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1.
The study of ageing and cell senescence has led to the recent interest in telomeres and telomerase. Telomeres are known to play a role in chromosomal replication and each time cells divide these telomeres shorten. Telomere shortening occurs with increased age. Telomerase is the main factor involved in the preservation of telomere length and therefore its activation is mooted to play a role in the immortalisation of cells. It is in this that our interest lies as it is thought that telomerase has a role to play not only in cell immortalisation but also in the development of neoplasia. Much research has been carried out in this exciting field with the aim of elucidating the role telomerase plays in carcinogenesis. This review is an attempt to summarise the recent advances in this area, which is striving to establish if telomerase does indeed have a role to play in either the early diagnosis of carcinoma or as a marker of prognosis.  相似文献   

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Leptin: does it have any role in childhood asthma?   总被引:8,自引:0,他引:8  
BACKGROUND: Although there is evidence of a positive association between asthma and obesity in adults and children, very little is known about the role of leptin in asthmatic children. OBJECTIVES: The aims of this study were to evaluate the relation between leptin and parameters of atopy and asthma in children. METHODS: Body mass index (BMI) and serum leptin levels were measured in 102 (37 female, 65 male; mean age, 5.9 +/- 3.4 years) asthmatic and 33 (14 female, 19 male; mean age, 6.1 +/- 3.4 years) healthy children. Skin prick tests, total serum IgE, and pulmonary function tests were performed and were completed. RESULTS: A significant difference was observed in serum leptin levels between asthmatic and healthy children. Median (interquartile range) levels were 3.53 (2.06-7.24) ng/mL and 2.26 (1.26-4.71) ng/mL, respectively (P=.008). Subgroup analysis revealed that this difference in leptin levels was confined entirely to boys: 3.09 (1.99-7.51) ng/mL in boys with asthma versus 1.52 (1.06-3.17) ng/mL in boys without asthma (P=.003). By logistic regression analysis, we found that leptin was a predictive factor for having asthma (odds ratio, 1.98; CI, 1.10-3.55; P=.021), whereas sex, age, or BMI were not. In a stepwise multiple regression analysis including sex (P=.001), age (P=.016), BMI (P <.001), and asthma (P=.022), all of these variables were found to affect log leptin levels (R2=0.404). There was no significant sex difference in serum leptin levels among asthmatic children, whereas healthy boys had significantly lower leptin levels than healthy girls (P=.019). Atopic asthmatic subjects had significantly higher leptin levels than nonatopic asthmatic subjects (P=.038) with similar BMI. A significant, but weak, correlation was observed between leptin levels and IgE in the overall group of asthmatic children (r=0.231; P=.019). Again, this correlation was confined entirely to boys (r=0.319; P=.010). There was no relation between leptin levels and skin prick tests, pulmonary function tests, passive smoking, birth weight, and duration of breast-feeding. CONCLUSION: Our findings suggest that leptin may play a role in atopic asthma. High serum leptin levels in asthmatic boys may partly explain the higher prevalence of childhood asthma in male sex.  相似文献   

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BACKGROUND: Serotonin (5-HT)-stimulated platelet intracellular calcium (Ca) mobilization has been reported to be enhanced in unmedicated depressive patients compared to those of normal healthy subjects, which suggests increased 5-HT2A receptor function in these patients. It has not been ascertained whether this enhanced response is specific to some type of affective disorders among various mental disorders. METHODS: We examined 5-HT-induced platelet intracellular Ca response in 152 unmedicated outpatients with various psychiatric disorders including bipolar disorder (BD), major depressive disorder with melancholia (DM), major depressive disorder without melancholia (DN), schizophrenia (SCH), panic disorder (PD), obsessive-compulsive disorder (OCD), social phobia (SP) and bulimia nervosa (BN), and 30 normal controls. RESULTS: We observed no significant differences in basal intracellular Ca concentration among all patient subgroups and normal controls. While the 5-HT-induced Ca response was significantly and specifically higher in patients with BD than in normal controls, no significant differences were found in the Ca response to 5-HT between patients with DM, DN, SCH, PD, OCD, SP and BN, and normal controls. LIMITATIONS: The sample sizes of each group are still small. Therefore, they have to be enlarged in the continuation of the study so as to increase the power of the statistical tests. CONCLUSION: These results indicate the possibility that enhanced signal transduction, mediated by the 5-HT2A receptor, may be specific to bipolar disorder.  相似文献   

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Assessing clinical significance: does it matter which method we use?   总被引:5,自引:0,他引:5  
Measures of clinical significance are frequently used to evaluate client change during therapy. Several alternatives to the original method devised by N. S. Jacobson, W. C. Follette, & D. Revenstorf (1984) have been proposed, each purporting to increase accuracy. However, researchers have had little systematic guidance in choosing among alternatives. In this simulation study, the authors systematically explored data parameters (e.g., reliability of measurement, pre-post effect size, and pre-post correlation) that might yield differing results among the most widely considered clinical significance methods. Results indicated that classification across methods was far more similar than different, especially at greater levels of reliability. As such, the existing methods of clinical significance appear highly comparable; future directions for clinical significance use and research are discussed.  相似文献   

