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S Temple

Publications and source records attributed to S Temple.

At least 19 recordsLinked to original sources

Functional nicotinic acetylcholine receptor expression on stem and progenitor cells of the early embryonic nervous system.

Although the adult brain contains nicotinic acetylcholine (ACh) receptors vital to cortical function, little is known about the assembly of embryonic receptor subunits into functional receptors or their role in fetal brain development. We now report the first evidence of functional nicotinic ACh receptors on stem and progenitor cells of fetal mouse cerebral cortex as early as embryonic day 10.

Animals↗

Functional nicotinic acetylcholine receptor expression in stem and progenitor cells of the early embryonic mouse cerebral cortex.

The adult cerebral cortex contains nicotinic acetylcholine (ACh) receptors vital to cortical function. However, little is known about the assembly of embryonic nicotinic receptor subunits into functional receptors or whether they play an active role in cortical development. We now report evidence of functional nicotinic acetylcholine receptor channels in fetal mouse cerebral cortex as early as embryonic day 10 (E10), when the cortex consists of dividing stem and progenitor cells. Patch-clamp electrophysiological measurements indicate that nicotine and ACh evoke sizable inward currents characteristic of nicotinic receptors, that are strongly rectifying with a reversal potential near 0 mV. Three different nicotinic agonists, ACh, nicotine, and dimethylphenylpiperazinium, evoked cytosolic Ca(2+) signals. Agonist-evoked Ca(2+) signals and electrophysiological responses were found in greater than 70% of all E10-E11 cells tested and were blocked by nicotinic receptor antagonists. The Ca(2+) response to nicotinic agonists was markedly prolonged in cells from early embryonic stages relative to later stages of development. alpha3, alpha4, and alpha7 receptor subunit proteins were detected immunocytochemically in cortical cells from E10 to birth. The incidence of each subunit declined with embryonic age, suggesting a role in early development. We discuss the possible function of nicotinic receptors in early cortical development and their role as a target for nicotine in the developmental pathologies associated with the fetal tobacco syndrome.

Acetylcholine↗

Multipotent stem cells from the mouse basal forebrain contribute GABAergic neurons and oligodendrocytes to the cerebral cortex during embryogenesis.

During CNS development, cell migrations play an important role, adding to the cellular complexity of different regions. Earlier studies have shown a robust migration of cells from basal forebrain into the overlying dorsal forebrain during the embryonic period. These immigrant cells include GABAergic neurons that populate the cerebral cortex and hippocampus. In this study we have examined the fate of other basal forebrain cells that migrate into the dorsal forebrain, identifying basal cells using an antibody that recognizes both early (dlx1/2) and late (dlx 5/6) members of the dlx homeobox gene family. We found that a subpopulation of cortical and hippocampal oligodendrocytes are also ventral-derived. We traced the origin of these cells to basal multipotent stem cells capable of generating both GABAergic neurons and oligodendrocytes. A clonal analysis showed that basal forebrain stem cells produce significantly more GABAergic neurons than dorsal forebrain stem cells from the same embryonic age. Moreover, stem cell clones from basal forebrain are significantly more likely to contain both GABAergic neurons and oligodendrocytes than those from dorsal. This indicates that forebrain stem cells are regionally specified. Whereas dlx expression was not detected within basal stem cells growing in culture, these cells produced dlx-positive products that are capable of migration. These data indicate that the developing cerebral cortex incorporates both neuronal and glial products of basal forebrain and suggest that these immigrant cells arise from a common progenitor, a dlx-negative basal forebrain stem cell.

Animals↗

The development of neural stem cells.

The discovery of stem cells that can generate neural tissue has raised new possibilities for repairing the nervous system. A rush of papers proclaiming adult stem cell plasticity has fostered the notion that there is essentially one stem cell type that, with the right impetus, can create whatever progeny our heart, liver or other vital organ desires. But studies aimed at understanding the role of stem cells during development have led to a different view - that stem cells are restricted regionally and temporally, and thus not all stem cells are equivalent. Can these views be reconciled?

Animals↗

Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells.

