Resident endothelial precursors in muscle, adipose, and dermis contribute to postnatal vasculogenesis

A novel population of tissue-resident endothelial precursors (TEPs) was isolated from small blood vessels in dermal, adipose, and skeletal muscle of mouse based on their ability to be grown as spheres. Cellular and molecular analyses of these cells revealed that they were highly related regardless of the tissue of origin and distinct from embryonic neural stem cells. Notably, TEPs did not express hematopoietic markers, but they expressed numerous characteristics of angiogenic precursors and their differentiated progeny, such as CD34, Flk-1, Tie-1, CD31, and vascular endothelial cadherin (VE-cadherin). TEPs readily differentiated into endothelial cells in newly formed vascular networks following transplantation into regenerating skeletal muscle. Taken together, these experiments suggest that TEPs represent a novel class of endothelial precursors that are closely associated with small blood vessels in muscle, adipose, and dermal tissue. This finding is of particular interest since it could bring new insight in cancer angiogenesis and collateral blood vessels developed following ischemia. Disclosure of potential conflicts of interest is found at the end of this article.     

Regulation of tissue-engineered products in the European Union: where are we heading?

The emergence of tissue-engineered products (TEPs) raises a standard question for regulators: is the existing regulatory regime appropriate or is there a case for a new regulatory framework? In the USA, the FDA has developed a risk-based approach to TEPs, whereas in Europe, a common regulatory strategy for these products has not yet been implemented. In order to fill this perceived gap, member states have set up domestic rules, which has led to an unclear and patchy regulatory situation. The Regulation on Advanced Therapy Medicinal Products, voted on by the European Commission in November 2005, has been developed by European Union regulators to provide the necessary framework to regulate TEPs. As the text is still to be discussed and to be passed, many concerns have been raised regarding the appropriateness of the proposed framework.     

Combining TMS and EEG Offers New Prospects in Cognitive Neuroscience

The combination of brain stimulation by transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) imaging has become feasible due to recent technical developments. The TMS-EEG integration provides real-time information on cortical reactivity and connectivity through the analysis of TMS-evoked potentials (TEPs), and how functional activity links to behavior through the study of TMS-induced modulations thereof. It reveals how these effects vary as a function of neuronal state, differing between individuals and patient groups but also changing rapidly over time during task performance. This review discusses the wide range of possible TMS-EEG applications and what new information may be gained using this technique on the dynamics of brain functions, hierarchical organization, and cortical connectivity, as well as on TMS action per se. An advance in the understanding of these issues is timely and promises to have a substantial impact on many areas of clinical and basic neuroscience.     

Candidate bone-tissue-engineered product based on human-bone-derived cells and polyurethane scaffold

Biodegradable polyurethanes (PURs) have recently been investigated as candidate materials for bone regenerative medicine. There are promising reports documenting the biocompatibility of selected PURs in vivo and the tolerance of certain cells toward PURs in vitro – potentially to be used as scaffolds for tissue-engineered products (TEPs). The aim of the present study was to take a step forward and create a TEP using human osteogenic cells and a polyurethane scaffold, and to evaluate the quality of the obtained TEP in vivo. Human-bone-derived cells (HBDCs) were seeded and cultured on polyurethane scaffolds in a bioreactor for 14 days. The TEP examination in vitro was based on the evaluation of cell number, cell phenotype and cell distribution within the scaffold. TEPs and control samples (scaffolds without cells) were implanted subcutaneously into SCID mice for 4 and 13 weeks. Explants harvested from the animals were examined using histological and immunohistochemical methods. They were also tested in mechanical trials. It was found that dynamic conditions for cell seeding and culture enable homogeneous distribution, maintaining the proliferative potential and osteogenic phenotype of the HBDCs cultured on polyurethane scaffolds. It was also found that HBDCs implanted as a component of TEP survived and kept their ability to produce the specific human bone extracellular matrix, which resulted in higher mechanical properties of the harvested explants when preseeded with HBDCs. The whole system, including the investigated PUR scaffold and the method of human cell seeding and culture, is recommended as a candidate bone TEP.     

