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Biomedical subjects

D E Elder

Publications and source records attributed to D E Elder.

At least 19 recordsLinked to original sources
PubMed2004

Fractal characteristics of breath to breath timing in sleeping infants.

We examined interbreath interval (IBI) time series of 19 term infants during active and quiet sleep for fractal properties using Fano factor analysis. For each time series we calculated the fractal exponent (alpha), comparing alpha for the original time series with two forms of surrogate data, a temporally independent surrogate set and an autoregressive surrogate set. alpha values were normally distributed between 0.79 and -0.22, and did not differ with sleep state. The fractal characteristics of the original time series were not retained in the temporally independent surrogate time series indicating that the distribution of intervals alone was not fractal, but were retained using autoregressive surrogates with an order of 10, suggesting that the fractal properties of the IBI time series were related to correlations between successive breaths. These observations suggest that some of the respiratory variability that occurs during sleep in infants, which in the past has been regarded as stochastic noise, may be the product of deterministic processes.

Factor Analysis, Statistical↗
PubMed2004

Lymphatic vessel density is significantly increased in melanoma.

BACKGROUND: Melanoma is well known for its ability to involve regional lymph nodes in the early stage. However, the presence of lymphangiogenesis in melanoma is still controversial due to lack of lymphatic-specific markers. The purpose of this study was to determine the intra- and peritumoral lymphatic vessel density (LVD) using a novel lymphatic vessel-specific marker D2-40 and compare it to general vessel density (GVD) as determined by CD31 immunostaining in a series of melanocytic lesions. METHODS: The intra- and peritumoral GVD and LVD were examined by immunohistochemistry using D2-40 and CD31 antibodies in a series of melanocytic lesions. RESULTS: We found significantly higher intratumoral LVD in melanomas as compared to either common acquired or dysplastic nevi (p < 0.01). Although peritumoral LVD in melanoma and malignant melanoma in situ was higher compared to nevi, the difference did not reach statistical significance (p = 0.059). There was no significant difference in GVD among the various groups of melanocytic lesions. CONCLUSIONS: Our results show that intratumoral LVD is significantly increased in melanomas compared to benign nevi. The higher intratumoral lymphatic density in invasive melanomas suggests that melanoma cells might promote lymphangiogenesis. In addition, assessment of intratumoral LVD may be potentially useful in the differential diagnosis of melanocytic lesions.

Antibodies, Monoclonal↗
PubMed2003

Interobserver reproducibility of ulceration assessment in primary cutaneous melanomas.

In the recently revised melanoma staging system proposed by the American Joint Committee on Cancer (AJCC), ulceration assessment by the pathologist is a pivotal parameter. Patients upstaged because of ulceration might be included in adjuvant trials conducted in AJCC stage II melanoma patients. Therefore, accuracy based on interobserver reproducibility for melanoma ulceration assessment is crucial for proper clinical management. In some cases, it is extremely difficult, even for an experienced pathologist, to distinguish between trauma-induced ulceration, artifact and tumoral ulceration. Whether this difficulty may be resolved by the use of a more precise definition of ulceration has not been evaluated. Therefore, we have proposed a refined definition of melanoma ulceration and we tested whether this definition might improve the interobserver interpretative reproducibility of ulceration in primary cutaneous melanomas. The results of this study support the need for a more precise definition of melanoma ulceration that rules out biopsy trauma or processing artifact and could be incorporated into a standardised pathology worksheet for reporting primary melanomas.

Biopsy↗
PubMed2002

Rarity of CDK4 germline mutations in familial melanoma.