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BACKGROUND: Depression with anger may be more common in bipolar disorders. The aim of the study was to assess whether major depressive disorder (MDD) with anger could be included in the bipolar spectrum, by comparing it to MDD without anger and to bipolar II disorder. METHODS: Consecutive outpatients (281 bipolar II disorder and 202 MDD) presenting for major depressive episode (MDE) treatment were interviewed with the DSM-IV structured clinical interview. Clinical variables used to support the inclusion of MDD with anger in the bipolar spectrum were age of onset, many MDE recurrences, atypical features of depression, depressive mixed state (an MDE plus some concurrent hypomanic symptoms), and bipolar family history. RESULTS: Frequency of MDE with anger was 50.5% [61.2% in bipolar II, and 35.6% in MDD (z = 5.5, p = 0.0000, 95% CI 16.8-43.3%)]. Logistic regression of MDE with anger (dependent variable) versus bipolar variables showed that MDE with anger was significantly associated with all bipolar variables, apart from recurrences. MDD with anger, compared with MDD without anger, had significantly lower age of onset, more marked depressive mixed state, a bipolar family history with more cases, but comparable atypical features and Global Assessment of Functioning scores. MDD with anger, compared with bipolar II disorder, had significantly higher age of onset, less atypical features, and a bipolar family history with less cases. CONCLUSIONS: MDE with anger was common in outpatients (more in bipolar II disorder). MDD with anger may be midway between MDD without anger and bipolar II disorder, and might be included into the bipolar spectrum. However, MDD with anger does not appear to be associated with the often reported negative response to monotherapy with antidepressants.  相似文献   

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BACKGROUND: The authors compared the effect of clonazepam supplement treatment on unipolar depression and bipolar depression. METHODS: A total of 38 protracted depression patients with unipolar depression (n = 19) or bipolar depression (n = 19) were treated with 3.0 mg clonazepam for 4 weeks. RESULTS: In the unipolar depression group, 84.2% of the subjects fulfilled the response criteria (at least an 80% reduction in their HDRS score). However, in the bipolar depression group, only 10.5% of them fulfilled these criteria. CONCLUSIONS: The difference in responses between the two groups supposes that the underlying abnormality in unipolar depression is not the same as that in bipolar depression. This trial also supposed that clonazepam can play active role in the treatment of protracted depression in patients with unipolar depression. LIMITATIONS: This finding was made in an open study, and the effect on clonazepam alone was not established.  相似文献   

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OBJECTIVES: To estimate the lifetime prevalence of bipolar II disorder in children and adolescents presenting with DSM-IV major depressive disorder (MDD). METHODS: Sixty-one consecutive subjects aged < or =18 years attending the outpatient services of the Child and Adolescent Psychiatric (CAP) services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India with a diagnosis of MDD were evaluated using the Missouri Assessment of Genetics Interview for children (MAGIC). Two psychiatrists, one of whom was a child psychiatrist diagnosed hypomania by consensus. RESULTS: Twelve children had a past episode of hypomania (20%), which was hitherto undiagnosed clinically. LIMITATIONS: We recruited subjects from a psychiatric hospital, thus limiting the generalizability of the finding. Sample size was relatively small and assessments were cross-sectional. CONCLUSIONS:: Our study shows that bipolar II disorder is often misdiagnosed as MDD in children. The study also highlights that the chance of diagnosing bipolarity is enhanced by using semi-structured interview in routine clinical practice.  相似文献   

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Lymphangiogenesis in malignant tumours: does it occur?   总被引:14,自引:0,他引:14  
The development of a vascular bed is essential for solid tumour growth and metastasis. In many tumours, mean vascular density can be related to the rate of metastasis and, therefore, to prognosis. In other tumour types, such as cutaneous melanoma and head-and-neck squamous cell carcinoma, this relation is absent. Until now, the reason for this has been unclear, but since these particular tumour types are also known for their propensity to spread via the lymphatic system, it may be speculated that the presence of a pre-existing lymphatic bed and the formation of new lymphatics (lymphangiogenesis) are important factors. Growth factors involved in lymphangiogenesis during embryogenesis have been recently identified and these are also expressed in many tumour types, but the existence of tumour-induced lymphangiogenesis has not so far been reported. Partly, this could be due to the lack of reliable endothelial markers, thereby hampering a consistent evaluation of lymphatic vasculature. This editorial discusses the role of the lymphatic bed in mediating the metastasis of solid tumours, summarizes known methods to detect lymphatics, and proposes a hypothetical mechanism of tumour-induced lymphangiogenesis.  相似文献   

