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Biomedical subjects

Heather M Young

Publications and source records attributed to Heather M Young.

At least 19 recordsLinked to original sources
PubMed2007

Effect of Gdnf haploinsufficiency on rate of migration and number of enteric neural crest-derived cells.

The enteric nervous system arises predominantly from vagal level neural crest cells that migrate into the foregut and then colonize the entire length of the gastrointestinal tract. Previous studies have demonstrated that glial cell line-derived neurotrophic factor (GDNF) promotes the migration of enteric neural crest-derived cells (ENCs) in vitro, but a role for GDNF in the migration of ENCs in vivo has yet to be demonstrated. In this study, the effects of Gdnf haploinsufficiency on ENC rate of migration and number during mid embryonic development were examined. Although the entire gut of embryonic Gdnf(+/-) mice was colonized, a significant delay in the migration of ENCs along the embryonic hindgut was found. However, significant effects of Gdnf haploinsufficiency on ENC number were detected before the stage at which migration defects were first evident. As previous studies have shown a relationship between ENC number and migration, the effects of Gdnf haploinsufficiency on migration may be due to an indirect effect on cell number and/or a direct effect of GDNF on ENC migration. Gdnf haploinsufficiency did not cause any detectable change in the rate of neuronal differentiation of ENCs.

Animals↗
PubMed2006

Development of colonic motility in the neonatal mouse-studies using spatiotemporal maps.

Colonic migrating motor complexes (CMMCs) are spontaneous, anally propagating constrictions, repeating every 3-5 min in mouse colon in vitro. They are regulated by the enteric nervous system and may be equivalent to mass movement contractions. We examined postnatal development of CMMCs and circular muscle innervation to gain insight into mechanisms regulating transit in the maturing colon. Video recordings of mouse colon in vitro were used to construct spatiotemporal maps of spontaneous contractile patterns. Development of nitric oxide synthase (NOS) and cholinergic nerve terminals in the circular muscle was examined immunohistochemically. In adults, CMMCs appeared regularly at 4.6 +/- 0.9-min intervals (n = 5). These intervals were reduced by inhibition of NOS (2.7 +/- 0.2 min; n = 5; P < 0.05). CMMCs were abolished by tetrodotoxin (n = 4). CMMCs at postnatal day (P)10 were indistinguishable from adult. At birth and P4, CMMCs were absent. Instead, small constrictions that propagated both orally and anally, "ripples," were seen. Ripples were unaffected by tetrodotoxin or inhibition of NOS and were present in Ret(-/-) mice (which lack enteric neurons) at embryonic day 18.5. In P6 mice, only ripples were seen in control, but NOS inhibition induced CMMCs (n = 8). NOS terminals were abundant in the circular muscle at birth; cholinergic terminals were sparse but were common by P10. In mouse, myogenic ripples are the only mechanism available to produce colonic transit at birth. At P6, neural circuits that generate CMMCs are present but are inhibited by tonic activity of nitric oxide. Adult patterns appear by P10.

Animals↗
PubMed2006

Quality of medication records and use of pharmacy resources in community residential care facilities.

BACKGROUND: In community residential care (CRC) facilities, medication administration is often performed by unlicensed personnel with minimal knowledge in medication use. Medication management is one of the top 3 quality-of-care issues facing these facilities. OBJECTIVE: To examine the type of medication assistance residents received, determine the proportion of facilities that used pharmacy resources, and examine the quality of facility medication records in CRC facilities (eg, adult family homes, adult residential care, assisted living facilities). METHODS: Baseline in-person interviews were conducted with 349 residents and 299 facility providers in the Puget Sound region of Washington. Information was also obtained from facility medication records at enrollment and state databases. A pharmacist determined quality of the records using a standardized form. RESULTS: The average resident was a 78-year-old white female taking 7 drugs. Medication records that were computer generated were significantly less likely to have misspelled names of drugs and errors in or absence of dose, directions for use, and route of administration. Overall, 26.3% of facilities reported that a consultant pharmacist reviewed residents' medication lists, 52.0% reported the use of preprinted lists, and 75.6% received prepackaged medications from the pharmacy. Adult family homes, the smallest facility type, were the least likely to use pharmacy-related services. CONCLUSIONS: The quality of handwritten medication records was a concern in CRC facilities. These facilities may benefit from services offered by pharmacies that may enhance medication management, many of which were underutilized.

