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Biomedical subjects

E Noll

Publications and source records attributed to E Noll.

At least 19 recordsLinked to original sources
PubMed2001

Oligodendrocyte lineage genes (OLIG) as molecular markers for human glial brain tumors.

The most common primary tumors of the human brain are thought to be of glial cell origin. However, glial cell neoplasms cannot be fully classified by cellular morphology or with conventional markers for astrocytes, oligodendrocytes, or their progenitors. Recent insights into central nervous system tumorigenesis suggest that novel molecular markers might be found among factors that have roles in glial development. Oligodendrocyte lineage genes (Olig1/2) encode basic helix-loop-helix transcription factors. In the rodent central nervous system, they are expressed exclusively in oligodendrocytes and oligodendrocyte progenitors, and Olig1 can promote formation of an chondroitin sulfate proteoglycon-positive glial progenitor. Here we show that human OLIG genes are expressed strongly in oligodendroglioma, contrasting absent or low expression in astrocytoma. Our data provide evidence that neoplastic cells of oligodendroglioma resemble oligodendrocytes or their progenitor cells and may derive from cells of this lineage. They further suggest the diagnostic potential of OLIG markers to augment identification of oligodendroglial tumors.

Astrocytoma↗
PubMed2001

Clinical reasoning of an experienced physiotherapist: insight into clinician decision-making regarding low back pain.

BACKGROUND AND PURPOSE: Investigation of the clinical reasoning skills of experienced clinicians provides insight into decision-making in the practice of physiotherapy. The purpose of the present study was to analyse the clinical reasoning skills of an experienced physiotherapist during her assessment and treatment of clients with low back pain. METHOD: Deconstruction of the physiotherapist's reasoning process was accomplished through observation of encounters between her and each of six patient subjects. Reconstruction and analysis of the physiotherapist's decision-making process was performed through retrospective interviews and reflective analysis of her clinical reasoning during each encounter. RESULTS: A working model of the physiotherapist's clinical reasoning was created from an integration of theoretical elements in the literature and the data. Through analysis of this framework, two core dimensions of her clinical reasoning were revealed: the influence of clinical experience and the influence of advanced training in a specific philosophy of treating the spine. CONCLUSIONS: The construction of these themes has contributed to the growing understanding of clinical reasoning strategies and skills used in orthopaedic physical therapy practice. Detailed description of the physiotherapist's reasoning process provides more meaningful understanding of physiotherapy treatments. In this case the physiotherapist employed a pattern recognition strategy and forward reasoning process in making a diagnosis. Further research is necessary to expand knowledge on the development of clinical reasoning skills.

Adult↗
PubMed2001

Prognostic and pathologic significance of quantitative protein expression profiling in human gliomas.

PURPOSE: Analysis of tumor-derived genetic lesions has provided insights into molecular pathogenesis of human gliomas. Because these changes represent only one of several mechanisms that alter gene expression during tumorigenesis, it is likely that further information will be obtained from a careful analysis of important regulatory proteins present in these tumors. EXPERIMENTAL DESIGN: We have quantified the levels of key cell cycle/signaling proteins in 94 prospectively collected, meticulously preserved, "snap frozen" glioma specimens and have compared these levels with histopathological data and patient outcome. RESULTS: The results of these experiments confirm that the levels of wild-type tumor suppressor proteins, such as p53, pRB, PTEN, p14(ARF), and p16(INK4), are lost or severely reduced in most gliomas, and that epidermal growth factor receptor, 2human telomerase reverse transcriptase, and cyclin-dependent kinase 4 are overexpressed frequently and with a few exceptions, almost exclusively, in glioblastomas. In addition, we report frequent underexpression of E2F-1 (in 55% of gliomas) and cyclin E overexpression (in 26% of gliomas), which have not yet been reported on the genomic level. Several of these markers significantly correlated with histopathological grade, and the levels of five proteins showed significant association with patient outcome. In particular, overexpression of epidermal growth factor receptor, human telomerase reverse transcriptase, cyclin-dependent kinase 4, and cyclin E was largely restricted to glioblastomas and was significantly associated with reduced patient survivals. CONCLUSIONS: We conclude that the quantitation of cell cycle/signaling proteins from meticulously preserved glioma specimens provides further insights into the molecular pathogenesis of human gliomas and yields valuable prognostic information.

