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K D Anderson

Publications and source records attributed to K D Anderson.

At least 19 recordsLinked to original sources
PubMed2007

Adaptive nanomechanical response of stratified polymer brush structures.

We have fabricated a stratified polymer surface film with tunable thickness (within 17-34 nm) through facile, room-temperature, UV-initiated polymerization with a temperature-sensitive pNIPAAM layer confined beneath a hydrophobic layer. AFM morphology and ellipsometric measurements were measured at each grafting step, along with XPS measurements of the overall layer to verify layer growth. The strong characteristic LCST behavior of pNIPAAM was observed in water, with a 100% change in thickness above and below this transition. The AFM nanomechanical results demonstrate vertical gradients of the elastic response tunable to a desired state by the external temperature. These temperature-sensitive, adaptive polymer structures with the pNIPAAM layer "hidden" beneath the rubbery, hydrophobic PBA topmost layer represent an interesting example of nanoengineering surfaces with properties such as adhesion, elastic modulus, and multi-level structural reorganization responsive to fluidic and temperature variations that can be important for biological purposes such as implant coatings, cell-surface mimicry, and drug delivery vehicles.

Acrylic Resins↗
PubMed2006

Gastroschisis in the United States 1988-2003: analysis and risk categorization of 4344 patients.

OBJECTIVE: Gastroschisis is a rare congenital abdominal wall defect through which intraabdominal organs herniate and it requires surgical management soon after birth. The objectives of this study were to profile patient characteristics of this anomaly utilizing data from two large national databases and to validate previous risk stratification categories of infants born with this condition. METHODS: An analysis was performed using 13 years of the National Inpatient Sample database (1988-1996, 1998, 1999, 2001, 2002) and 3 years of the Kids' Inpatient Database (1997, 2000, 2003). These combined databases contain information from nearly 93 million discharges in the United States. Infants with gastroschisis were identified by International Classification of Disease-9 procedure code 54.71 (repair of gastroschisis) and an age at admission of <8 days. Variables of gender, race, geographic region, co-existing diagnoses, length of stay, hospital charges adjusted to 2005 dollars, complications and inpatient mortality were collected from the databases. Infants were divided into simple and complex categories based on the absence or presence of intestinal atresia, stenosis, perforation, necrosis or volvulus. Comparisons between groups were performed using Pearson's chi (2) for categorical outcomes and the Kruskal-Wallis test for non-normally distributed continuous variables. RESULTS: A total of 4344 infants with gastroschisis were identified. These were comprised of 44.0% female infants (n=1910), 46.4% male infants (n=2017) whereas 9.6% were not reported (n=415). Racial analysis showed the largest subset being white in 40.9% of infants (n=1775) with Hispanic infants being the next highest group reported at 17.2% (n=745). Co-existing intestinal anomalies were the most common, affecting 9.9% (n=429) infants, whereas certain cardiac (6.8%, n=294) and pulmonary (1.7%, n=72) conditions were also identified. Simple gastroschisis represented 89.1% (n=3870) of the group whereas 10.9% (n=474) were complex in nature. Simple and complex patients differed in median length of stay (28 vs 67 days, P<0.01), inpatient mortality (2.9 vs 8.7%, P<0.01) and median inflation-adjusted hospital charges (90,788 dollars vs 197,871 dollars, P<0.01). CONCLUSIONS: These data represent a national analysis of the largest group of infants with gastroschisis to date which further aids the characterization and understanding of this serious congenital condition.

Female↗
PubMed2006

The impact of spinal cord injury on sexual function: concerns of the general population.

STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Obtain information from the spinal cord injured (SCI) population regarding sexual dysfunctions, with the aim of developing new basic science and clinical research and eventual therapies targeting these issues. SETTING: Worldwide web. METHODS: Individuals 18 years or older living with SCI. Participants obtained a pass-code to enter a secure website and answered survey questions. A total of 286 subjects completed the survey. RESULTS: The majority of participants stated that their SCI altered their sexual sense of self and that improving their sexual function would improve their quality of life (QoL). The primary reason for pursuing sexual activity was for intimacy need, not fertility. Bladder and bowel concerns during sexual activity were not strong enough to deter the majority of the population from engaging in sexual activity. However, in the subset of individuals concerned about bladder and/or bowel incontinence during sexual activity, this was a highly significant issue. In addition, the occurrence of autonomic dysreflexia (AD) during typical bladder or bowel care was a significant variable predicting the occurrence and distress of AD during sexual activity. CONCLUSION: Sexual function and its resultant impact on QoL is a major issue to an overwhelming majority of people living with SCI. This certainly constitutes the need for expanding research in multiple aspects to develop future therapeutic interventions for sexual health and SCI.

Adolescent↗
PubMed2006

Long-term effects of spinal cord injury on sexual function in men: implications for neuroplasticity.

STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Elicit specific information about sexual function from men with spinal cord injuries (SCI). SETTING: World-wide web. METHODS: Individuals 18 years or older living with SCI obtained a pass-code to enter a secure website and then answered survey questions. RESULTS: The presence of genital sensation was positively correlated with the ability to feel a build up of sexual tension in the body during sexual stimulation and in the feeling that mental arousal translates to the genitals as physical sensation. There was an inverse relationship between developing new areas of arousal above the level of lesion and not having sensation or movement below the lesion. A positive relationship existed between the occurrence of spasticity during sexual activity and erectile ability. Roughly 60% of the subjects had tried some type of erection enhancing method. Only 48% had successfully achieved ejaculation postinjury and the most commonly used methods were hand stimulation, sexual intercourse, and vibrostimulation. The most commonly cited reasons for trying to ejaculate were for pleasure and for sexual intimacy. Less than half reported having experienced orgasm postinjury and this was influenced by the length of time postinjury and sacral sparing. CONCLUSION: SCI not only impairs male erectile function and ejaculatory ability, but also alters sexual arousal in a manner suggestive of neuroplasticity. More research needs to be pursued in a manner encompassing all aspects of sexual function.

Adaptation, Psychological↗
PubMed2006

Spinal cord injury influences psychogenic as well as physical components of female sexual ability.

STUDY DESIGN: Secure, web-based survey. OBJECTIVES: Elicit specific information about sexual function from women with spinal cord injuries (SCI). SETTING: World-wide web. METHODS: Individuals 18 years or older living with SCI obtained a pass code to enter a secure website and then answered survey questions. RESULTS: Bladder and/or bowel incontinence during sexual activity and/or sexual intercourse were significant concerns and prevented some women from seeking sexual activity. Autonomic dysreflexia (AD) during sexual activity was interpreted negatively by many and was found to interfere with sexual activity. Most subjects reported difficulty becoming psychologically aroused as well as physically aroused, which were both correlated with feeling that their SCI had altered their sexual sense of self. An inverse relationship existed between developing new areas of arousal above the level of lesion and not having sensation or movement below the lesion. The most commonly reported sexual stimulation leading to the best arousal involved stimulation of the head/neck and torso areas. The majority of subjects reported having experienced intercourse postinjury. Most participants reported difficulty with positioning during foreplay and intercourse, vaginal lubrication, and spasticity during intercourse. Almost half reported experiencing orgasm postinjury and this was positively associated with the presence of genital sensation. CONCLUSION: SCI significantly impairs psychological and physical aspects of female sexual arousal. In addition, bladder and bowel incontinence as well as AD negatively impact sexual activity and intercourse.

Adolescent↗
PubMed2004

Requirement for fibroblast growth factor 10 or fibroblast growth factor receptor 2-IIIb signaling for cecal development in mouse.

