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C Walker

Publications and source records attributed to C Walker.

At least 37 records · Page 2Linked to original sources
PubMed2002

Inhibition of ultraviolet B radiation-induced interleukin 10 expression in murine keratinocytes by selenium compounds.

BACKGROUND: Selenium is an essential trace nutrient necessary for the normal function of the immune system. Selenium compounds protect mice against ultraviolet (UV) B-induced tumours, probably by preventing oxidative damage to the host skin cells and to the host immune system. One possible mechanism of protection is that selenium can prevent oxidative stress-induced release of cytokines such as interleukin (IL)-10, which could suppress cell-mediated immunity. OBJECTIVES: To determine whether selenium compounds can inhibit UVB induction of IL-10 protein in murine keratinocytes. METHODS: The murine keratinocyte cell line PAM 212 was treated with or without selenomethionine (50-200 nmol L-1) or sodium selenite (1-50 nmol L(-1)) for 24 h before exposure to 200 J m(-2) UVB. The cells were stained with an antibody to IL-10, 24 h after irradiation. RESULTS: Preincubation with both selenium compounds inhibited UVB induction of IL-10 immunostaining, although selenomethionine was more effective. Pretreatment with 200 nmol L(-1) selenomethionine decreased IL-10 immunostaining to levels seen in the unirradiated controls. CONCLUSIONS: The protective effects of selenium against UVB-induced skin cancer in murine models may result, in part, from its ability to inhibit release of cytokines that are capable of suppressing cell-mediated immunity.

Animals↗
PubMed2001

Glomus, the largest genus of the arbuscular mycorrhizal fungi (Glomales), is nonmonophyletic.

Arbuscular mycorrhizal (AM) fungi form a widespread and ecologically important symbiosis with plants in the land ecosystem. The phylogeny of the largest presently accepted genus, Glomus, of the monogeneric family Glomaceae (Glomales; AM fungi) was analyzed. Phylogenetic trees were computed from nearly full-length SSU rRNA gene sequences of 30 isolates, and show that "Glomus" is not monophyletic. Even after the very recent separation of Archaeospora and Paraglomus from "Glomus," the genus further separates into two suprageneric clades. One of them diverges further into two subclades, differing by phylogenetic distances equivalent to family level. The other, comprising Glomus versiforme, G. spurcum, and a species morphologically similar to G. etunicatum, is not closely related to the Glomaceae, but clusters together with the Acaulosporaceae and Gigasporaceae in a monophyletic clade. Based on the molecular evidence, a new family, separate from the Glomaceae, is required to accommodate this group of organisms, initially named Diversisporaceae fam. ined. The current taxonomic concept of the recently erected family Archaeosporaceae also requires future emendation, because Geosiphon pyriformis (Geosiphonaceae) renders Archaeospora, the sole genus formally included in this family, paraphyletic. The suborders Gigasporineae and Glominaeae are not congruent with the natural phylogeny of the AM fungi. Our data necessitate a general reexamination of the generic concepts within the Glomales. In addition to the new family structure hypothesized herein, establishment of at least three new genera will be necessary in the future.

DNA, Fungal↗
PubMed2001

Characterisation of molecular alterations in microdissected archival gliomas.

Classification of gliomas according to their molecular characteristics may be important in future histopathological diagnosis. However, gliomas frequently display heterogeneity at the histological, biological and molecular level. In this study of archival diagnostic gliomas, precision microdissection was used to enrich samples in the most malignant cells or to investigate intratumoural histological heterogeneity. Analysis of tumour samples microdissected from the most aggressive regions, representative of the histopathological diagnosis, revealed PTEN mutations in 4/14 anaplastic astrocytomas, 4/13 glioblastomas and 1 gliosarcoma, but not in 19 low-grade gliomas. Using a novel PCR procedure and direct sequence analysis of the entire coding sequence, TP53 mutations were detected in 1/3 pilocytic astrocytomas, 3/13 astrocytomas, 4/14 anaplastic astrocytomas, 5/13 glioblastomas and 1 gliosarcoma. All but one of the tumours with TP53 mutation showed p53 immunopositivity, but 5 low-grade and 10 high-grade gliomas had p53 protein nuclear accumulation in the absence of detectable mutation. p53 status was unrelated to p21 expression. Neither PTEN nor TP53 mutations influenced the proliferative index or microvessel density of high-grade astrocytomas. Unusual findings include: TP53 mutation in a juvenile pilocytic astrocytoma; TP53 and PTEN mutations in a de novo glioblastoma, a gliosarcoma with identical mutations in gliomatous and sarcomatous components, and an infratentorial anaplastic astrocytoma with an earlier supratentorial grade II astrocytoma bearing the same TP53 mutation but not the PTEN mutation or loss of heterozygosity (LOH) of 10q23. Similarly, the transition to high-grade histology was associated with acquisition of PTEN mutations and 10q23.3 LOH in two de novo high-grade tumours with regions of low-grade histology.