Blotting, Western↗
PubMed2000

Presenilin affects arm/beta-catenin localization and function in Drosophila.

Presenilin is an essential gene for development that when disrupted leads to a neurogenic phenotype that closely resembles Notch loss of function in Drosophila. In humans, many naturally occurring mutations in Presenilin 1 or 2 cause early onset Alzheimer's disease. Both loss of expression and overexpression of Presenilin suggested a role for this protein in the localization of Armadillo/beta-catenin. In blastoderm stage Presenilin mutants, Arm is aberrantly distributed, often in Ubiquitin-immunoreactive cytoplasmic inclusions predominantly located basally in the cell. These inclusions were not observed in loss of function Notch mutants, suggesting that failure to process Notch is not the only consequence of the loss of Presenilin function. Human presenilin 1 expressed in Drosophila produces embryonic phenotypes resembling those associated with mutations in Armadillo and exhibited reduced Armadillo at the plasma membrane that is likely due to retention of Armadillo in a complex with Presenilin. The interaction between Armadillo/beta-catenin and Presenilin 1 requires a third protein which may be delta-catenin. Our results suggest that Presenilin may regulate the delivery of a multiprotein complex that regulates Armadillo trafficking between the adherens junction and the proteasome.

Animals↗
PubMed2000

Identification of autosomal regions involved in Drosophila Raf function.

Raf is an essential downstream effector of activated p21(Ras) (Ras) in transducing proliferation or differentiation signals. Following binding to Ras, Raf is translocated to the plasma membrane, where it is activated by a yet unidentified "Raf activator." In an attempt to identify the Raf activator or additional molecules involved in the Raf signaling pathway, we conducted a genetic screen to identify genomic regions that are required for the biological function of Drosophila Raf (Draf). We tested a collection of chromosomal deficiencies representing approximately 70% of the autosomal euchromatic genomic regions for their abilities to enhance the lethality associated with a hypomorphic viable allele of Draf, Draf(Su2). Of the 148 autosomal deficiencies tested, 23 behaved as dominant enhancers of Draf(Su2), causing lethality in Draf(Su2) hemizygous males. Four of these deficiencies identified genes known to be involved in the Drosophila Ras/Raf (Ras1/Draf) pathway: Ras1, rolled (rl, encoding a MAPK), 14-3-3epsilon, and bowel (bowl). Two additional deficiencies removed the Drosophila Tec and Src homologs, Tec29A and Src64B. We demonstrate that Src64B interacts genetically with Draf and that an activated form of Src64B, when overexpressed in early embryos, causes ectopic expression of the Torso (Tor) receptor tyrosine kinase-target gene tailless. In addition, we show that a mutation in Tec29A partially suppresses a gain-of-function mutation in tor. These results suggest that Tec29A and Src64B are involved in Tor signaling, raising the possibility that they function to activate Draf. Finally, we discovered a genetic interaction between Draf(Su2) and Df(3L)vin5 that revealed a novel role of Draf in limb development. We find that loss of Draf activity causes limb defects, including pattern duplications, consistent with a role for Draf in regulation of engrailed (en) expression in imaginal discs.

Animals↗
PubMed2000

Retinoids inhibit human glioma cell proliferation and migration in primary cell cultures but not in established cell lines.