Adult↗
PubMed2006

Neural crest and the development of the enteric nervous system.

The formation of the enteric nervous system (ENS) is a particularly interesting example of the migratory ability of the neural crest and of the complexity of structures to which neural crest cells contribute. The distance that neural crest cells migrate to colonize the entire length of the gastrointestinal tract exceeds that of any other neural crest cell population. Furthermore, this migration takes a long time--over 25% of the gestation period for mice and around 3 weeks in humans. After colonizing the gut, neural crest-derived cells within the gut wall then differentiate into glial cells plus many different types of neurons, and generate the most complex part of the peripheral nervous system.

Animals↗
PubMed2006

The cell adhesion molecule l1 is required for chain migration of neural crest cells in the developing mouse gut.

BACKGROUND & AIMS: During development, the enteric nervous system is derived from neural crest cells that emigrate from the hindbrain, enter the foregut, and colonize the gut. Defects in neural crest migration can result in intestinal aganglionosis. Hirschsprung's disease (congenital aganglionosis) is a human condition in which enteric neurons are absent from the distal bowel. A number of clinical studies have implicated the cell adhesion molecule L1 in Hirschsprung's disease. We examined the role of L1 in the migration of neural crest cells through the developing mouse gut. METHODS: A variety of in vitro and in vivo assays were used to examine: (1) the effect of L1 blocking antibodies or exogenous soluble L1 protein known to compromise L1 function on the rate of crest cell migration, (2) the effect of blocking L1 activity on the dynamic behavior of crest cells using time-lapse microscopy, and (3) whether the colonization of the gut by crest cells in L1-deficient mice differs from control mice. RESULTS: We show that L1 is expressed by neural crest cells as they colonize the gut. Perturbation studies show that disrupting L1 activity retards neural crest migration and increases the number of solitary neural crest cells. L1-deficient mice show a small but significant reduction in neural crest cell migration at early developmental stages, but the entire gastrointestinal tract is colonized. CONCLUSIONS: L1 is important for the migration of neural crest cells through the developing gut and is likely to be involved in the etiology of Hirschsprung's disease.

Animals↗
PubMed2004

Neural cells in the esophagus respond to glial cell line-derived neurotrophic factor and neurturin, and are RET-dependent.

Glial cell line-derived neurotrophic factor (GDNF) is expressed in the gastrointestinal tract of the developing mouse and appears to play an important role in the migration of enteric neuron precursors into and along the small and large intestines. Two other GDNF family members, neurturin and artemin, are also expressed in the developing gut although artemin is only expressed in the esophagus. We examined the effects of GDNF, neurturin, and artemin on neural crest cell migration and neurite outgrowth in explants of mouse esophagus, midgut, and hindgut. Both GDNF and neurturin induced neural crest cell migration and neurite outgrowth in all regions examined. In the esophagus, the effect of GDNF on migration and neurite outgrowth declined with age between E11.5 and E14.5, but neurturin still had a strong neurite outgrowth effect at E14.5. Artemin did not promote neural migration or neurite outgrowth in any region investigated. The effects of GDNF family ligands are mediated by the Ret tyrosine kinase. We examined the density of neurons in the esophagus of Ret-/- mice, which lack neurons in the small and large intestines. The density of esophageal neurons in Ret-/- mice was only about 4% of the density of esophageal neurons in Ret+/- and Ret+/+ mice. These results show that GDNF and neurturin promote migration and neurite outgrowth of crest-derived cells in the esophagus as well as the intestine. Moreover, like intestinal neurons, the development of esophageal neurons is largely Ret-dependent.

Animals↗
PubMed2004

Healthy aging for older women.

Healthy aging is a multifaceted phenomenon, incorporating biological and psychosocial developmental factors. The population of older women is diverse in health, function, social context, and age. Health promotion strategies, therefore, should be customized accordingly to optimize the health of the varied subgroups of older women, according to their health trajectory and personal preferences. Research and evaluation of approaches to promote health among these subgroups is an important next step in understanding and influencing the health of older women.

