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Selected AbstractsCritical role for retinol in the generation/differentiation of angioblasts required for embryonic blood vessel formation,DEVELOPMENTAL DYNAMICS, Issue 4 2004Amanda C. LaRue Abstract Numerous studies demonstrate that vitamin A (retinol) deficiency causes abnormal cardiovascular morphogenesis. We evaluated the impact of retinol deficiency on the regulation of the numbers of endothelial cells and angioblasts (endothelial progenitors) produced during embryonic quail development. At the one-somite stage, there were no discernible differences in the mean number of endothelial cells or angioblasts in normal and retinol-deficient embryos. However, retinol-deficient embryos at the three-somite stage had an increase in the mean number of endothelial cells but no difference in the mean number of angioblasts. By contrast, retinol-deficient embryos at the five-somite stage have 61% of the normal number of endothelial cells and 12% of the normal number of angioblasts. Similarly, retinol-deficient embryos at the 10-somite stage had 71% and 60% of normal numbers of endothelial cells in capillary-like networks and the sinuses venosus, respectively. Furthermore, we show that retinol deficiency did not elicit a global reduction in mesodermal cell numbers but was specific to cells of the endothelial lineage. Taken together, our findings suggest that vascular abnormalities observed under conditions of retinol deficiency are due to reduction in the number of angioblasts and consequently an insufficiency in the number of endothelial cells required to build complex vascular networks. Developmental Dynamics 230:666,674, 2004. © 2004 Wiley-Liss, Inc. [source] Mixed primary culture and clonal analysis provide evidence that NG2 proteoglycan-expressing cells after spinal cord injury are glial progenitorsDEVELOPMENTAL NEUROBIOLOGY, Issue 7 2007Soonmoon Yoo Abstract NG2+ cells in the adult rat spinal cord proliferate after spinal cord injury (SCI) and are postulated to differentiate into mature glia to replace some of those lost to injury. To further study these putative endogenous precursors, tissue at 3 days after SCI or from uninjured adults was dissociated, myelin partially removed and replicate cultures grown in serum-containing or serum-free medium with or without growth factors for up to 7 days in vitro (DIV). Cell yield after SCI was 5,6 times higher than from the normal adult. Most cells were OX42+ microglia/macrophages but there were also more than twice the normal number of NG2+ cells. Most of these coexpressed A2B5 or nestin, as would be expected for glial progenitors. Few cells initially expressed mature astrocyte (GFAP) or oligodendrocyte (CC1) markers, but more did at 7 DIV, suggesting differentiation of glial precursors in vitro. To test the hypothesis that NG2+ cells after SCI express progenitor-like properties, we prepared free-floating sphere and single cell cultures from purified suspension of NG2+ cells from injured spinal cord. We found that sphere cultures could be passaged in free-floating subcultures, and upon attachment the spheres clonally derived from an acutely purified single cell differentiated into oligodendrocytes and rarely astrocytes. Taken together, these data support the hypothesis that SCI stimulates proliferation of NG2+ cells that are glial progenitor cells. Better understanding the intrinsic properties of the NG2+ cells stimulated by SCI may permit future therapeutic manipulations to improve recovery after SCI. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] Chloracne: histopathologic findings in one caseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2002Maria Antonia Pastor Background: Chloracne is an acneiform eruption due to poisoning by halogenated aromatic compounds having a specific molecular shape. This condition is always a symptom of systemic poisoning by chemical chloracnegens and not just a cutaneous disorder. Methods: We have studied a patient with severe chloracne who showed cutaneous lesions involving mostly the face and the axillae. Results:, Histopathologic study of the facial lesions demonstrated that almost every vellus hair follicle was involved, showing a dilated infundibulum filled by a keratotic plug. This keratotic material was mostly composed of orthokeratotic basket-weave basophilic corneocytes, namely infundibular keratin, although there were also some dilated infundibula containing eosinophilic laminated or granular sebum at their center. Small infundibular cysts were more numerous than comedones. Mature and well-developed sebaceous glands were seen at the base of many of the dilated infundibula and no squamous metaplasia of the sebaceous glands or ducts could be demonstrated. Hyperpigmentation of the lesions resulted from hyperproduction of melanin by a normal number of melanocytes along the basal layer of the epidermis and infundibular epithelium. Abundant melanin granules also impregnated the corneocytes