Adolescent↗
PubMed2001

New trends in immunotherapy to prevent atopic diseases.

Advances in the understanding of the molecular and cellular immunological mechanism of atopy have led to the development of new therapies for allergic diseases. However, only a few new drugs have reached the clinic and none provides long-term immunomodulatory effects. Immunotherapy, through its capacity to produce a long-term, antigen-specific, protective immune response, is the only aetiologic treatment that offers the possibility of preventing or even curing atopic diseases. However, the potential severe side-effects associated with conventional immunotherapy using whole allergen extract limits its widespread use. Thus, novel strategies to minimize the side-effects and improve the efficacy of immunotherapy are of considerable interest in the treatment of atopic diseases. Promising animal and human studies, using approaches such as peptide immunotherapy, DNA vaccination, CpG oligonucleotides and mycobacterial vaccines, suggest that it might be possible to prevent or cure atopic diseases in the future.

Humans↗
PubMed2001

Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene.

The PKD1 gene accounts for 85% of autosomal dominant polycystic kidney disease (ADPKD), the most common human genetic disorder. Rats with a germline inactivation of one allele of the Tsc2 tumor suppressor gene developed early onset severe bilateral polycystic kidney disease, with similarities to the human contiguous gene syndrome caused by germline codeletion of PKD1 and TSC2 genes. Polycystic rat renal cells retained two normal Pkd1 alleles but were null for Tsc2 and exhibited loss of lateral membrane-localized polycystin-1. In tuberin-deficient cells, intracellular trafficking of polycystin-1 was disrupted, resulting in sequestration of polycystin-1 within the Golgi and reexpression of Tsc2 restored correct polycystin-1 membrane localization. These data identify tuberin as a determinant of polycystin-1 functional localization and, potentially, ADPKD severity.

Alleles↗
PubMed2001

The zebrafish glypican knypek controls cell polarity during gastrulation movements of convergent extension.

Mutations in the zebrafish knypek locus impair gastrulation movements of convergent extension that narrow embryonic body and elongate it from head to tail. We demonstrate that knypek regulates cellular movements but not cell fate specification. Convergent extension movement defects in knypek are associated with abnormal cell polarity, as mutant cells fail to elongate and align medio-laterally. Positional cloning reveals that knypek encodes a member of the glypican family of heparan sulfate proteoglycans. Double mutant and overexpression analyses show that Knypek potentiates Wnt11 signaling, mediating convergent extension. These studies provide experimental and genetic evidence that glypican Knypek acts during vertebrate gastrulation as a positive modulator of noncanonical Wnt signaling to establish polarized cell behaviors underlying convergent extension movements.

Amino Acid Sequence↗
PubMed2001

Subantimicrobial dose doxycycline as an adjunct to scaling and root planing: post-treatment effects.

BACKGROUND/OBJECTIVE: Subantimicrobial dose doxycycline (SDD 20 mg bid) plus scaling and root planing (SRP) significantly improved clinical attachment level (CAL) and reduced probing depth (PD) compared with placebo plus SRP in a double-blind, placebo-controlled, multicenter study of patients with adult periodontitis (AP). In a study conducted as a follow-up, the post-treatment effects of SDD were assessed in patients who completed the SRP study. METHODS: The SRP study was a 9-month, active-treatment study and the follow-up was a 3-month, no-treatment study. In the SRP study, tooth sites in qualifying quadrants were scaled and root planed and patients were randomized to receive twice daily SDD 20 mg or placebo. In the follow-up, patients received no study drug; investigators and patients remained blinded to the previous treatment group assignments. Efficacy measures included the change in CAL and PD from baseline values determined at the start of the SRP study in tooth sites stratified by baseline PD (i.e., 0-3 mm, 4-6 mm, > or =7 mm). Safety was evaluated using adverse event data and the results of clinical laboratory tests, oral pathology examinations, and microbiological assessments. RESULTS: Within each disease stratum, the incremental improvements in PD and CAL demonstrated in the SDD group over 9 months of active treatment were maintained through 3 additional months of no treatment. Treatment cessation did not result in an accelerated regression of periodontal health. No differences in the incidence of adverse events (including those related to infection) or laboratory or microbiological parameters were noted between the SDD group and the placebo group. CONCLUSIONS: The administration of SDD 20 mg bid for a period of up to 9 months is not associated with rebound effects or delayed or negative after-effects for a 3-month period after cessation of therapy.