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In the female genital tract, CD10 was initially found to be expressed in endometrial stromal tumors of the uterus as well as in mesonephric remnants and related lesions and was thought to be helpful in distinguishing these tumors from their mimics. However, new studies have shown CD10 to be expressed in a wide range of tumors of the female genital tract, making this antibody of limited diagnostic value. This review discusses diagnostic applications of CD10 in the female genital tract, with emphasis on CD10 use in mesenchymal tumors of the uterus and in the differential diagnosis of mesonephric versus non-mesonephric carcinomas, where CD10 positivity alone may be misleading in the final classification of a tumor. CD10 may be useful in establishing the diagnosis of endometriosis (with the exception of the cervix), distinguishing metastatic renal clear cell carcinoma from a primary ovarian clear cell carcinoma, and distinguishing mesonephric hyperplasia from other benign glandular proliferations of the cervix.  相似文献   

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BACKGROUND: To clarify the nosologic status of girls with attention deficit hyperactivity disorder (ADHD) who also satisfy diagnostic criteria for bipolar disorder (BPD). METHODS: Using blind raters and structured psychiatric interviews, we examined 140 girls with ADHD, 122 non-ADHD comparisons and their 786 first degree relatives. Analyses tested specific hypotheses about the familial relationship between ADHD and bipolar disorder in girls. RESULTS: After stratifying our ADHD sample into those with and without BPD, we found that: (1) relatives of both ADHD subgroups were at significantly greater risk for ADHD than relatives of non-ADHD controls, (2) the two subgroups did not significantly differ in their relatives' risk for ADHD; (3) an elevated risk for bipolar disorder was observed among relatives when the proband child had BPD but not ADHD alone; (4) weak evidence of cosegregation between ADHD and BPD, and (5) no evidence of a trend for random mating between ADHD parents and those with mania. LIMITATIONS: Limitations of this study include the lack of direct interviewing of probands and the limited number of ADHD/BPD probands available. CONCLUSIONS: These findings extend to girls what was previously documented in boys and suggest that comorbid ADHD with BPD in girls is familially distinct from other forms of ADHD and may be related to what others have termed childhood onset BPD. Future work could determine if this subgroup has a characteristic course, outcome and response to treatment.  相似文献   

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PURPOSE OF REVIEW: The review characterizes airway remodelling in childhood asthma and describes how early in life it is possible to detect, and possibly cure, the cellular and biochemical changes that characterize this event. This topic is timely and relevant since a variety of clinical and epidemiologic studies strongly suggest that in asthma, remodelling may start very early in life and that current prevention and treatment measures, including early avoidance measures and pharmaceutical interventions, are relatively ineffective in preventing the development of irreversible airway changes or in reverting them, once established. RECENT FINDINGS: Recent findings show that structural changes characterizing remodelling, such as subepithelial basement membrane thickening, epithelial cell disruption, protease/antiprotease imbalance and neoangiogenesis, are detectable in children with asthma and even in children with respiratory symptoms or with atopy, before a clear clinical diagnosis of bronchial asthma is made. SUMMARY: Identification of the early structural changes that may precede the development of asthma and of factors leading to permanent loss of lung function appear central to future asthma management.  相似文献   

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BACKGROUND: Cognitive dysfunctions are being recognized as a major roadblock to functional recovery in patients with bipolar disorders. Little is known about the treatment of these cognitive dysfunctions. Donepezil, approved to treat memory dysfunction in Alzheimer's disease, is evaluated for cognitive dysfunctions common in bipolar disorder. Of concern is some evidence that donepezil may trigger affective instability. METHODS: All bipolar disordered patients in a private practice setting treated with donepezil for memory problems were analyzed. Patients were assessed for memory improvement and change in psychiatric status with the Clinical Global Impression of Improvement Scale. RESULTS: Thirty-nine of 58 patients (67%) reported improvement with a mean score of 1.82 (standard deviation+/-0.82). Nine treatments were stopped because of side effects and 4 showed no response. No bipolar I patient received benefits. Thirty-six of 43 (84%) of bipolar II patients showed improvement. Fifty percent of bipolar NOS showed improvement. Four bipolar I patients (57%), 1 bipolar II patient (2%) and 2 bipolar NOS patients (25%) stopped donepezil due to worsening affective symptoms. LIMITATIONS: This is a naturalistic case series with a single evaluator. Other medications used in treatment were changed as clinically indicated. CONCLUSIONS: This case series suggests utility for donepezil in the treatment of cognitive problems associated with bipolar II disorder and bipolar disorder NOS. Bipolar I patients showed no improvement and a concerning trend to destabilize with donepezil treatment.  相似文献   

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Anticipation has been suggested among the genetic mechanisms of bipolar disorder (BD), prompting the search for unstable DNA sequences. Past studies of anticipation in BD have generally relied on observed shift in the age at onset between parental and offspring generations. Such a shift, however, may be caused by a number of other factors difficult to correct for. We investigated age at onset distributions in a sample of 161 related subjects and in a sample of "pseudofamilies" consisting of 320 unrelated subjects selected from a large epidemiological cohort using Monte-Carlo simulation to mimic the family sample. Comparison of age at onset distributions in both samples shows a difference between the generations, but of a similar magnitude in each sample. This suggests that age at onset alone may not be a sufficient criterion of anticipation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:804-807, 2000.  相似文献   

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