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Biomedical subjects

D Knapp

Publications and source records attributed to D Knapp.

At least 19 recordsLinked to original sources
PubMed2001

Description and dosimetric verification of the PEREGRINE Monte Carlo dose calculation system for photon beams incident on a water phantom.

PEREGRINE is a three-dimensional Monte Carlo dose calculation system written specifically for radiotherapy. This paper describes the implementation and overall dosimetric accuracy of PEREGRINE physics algorithms, beam model, and beam commissioning procedure. Particle-interaction data, tracking geometries, scoring, variance reduction, and statistical analysis are described. The BEAM code system is used to model the treatment-independent accelerator head, resulting in the identification of primary and scattered photon sources and an electron contaminant source. The magnitude of the electron source is increased to improve agreement with measurements in the buildup region in the largest fields. Published measurements provide an estimate of backscatter on monitor chamber response. Commissioning consists of selecting the electron beam energy, determining the scale factor that defines dose per monitor unit, and describing treatment-dependent beam modifiers. We compare calculations with measurements in a water phantom for open fields, wedges, blocks, and a multileaf collimator for 6 and 18 MV Varian Clinac 2100C photon beams. All calculations are reported as dose per monitor unit. Aside from backscatter estimates, no additional, field-specific normalization is included in comparisons with measurements. Maximum discrepancies were less than either 2% of the maximum dose or 1.2 mm in isodose position for all field sizes and beam modifiers.

Algorithms↗
PubMed2001

Spatial representations of virtual mazes: the role of visual fidelity and individual differences.

Twenty-four people learned three versions of a room-sized maze: a wire-frame desktop virtual environment (VE), a normal surface-rendered desktop VE, and a real-world maze. Differences among the mental representations formed from each environment were measured with pointing and distance estimation tasks in a real-world version of each maze. People were more accurate at pointing after having learned the real and wire-frame VE maze than the surface-rendered VE maze; however, this effect was small compared with the effect of individual differences. Differences in gender, spatial ability, and prior computer experience were significantly related to the ability to acquire spatial information from the desktop VE. There was a high correlation between spatial knowledge when it was measured in the VE and spatial knowledge measured in the real world. Actual or potential applications include the design of effective VE training systems.

Adolescent↗
PubMed1999

Subcellular immunolocalization of protein kinase CK2 in normal and carcinoma cells.

CK2 is a messenger-independent protein serine/threonine kinase that has been implicated in cell growth and proliferation. Our recent analysis of squamous cell carcinomas of the head and neck (SCCHN) revealed a significant elevation in CK2 activity in these tumor cells relative to normal mucosa of the upper aerodigestive tract and suggested a correlation with aggressive tumor behavior and poor clinical outcome. In order to further define the distribution of CK2 in these tissues, we have examined the immunohistochemical staining pattern of surgical specimens of both SCCHN tumors and normal upper aerodigestive tract mucosa using a monoclonal antibody directed against the catalytic subunit CK2-alpha of the kinase, and have compared these data with the subcellular distribution of CK2 activity in these same tissues. These measurements showed that CK2 is predominantly localized to the nuclei of the tumor cells, which agreed closely with the immunohistochemical staining pattern of CK2-alpha in tumor cells. The chiefly nuclear distribution of CK2-alpha immunostaining found consistently in SCCHN tumor cells and tumor-infiltrating lymphocytes contrasted with a relatively more predominant cytosolic staining pattern exhibited by various cellular constituents of normal oropharyngeal mucosa. The immunostaining pattern of CK2-alpha revealed that staining was observed in the cells stained for the proliferation-marker Ki-67; however, strong distinct immunostaining for CK2-alpha was also observed in large numbers of other cells in these same tumors, suggesting that CK2 elevation in these tumors is not a reflection of proliferative activity alone, but may also relate to the pathobiological behavior of the tumor.

Carcinoma, Squamous Cell↗
PubMed1998

Comparison of the characteristics and features of pressure garments used in the management of burn scars.