OBJECTIVE: Retinoids are known to exhibit a broad spectrum of biological activities, and they participate in the onset of differentiation and the inhibition of growth in a wide variety of cancer cells. Some of these vitamin A derivatives are already in clinical use. However, data on retinoid actions in glial tumors are rather sparse. Therefore, we studied the effects of the natural retinoic acid (RA) forms all-trans-RA, 9-cis-RA, and 13-cis-RA on glioma cell lines and primary cultures from patients with glioblastomas multiforme. METHODS: Six human glioma cell lines, one rat glioma cell line, and 20 primary cultures established from biopsies from patients with glioblastomas multiforme were investigated. Tumor cell proliferation was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and cell-counting assays. Random migration out of tumor spheroids was quantified using a video-morphometry system. Invasion was investigated using a confrontational coculture test system. Retinoid receptor (RA receptor [RAR]alpha, -beta, and -gamma and retinoid X receptor [RXR]alpha, -beta, and -gamma) expression status was determined using reverse transcription-polymerase chain reaction studies. RESULTS: Treatment of five human glioma cell lines with the different retinoids at concentrations up to 10(-5) mol/L produced no reduction of proliferation, using various incubation times. For one human glioma cell line (U343MG-A) and one rat glioma cell line (C6), which were previously reported to be sensitive to retinoids, we could confirm strong inhibitory effects on proliferation and clear changes in morphological features after retinoid treatment. Application of the different retinoids to low-passage primary cultures of human glioblastomas resulted in marked inhibition of proliferation (30-95%) for all tested samples. Using three-dimensional spheroid cultures, we detected retinoid-induced decreases in cell migration (24-65%). Invasion was not affected by these vitamin A derivatives. In an analysis of the expression patterns for retinoid receptors (RARs and RXRs), all primary culture samples yielded positive results for RAR gamma and RXR alpha and negative results for RAR alpha, RAR beta, and RXR gamma, whereas the results of RXR beta expression were heterogeneous among different patients. The cell lines, irrespective of their RA sensitivities, did not exhibit any major differences in receptor expression. CONCLUSION: Retinoids strongly inhibit proliferation and migration in primary cultures of human glioblastomas multiforme. Our data support a clinical trial of retinoids for the treatment of human malignant gliomas. We observed that most established cell lines were not sensitive to RA. This difference between long-term cell lines and primary cultures cannot be explained by different retinoid receptor expression patterns.

Adult↗
PubMed1999

A temporal switch in DER signaling controls the specification and differentiation of veins and interveins in the Drosophila wing.

The Drosophila EGF receptor (DER) is required for the specification of diverse cell fates throughout development. We have examined how the activation of DER controls the development of vein and intervein cells in the Drosophila wing. The data presented here indicate that two distinct events are involved in the determination and differentiation of wing cells. (1) The establishment of a positive feedback amplification loop, which drives DER signaling in larval stages. At this time, rhomboid (rho), in combination with vein, initiates and amplifies the activity of DER in vein cells. (2) The late downregulation of DER activity. At this point, the inactivation of MAPK in vein cells is necessary for the maintenance of the expression of decapentaplegic (dpp) and becomes essential for vein differentiation. Together, these temporal and spatial changes in the activity of DER constitute an autoregulatory network that controls the definition of vein and intervein cell types.

Animals↗
PubMed1998

Retention of an appropriate astrocytic response to retinoids by human brain tumors comprised of predominantly glial fibrillary acidic protein-positive cells.

It has been demonstrated that glial fibrillary acidic protein (GFAP)-positive astrocyte precursors will differentiate in response to application of retinoic acid (RA), whereas GFAP/oligodendrocyte type 2-astrocyte progenitors will be inhibited from differentiating and continue to be mitotically active in the presence of RA. The authors sought to determine if cells taken from glial tumors that were GFAP positive retained the ability to differentiate following application of RA in vitro, as their normal astrocytic counterparts do. Primary cultures of seven astrocytic tumors were observed to have significantly fewer cells following 1 month of continuous exposure to 100 microM RA. Comparisons with sister control cultures indicated that in control conditions the tumor cells had undergone proliferation, whereas the number of cells in the RA-exposed cultures remained closer to the number of cells initially plated. This response to RA was demonstrated to be specific to the astrocytic tumors by virtue of the fact that cultures of normal brain and an anaplastic ependymoma both showed a strong proliferative response to retinoids.

Journal Article↗
PubMed1997

[Screening for microalbuminuria in diabetic patients in the primary health care system].