of the infundibular plugs. Conclusions:, Our findings support the notion that tiny infundibular cysts rather than comedones represent the basic lesions of chloracne. [source] Severe generalized dystonia due to primary putaminal degeneration: Case report and review of the literature,MOVEMENT DISORDERS, Issue 3 2002Ruth H. Walker MB Abstract Putaminal lesions of a variety of etiologies may cause secondary dystonia. We report on a case of primary putaminal degeneration as a cause of severe childhood-onset generalized dystonia and review the literature of the pathology of dystonia. A 44-year-old patient with severe generalized childhood-onset dystonia and macrocephaly underwent neurological evaluation and neuropathological examination. Neurological examination was normal apart from dystonia and signs referable to prior cryothalamotomy. Workup for metabolic and genetic causes of dystonia was negative. Neuroimaging showed severe bilateral putaminal degeneration, which subsequently correlated with the neuropathological findings of gliosis, spongiform degeneration, and cavitation. The substantia nigra pars compacta contained a normal number of neurons but decreased tyrosine hydroxylase immunoreactivity. There were no histopathological markers of other metabolic or degenerative diseases. © 2002 Movement Disorder Society. [source] Association of normal nailfold end row loop numbers with a shorter duration of untreated disease in children with juvenile dermatomyositisARTHRITIS & RHEUMATISM, Issue 5 2010Rochella A. Ostrowski Objective To determine the association of normal numbers of end row loops (ERLs) in nailfold capillaries at the time of diagnosis of juvenile dermatomyositis (DM) with clinical findings in untreated children with the disease and to identify predictors of the development of decreased numbers of ERLs. Methods Clinical and laboratory data from 80 untreated children with juvenile DM were collected. ERL numbers were recorded at the time of diagnosis and at 24 months and 36 months thereafter. The 12 children who had normal ERLs at diagnosis were compared with the remaining 68 children. Outcomes included the duration of untreated disease, the duration of treatment with immunosuppressive medications, family medical history, Disease Activity Score (DAS) for juvenile DM, creatinine phosphokinase level, aldolase level, absolute number of CD3,CD56+/16+ natural killer cells, and von Willebrand factor antigen level. Cross-sectional and longitudinal analyses were performed. Results At diagnosis, children with normal ERLs had a shorter duration of untreated disease (P = 0.03) and a lower skin DAS (P = 0.045). Over time, an increased likelihood of having decreased numbers of ERLs was associated with a longer duration of untreated disease and with a higher skin DAS. Conclusion The presence of a normal number of ERLs in juvenile DM appears to be associated with a shorter duration of symptoms and may be a useful indicator of disease chronicity in the newly diagnosed child. Normal ERLs is also associated with a lower skin DAS. The lack of association between normal ERLs and other variables indicates that normal findings on nailfold capillaroscopy should not be used as justification to delay immunosuppressive therapy in children with typical symptoms of juvenile DM. [source] Oda16/Wdr69 is essential for axonemal dynein assembly and ciliary motility during zebrafish embryogenesisDEVELOPMENTAL DYNAMICS, Issue 8 2010Chunlei Gao Abstract In the alga Chlamydomonas reinhardtii, Oda16 functions during ciliary assembly as an adaptor for intraflagellar transport of outer arm dynein. Oda16 orthologs only occur in genomes of organisms that use motile cilia; however, such cilia play multiple roles during vertebrate development and the contribution of Oda16 to their assembly remains unexplored. We demonstrate that the zebrafish Oda16 ortholog (Wdr69) is expressed in organs with motile cilia and retains a role in dynein assembly. Antisense morpholino knockdown of Wdr69 disrupts ciliary motility and results in multiple phenotypes associated with vertebrate ciliopathies. Affected cilia included those in Kupffer's vesicle, where Wdr69 plays a role in generation of asymmetric fluid flow and establishment of organ laterality, and otic vesicles, where Wdr69 is needed to develop normal numbers of otoliths. Analysis of cilium ultrastructure revealed loss of outer dynein arms in morphant embryos. These results support a remarkable level of functional conservation for Oda16/Wdr69. Developmental Dynamics 239:2190,2197, 2010. © 2010 Wiley-Liss, Inc. [source] Critical role for retinol in the generation/differentiation of angioblasts required for embryonic blood vessel formation,DEVELOPMENTAL DYNAMICS, Issue 4 2004Amanda C. LaRue Abstract Numerous studies demonstrate that vitamin A (retinol) deficiency causes abnormal cardiovascular morphogenesis. We evaluated the impact of retinol deficiency on the regulation of the numbers of endothelial cells and angioblasts (endothelial progenitors) produced during embryonic quail development. At the one-somite stage, there were no discernible differences in the mean number of endothelial cells or angioblasts in normal and retinol-deficient embryos. However, retinol-deficient embryos at the three-somite stage had an increase in the mean number of endothelial cells but no difference in the mean number of angioblasts. By contrast, retinol-deficient embryos at the five-somite stage have 61% of the normal number of endothelial cells and 12% of the normal number of angioblasts. Similarly, retinol-deficient embryos at the 10-somite stage had 71% and 60% of normal numbers of endothelial cells in capillary-like networks and the sinuses venosus, respectively. Furthermore, we show that retinol deficiency did not elicit a global reduction in mesodermal cell numbers but was specific to cells of the endothelial lineage. Taken together, our findings suggest that vascular abnormalities observed under conditions of retinol deficiency are due to reduction in the number of angioblasts and consequently an insufficiency in the number of endothelial cells required to build complex vascular networks. Developmental Dynamics 230:666,674, 2004. © 2004 Wiley-Liss, Inc. [source] Hippocampal Malformations Do Not Necessarily Evolve into Hippocampal SclerosisEPILEPSIA, Issue 6 2005Arjune Sen Summary:,Purpose: Hippocampal malformations have been proposed to underlie or evolve into hippocampal sclerosis, a common cause of refractory partial epilepsy. We report two patients with chronic epilepsy and developmental abnormalities of the hippocampus and cortex. We seek to address, in patients with recurrent convulsive seizures over many decades, whether hippocampal malformations necessarily progress to hippocampal sclerosis. Methods: The first patient died at age 76 years and had experienced convulsive seizures for 43 years. The second patient, aged 64 years at death, had experienced convulsive seizures for 49 years. The brains were processed routinely. Immunohistochemistry for dynorphin and neuropeptide Y was performed. Results: The first case exhibited bilateral perisylvian polymicrogyria. Both hippocampi demonstrated abnormal convolution in the CA1 subfield and subiculum. In the second case, periventricular heterotopia was found in the wall of the right lateral ventricle. The right hippocampus was abnormally oriented with excessive convolutions of the pyramidal cell layer between CA1 and the subiculum. In neither patient did the hippocampi exhibit neuronal loss. Furthermore, dynorphin immunohistochemistry revealed no reactivity in the molecular layers, and staining with neuropeptide Y confirmed normal numbers of hilar interneurons. Conclusions: These two cases demonstrate histologically that, even in long-standing epilepsy, malformations of the hippocampus do not necessarily develop into hippocampal sclerosis. [source] TLR2-independent induction and regulation of chronic intestinal inflammationEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2010Olivier Boulard Abstract Interactions between the intestinal microflora and host innate immune receptors play a critical role in intestinal homeostasis. Several studies have shown that TLR2 can modulate inflammatory responses in the gut. TLR2 signals enhance tight junction formation and fortify the epithelial barrier, and may play a crucial role in driving acute inflammatory responses towards intestinal bacterial pathogens. In addition, TLR2 agonists can have direct effects on both Th1 cells and Treg. To define the role of TLR2 in the induction and regulation of chronic intestinal inflammation we examined the effects of TLR2 deletion on several complementary models of inflammatory bowel disease. Our results show that TLR2 signals are not required for the induction of chronic intestinal inflammation by either innate or adaptive immune responses. We further show that TLR2,/, mice harbor normal numbers of Foxp3+ Treg that are able to suppress intestinal inflammation as effectively as their WT counterparts. We also did not find any intrinsic role for TLR2 for pathogenic effector T-cell responses in the gut. Thus, in contrast to their role in acute intestinal inflammation and repair, TLR2 signals may have a limited impact on the induction and regulation of chronic intestinal inflammation. [source] MSK regulate TCR-induced CREB phosphorylation but not immediate early gene transcriptionEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2007Madlen Kaiser Abstract Stimulation of the T cell receptor activates the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) cascades. We demonstrate that TCR stimulation also activates the mitogen- and stress-activated kinases (MSK) downstream of ERK1/2 and p38 in both a T cell line and primary peripheral T cells. MSK1/2-knockout mice were found to have normal numbers of T cells in the thymus, and development of these cells appeared unaffected. Using naive T cells and T lymphoblasts from MSK1/2-knockout