Henry Gray and Henry Vandyke Carter: creators of a famous textbook.
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Biomedical subjects
Publications and source records attributed to S Roberts.
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Fibroblast growth factor-mediated signalling was studied in porcine aortic endothelial cells expressing either wild-type fibroblast growth factor receptor-1 or a mutant receptor (Y766F) unable to bind phospholipase C-(&ggr;). Stimulation of cells expressing the wild-type receptor resulted in activation of phospholipases C, D and A(2) and increased phosphoinositide 3-kinase activity. Stimulation of the wild-type receptor also resulted in stress fibre formation and a cellular shape change. Cells expressing the Y766F mutant receptor failed to stimulate phospholipase C, D and A(2) as well as phosphoinositide 3-kinase. Furthermore, no stress fibre formation or shape change was observed. Both the wild-type and Y766F receptor mutant activated MAP kinase and elicited proliferative responses in the porcine aortic endothelial cells. Thus, fibroblast growth factor receptor-1 mediated activation of phospholipases C, D and A(2) and phosphoinositide 3-kinase was dependent on tyrosine 766. Furthermore, whilst tyrosine 766 was not required for a proliferative response, it was required for fibroblast growth factor receptor-1 mediated cytoskeletal reorganisation.
Mudford, Hogg, and Roberts (1999) published additional concerns about their failure to achieve interobserver agreement on adults with mental retardation when using an experimental, 13-category behavior state code we earlier provided to them at their request. They presented findings of interobserver agreements from a videotape of their 3 adult participants that was scored by observers at the University of Kansas. In this response we present extensive investigations demonstrating the reliable measurement of behavior state among infants and adults with mental retardation, including independent data from other state researchers. We give arguments showing why their "videotape study" does not meet requirements for acceptable research methodology and discuss other procedural issues for measuring state behavior among infants with and those without disabilities.
2-Chlorodeoxyadenosine (2-CdA) is associated with prolonged suppression of CD4 lymphocytes. Cases of tuberculosis or mycobacterium avium intracellulare complex (MAC) infection complicating 2-CdA administration have not been reported despite the low CD4 counts. We report a patient with Hairy Cell Leukaemia (HCL) who developed MAC infection one month following 2-CdA treatment. This patient had been previously treated with prednisone for Sweets Syndrome. It would appear that the combination of 2-CdA and prednisone predisposes patients to MAC infection, and if possible this combination of treatment should be avoided.
The influence of bcl-2 and bax expression on apoptotic cell death in mouse intestinal epithelia was assessed using homozygously null mice. Apoptosis was induced in vivo by the enterotoxin 5-fluorouracil (5FU) or by gamma-irradiation and its cell positional incidence was assessed. 5FU and gamma-radiation treated bax-null mice surprisingly showed no reductions in apoptotic yield in the small intestine or midcolon at 4.5 h at cell positions in which both agents had previously been shown to strongly induce p53 protein expression. The colonic epithelia of 5FU treated bcl-2-null mice showed elevated levels of apoptosis at 4.5 h: from 48 apoptotic events in wild-type mice to 273 in the nulls, scoring 200 half crypts. The increase occurred specifically in the cell positions considered to harbour colonic stem cells, at the base of crypts, where there is selective expression of bcl-2. There was a modest but significant increase in apoptosis in the small intestine of the bcl-2-null mice although the epithelia of wild-type mice here are not immunohistochemically positive for bcl-2 protein. These findings show that bcl-2 plays a key role in determining the sensitivity of colonic stem cells to damage-induced death but that bax is not responsible for the p53-dependent induction of apoptosis in this context.
Independent component analysis (ICA) finds a linear transformation to variables that are maximally statistically independent. We examine ICA and algorithms for finding the best transformation from the point of view of maximizing the likelihood of the data. In particular, we discuss the way in which scaling of the unmixing matrix permits a "static" nonlinearity to adapt to various marginal densities. We demonstrate a new algorithm that uses generalized exponential functions to model the marginal densities and is able to separate densities with light tails. We characterize the manifold of decorrelating matrices and show that it lies along the ridges of high-likelihood unmixing matrices in the space of all unmixing matrices. We show how to find the optimum ICA matrix on the manifold of decorrelating matrices, and as an example we use the algorithm to find independent component basis vectors for an ensemble of portraits.