To date, two genes have been implicated in melanoma pathogenesis. The first, CDKN2A, is a tumour suppressor gene with germline mutations detected in 20% of melanoma-prone families. The second, CDK4, is an oncogene with co-segregating germline mutations detected in only three kindreds worldwide. We examined 16 American melanoma-prone families for mutations in all coding exons of CDK4 and screened additional members of two previously reported families with the Arg24Cys germline CDK4 mutation to evaluate the penetrance of the mutation. No new CDK4 mutations were identified. In the two Arg24Cys families, the penetrance was estimated to be 63%. Overall, 12 out of 12 invasive melanoma patients, none out of one in situ melanoma patient, five out of 13 dysplastic naevi patients, two out of 15 unaffected family members, and none out of 10 spouses carried the Arg24Cys mutation. Dysplastic naevi did not strongly co-segregate with the Arg24Cys mutation. Thus the phenotype observed in melanoma-prone CDK4 families appears to be more complex than just the CDK4 mutation. Both genetic and environmental factors are likely to contribute to the occurrence of melanoma and dysplastic naevi in these families. In summary, although CDK4 is a melanoma susceptibility gene, it plays a minor role in hereditary melanoma.

Cyclin-Dependent Kinase 4↗
PubMed2002

A versatile method for the removal of melanin from ribonucleic acids in melanocytic cells.

Melanin pigments often co-purify during preparation of nucleic acids from cells or tissues of melanocytic origin. Contaminating melanin can severely impede subsequent analyses of RNA. We attempted to eliminate melanin in RNA preparations using selected gel matrices. We show here that co-purified melanin pigments can be largely eliminated from RNA samples after passing through polyacrylamide-based beads (Bio-Gel P-60). After isolation from the pigment-containing cells or tissues, RNA was subsequently processed through batch or column purification under acidic pH conditions. The resulting RNA was devoid of contaminating melanin pigments and amenable to molecular reactions such as polymerase chain reaction and cDNA synthesis by reverse transcriptase. Although the process results in some loss of input RNA, this purification procedure is simple, robust and can easily be adopted in any laboratory for the molecular analysis of RNA that requires removal of melanin contamination.

Acrylic Resins↗
PubMed2001

Locally recurrent malignant melanoma characteristics and outcomes: a single-institution study.

Despite improvements in the identification and treatment of melanoma, local recurrence continues to challenge the success of current melanoma therapy. A retrospective analysis of 1,996 patients presenting from 1990 to 1997 at the Pigmented Lesion Group of the University of Pennsylvania was performed to assess clinical characteristics and outcomes of locally recurrent melanoma. The cases were analyzed by chart and pathological slide review. A control group was identified for statistical comparison. The incidence of locally recurrent melanoma during the study period was 2.2%. Lentigo maligna melanoma (LMM) accounted for 37% of the local recurrences. Increased tumor thickness and microsatellites were associated with "early" local recurrence and decreased survival from time of recurrence. Nineteen percent of the local recurrences occurred more than 5 years after the initial definitive treatment. The preponderance of locally recurrent LMM suggests the need for refinements in the techniques of margin identification and surgical excision of LMM. Tumors with increased thickness and microsatellites should receive particularly close attention. Lastly, with nearly 20% of the local recurrences occurring more than 5 years after the initial date of treatment, the authors suggest extending the follow-up time for all melanoma lesions beyond 5 years.

Adult↗
PubMed2000

Incidence of sentinel node metastasis in patients with thin primary melanoma (< or = 1 mm) with vertical growth phase.

BACKGROUND: Patients with thin primary melanomas (< or = 1 mm) generally have an excellent prognosis. However, the presence of a vertical growth phase (VGP) adversely impacts the survival rate. We report on the rate of occurrence of nodal metastasis in patients with thin primary melanomas with a VGP who are offered sentinel lymph node (SLN) biopsy. METHODS: Among 235 patients with clinically localized cutaneous melanomas who underwent successful SLN biopsy, 71 had lesions 1 mm or smaller with a VGP. The SLN was localized by using blue dye and a radiotracer. If negative for tumor by using hematoxylin and eosin staining, the SLN was further examined by immunohistochemistry. RESULTS: The rate of occurrence of SLN metastasis was 15.2% in patients with melanomas deeper than 1 mm and 5.6% in patients with thin melanomas. Three patients with thin melanomas and a positive SLN had low-risk lesions, based on a highly accurate six-variable multivariate logistic regression model for predicting 8-year survival in stage I/II melanomas. The fourth patient had a low- to intermediate-risk lesion based on this model. At the time of the lymphadenectomy, one patient had two additional nodes with metastasis. CONCLUSIONS: VGP in a melanoma 1 mm or smaller seems to be a risk factor for nodal metastasis. The risk of nodal disease may not be accurately predicted by the use of a multivariate logistic regression model that incorporates thickness, mitotic rate, regression, tumor-infiltrating lymphocytes, sex, and anatomical site. Patients with thin lesions having VGP should be evaluated for SLN biopsy and trials of adjuvant therapy when stage III disease is found.