Activities of Daily Living↗
PubMed2003

Characterization of lacZ-expressing cells in the gut of embryonic and adult DbetaH-nlacZ mice.

In mice that express lacZ under the control of a human dopamine beta-hydroxylase gene promoter (DbetaH-nlacZ mice), the nuclei of enteric neurons express the transgene, as shown by the presence of beta-galactosidase (beta-gal) staining (Mercer et al. [1991] Neuron 7:703-716). The transgene is also expressed by neural crest-derived cells in the developing gut before their differentiation into neurons or glial cells (Kapur et al. [1992] Development 116:167-175). However, the cell types expressing the DbetaH-nlacZ transgene within the developing and adult gut have not been fully characterized. Whole-mount preparations of embryonic and adult gut were processed for histochemistry or immunohistochemistry to reveal beta-gal plus markers of undifferentiated neural crest cells (in embryos) or enteric neurons (in adults). In embryonic mice, over 90% of undifferentiated neural crest-derived cells (identified using antibodies to p75) were beta-gal(+). Importantly, crest-derived cells at the migratory wavefront were all beta-gal(+). In adult mice, only a subpopulation of enteric neurons was beta-gal(+), while glial cells showed no beta-gal staining. Considerable variation was observed between the small intestine and colon in the proportion of myenteric neurons that showed beta-gal staining. We examined whether known classes of enteric neurons varied in their expression of DbetaH-nlacZ. In the myenteric plexus of the jejunum and colon, large calretinin(+) neurons did not express lacZ, suggesting that the incomplete penetrance of the DbetaH-nlacZ transgene observed in adult mice is not random. We conclude that the DbetaH-nlacZ transgene provides a reliable marker for examining the colonization of the developing gut by neural crest cells. However, in adult mice, there is variation between mice, between gut regions, and between different classes of enteric neurons in the expression of the transgene.

Animals↗
PubMed2003

Acquisition of neuronal and glial markers by neural crest-derived cells in the mouse intestine.

Enteric neurons and glia arise from the neural crest. The phenotype of crest-derived cells was examined as they differentiated into neurons or glia in the mouse small and large intestine. Previous studies have shown that undifferentiated enteric crest-derived cells are Phox2b(+)/Ret(+)/p75(+)/Sox10(+), and at embryonic day (E) 10.5, about 10-15% of the crest-derived cells in the small intestine have started to differentiate into neurons. In the current study, by E12.5 and E14.5, about 25% and 47%, respectively, of Phox2b(+) cells in the small intestine were immunoreactive to the pan-neuronal protein, ubitquitin hydrolase (PGP9.5), and the percentage did not change dramatically from E14.5 onward. The differentiation of crest-derived cells into neurons in the colon lagged behind that in the small intestine by several days. Differentiating enteric neurons showed high Ret, low p75, and undetectable Sox10 immunostaining. Glial precursors were identified by the presence of brain-specific fatty acid binding protein (B-FABP) and detected first in the fore- and rostral midgut at E11.5. Glial precursors appeared to be B-FABP(+)/Sox10(+)/p75(+) but showed low Ret immunostaining. S100b was not detected until E14.5. Adult glial cells were B-FABP(+)/Sox10(+)/p75(+)/S100b(+). A nucleic acid stain (to identify all ganglion cells) was combined with immunostaining for PGP9.5 and S100b to detect neurons and glial cells, respectively, in the postnatal intestine. At postnatal day 0, fewer than 5% and 10% of cells in myenteric ganglia of the small and large intestine, respectively, were neither PGP9.5(+) nor S100b(+). Because some classes of neurons are not present in significant numbers until after birth, the expression of PGP9.5 by developing enteric neurons appeared to precede the expression of neuron type-specific markers.

Animals↗
PubMed2003

Challenges and solutions for care of frail older adults.

