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Biomedical subjects

P Newcomb

Publications and source records attributed to P Newcomb.

14 recordsLinked to original sources
PubMed2000

Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells.

We investigated the expression of insulin-like growth factor binding protein 3 (IGFBP-3) in normal human colonic epithelium and whether IGFBP-3 is involved in the induction of apoptosis in colonic epithelial cells. A gradient of IGFBP-3 protein expression was observed within the normal colonic crypt, and increased IGFBP-3 expression was coincident with the region of increased differentiation and apoptosis. Treatment of human colonic tumor cell lines with IGFBP-3 alone was shown to have no effect on growth. However, an increase in p53-dependent apoptosis was observed in the presence of 100 ng/ml IGFBP-3 24 h after the induction of DNA damage by gamma-irradiation. These results suggest that IGFBP-3 enhances the p53-dependent apoptotic response of colorectal cells to DNA damage.

Adenocarcinoma↗
PubMed1999

An immunohistochemical study of type I insulin-like growth factor receptors in the placentae of pregnancies with appropriately grown or growth restricted fetuses.

Insulin-like growth factors (IGFs) and their receptors in the fetus are essential for growth and postnatal survival but the role of maternal IGFs is less well understood. Animal and in vitro evidence suggests that maternal IGF-I may have important effects on placental function. Recent work in humans suggests that although there is no relationship between maternal serum IGF-I and normal fetal growth, levels are low in pregnancies complicated by fetal growth restriction due to placental dysfunction. A prospective and observational study was undertaken of the distribution and concentration of placental type I IGF receptors (IGF-IR) in women with small for gestational age (n=26) or appropriately grown (n=14) fetuses. Women were scanned biweekly from 24 weeks to delivery and cases (birthweight <5th centile) were assigned to two groups: 'fetal growth restriction' (FGR; umbilical artery pulsatility index [UAPI] > +2 s.d.; n=16) and 'normal small for gestational age' (SGA; normal UAPI, growth velocity and amniotic fluid; n=10). Immunohistochemistry of the IGF-IR was performed on formol saline-fixed placental biopsies obtained at delivery. In control pregnancies IGF-IR were present in villous endothelium and stroma, trophoblast and decidua and their distribution and density were unchanged in both SGA and FGR pregnancies. We hypothesize that a therapeutic elevation of maternal IGF-I in FGR pregnancy might lead to enhanced placental function and so fetal growth. Our findings of normal localization and density of placental IGF-IR in FGR encourage us to extend our work to look at the effects of maternal IGF-I on the transport of glucose and amino acids.

Chorionic Villi↗
PubMed1999

Vitamin D receptor expression in colorectal cancer.

AIMS: To determine whether the vitamin D receptor is expressed in colorectal cancer, and its relation to stage of disease. METHODS: Paraffin embedded sections of colorectal cancer from 30 patients who had undergone surgery were studied. Immunohistochemistry using the specific monoclonal antibody 9A7 gamma directed against the nuclear vitamin D receptor was used to identify receptors for the active metabolite of vitamin D3 (1,25-dihydroxyvitamin D3). RESULTS: Microscopically normal human colorectal epithelium showed vitamin D receptor expression predominantly in the mid and upper crypts. All the colorectal cancer tissue studied showed vitamin D receptor expression, with a median of 25.3 (range 10.1 to 43.7) cells/graticule field (x 400). Although vitamin D receptor staining was heterogeneous within the individual cancers, neither Dukes stage nor the degree of differentiation appeared to influence expression of the receptor. CONCLUSIONS: Colorectal cancer tissue expresses the nuclear vitamin D receptor and this could act as a potential therapeutic target for synthetic vitamin D3 differentiating agents.

Cell Nucleus↗
PubMed1995

A brief, telephone-administered food frequency questionnaire can be useful for surveillance of dietary fat intakes.