Café-au-lait macules and intertriginous freckling in piebaldism: clinical overlap with neurofibromatosis type 1 and Legius syndrome

Piebaldism is an autosomal dominant disorder characterized by congenital hypopigmented patches of skin and hair and has been found to be associated with mutations in the KIT or SLUG genes. Café-au-lait macules (CALM) may occasionally be seen in piebaldism. There are four reports describing six patients who were said to have both piebaldism and neurofibromatosis type 1 (NF1) due to the presence of multiple CALM and intertriginous freckling, but none of these patients had undergone comprehensive NF1 mutation analysis. We describe a large family with piebaldism in which two members meet diagnostic criteria for NF1 based on the presence of >5 CALM and intertriginous freckling. Interestingly, only these two family members are of mixed race, which could be of importance. A novel complex mutation in the KIT gene was identified in several family members affected with piebaldism; the proband meeting diagnostic criteria for NF1 also underwent comprehensive NF1 and SPRED1 testing with no mutations detected. These findings suggest that piebaldism may occasionally include CALM and intertriginous freckling, which may create diagnostic confusion especially in the absence of a family history of piebaldism. However, careful clinical evaluation and molecular testing if necessary should distinguish these two disorders.     

Development and validation of a multidimensional scale of perceived work-family positive spillover

Although the benefits of participating in both work and family have been recognized for more than 30 years (Sieber, 1974), limited empirical research exists. One reason for this oversight is the absence of a well-established scale to measure these benefits. We present a new multidimensional scale of perceived work-family positive spillover. We conducted two studies that aided the development and validation of this scale. Our scale measures three types of work-family positive spillover: behavior-based instrumental positive spillover, value-based instrumental positive spillover, and affective positive spillover. Each of these three types of positive spillover occurs in two directions: from work to family and from family to work. We further evaluate the scale's construct validity in relation to role satisfaction and self-reported mental health.     

Psychotic features in major depression: Is mood congruence important?

We studied outcome and family history in 203 patients with psychotic depression. Patients whose psychotic features were mood-incongruent were significantly younger and had a slightly poorer outcome. Morbid risks for affective disorder and schizophrenia among relatives distinguished these mood-incongruent patients from patients with non-psychotic depression but not from patients with schizophrenia. In contrast, depressive probands with mood-congruent psychotic features resembled probands with non-psychotic depression and differed significantly from schizophrenia probands in terms of family history. While depressed patients with mood-congruent psychotic features experienced poorer short-term outcome relative to non-psychotic depressed patients, a 40-year follow-up has shown that these differences disappear over time. Moreover, these two groups are quite similar according to family history data. Both family history and short-term outcome data suggest that major depression with mood-incongruent psychotic features cannot be classified altogether with either affective disorders or schizophrenia. More definite conclusions must await the results of long-term outcome and family studies of these patients presently underway.     

Age-of-onset heterogeneity in Huntington disease families

Ten Huntington disease (HD) families are analyzed using maximum likelihood methods to study age-of-onset (AO) heterogeneity. Both age of onset and age at examination are used in calculating an individual's likelihood of being affected; familial correlations and family structure are not included in the model. The model allows for differences in current age distributions by considering the distribution of age of onset conditional on age at examination. Families are grouped according to family type (ie, juvenile-onset families and adult-onset families) and then analyzed within each family type as well as between the two types, using both a chi-square test for heterogeneity and F-ratios. The results of the chi-square analyses indicate heterogeneity in AO among the individual families as well as between the two family types. However, the results of the F-ratios show no significant difference between the two family types, indicating that the difference in the chi-square analysis between the two family types is mostly owing to variation among the families. Thus, the results demonstrate that the existing variation in age of onset between these two family types is dwarfed by the magnitude of the variation among the families within each type. This implies that families of sufficient size should be evaluated individually for age-of-onset data for the purpose of either genetic counseling or linkage studies.     