Epithelial-mesenchymal interactions are critical for the formation of gastrointestinal buds such as the cecum from the midgut, but the mechanisms regulating this process remain unclear. To investigate this problem, we have studied the temporal and spatial expression of key genes known to orchestrate branching morphogenesis. At E10.5, Fibroblast growth factor 10 (Fgf10) is specifically expressed in the mesenchyme above the future cecal epithelial bud, whereas Fgfr2b is found throughout the gut epithelium. From E11.5 onwards, Fgf10 expression is found throughout the cecum mesenchyme. Other relevant signaling molecules such as Sonic hedgehog, Wnt2b, and Tbx4 transcripts are found throughout the gut epithelium, including the cecum. Epithelial expression is also seen for Sprouty2, but only from E14.5 onwards. By contrast, Bone morphogenetic 4 (Bmp4) and Pitx2 are specifically expressed in the mesenchyme of the cecal bud at E11.5. Abrogation of either Fgf10 or Fgfr2b leads to similar phenotypes characterized by an arrest of epithelial invasion into the cecal mesenchymal tissue. However, a bud of undifferentiated cecal mesenchymal tissue is maintained throughout development. Our results further indicate that mesenchymal FGF10 acts mostly through the epithelial FGFR2b receptor; thereby triggering invasion of the midgut epithelium into the adjacent mesenchyme via an increased rate of epithelial proliferation at the tip of the cecum. Thus, FGF10 signaling via FGFR2b appears to be critical in the extension of the epithelium into the mesenchyme during cecal development.

Actins↗
PubMed2004

Differential loss of striatal projection systems in Huntington's disease: a quantitative immunohistochemical study.

Prior studies suggest differences exist among striatal projection neuron types in their vulnerability to Huntington's disease (HD). In the present study, we immunolabeled the fibers and terminals of the four main types of striatal projection neuron in their target areas for substance P, enkephalin, or glutamic acid decarboxylase (GAD), and used computer-assisted image analysis to quantify the abundance of immunolabeled terminals in a large sample of HD cases ranging from grade 0 to grade 4 [J. Neuropathol. Exp. Neurol. 44 (1985) 559], normalized to labeling in control human brains. Our goal was to characterize the relative rates of loss of the two striatopallidal projection systems (to the internal versus the external pallidal segments) and the two striatonigral projections systems (to pars compacta versus pars reticulata). The findings for GAD and the two neuropeptides were similar--the striatal projection to the external pallidal segment was the most vulnerable, showing substantial loss by grade 1. Loss of fibers in both subdivisions of the substantia nigra was also already great by grade 1. By contrast, the loss in the striatal projection system to the internal segment of globus pallidus proceeded more gradually. By grade 4 of HD, however, profound loss in all projection systems was apparent. These findings support the notion that the striatal neurons preferentially projecting to the internal pallidal segment are, in fact, less vulnerable in HD than are the other striatal projection neuron types.

Adolescent↗
PubMed2004

A genetic mechanism for cecal atresia: the role of the Fgf10 signaling pathway.

BACKGROUND: Intestinal atresia represents a significant surgically correctable cause of intestinal obstruction in neonates. Intestinal development proceeds as a tube-like structure with differentiation along its axis. As the intestine differentiates, the cecum develops at the transition from small to large intestine. Fgf10 is known to serve a key role in budding morphogenesis; however, little is known about its role in the development of this transitional structure. Here we evaluate the effect of Fgf10/Fgfr2b invalidation on the developing cecum. MATERIALS AND METHODS: Wild-type C57Bl/6, Fgf10(-/-), and Fgfr2b(-/-) embryos harvested from timed pregnant mothers were analyzed for cecal phenotype, Fgf10 expression, and differentiation of smooth muscle actin. RESULTS: Wt cecal development is first evident at E11.5. FGF10 is discreetly expressed in the area of the developing cecum at early stages of development. One hundred percent of Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with absence of epithelial and muscular layers. The development of neighboring anatomical structures such as the ileocecal valve is not affected by Fgf10/Fgfr2b invalidation. CONCLUSIONS: FGF10 expression is localized to the cecum early in the normal development of the cecum. Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with complete penetrance. Epithelial and muscular layers of the cecum are not present in the atretic cecum. The Fgf10(-/-) and Fgfr2b(-/-) mutants represent a genetically reproducible animal model of autosomal recessive intestinal atresia.

