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Biomedical subjects

J Keller

Publications and source records attributed to J Keller.

At least 127 records · Page 7Linked to original sources
PubMed1997

Toward implementation of artificial neural networks that "really work".

Artificial neural networks are established analytical methods in bio-medical research. They have repeatedly outperformed traditional tools for pattern recognition and clinical outcome prediction while assuring continued adaptation and learning. However, successful experimental neural networks systems seldom reach a production state. That is, they are not incorporated into clinical information systems. It could be speculated that neural networks simply must undergo a lengthy acceptance process before they become part of the day to day operations of health care systems. However, our experience trying to incorporate experimental neural networks into information systems lead us to believe that there are technical and operational barriers that greatly difficult neural network implementation. A solution for these problems may be the delineation of policies and procedures for neural network implementation and the development a new class of neural network client/server applications that fit the needs of current clinical information systems.

Hospital Information Systems↗
PubMed1997

Homologue matching using the Choquet integral.

Automated Giemsa-banded chromosome image research has been largely restricted to classification schemes associated with isolated chromosomes within metaphase spreads. In normal human metaphase spreads, there are 46 chromosomes occurring in homologous pairs for the autosomal classes, 1-22, and X chromosome for females. For optimizing automated human chromosome image analysis, many existing techniques assume cell normalcy. With many genetic abnormalities directly linked to structural and numerical aberrations of chromosomes within the metaphase spread, the two chromosome per class assumption may not be appropriate for anomaly analysis. At the University of Missouri, a data-driven homologue matching approach has been developed to identify all normal chromosomes within a metaphase spread from a selected class. Chromosome assignment to a specific class is initially based on neural networks, followed by banding pattern and centromeric index criteria checking, and concluding with homologue matching utilizing a density profile-based classifier, a shape profile-based classifier, and a binary band profile-based classifier. Based on preliminary results for the profile-based classifiers assigning chromosome 17, the Choquet integral is presented as an extension to the homologue matching approach. Experimental results are presented comparing the extended homologue matching approach to the transportation algorithm for identifying chromosome 21 within normal metaphase spreads.

Chromosome Aberrations↗
PubMed1997

The effects of image manipulation on automated karyotyping.

Karyotyping is one of the standard tools for human genetic investigations. Karyotyping involves the classification and interpretation of chromosomes found in a metaphase spread. As part of the automated karyotyping process, image manipulation is required for appropriately positioning metaphase spread chromosomes in their corresponding karyotype. Image manipulation, specifically image rotation, reorganizes the grey-level information within chromosomes to facilitate analysis. Statistical tests are performed to compare features related to banding pattern and length between unmanipulated chromosomes and corresponding rotated chromosomes. Based on experimental results, reorganizing the grey-level information yields statistically different chromosome features. Depending on the purpose of chromosome image analysis, the interpretation process of karyotyping could be impaired with chromosome feature distortion due to image rotation.

Humans↗
PubMed1996

Restoration of Clostridium difficile toxin-B-inhibited phospholipase D by phosphatidylinositol 4,5-bisphosphate.

Receptor signalling to phospholipase D (PLD) in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor apparently involves Rho proteins. Since phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has been recognized as an essential cofactor for PLD activity and since activated Rho proteins have been reported to stimulate the synthesis of PtdIns(4,5)P2, we studied whether in HEK cells PLD activity is regulated by PtdIns(4,5)P2 and, in particular, whether PtdIns(4,5)P2 can restore PLD activity inhibited by Clostridium difficile toxin B, which inactivates Rho proteins. Addition of MgATP to permeabilized HEK cells increased basal PLD activity and potentiated PLD stimulation by the stable GTP analogue, guanosine 5'-[gamma-thio]triphosphate (GTP[S]), concomitant with a large increase in PtdIns(4,5)P2. On the other hand, neomycin, which binds to PtdIns(4,5)P2, inhibited basal and GTP[S]-stimulated PLD activities. Addition of PtdIns(4,5)P2 increased PLD activity in HEK cell membranes by 2-3-fold, whereas various other phospholipids were ineffective. Prior treatment of HEK cells with toxin B reduced the level of PtdIns(4,5)P2, measured either in intact cells or in membrane preparations, by about 40%. In membranes of toxin-B-treated cells, basal and GTP[S]-stimulated PLD activities were reduced, when measured with exogenous phosphatidylcholine as enzyme substrate. Inclusion of PtdIns(4,5)P2 with phosphatidylcholine in the substrate vesicles or addition of PtdIns(4,5)P2 fully restored basal and GTP[S]-stimulated PLD activities in membranes of toxin-B-treated cells. In conclusion, the data indicate that PtdIns(4,5)P2 is an essential cofactor for PLD activity in HEK cells and that inhibition of PLD activity by the Rho-inactivating toxin B is apparently caused by depletion of the PLD cofactor, PtdIns(4,5)P2.