Reporting of life events, family history of hypertension, and cardiovascular activity at rest and during psychological stress

This study investigated whether relations between stressful life events and cardiovascular activity obtained during periods of rest and stress varied as a function of family history of hypertension. Within the family history of hypertension group, males exhibited a positive association between the number of negative avoidable events and resting systolic blood pressure, whereas an inverse association between these two variables was obtained for females. Among females with a family history of hypertension, inverse associations between resting diastolic blood pressure and the subjective effects of life event and number of avoidable events were obtained. Analyses revealed that diastolic blood pressure reactivity to stress was associated with those persons with a family history of hypertension who reported fewer negative life events and less subjective effects for these events.     

New familial association between ocular coloboma and loose anagen syndrome

We present two cases of loose anagen syndrome associated with ocular coloboma in two siblings of unaffected parents and with no family history. We believe they represent a new familial association between these two conditions.     

Cross-reactivity between the pollens of Cupressus sempervirens (common cypress) and of Cryptomeria japonica (Japanese cedar)

A clinical and immunologic study was performed comparing a group of French patients allergic to the pollens of cypress (Cupressus sempervirens, which belongs to the Cupressaceae family) and a group of Japanese patients allergic to the pollens of Sugi (Cryptomeria japonica, which belongs to the Taxodiaceae family). By skin testing, RAST, and RAST inhibition, clear cross-reactivity was detected between the two pollens. No cross-reactivity was detected between the pollens of Cupressus sempervirens and Sugi and the Pinaceae family. In addition, one can speculate that an antigen in Cupressus sempervirens is cross-reactive with SBP, the major allergen of Sugi, suggesting that there is a closer relationship between the Taxodiaceae family and the Cupressaceae family than between these two families and the other families of the gymnosperms. This finding throws new light on the taxonomy of the gymnosperms.     

一种鉴定结核分枝杆菌"北京家族"菌株的新方法

目的 研究结核分枝杆菌"北京家族"菌株鉴定的新方法——RD105缺失检测的可行性.方法 分别应用间隙寡核苷酸分型(Spoligotyping)和RD105缺失检测两种方法对结核分枝杆菌进行"北京家族"的鉴定,比较分析两种方法进行菌株鉴定结果的差异.结果 共对来自北京、福建、新疆和吉林的342株结核分枝杆菌临床分离菌株进行了鉴定,"北京家族"菌株261株,占76.32%.非"北京家族"菌株81株,占23.68%.两种方法鉴定结果的符合度达100%.结论 简单、快速的新方法——RD105缺失检测可替代原始经典方法Spoligotyping用于结核分枝杆菌"北京家族"菌株的鉴定.     

Delusional depression. Phenomenology, Neuroendocrine function, and tricyclic antidepressant response

The authors studied clinical variables, family history, cortisol secretion, and 4-week tricyclic antidepressant response in 13 delusional and 12 non-delusional, hospitalized depressives. Comparison in these parameters between the two groups revealed more family history of depression but less of alcoholism, greater frequency of cortisol hypersecretion, and poorer response to tricyclics in the delusional group. This lack of complete response was found despite full remission of delusions in 84.6% of the delusional subjects. The clinical and theoretical implications of these findings are discussed.     

Detection of expansion regions in Portuguese bipolar families

We have studied 24 families with multiple affected members with bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation [Macedo et al., 1999] we would find large repeat expansions. The families meeting inclusion criteria had a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We used the repeat expansion detection (RED) method to test patients (n = 24) and controls from these families and unrelated controls (n = 53). We also genotyped patients and family members from two families with large expansions at the known expansion loci on chromosomes 13, 17, and 18. The RED method revealed a higher number of large expansions in patients compared with controls (t-test; P < 0.0055: Mann-Whitney U; P = 0.02). The patients with the largest expansions were typed at the specific loci on chromosomes 13, 17, and 18 and the chromosome 18 expansion locus segregated with disease in one family, and a second family showed segregation with the expansion located at the SCA8 locus on chromosome 13. Genetic anticipation had been analyzed in this cohort of families, with correction for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal vs. paternal transmission. None of these potential confounds appeared to account for the observed anticipation. We also identified that the presence of large expansions in affected family members derives primarily from two families from the genetically isolated Azores population. One family shows segregation with the chromosome 18 locus, whereas the other family segregates with expansions at the SCA8 locus. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:854-857, 2000.