASIL locus at chromosome 19. The phenotype at presentation of CADASIL in this family was variable and age related and included familial hemiplegic migraine, migraine with and without aura, transient ischemic attacks, strokes, and spinal cord infarction. This family study increases our understanding of the spectrum of clinical manifestations of this underrecognized familial cerebrovascular disorder.  相似文献   
4.
Abstract: The galactoside-specific plant lectin, Viscum album agglutinin (VAA-I) increases cellular parameters of natural host defence. It also binds to a variety of haematopoietic cells, including progenitors. We investigated whether VAA-I has a stimulatory effect on haematopoietic progenitor cells. Peripheral blood progenitor cells from 7 healthy volunteers were cultured in a colony assay with VAA-I plus erythropoietin (EPO) and stem cell factor (SCF). At 50 pg/ml VAA-I induced a significant increase in the cytokine-dependent clonogenic growth (52% in median, p<0.05). In another set of experiments purified CD34+ cells were isolated from the bone marrow aspirate of 4 patients with non-metastatic breast cancer using fluorescence-activated cell sorting. Binding to CD34+ cells was demonstrated by using directly fluorescence-conjugated VAA-I. Co-incubation with d -galactose significantly abrogated this effect. CD34+ cells were cultured in the presence of EPO, SCF, interleukin-3, granulocyte/monocyte colony-stimulating factor and granulocyte colony-stimulating factor. VAA-I alone had no measurable effect on the clonogenic growth of the isolated cells. However, at concentrations of 100 and 250 pg/ml VAA-I increased the cytokine-dependent proliferation and differentiation of CD34+ cells by a median of 75 and 85%, respectively. The results show that VAA-I binds to haematopoietic progenitor cells and has a co-stimulatory effect on their proliferation.  相似文献   
5.
The Nd-YAG laser was used to provide palliative treatment for eight patients (two women and six men), ranging in age from 53 to 76 years, who had locally advanced colorectal cancer. The main indications for treatment were obstruction, bleeding and copious rectal mucus discharge. Only one complication, a Staphylococcus aureus infection, followed the treatment; the infection was easily controlled. The laser treatment was considered to ease the symptoms in five patients, but survival was not influenced by the treatment. This form of palliation must be evaluated in larger numbers of patients to assess its real value in advanced colorectal cancer.  相似文献   
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7.
Abstract Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a trinucleotide repeatexpansion, cytosine-thymine-guanine (CTG)n, in the 3′ untranslated region of a gene encoding the myotonic dystrophy protein kinase (DMPK). To correlate CTG expansion and protein expression, we studied muscle specimens from 16 adult DM1 patients using three anti-DMPK antibodies for immunoblotting. We estimated the amount of the full-length DMPK (85 kDa) in muscle biopsies from normal controls and from DM1 patients carrying different (CTG)n expansions. We found that DMPK concentration was decreased to about 50% in DM patients’ muscles; the protein decrease did not seem correlated with the CTG repeat length. However, the fibre type composition in skeletal muscle seemed somehow to affect DMPK decrease, as the lowest level of the enzyme was found in patients with the lowest content of type 1 fibre.  相似文献   
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9.
J Strausz  S Kis  J Juhász  A Bede  J Elek  Z Monostori  G Nagy  I Repa 《Orvosi hetilap》1992,133(36):2293-2296
Six patients with obstruction of the trachea were treated with silicone rubber endothracheal stents implanted with flexible bronchoscope. In every case the stent caused significant clinical improvement of the ventilation. At the postintubation stenosis the stent can result a final recovery, at the malignant processes the implantation seems to be a new palliative method.  相似文献   
10.
17 beta-Estradiol (E2) has been shown to exert an acute stimulatory effect on PRL secretion via an indirect action involving the neurointermediate lobe (NIL). In the present study we used a reverse hemolytic plaque assay to determine whether this effect was manifested as an augmentation of the number of PRL secretors and/or an increase in the amount of hormone released per PRL cell. Cultures of anterior pituitary (AP) and NIL cells from ovariectomized rats were cultured overnight, exposed to the treatment (E2 or vehicle) for 3 h, and then subjected to a reverse hemolytic plaque assay that was carried out in the presence or absence of TRH. Concurrent exposure of AP cells to E2 and NIL cells evoked an 11-12% increase in the overall proportion of PRL-secreting cells. This was true when the AP and NIL cells were incubated as a mixed culture and when the two cell types were maintained in the same petri dish but on separate plastic supports, and TRH did not significantly influence this response. The effect of E2 on the number of PRL secretors was negated when NIL cells were not present throughout the experiment or when they were removed from the cultures just before commencement of E2 treatment. Simultaneous treatment with E2 and NIL cells also significantly augmented the sizes of PRL plaques produced under basal conditions by AP cells. Taken together, these results demonstrate that E2 stimulates NIL cells to release an activity that enhances PRL secretion in two ways: 1) by recruiting additional PRL cells into the secretory pool, and 2) by augmenting the secretory capacity of individual PRL cells.  相似文献   
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