Bacterial Proteins↗
PubMed1996

The relationship between tumor oxygenation and cell proliferation in human soft tissue sarcomas.

PURPOSE: In malignant tumors the oxygenation status and tumor cell proliferation are known to influence local tumor control after radiotherapy. However, the relationship between oxygenation status and tumor cell kinetics in human tumors has not yet been described. Newly developed clinically applicable techniques such as oxygen electrode measurements and assessment of tumor cell proliferation rates have been suggested as promising predictive assays. The purpose of the present study was to characterize tumor oxygenation status in soft tissue sarcomas and to compare this with tumor cell kinetics and clinical parameters. METHODS AND MATERIALS: Pretreatment tumor oxygenation status was measured by polarographic oxygen needle electrodes and evaluated as the median pO2 and the percentage of pO2 values < or = 5 mmHg and < or = 2.5 mmHg in 22 patients with primary soft tissue sarcomas. All tumors were characterized by histology, grade of malignancy, the level of microscopic necrosis, the level of effective hemoglobin, and magnetic resonance imaging estimation of tumor volume. The tumor cell potential doubling time and labeling index were measured by flow cytometric and immunohistochemical analysis of tumor biopsy specimens after in vivo incorporation of iododeoxyuridine. RESULTS: There was a significant correlation between the median pO2 and the tumor cell potential doubling time (p = 0.041), whereas no correlation was found between the level of hypoxia expressed by the percentage of pO2 values < or = 2.5 and < or = 5 mmHg, respectively, and tumor cell potential doubling time. Furthermore, no correlation was found between either of the three tumor oxygenation parameters and labeling index. The material represented large intertumor heterogeneity in oxygenation status, cell kinetics, and tumor volume, and no correlation was found between oxygenation status and either volume, histopathology, grade of malignancy, or effective hemoglobin. CONCLUSION: This report is the first to suggest a correlation between tumor oxygenation and tumor cell doubling time, as the fastest proliferating tumor cells were found in the poorest oxygenated soft tissue sarcomas. More data are needed to clarify if this relation is really a true biological phenomenon. Furthermore, tumor oxygenation status of soft tissue sarcomas was heterogeneous and independent of clinical and histopathological parameters.

Adult↗
PubMed1996

Inhibition of receptor signaling to phospholipase D by Clostridium difficile toxin B. Role of Rho proteins.

Rho proteins have been reported to activate phospholipase D (PLD) in in vitro preparations. To examine the role of Rho proteins in receptor signaling to PLD, we studied the effect of Clostridium difficile toxin B, which glucosylates Rho proteins, on the regulation of PLD activity in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor (mAChR). Toxin B treatment of HEK cells potently and efficiently blocked mAChR-stimulated PLD. In contrast, basal and phorbol ester-stimulated PLD activities were not or only slightly reduced. Cytochalasin B and Clostridium botulinum C2 toxin, mimicking the effect of toxin B on the actin cytoskeleton but without involving Rho proteins, had no effect on mAChR-stimulated PLD. Toxin B did not alter cell surface mAChR number and mAChR-stimulated binding of (guanosine 5'-O-(thio)triphosphate (GTP gamma S) to G proteins. In addition to mAChR-stimulated PLD, toxin B treatment also inhibited PLD activation by the direct G protein activators, AlF4- and GTP gamma S, studied in intact and permeabilized cells, respectively. Finally, C. botulinum C3 exoenzyme, which ADP-ribosylates Rho proteins, mimicked the inhibitory effect of toxin B on GTP gamma S-stimulated PLD activity. In conclusion, the data presented indicate that toxin B potently and selectively interferes with receptor coupling mechanisms to PLD, and furthermore suggest an essential role for Rho proteins in receptor signaling to PLD.

ADP Ribose Transferases↗
PubMed1996

MIB-1 expression and iododeoxyuridine labelling in soft tissue sarcomas: an immunohistochemical study including correlations with p53, bcl-2 and histological characteristics.