Adult↗
PubMed2001

Medical repatriation via fixed-wing air ambulance: a review of patient characteristics and adverse events.

Anaesthetists are often employed as medical escorts for patients undergoing international transfer by air ambulance. There is little published data on the types of patients being transferred and on the incidence of adverse events. We performed a retrospective review of the documentation of all air ambulance transfers performed by a single company over a 2-year period followed by a prospective assessment of all high-risk patients transferred over a 1-year period. Of 483 transfers identified, 47% were defined as high-risk and 20% were of patients receiving mechanical ventilation. In the prospective group, 28% of patients required pretransfer optimisation, 7% required a major therapeutic intervention during transfer and there was a major adverse event in 12% of transfers. There were two deaths during transport. These data support the recommendation that escorting personnel should be from an appropriate speciality, have reasonable seniority and be adequately trained and supervised.

Adolescent↗
PubMed2001

Leukaemia inhibitory factor and interleukin-8 expression in nonmelanoma skin cancers.

Leukaemia inhibitory factor (LIF) and interleukin (IL)-8 possess activities which may contribute to the development of carcinomas. LIF can stimulate proliferation of some tumour cell lines and IL-8 is angiogenic. Using semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), we measured the expression of LIF and IL-8 mRNA in cultured normal keratinocytes (NKC) and the malignant carcinoma cells lines A431, SiHa, HeLa, and in biopsies of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and normal skin. Protein expression for LIF was assessed by immunohistochemistry in the biopsies. LIF mRNA expression was increased significantly (P < 0.01) in all carcinoma lines, except SiHa, compared with NKC but the IL-8 mRNA expression in carcinoma cell lines was similar to that in NKC. Expression of LIF mRNA was elevated in BCC and SCC compared with normal skin, but a significant difference was observed only between SCC and normal skin (P < 0.01). Both BCC and SCC showed significantly greater expression of IL-8 compared with normal skin (P < 0.01). There was no correlation between LIF and IL-8 mRNA expression either in BCCs or in SCCs. Immunoreactivity for LIF was absent throughout BCC and SCC, however, normal epidermis surrounding the tumour stained positive, as in normal skin. These data may suggest a role for LIF and IL-8 in the development of skin carcinomas, but without co-ordinate regulation of these two cytokines in this process.

Adult↗
PubMed2001

Infection of murine keratinocytes with herpes simplex virus type 1 induces the expression of interleukin-10, but not interleukin-1 alpha or tumour necrosis factor-alpha.

Herpes simplex virus (HSV) is known to possess several mechanisms whereby it can evade the normal host immune defences. In this study the expression of the immunosuppressive cytokine, interleukin (IL)-10, was monitored following infection of a murine keratinocyte cell line (PAM-212) and compared with the expression of two proinflammatory cytokines: IL-1 alpha and tumour necrosis factor (TNF)-alpha. The PAM-212 cells were infected at a multiplicity of 0.5 with a clinical isolate of HSV type 1, and the mRNA of the three cytokines was assessed by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) over the following 24 hr. By 12 hr postinfection the amount of IL-10 mRNA had increased significantly to five-fold greater than that found in uninfected cells (P < 0.01), and this elevated level was maintained until at least 24 hr postinfection. In contrast, IL-1 alpha and TNF-alpha mRNAs were not significantly up-regulated by the HSV infection. Immunostaining with an IL-10 monoclonal antibody (mAb) revealed that cytoplasmic IL-10 protein had increased by 6-12 hr postinfection. This quantity was further increased at 24 hr postinfection, when the viral cytopathic effect was apparent. Viral replication was necessary, but not sufficient on its own, for IL-10 induction. Experiments with HSV mutants lacking functional transactivating factors suggested that the viral transactivating proteins ICP-0 and VP-16 may be necessary for HSV-induced IL-10 expression. Thus, the up-regulation in the expression of IL-10 mRNA and protein induced by HSV early in the infection of keratinocytes represents a specific response and may be part of the viral strategy to avoid local immune defence mechanisms in the skin.

Animals↗
PubMed2001

The diagnosis of invasive lobular breast carcinoma. Does MRI have a role?