A 13-item questionnaire designed for quick telephone administration was evaluated for use in surveillance of fat intake in the United States. Study populations included 560 middle-aged and older adults from Beaver Dam, WI, 252 middle-aged and older women from Wisconsin, 73 young, low income Hispanic women from Chicago, IL, 52 older adults from Arizona and 135 younger adults from Augusta, GA. Correlations between fat scores and fat intakes measured by multiple food records or recalls or by more extensive food frequency questionnaires ranged from 0.33 to 0.60, similar to results from other published questionnaire validation studies. Correlations with percentage of energy from fat were lower (0.26 to 0.42), except for the Chicago population, for which there was no correlation (-0.02). There was no systematic variation in correlations among other subgroups defined by demographic and health-related characteristics, including race (black vs. white). Most, but not all, of the substantial differences in fat intakes among subgroups were identified by the questionnaire. The questionnaire will not capture small differences in intakes among groups and is inappropriate when the sample size is limited or for populations with diets substantially different from the typical U.S. diets, such as the Chicago population. However, with attention to its limitations, the questionnaire is useful for surveillance.

Adolescent↗
PubMed1994

Comparison of radioligand assay and immunostaining for epidermal growth factor receptor in human breast cancer.

Epidermal growth factor (EGF) receptor status is a useful prognostic indicator in women with breast cancer. Lack of standardization and correlation of methodology for the detection of EGF receptor has hampered its further evaluation. EGF receptor status was ascertained by immunohistochemistry and radioligand assay in 120 breast cancers. Of 52 tumours negative for EGF receptor on radioligand assay, 47 were negative on immunohistochemistry and, of 68 tumours positive for the receptor on assay, 52 were positive on immunohistochemistry. If the more widely evaluated radioligand assay is assumed to be the 'gold standard', immunohistochemistry has a sensitivity of 81 per cent and a specificity of 91 per cent.

Biomarkers, Tumor↗
PubMed1993

Correlation between p53 mutations and antibody staining in breast carcinoma.

Abnormalities of the p53 gene and protein were examined in 81 primary breast carcinoma samples. Using a polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP) analysis, mutations in p53 exons 5-8 were identified in 13 of 81 tumours (16 per cent) and confirmed by DNA sequencing. Positive staining for p53 protein was detected in ten of 77 (13 per cent) of these tumours using polyclonal CM1 antibody on formalin-fixed tissue. Mutations detected by PCR-SSCP analysis were more common in grade III tumours (P = 0.015), but no correlation was found with tumour size, node status or level of epidermal growth factor receptor expression. A p53 mutation was associated with positive antibody staining in only two patients. Positive immunohistochemical staining using a p53 antibody may detect p53 protein expression, but this may not correlate directly with an underlying mutation in the hot spot region examined.

Adult↗
PubMed1993

Evaluation of a brief telephone questionnaire to estimate fruit and vegetable consumption in diverse study populations.

We evaluated the use of a six-item telephone questionnaire to estimate fruit and vegetable intakes in five diverse populations. Researchers administered the telephone questionnaire to persons who had previously undergone more extensive dietary assessment. The study population included 553 middle-aged and older adults in Beaver Dam, WI; 252 middle-aged and older women throughout Wisconsin; 150 parents of school children in Augusta, GA; 73 low-income, Hispanic mothers in Chicago, IL; and 51 older adults in Arizona. Spearman correlation coefficients between total fruit and vegetable intakes measured by the brief telephone survey and by more extensive food frequency questionnaires were 0.47 (Augusta), 0.48 (Arizona), 0.56 (Wisconsin), and 0.57 (Beaver Dam). Correlations between intakes measured by the brief telephone survey and by multiple diet records or recalls were 0.29 (Arizona), 0.46 (Chicago), and 0.54 (Beaver Dam). With the exception of Arizona, mean daily fruit and vegetable intakes measured by the telephone survey were similar to intakes estimated by multiple diet records or recalls and lower than those estimated by extensive food frequency questionnaires. Although caution may be needed in interpreting dietary reports from some ethnic subgroups, this brief telephone questionnaire may be useful for surveillance of fruit and vegetable intake in the United States.

