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Kathleen Smith

Publications and source records attributed to Kathleen Smith.

18 recordsLinked to original sources
PubMed2007

Histone methylation is required for oogenesis in Drosophila.

SET domain proteins are histone lysine methyltransferases (HMTs) that play essential roles in development. Here we show for the first time that histone methylation occurs in both the germ cells and somatic cells of the Drosophila ovary, and demonstrate in vivo that an HMT, the product of the eggless (egg) gene, is required for oogenesis. Egg is a SET domain protein that is similar to the human protein SETDB1 and its mouse ortholog ESET. These proteins are members of a small family of HMTs that contain bifurcated SET domains. Because depletion of SETDB1 in tissue culture cells is cell-lethal, and an ESET mutation causes very early periimplantation embryonic arrest, the role of SETDB1/ESET in development has proven difficult to address. We show that egg is required in the Drosophila ovary for trimethylation of histone H3 at its K9 residue. In females bearing an egg allele that deletes the SET domain, oogenesis arrests at early stages. This arrest is accompanied by reduced proliferation of somatic cells required for egg chamber formation, and by apoptosis in both germ and somatic cell populations. We propose that other closely related SET domain proteins may function similarly in gametogenesis in other species.

Animals↗
PubMed2006

IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis.

Aberrant cytokine expression has been proposed as an underlying cause of psoriasis, although it is unclear which cytokines play critical roles. Interleukin (IL)-23 is expressed in human psoriasis and may be a master regulator cytokine. Direct intradermal administration of IL-23 in mouse skin, but not IL-12, initiates a tumor necrosis factor-dependent, but IL-17A-independent, cascade of events resulting in erythema, mixed dermal infiltrate, and epidermal hyperplasia associated with parakeratosis. IL-23 induced IL-19 and IL-24 expression in mouse skin, and both genes were also elevated in human psoriasis. IL-23-dependent epidermal hyperplasia was observed in IL-19-/- and IL-24-/- mice, but was inhibited in IL-20R2-/- mice. These data implicate IL-23 in the pathogenesis of psoriasis and support IL-20R2 as a novel therapeutic target.

Animals↗
PubMed2006

Identification of overexpression of orphan G protein-coupled receptor GPR49 in human colon and ovarian primary tumors.

We used gene expression profiling to probe differences in transcriptional output between 15 panels of colon tumor and matched normal colon tissues. This analysis revealed that GPR49, an orphan G Protein-Coupled Receptor (GPCR) is overexpressed in 66% (10/15) colon tumors compared with normal colon tissues. Subsequent analysis of an additional 39 sets of matched normal and tumor colon tissues by real-time quantitative reverse transcriptase confirmed the upregulation of this receptor. The differential expression of GPR49 between normal and tumor tissue was significant (p > 0.001). GPR49 was upregulated in 25 of 39 (64%) colon primary tumor tissues. In addition to colon tumors, GPR49 was also found to be upregulated in 18 of 33 (53%) ovarian primary tumor tissues analyzed by RT-PCR. Moreover, the expression level of GPR49 in colon and ovarian tumors increased in more advanced tumors suggesting a role for the receptor in tumor progression. The selective overexpression of GPR49 in tumor tissues was further illustrated by specific immunohistochemical staining of colon and ovarian tumor tissues, a finding that correlates with the mRNA expression of the receptor. In addition, expression of GPR49 induced transformation in a ligand-dependent manner and Knockdown of GPR49 mRNA level induced apoptosis in colon tumor cells. These novel findings provide a foundation for further studies and suggest a potential role for GPR49 in tumorigenesis.

Apoptosis↗
PubMed2006

From golden beaches to the heartland: reflections of NSW rural trainees.