Two companies provide custom-made pressure garments to clients with burn scars at Westmead Hospital. This prospective study was completed in order to make objective decisions about which garments were most appropriate and cost effective to provide to clients. Issues such as cost, durability, fit and client preferences were investigated. Data were collected from 43 clients; at the time of initial fitting, at a follow-up appointment 4-6 weeks later, and at the time one of the garments required replacement. One Second Skin and one Jobst garment were provided to each client and the garments were compared using therapists' evaluation and clients' perspectives on a number of variables. Second Skin garments had significantly more favourable results on the variables of time for delivery, fit at follow-up, garment design, quality of fabric and seams, overall satisfaction and garment preference for ongoing wear. On all other variables there was no significant difference between the garments. Second Skin provided the most optimal and appropriate option for pressure garments in the management of burn scars for our clients.

Adolescent↗
PubMed1997

Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs.

In eukaryotic cells, firing of DNA replication origins normally does not recur until after M phase. This characteristic is thought to be due to the properties of "initiation" proteins like Orc, Cdc6, and Mcms. Using formaldehyde cross-linking, we show that Cdc6p and Mcm7p associate specifically with replication origins during G1 but not during G2 in S. cerevisiae. Mcm7p's association with origins depends on Cdc6p. Ectopic expression of Cdc6p enables it to associate with origins during G2, but this fails to recruit Mcm7p. Our data suggest that the loading of Mcm proteins onto origins is regulated by two mechanisms: first, by Cdc6p occupancy, and second, by S- and M-CDKs, whose activity during S, G2, and M phases prevents Mcm loading.

Binding Sites↗
PubMed1997

Crystal structure of the DNA-binding domain of Mbp1, a transcription factor important in cell-cycle control of DNA synthesis.

BACKGROUND: During the cell cycle, cells progress through four distinct phases, G1, S, G2 and M; transcriptional controls play an important role at the transition between these phases. MCB-binding factor (MBF), a transcription factor from budding yeast, binds to the so-called MCB (MluI cell-cycle box) elements found in the promoters of many DNA synthesis genes, and activates the transcription of those at the G1-->S phase transition. MBF is comprised of two proteins, Mbp1 and Swi6. RESULTS: The three-dimensional structure of the N-terminal DNA-binding domain of Mbp1 has been determined by multiwavelength anomalous diffraction from crystals of the selenomethionyl variant of the protein. The structure is composed of a six-stranded beta sheet interspersed with two pairs of alpha helices. The most conserved core region among Mbp1-related transcription factors folds into a central helix-turn-helix motif with a short N-terminal beta strand and a C-terminal beta hairpin. CONCLUSIONS: Despite little sequence similarity, the structure within the core region of the Mbp1 N-terminal domain exhibits a similar fold to that of the DNA-binding domains of other proteins, such as hepatocyte nuclear factor-3gamma and histone H5 from eukaryotes, and the prokaryotic catabolite gene activator. However, the structure outside the core region defines Mbp1 as a larger entity with substructures that stabilize and display the helix-turn-helix motif.

Amino Acid Sequence↗
PubMed1997

Patient specific color texture mapping of CT-based anatomical surface models utilizing cryosection data.

In traditional medical imaging modalities, color and texture information can add considerable information for diagnostics. Presently, multimodal images of a patient are unregistered and referenced independent of each other, or registered and fused into a single hybrid volume. Doctors and other medical professionals need to be able to visualize and interrogate, on a per-patient basis, a wide variety of 2D and 3D data representations that can be created from non-invasive imaging modalities, such as MRI and CT. In addition, any colorization that may be applied to the image data is strictly based on tissue density, radiation emission, or magnetic signature, and not on any physiological foundation. In order for "true-to-life" color information to be incorporated with non-invasive imaging techniques, and for it to be of consistent quality across the entire body, a single whole-body cryosection specimen with associated medical image data is needed. The National Library of Medicine's Visible Human Project offers just such a specimen. Using the full-body medical image data along with the cryosection images of the Visible Human subject, a set of color lookup tables for all visually well defined structures and organs can be created. As a result, patient-specific colorization based on real tissue color and characteristics can be incorporated into traditional intensity-based imaging modalities. The primary goal of this work has been to create CT color lookup tables for all visually well-defined structures in the Visible Human male cryosection data set. The subsequent goal has been to develop a method for stripping textures from a volumetric data set for polygonal models and non-uniform rational B-spline (NURBS) models, also generated from the volumetric data.