Adolescent↗
PubMed1993

Epidermal growth factor receptor determination on tumour imprints.

Epidermal growth factor receptor (EGFR) is a sensitive prognostic indicator in women with breast cancer. A new technique for the detection of EGFR on breast cancer imprints is described and evaluated in relation to immunohistochemistry on frozen sections. The standard streptavidin-biotin method using the R1 antibody on frozen sections was modified for use on tumour imprints. In the first group (group 1 imprints) 43 tumours were assessed by frozen section and imprint staining. The group 1 imprint method had a sensitivity of 50% and a specificity of 89% compared with the frozen sections. Further modifications were made for the following 32 tumours (group 2) and this method had a much improved sensitivity of 94% while specificity was preserved. This method is simple and could be performed in any hospital histopathology department.

Bacterial Proteins↗
PubMed1991

Tricyclic antidepressants and children.

Tricyclic antidepressants have been used in the treatment of certain childhood disorders for more than 20 years, and indications for their use in the pediatric population are increasing. Research supports the use of tricyclics for preadolescent children as adjunctive therapy for major depression, attention deficit hyperactivity disorder, enuresis, tic disorders, anxiety disorders and eating disorders. The range of indications and effects of tricyclics in the treatment of children, and issues related to management by health care providers are discussed in this article.

Adolescent↗
PubMed1987

A clinicopathologic and immunohistochemical study of 16 patients with small intestinal leiomyosarcoma. Limited utility of immunophenotyping.

Clinicopathologic data including immunophenotypic expression of 16 new cases of small intestinal leiomyosarcoma are presented. Patient age ranged from 27 to 87 years (mean, 61 years) with a 2.2:1 male-female ratio. Eighty-eight percent of tumors occurred distally, i.e., in the jejunoileum. Considerable histologic heterogeneity was noted including epithelioid, myxoid, and sclerotic variants. Stratification by histologic grade suggests important clinical subsets. Only in grade I tumors is surgical extirpation alone potentially curative. Grade II tumors are associated with meaningful survival usually measured in years, however, nearly all patients can be expected to die from their tumors. Grade III sarcomas are fully malignant and rapidly progressive: except for one case with limited follow-up, all patients with Grade III sarcomas died of disease with a mean survival of only nine months (median, 2 months). Immunostaining with antibodies directed against vimentin, muscle-specific actin, desmin, and S-100 protein were performed. Only antivimentin was uniformly reactive. Sixty-three percent of cases tested showed actin immunoreactivity, and no tumors revealed immunohistochemically detectable desmin or S-100 protein. Although many small bowel stromal sarcomas appear "poorly differentiated" by immunohistochemical methods presently available, that they are indeed leiomyosarcomas seems most likely from their intramural location and light histologic study. The limited utility of immunophenotyping and the importance of histologic grading are stressed.

Actins↗
PubMed1986

Human chromosome 21-encoded cDNA clones.

We have employed two strategies to isolate random cDNA clones encoded by chromosome 21. In the first approach, a cDNA library representing expressed genes of WA17, a mouse-human somatic cell hybrid carrying chromosome 21 as its sole human chromosome, was screened with total human DNA to identify human chromosome 21-specific cDNAs. The second approach utilized previously characterized single-copy genomic fragments from chromosome 21 as probes to retrieve homologous coding sequences from a human fetal brain cDNA library. Six cDNA clones on chromosome 21 were obtained in this manner. Two were localized to the proximal long arm of chromosome 21, two to the distal portion of the long arm, and one to the region of 21q22 implicated in the pathology of Down syndrome.

Chromosome Mapping↗
PubMedDate not supplied

Making a difference. The physician liaison.

Physician liaison profile ... Who are they and what role do they play in the physician hospital relationship? The Virginia hospital featured found even the smallest changes and improvements can make a big difference.

Hospital Administration↗