OBJECTIVE: To describe the training experiences of rural-based psychiatry trainees in New South Wales. METHOD: Semistructured interviews were conducted with psychiatry trainees, rural psychiatrists and rural mental health administrators. The interviews were, for the most part, conducted face to face. RESULTS: Three factors that make this programme work are the opportunity to start training in a rural centre, a local psychiatrist who can act as guide and mentor and the initiative of this group of registrars. Three obstacles are a perceived lack of flexibility in College guidelines, isolation from peers and insufficient support when relocating to the city for specialty terms. CONCLUSIONS: The NSW rural psychiatry training project is an exciting development. Three years on, it represents the best avenue for creating a locally based rural psychiatrist network. It stands as a model for the rest of the country.

Community Mental Health Centers↗
PubMed2006

Case study: A view of informatics nursing from a clinical nurse's perspective.

The Surgical Ambulatory Care Units at our large metropolitan hospital completed major redesign and renovation of the outpatient surgical clinic area. The design and architectural drawings were initiated in 2002 with the space finished and finally occupied in May 2005. An informatics nurse was not assigned to the project. The registered nurse manager for the nursing services in these surgical clinics found the lack of planning for informatics support and supplies for the clinic areas to be an impediment that prevented a smooth move into the new spaces and transition to new business processes. The absence in the existing clinical information system patient education documentation form of post surgical procedure teaching information created significant problems. The surgical clinic nurse requested assistance from the nursing informatics department to modify the form to include documentation of the patient education, a request due in part to fulfill the documentation requirements from the Joint Commission on Accreditation of Hospital Organization (JCAHO). Other issues needed the attention of an informatics nurse.

Humans↗
PubMed2005

Distinctive clinical presentation of a NF-1 patient with loss of heterozygosity of PTCH in his epithelial tumors.

Although patients with neurofibromatosis (NF) have an increased incidence of tumors, there is only one study that suggests that NF1 patients may have an increased risk for epithelial malignancies. We present a patient with known NF1 who had developed multiple epithelial tumors since early in his life. All but one of these tumors were morphologically most consistent with trichoepitheliomas. Loss of heterozygosity (LOH) for Patched 1 gene (PTCH) was demonstrated within two of the trichoepitheloma-like tumors and one tumor diagnosed as basal cell carcinoma, and the patient was show to have a PTCH gene deletion. To our knowledge, a patient presenting with both NF1 and multiple trichoepitheliomas (MTE) has not previously been reported. The dysregulation in cellular proliferation and signaling induced by decreased NF1 along with the PTCH gene mutation may explain the pattern of immunohistochemical staining within these tumors, and the rare association of NF1 with epithelial neoplasms.

Adult↗
PubMed2004

Giant basal cell carcinoma associated with human papillomaviruses infection.

Different criteria have been used to define giant basal cell carcinoma (BCC). However, the majority of tumors of 10 cm or greater in diameter have a characteristic clinical and histopathologic presentation. As a group, these tumors often show metastatic spread as opposed to all other BCCs that rarely metastasize. We present an additional patient with a giant BCC greater than 100 cm2. This tumor had a characteristic location and infiltrative growth pattern. Unusual features of this tumor included a lack of expression of BCL-2 with a greater proportion of cycling tumor cells expressing proliferation markers than conventional BCC, as well as expression of anogenital human papillomaviruses (HPV) subtypes with oncogenic potential. The association of HPV with BCCs has rarely been studied and may not be identical to HPV-induced genital squamous cell carcinomas. However, the findings in this patient suggest that HPV may play a role in the development of some chronic giant BCCs.

Biomarkers, Tumor↗
PubMed2002

Do the physical and histologic features and time course in acute generalized exanthematous pustulosis reflect a pattern of cytokine dysregulation?