Invasive lobular breast carcinoma accounts for approximately 15% of all breast cancers and is difficult to detect using conventional breast imaging techniques. We report a comparison between clinical, ultrasound scan (USS), mammographic and magnetic resonance imaging (MRI) of 22 patients with invasive lobular breast carcinomas. Actual tumour size was ascertained by histopathology. MRI detected 21 of the 22 invasive lobular cancers whilst mammography and USS detected 16 and 20 respectively. 19 tumours were clinically palpable. MRI was more accurate at assessing tumour size than USS and clinical examination, both of which underestimated tumour size.

Journal Article↗
PubMed2001

Recognising the changing boundaries of illness in defining terms of chronic illness: a prelude to understanding the changing needs of people with chronic illness.

Definitions of chronic illness do not reflect the changing nature of chronic illnesses. When definitions in the literature, which guide and inform thinking in a field, remain static they are in danger of creating stereotypes. This can have an adverse influence on the care of people with chronic illness. Debates over the use of terms associated with chronic illness will lead to a better understanding of the place of chronic illness in the world of health and illness and ultimately lead to services that better meet the needs of consumers.

Australia↗
PubMed2001

Improved care for diabetes in underserved populations.

UNLABELLED: Diabetes mellitus (DM) is a common chronic health condition among the adult population in the United States. DM is more prevalent and complications higher in Latinos, possibly due to inadequate medical and self-care as well as inaccurate culture-bound beliefs. Project Dulce is a nurse-managed DM educational and treatment program designed to measure the effect on clinical outcomes, adherence to American Diabetes Association and American Heart Association standards of care, and cultural beliefs in 210 high risk (HbA1c > 9.5%) and 346 lower risk (HbA1c < 9.5%) indigent Latinos with DM. METHODS: All patients were given a 12-week culturally sensitive educational program. Nurse manager/certified diabetes educators working together with primary care providers treated high-risk patients using protocols from Staged Diabetes Management. Physical exam and biochemical markers of DM were followed. Pre- and post-program questionnaires measured changes in diabetes knowledge, cultural beliefs practices, treatment satisfaction, and health locus of control. Chart reviews of Latinos with diabetes (n = 311) not enrolled in Project Dulce provided the case controls. RESULTS: After 1 year, the high-risk group showed significant improvements in HbA1c (11.5% to 8.3%, p < 0.0001), total cholesterol (219 to 181 mg/dL, p < 0.00001), SBP (129 to 122 mmHg, p < 0.03), and DBP (79 to 75 mmHg, p < 0.006). Pre- and post-test evaluations showed improved diabetes knowledge (p = .024), treatment satisfaction (p = .001) and internal locus of control (p = 0.04), and fewer inaccurate culture-bound beliefs (p = 0.001). Compliance was 100% in the high-risk group in obtaining HbAlc, lipids, urine microalbumin, and foot exams and 47% in obtaining eye exams, while the case controls had 28%, 46%, 31%, 14%, and 6% respectively. Mean TC and LDL values improved in Project Dulce patients compared to case controls (181 vs 221 Img/dL, p < 0.0001 and 99 vs 1241 mg/dL, p < 0.0004). CONCLUSION: Patients enrolled in Project Dulce had significantly improved clinical outcomes, adherence to standards of care, and culture bound beliefs. Nurse managed diabetes management programs that are culturally sensitive may decrease the incidence of complications of diabetes and improve health outcomes.

California↗
PubMed2001

Elevated leukaemia inhibitory factor (LIF) expression in lesional psoriatic skin: correlation with interleukin (IL)-8 expression.

Psoriasis is a disease marked by keratinocyte hyperproliferation, neutrophil and lymphocyte infiltration, and aberrant epidermal and dermal expression of cytokines. Previously, it has been shown that LIF appears to be involved in skin inflammation and can induce the expression of IL-8. We sought to determine whether expression of LIF is abnormal in lesional psoriatic skin and whether this correlates with the expression of IL-8. Using reverse transcription polymerase chain reaction, we measured the expression of LIF and IL-8 mRNA in biopsies from normal individuals, non-lesional psoriatic skin, and lesional psoriatic skin. No difference was seen between the expression of IL-8 and LIF in normal and in non-lesional psoriatic skin. However, LIF expression in lesional skin was increased 160% compared with normal biopsies or non-lesional skin (p < 0.001). Immunostaining of frozen sections showed that the expression of LIF protein was principally suprabasal and, in the majority of sections, concentrated mainly in the stratum corneum of the lesional skin, whereas it was mainly in the stratum spinosum of the normal/non-lesional skin. IL-8 mRNA expression did not differ between the non-lesional and normal skin, but expression in the lesional skin was 17.6-fold greater than in normal skin (p < 0.001), and this expression was correlated with the increased LIF expression (r = 0.67, p < 0.001). Although a significant negative correlation was demonstrated between LIF mRNA expression and the duration of the last outbreak of the disease, no other correlations were found between levels of cytokine expression and a variety of parameters including PASI score. These data suggest a role for keratinocyte LIF in the psoriatic lesion and a link between LIF and IL-8 expression.