We investigated the relationship between immunohistochemical estimates of proliferative activity and expression of bcl-2 protein and mutant p53 protein in 23 cases of soft tissue sarcoma. Furthermore, the reproducibility of estimates of proliferative activity was analysed and correlations between the variables and with mitotic score were investigated. Proliferative activity was assessed by use of monoclonal antibody MIB-1 and staining for iododeoxyuridine (IdUrd), and evaluated in multiple, random, systematically sampled fields of vision. MIB-1 indices were higher than those of IdUrd but for each case the two values were positively correlated (r = 0.78). The MIB-1 index correlated positively with mitotic score (2P < 0.001) and malignancy grade (2P = 0.001). The intraobserver reproducibility of the MIB-1 and IdUrd indices were excellent (r = 0.98 and r = 0.90, respectively). p53 expression was detected in 43% and strong bcl-2 expression was present in 57% of the studied cases. Expression of p53 and bcl-2 were not significantly correlated to proliferative activity or the histological features. We conclude, that the MIB-1 index is a reliable and reproducible estimate of proliferative activity and might improve the accuracy of conventional malignancy grading of soft tissue sarcomas. Furthermore, the results indicate that neither mutant p53 protein nor bcl-2 oncogene alone are sufficient to induce increased proliferation in these sarcomas.

Antigens, Nuclear↗
PubMed1996

Intradermal and subcutaneous leiomyosarcoma: a clinicopathological and immunohistochemical study of 41 cases.

Superficial leiomyosarcomas are rare tumours. The lesions confined to the dermis, contrary to those involving the subcutis, have been reported to carry a favourable prognosis. A retrospective study of 41 consecutive cases of surgically treated intradermal and subcutaneous leiomyosarcomas was undertaken in order to determine the prognostic factors that may influence the survival of these patients. Seven tumours were predominantly intradermal and 34 involved the subcutaneous tissue. Fifty-four percent of the tumours were located in the lower extremities. All cases stained positively for smooth muscle antigen and 66% for desmin. The tumours were classified with regard to tumour grade I (low grade, 3%), II (intermediate, 12%), IIIA (high grade, 46%) and IIIB (high grade, 39%). In all patients, follow-up information was available. Mean follow-up time was 5 years. The patients with intradermal tumours were all alive without signs of recurrence, whereas 14 of those with leiomyosarcomas involving the subcutis have died with pulmonary metastases. Our study confirms that "pure" intradermal leiomyosarcomas independent of tumour grade behave in a benign fashion, probably due to small tumour size. Tumour size > or = 5 cm, deep localization with fascia involvement, and high malignancy grade (IIIB) were found to deteriorate survival based on a univariate analysis. However, in a multivariate analysis only tumour size was found to be an independent prognostic factor.

Adult↗
PubMed1996

Periosteal insulin-like growth factor I and bone formation. Changes during tibial lengthening in rabbits.

We investigated changes in periosteal insulin-like growth factor I (IGF-I) during tibial lengthening. In 37 rabbits, an osteotomy of the right middle tibia was made and fixed by a unilateral external fixator. The rabbits were randomized into 6 groups: the tibiae were distracted at 0.5 mm/day up to 4 weeks and the animals killed after 2 weeks, 4 weeks or 6 weeks, for each period there was a control group with no distraction. Periosteal IGF-I was measured by radioimmunoassay and bone formation was quantified by CT scanning. During bone lengthening, CT showed moderate bone formation, while IGF-I was increased. When lengthening was stopped, IGF-I returned to a basal level, and CT scanning showed considerable bone formation. Our study suggests that IGF-I plays a role in an early stage of bone formation.

Animals↗
PubMed1996

A centromere attribute integration approach to centromere identification.

Automated and nonautomated approaches to chromosome classification involves assessing several chromosome attributes. The centromere is an important attribute which provides insight to other features such as chromosome orientation and the banding pattern sequence. Improving the ability to identify the centromere will enhance feature determination and analysis. Techniques to identify the centromere attempt to isolate specific centromere attributes. The centromere can be characterized as possessing the following properties: 1) usually the narrowest region in the chromosome image, 2) usually located in a region containing extreme concavities along the chromosome contour, and 3) usually located in a region of uniform dark grey-level. A centromere attribute integration approach for automated centromere identification has been developed which has a correct identification rate of 93.5% on a diversified data set. This approach determines and evaluates centromere candidates based on quantified centromere attributes. Centromere attribute integration incorporates other commonly used techniques for centromere identification. Some of the techniques integrated into the experimental algorithm include evaluating chromosome curvature, analyzing the shape profile, and inspecting the width profile.