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is characterized by fever and an indurated erythematous eruption early, with the development of nonfollicular pinhead sterile pustules on an erythematous background. The eruption progresses and resolves relatively rapidly. Although drugs are believed to be the major etiologic agents, other immune modulators, including infections, heavy metals, and radiation, have been implicated. OBJECTIVE: The purpose of this study was to document underlying diseases in patients with AGEP and to determine if this data and the histologic features suggested an underlying pattern of immune dysregulation. METHODS: Twenty-one patients with new or recurrent episodes of AGEP were questioned concerning underlying diseases. The histopathologic features seen in the biopsy sections and the approximate time of biopsy during the course of their eruptions were recorded. RESULTS: Two patients had a history of psoriasis and one patient had a family history of psoriasis, two patients had diagnoses of sarcoid, two patients had inflammatory bowel disease, one had autoimmune thyroiditis, and one patient had multiple sclerosis. Biopsies done at the onset of the eruption showed marked to moderate papillary dermal edema and a mixed dermal inflammatory infiltrate. Shortly thereafter, biopsies showed spongiform pustules within the epidermis and occasional dyskeratotic cells with residual perivascular dermal edema. Although no definitive vasculitis was seen, there was leukocytoclasis within the dermal infiltrate in the majority of biopsy specimens performed more than 48 hours after the onset of the eruption. CONCLUSION: The histologic features seen in AGEP and the disease associations suggest that patients who develop this eruption may have an underlying tendency for development of a pattern of immune dysregulation characterized by a T helper-1 cytokine pattern.

Acute Disease↗
PubMed2002

Antimicrobial residues in animal waste and water resources proximal to large-scale swine and poultry feeding operations.

Expansion and intensification of large-scale animal feeding operations (AFOs) in the United States has resulted in concern about environmental contamination and its potential public health impacts. The objective of this investigation was to obtain background data on a broad profile of antimicrobial residues in animal wastes and surface water and groundwater proximal to large-scale swine and poultry operations. The samples were measured for antimicrobial compounds using both radioimmunoassay and liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS) techniques. Multiple classes of antimicrobial compounds (commonly at concentrations of > 100 microg/l) were detected in swine waste storage lagoons. In addition, multiple classes of antimicrobial compounds were detected in surface and groundwater samples collected proximal to the swine and poultry farms. This information indicates that animal waste used as fertilizer for crops may serve as a source of antimicrobial residues for the environment. Further research is required to determine if the levels of antimicrobials detected in this study are of consequence to human and/or environmental ecosystems. A comparison of the radioimmunoassay and LC/ESI-MS analytical methods documented that radioimmunoassay techniques were only appropriate for measuring residues in animal waste samples likely to contain high levels of antimicrobials. More sensitive LC/ESI-MS techniques are required in environmental samples, where low levels of antimicrobial residues are more likely.

Animal Feed↗
PubMed2002

Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP.

Whether epithelial cells play a role in triggering the immune cascade leading to T helper 2 (T(H)2)-type allergic inflammation is not known. We show here that human thymic stromal lymphopoietin (TSLP) potently activated CD11c(+) dendritic cells (DCs) and induced production of the T(H)2-attracting chemokines TARC (thymus and activation-regulated chemokine; also known as CCL17) and MDC (macrophage-derived chemokine; CCL22). TSLP-activated DCs primed naïve T(H) cells to produce the proallergic cytokines interleukin 4 (IL-4), IL-5, IL-13 and tumor necrosis factor-alpha, while down-regulating IL-10 and interferon-gamma. TSLP was highly expressed by epithelial cells, especially keratinocytes from patients with atopic dermatitis. TSLP expression was associated with Langerhans cell migration and activation in situ. These findings shed new light on the function of human TSLP and the role played by epithelial cells and DCs in initiating allergic inflammation.

Adult↗
PubMed2002

Host-vs.-altered-host eruptions in patients on liposomal doxorubicin.