Adult↗
PubMed2001

In vitro and in vivo inhibition of interleukin (IL)-5-mediated eosinopoiesis by murine IL-5Ralpha antisense oligonucleotide.

The unique role of interleukin (IL)-5 in eosinophil production, activation, and localization makes this cytokine a prime target for therapeutic intervention in diseases characterized by a selective blood and tissue eosinophilia. In an attempt to block the effects of IL-5 on eosinophils, a strategy was developed to suppress the expression of the IL-5 receptor alpha chain (IL-5Ralpha) by antisense oligonucleotides (ASOs). IL-5Ralpha ASOs were identified which selectively and specifically suppress the expression of messenger RNA and proteins of both the membrane and the soluble form of the receptor in constitutively IL-5R-expressing murine BCL-1 cells in vitro. Moreover, these IL-5Ralpha-specific ASOs were able to selectively inhibit the IL-5-induced eosinopoesis from murine fetal liver and bone marrow cells in vitro, suggesting that these molecules may affect the development of IL-5-mediated eosinophilia in vivo. Indeed, intravenous administration of IL-5Ralpha-specific ASOs not only suppressed the bone-marrow and blood eosinophilia in mice after short-term treatment with recombinant murine IL-5 but also inhibited the development of blood and tissue eosinophilia in a ragweed-induced allergic peritonitis model. Thus, blocking the expression of IL-5Ralpha on eosinophil using ASOs may have therapeutic benefits in eosinophilic diseases such as asthma.

Animals↗
PubMed2001

mosaic eyes: a zebrafish gene required in pigmented epithelium for apical localization of retinal cell division and lamination.

For proper function of the retina, the correct proportions of retinal cell types must be generated, they must be organized into cell-specific laminae, and appropriate synaptic connections must be made. To understand the genetic regulation of retinal development, we have analyzed mutations in the mosaic eyes gene that disrupt retinal lamination, the localization of retinal cell divisions to the retinal pigmented epithelial surface and retinal pigmented epithelial development. Although retinal organization is severely disrupted in mosaic eyes mutants, surprisingly, retinal cell differentiation occurs. The positions of dividing cells and neurons in the brain appear normal in mosaic eyes mutants, suggesting that wild-type mosaic eyes function is specifically required for normal retinal development. We demonstrate that mosaic eyes function is required within the retinal pigmented epithelium, rather than in dividing retinal cells. This analysis reveals an interaction between the retinal pigmented epithelium and the retina that is required for retinal patterning. We suggest that wild-type mosaic eyes function is required for the retinal pigmented epithelium to signal properly to the retina.

Animals↗
PubMed2001

Synthesis and structure-activity relationship of N-arylrolipram derivatives as inhibitors of PDE4 isozymes.

Structure activity studies of N-phenylrolipram derivatives have led to the identification of highly potent PDE4 inhibitors. The potential of these inhibitors for cellular activity was routinely assessed in an assay of fMLP induced oxidative burst in human eosinophils. Since first generation PDE4 inhibitors have been plagued with a number of unwanted side effects, parallel structure activity studies for competition with the [3H]-rolipram binding site in rat brain were performed. In this fashion 5-[4-(3-cyclopentyloxy-4-methoxyphenyl)-2-oxo-pyrrolidin-1-yl]-3-(3-methoxybenzyloxy)benzoic acid N',N'-dimethylhydrazide (22) was identified as a potent inhibitor of PDE4 which exhibits >1000 fold selectivity versus PDE3, and is a nanomolar inhibitor in all the cellular assays tested. Studies on the stereoselectivity of PDE4 inhibition of this class of rolipram based compounds revealed, that for example (S)-11 is a more potent inhibitor than (R)-11. This effect can also be observed in primary human cells where the (S)-enantiomer is about 10 fold more potent than the corresponding (R)-enantiomer.

3',5'-Cyclic-AMP Phosphodiesterases↗