Centromere↗
PubMed1996

Multiple neural network response variability as a predictor of neural network accuracy for chromosome recognition.

Human chromosome classification requires all chromosome appearing in a microphotograph of a dividing human cell to be classified within the known normal or abnormal 24 chromosome types. In recent years, research has focused on the use of neural networks for classification of normal chromosomes. Experimental work in this area led us to question whether learning variability, resulting when multiple neural networks are trained to solve the same problem, could be used as a predictor of classification performance. The Copenhagen chromosome data bank, consisting of 30-component feature vectors from 8106 chromosomes isolated from 180 cells, was divided into a training and a test subsets. Back propagation neural networks with 30 input nodes, 1 to 100 nodes in the hidden layer, and 24 output nodes were trained with the same learning parameters. After training, each neural network was tested. The neural network yielding the best classification was labeled as the optimal neural network. An error variability score was calculated for each test chromosome. This score was a function of all (100) neural network outputs obtained for that chromosome. The error variability scores ranged from 0.16 to 1.31 with a mean value of 0.41 and a SD of 0.12. There was significant difference (p < 0.0001) between the variability scores from chromosomes classified correctly (mean = 0.4, SD = 0.1, n = 3804) and incorrectly (mean = 0.62, SD = 0.19, n = 241) by the optimal neural network. When the variability score was used as a threshold to decide whether or not to accept the output of the optimal neural network, a peak classification rate of 98.93% was observed for chromosomes with an error variability score < 0.35. Results indicate that the error variability of multiple neural network responses can be used as a confidence indicator for a optimal neural network.

Humans↗
PubMed1996

Centromere attribute integration based chromosome polarity assignment.

Automated karyotyping involves evaluating quantified chromosome attributes for proper classification. Chromosome attributes derived from the banding pattern require the correct chromosome polarity for correct banding sequence interpretation. Chromosome polarity is defined in terms of determining the short and long arms of the chromosome using the centromere as the reference point for measuring the chromosome length on both sides of the centromere. In addition to banding sequence interpretation, polarity is used in the chromosome orientation for chromosome repositioning from the metaphase spread to the karyotype. Automated polarity determination is often not performed for classifying chromosomes in the metaphase spread image. Polarity may be determined user interactively, by the system, or not at all. In order to reduce the computational complexity of evaluating banding sequence features using both chromosome ends as reference points, there is a need to improve chromosome polarity determination in automated karyotyping. A centromere attribute integration approach has been developed at the University of Missouri-Columbia which performs correct chromosome polarity assessment at a rate comparable to other studies of 96.1% on a diversified data set.

Algorithms↗
PubMed1996

Long-term follow-up of endometriosis after two different therapies (Gestrinone and Buserelin).

OBJECTIVE: To compare the efficacy, tolerance and recurrence rate of endometriosis after 5-year follow-up of treatment with Gestrinone and Buserelin, respectively. STUDY DESIGN: A prospective study with randomized follow-up of 5 years duration (minimum) for each patient was done. We included 43 cases of endometriosis diagnosed by laparoscopy or laparotomy and treated them with Gestrinone (Group G, n = 25 cases) or Buserelin intranasal spray (Group B, n = 18) for 6 months. RESULTS: General data: Age, height, weight of patients and AFS score of endometriosis were without significant differences in either group. Specific data: A) Global clinical efficacy was good or excellent in 74% (16/25) of group G and in 78% (14/18) of group B without significant differences. B) Global clinical tolerance was good in 50% of the patients in group G and in 0% in group B (p < 0.001). C) Global evaluation after 5-year follow-up showed "success" only for 36% of patients in group G and in 33% in group B (no significant differences), with "failure" in 40% and 33%, respectively (no significant differences). CONCLUSIONS: 1) Gestrinone and Buserelin intranasal spray are valid treatments for the remission of endometriosis, with "success", "failure" and "clinical recurrence" rates similar after a follow-up of 5 years of initial treatment. 2) The most significant androgenic effect of Gestrinone was the presence of acne. Vascular effects were also considered as very undesirable effects according to the comments of patients. On the contrary, the effects of analogs are generally better tolerated.

Adult↗