Frail older adults are at risk for negative outcomes and are the most significant consumers of health resources across both acute and community settings. Both formal systems and families are involved in this care of frail elders. This article reviews health care issues for frail older adults and addresses the impact of frailty on the future health care system. It also presents challenges for future care, creative solutions that are currently being tested and explored, and suggestions for future nursing priorities. Challenges in the care of frail elders include: the organization and sustainability of the continuum of services, resource allocation, and cultural competence in service delivery. Creative solutions include intensive case management programs, targeting at risk older adults, partnerships with families, enhanced use of telemedicine and assistive technology, and promoting healthy aging. Nurses have the potential to improve elder health across settings through clinical practice, education, leadership, and research.

Aged↗
PubMed2002

Identification of cells expressing somatostatin receptor 2 in the gastrointestinal tract of Sstr2 knockout/lacZ knockin mice.

Somatostatin is found in neurons and endocrine cells in the gastrointestinal tract. The actions of somatostatin are mediated by a family of G-protein-coupled receptors that compose five subtypes (SSTR1-5), each of which is encoded by a separate gene. lacZ "knockin" mice, in which the reporter gene lacZ was engineered into the genomic locus of Sstr2 by gene targeting, were used to examine the expression pattern of Sstr2 and identify potential targets for neurally released and hormonal somatostatin in the gastrointestinal tract. In the body of the stomach, a large proportion of epithelial cells and subpopulations of myenteric neurons expressed Sstr2. Double- or triple-labeling with antisera to H(+)K(+)ATPase (to identify parietal cells) and/or histidine decarboxylase (to identify enterochromaffin-like [ECL] cells) combined with beta-galactosidase staining revealed that both parietal cells and ECL cells expressed Sstr2, and these two cell types accounted for almost all of the Sstr2-expressing epithelial cells. Somatostatin inhibits gastric acid secretion. The presence of SSTR2 on both parietal and ECL cells suggests that somatostatin acting on SSTR2 may reduce acid secretion by both acting directly on parietal cells and by reducing histamine release from ECL cells. In the small and large intestine, subpopulations of neurons in the myenteric and submucosal plexuses expressed Sstr2, and many of the Sstr2-expressing myenteric neurons also showed SSTR2(a) immunostaining. Most of Sstr2-expressing neurons in the myenteric plexus showed nitric oxide synthase (NOS) immunoreactivity. Previous studies have shown that NOS neurons are descending interneurons and anally projecting, inhibitory motor neurons. Thus, somatostatin acting at SSTR2 receptors on NOS neurons might modulate descending relaxation.

Animals↗
PubMed2002

Enteric nervous system: development and developmental disturbances--part 2.

This review, which is presented in two parts, summarizes and synthesizes current views on the genetic, molecular, and cell biological underpinnings of the early embryonic phases of enteric nervous system (ENS) formation and its defects. Accurate descriptions of the phenotype of ENS dysplasias, and knowledge of genes which, when mutated, give rise to the disorders (see Part 1 in the previous issue of this journal), are not sufficient to give a real understanding of how these abnormalities arise. The often indirect link between genotype and phenotype must be sought in the early embryonic development of the ENS. Therefore, in this, the second part, we provide a description of the development of the ENS, concentrating mainly on the origin of the ENS precursor cells and on the cell migration by which they become distributed throughout the gastrointestinal tract. This section also includes experimental evidence on the controls of ENS formation derived from classic embryological, cell culture, and molecular genetic approaches. In addition, for reasons of completeness, we also briefly describe the origins of the interstitial cells of Cajal, a cell population closely related anatomically and functionally to the ENS. Finally, a brief sketch is presented of current notions on the developmental processes between the genes and the morphogenesis of the ENS, and of the means by which the known genetic abnormalities might result in the ENS phenotype observed in Hirschsprung's disease.

Abnormalities, Multiple↗
PubMed2002

Similarities and differences in attitudes toward long-term care between Japanese Americans and Caucasian Americans.