Multipotent stem cells that generate both neurons and glia are widespread components of the early neuroepithelium. During CNS development, neurogenesis largely precedes gliogenesis: how is this timing achieved? Using clonal cell culture combined with long-term time-lapse video microscopy, we show that isolated stem cells from the embryonic mouse cerebral cortex exhibit a distinct order of cell-type production: neuroblasts first and glioblasts later. This is accompanied by changes in their capacity to make neurons versus glia and in their response to the mitogen EGF. Hence, multipotent stem cells alter their properties over time and undergo distinct phases of development that play a key role in scheduling production of diverse CNS cells.

Animals↗

CNS development: The obscure origins of adult stem cells.

Stem cells of the adult central nervous system are the focus of a great deal of attention because of their potential for making new neural cells. A recent study has claimed to identify their in vivo location, but this important issue remains controversial.

Adult↗

Stem cells in the adult mammalian central nervous system.

Over the past year, evidence has accrued that adult CNS stem cells are a widespread progenitor cell type. These cells may normally replace neurons and/or glia in the adult brain and spinal cord. Advances have been made in understanding the signals that regulate stem cell proliferation and differentiation. A deeper understanding of the structure of germinal zones has helped us move towards identifying stem cells in vivo. Recent studies suggest that the fate of stem cell progeny in vivo may be linked to the complexity of the animal's environment.

Age Factors↗

Cancer among first-degree relatives of probands with invasive and borderline ovarian cancer.

OBJECTIVE: The familial clustering of ovarian, breast, endometrial, colon; and prostate cancer was compared in first-degree relatives of probands with invasive and borderline ovarian cancer to determine coaggregation. METHODS: Probands (n=392), who had been patients in the Division of Gynecologic Oncology at Washington University, were ascertained consecutively. Family history on 2192 first-degree relatives was collected by personal interviews of the probands and other family members. Estimates of prevalence of cancers in first-degree relatives of the two proband groups were compared. Survival analysis was used to examine the age-at-onset distribution of each cancer in relatives of invasive probands versus relatives of borderline probands. RESULTS: Among the relatives were 24 cases of ovarian cancer, 46 cases of breast cancer, 13 cases of endometrial cancer, and 25 and 28 cases of colon and prostate cancer, respectively. There were no significant differences in the prevalence of any of these cancers in relatives of the invasive and borderline probands. Cumulative lifetime risk estimates did not differ between the relatives of the two groups for any cancers. Age-at-onset of ovarian cancer did not differ between probands with positive family histories of the five cancers and those with negative histories. The inability to reject the null hypothesis of no differences in the first-degree relatives of our two study groups might be from insufficient power to detect small differences, given our sample size. CONCLUSION: These results suggest that relatives of patients with invasive and borderline ovarian cancer might share similar cancer risks and age-at-onset distributions.

Age of Onset↗

Intrinsic programs of patterned cell lineages in isolated vertebrate CNS ventricular zone cells.

Using long-term, time-lapse video-microscopy, we investigated how single progenitor cells isolated from the early embryonic cerebral cortex produce neurons and glia over time. Clones of 10 cells or less were produced by short symmetric or asymmetric division patterns, commonly terminating in a 'pair progenitor' for two morphologically identical neurons. Larger trees were composites of these short sub-lineages: more prolific neuroblasts underwent repeated asymmetric divisions, each producing a minor neuroblast that typically made (3/4)10 progeny, and a sister cell capable of generating more progeny. Particular division patterns were seen repeatedly. In contrast, glioblasts underwent a prolonged series of symmetric divisions. These patterned lineage trees were generated from isolated cells growing on plastic, suggesting they are largely intrinsically programmed. Our data demonstrate for the first time that CNS progenitor cells have stereotyped division patterns, and suggest that as in invertebrates, these may play a role in neural development.

Animals↗

Stem cells in the embryonic cerebral cortex: their role in histogenesis and patterning.

The cytoarchitectural simplicity of the cerebral cortex makes it an attractive system to study central nervous system (CNS) histogenesis--the process whereby diverse cells are generated in the right numbers at the appropriate place and time. Recently, multipotent stem cells have been implicated in this process, as progenitor cells for diverse types of cortical neurons and glia. Continuous analysis of stem cell clone development reveals stereotyped division patterns within their lineage trees, highly reminiscent of neural lineage trees in arthropods and Caenorhabditis elegans. Given that these division patterns play a critical part in generating diverse neural types in invertebrates, we speculate that they play a similar role in the cortex. Because stereotyped lineage trees can be observed from cells growing at clonal density, cell-intrinsic factors are likely to have a key role in stem cell behavior. Cortical stem cells also respond to environmental signals to alter the types of cells they generate, providing the means for feedback regulation on the germinal zone. Evidence is accumulating that cortical stem cells, influenced by intrinsic programs and environmental signals, actually change with development-for example, by reducing the number and types of neurons they produce. Age-related changes in the stem cell population may have a critical role in orchestrating development; whether these cells truly self-renew is a point of discussion. In summary, we propose that cortical stem cells are the focus of regulatory mechanisms central to the development of the cortical cytoarchitecture.