In order to detect the prevalence of microalbuminuria, a screening procedure was carried out in 1016 adult (age > 14 years) diabetic patients registered in primary health care system at the 17st district of the capital. The clinical characteristics of patients were investigated and microalbuminuria was measured by immunoturbidimetric method using first void morning urinary samples. In this way, the urinary albumin/creatinine ratio was calculated (abnormal value in men > or = 2.5 mg/mmol, in women > or = 3.5 mg/mmol). Moreover, serum creatinine, blood glucose, serum cholesterol and triglycerides were measured in fasting blood samples. After applying exclusion criteria data of 933 diabetic patients [129 insulin-dependent (IDDM) and 804 non-insulin-dependent (NIDDM) patients; 424 men, 509 women] were analysed. Abnormal urinary albumin/creatinine ratio was found in 315 (33.8%) patients. Microalbuminuria was detected in 32 (24.8%) IDDM and in 201 (25.0%) NIDDM patients. Macroalbuminuria was found in 13 (10.1%) IDDM and in 69 (8.6%) NIDDM patients. Abnormal urinary albumin/creatinine ratio was more often found in men than in women (IDDM men 41.3%, IDDM women 28.8%; NIDDM men 38.0%, NIDDM women 30.0%). Significant difference was found between diabetic patients with (n = 315) and without (n = 618) abnormal urinary albumin/creatinine ratio regarding age (64.3 +/- 0.7 years vs. 61.4 +/- 0.5 years; p < 0.001), duration of diabetes (10.3 +/- 0.5 years vs 7.9 +/- 0.3 years; p < 0.001) systolic blood pressure (151 +/- 1 mmHg vs 146 +/- 1 mmHg; p < 0.01), serum creatinine (99 +/- 2 mumol/l vs 88 +/- 1 mumol/l; p < 0.001) and blood glucose (10.4 +/- 0.2 mmol/l vs 9.4 +/- 0.1 mmol/l; p < 0.001). One third (33.8%) of diabetic patients in primary health care setting exhibited signs or were at risk of renal involvement of diabetes. Diabetic patients with micro- or macroalbuminuria should be carefully controlled in order to prevent or to decrease deterioration of renal function due to diabetic nephropathy.

Adult↗
PubMed1996

Zygotic lethal mutations with maternal effect phenotypes in Drosophila melanogaster. II. Loci on the second and third chromosomes identified by P-element-induced mutations.

Screens for zygotic lethal mutations that are associated with specific maternal effect lethal phenotypes have only been conducted for the X chromosome. To identify loci on the autosomes, which represent four-fifths of the Drosophila genome, we have used the autosomal "FLP-DFS" technique to screen a collection of 496 P element-induced mutations established by the Berkeley Drosophila Genome Project. We have identified 64 new loci whose gene products are required for proper egg formation or normal embryonic development.

Animals↗
PubMed1995

Mitotic frequency as a prognostic factor in breast cancer.

Grading of tumor malignancy in breast cancer should contribute essential information both for the prospective outcome of the individual patient as well as for TNM staging. In a series of 104 breast cancer patients we tested the prognostic validity and reproducibility of mitotic figure counting compared with TNM staging, Bloom and Richardson grading, DNA single cell cytometry, and morphometry. Four-micrometer thick hematoxylin-eosin-stained routine slides were investigated. Mitotic figures were counted in representative areas of the tumor in 10 159-microns 2-sized high power fields (HPFs) at a 400X magnification; the median value was seven and the threshold for the 25th percentile was three. This value should replace the common but prognostically invalid threshold of 10. Univariate survival analysis showed that mitotic figure counting allows the identification of three groups of patients (< or = 3, 4 to 20, > 20 mitoses per HPF) with significantly different survival probabilities (P < .0001; P = .0178). Depending on the number of mitotic figures, length of survival was significantly different within the group of T1N0 tumors (P = .0082) and the group of T1N1 or T2N0 tumors (P = .0251). In a Cox stepwise regression model mitotic frequency counting added prognostic information to tumor size and was of higher prognostic significance than lymph node status, DNA ploidy, or mean nuclear area. The 95% confidence limit for interobserver reproducibility, tested in 20 cases, was plus/minus 8 mitoses. After quartilization an agreement of 75% was observed.

Aged↗
PubMed1994

Use of transdermal nicotine in a state-level prescription plan for the elderly. A first look at 'real-world' patch users.

OBJECTIVE: To assess transdermal nicotine use patterns and outcomes in a population of low-income older smokers. DESIGN: A 6-month telephone follow-up survey of smokers filling prescriptions for transdermal nicotine in the first 3 months of 1992. SETTING: Pennsylvania's Pharmaceutical Assistance Plan for the Elderly, the nation's largest state-level prescription plan for the elderly. POPULATION: A total of 1070 noninstitutionalized male and female smokers aged 65 through 74 years. MAIN OUTCOME MEASURES: Self-reported physician/pharmacist advice and adjunctive treatments, concomitant smoking, and 6-month smoking abstinence. RESULTS: Respondents were predominantly long-term heavy smokers. They used nicotine patches for an average of 5 weeks, with few reporting use beyond 3 months or recalling bothersome side effects. Most of those with previous quit attempts rated quitting with the patch "easier." The 29% self-reported 6-month quit rate observed is encouraging. However, compliance with patch use guidelines was far from ideal in this high-risk population: only 54% of respondents received any initial advice or materials from their physicians or pharmacists, fewer than 2% took part in a formal clinic or one-to-one treatment program, and almost half (47%) smoked while using the patch, including 20% who smoked every day. Concomitant smoking was strongly associated with failure to achieve abstinence (P < .001). More frequent contact with physicians and/or pharmacists was associated with less concomitant smoking (P < .001) and higher quit rates (P = .005). CONCLUSIONS: This survey offers an important first look at problems and prospects for nicotine patch therapy in older adults, with implications for other groups as well. Prospective studies are needed to clarify optimal treatment regimens and adjuncts.