The purpose of this study was to compare attitudes toward the use of long-term care between older Japanese Americans (n = 1,244) and older Caucasian Americans (n = 1,354). When presented with a hypothetical situation in which they have dementia, 39% of older Japanese Americans and 42% of older Caucasians intended to be cared for at home, whereas 53% versus 38%, respectively, intended to use nursing home care (P <.001). If the hypothetical situation was hip fracture, 81% of older Japanese Americans and 72% of older Caucasians intended to be cared for at home, with 13% of both groups intending to use nursing home care (P = NS). The subjects' perceptions of what their families, friends, ministers, and communities would want them to choose differed, with more uncertainty among Caucasians (P <.001). For provision of home care, Japanese Americans were more likely to rely on loved ones than Caucasians, who were more likely to rely on paid providers. Multivariate logistic regression showed ethnicity to be independently related to intention to use nursing home care in the dementia scenario, controlling for demographic variables. Being married lowered the odds of intending to use nursing homes in any situation. We conclude that Caucasian Americans intend to use paid home health care at higher rates than Japanese Americans if they become disabled by dementia. Japanese Americans demonstrated more certainty about the influences of others on their opinions, suggesting a more stable cultural norm in this population, and intended to use more nursing home care in the event of permanent debility (dementia).

Aged↗
PubMed2002

Attitudes toward community-based services among Japanese American families.

PURPOSE: This descriptive study explored attitudes toward community-based long-term care services and factors influencing service utilization among Japanese American families. DESIGN AND METHODS: Using grounded theory methodology, the Japanese American sample included 26 family caregivers, 4 persons receiving care, and 14 professional providers (n = 44). RESULTS: Attitudes toward services were identified along six dimensions: ability to meet care needs, autonomy in daily life, quality of care and staff, cost, emotional connotations, and social and physical environment. Participants used formal services in a dynamic manner, meeting both episodic and chronic needs. Families played an active role in sustaining and augmenting the caregiving situation, regardless of living arrangement. IMPLICATIONS: This research highlights the range of criteria included in attitude formation about services and the dynamic nature of the interplay between families and formal services.

Activities of Daily Living↗
PubMed2002

Evolving values in community-based long-term care services for Japanese Americans.

This study used grounded theory to explore how long-term care services are perceived and what factors influence family caregiving and long-term care service utilization choices among Japanese Americans. Family and generational perspectives elucidated a dialectic between forces of integration into the broader culture, and reconnection with the culture of origin within the context of powerful ethnically based historical and generational experiences. This study describes the evolution of the values underlying service delivery and family expectations and demonstrates the dynamic relationships among cultural expectations, historical context, and service evolution for a group of members involved in the caregiving experience.

Aged↗
PubMedDate not supplied

Enteric nervous system: development and developmental disturbances--part 1.

This review, which is presented in two parts, summarizes and synthesizes current views on the genetic, molecular, and cell biological underpinnings of the early embryonic phases of enteric nervous system (ENS) formation and its defects. In the first part, we describe the critical features of two principal abnormalities of ENS development: Hirschsprung's disease (HSCR) and intestinal neuronal dysplasia type B (INDB) in humans, and the similar abnormalities in animals. These represent the extremes of the diagnostic spectrum: HSCR has agreed and unequivocal diagnostic criteria, whereas the diagnosis and even existence of INDB as a clinical entity is highly controversial. The difficulties in diagnosis and treatment of both these conditions are discussed. We then review the genes now known which, when mutated or deleted, may cause defects of ENS development. Many of these genetic abnormalities in animal models give a phenotype similar or identical to HSCR, and were discovered by studies of humans and of mouse mutants with similar defects. The most important of these genes are those coding for molecules in the GDNF intercellular signaling system, and those coding for molecules in the ET-3 signaling system. However, a range of other genes for different signaling systems and for transcription factors also disturb ENS formation when they are deleted or mutated. In addition, a large proportion of HSCR cases have not been ascribed to the currently known genes, suggesting that additional genes for ENS development await discovery.

Abnormalities, Multiple↗
PubMedDate not supplied

Linking theory and gerontological nursing practice in senior housing.

This article illustrates the use of 2 theoretical models in planning and implementing health programs in senior housing. The Person-Environment Fit Model, developed by Lawton, and the Transitions Theory, developed by Meleis and colleagues, form the basis for understanding the interaction between people and their environments through transitions common in late life. The models and their application to practice are described, with examples at the individual, group, and community levels. Implications and future directions are identified for the use of such models in gerontological nursing practice.

Aged↗