Animals↗

FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells.

The embryonic cerebral cortex contains a population of stem-like founder cells capable of generating large, mixed clones of neurons and glia in vitro. We report that the default state of early cortical stem cells is neuronal, and that stem cells are heterogeneous in the number of neurons that they generate. In low fibroblast growth factor (FGF2) concentrations, most maintain this specification, generating solely neuronal progeny. Oligodendroglial production within these clones is stimulated by a higher, threshold level of FGF2, and astrocyte production requires additional environmental factors. Because most cortical neurons are born before glia in vivo, these data support a model in which the scheduled production of cortical cells involves an intrinsic neuronal program in the early stem cells and exposure to environmental, glia-inducing signals.

Animals↗

Treating inner-city families of homicide victims: a contextually oriented approach.

Violence, including youth homicide, has assumed near epidemic proportions in US inner cities, with few signs that such violence is abating. Professionals working with families after the murder of a family member, are faced with the task of helping such families achieve a meaningful restoration of functioning. At the same time, there is a need to prevent retaliatory violence by surviving siblings and other family members. A treatment model will be discussed that uses the basic, theoretical principles of Boszormenyi-Nagy's Contextual Therapy (CT) while incorporating White and Epston's technique of "therapeutic certificates" in work with young people coping with loss via homicide. Case examples, drawn from the author's work at a unique, predominantly African American agency in an urban inner city will be used to illustrate applications of CT principles, and to show how therapeutic certificates can provide tools to clinicians working with this deeply troubling problem.

Adaptation, Psychological↗

Vertebrate neural progenitor cells: subtypes and regulation.

Several advances have been made recently in characterizing neural progenitor cells. In vertebrates, multipotential stem cells have been demonstrated in the developing forebrain both in vitro and in vivo, and a class of stem cells has been identified in the adult CNS. Factors that regulate the proliferation and differentiation of subtypes of neural progenitor cells have also been described. In invertebrates, progress has been made in identifying genes involved in neural progenitor cell specification, cell-fate choices and regulation.

Animals↗

Mothers' emotional needs and difficulties after childbirth.

OBJECTIVE: To set up and evaluate weekly group sessions for mothers experiencing difficulties after childbirth. METHOD: These sessions were held at Barwon Region Child Health Centre in Geelong, Victoria, with input from a general practitioner and a clinical psychologist. RESULTS: Questionnaires confirmed the group sessions were effective in allaying the mothers' concerns about their babies' health, and that the mothers had low self esteem. Records of the meetings indicated that mothers were mainly concerned about their babies' health, anxiety, lifestyle changes, depression, relationship problems, their own health, the birth experience and lack of support. Social factors often predisposed mothers to these problems. CONCLUSION: There is clearly scope for the general practitioner to be involved in the diagnosis and management of postnatal problems and group sessions are an effective way of achieving this.

Adult↗

Environmental and policy approaches to cardiovascular disease prevention through nutrition: opportunities for state and local action.

This article reviews environmental and policy intervention approaches to cardiovascular disease prevention through nutrition and recommends opportunities for state and local health departments to initiate and participate in environmental and nutrition policy initiatives. By addressing these complementary aims, the authors hope to stimulate further efforts to achieve progress in nutrition promotion among state and local health-related organizations. Key categories of opportunity to develop new or expanded nutrition policies and environmental strategies include economic incentives, food assistance and feeding programs, regulations for institutional food service operations, and nutrition services in health care. Environmental strategies to reduce barriers to following dietary guidelines, such as point-of-choice programs and school nutrition programs, should be tailored for local communities and widely disseminated. In addition, current federal policy efforts, notably nutrition labeling rules, will provide a valuable focal point for state and local advocacy, education, and monitoring.

Cardiovascular Diseases↗