BACKGROUND: Anthracycline antitumor antibiotics are the most commonly used chemotherapeutic agents. One of these is doxorubicin. Liposomal doxorubicin was developed as a drug delivery system in order to deliver the active drug intracellularly while decreasing the systemic toxicity, particularly hematological and cardiac toxicity. METHODS: The clinical and histologic findings of the cutaneous eruptions of associated with liposomal doxorubicin are reviewed. RESULTS: The eruptions occurred in three women with metastatic ovarian carcinoma who were treated with liposomal doxorubicin. These three patients developed erythematous macular/papular to plaque cutaneous lesions, and in one patient a vesicular component. The eruptions involved the trunk and extremities approximately 3-4 weeks after completions of therapy. None of the patients had any documented infections, and none of the patients had symptoms other than pruritus. The eruptions cleared over a period of weeks to months. Histologic features included an interface dermatitis with numerous apoptotic/dyskeratotic cells within the epidermis, with involvement the intra-epidermal sweat ducts and the infundibulum of hair follicles. CONCLUSION: We believe that these eruptions represented a chemotherapy induced host-vs.-altered host reaction.

Acanthosis Nigricans↗
PubMed2002

Cutaneous lesions showing giant yeast forms of Blastomyces dermatitidis.

BACKGROUND: The yeast forms of Blastomyces dermatitidis usually range from 8 to 15-20 micro m in diameter. Larger yeast forms have previously been reported only twice in immunosuppressed patients. In both patients these large forms were seen within the lung. CASE REPORT: We present a 14-year-old cardiac transplant patient, who presented 36 days following his transplantation with acute respiratory distress followed a few days later by erythematous cutaneous papules. RESULTS: Biopsy of a skin lesion showed yeast forms, some greater than 40 micro m in diameter, within and surrounding dermal vessels. Cultures later grew Blastomyces dermatitidis. CONCLUSIONS: To our knowledge this is the first reported case of giant forms of Blastomyces dermatitidis within the skin. With increased iatrogenic immunosuppression, we may expect to see more diverse morphologic forms with deep fungal infections.

Adolescent↗
PubMed2002

Successful interdisciplinary documentation through nursing interventions classification.

Automated documentation systems enable health care professionals to develop dynamic, interdisciplinary care plans. Use of a standardized nomenclature provides a common framework and language for the communication of the plan, and also can support data collection to determine best clinical practices. A comprehensive patient care record will link the interdisciplinary care plan to clinical charting and the documentation of outcomes. This article reviews efforts to improve interdisciplinary communication by computerizing the documentation system, using the Nursing Interventions Classification (NIC).

Benchmarking↗
PubMedDate not supplied

A public health nursing practice model: melding public health principles with the nursing process.

There has been a shift in emphasis in public health from the provision of personal health services for individuals to efforts targeted at improving the health of the whole community. Many in public health nursing (PHN) have welcomed this shift, recognizing the important role PHN can play in promoting health and preventing disease for all. There continues to be a need to redefine PHN roles and practice so that public health nurses can participate more effectively. Los Angeles County Department of Health Services Public Health Nursing (LAC PHN) has developed a practice model grounded in nationally recognized components: the public health team, PHN standards of practice, the 10 Essential Public Health Services, Healthy People 2010's 10 Leading Health Indicators and additional local indicators, and the Minnesota Public Health Nursing Interventions Model. The LAC PHN Practice Model provides a conceptual framework that assists in clarifying the role of the public health nurse and presents a guide for public health practice applicable to all public health disciplines.

Community Health Planning↗
PubMedDate not supplied

The reinvigoration of public health nursing: methods and innovations.

Los Angeles County (LAC) restructured and reinvigorated public health in response to nationwide concern over the adequacy of all public health infrastructures and functions. LAC's reorganization into geographically defined service planning areas (SPAs) has facilitated the integration of core public health functions into local practice. Public health nurses practicing as generalists within their SPA identified three initial objectives to address in population-based care: (1) expanding practice beyond disease control to a more holistic approach, (2) providing consultation using the Ask-the-Nurse innovation, and (3) developing a community assessment database for interdisciplinary SPA health planning. Additional innovative objectives are planned for the future.

Community Health Planning↗