Color↗
PubMed1996

Immunohistochemical staining for markers of future neoplastic progression in the larynx.

We performed a retrospective, longitudinal study to determine whether abnormalities in immunohistochemical staining for the epidermal growth factor receptor (EGFR), p53, or cyclin D1 occur before the development of laryngeal carcinoma. Staining was performed on 63 paraffin-embedded biopsies from 18 patients who subsequently developed carcinoma in situ (CIS) or invasive carcinoma of the larynx. These were compared to 71 biopsies from 20 patients who did not develop CIS/cancer (minimum follow-up period, 4 years). Also studied were the 34 biopsies containing CIS and/or carcinoma from those patients who progressed and 22 biopsies obtained concurrently. The two patient groups did not differ significantly in terms of tobacco and alcohol use. Distinct patterns of staining correlated with malignant progression. These included EGFR staining of two thirds or more of the epithelium thickness, a linear basal p53 staining pattern, and strong (3+) staining for cyclin D1 (P < 0.01 for each). These staining patterns also correlated with increasing atypia. In our study population, linear basal staining for p53 and strong staining for cyclin D1 had higher specificity for progression than did EGFR overexpression, which was also seen in association with inflammation and chronic irritation. Marked site-to-site variation was seen in the immunohistochemical staining and in the degree of atypia, suggesting that multiple biopsies are necessary to properly assess risk. These immunohistochemical staining patterns may be clinically useful to predict patients at risk for neoplastic progression.

Adult↗
PubMed1996

The transcription factor Swi5 regulates expression of the cyclin kinase inhibitor p40SIC1.

DNA replication in budding yeast cells depends on the activation of the Cdc28 kinase (Cdk1 of Saccharomyces cerevisiae) associated with B-type cyclins Clb1 to Clb6. Activation of the kinase depends on proteolysis of the Cdk inhibitor p40SIC1 in late G1, which is mediated by the ubiquitin-conjugating enzyme Cdc34 and two other proteins, Cdc4 and Cdc53. Inactivation of any one of these three proteins prevents p40SIC1 degradation and causes cells to arrest in G1 with active Cln kinases but no Clb-associated Cdc28 kinase activity. Deletion of SIC1 allows these mutants to replicate. p40SIC1 disappears at the G1/S transition and reappears only after nuclear division. Cell cycle-regulated proteolysis seems largely responsible for this pattern, but transcriptional control could also contribute; SIC1 RNA accumulates to high levels as cells exit M phase. To identify additional factors necessary for the inhibition of the Cdk1/Cdc28 kinase in G1, we isolated mutants that can replicate DNA in the absence of Cdc4 function. Mutations in three loci (SIC1, SWI5, and RIC3) were identified. We have shown that high SIC1 transcript levels at late M phase depend on Swi5. Swi5 accumulates in the cytoplasm during S, G2, and M phases of the cell cycle but enters the nuclei at late anaphase. Our data suggest that cell cycle-regulated nuclear accumulation of Swi5 is responsible for the burst of SIC1 transcription at the end of anaphase. This transcriptional control may be important for inactivation of the Clb/Cdk1 kinase in G2/M transition and during the subsequent G1 period.

Base Sequence↗
PubMed1995

Promyelocytic blast crisis of chronic myelogenous leukemia. A rare subtype associated with disseminated intravascular coagulation.

Two patients with chronic myelogenous leukemia (CML) developed blast crisis that morphologically appeared to be the microgranular variant of acute promyelocytic leukemia. This represented 8% of CML patients developing blast crisis from 1984 to 1993. Cytogenetic studies revealed translocation 15;17 in addition to translocation 9;22 that had been documented at initial diagnosis. Both patients had evidence of disseminated intravascular coagulation at the onset or during treatment of blast crisis, which was not documented in any other patients with CML blast crisis. One patient died of sepsis during intensive chemotherapy. The second returned to a chronic phase of the disease after therapy. Although rare, a promyelocytic blast crisis of CML can occur which, as in de novo acute promyelocytic leukemia, has a propensity to produce disseminated intravascular coagulation.