Animals↗
PubMed2003

Increased expression and localization of the RNA-binding protein HuD and GAP-43 mRNA to cytoplasmic granules in DRG neurons during nerve regeneration.

The neuronal-specific RNA-binding protein, HuD, binds to a U-rich regulatory element of the 3' untranslated region (3' UTR) of the GAP-43 mRNA and delays the onset of its degradation. We have recently shown that overexpression of HuD in embryonic rat cortical cells accelerated the time course of normal neurite outgrowth and resulted in a twofold increase in GAP-43 mRNA levels. Given this evidence, we sought to investigate the involvement of HuD during nerve regeneration. It is known that HuD protein and GAP-43 mRNA are expressed in the dorsal root ganglia (DRG) of adult rat and that GAP-43 is upregulated in DRG neurons during regeneration. In this study, we examined the expression patterns and levels of HuD and GAP-43 mRNA in DRG neurons following sciatic nerve injury using a combination of in situ hybridization, immunocytochemistry, and quantitative RT-PCR. GAP-43 and HuD expression increased in the ipsilateral DRG during the first 3 weeks of regeneration, with peak values seen at 7 days postcrush. At this time point, the levels of HuD and GAP-43 mRNAs in the ipsilateral DRG increased by twofold and sixfold, respectively, relative to the contralateral DRG. Not only were the temporal patterns of expression of HuD protein and GAP-43 mRNA similar, but also they were found to colocalize in the cytoplasm of DRG neurons. Moreover, both molecules were distributed in cytoplasmic granules containing ribosomal RNA. In conclusion, our results suggest that HuD is involved in the upregulation of GAP-43 expression observed at early stages of peripheral nerve regeneration.

Animals↗
PubMed2003

Activation of the hypothalamic arcuate nucleus predicts the anorectic actions of ciliary neurotrophic factor and leptin in intact and gold thioglucose-lesioned mice.

Similar to leptin, ciliary neurotrophic factor (CNTF) suppresses appetite and selectively reduces body fat in leptin-deficient ob/ob mice. To assess the relative importance of specific regions of the hypothalamus in mediating these effects, we administered a CNTF analogue (CNTFAx15) or leptin to mice made obese by administration of gold thioglucose (GTG), which destroys a well-defined portion of the medial basal hypothalamus. CNTFAx15 treatment reduced appetite and body weight in obese GTG-lesioned C57BL/6 mice, whereas leptin failed to effect similar changes regardless of whether treatment was initiated before or after the lesioned mice had become obese. Because leptin does not reduce food intake or body weight in most forms of obesity (a condition termed 'leptin resistance'), we also investigated the actions of leptin in GTG-lesioned leptin-deficient (ob/ob) mice. By contrast to C57BL/6 mice, leptin treatment reduced food intake and body weight in GTG-lesioned ob/ob mice, although the effect was attenuated. To further compare the neural substrates mediating the anorectic actions of leptin and CNTF, we determined the patterns of neurone activation induced by these proteins in the hypothalamus of intact and GTG-lesioned mice by staining for phosphorylated signal transducer and activator of transcription 3 (pSTAT3). CNTFAx15 stimulated robust pSTAT3 signalling in neurones of the medial arcuate nucleus in both intact and lesioned C57BL/6 and ob/ob mice. Leptin administration stimulated pSTAT3 signalling in only a few neurones of the medial arcuate nucleus in intact or lesioned C57BL/6 mice, but elicited a robust response in intact or lesioned ob/ob mice. By contrast to CNTFAx15, leptin treatment also resulted in prominent activation of STAT3 in several areas of the hypothalamus outside the medial arcuate nucleus. This leptin-induced pSTAT3 signal was at least as prominent in intact and GTG-lesioned C57BL/6 mice as it was in ob/ob mice, and thus was not correlated with appetite suppression or weight loss. These results indicate that the medial arcuate nucleus is a key mediator of appetite suppression and weight loss produced by CNTF and leptin, whereas GTG-vulnerable regions play a role only in leptin-induced weight loss. Other regions of hypothalamus in which pSTAT3 signal is induced by leptin may regulate energy metabolism through mechanisms other than appetite reduction.