Adolescent↗
PubMed2000

Human melanoma progression in skin reconstructs : biological significance of bFGF.

Human skin reconstructs are three-dimensional in vitro models consisting of epidermal keratinocytes plated onto fibroblast-contracted collagen gels. Cells in skin reconstructs more closely recapitulate the in situ phenotype than do cells in monolayer culture. Normal melanocytes in skin reconstructs remained singly distributed at the basement membrane which separated the epidermis from the dermis. Cell lines derived from biologically early primary melanomas of the radial growth phase proliferated in the epidermis and the basement membrane was left intact. Growth and migration of the radial growth phase melanoma cells in the dermal reconstruct and tumorigenicity in vivo were only observed when cells were transduced with the basic fibroblast growth factor gene, a major autocrine growth stimulator for melanomas. Primary melanoma cell lines representing the more advanced stage vertical growth phase invaded the dermis in reconstructs and only an irregular basement membrane was formed. Metastatic melanoma cells rapidly proliferated and aggressively invaded deep into the dermis, with each cell line showing typical invasion and growth characteristics. Our results demonstrate that the growth patterns of melanoma cells in skin reconstructs closely correspond to those in situ and that basic fibroblast growth factor is critical for progression.

Basement Membrane↗
PubMed2000

E-cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors.

In human epidermis, functional symbiosis requires homeostatic balance between keratinocytes and melanocytes. Compelling evidence from co-culture studies demonstrated a sophisticated, multileveled regulation of normal melanocytic phenotype orchestrated by undifferentiated, basal-type keratinocytes. Keratinocytes control cell growth and dendricity, as well as expression of melanoma-associated cell surface molecules of normal melanocytes. In contrast, melanoma cells are refractory to the keratinocyte-mediated regulation. The loss of regulatory dominance by keratinocytes occurs in concert with down-regulation of E-cadherin expression in melanoma cells. To investigate the potential role of E-cadherin in melanoma-keratinocyte interaction, we transduced E-cadherin-negative melanoma cells with full-length E-cadherin cDNA using an adenoviral vector. Our results show that functional E-cadherin expression in melanoma cells leads to cell adhesion to keratinocytes rendering them susceptible for keratinocyte-mediated control. In a skin reconstruction model, ectopic E-cadherin expression inhibits invasion of melanoma cells into dermis by down-regulating invasion-related adhesion receptors, MelCAM/MUC18 and beta3 integrin subunit, and by induction of apoptosis. Thus, disruption of the E-cadherin-mediated, normal regulatory control from keratinocytes may represent one of the mechanisms accounting for melanocyte transformation.

Adenoviridae↗
PubMed2000

The effect of selenium supplementation on outcome in very low birth weight infants: a randomized controlled trial. The New Zealand Neonatal Study Group.

BACKGROUND: Low selenium (SE) status has been documented in preterm infants and has been suggested to be a risk factor for chronic lung disease. METHODS: A total of 534 infants with birth weight <1500 g were enrolled in 8 New Zealand centers in a double-blind placebo-controlled randomized trial of SE supplementation from week 1 of life until 36 weeks' postmenstrual age or discharge home. Supplemented infants received 7 microg/kg/d of SE when fed parenterally and 5 microg/kg/d when fed orally. Plasma SE and glutathione peroxidase concentrations were measured in mothers after delivery and in infants before randomization and at 28 days and 36 weeks' postmenstrual age. Primary outcome measures were oxygen dependency at 28 days and total days oxygen dependency. RESULTS: No significant differences were seen between the groups with respect to primary or secondary outcome measures, with the exception that fewer supplemented infants had an episode of sepsis after the first week of life (P <.038). Mean plasma SE concentrations were 0.33 micromol/L before randomization in both groups and at 28 days had risen in the supplemented group (0.56 micromol/L) but fallen in the control group (0.29 micromol/L) (P <.0001). There was no association between outcome measures and SE concentrations at 28 days or 36 weeks' postmenstrual age. However, lower maternal and infant prerandomization SE concentrations were associated with increased respiratory morbidity. CONCLUSIONS: Postnatal SE supplementation in very low birth weight infants did not improve neonatal outcome. Further investigation of SE supplementation of mothers from the second half of pregnancy is warranted.