mice, it was found that MSK was the kinase responsible for phosphorylation of the transcription factor CREB in response to TCR stimulation. Phosphorylation of CREB by MSK has been linked to the transcription of nur77, nor1 and c-fos downstream of MAPK signalling in various cell types. In T cells, the TCR-dependent transcription of these genes was found to require a MAPK-dependent but MSK-independent signalling pathway. Nevertheless, the number of T cells present in the spleens of MSK1/2-knockout mice and the IL-2-induced proliferation of these cells was reduced compared to wild-type mice. This correlated to a reduction in the TCR-induced up-regulation of the IL-2 receptor CD25 and a requirement for MSK in IL-2-induced CREB phosphorylation. [source] IL-18, but not IL-12, is required for optimal cytokine production by influenza virus-specific CD8+ T cellsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 2 2007Alice Abstract The potent innate cytokines IL-12 and IL-18 are considered to be important antigen-independent mediators of IFN-, production by NK cells and T,lymphocytes. The present analysis addresses the physiological role of IL-12 and IL-18 in the generation of virus-specific CD8+ T cells. Both wt C57BL/6J (B6) mice and mice with disrupted IL-12p40 (IL-12p40,/,) or IL-18 (IL-18,/,) genes were infected with an influenza,A virus and the characteristics of the resultant epitope-specific CD8+ T cell responses were compared. While IL-12 appeared to have no notable effect on either virus growth or on CD8+ T cell response profiles, the absence of IL-18 was associated with delayed virus clearance from the lung and, despite normal numbers, a significantly reduced production of IFN-,, TNF-,, and IL-2 by epitope-specific CD8+ T cells. While this cytokine phenotype was broadly maintained in IL-12p40/IL-18 double-knockout mice, no evidence was seen for any additive effect. Together, our results suggest that IL-18, but not IL-12, induces optimal, antigen-specific production of key cytokines by CD8+ T cells for the efficient clearance of influenza virus from the lungs of infected mice. [source] Specific bronchoalveolar lavage fluid T cells associate with disease in a pair of monozygotic twins discordant for sarcoidosisJOURNAL OF INTERNAL MEDICINE, Issue 6 2001J. Grunewald Abstract.,Grunewald J, Eklund A (Karolinska Hospital, Stockholm, Sweden). Specific bronchoalveolar lavage fluid T cells associate with disease in a pair of monozygotic twins discordant for sarcoidosis (Case report). J Intern Med 2001; 250: 535,539. A 49-year-old Caucasian woman had an acute onset of sarcoidosis. Bronchoscopy with bronchoalveolar lavage (BAL) showed a pronounced accumulation of BAL fluid CD4+ T cells expressing the T-cell receptor (TCR) AV2S3 gene. In line with this observation, the patient was HLA-DR17 positive, previously shown to strongly correlate with lung compartmentalized AV2S3+ T cells. At follow-up after recovery, reduced numbers of BAL fluid AV2S3+ T cells were found. Interestingly, BAL fluid of a healthy monozygotic twin sister contained normal numbers of AV2S3+ lung T cells. This report shows the T-cell repertoire of BAL fluid T cells to correlate with the disease (sarcoidosis), indicating a local and specific immune response triggered by an unknown antigen in sarcoidosis. [source] PbSR is synthesized in macrogametocytes and involved in formation of the malaria crystalloidsMOLECULAR MICROBIOLOGY, Issue 6 2008Victoria Carter Summary Crystalloids are transient organelles that form in developing malaria ookinetes and disappear after ookinete-to-oocyst transition. Their origins and functions remain poorly understood. The Plasmodium berghei scavenger receptor-like protein PbSR is essential for mosquito-to-host transmission of the parasite: PbSR knockout parasites produce normal numbers of oocysts that fail to form sporozoites, pointing to a role for PbSR in the oocyst during sporogony. Here, using fluorescent protein tagging and targeted gene disruption, we show that PbSR is synthesized in macrogametocytes, gets targeted to the crystalloids of developing ookinetes and is involved in crystalloid formation. While oocyst sporulation rates of PbSR knockout parasites are highly reduced in parasite-infected mosquitoes, sporulation rates in vitro are not adversely affected, supporting the view that mosquito factors could be involved in the PbSR loss-of-function phenotype. These findings are the first to identify a parasite protein involved with the crystalloid organelle, and suggest a novel protein-trafficking mechanism to deliver PbSR to the oocysts. [source] Effect of L -arginine supplementation on immune responsiveness in patients with sickle cell disease,PEDIATRIC BLOOD & CANCER, Issue 2 2010Arnette Scavella MD Abstract Background L -arginine (L -Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L -Arg deficiency and immune dysfunction in SSD in steady-state. Procedure Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L -Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3,) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-,) were evaluated with and without L -Arg. Results SSD patients had significantly lower L -Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P,=,0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L -Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L -Arg supplementation did not increase this response. L -Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-, after addition of L -Arg. CD3, chain expression increased after addition of L -Arg in both groups; differences were insignificant. Conclusion L -Arg levels in steady-state SSD are significantly lower than in controls. L -Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3, chain expression although upregulation of expression occurred after L -Arg supplementation for both groups. Pediatr Blood Cancer. 2010;55:318,323. © 2010 Wiley,Liss, Inc. [source] Hypothalamic input is required for development of normal numbers of thyrotrophs and gonadotrophs, but not other anterior pituitary cells in late gestation sheepTHE JOURNAL OF PHYSIOLOGY, Issue 4 2008Eva Szarek To evaluate the hypothalamic contribution to the development of anterior pituitary (AP) cells we surgically disconnected the hypothalamus from the pituitary (hypothalamo-pituitary disconnection, HPD) in fetal sheep and collected pituitaries 31 days later. Pituitaries (n= 6 per group) were obtained from fetal sheep (term = 147 ± 3 days) at 110 days (unoperated group) of gestation and at 141 days from animals that had undergone HPD or sham surgery at 110 days. Cells were identified by labelling pituitary sections with antisera against the six AP hormones. Additionally, we investigated the colocalization of glycoprotein hormones. The proportions of somatotrophs and corticotrophs were unchanged by age or HPD. Lactotrophs increased 80% over time, but the proportion was unaffected by HPD. Thyrotrophs, which were unaffected by age, increased 70% following HPD. Gonadotrophs increased with gestational age (LH+ cells 55%; FSH+ cells 19-fold), but this was severely attenuated by HPD. We investigated the possible existence of a reciprocal effect of HPD on multipotential glycoprotein-expressing cells. Co-expression of LH and TSH was extremely rare (< 1%) and unchanged over the last month of gestation or HPD. The increase of gonadotrophs expressing FSH only or LH and FSH was attenuated by HPD. Therefore, the proportions of somatotrophs, lactotrophs and corticotrophs are regulated independently of hypothalamic input in the late gestation fetal pituitary. In marked contrast, the determination of the thyrotroph and gonadotroph lineages over the same time period is subject to complex mechanisms involving hypothalamic factors, which inhibit differentiation and/or proliferation of thyrotrophs, but stimulate gonadotrophs down the FSH lineage. Development of a distinct population of gonadotrophs, expressing only LH, appears to be subject to alternative mechanisms. [source] Association of normal nailfold end row loop numbers with a shorter duration of untreated disease in children with juvenile dermatomyositisARTHRITIS & RHEUMATISM, Issue 5 2010Rochella A. Ostrowski Objective To determine the association of normal numbers of end row loops (ERLs) in nailfold capillaries at the time of diagnosis of juvenile dermatomyositis (DM) with clinical findings in untreated children with the disease and to identify predictors of the development of decreased numbers of ERLs. Methods Clinical and laboratory data from 80 untreated children with juvenile DM were collected. ERL numbers were recorded at the time of diagnosis and at 24 months and 36 months thereafter. The 12 children who had normal ERLs at diagnosis were compared with the remaining 68 children. Outcomes included the duration of untreated disease, the duration of treatment with immunosuppressive medications, family medical history, Disease Activity Score (DAS) for juvenile DM, creatinine phosphokinase level, aldolase level, absolute number of CD3,CD56+/16+ natural killer cells, and von Willebrand factor antigen level. Cross-sectional and longitudinal analyses were performed. Results At diagnosis, children with normal ERLs had a shorter duration of untreated disease (P = 0.03) and a lower skin DAS (P = 0.045). Over time, an increased likelihood of having decreased numbers of ERLs was associated with a longer duration of untreated disease and with a higher skin DAS. Conclusion The presence of a normal number of ERLs in juvenile DM appears to be associated with a shorter duration of symptoms and may be a useful indicator of disease chronicity in the newly diagnosed child. Normal ERLs is also associated with a lower skin DAS. The lack of association between normal ERLs and other variables indicates that normal findings on nailfold capillaroscopy should not be used as justification to delay immunosuppressive therapy in children with typical symptoms of juvenile DM. [source] | |||||||||||||