Adult↗
PubMed1995

Cervical lymph node status and survival in laryngeal carcinoma: prognostic factors.

Elective cervical lymphadenectomy often is performed for laryngeal carcinoma to eliminate metastatic disease that escapes clinical and radiographic detection. We investigated characteristics of the primary tumor that might predict cervical lymph node status. We obtained archival tissue from 88 laryngectomies--65 with concurrent cervical lymphadenectomies. Of the 40 clinically negative necks that were dissected, 17% showed lymph node metastasis by pathologic examination. The primary tumors were examined immunohistochemically for expression of epidermal growth factor receptor (EGFR), p53, cathepsin D, proliferating cell nuclear antigen (PCNA), and Ki-67-specific antigen, and by flow cytometry for DNA ploidy-cell cycle analysis. Seventy-seven percent of the cases showed aberrant p53 staining, 99% expressed EGFR, 40% produced cathepsin D, 29% were aneuploid, and 54% had a moderate or high synthesis phase fraction (SPF). High grade, aneuploidy, and tumor vascular invasion independently predicted cervical node metastasis (p < .04 each). Supraglottic locale (p < .16) and a raggedly infiltrating invading margin (p < .13) were weakly associated with node positivity. Advanced clinical T status, the expression of EGFR, p53, and cathepsin D, the PCNA and Ki-67 indices, and SPF did not correlate with node metastasis. The presence of cervical node metastasis predicted poor disease-free (p < .005) and overall survival (p < .04). Advanced clinical T status correlated with brief overall survival (p < .02). Tumor site, histopathologic parameters, ploidy, SPF, PCNA and Ki-67 indices, and the expression of p53, EGFR, and cathepsin D did not affect survival. The presence of vascular invasion, high grade, and aneuploidy may help identify which patients would benefit from elective cervical lymphadenectomy. The correlation of cervical lymph node status and clinical T category with survival confirms the results of previous studies.

Adult↗
PubMed1995

A microwave method that enhances detection of aberrant p53 expression in formalin-fixed, paraffin-embedded tissues.

OBJECTIVE: Detection of aberrantly accumulated p53 protein by immunohistochemistry may have prognostic significance in many human neoplasms. We wished to identify a technique applicable to formalin-fixed, paraffin-embedded sections that would reliably yield results equivalent to frozen-section immunohistochemistry. DESIGN: We compared the frequency of p53 immunostaining obtained by applying monoclonal antibodies PAb1801, DO7, or DO1, a 1:1 PAb1801-DO7 cocktail, and a 1:1 PAb1801-DO1 cocktail to fresh-frozen and formalin-fixed, paraffin-embedded tissues from 36 lung and upper aerodigestive-tract carcinomas. With the formalin-fixed tissues, we compared pepsin predigestion with microwave irradiation in citrate buffer as means of enhancing the sensitivity of p53 detection. SETTING AND PATIENTS: All tissues were obtained from surgical resections of tumors, from patients who underwent surgery at the Minneapolis Department of Veterans Affairs Medical Center between 1990 and 1992. MAIN OUTCOME MEASURES: The sensitivity of different paraffin section techniques for immunohistochemical detection of accumulated p53 protein was determined in reference to the optimal frozen section method (defined as the method that yielded the greatest number of p53-positive cases in frozen tissue). RESULTS: Microwave antigen retrieval markedly enhanced staining with PAb1801 and DO7 in paraffin sections, as compared with pepsin predigestion and no pretreatment. This technique was 100% sensitive relative to the optimal frozen tissue method. In contrast, staining with DO1 alone was not enhanced by microwaving. CONCLUSIONS: Microwave pretreatment in conjunction with the use of either PAb1801 or DO7 is highly efficacious in the immunohistochemical detection of aberrant p53 expression in formalin-fixed, paraffin-embedded tissues.

Antibodies, Monoclonal↗