Double-Blind Method↗
PubMed2000

Signs and symptoms of melanoma in older populations.

We conducted a descriptive study to assess the relationship between increasing age and the reporting of melanoma signs/symptoms in 634 hospital-based and 624 population-based incident cases of melanoma. Multivariate logistic regression was used to evaluate the relationship between older age (> or = 50 years) and the reporting of melanoma signs/symptoms. Older patients were less likely to report itching and change in elevation of their lesions (P < 0.05). Change in color was also less likely to be reported by older patients, although not statistically significant. Ulceration of the lesion was reported significantly more by older patients (P < 0.05). Older individuals may be less likely to report itching and change in elevation/color of their lesions, but more likely to report ulceration, a symptom associated with advanced disease and poor prognosis. Further research is necessary to provide a better understanding of the development of melanoma in older populations so that new strategies can be explored to improve early detection in this age group.

Adult↗
PubMed2000

TIA-1 positive tumor-infiltrating lymphocytes in nevi and melanomas.

Tumor-infiltrating lymphocytes (TIL) have been shown to be an independent prognostic factor in melanomas. To better characterize the host immune response, we have classified TIL by their immunoreactivity against lymphoid markers in formalin-fixed, paraffin-embedded tissue. Monoclonal antibodies to leukocyte common antigen (LCA) and TIA-1 (a granule-associated protein of cytotoxic T cells and NK cells) were used to immunostain a series of benign nevi, nontumorigenic radial growth phase, and tumorigenic vertical growth phase melanomas and metastases. Among nine nevi, few LCA+ TIL were found, among which rare cells were positive for TIA-1 (mean, 2.0). Five nontumorigenic radial growth phase melanomas also had few total TIL and rare TIA-1+ TIL (mean, 3.4); the nontumorigenic radial growth phase component of seven tumorigenic vertical growth phase melanomas had higher numbers of TIA-1+ TIL (mean, 11). Twelve cases of tumorigenic vertical growth phase melanoma showed a variable but significantly greater number of both LCA+ TIL and TIA-1+ TIL (mean, 30.6). Nine cases of metastatic melanoma had a wide range of variation in LCA as well as in TIA-1+ TIL (mean, 46). Although the mean total number of TIA-1+ TIL increased from nontumorigenic radial growth phase to tumorigenic vertical growth phase to metastases, TIA-1+ as a percentage of TIL declined across these categories of tumor progression (42%, 31%, and 26%, respectively). Our results show that these attributes of TIA-1+ TIL, both increasing total number but decreasing percentage, appear to be a marker of tumor progression of malignant melanomas. In addition, there was significant variability in the number of TIA-1+ TIL among advanced melanomas, raising the possibility that an assessment of TIA-1+ TIL may prove a useful prognostic tool for the evaluation of primary melanomas.

Humans↗
PubMed1999

Progression-related expression of beta3 integrin in melanomas and nevi.

The expression of the beta3 integrin subunit was investigated in 130 fixed, paraffin-embedded specimens of human melanomas and nevi using two different monoclonal antibodies. Expression was not observed in melanocytes and was absent or low in most nevi. In primary melanomas, expression was absent or low in the nontumorigenic radial growth phase, which includes the classes of in situ and microinvasive melanomas. In contrast, expression was high in the tumorigenic or vertical growth phase compartment of many primary melanomas and in most metastatic melanomas. Expression patterns were similar with the two antibodies, SSA6 and SAP, and was membrane-related as well as cytoplasmically expressed. In those nevi that reacted focally, the reactivity tended to occur in the dermal component of neurotized nevi, and in Spitz nevi, where the reactivity was stronger and more diffuse. A few dysplastic nevi showed focal reactivity of the junctional component. These results are consistent with tumor progression-related expression of the beta3 integrin, which is expressed in melanocytic tumors as the alphavbeta3 integrin, having affinity for matrix molecules, including vitronectin and fibronectin. In all melanomas, and in the subset of tumorigenic vertical growth phase melanomas, expression increased with thickness (P < .01). For this reason, and because ligation of this integrin has been shown in vitro to have several properties that may be related to the malignant phenotype, it is likely that expression of this marker may have prognostic value. However, because of its consistent and strong expression in Spitz nevi, the diagnostic utility of this marker will likely be limited.