Administration, Cutaneous↗
PubMed1994

Regulation of oligodendrocyte differentiation: a role for retinoic acid in the spinal cord.

During development, oligodendrocyte precursors undergo sequential stages of differentiation characterized by expression of distinct cell surface properties and proliferative responses. Although both PDGF and bFGF are mitogenic for these cells, the factors that regulate the progression of oligodendrocyte precursors through their differentiative program remain unclear. One factor present in the embryonic spinal cord that may regulate differentiation of oligodendrocyte precursors is retinoic acid. Here we show that retinoic acid inhibits the maturation of embryonic spinal cord oligodendrocyte precursors in vitro at an early, highly motile stage of differentiation, characterized by the expression of A2B5 immunoreactivity. Basic FGF acts both as a mitogen and an inhibitor of spinal cord oligodendrocyte precursor maturation, but at a significantly later stage of differentiation, characterized by the expression of O4 immunoreactivity. In the presence of RA both the mitogenic and differentiation inhibiting effects of bFGF are abolished, consistent with RA acting as an early regulator of oligodendrocyte differentiation. During embryonic development, oligodendrocyte precursors arise initially from a distinct group of cells at the ventral ventricular zone of the spinal cord. Myelination of the entire spinal cord is dependent on the migration of immature precursor cells to peripheral developing white matter. Since the embryonic spinal cord has the capacity to release relatively high levels of retinoids, we propose that RA inhibits oligodendrocyte differentiation during early embryonic development permitting their dispersal throughout the entire spinal cord.

Animals↗
PubMed1993

Approaches to identify genes involved in Drosophila embryonic CNS development.

Many of the steps involved in formation of the Drosophila embryonic central nervous system (CNS) have been identified by both descriptive and experimental studies. In this review we will describe the various approaches that have been used to identify molecules involved in CNS development and the advantages and disadvantages of each of them. Our discussion will by no means be exhaustive; but rather we will discuss our experiences with each approach and provide an overview of what has been learned by using these methodologies. Finally, we will discuss methods that have been recently developed and how they are likely to provide further insight into CNS development.

Animals↗
PubMed1993

The Drosophila stubarista phenotype is associated with a dosage effect of the putative ribosome-associated protein D-p40 on spineless.

We describe the molecular characterization of the Drosophila melanogaster gene stubarista (sta) that encodes the highly conserved putative ribosome-associated protein D-p40. sta maps to cytological position 2A3-B2 on the X chromosome and encodes a protein (D-p40) of 270 amino acids. D-p40 shares 63% identity with the human p40 ribosomal protein. P element-mediated transformation of a 4.4-kb genomic fragment encompassing the 1-kb transcript corresponding to D-p40 was used to rescue both a lethal (sta2) and a viable (sta1) mutation at the stubarista (sta) locus. Developmental analysis of the sta2 mutation implicates a requirement for D-p40 during oogenesis and imaginal development, which is consistent with the expression of sta throughout development. In addition, we have analyzed the basis of the sta1 visible phenotype which consists of shortened antennae and bristles. sta1 is a translocation of the 1E1-2 to 2B3-4 region of the X chromosome onto the third chromosome at 89B21-C4. We provide genetic evidence that Dp(1;3)sta1 is mutant at the spineless (ss) locus and that it is associated with partial D-p40 activity. We demonstrate that sta1 acts as a recessive enhancer of ss; reduction in the amount of D-p40 provided by the transposed X chromosomal region of sta1 reveals a haplo-insufficient phenotype of the otherwise recessive ss mutations. This phenomenon is reminiscent of the enhancing effect observed with Minute mutations, one of which, rp49, has previously been shown to encode a ribosomal protein.

Amino Acid Sequence↗