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PURPOSE: The aim of this study was to investigate changes in tumor oxygenation, assessed by polarographic needle electrode measurements, following fractionated external beam radiotherapy in carcinoma of the cervix. METHODS AND MATERIALS: Normal and tumor tissue oxygenation was measured in 19 patients prior to radiotherapy and after 40-45 Gy of external beam radiotherapy delivered in 20 fractions over 4 weeks. All measurements were performed during anesthesia. RESULTS: There was no significant difference in the level of normal tissue oxygenation pre- and post radiotherapy. The individual patient median tumor pO2 values ranged from 0 to 31 mmHg pre-radiotherapy and 1 to 61 mmHg post-radiotherapy. The mean of the 19 median pO2 values increased from 8 (SD +/- 10) mmHg to 20 (+/- 20) mmHg following external beam radiotherapy. The increase was significant by paired Wilcoxon test (p = 0.011). There was also a significant fall in the proportion of values < 5 mmHg (p = 0.040). Although this value remained constant, or fell, in the majority of patients (15/19), it increased in 4 tumors. Tumor size pre- and postradiotherapy did not correlate with the level of pretreatment oxygenation; neither did the change in tumor size and change in level of oxygenation. CONCLUSION: The level of tumor oxygenation increased in the majority of patients (15/19) following 40-45 Gy of radiotherapy in carcinoma of the cervix.
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Previous studies have established that adenovirus 2/5 early region 1B (Ad E1B) 58K protein binds p53 strongly and co-localizes with it to cytoplasmic dense bodies whilst the homologous Ad12E1B54K protein binds only weakly and co-localizes primarily to the nucleus in Ad12E1 transformed cells. We have used these properties of the E1B proteins from different viral serotypes to map the p53 binding site on the Ad2/5 protein. A set of chimaeric genes was constructed containing different proportions of the Ad12 and Ad2E1B DNA. These, together with Ad12E1A and E1B19K DNA, were transfected into baby rat kidney cells and transformed lines isolated. From an examination of the properties of these Ad12/Ad2E1B fusion proteins in co-immunoprecipitation and subcellular localization experiments it has been concluded that the p53 binding site on Ad2E1B58K protein lies between amino acids 216 and 235 and that the homologous region on Ad12E1B54K protein also binds p53. In addition, a unique nuclear localization signal is located on Ad12E1B54K between residues 228 and 239. We suggest that primary structure differences in these regions of the Ad2 and Ad12E1B proteins are responsible for the different subcellular localizations in AdE1 transformants.
The Saccharomyces Genome Database (SGD) collects and organizes information about the molecular biology and genetics of the yeast Saccharomyces cerevisiae. The latest protein structure and comparison tools available at SGD are presented here. With the completion of the yeast sequence and the Caenorhabditis elegans sequence soon to follow, comparison of proteins from complete eukaryotic proteomes will be an extremely powerful way to learn more about a particular protein's structure, its function, and its relationships with other proteins. SGD can be accessed through the World Wide Web at http://genome-www.stanford.edu/Saccharomyces/
The use of membrane filters to concentrate cytology specimens was first described by Seal (Cancer 1956; 9:866-868). We report on a technique in which a portion of Papanicolaou-stained Millipore filter (Millipore Corp, Bedford, MA) preparation can be converted into a paraffin block for hematoxylin-eosin (H&E) preparations and immunocytochemical analysis (ICC). Seven cases with moderate cellularity and no cell block preparation were retrieved from our cytopathology files. The specimens included: 4 pleural effusions with metastatic adenocarcinoma, and 3 FNA specimens (1 metastatic melanoma, 1 metastatic adenocarcinoma, and 1 thyroid/papillary carcinoma). The filter was removed from the slide, cut in half, and subjected to paraffin embedding in the usual fashion (postfixed in 10% neutral-buffered formalin). Four-micron-thick sections were cut onto Probe-On (Fisher Scientific, Pittsburgh, Pa) slides. ICC was performed using the avidin-biotin-peroxidase complex technique and capillary gap technology. Antibodies included CAM5.2, AE1/AE3, CEA, CD15, LCA, PanCK, S100, HMB45, and thyroglobulin. All cases showed excellent preservation of cellular morphology on H&E. ICC performed on Millipore filter cell block preparations showed specific antibody staining patterns with preservation of cellular details. All antibodies showed their specific staining patterns with clean background and lack of nonspecific staining. This technique has the following advantages: 1) offers an alternative to cell blocks in moderately cellular specimens; 2) clean background; 3) preservation of cytology specimens for future studies.