Animals↗
PubMed2002

The impact of changing neonatal respiratory management on extracorporeal membrane oxygenation utilization.

BACKGROUND: The introduction of inhaled nitric oxide (INO) and high-frequency oscillatory ventilation (HFV) has had a profound effect on the use of extracorporeal membrane oxygenation (ECMO) for respiratory failure in neonates without congenital diaphragmatic hernia (CDH). The purpose of this study was to evaluate the changes in the demographics and outcome of non-CDH neonates who underwent ECMO for hypoxemic respiratory failure. METHODS: All neonates (non-CDH and noncardiac) who underwent ECMO between January 1, 1989 and January 1, 2001 were reviewed. Patients were separated into 3, 4-year periods for comparison (period A, 1989 through 1992; B, 1993 through 1996; C, 1997 through 2000). Data were examined by analysis of variance and contingency table analysis. RESULTS: There was a progressive decline in the total number of neonates requiring ECMO over time (period A, 172; B, 114; C, 56; P <.01). The utilization of pre-ECMO alternate respiratory therapies such as INO (period A, 0%; B, 23%; C, 98%; P <.01) and HFV (period A, 9%; B, 61%; C, 89%; P <.01) have increased significantly associated with an increase in the age of ECMO initiation (Period A, 40.5 hours; B, 58.3 hours; C, 68.5 hours; P <.01). The length of ECMO run also has increased (period A, 154.7 hours; B, 193.0 hours; C, 174.5 hours; P <.01), but the overall mortality rate has remained unchanged. CONCLUSIONS: With the increasing use of INO and HFO, the absolute number of non-CDH, noncardiac neonates with hypoxemic respiratory failure requiring ECMO has decreased. Initiation of ECMO has become progressively later likely because of the use of these rescue therapies, but the overall mortality rate remains unchanged despite this delay.

Extracorporeal Membrane Oxygenation↗
PubMed2001

Nongenomic estrogen action in human lung myofibroblasts.

Recent studies have suggested that the antiproliferative effects of E2 may be mediated through a nongenomic action. Herein, we asked whether nongenomic estrogen action regulates phosphorylation of Raf1 and ERK1/2 mitogen-activated protein (MAP) kinase in lung myofibroblasts. We demonstrated that lung myofibroblasts, incubated in the presence of E2, showed a rapid phosphorylation on serine-259 of Raf1 and tyrosine-204 of ERK1/2 MAP kinase at 15 min, by approximately 3- and 5-fold, respectively. This phosphorylation was followed by dephosphorylation between 30 and 60 min. Western blot analysis showed that E2 regulates tyrosine phosphorylation of four main cytoplasmic proteins in lung myofibroblasts, of 42, 44, 70 and 100 kDa. Furthermore, our results indicated that E2 inhibits cell proliferation (BrdU index) in lung myofibroblasts by approximately 30% (P < 0.01). These data provide evidence that nongenomic action of E2, regulates both serine and tyrosine phosphorylation of cytoplasmic proteins in lung myofibroblasts, including Raf1 and ERK1/2 MAP kinase, which may regulate proliferation in lung myofibroblasts.

Binding Sites↗
PubMed2001

Ciliary neurotrophic factor activates leptin-like pathways and reduces body fat, without cachexia or rebound weight gain, even in leptin-resistant obesity.

Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce cachectic-like effects. Countering this possibility was the suggestion that CNTF was working via a leptin-like mechanism to cause weight loss, based on the findings that CNTF acts via receptors that are not only related to leptin receptors, but also similarly distributed within hypothalamic nuclei involved in feeding. However, although CNTF mimics the ability of leptin to cause fat loss in mice that are obese because of genetic deficiency of leptin (ob/ob mice), CNTF is also effective in diet-induced obesity models that are more representative of human obesity, and which are resistant to leptin. This discordance again raised the possibility that CNTF might be acting via nonleptin pathways, perhaps more analogous to those activated by cachectic cytokines. Arguing strongly against this possibility, we now show that CNTF can activate hypothalamic leptin-like pathways in diet-induced obesity models unresponsive to leptin, that CNTF improves prediabetic parameters in these models, and that CNTF acts very differently than the prototypical cachectic cytokine, IL-1. Further analyses of hypothalamic signaling reveals that CNTF can suppress food intake without triggering hunger signals or associated stress responses that are otherwise associated with food deprivation; thus, unlike forced dieting, cessation of CNTF treatment does not result in binge overeating and immediate rebound weight gain.

Adipose Tissue↗
PubMed2001

Overexpression of HuD accelerates neurite outgrowth and increases GAP-43 mRNA expression in cortical neurons and retinoic acid-induced embryonic stem cells in vitro.

The neuron-specific RNA-binding protein HuD binds to a U-rich regulatory element of the 3' untranslated region (3' UTR) of the GAP-43 mRNA and stabilizes the mRNA. We have previously shown that overexpression of HuD in PC12 cells increases GAP-43 protein expression and induces the spontaneous formation of multiple neurites (K. D. Anderson et al. 2000. J. Neurochem. 75: 1103-1114). In this study, we examined the effects of HuD overexpression on the initial stages of neurite outgrowth and on GAP-43 gene expression using two in vitro systems: E19 rat cortical neurons and retinoic acid (RA)-induced embryonic stem (ES) cells. Normal neurite outgrowth of cortical neurons in vitro occurs over a 3-day period with a concomitant increase in GAP-43 and HuD expression. Cortical cells were infected with a replication-deficient HSV-1 vector containing the HuD cDNA in the sense orientation (HSV-HuD). Overexpression of HuD accelerated the formation of neurites. Immunocytochemical analysis showed that excess HuD resulted in a threefold increase in the number of GAP-43-positive cells undergoing morphological differentiation after 24 h of treatment. Using in situ hybridization, we found that the increased HuD expression resulted in a twofold increase in the levels of GAP-43 mRNA. Similarly, overexpression of HuD in RA-induced embryonic stem cells was found to increase the number of GAP-43-positive cells undergoing process outgrowth. In conclusion, our results demonstrate that HuD functions in the initiation of neurite outgrowth in a manner due, at least in part, to its regulation of GAP-43 expression.

Animals↗
PubMed2001

Prenatal exposure to nitrofen induces Fryns phenotype in mice.

Prenatal exposure to nitrofen is known to cause multiple malformations in mice. The reported malformations include lung hypoplasia, diaphragmatic hernia, cardiovascular defects, skeletal malformations, cleft palate, and renal abnormalities. The authors present detailed findings of craniofacial defects after prenatal exposure to nitrofen, and propose that together with the previously reported malformations, nitrofen exposure induces a Fryns phenotype in mice. Fryns syndrome is a rare human genetic syndrome that is an autosomal recessive disorder characterized by lung hypoplasia, diaphragmatic hernia, craniofacial malformations, skeletal malformations, cardiovascular malformations, and genitourinary malformations. Timed-pregnant Swiss Webster mice were gavage-fed 25 mg of nitrofen on day 8 of gestation. Control animals received olive oil. Osteogenesis and chondrogenesis were studied in fetuses recovered on day 17 after Alcian blue-Alizarin red staining. Approximately 26% of the nitrofen-exposed embryos had severe craniofacial defects, and there was generalized delay in chondrogenesis and osteogenesis throughout the skeleton. No such defects were noted in the control group. The authors propose that prenatal exposure to nitrofen induces a Fryns phenotype in mice, and thus speculate that nitrofen may target similar molecular mechanisms to those that lead to Fryns syndrome.

Abnormalities, Drug-Induced↗