Aged↗
PubMed1999

Human hair follicle bulge cells are biochemically distinct and possess an epithelial stem cell phenotype.

Stem cells are vital for the homeostasis of self-renewing tissues and their manipulation may have wide ranging applications, including gene therapy, wound repair, and tissue transplantation. Although rodent hair follicle stem cells have been localized to the follicle bulge, the location of human hair follicle stem cells is less clear, and their characterization has been hampered by a lack of cellular markers for the bulge area. We demonstrate that the C8/144B monoclonal antibody, originally raised against a CD8 peptide sequence, immunostains the human hair follicle bulge. We show that this antibody recognizes cytokeratin 15 (K15) in keratinocytes, and that K15-positive bulge cells possess a stem cell phenotype characterized by their slowly cycling nature, proliferation at the onset of new hair follicle growth, and high level of beta1 integrin expression. These results localize human hair follicle stem cells to the bulge and suggest that K15 is preferentially expressed in epithelial stem cells.

Antibodies, Monoclonal↗
PubMed1999

Hospital admissions in the first year of life in very preterm infants.

OBJECTIVE: To analyse hospital readmissions to 1 year in infants < 33 weeks' gestation. STUDY DESIGN: Cohort of very preterm infants born in Western Australia. METHODS: Parental social class, history of asthma, race, gestational age, birthweight, sex, severity of respiratory disease and oxygen requirement at 28 days chronic lung disease (CLD), 36 weeks and term, maternal smoking, cohabitation with siblings, breast-feeding duration and hospital readmissions were recorded prospectively. RESULTS: Data were available for 538 of 560 (96%) infants discharged. Eight died in the first year. Two hundred and twenty-five infants (42%) had 443 readmissions, of which 370 were medical and 73 surgical. Risk factors for medical readmission were Aboriginal race, male sex and CLD. Breast-feeding was protective. Risk factors for surgical admission were male sex, lower gestation, severe hyaline membrane disease, severe CLD and birthweight < 10th centile. CONCLUSIONS: Readmission is common after very preterm birth. Risk factors for medical and surgical admission differ with CLD being the only perinatal factor associated with both medical and surgical admission.

Australia↗
PubMed1999

Cytokeratin 15 expression in trichoepitheliomas and a subset of basal cell carcinomas suggests they originate from hair follicle stem cells.

Trichoepitheliomas and many basal cell carcinomas appear to arise from the hair follicle, and in particular from the hair follicle bulge. This histogenesis is suggested from both morphological and immunohistochemical studies on tumor cells and stroma. Epithelial stem cells are thought to be important in tumorigenesis, and we previously localized a population of stem cells to the bulge area of the outer root sheath. We recently identified an anti-CD8 monoclonal antibody (DAKO clone C8/144B) that cross-reacts with cytokeratin 15 (K15), and serves as a specific marker for the bulge. In this study, we screened a series of trichoepitheliomas (n=13), basal cell carcinomas (n=37) and a variety of other skin tumors with this antibody. All trichoepitheliomas (100%) showed keratin 15 expression, while only a subset of basal cell carcinomas (27%) was K15-positive. Epidermal tumors, including squamous cell carcinomas, were K15-negative. Tumors of follicular derivation such as proliferating trichilemmal cysts were also K15-positive, while others such as pilomatricoma were K15-negative. Expression of K15 in trichoepitheliomas, some basal cell carcinomas and other follicular tumors suggests that these tumors are related to hair follicle stem cells in the bulge.

Antibodies, Monoclonal↗