Under some conditions (dark or light inspection areas) illusory gratings often appear to be in-phase with the inducing gratings and under others (gray inspection area) illusory gratings often appear to be out-of-phase with the inducing gratings. McCourt reported that point-by-point brightness matches reveal only out-of-phase illusory gratings, no matter what the luminance of the inspection area (McCourt, M. E. (1994). Vision Research, 34, 1609-1617). Since the technique used might have led to afterimages which mimic out-of-phase illusory gratings, the present series of experiments was undertaken to determine how such afterimages might bias illusory grating judgments. Afterimages were induced during fixation with brief flashes of inducing gratings within the inspection area (Experiment 1), or by vertical shifts in the entire stimulus which exposed the retina to real gratings prior to judgments within the inspection area (Experiment 2). Experiment 2 was replicated with drifting inducing gratings (Experiment 3). The subjects were asked to indicate whether illusory gratings appeared in- or out-of-phase. The results of all three experiments reveal that out-of-phase illusory gratings predominate, and that afterimages can only bias judgments with stationary displays. It is suggested that grating induction is perceived when subjects attend to local contrast differences, while phantom visibility is facilitated when attention is captured by the more global aspects of the stimulus.
The follicular variant of papillary carcinoma (FVPTC) is characterized by follicular growth pattern and tumor cells with appropriate nuclear features of papillary carcinoma. However, occasionally these lesions may show focal or multifocal instead of diffuse distribution of nuclear features of papillary carcinoma. Such lesions can be underdiagnosed as benign follicular nodule. Previous studies have shown that cytokeratins, especially 19, are helpful in differentiating papillary carcinoma from other benign and malignant follicular patterned lesions. In this study, we applied monoclonal antibodies to CK5/6/18, CK18, CK10/13, CK20, CK17, and CK19 to paraffin sections of formaldehyde-fixed tissue from 26 cases of FVPTC with multifocal distribution of papillary cancer nuclei, 10 cases of usual variant of papillary carcinoma, 1 case of Warthin's tumor-like papillary carcinoma, and 2 cases of the columnar cell carcinoma. CK19 stained strongly and diffusely all cases of papillary carcinoma. FVPTC cases showed strong staining of the areas with papillary cancer nuclei in all cases and moderate to strong staining in areas of tumor without obvious nuclear features of papillary cancer. Normal thyroid parenchyma adjacent to the tumor nodule showed focal staining in most cases; however, tissue away from the tumor nodule failed to show any staining. All cases of usual type of papillary carcinoma, 2 of columnar cell carcinoma, and 1 Warthin's tumor-like papillary carcinoma showed strong and diffuse staining with CK19 and failed to show any staining of adjacent normal thyroid parenchyma. Similar but less intense staining patterns were seen with CK17 and CK20. The control group, consisting of cases of follicular adenoma, follicular carcinoma, and hyperplastic nodule, showed no staining with CK19. We suggest that if one is using immunohistochemistry to aid in the diagnosis of cases of FVPTC with multifocal distribution of nuclear features of papillary cancer, an antibody panel comprising CKs 17, 19, and 20 may prove helpful. In addition, we hypothesize that the staining of adjacent nontumorous thyroid parenchyma with CK19, seen only in cases of FVPTC, suggests that some factors secreted/produced by this particular tumor may lead to modification in keratin expression of surrounding follicular epithelium.
OBJECTIVE: The study was commissioned by the Welsh Office to pull together lessons from all reports on cases involving either a child abuse fatality or serious child protection concern ("Part 8 Reviews") since the introduction of the Children Act 1989. METHOD: Twenty-one such reports were identified and subjected to a content analysis to extract practice issues. RESULTS: From 19 reports (excluding Reviews concerning adult sexual abusers), the authors identify seven practice themes emerging from that analysis which are related to those identified in previous studies and to six previously undertaken British overviews of child abuse fatalities. The themes are assessment, interagency communications, responsibility, number of professionals involved, role of general practitioners, insufficient training for pediatricians/radiologists, and parental choice. CONCLUSIONS: British child protection agencies are attempting to address apparently conflicting policy objectives. On the one hand they are required to ensure the protection of the most vulnerable children within the child protection system. At the same time they are also being encouraged to adopt a "lighter touch" in child protection work. The authors conclude that the seven themes may provide some indicators as to how these conflicting objectives may be reconciled.
Attentional deficits are well-established characteristics of patients with schizophrenia and their at-risk offspring, suggesting a biological connection between attention and schizophrenia. The goal of this study is to clarify the developmental role of attention in the illness. Data has been collected from 87 subjects at high and low risk for schizophrenia who have participated in the New York High-Risk Project from 1977 to the present. Individuals are considered to be at high risk if either or both of their parents has schizophrenia. Analyses of attention and global behaviors, measured at intervals from about 12 to 26 years of age, indicate (a) attentional deficits can be reliably detected in high-risk children who will develop future schizophrenia-spectrum disorders (the prespectrum [PSP] group); (b) these deficits are stable, enduring over time, and appear to reflect a compromised attentional capacity; (c) attention is not affected by the onset of illness in the PSP group; (d) for all subjects, attention and global behaviors follow independent developmental pathways; and (e) behavioral difficulties, but not attention deficits, appear to be highly sensitive to environmental factors, especially rearing by a mentally ill parent. It is concluded that in PSP individuals impaired attention probably results from prenatal developmental abnormalities (possibly on the cellular level) and is likely to be a marker of a biological vulnerability to schizophrenia. In addition, attentional deficits, as opposed to early behavioral difficulties, are concluded to be a useful first step in screening for youngsters in need of early intervention.
Two studies examined the efficacy of context reinstatement as a reminder in enhancing 5- to 7-year-old children's recall. In Experiment 1, children who had been interviewed shortly after an event were reinterviewed 6 months later. Children exposed to a context reminder 24 hr before the 6-month interview and children interviewed in the event context did not differ but reported significantly more information in a verbal interview than children receiving a standard interview. A control group experienced the reminder but not the event and established that the effects of the reminder were not due to new learning. There was no effect of the reminder on accuracy and no effect in reenactment. In Experiment 2, children were interviewed for the first time after 6 months, and effects of the reminder were found for both verbal recall and reenactment. Nonverbal reminders may effectively enhance the amount of information children report without decreasing accuracy.
Quantitative analysis of sleep EEG data can provide valuable additional information in sleep research. However, analysis of data contaminated by artifacts can lead to spurious results. Thus, the first step in realizing an automatic sleep analysis system is the implementation of a reliable and valid artifact processing strategy. This strategy should include: (1) high-quality recording techniques in order to minimize the occurrence of avoidable artifacts (e.g. technical artifacts); (2) artifact minimization procedures in order to minimize the loss of data by estimating the contribution of different artifacts in the EEG recordings, thus allowing the calculation of the 'corrected' EEG (e.g. ocular and ECG interference), and finally (3) artifact identification procedures in order to define epochs contaminated by remaining artifacts (e.g. movement and muscle artifacts). Therefore, after a short description of the types of artifacts in the sleep EEG and some typical examples obtained in different sleep stages, artifact minimization and identification procedures will be reviewed.